SecProbe.io

<DOCUMENT>
<TYPE>TEXT-EXTRACT
<SEQUENCE>2
<FILENAME>filename2.txt
<TEXT>
 June 25, 2025

Daniel Otto
Chief Financial Officer
22nd Century Group, Inc.
321 Farmington Rd
Mocksville, NC 27028

 Re: 22nd Century Group, Inc.
 Registration Statement on Form S-3
 Filed on June 20, 2025
 File No. 333-288216
Dear Daniel Otto:

 This is to advise you that we have not reviewed and will not review your
registration
statement.

 Please refer to Rules 460 and 461 regarding requests for acceleration.
We remind you
that the company and its management are responsible for the accuracy and
adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action
by the staff.

 Please contact Bradley Ecker at 202-551-4985 with any questions.

 Sincerely,

 Division of
Corporation Finance
 Office of
Manufacturing
</TEXT>
</DOCUMENT>

CORRESP
 1
 filename1.htm

 22nd
Century Group, Inc.

 321
Farmington Road

 Mocksville,
NC 27028

 (336)
940-3769

 June
25, 2025

 VIA
EDGAR

 Securities
and Exchange Commission

 Division
of Corporation Finance

 100
F Street, NE Washington, DC 20549

 Attn:
 Bradley Ecker

 Re:
 22nd Century Group, Inc.

 Registration Statement on
 Form S-3

 File No. 333-288216

 Acceleration
Request

 Requested
Date: Monday, June 30, 2025

 Requested
Time: 4:00 P.M. Eastern time

 Ladies
and Gentlemen:

 Pursuant
to Rule 461 promulgated under the Securities Act of 1933, as amended, 22nd Century Group, Inc. (the "Company") hereby requests
that the effectiveness of the above-referenced Registration Statement on Form S-3 be accelerated so that such Registration Statement
will become effective at 4:00 p.m., Eastern Time, on Monday, June 30, 2025, or as soon thereafter as practicable. The Company respectfully
requests that you notify Mr. John Wolfel of Foley & Lardner, LLP of such effectiveness by a telephone call to (904) 359-8778.

 Sincerely,

 22ND CENTURY
 GROUP, INC.

 By:
 /s/
 Daniel A. Otto

 Daniel A. Otto

 Chief Financial Officer

 cc:
John J. Wolfel of Foley Lardner, LLP

<DOCUMENT>
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<FILENAME>filename2.txt
<TEXT>
 June 10, 2025

Lawrence Firestone
Chief Executive Officer
22nd Century Group, Inc.
321 Farmington Road
Mocksville, NC 27028

 Re: 22nd Century Group, Inc.
 Preliminary Proxy Statement on Schedule 14A
 Filed May 22, 2025
 File No. 001-36338
Dear Lawrence Firestone:

 We have completed our review of your filing. We remind you that the
company and
its management are responsible for the accuracy and adequacy of their
disclosures,
notwithstanding any review, comments, action or absence of action by the staff.

 Sincerely,

 Division of Corporation
Finance
 Office of Manufacturing
</TEXT>
</DOCUMENT>

<DOCUMENT>
<TYPE>TEXT-EXTRACT
<SEQUENCE>2
<FILENAME>filename2.txt
<TEXT>
 June 9, 2025

Lawrence Firestone
Chief Executive Officer
22nd Century Group, Inc.
321 Farmington Road
Mocksville, NC 27028

 Re: 22nd Century Group, Inc.
 Revised Preliminary Proxy Statement on Schedule 14A
 Filed June 6, 2025
 File No. 001-36338
Dear Lawrence Firestone:

 We have reviewed your filing and have the following comment.

 Please respond to this letter within ten business days by providing the
requested
information or advise us as soon as possible when you will respond. If you do
not believe a
comment applies to your facts and circumstances, please tell us why in your
response.

 After reviewing your response to this letter, we may have additional
comments.

Revised Preliminary Proxy Statement on Schedule 14A
General

1. We note your response to prior comment 4 and reissue in part. Please
revise
 the Possible Effects of the Proposal sections in proposals 7 and 8
to reinsert the
 deleted disclosure that the warrants could have a reduced exercise price
which could
 result in substantial dilution to stockholders. In addition, where you
state that the
 issuance would result in the "issuance of over 20% of the Company's
outstanding
 shares of common stock on a pre-transaction basis," please provide the
actual
 percentages of the Company's outstanding shares that could be issued on
a pre-
 transaction basis.
 We remind you that the company and its management are responsible for
the accuracy
and adequacy of their disclosures, notwithstanding any review, comments, action
or absence
of action by the staff.

 Please contact Eranga Dias at 202-551-8107 or Erin Purnell at
202-551-3454 with any
questions.
 June 9, 2025
Page 2

 Sincerely,

 Division of Corporation Finance
 Office of Manufacturing
</TEXT>
</DOCUMENT>

CORRESP
 1
 filename1.htm

 22nd
Century Group, Inc.

 321
Farmington Road

 Mocksville,
NC 27028

 (336)
940-3769

 June
9, 2025

 VIA
EDGAR

 Securities
and Exchange Commission

 Division of Corporation Finance

 100
F Street, NE

 Washington, DC 20549

 Attn:
 Eranga Dias

 Re:
 22nd Century Group, Inc.

 Revised
 Preliminary Proxy Statement on Schedule 14A

 Filed June 6, 2025

 File No. 001-36338

 Ladies and Gentlemen:

 On
behalf of 22 nd Century Group, Inc. (the "Company"), please find below the responses to the comments issued by
the staff of the Division of Corporation Finance (the "Staff") of the Securities and Exchange Commission (the "Commission")
contained in the Staff's letter dated June 9, 2025 (the "Comment Letter"), concerning the Company's Revised
Preliminary Proxy Statement on Schedule 14A filed on June 6, 2025 (the "Preliminary Proxy Statement"). In addition,
we are filing herewith an Amendment No. 2 Revised Preliminary Proxy Statement on Schedule 14A (the "Amendment No. 2
Revised Preliminary Proxy Statement") to reflect amendments to the Revised Preliminary Proxy Statement that address the
Staff's comments contained in the Comment Letter, as well as to supplement certain disclosures in the Preliminary Proxy Statement.

 For
your convenience, we have included the text of the Staff's comments preceding each of the Company's responses. Set forth
below are the Company's responses to the comments presented in the Comment Letter.

 Revised
 Preliminary Proxy Statement filed
June 6, 2025

 1. We
 note your response to prior comment 4 and reissue in part. Please revise the "Possible
 Effects of the Proposal" sections in proposals 7 and 8 to reinsert the deleted disclosure
 that the warrants could have a reduced exercise price which could result in substantial dilution
 to stockholders. In addition, where you state that the issuance would result in the "issuance
 of over 20% of the Company's outstanding shares of common stock on a pre-transaction basis,"
 please provide the actual percentages of the Company's outstanding shares that could be issued
 on a pretransaction basis.

 Response :
The Company has revised the Preliminary Proxy Statement to clarify the potentially substantial dilution to stockholders as a result
of a reduced exercise price or zero exercise price exercise. Additionally, the Company has added the actual percentages of the Company's
outstanding shares that could be issued on a pre-transaction basis. Please see proposals 7 and 8 of Amendment No. 2 Revised
Preliminary Proxy Statement.

 The
Company hereby acknowledges that it is responsible for the adequacy and accuracy of the disclosures in the filing. The Company additionally
acknowledges that Staff comments or changes to disclosures in response to Staff comments do not foreclose the Commission from taking
any action with respect to the filing. The Company further acknowledges that it may not assert Staff comments as a defense in any proceeding
initiated by the Commission or any person under the federal securities laws of the United States.

 *
* *

 If
you have any questions, please do not hesitate to contact the undersigned at (213) 926-1580 or the Company's outside counsel at
Foley Lardner LLP at (904) 868-1200. Thank you in advance for your prompt attention to this matter.

 Sincerely,

 22ND CENTURY GROUP, INC.

 By:
 /s/ Jonathan Staffeldt

 Jonathan Staffeldt

 General Counsel

 cc:
 John J. Wolfel of Foley Lardner, LLP

CORRESP
 1
 filename1.htm

 22nd
Century Group, Inc.

 321
Farmington Road

 Mocksville,
NC 27028

 (336)
940-3769

 June
6, 2025

 VIA
EDGAR

 Securities
and Exchange Commission

 Division of Corporation Finance

 100
F Street, NE

 Washington, DC 20549

 Attn:
 Eranga Dias

 Re:
 22nd Century Group, Inc.

 Preliminary Proxy Statement
 on Schedule 14A

 Filed May 22, 2025

 File No. 001-36338

 Ladies and Gentlemen:

 On
behalf of 22 nd Century Group, Inc. (the "Company"), please find below the responses to the comments issued by
the staff of the Division of Corporation Finance (the "Staff") of the Securities and Exchange Commission (the "Commission")
contained in the Staff's letter dated June 5, 2025 (the "Comment Letter"), concerning the Company's Preliminary
Proxy Statement on Schedule 14A filed on May 22, 2025 (the "Preliminary Proxy Statement"). In addition, we are filing herewith
a revised Preliminary Proxy Statement on Schedule 14A (the "Revised Preliminary Proxy Statement") to reflect amendments to
the Preliminary Proxy Statement that address the Staff's comments contained in the Comment Letter, as well as to supplement certain
disclosures in the Preliminary Proxy Statement.

 For
your convenience, we have included the text of the Staff's comments preceding each of the Company's responses. Set forth
below are the Company's responses to the comments presented in the Comment Letter.

 Preliminary
Proxy Statement filed May 22, 2025

 1. We
 note your references in your preliminary proxy statement to an "alternative cashless
 exercise" feature in warrants pertaining to proposals 7 and 8. The term "cashless
 exercise" is generally understood to allow a warrant holder to exercise a warrant without
 paying cash for the exercise price and reducing the number of shares receivable by the holder
 by an amount equal in value to the aggregate exercise price the holder would otherwise pay
 to exercise the warrant(s). In cashless exercises, it is expected that the warrant holder
 receives fewer shares than they would if they opted to pay the exercise price in cash. Please
 clarify your disclosure throughout by removing the references to "alternative cashless
 exercise" and exclusively use the term "zero exercise price" or another
 appropriate term that conveys that, in addition to the company receiving no cash upon the
 "alternative cashless exercise," the warrant holders would be entitled to receive
 more shares than they would under the cash exercise terms or the cashless exercise terms
 of the warrants.

 Response :
The Company has revised the Preliminary Proxy Statement to clarify (i) the concept of the "alternative cashless exercise"
by further explaining there is a zero exercise price and using the new defined term "Zero Exercise Price Exercise",
(ii) no cash proceeds would be received upon a Zero Exercise Price Exercise and (iii) upon effecting a Zero Exercise Price
Exercise the warrant holders would receive two shares, as opposed to one share or less in a cash exercise or cashless exercise. Please
see proposals 7 and 8 of the Revised Preliminary Proxy Statement.

 2. We
 note that the aggregate number of shares of common stock issuable in the alternative cashless
 exercise contemplated in proposals 7 and 8 may result in a higher number of shares to be
 issued than the amounts disclosed in the first paragraphs of each proposal. Please revise
 your disclosure to state the number of shares issuable upon the exercise of the warrants
 under the alternative cashless exercise provisions. In addition, in order to reflect the
 actual dilutive features of these securities, please compare the number of shares issuable
 to the number of shares that are currently outstanding.

 Response :
The Company has revised the Preliminary Proxy Statement to include disclosure of the number of potential shares to be issued upon the
warrant holders fully exercising an "alternative cashless exercise" (now defined as Zero Exercise Price Exercise),
as well as a comparison to the number of shares currently outstanding. Please see proposals 7 and 8 of the Revised Preliminary Proxy
Statement.

 3. We
 note your disclosure in proposals 7 and 8 under the heading "Use of Proceeds"
 that you intend "to use the net proceeds from any Warrant exercises for general corporate
 purposes." Please expand your disclosure here to highlight that the alternative cashless
 exercise provision would allow a warrant holder to receive, without having to make any exercise
 payment, twice the number of shares of common stock the warrant holder would otherwise receive
 by means of a cash exercise. Explain that as a result you do not expect to receive any cash
 proceeds from the exercise of the warrants pertaining to proposals 7 and 8 because, if true,
 it is highly unlikely that a warrant holder would wish to pay an exercise price to receive
 a certain number of shares when they could choose the alternative cashless exercise option
 and pay no money to receive twice as many shares.

 Response :
The Company has revised the Preliminary Proxy Statement to clarify that the Company believes the warrant holders will fully exercise
under the "alternative cashless exercise" (now defined as Zero Exercise Price Exercise) and no cash proceeds will
be received, as the warrant holder will receive two shares of common stock in exchange for no cash, as opposed to one share or less upon
a cash or cashless exercise. Please see proposals 7 and 8 of the Revised Preliminary Proxy Statement.

 4. We
 note your disclosure under proposals 7 and 8 stating that warrants pertaining to these proposals
 "are subject to adjustment in certain circumstances" that may increase the number
 of shares of common stock underlying each warrant and reduce the exercise price of the warrants.
 Please expand your disclosure under the "Possible Effects of the Proposal" sections
 in proposals 7 and 8 to prominently disclose this result and explain the potential
 additional dilution upon the "adjustment." In addition, please disclose that
 these issuances could cause your common stock price to fall below the minimum bid price,
 which could result in your shares being delisted from Nasdaq.

 Response :
The Company has revised the Preliminary Proxy Statement to add disclosure under the heading "Possible Effects of the Proposal"
to include the potential additional dilution from an increase in the number of shares of common stock underlying each warrant and decrease
in exercise price of the warrants that could result from a share combination event, as defined in the Form of Warrant under section 3(f).
Please see proposal 8 of the Revised Preliminary Proxy Statement. With respect to the warrants subject to proposal 7, there are no
subsequent "share combination events" that could lower the exercise price or increase the number of shares issuable.

 The
Company hereby acknowledges that it is responsible for the adequacy and accuracy of the disclosures in the filing. The Company additionally
acknowledges that Staff comments or changes to disclosures in response to Staff comments do not foreclose the Commission from taking
any action with respect to the filing. The Company further acknowledges that it may not assert Staff comments as a defense in any proceeding
initiated by the Commission or any person under the federal securities laws of the United States.

 *
* *

 If
you have any questions, please do not hesitate to contact the undersigned at (213) 926-1580 or the Company's outside counsel at
Foley Lardner LLP at (904) 868-1200. Thank you in advance for your prompt attention to this matter.

 Sincerely,

 22ND CENTURY GROUP, INC.

 By:
 /s/ Jonathan Staffeldt

 Jonathan Staffeldt

 General Counsel

 cc:
 John J. Wolfel of Foley Lardner, LLP

<DOCUMENT>
<TYPE>TEXT-EXTRACT
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<FILENAME>filename2.txt
<TEXT>
 June 5, 2025

Lawrence Firestone
Chief Executive Officer
22nd Century Group, Inc.
321 Farmington Road
Mocksville, NC 27028

 Re: 22nd Century Group, Inc.
 Preliminary Proxy Statement on Schedule 14A
 Filed May 22, 2025
 File No. 001-36338
Dear Lawrence Firestone:

 We have reviewed your filing and have the following comments.

 Please respond to this letter within ten business days by providing the
requested
information or advise us as soon as possible when you will respond. If you do
not believe a
comment applies to your facts and circumstances, please tell us why in your
response.

 After reviewing your response to this letter, we may have additional
comments.

Preliminary Proxy Statement on Schedule 14A
General

1. We note your references in your preliminary proxy statement to an
"alternative
 cashless exercise" feature in warrants pertaining to proposals 7 and 8.
The term
 "cashless exercise" is generally understood to allow a warrant holder to
exercise a
 warrant without paying cash for the exercise price and reducing the
number of shares
 receivable by the holder by an amount equal in value to the aggregate
exercise price
 the holder would otherwise pay to exercise the warrant(s). In cashless
exercises, it is
 expected that the warrant holder receives fewer shares than they would
if they opted
 to pay the exercise price in cash. Please clarify your disclosure
throughout by
 removing the references to "alternative cashless exercise" and
exclusively use the term
 "zero exercise price" or another appropriate term that conveys that, in
addition to the
 company receiving no cash upon the "alternative cashless exercise," the
warrant
 holders would be entitled to receive more shares than they would under
the cash
 exercise terms or the cashless exercise terms of the warrants.
 June 5, 2025
Page 2
2. We note that the aggregate number of shares of common stock issuable in
the
 alternative cashless exercise contemplated in proposals 7 and 8 may
result in a higher
 number of shares to be issued than the amounts disclosed in the first
paragraphs of
 each proposal. Please revise your disclosure to state the number of
shares issuable
 upon the exercise of the warrants under the alternative cashless
exercise provisions. In
 addition, in order to reflect the actual dilutive features of these
securities, please
 compare the number of shares issuable to the number of shares that are
currently
 outstanding.
3. We note your disclosure in proposals 7 and 8 under the heading "Use of
 Proceeds" that you intend "to use the net proceeds from any Warrant
exercises for
 general corporate purposes." Please expand your disclosure here to
highlight that the
 alternative cashless exercise provision would allow a warrant holder to
receive,
 without having to make any exercise payment, twice the number of shares
of common
 stock the warrant holder would otherwise receive by means of a cash
exercise.
 Explain that as a result you do not expect to receive any cash proceeds
from the
 exercise of the warrants pertaining to proposals 7 and 8 because, if
true, it is highly
 unlikely that a warrant holder would wish to pay an exercise price to
receive a certain
 number of shares when they could choose the alternative cashless
exercise option and
 pay no money to receive twice as many shares.
4. We note your disclosure under proposals 7 and 8 stating that warrants
pertaining to
 these proposals "are subject to adjustment in certain circumstances"
that may increase
 the number of shares of common stock underlying each warrant and reduce
the
 exercise price of the warrants. Please expand your disclosure under the
"Possible
 Effects of the Proposal" sections in proposals 7 and 8 to prominently
disclose this
 result and explain the potential additional dilution upon the
"adjustment." In addition,
 please disclose that these issuances could cause your common stock price
to fall
 below the minimum bid price, which could result in your shares being
delisted from
 Nasdaq.

 We remind you that the company and its management are responsible for
the accuracy
and adequacy of their disclosures, notwithstanding any review, comments, action
or absence
of action by the staff.

 Please contact Eranga Dias at 202-551-8107 or Erin Purnell at
202-551-3454 with any
questions.

 Sincerely,

 Division of
Corporation Finance
 Office of
Manufacturing
</TEXT>
</DOCUMENT>

CORRESP
 1
 filename1.htm

 22nd
Century Group, Inc.

 321
Farmington Road

 Mocksville,
NC 27028

 (336)
940-3769

 May
19, 2025

 VIA
EDGAR

 Securities
and Exchange Commission

 Division of Corporation Finance

 100
F Street, NE

 Washington, DC 20549

 Attn:

 Eranga
 Dias

 Re:

 22nd
 Century Group, Inc.

 Registration
 Statement on Form S-3

 File
 No. 333-287095

 Acceleration
Request

 Requested
 Date: Thursday, May 22, 2025

 Requested
 Time: 9:30 A.M. Eastern time

 Ladies
and Gentlemen:

 Pursuant
to Rule 461 promulgated under the Securities Act of 1933, as amended, 22nd Century Group, Inc. (the "Company") hereby requests
that the effectiveness of the above-referenced Registration Statement on Form S-3 be accelerated so that such Registration Statement
will become effective at 9:30 a.m., Eastern Time, on Thursday, May 22, 2025, or as soon thereafter as practicable. The Company respectfully
requests that you notify Mr. John Wolfel of Foley & Lardner, LLP of such effectiveness by a telephone call to (904) 359-8778.

 Sincerely,

 22ND
CENTURY GROUP, INC.

 By:
 /s/
 Daniel A. Otto

 Daniel
 A. Otto

 Chief
 Financial Officer

 cc:
John J. Wolfel of Foley Lardner, LLP

<DOCUMENT>
<TYPE>TEXT-EXTRACT
<SEQUENCE>2
<FILENAME>filename2.txt
<TEXT>
 May 15, 2025

Lawrence Firestone
Chief Executive Officer
22nd Century Group, Inc.
321 Farmington Rd
Mocksville, NC 27028

 Re: 22nd Century Group, Inc.
 Registration Statement on Form S-3
 Filed May 8, 2025
 File No. 333-287095
Dear Lawrence Firestone:

 This is to advise you that we have not reviewed and will not review your
registration
statement.

 Please refer to Rules 460 and 461 regarding requests for acceleration.
We remind you
that the company and its management are responsible for the accuracy and
adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action
by the staff.

 Please contact Eranga Dias at 202-551-8107 with any questions.

 Sincerely,

 Division of
Corporation Finance
 Office of
Manufacturing
</TEXT>
</DOCUMENT>

CORRESP
1
filename1.htm

22nd
Century Group, Inc.

321
Farmington Road

Mocksville,
NC 27028

(336)
940-3769

February
6, 2025

VIA
EDGAR

Securities
and Exchange Commission

Division of Corporation Finance

100
F Street, NE

Washington, DC 20549

    Attn:
    Jenny
O’Shanick

    Re:
    22nd
    Century Group, Inc.

    Registration
    Statement on Form S-3

    File
    No. 333-284644

Acceleration
Request

Requested
Date: Tuesday, February 11, 2025

Requested
Time: 9:30 A.M. Eastern time

Ladies
and Gentlemen:

Pursuant
to Rule 461 promulgated under the Securities Act of 1933, as amended, 22nd Century Group, Inc. (the “Company”) hereby requests
that the effectiveness of the above-referenced Registration Statement on Form S-3 be accelerated so that such Registration Statement
will become effective at 9:30 a.m., Eastern Time, on Tuesday, February 11, 2025, or as soon thereafter as practicable. The Company respectfully
requests that you notify Mr. John Wolfel of Foley & Lardner, LLP of such effectiveness by a telephone call to (904) 359-8778.

Sincerely,

    22ND
    CENTURY GROUP, INC.

    By:

    /s/
    Daniel A. Otto

    Daniel
    A. Otto

    Chief
    Financial Officer

    cc:
    John
    J. Wolfel of Foley Lardner, LLP

CORRESP
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22nd
Century Group, Inc.

February
5, 2025

Securities
and Exchange Commission

Division
of Corporation Finance

100
F. Street, N.E.

Washington,
D.C. 20549

    Attention:
    Ms.
    Jenny O’Shanick

    Mr.
    Jay Ingram

    Re:
    22nd
    Century Group, Inc.

    Registration
    on Form S-3

    Filed
    January 31, 2025

    File
    No. 333-284644

This
letter is in response to your comment letter dated February 4, 2025. Your comment is reproduced below in bold italics, followed by the
response of 22nd Century Group, Inc. (the “Company”).

Registration
Statement on Form S-3

Selling
Stockholders, page 7

 1. Please
                                            disclose the nature of any position, office or other material relationship that the selling
                                            stockholders have had within the past three years with you or any of your predecessors or
                                            affiliates. Additionally, disclose Item 507 information about any persons (entities or natural
                                            persons) who have control over the selling stockholders and who have had a material relationship
                                            with you or any of your predecessors or affiliates within the past three years, identifying
                                            each such person and describing the nature of any relationships. See Item 507 of Regulation
                                            S-K. For additional guidance, refer to Question 140.02 of our Regulation S-K Compliance and
                                            Disclosure Interpretations.

Response:

The
Company has revised the disclosure on page 7 of the Registration Statement (Selling Stockholders) to disclose the information required
by Item 507 of Regulation S-K with respect to the natural persons that have control over the selling stockholders. In addition, the Company
has expanded the disclosure with respect to North Carolina State University to disclose the Company’s relationship. Please be advised
that no other selling stockholder (or control person with respect to a selling stockholder) has held any position, office or other material
relationship during the past three years with the Company, its affiliates or predecessors.

*****

We
acknowledge that the Company is responsible for the accuracy of its disclosures, that the Commission is not foreclosed from taking action
with respect to its filing and that the Company may not use the staff comments as a defense in any proceeding.

Please
contact me at 585-734-5678 if you need any additional information.

    Sincerely,

    /s/
    Daniel Otto

    Daniel
    Otto

    Chief
    Financial Officer

    cc:
    John
    Wolfel, Foley & Lardner LLP

    2

February 4, 2025
Lawrence D. Firestone
Chief Executive Officer
22nd Century Group, Inc.
321 Farmington Rd
Mocksville, NC 27028
Re:22nd Century Group, Inc.
Registration Statement on Form S-3
Filed January 31, 2025
File No. 333-284644
Dear Lawrence D. Firestone:
            We have conducted a limited review of your registration statement and have the
following comment(s).
            Please respond to this letter by amending your registration statement and providing
the requested information. If you do not believe a comment applies to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why in your
response.
            After reviewing any amendment to your registration statement and the information
you provide in response to this letter, we may have additional comments.
Registration Statement on Form S-3
Selling Stockholders, page 7
1.Please disclose the nature of any position, office or other material relationship that the
selling stockholders have had within the past three years with you or any of your
predecessors or affiliates. Additionally, disclose Item 507 information about any
persons (entities or natural persons) who have control over the selling stockholders
and who have had a material relationship with you or any of your predecessors or
affiliates within the past three years, identifying each such person and describing the
nature of any relationships. See Item 507 of Regulation S-K. For additional guidance,
refer to Question 140.02 of our Regulation S-K Compliance and Disclosure
Interpretations.

February 4, 2025
Page 2
            We remind you that the company and its management are responsible for the accuracy
and adequacy of their disclosures, notwithstanding any review, comments, action or absence
of action by the staff.
            Refer to Rules 460 and 461 regarding requests for acceleration. Please allow adequate
time for us to review any amendment prior to the requested effective date of the registration
statement.
            Please contact Jenny O'Shanick at 202-551-8005 or Jay Ingram at 202-551-3397 with
any questions.
Sincerely,
Division of Corporation Finance
Office of Manufacturing
cc:John J. Wolfel

CORRESP
1
filename1.htm

22nd Century Group, Inc.

321 Farmington Road

Mocksville, NC 27028

(716) 270-1523

November 6, 2024

VIA EDGAR

Securities and Exchange Commission Division of Corporation
Finance

100 F Street, NE Washington, DC 20549

Attn:	Mr. Patrick Fullem

  Re:
  22nd Century Group, Inc.

  Registration Statement on Form S-3

  Filed November 1,
2024

  File No. 333-282963

Acceleration Request

    Requested Date: Friday, November 8, 2024

    Requested Time: 4:30 P.M. Eastern time

Ladies and Gentlemen:

Pursuant to Rule 461 promulgated under
the Securities Act of 1933, as amended, 22nd Century Group, Inc. (the “Company”) hereby requests that the effectiveness of
the above-referenced Registration Statement on Form S-3 be accelerated so that such Registration Statement will become effective at 4:30
p.m., Eastern Time, on Friday, November 8, 2024, or as soon thereafter as practicable. The Company respectfully requests that you notify
Mr. John Wolfel of Foley & Lardner, LLP of such effectiveness by a telephone call to (904) 359-8778.

Sincerely,

22ND CENTURY GROUP, INC.

  By:
  /s/ Jonathan P. Staffeldt

  Jonathan P. Staffeldt

  General Counsel

  cc:
  John J. Wolfel of Foley Lardner, LLP

November 6, 2024
Lawrence Firestone
Chief Executive Officer
22nd Century Group, Inc.
321 Farmington Rd
Mocksville, NC 27028
Re:22nd Century Group, Inc.
Registration Statement on Form S-3
Filed November 1, 2024
File No. 333-282963
Dear Lawrence Firestone:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Patrick Fullem at 202-551-8337 with any questions.
Sincerely,
Division of Corporation Finance
Office of Manufacturing
cc:John J. Wolfel

CORRESP
1
filename1.htm

22nd Century Group, Inc.

321 Farmington Road

Mocksville, NC 27028

(716) 270-1523

September 23, 2024

VIA EDGAR

Securities and Exchange Commission Division of Corporation
Finance

100 F Street, NE Washington, DC 20549

    Attn:
    Jenny O’Shanick

  Re:
  22nd Century Group, Inc.

  Registration Statement on Form S-3

  File No. 333-282157

    Acceleration Request

    Requested Date: Wednesday, September 25, 2024

    Requested Time: 9:30 A.M. Eastern time

Ladies and Gentlemen:

Pursuant to Rule 461 promulgated under
the Securities Act of 1933, as amended, 22nd Century Group, Inc. (the “Company”) hereby requests that the effectiveness of
the above-referenced Registration Statement on Form S-3 be accelerated so that such Registration Statement will become effective at 9:30
a.m., Eastern Time, on Wednesday, September 25, 2024, or as soon thereafter as practicable. The Company respectfully requests that you
notify Mr. John Wolfel of Foley & Lardner, LLP of such effectiveness by a telephone call to (904) 359-8778.

Sincerely,

22ND CENTURY GROUP, INC.

  By:
  /s/ Jonathan P. Staffeldt

  Jonathan P. Staffeldt

  General Counsel

  cc:
   John J. Wolfel of Foley Lardner, LLP

September 20, 2024
Lawrence D. Firestone
Chief Executive Officer
22nd Century Group, Inc.
321 Farmington Rd
Mocksville, NC 27028
Re:22nd Century Group, Inc.
Registration Statement on Form S-3
Filed on September 16, 2024
File No. 333-282157
Dear Lawrence D. Firestone:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you that
the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Jenny O'Shanick at 202-551-8005 with any questions.
Sincerely,
Division of Corporation Finance
Office of Manufacturing
cc:John J. Wolfel

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22nd Century Group, Inc.

321 Farmington Rd

Mocksville, NC 27028

August 8, 2024

VIA EDGAR

Office of Manufacturing

Division of Corporation Finance

Securities and Exchange Commission

100 F Street, N.E.

Washington, D.C. 20549

Attention: Patrick Fullem

 Re: 22nd Century Group, Inc. (the “Company”)

Offering Statement on Form 1-A

Filed August 2, 2024 (the “Offering Statement”)

Commission File No. 024-12477

Dear Mr. Fullem:

On behalf of the Company, I respectfully request that the qualification
date of the Offering Statement be accelerated and that the Offering Statement be declared qualified August 13, 2024, at 4:30 p.m. EST,
or as soon thereafter as is reasonably practicable.

In making this request, the Company acknowledges the following:

 · should the Securities and Exchange Commission (the “Commission”)
or the Staff, acting pursuant to delegated authority, declare the filing qualified, it does not foreclose the Commission from taking any
action with respect to the filing;

 · the action of the Commission or the staff, acting pursuant to delegated authority,
to declare the filing qualified does not relieve the Company from its full responsibility for the adequacy and accuracy of disclosure
in the filing; and

 · the Company may not assert staff comments and/or qualification as a defense
in any proceeding initiated by the Commission or any person under the federal securities law of the United States.

Very truly yours,

    /s/ Lawrence D. Firestone

    Lawrence D. Firestone

    Chief Executive Officer

    22nd Century Group, Inc.

August 7, 2024
Lawrence Firestone
Chief Executive Officer
22nd Century Group, Inc.
321 Farmington Road
Mocksville, NC 27028
Re:22nd Century Group, Inc.
Offering Statement on Form 1-A
Filed August 2, 2024
File No. 024-12477
Dear Lawrence Firestone:
            This is to advise you that we do not intend to review your offering statement.
            We will consider qualifying your offering statement at your request. If a participant in
your offering is required to clear its compensation arrangements with FINRA, please have
FINRA advise us that it has no objections to the compensation arrangements prior to
qualification.
            We remind you that the company and its management are responsible for the accuracy and
adequacy of their disclosures, notwithstanding any review, comments, action or absence of action
by the staff. We also remind you that, following qualification of your Form 1-A, Rule 257 of
Regulation A requires you to file periodic and current reports, including a Form 1-K which will
be due within 120 calendar days after the end of the fiscal year covered by the report.
            Please contact Patrick Fullem at 202-551-8337 with any questions.
Sincerely,
Division of Corporation Finance
Office of Manufacturing
cc:John J. Wolfel

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22nd Century Group, Inc.

321 Farmington Road

Mocksville, NC 27028

(716) 270-1523

May 6, 2024

VIA EDGAR

Securities and Exchange Commission Division of Corporation
Finance

100 F Street, NE Washington, DC 20549

    Attn:
    Mr. Eranga Dias

    Re:
    22nd Century Group, Inc.

Registration Statement on Form S-3 Filed May 1, 2024

File No. 333-279046

Acceleration Request

Requested Date: Thursday, May 9, 2024

Requested Time: 9:30 A.M. Eastern time

Ladies and Gentlemen:

Pursuant to Rule 461 promulgated under
the Securities Act of 1933, as amended, 22nd Century Group, Inc. (the “Company”) hereby requests that the effectiveness of
the above-referenced Registration Statement on Form S-3 be accelerated so that such Registration Statement will become effective at 9:30
a.m., Eastern Time, on Thursday, May 9, 2024, or as soon thereafter as practicable. The Company respectfully requests that you notify
Mr. John Wolfel of Foley & Lardner, LLP of such effectiveness by a telephone call to (904) 359-8778.

Sincerely,

22ND CENTURY GROUP, INC.

    By:
    /s/ Jonathan P. Staffeldt

    Jonathan P. Staffeldt

    General Counsel

cc: John J. Wolfel of Foley Lardner, LLP

United States securities and exchange commission logo
May 6, 2024
Lawrence Firestone
Chief Executive Officer
22nd Century Group, Inc.
321 Farmington Rd
Mocksville, NC 27028
Re:22nd Century Group, Inc.
Registration Statement on Form S-3
Filed May 1, 2024
File No. 333-279046
Dear Lawrence Firestone:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Eranga Dias at 202-551-8107 with any questions.
Sincerely,
Division of Corporation Finance
Office of Manufacturing

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22nd Century Group,
Inc.

500 Seneca Street,
Suite 507

Buffalo, NY 14204

April 26, 2023

VIA EDGAR

Securities and Exchange Commission

100 F Street, N.E.

Washington, D.C. 20549

 Re: 22nd
                                            Century Group, Inc.

    Registration
                                            Statement on Form S-3

    File
                                            Number 333-271217

Ladies and Gentlemen:

22nd
Century Group, Inc. (the “Company”) hereby requests that the effectiveness of the above-referenced registration statement
on Form S-3 be accelerated so that it will become effective at 4:00 p.m. Eastern time on April 27, 2023, or as soon thereafter as practicable.

Please
telephone the undersigned at (561) 271-4047 or Flora R. Perez of Greenberg Traurig, P.A. at (954) 768-8210 if you have any questions
with respect to the foregoing.

    Very truly yours,

    22ND CENTURY GROUP, INC.

    By:
    /s/ Peter Ferola

    Name:
    Peter Ferola

    Title:
    Chief Legal Officer

United States securities and exchange commission logo
April 14, 2023
Peter Ferola
Chief Legal Officer
22nd Century Group, Inc.
500 Seneca Street, Suite 507
Buffalo, New York, 14204
Re:22nd Century Group, Inc.
Registration Statement on Form S-3
Filed on April 11, 2023
File No. 333-271217
Dear Peter Ferola:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Bradley Ecker at (202) 551-4985 with any questions.
Sincerely,
Division of Corporation Finance
Office of Manufacturing

CORRESP
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22nd Century Group, Inc.

500 Seneca Street, Suite 507

Buffalo, New York 14204

(716) 270-1523

March 29, 2023

VIA EDGAR

Securities and Exchange Commission Division of Corporation
Finance

100 F Street, NE Washington, DC 20549

  Attn: Mr. Eranga Dias

  Re: 22nd Century Group, Inc.

 Registration Statement on Form S-3 Filed March 10, 2023

 File No. 333-270473

Acceleration Request

 Requested Date: Friday, March 31, 2023

 Requested Time: 4:30 P.M. Eastern time

Ladies and Gentlemen:

Pursuant to Rule 461 promulgated under
the Securities Act of 1933, as amended, 22nd Century Group, Inc. (the “Company”) hereby requests that the effectiveness of
the above-referenced Registration Statement on Form S-3 be accelerated so that such Registration Statement will become effective at 4:30
p.m., Eastern Time, on Friday, March 31, 2023, or as soon thereafter as practicable. The Company respectfully requests that you notify
Mr. John Wolfel of Foley & Lardner, LLP of such effectiveness by a telephone call to (904) 359-8778.

Sincerely,

    22ND
    CENTURY GROUP, INC.

    By:
    /s/
    Peter Ferola

    Peter
    Ferola

    Chief
    Legal Officer

cc: John J. Wolfel of Foley Lardner, LLP

United States securities and exchange commission logo
March 20, 2023
Peter Ferola
Chief Legal Officer
22nd Century Group, Inc.
500 Seneca Street, Suite 507
Buffalo, New York 14204
Re:22nd Century Group, Inc.
Registration Statement on Form S-3
Filed March 10, 2023
File No. 333-270473
Dear Peter Ferola:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Eranga Dias at 202-551-8107 with any questions.
Sincerely,
Division of Corporation Finance
Office of Manufacturing

CORRESP
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22nd
CENTURY GROUP, INC.

500 Seneca Street, Suite 507

Buffalo, New York, 14204

September 12, 2022

VIA EDGAR Correspondence

United States Securities and Exchange Commission

Division of Corporation Finance

Office of Manufacturing

100 F. Street, N.E.

Washington, D.C. 20549

Attn: Mr. Gregory Herbers

    Re:
    Acceleration of Effective Date

    22nd Century Group, Inc.

    Registration Statement on Form S-3 (File No. 333-267266)

Ladies and Gentlemen:

Pursuant to Rule 461 under
the Securities Act of 1933, as amended (the “Securities Act”), 22nd Century Group, Inc. (the “Registrant”),
hereby requests that the effective date of the above-referenced Registration Statement (the “Registration Statement”), be
accelerated so that the Registration Statement becomes effective under the Securities Act by 4:00 p.m., Eastern Time, on September 14,
2022, or as soon thereafter as practicable. For purposes of Rules 460 and 461 of the Securities Act, there is no underwriter.

The Registrant respectfully
requests that you notify Mr. John Wolfel of Foley & Lardner LLP of such effectiveness by a telephone call to (904) 359-8778.

    Very truly yours,

    22nd Century Group, Inc.

    By:
    /s/ Steven P. Przybyla

    Steven P. Przybyla

    Vice President, General Counsel and Secretary

United States securities and exchange commission logo
September 12, 2022
James Mish
Chief Executive Officer
22nd Century Group, Inc.
500 Seneca Street, Suite 507
Buffalo, New York, 14204
Re:22nd Century Group, Inc.
Registration Statement on Form S-3
Filed September 2, 2022
File No. 333-267266
Dear Mr. Mish:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Gregory Herbers at 202-551-8028 with any questions.
Sincerely,
Division of Corporation Finance
Office of Manufacturing
cc:       John Wolfel

CORRESP
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22nd Century
Group, Inc.

8560 Main Street, Suite 4

Williamsville, New York 14221

July 27, 2020

VIA EDGAR

United States Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, D.C. 20549

Attention: Erin Purnell

 Re: 22nd Century Group, Inc.

Registration Statement on Form S-3 (Registration
No. 333-239981)

Ms. Purnell:

Pursuant to Rule 461
under the Securities Act of 1933, as amended, the undersigned registrant, 22nd Century Group, Inc., hereby requests that the above-referenced
Registration Statement be declared effective at 12:00 p.m., eastern time, on July 30, 2020, or as soon as practicable thereafter.

    Very truly yours,

    22nd Century Group, Inc.

    By:
    /s/ James A. Mish

    James A. Mish
Chief Executive Officer

United States securities and exchange commission logo
July 27, 2020
James Mish
Chief Executive Officer
22nd Century Group, Inc.
8560 Main Street, Suite 4
Williamsville, New York 14221
Re:22nd Century Group, Inc.
Registration Statement on Form S-3
Filed July 21, 2020
File No. 333-239981
Dear Mr. Mish:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Erin Purnell at 202-551-3454 with any questions.
Sincerely,
Division of Corporation Finance
Office of Manufacturing

CORRESP
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22ND CENTURY GROUP, INC.

9530 Main Street

Clarence, New York 14031

November 21, 2017

VIA EDGAR

United States Securities and Exchange Commission

Division of Corporation Finance – Mail Stop 3561

100 F Street, NE

Washington, D.C. 20549

Attn: Ms. Julie Griffith

 Re: 22nd Century Group, Inc.

Registration Statement on Form S-3 (Registration
No. 333-221270)

Ms. Griffith:

In accordance with Rules
460 and 461 under the Securities Act of 1933, as amended, the undersigned registrant, 22nd Century Group, Inc. (the “Registrant”),
hereby requests acceleration of effectiveness of its above-referenced Registration Statement to 12:00 p.m., eastern time, on November
28, 2017, or as soon as practicable thereafter.

    Very truly yours,

    22nd Century Group, Inc.

    By:
    /s/ John T. Brodfuehrer

    John T. Brodfuehrer

    Chief Financial Officer

Mail Stop 3561       November 21, 2017

Henry Sicig nano, III
Chief Executive Officer
22nd Century Group, Inc.
9530 Main Street
Clarence, NY 14031

Re:  22nd Century Group, Inc.
Registration Statement on Form S -3
Filed November 1, 2017
File No. 333 -221270

Dear Mr. Sicig nano :

This is to advise you that we have not  reviewed and will not review your registration
statement .

Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.

Please  contact Julie Griffith  at 202-551-3267  with any questions.

Sincerely,

 /s/ Justin Dobbie

Justin Dobbie
Legal Branch Chief
Office of Transportation and Leisure

May 15 , 201 4

Via E -mail
Joseph Pandolfino
Chief Executive  Officer
22nd Century Group, Inc .
9530 Main Street
Clarence, NY 14031

Re: 22nd Century Group, Inc .
  Registration Statement on Form S-3
Filed  April 18 , 2014
  File No.  333-195386

Dear Mr. Pandolfino :

We have limited our review of your registration statement to those issues we have
addressed in our comments.  In  some of our comments, we may ask you to provide us with
information so we may better understand your disclosure.

Please respond to this letter by amending your registration statement and providing the
requested information .  Where you do not believe our comments apply to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why in your
response.

After reviewing any amendment to your registration statement and the information you
provide in response to these  comments , we may have  additional comments.

Calculation of Registration Fee Table

1. We note your disclosure in footnote 2 to this table that any securities registered under the
registration statement may be sold separately or as units.  Please explain to us why you
are not registering the se units.  If you do intend to register them, please revise the
registration statement and opinion accordingly .

Description of Stock Purchase Contracts and Stock Purchase Units , page 1 6

2. We note that you contemplate offering  stock purchase units which  may consist of other
securities or debt obligations of third parties .  Please explain to us what plans you have
for issuing such stock purchase units and provide us with an example of the disclosure
you intend to provide about these  securities in connection with any such offering.
Additionally, to the extent that you offer stock purchase units consisting of securities or
debt obligations of third parties, please have counsel revise its legality opinion to address

Joseph Pandolfino
22nd Century Group, Inc .
May 15 , 2014
Page 2

 the legality of eac h component of the stock purchase unit.  Alternatively, please remove
any language regarding the offering of stock purchase units consisting of securities or
debt obligations of third parties.

Exhibit 5.1

3. We note that the legality opinion is limited to Nevada law yet the indenture is governed
by New York law.  As debt securities are contractual obligations, counsel must opine on
the law of the jurisdiction governing the indenture  to determine whether or not  it is an
enforceable contract and, therefore, a binding obligation .  Please either revise the legality
opinion to state that it also covers the laws of the State of New York or provide a separate
opinion from New York counsel.

We urge all persons who are responsible for the accuracy and adequacy of the disclosure
in the filing to be certain that the filing includes the information the Securities Act of 193 3 and
all applicable Securities  Act rules require.   Since the company and its management are in
possession of all facts relating to a company’s disclosure, they are responsible for the accuracy
and adequacy of the disclosures they have made.

Notwithstanding our comments, in the event you request acceleration of the effective date
of the pending registration statement please provide a written statement from the company
acknowledging that:

 should the Commission or the staff, acting pursuant to delegated authority, declare the
filing effective, it does not foreclose the Commissi on from taking any action with respect
to the filing;

 the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and acc uracy of the disclosure in the filing; and

 the company may not assert staff comments and the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.

Please refer to Rules 460 and 461 regarding requests for  acceleration .  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation
of the fact that those requesting acceleration are aware of their respective responsibilities under
the Securities Act of 1933 and the Securities Exchange Act of 1934 as they relate to the proposed
public offering of the securities specified in the above registration statement.  Please allow
adequate time  for us to revie w any amendment prior to the requested effective date of the
registration statement.

Joseph Pandolfino
22nd Century Group, Inc .
May 15 , 2014
Page 3

 Please contact Ada D. Sarmento at (202) 551-3798 or me at (202) 551-3859  with any
questions.

Sincerely,

 /s/ John Dana Brown

John Dana Brown
Attorney Advisor

cc: Via E -mail
 Michael B. Kirwan , Esq.

CORRESP
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22nd Century Group, Inc.

9530 Main Street

Clarence, New York 14031

Tel.: 716-270-1523

March 27, 2013

Via EDGAR

Securities and Exchange Commission

100 F Street, N.E.

Washington, D.C. 20549

 Re: 22nd Century Group, Inc.

Registration Statement on Form S-1

Commission File No. 333-186449

Ladies and Gentlemen:

The undersigned registrant hereby requests,
pursuant to Rules 460 and 461 under the Securities Act of 1933, as amended, that the effective date of the above captioned Registration
Statement (File No. 333-186449), as amended by any pre-effective amendments thereto, be accelerated to:

4:00 P.M., EST, on March 29, 2013

or as soon as practicable thereafter.

The Company hereby acknowledges that:

 · should the Commission or the Staff, acting pursuant to delegated authority,
declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

 · the action of the Commission or the Staff, acting pursuant to delegated
authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy
of the disclosure in the filing; and

 · the Company may not assert Staff comments and the declaration of effectiveness
as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

22nd Century Group, Inc.

By: /s/ Joseph Pandolfino

       Joseph Pandolfino

       Chief Executive Officer

CORRESP
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        22nd Century Group, Inc.

March 8, 2013

VIA EDGAR

        United States Securities and Exchange Commission

        Division of Corporation Finance

        100 F Street NE

        Washington, DC 20549

        Attn: Max A. Webb

 Re: 22nd Century Group, Inc.

Registration Statement on Form S-1

Filed February 4, 2013

File No.: 333-186449

Dear Mr. Webb:

The following information
is furnished in response to the comments in your letter to Joseph Pandolfino regarding 22nd Century Group, Inc. (the “Company”)
dated February 28, 2013. In accordance with our subsequent discussions with your colleague, Mr. Donald E. Field, this response
has been limited to the Staff’s Comment #2.

Comment #2 has been
reproduced below in bold italics, followed by our response.

2.	We
note that you are registering the resale of 27,500,000 shares of your common stock on a delayed or continuous basis pursuant to
Rule 415 of the Securities Act of 1933. Given the size of the offering relative to the number of shares of your common stock outstanding
held by non-affiliates, the nature of the offering and the selling stockholders, the transaction appears to be a primary offering.
Because you are not eligible to conduct a primary offering on Form S-3, you are not eligible to conduct a primary at-the-market
offering under Rule 415(a)(4) of the Securities Act of 1933. If you disagree with our analysis, please advise regarding your basis
for determining that the transaction is appropriately characterized as a transaction that is eligible to be made under Rule 415(a)(1)(i)
of the Securities Act of 1933. In your analysis, please address the following among any other relevant factors:

 · The number of shares of your common stock outstanding held by non-affiliates prior to the private
placement of the Series A-1 Preferred Stock and Series A, B and C Warrants on January 11, 2013;

 · The dollar value of the shares of common stock registered in relation to the proceeds that you
received from the selling stockholders for the securities, excluding amounts of proceeds that were returned (or will be returned)
to the selling stockholders and/or their affiliates in fees or other payments;

 9530 Main Street • Clarence,
New York 14031 • TEL 716-270-1523 • FAX 716-877-3064 • www.xxiicentury.com

United States Securities and Exchange Commission

Page 2

 · The relationship of each selling stockholder with the company, including an analysis of whether
each selling stockholder is an affiliate of the company; and

 · Whether or not any of the selling stockholders are in the business of buying and selling securities.

Response

Although we believe
that the offering is a valid secondary offering, the Company and selling stockholders have decided to reduce the size of the offering
significantly. The Company and selling stockholders will amend the Registration Statement to register the 4,166,666 shares of common
stock initially issuable upon conversion of the Series A-1 Preferred Stock and 2,083,334 shares of common stock issuable upon exercise
of the Series B Warrants. Although this amount represents 37.8% of the Company’s pre-transaction float and 15.2% of our total
shares of common stock outstanding after issuance of such shares, since the Series A-1 Preferred Stock and warrants contain exercise
and conversion limitations, the selling stockholders will never own in excess of 9.99% of the Company’s outstanding shares
of common stock.

Analysis

For the reasons set
forth below, the Company respectfully submits that the offering to be registered pursuant to the Registration Statement is eligible
to be made on a shelf basis under Rule 415(a)(1)(i) and that the selling stockholders are not “underwriters” within
the meaning of Section 2(a)(11) of the Securities Act of 1933, as amended (the “Act”).

As an initial matter,
the Company wishes to assert that none of the two selling stockholders is a conduit for the Company, but rather purchased their
securities for their own account. Each of the selling stockholders were immediately at market risk once their securities were purchased,
and such market risk has continued through the time of filing the Registration Statement. Each of the selling stockholders executed
a Securities Purchase Agreement (as described below) for the purchase of their securities which contained representations of the
selling stockholders that stated, among other provisions, that each selling stockholder was purchasing the securities as principal
for its own account for investment only and not with a view toward, or for resale in connection with, the public sale or any distribution
thereof. There is no evidence to suggest that those representations are false and the Company respectfully submits that there is
no basis for concluding that the selling stockholders do not have the intention or ability to hold their shares for investment
purposes for an indefinite period.

There are a number
of reasons why investors would want purchased shares to be registered other than to effect an immediate resale. Many private investment
funds are required to mark their portfolios to market. If portfolio securities are not registered, such investors are typically
required to mark down the book value of those securities to reflect an illiquidity discount. That portfolio valuation does not
depend on whether the selling stockholders intend to dispose of their shares or to hold them for an indefinite period. In addition,
the selling stockholders are fiduciaries for their limited partners and other investors in their funds. As such, the selling stockholders
have a common law duty to act prudently. Accordingly, the Company understands that the selling stockholders wish to have their
securities in a more liquid form, whereas not registering the shares could prevent them from taking advantage of market opportunities
or from liquidating their investment if there is a fundamental shift in their investment judgment about the Company. Finally, registered
shares of many issuers are eligible to be used as margin collateral under the Federal Reserve’s margin regulations. Restricted
securities do not qualify as “margin stock.”

United States Securities and Exchange Commission

Page 3

Transaction Overview

On January 11, 2013,
the Company entered into a Securities Purchase Agreement with certain accredited investors indentified therein (referred to herein
as the selling stockholders), whereby the Company sold 2,500 shares of newly created Series A-1 10% Convertible Preferred Stock
(the “Series A-1 Preferred Stock”) and Warrants (as defined below) for an aggregate purchase price of $2,500,000. The
Company also entered into a Registration Rights Agreement with the selling stockholders whereby the Company agreed to file a registration
statement to register the resale of 200% of the shares of common stock that are potentially issuable under each of
the securities described below as well as anticipated stock dividends over a three year period. The dividends are payable on the
Series A-1 Preferred Stock in cash or stock, at the Company’s option.

The shares of Series
A-1 Preferred Stock are initially convertible into a total of 4,166,666 shares of the Company’s common stock at a conversion
price of $0.60 per share (the “Conversion Price”), subject to future adjustments. The Series A-1 Preferred Stock will
pay a 10.0% annual cash dividend and will have a liquidation preference equal to the stated value of the Series A-1 Preferred Stock
of $1,000 per share plus any accrued and unpaid dividends thereon. The Series A-1 Preferred Stock is not entitled to vote in the
election of directors and generally has no voting rights, other than with respect to certain extraordinary events, such as an amendment
to the rights, preferences or privileges of the Series A-1 Preferred Stock or any liquidation or dissolution of the Company.

The Conversion Price
of the Series A-1 Preferred Stock is subject to adjustment as follows:

    (i)
    on the effective date of a registration statement, the Conversion Price will be reduced to the lesser of (1) the then Conversion Price, as adjusted and taking into consideration any prior resets, (2) the greater of $0.35 (subject to adjustment for reverse and forward stock splits and the like) and 70% of the average of the five (5) trading day volume weighted average prices (“VWAPs”) immediately prior to each such effective date or (3) $0.60 (subject to adjustment for forward and reverse stock splits and the like);

    (ii)
    if on the 180th day immediately following the closing date of January 11, 2013 (the “Closing Date”), 70% of the average of the five (5) trading day VWAPs immediately prior to such date is less than the then Conversion Price, then on such 180th day the Conversion Price shall be reduced to the lesser of (1) the then Conversion Price, as adjusted and taking into consideration any prior resets, (2) the greater of $0.15 (subject to adjustment for reverse and forward stock splits and the like) and 70% of the average of the five (5) trading day VWAPs immediately prior to each such 180th day immediately following the Closing Date or (3) $0.35 (subject to adjustment for forward and reverse stock splits and the like); and

    (iii)
    if all of the shares required to be registered are not registered pursuant to an effective registration statement within the 120th day anniversary of the Closing Date, then on the 180th day and 270th day following the Closing Date, the Conversion Price shall be reduced to the lesser of (1) the then Conversion Price, as adjusted and taking into consideration any prior resets, (2) the greater of $0.15 (subject to adjustment for reverse and forward stock splits and the like) and 70% of the average of the five (5) trading day VWAPs immediately prior to each such date or (3) $0.35 (subject to adjustment for forward and reverse stock splits and the like).

United States Securities and Exchange Commission

Page 4

We also issued to the
selling stockholders a Series A warrant (the “Series A Warrant”), a Series B warrant (the “Series B Warrant”),
and a Series C warrant (the “Series C Warrant”) (with the Series A Warrant, Series B Warrant and Series C Warrant being
collectively referred to herein as the “Warrants,” and together with the Series A-1 Preferred Stock, the “Securities”).
None of the Warrants have adjustments to their exercise price based on the market price of the Company’s common stock rather
each of the Warrants have standard anti-dilution language for future issuances of shares at a price under the conversion price
of such Warrants.

The Series A Warrants
allow the selling stockholders the right to acquire up to an additional 4,166,666 shares of the Company’s common stock at
an exercise price of approximately $0.72 per share over a period of five (5) years, subject to anti-dilution provisions. The Series
A Warrants also allow for such warrants to be exercised on a cashless basis.

The Series B Warrants
allows the selling stockholders a one-year period to exercise an overallotment option as contained in the Series B Warrant to purchase
up to an additional aggregate of 2,083,334 shares of the Company’s common stock at a price of $0.60 per share, subject to
anti-dilution provisions. The Series B Warrants may not be exercised on a cashless basis except only in certain limited circumstances.

In the event the selling
stockholders exercise, in whole or in part the overallotment option as contained in the Series B Warrants, then the selling stockholders
shall have the right to exercise on a pro rata basis the portion of the Series C Warrants issued to the selling stockholders to
acquire up to an additional aggregate of 2,083,334 shares of the Company’s common stock at an exercise price of approximately
$0.72 per share over a period of five (5) years, subject to anti-dilution provisions. The Series C Warrants allow for such warrants
to be exercised on a cashless basis.

The Series A-1 Preferred
Stock and the Warrants contain exercise and conversion limitations providing that a holder thereof may not convert or exercise
(as the case may be) to the extent that, if after giving effect to such conversion or exercise (as the case may be), the holder
or any of its affiliates would beneficially own in excess of 9.99% of the outstanding shares of common stock immediately after
giving effect to such conversion or exercise (as the case may be). This 9.99% blocker is binding and valid (e.g., the provisions
are non-waivable, enforceable, established in the Company’s Certificate of Designations and is applicable to affiliates and
assigns) and effectively eliminates the right of the selling stockholders to acquire in excess of 9.99% of the Company’s
outstanding common stock. Such “blockers” have been upheld by many courts and the factors that indicate that a conversion
cap is binding and valid were discussed in the Brief of the Securities and Exchange Commission, Amicus Curiae in Levy v. Southbrook
International Investments, Ltd. (Sep. 14, 2009).

United States Securities and Exchange Commission

Page 5

Analysis of Purchase Price in Relation
to Proceeds Received by the Company

The Company sold 2,500
shares of Series A-1 Preferred Stock to the selling stockholders for an aggregate purchase price of $2,500,000. The shares of Series
A-1 Preferred Stock are initially convertible into a total of 4,166,666 shares of the Company’s common stock at a conversion
price of $0.60 per share, subject to future adjustments. The Series A Warrants allow the selling stockholders the right to acquire
up to an additional 4,166,666 shares of the Company’s common stock at an exercise price of approximately $0.72 per share
over a period of five (5) years, subject to anti-dilution provisions. The Series A Warrants also allow for such warrants to be
exercised on a cashless basis. The proceeds received by the Company is as follows:

    Proceeds to Company Without Cashless Exercise of Series A Warrants
    Proceeds to Company With Cashless Exercise of Series A Warrants

    Series A-1 Preferred Stock
    $2,500,000
    $2,500,000

    Series A Warrants
    $2,999,999
    N/A

    Total
    $5,499,999
    $2,500,000

The Series B Warrants
allows the selling stockholders a one-year period to exercise an overallotment option as contained in the Series B Warrant to purchase
up to an additional aggregate of 2,083,334 shares of the Company’s common stock at a price of $0.60 per share, subject to
anti-dilution provisions. The Series B Warrants may not be exercised on a cashless basis except only in certain limited
circumstances (if the shares issuable upon exercise are not registered within 18 months following the Closing Date). In the
event the selling stockholders exercise, in whole or in part the overallotment option as contained in the Series B Warrants,
then the selling stockholders shall have the right to exercise on a pro rata basis the portion of the Series C Warrants issued
to the selling stockholders to acquire up to an additional aggregate of 2,083,334 shares of the Company’s common stock at
an exercise price of approximately $0.72 per share over a period of five (5) years, subject to anti-dilution provisions. The Series
C Warrants allow for such warrants to be exercised on a cashless basis. If the Series B Warrants are exercised, the additional
proceeds to the Company are as follows.

    Proceeds to Company Without Cashless Exercise of Series A and C Warrants
    Proceeds to Company With Cashless Exercise of Series A and C Warrants

    Series A-1 Preferred Stock
    $2,500,000
    $2,500,000

    Series A Warrants
    $2,999,999
    N/A

    Series B Warrants
    $1,250,000
    $1,250,000

    Series C Warrants
    $1,500,000
    N/A

    Total
    $8,249,999
    $3,750,000

The Registration Rights
Agreement with the selling stockholders required the Company to register the resale of 200% the shares of com

February 28 , 2013

Via E -mail
Joseph Pandolfino
Chief Executive Officer
22nd Century Group, Inc.
9530 Main Street
Clarence, NY  14031

Re: 22nd C entury Group, Inc.
  Registration Statement on Form S-1
Filed  February 4, 2013
  File No.  333-186449

Dear Mr. Pandolfino :

We have limited our review of your registration statement to those issues we have
addressed in our comments.  In  some of our comments, we may ask you to provide us with
information so we may better understand your disclosure.

Please respond to this letter by amending your registration statement and providing the
requested information .  Where you do not believe our comments apply to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why in your
response.

After reviewing any amendment to your registration statement and the information you
provide in response to these  comments, we may have  additional comments.

General

1. Prior to printing and distribution of the preliminary prospectus, please provide us with
mock -ups of any pages that include any pictures or graphics to be presented.
Accompanying captions, if any, should also be provided.  We may have comments after
reviewing the material.

Registration Statement Cover Page

2. We note that you are registering the resale of 27,500,000 shares of your common stock
on a delayed or continuous basis pursuant to Rule 415 of the Securities Act of 1933.
Given the size of the offering relative to the number of shares of your common stock
outstanding held by non -affiliates, the nature of the offering and the selling stockholders,
the transaction appears to be a primary offering .  Because you are not eligible to conduct

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 2

 a primary offering on Form S -3, you are not eligible to conduct a primary at -the-market
offering under Rule 415(a)(4) of the Securities Act of 1933 .  If you disagree with our
analysis, please advise regarding  your basis for determining that the transaction is
appropriately characterized as a transaction that is eligible to be made under Rule
415(a)(1)(i) of the Securities Act of 1933 .  In your analysis, please address the following
among any other relevant factors :

 The number of shares of your common stock outstanding held by non -affiliates prior
to the private placement of the Series A -1 Preferred Stock and Series A, B and C
Warrants on January 11, 2013;
 The dollar value of the shares of common stock registered i n relation to the proceeds
that you received from the selling stockholders for the securities, excluding amounts
of proceeds that were returned (or will be returned) to the selling stockholders and/or
their affiliates in fees or other payments;
 The relationship of each selling stockholder with the company, including an analysis
of whether each selling stockholder is an affiliate of the company; and
 Whether or not any of the selling stockholders are in the business of buying and
selling securities.

3. We note the reference to Rule 416  of the Securities Act of 1933  in footnote 1 to the fee
table.  Please confirm that you understand that issuing additional shares because of
changes in the stock price is not covered by the transactions involving Rule 416.

Prospectus Summary, page 1

Overview, page 1

4. We note your disclosure in the first and second paragraphs only briefly discusses your
two primary lines of business related to (i) smoking cessation products and (ii) premium
cigarettes and modified risk tobacco products.  Please revise to provide a more detailed
summary of your business and current operations.

5. Additionally, we find missing from the summary the picture of the company revealed in
the Risk Factor  and Business sections on page 7 and 27  of a company facing financial
difficulties  and which has recently limited certain operations .  For example, we note that
you have suspended further clinical trials for FDA approval of your X -22 smoking
cessation product and that you will need significant additi onal capital to complete the
FDA authorization process for your modified risk cigarettes.  We also note that you are
limited in your abilities to raise additional capital due to your outstanding Series A -1
Preferred Stock.  Please revise the summary so tha t the narrative discussion reflects what
appears to be a challenging time for the company .

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 3

 6. Please revise to disclose in the summary the failure of X -22 in the most recent test and
the effect that failure has had upon your situation.

7. We note your disclos ure in the second paragraph that in March 2011 you introduced two
of your own products, RED SUN and MAGIC cigarettes, into the U.S. market.  Please
revise this paragraph to disclose the revenue and net income or loss that you have
realized from these produ cts during the most recent audited and interim period s.  To the
extent these products have only been introduced into the U.S. market in a limited
capacity, please revise to disclose such fact.

Current Financial Condition, page 1

8. Please revise the first paragraph to disclose that your auditors  have  issued a going
concern opinion on your audited financial statements.

9. Please bold the last sentence of the first paragraph and update in the  next amendment.

10. We note your disclosure in t he second paragraph that your expected capital requirements
over the next 12 months without any extraordinary expenses are approximately $1
million.  We also note that your September 30, 2012 balance sheet list s significant
accounts payable, accrued expens es, a demand bank loan, and notes  payable and
convertible notes payable as compared to your limited cash position.  In this regard, we
note that $1.3 million of convertible notes payable mature in April of 2013.  Please
confirm that this section accurately  discloses your near -term capital requirements and
detail the requirements and expected uses of such funds.

11. We note your disclosure in the fourth risk factor on page 7 that the certificate of
designation of your Series A -1 Preferred Stock contains restric tive covenants that limit
your ability to incur or assume additional debt or provide guarantees in respect of
obligations of other persons.  Please revise the second paragraph to disclose this
limitation on your ability to raise capital and include a cross  reference to the fourth risk
factor on page 7.

Risk Factors, page 7

12. We note your disclosure in the first paragraph of this section of “[t]he following
discussion addresses those risks that management believes are the most significant,
although there may  be other risks that could arise or may prove to be more significant
than expected, that may affect our operations or financial results.”  All material risks
should be discussed in this section.  This section should not reference unknown or
immaterial risks.  Please revise  this paragraph to clarify that you have discu ssed all
known material risks.

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 4

 We have had a history of losses, and we may be unable to achieve or sustain profitability, page 7

13. We note your disclosure that you expect to continue to incur net losses and negative
operating cash flows in the foreseeable future.  Please revise to quantify the amount of
net losses that you expect to incur in to the foreseeable future or alternatively qu antify
your monthly “burn rate.”

14. We note your disclosure that you will need to spend significant capital to fulfill planned
operating goals and conduct clinical studies, achieve regulatory approvals and, subject to
such approvals, successfully produce products for commercialization.  Plea se revise to
quantify these long-term capital requirements .  Please also revise the Overview and
Current Financial Condition sections  on page 1 to discuss and quantify such long-term
capital requirements.

Business, page 27

15. We note your disclosure through out this section with respect to your future business
plans  and products , such as completing additional clinical trials related to X -22, obtaining
FDA approval of X -22 as a smoking cessation product and obtaining FDA approval of
Brand A and Brand B cigaret tes as modified risk tobacco products.  To the extent that
you discuss future business plans  or the development of future products  in this section,
the discussion should be balanced with a brief discussion on the time frame  for
implementing future plans  and finalizing the development of  future products , the steps
involved, the associated costs, and any obstacles involved before you can commence the
planned operations.  This includes the need for any additional financing.  If additional
financing may not be available, please clarify that.   In this regard, we note your
disclosure in the fourth risk factor on page 8 disclosing certain cost estimates and the first
risk factor on page 12 disclosing certain FDA approval time frame estimates related to
your futu re plans  and products .  Please also revise the Prospectus Summary on page 1 so
that investors can clearly understand your future business plans and the development
status of your future products to include timing and cost s.

Overview, page 27

16. We note your  disclosure in the fifth paragraph that you believe that X -22, upon the
completion of additional clinical trials that demonstrate efficiency, can capture significant
share of the smoking cessation product market.  Please revise to add balancing language
that there is no guarantee that you will obtain the funds necessary to complete additional
clinical trials, that you will obtain necessary FDA approvals and that will capture
significant share of the smoking cessation product market.

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 5

 Smoking Cessation Ai ds, page 28

17. We note your disclosure in the last sentence that you believe X -22, upon the completion
of additional clinical trials that demonstrate efficiency, will qualify for “Fast Track”
designation by the FDA.  We note that X -22 has in the past already  been denied “Fast
Track” designation by the FDA.  Please revise to add balancing language that there is no
guarantee that the FDA will grant “Fast Track” designation to X -22.  Please also include
a cross reference to the Fast Track Development section on page 41.

Modified Risk Cigarettes, page 28

18. We note your disclosure that you believe Brand A and Brand B will achieve significant
market share in the global cigarette market among a specified subgroup of smokers.
Please revise to add balancing language t hat there is no guarantee that you will obtain
necessary FDA approvals and that you will achieve a significant market share of this
specified subgroup of smokers.

Tar, Nicotine, and Smoking Behavior, page 29

19. We note your disclosure in the last sentence of the second paragraph that studies have
demonstrated that compensatory smoking of low -tar research cigarettes, similar to Brand
B, is greatly curtailed resulting in smokers inhaling less “tar” and carbon monoxide.
Please revise to add balancing language  that Brand B was not used in such studies and
that additional studies may be necessary to establish whether Brand B cigarettes achieve
similar result s.

Products, page 31

Brand A Cigarettes, page 32

20. We note your disclosure in the last paragraph that you  believe Brand A will receive a
modified risk cigarette classification  from the FDA.  Please revise to add balancing
language that there is no guarantee that the FDA will grant such classification .  Please
revise the Brand B Cigarettes section on page 32 i n a similar manner.

Brand B Cigarettes, page 32

21. We note your disclosure that Brand B cigarettes’ smoke contains the lowest amount of
“tar” per milligram of nicotine compared to other commercial tobac co cigarettes.  Please
provide  us with support for this  statement or revise.

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 6

 RED SUN and MAGIC  Cigarettes, page 33

22. We note your disclosures in footnotes 2 to your audited and interim financial statements
that you are still exploring distribution channels for your RED SUN and MAGIC
cigarettes and that you are not currently taking orders for these products in the U.S.
market.  Please revise this section and the Overview section on page 1 as applicable.
Please include enough information so that investors can understand the status of these
products.

Sales and Marketing, page 36

23. Please revise to disclose when you intend to begin marketing each product and the
expected costs.

Management’s Discussion and Analysis of Financial Condition, page 44

Liquidity and Capital Resources, page 48

Cash demands on opera tions, page 48

24. We note your disclosure in the first paragraph that your cash position is insufficient to
maintain your operations for the next 12 months.  Please revise to quantify your expected
near term and long term financing requirements which are nec essary to maintain your
current operations and to implement your future business plans .

Description of Securities, page 64

General, page 64

25. We note that you qualify the summary of your capital stock by the provisions of
applicable law.  Such a qualifica tion is inappropriate unless you file the applicable
provisions as exhibit s to the registration statement.  Please revise accordingly.

Exhibit 5.1

26. We note that the r egistration statement registers  shares of the company’s common stock
issuable (i) upon conversion of the Series A Preferred Stock, (i i) as dividends on the
Series A Preferred Stock and (iii) upon exercise of the Series A, B and C Warrants.  We
also note that counsel has only opined upon  the securities mentioned in clauses (i) and
(iii) above.  Please have counsel revise the opinion to opine that the  shares of common
stock issuable as dividends on the Series A Preferred Stock  will be validly issued, fully
paid and non -assessable .

Joseph Pandolfino
22nd  Century Group, Inc.
February 28 , 2013
Page 7

 We urge all persons who are responsible for the accuracy and adequacy of the disclosure
in the filing to be certain that the filing includes the information the Securities Act of 193 3 and
all applicable Securities  Act rules require.  Since the company and its management are in
possession of all facts relating to a company’s disclosure, they are responsible for the accuracy
and adequacy of the disclosures they have made.

Notwithstanding our comments, in the event you request acceleration of the effective da te
of the pending registration statement please provide a written statement from the company
acknowledging that:

 should the Commission or the staff, acting pursuant to delegated authority, declare the
filing effective, it does not foreclose the Commission  from taking any act ion with respect
to the filing;

 the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accura cy of th e disclosure in the filing; and

 the company may not assert staff comments and the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.

Please  refer to Rules 460 and 461 regarding requests for  acceleration .  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation
of the fact that those requesting acceleration are aware of their respective responsibilities under
the Securities Act of 1933 and the Securities Exchange Act of 1934 as they relate to the proposed
public offering of the securities specified in the above registration statement.  Please allow
adequate time  for us to revie w any amendment prior t

CORRESP
1
filename1.htm

    Unassociated Document

22nd Century Group, Inc.

9530 Main Street

Clarence, NY 14031

Tel.: 716-270-1523

September 19, 2011

Mr. John Dana Brown

Attorney-Advisor

UNITED STATES SECURITIES AND EXCHANGE COMMISSION

100 F Street, N.E.

Washington, D.C. 20549

Re:

22nd Century Group, Inc. (the “Company”)

Amendment No. 7 (“Amendment No. 7”) to Registration Statement on Form S-1 (the “Form S-1”)

Filed September 12, 2011

File No. 333-173420

Dear Mr. Brown:

In response to oral comments of the Staff of the SEC regarding Amendment No. 7 (the “September 19 Comments”) that Ms. Sonia Bednarowski communicated in a telephone call today to the Company’s outside counsel, Mr. Patrick G. Quick of Foley & Lardner LLP, the Company has filed Amendment No. 8 to the Form S-1 (“Amendment No. 8”).  Amendment No. 8 includes the following revisions in response to the September 19 Comments:

·

On page 1, the Company added the heading “Private Placement Offering” above the disclosure regarding the January 25, 2011 private placement offering.

·

The Company moved the paragraph that appeared on page 3 of Amendment No. 7 regarding the January 25, 2011 private placement offering not generating sufficient funds to complete the FDA approval process to page 1 under the heading “Private Placement Offering” and emphasized introductory and closing sentences of that paragraph by bolding the font.

·

On page 2, the Company added the following headings: “Current Default Under NCSU License” and “Operations”.

·

On page 2, the Company added a sentence to disclose the current balance owed to NCSU under the heading “Current Default Under NCSU License”.

Other than the revisions above in response to the September 19 Comments, Amendment No. 8 does not reflect any other substantive revisions.

*           *           *

In connection with responding to the September 19 Comments, the Company acknowledges that:

·

should the Commission or the staff, acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

·

the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and

·

the Company may not assert staff comments as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

If you have any further comments regarding this letter, the response contained herein or the Registration Statement on Form S-1 referred to above, please contact the undersigned or Patrick G. Quick of the Company’s outside counsel, Foley & Lardner LLP, 777 East Wisconsin Avenue, Milwaukee, WI 53202; Telephone No.: (414) 297-5678, Facsimile No.: (414) 297-4900; email: pgquick@foley.com.  Thank you for your cooperation.

Sincerely,

/s/ Joseph Pandolfino

Joseph Pandolfino

Chief Executive Officer

22nd Century Group, Inc.

CORRESP
1
filename1.htm

    Unassociated Document

22nd Century Group, Inc.

9530 Main Street

Clarence, NY 14031

Tel.: 716-270-1523

September 16, 2011

Via EDGAR

Securities and Exchange Commission

100 F Street, N.E.

Washington, D.C. 20549

Re:

22nd Century Group, Inc.

Registration Statement on Form S-1

Commission File No. 333-173420

Ladies and Gentlemen:

The undersigned registrant hereby requests, pursuant to Rule 461 under the Securities Act of 1933, as amended, that the effective date of the above captioned Registration Statement (File No. 333-173420), as amended by any pre-effective amendments thereto, be accelerated to:

9:00 a.m. (EST) on September 20, 2011

or as soon as practicable thereafter. For purposes of Rule 461, there is no underwriter at this time.

The Company hereby acknowledges that:

·

should the Commission or the Staff, acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

·

the action of the Commission or the Staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and

·

the Company may not assert Staff comments and the declaration of effectiveness as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

22nd Century Group, Inc.

By:

/s/ Joseph Pandolfino

Joseph Pandolfino

Chief Executive Officer

CORRESP
1
filename1.htm

    Unassociated Document

22nd Century Group, Inc.

9530 Main Street

Clarence, NY 14031

Tel.: 716-270-1523

September 16, 2011

Via EDGAR

Securities and Exchange Commission

100 F Street, N.E.

Washington, D.C. 20549

Re:

22nd Century Group, Inc.

Registration Statement on Form S-1

Commission File No. 333-173420

Ladies and Gentlemen:

The undersigned registrant hereby requests, pursuant to Rule 461 under the Securities Act of 1933, as amended, that the effective date of the above captioned Registration Statement (File No. 333-173420), as amended by any pre-effective amendments thereto, be accelerated to:

September 20, 2011

or as soon as practicable thereafter. For purposes of Rule 461, there is no underwriter at this time.

The Company hereby acknowledges that:

·

should the Commission or the Staff, acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

·

the action of the Commission or the Staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and

·

the Company may not assert Staff comments and the declaration of effectiveness as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

22nd Century Group, Inc.

By:

/s/ Joseph Pandolfino

Joseph Pandolfino

Chief Executive Officer

CORRESP
1
filename1.htm

22nd Century Group, Inc.

9530 Main Street

Clarence, NY 14031

Tel.: 716-270-1523

September 12, 2011

Mr. John Dana Brown

Attorney-Advisor

UNITED STATES SECURITIES AND EXCHANGE COMMISSION

100 F Street, N.E.

Washington, D.C. 20549

Re:          22nd Century Group, Inc. (the “Company”)

Amendment No. 6 (“Amendment No. 6”) to Registration Statement on Form S-1 (the “Form S-1”)

Filed September 6, 2011

File No. 333-173420

Dear Mr. Brown:

The Company received your September 9, 2011 letter (the “September 9 Comment Letter”) containing the comments and questions of the Staff of the SEC regarding Amendment No. 6. Accompanying this letter is Amendment No. 7 to the Form S-1 (“Amendment No. 7”), which includes revisions in response to the September 9 Comment Letter. In addition, we discuss the Company’s responses to the September 9 Comment Letter below.  Further, for your convenience, we have restated each of your comments as set forth in the September 9 Comment Letter immediately preceding each of our responses below.  Finally, please note that, simultaneously herewith, we are filing a revised Request for Confidential Treatment relating to Exhibits 10.21 and 10.22 that were previously filed with Amendment No. 6.

Prospectus Summary, page 1

1. We note your revised disclosure on page 22 regarding your failure to meet certain required development and commercialization terms of your exclusive worldwide license agreement with NCSU. Please add this disclosure to your prospectus summary, your Overview section on page 36 and your Intellectual Property section on page 48.

RESPONSE:  We have added the disclosure referenced above to the prospectus summary section on page 2, the overview section on page 37 and the intellectual property section on page 48.

Risk Factors, page 9

Risks Related to Regulatory Approvals and Insurance Reimbursement, page 14

If we fail to obtain FDA and foreign regulatory approvals of X-22, page 14

2. Please revise to clarify what you mean by “compliance” on page 14.

RESPONSE: We have revised our disclosure on pages 3, 14, 15, 38, 41, 54 and 59 to clarify that “compliance” means a patient using a product as directed.

*           *           *

In connection with responding to the September 9 Comment Letter, the Company acknowledges that:

·

should the Commission or the staff, acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

·

the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and

·

the Company may not assert staff comments as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

Following the filing of the amendment, we remain hopeful that the next step in the process is to have the Form S-1 declared effective by the Commission. As you are aware, after September 23, 2011, the holders of our common stock being registered pursuant to the Form S-1 will become entitled to monetary penalties unless the Form S-1 has been declared effective, as detailed in the last paragraph on page F-30 of Amendment No. 7. Moreover, effectiveness of the Form S-1 as soon as practicable and in advance of that date would assist us in our capital raising efforts. We are prepared to file an acceleration request to that end and look forward to receiving your direction.

If you have any further comments regarding this letter, the response contained herein or the Registration Statement on Form S-1 referred to above, please contact the undersigned or Patrick G. Quick of the Company’s outside counsel, Foley & Lardner LLP, 777 East Wisconsin Avenue, Milwaukee, WI 53202; Telephone No.: (414) 297-5678, Facsimile No.: (414) 297-4900; email: pgquick@foley.com.  Thank you for your cooperation.

Sincerely,

/s/ Joseph Pandolfino

Joseph Pandolfino

Chief Executive Officer

22nd Century Group, Inc.

September 9, 2011
 Via E-mail

Joseph Pandolifino Chief Executive Officer 22nd Century Group, Inc. 9530 Main Street Clarence, NY 14031
Re: 22nd Century Group, Inc.
  Amendment No. 6 to Registra tion Statement on Form S-1
Filed September 6, 2011
  File No. 333-173420

Dear Mr. Pandolifino:
 We have reviewed your responses to the co mments in our letter dated August 29, 2011
and have the following additional comments.  All page numbers below correspond to the marked version of your filing.

Prospectus Summary, page 1

1. We note your revised disclosure on page 22 regarding your failure to meet certain
required development and commercialization te rms of your exclusive worldwide license
agreement with NCSU.  Please add this di sclosure to your prospectus summary, your
Overview section on page 36 and your Inte llectual Property section on page 48.

Risk Factors, page 9
 Risks Related to Regulatory Approvals and Insurance Reimbursement, page 14

 If we fail to obtain FDA and foreign regulatory approvals of X-22, page 14

2. Please revise to clarify what you mean by “compliance” on page 14.

Joseph Pandolifino 22nd Century Group, Inc. September 9, 2011 Page 2

 Please contact Sonia Bednarowski at (202) 551-3666 or me at (202) 551-3859 with any
questions.
Sincerely,
   /s/ John Dana Brown   John Dana Brown
Attorney-Advisor
cc: Via E-mail

             Patrick G. Quick              Foley & Lardner LLP

CORRESP
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    Unassociated Document

22nd Century Group, Inc.

9530 Main Street

Clarence, NY 14031

Tel.: 716-270-1523

September 6, 2011

Mr. John Dana Brown

Attorney-Advisor

UNITED STATES SECURITIES AND EXCHANGE COMMISSION

100 F Street, N.E.

Washington, D.C.  20549

Re:

22nd Century Group, Inc. (the “Company”)

Amendment No. 5 (“Amendment No. 5”) to Registration Statement on Form S-1 (the “Form S-1”)

Filed August 26, 2011

File No. 333-173420

Dear Mr. Brown:

The Company received your August 29, 2011 letter (the “August 29 Comment Letter”) containing the comments and questions of the SEC regarding Amendment No. 5.  Accompanying this letter is Amendment No. 6 to the Form S-1 (“Amendment No. 6”), which includes the following:

(i)

revisions in response to the August 29 Comment Letter;

(ii)

revisions in response to your September 1, 2011 letter regarding the Company’s request for confidential treatment (including re-filing Exhibits 10.21 and 10.22); and

(iii)

the Company’s Interactive Data Files as Exhibit 101.

In addition, we discuss the Company’s responses to the August 29 Comment Letter below. Further, for your convenience, we have restated each of your comments as set forth in the August 29 Comment Letter immediately preceding each of our responses below.  Finally, please note that, simultaneously herewith, we are filing a revised Request for Confidential Treatment relating to Exhibits 10.21 and 10.22 to the Form S-1, which the Company is re-filing in redacted form by means of Amendment No. 6.

General

1.               With a view to revised disclosure, please explain to us any reasons the FDA gave for denying fast-track designation for X-22.

RESPONSE:  On August 18, 2011, the FDA informed us that Fast Track designation could not be granted at this time.  The FDA provided the following explanation in the letter:

We have reviewed your request, and, although tobacco dependence is considered a serious disease, you have not demonstrated that your product shows potential to address an unmet medical need. Consequently, designation as a Fast Track Product cannot be granted at this time. Should you desire further consideration, please submit a new request with rationale supporting that there is an unmet medical need for smoking cessation along with your revised development plan.

We have revised our disclosures on page 3 (under the heading “Smoking Cessation Aids”), page 14 (last paragraph), page 38 (under the heading “Smoking Cessation Aids”), page 54 (under the heading “Fast Track Development”) and page 59 (under “Overview”) to explain that our request was denied because we did not demonstrate that X-22 shows potential to address an unmet medical need and that when we submit a new Fast Track request in the fourth quarter of 2011, we will include our Phase II-B clinical trial results that will be available in November 2011. We also added language that discloses our belief that we will obtain Fast Track designation if our Phase II-B clinical trial results to be submitted with our new Fast Track request demonstrate potential to address an unmet medical need for smoking, which pursuant to FDA regulations can include one of the following advantages over currently approved smoking cessation products: efficacy, safety or improvement in some other factor like compliance or convenience.

We have also revised our disclosures on page 54 (under the heading “Fast Track Development”) to clarify that designation as a Priority Review product mainly benefits developmental products during the FDA’s review of the New Drug Application (NDA), which is filed after the completion of the Phase III clinical trials. Generally, products that are granted Fast Track designation are also granted Priority Review by the FDA.  The revised disclosures explain that the length of the FDA’s review of an NDA without a Priority Review designation is normally ten months from the date of filing of an NDA, although it is possible in certain cases for such review time to be longer.  However, the FDA’s goal for reviewing a product with Priority Review status is normally six months from the date of the filing of an NDA.

Risk Factors, page 9

Risks Related to Regulatory Approvals and Insurance Reimbursement, page 14

If we fail to obtain FDA and foreign regulatory approvals of X-22, page 14

2.               We note your disclosure on page 14 that “if you are not able to have X-22 qualify for Fast Track designation by the FDA, [you] will not receive the benefit of a priority review from the FDA” on page 14. Please expand this risk factor to disclose that you “previously submitted a request for Fast Track designation and on August 18, 2011, the FDA informed [you] that designation of X-22 as a Fast Tract Product [could not] be granted at this time, but, if [you] desire further consideration, [you] should submit a new request for Fast Track designation.”

RESPONSE:  We have expanded the above referenced risk factor on page 14 accordingly.

3.               Please revise to provide a separate risk factor addressing how your business will be impacted if you are unable to receive Fast Track designation and a priority review of X-22 from the FDA, including what the effects may be on the timing and costs of obtaining FDA approval for X-22 and its impact on your financial condition. This disclosure will help investors better understand this risk.

RESPONSE:  We have included a new risk factor on page 15 to describe the risks associated with our inability to receive Fast Track designation and Priority Review status of X-22 from the FDA.

2

Principal and Selling Shareholders, page 28

Selling Shareholders’ Table, page 29

4.               Please revise footnote 14 to identify the individual or individuals who have voting or investment power with respect to the shares held by Gibralt US, Inc.

RESPONSE: We have revised footnote 14 on page 29 to disclose the individual who has voting and investment power with respect to the shares held by Gibralt US, Inc.

Management’s Discussion and Analysis of Financial Condition and Results of Operation, page 58

5.               We note your revision to the first sentence in the third paragraph of this section.  Please delete this sentence as this is not a quarterly report. We also note that the PSLRA safe harbor for forward-looking statements in Section 27A of the Securities Act is not applicable to you.

RESPONSE:  We have deleted the sentence referenced above from page 58.

6.               We note your response to our prior comment two and reissue in part. Please revise to include disclosure regarding the annual “clean-up” provision that requires you to repay all principal amounts outstanding and disclosure that you have not complied with the “clean-up” provision. In addition, please revise to add a risk factor that addresses your failure to comply with the “clean-up” provision or tell us why this is not necessary.

RESPONSE:  We have revised our disclosure regarding the annual “clean-up” provision on page 61 and have added a separate risk factor on page 11 accordingly.

7.               We note your revision on page F-28 regarding the promissory note dated June 30, 2011 that is due on August 30, 2011. Please revise to add disclosure here regarding this note or advise.

RESPONSE: We have added disclosure regarding the promissory note dated June 30, 2011 on page 61.  Please note that the term of the promissory note has been extended to November 1, 2011 as revised on pages 61, 73 and F-28.  Please see Exhibit 10.20.

*******

In connection with responding to the August 29 Comment Letter, the Company acknowledges that:

•

should the Commission or the staff, acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

•

the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and

3

•

the Company may not assert staff comments as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

Please note that as of September 3, 2011 the Company has moved its principal executive offices to a new location at 9530 Main Street, Clarence, New York 14031.  We have revised our address in Amendment 6 on the cover page and on pages 7, 28, 57 and 67.  All other Company contact information has remained the same.

Following the filing of the amendment, we remain hopeful that the next step in the process is to have the Form S-1 declared effective by the Commission. As you are aware, after September 23, 2011, the holders of our common stock being registered pursuant to the Form S-1 will become entitled to monetary penalties unless the Form S-1 has been declared effective, as detailed in the last paragraph on page F-30 of Amendment No. 6. Moreover, effectiveness of the Form S-1 as soon as practicable and in advance of that date would assist us in our capital raising efforts. We are prepared to file an acceleration request to that end and look forward to receiving your direction.

If you have any further comments regarding this letter, the response contained herein or the Registration Statement on Form S-1 referred to above, please contact the undersigned or Patrick G. Quick of the Company’s outside counsel, Foley & Lardner LLP, 777 East Wisconsin Avenue, Milwaukee, WI 53202; Telephone No.: (414) 297-5678, Facsimile No.: (414) 297-4900; email: pgquick@foley.com. Thank you very much for your cooperation.

Sincerely,

/s/ Joseph Pandolfino

Joseph Pandolfino

Chief Executive Officer

22nd Century Group, Inc.

4

August 29, 2011
 Via E-mail

Joseph Pandolifino Chief Executive Officer 22nd Century Group, Inc. 8201 Main Street, Suite 6 Williamsville, NY 14221
Re: 22nd Century Group, Inc.
  Amendment No. 5 to Registra tion Statement on Form S-1
Filed August 26, 2011
  File No. 333-173420

Dear Mr. Pandolifino:
 We have reviewed your responses to the co mments in our letter dated August 22, 2011
and have the following additional comments.  All page numbers below correspond to the marked version of your filing.

General

1. With a view to revised disclosure, please ex plain to us any reasons the FDA gave for
denying fast-track designation for X-22.

Risk Factors, page 9

Risks Related to Regulatory Approvals and Insurance Reimbursement, page 14
 If we fail to obtain FDA and foreign regulatory approvals of X-22, page 14

2. We note your disclosure on page 14 that “if you are not able to have X-22 qualify for Fast
Track designation by the FDA, [you] will not recei ve the benefit of a priority review from
the FDA” on page 14.  Please expand this risk factor to disclose that you “previously
submitted a request for Fast Track designation and on August 18, 2011, the FDA informed [you] that designation of X-22 as a Fast Tract Product [coul d not] be granted at
this time, but, if [you] desire further consid eration, [you] should submit a new request for
Fast Track designation.”

3. Please revise to provide a separate risk factor addressing how your business will be
impacted if you are unable to receive Fast Track designation and a priority review of X-
22 from the FDA, including what the effects may be on the timing and costs of obtaining

Joseph Pandolifino 22nd Century Group, Inc. August 29, 2011 Page 2

 FDA approval for X-2 and its impact on your financial condition.  This disclosure will
help investors better understand this risk.
 Principal and Selling Shareholders, page 28

 Selling Shareholders’ Table, page 29

4. Please revise footnote 14 to identify the indi vidual or individual s who have voting or
investment power with respect to the shares held by Gibralt US, Inc.
 Management’s Discussion and Analysis of Fina ncial Condition and Results of Operation, page
58

5. We note your revision to the firs t sentence in the third paragra ph of this section.  Please
delete this sentence as this is not a quarterl y report.  We also note that the PSLRA safe
harbor for forward-looking statements in Section 27A of the S ecurities Act is not
applicable to you.

6. We note your response to our pr ior comment two and reissue in  part.  Please revise to
include disclosure regarding the annual “cl ean-up” provision that requires you to repay
all principal amounts outstandi ng and disclosure that you have not complied with the
“clean-up” provision.  In addition, please revise to add a risk factor that addresses your
failure to comply with the “cl ean-up” provision or tell us w hy this is not necessary.

7. We note your revision on page F-28 regard ing the promissory note dated June 30, 2011
that is due on August 30, 2011.  Please revise to add disclosure here  regarding this note
or advise.

Please contact Sonia Bednarowski at (202) 551-3666 or me at (202) 551-3859 with any
questions.
Sincerely,
   /s/ John Dana Brown     John Dana Brown
Attorney-Advisor
cc: Via E-mail

             Patrick G. Quick              Foley & Lardner LLP

CORRESP
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22nd Century Group, Inc.

8201 Main Street, Suite 6

Williamsville, NY 14221

Tel.: 716-270-1523

August 26, 2011

Mr. John Dana Brown

Attorney-Advisor

UNITED STATES SECURITIES AND

  EXCHANGE COMMISSION

100 F Street, N.E.

Washington, D.C. 20549

Re:

22nd Century Group, Inc. (the “Company”)

Amendment No. 4 (“Amendment No. 4”) to Registration Statement on Form S-1 (the “Form S-1”)

Filed August 8, 2011

File No. 333-173420

Dear Mr. Brown:

The Company received your August 22, 2011 letter (the “August 22 Comment Letter”) containing the comments and questions of the Staff of the SEC regarding Amendment No. 4. Accompanying this letter is Amendment No. 5 to the Form S-1 (“Amendment No. 5”), which includes revisions in response to the August 22 Comment Letter and certain other updating changes. In addition, we discuss the Company’s responses to the August 22 Comment Letter below.  Further, for your convenience, we have restated each of your comments as set forth in the August 22 Comment Letter immediately preceding each of our responses below.

Please note that, simultaneously herewith, we have filed a Request for Confidential Treatment with the Office of the Secretary of the Securities and Exchange Commission relating to Exhibits 10.21 (License Agreement dated March 6, 2009 between North Carolina State University (NCSU) and 22nd Century Limited, LLC) and 10.22 (License Agreement dated May 1, 2009 between the National Research Council of Canada (NRC) and 22nd Century Limited, LLC) to the Form S-1, which the Company is filing in redacted form by means of Amendment No. 5 as discussed more fully below in the response to comment  3.

Business, page 36

Products, page 41

X-22 Smoking Cessation Aid, page 41

1. Please provide the basis of your belief that X-22 provides greater relief from withdrawal symptoms than all FDA-approved nicotine lozenges and that it reduces cravings more than all FDA-approved prescription nicotine inhalers, or please advise. Alternatively, please remove this bullet point.

RESPONSE: We have deleted the referenced bullet point from page 41 of Amendment No. 5, however, this statement was based on the finding of the following published research papers which are publicly available: (i) Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation by Hatsukami et al., 2010, Addiction, 105:343-355 and (ii) The effects of nicotine, denicotinized tobacco, and nicotine-containing tobacco on cigarette craving, withdrawal, and self-administration in male and female smokers by Sean P. Barrett, 2010, Behav Pharmacol. Mar, 21(2):144-52, respectively.

Liquidity and Capital Resources, page 61

2. Please include a discussion of your demand bank loan as discussed in Note 4 on page F-27 and convertible note dated March 31, 2011, note dated date March 30, 2011, and note dated January 25, 2011 as discussed in Note 6 beginning on page F-29.

RESPONSE: We have included a discussion of the notes referenced above on page 61 of Amendment No. 5.

Exhibits and Financial Statement Schedules, page II-3

3. Please file your worldwide exclusive license agreements with NCSU and NRC as exhibits to your next amendment.

RESPONSE: We have filed our worldwide exclusive license agreements with NCSU and NRC as Exhibits 10.21 and 10.22 to Amendment No. 5.  Please note that we have omitted certain confidential information contained in the Exhibits 10.21 and 10.22.  The omitted information is the subject of a confidential treatment request, and we have filed complete copies of the exhibits separately with the Office of the Secretary pending a ruling pursuant to Rule 406 of the Securities Act.

Other

4. The financial statements should be updated, as necessary, to comply with Rule 8-08 of Regulation S-X.

RESPONSE: We have updated Amendment No. 5 to include the financial statements as of and for the six months ended June 30, 2011.  We have also updated other disclosures as appropriate to reflect the updated financial statements.

*           *           *

In connection with responding to the August 22 Comment Letter, the Company acknowledges that:

·

should the Commission or the staff, acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

2

·

the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and

·

the Company may not assert staff comments as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

We expect to file an amendment to the Form S-1 next week solely to file our Interactive Data File as an Exhibit.

Following the filing of the amendment, we sincerely hope the next step in the process is to have the Form S-1 declared effective by the Commission.  We respectfully advise that it would be extremely helpful for that to occur no later than September 9, 2011, especially due to the fact that after September 23, 2011, the holders of our common stock being registered pursuant to the Form S-1 will become entitled to monetary penalties unless the  Form S-1 has been declared effective, as detailed in the last paragraph on page F-30 of Amendment No. 5. Following the filing of the amendment, we are prepared to immediately file an acceleration request to that end and look forward to receiving your direction.

If you have any further comments regarding this letter, the response contained herein or the Registration Statement on Form S-1 referred to above, please contact the undersigned or Patrick G. Quick of the Company’s outside counsel, Foley & Lardner LLP, 777 East Wisconsin Avenue, Milwaukee, WI 53202; Telephone No.: (414) 297-5678, Facsimile No.: (414) 297-4900; email: pgquick@foley.com.

Thank you very much for your cooperation.

Sincerely,

/s/ Joseph Pandolfino_____________

Joseph Pandolfino

Chief Executive Officer

22nd Century Group, Inc.

3

August 22, 2011
 Via E-mail

Joseph Pandolifino Chief Executive Officer 22nd Century Group, Inc. 8201 Main Street, Suite 6 Williamsville, NY 14221
Re: 22nd Century Group, Inc.
  Amendment No. 4 to Registra tion Statement on Form S-1
Filed August 8, 2011
  File No. 333-173420

Dear Mr. Pandolifino:
 We have reviewed your responses to the comm ents in our letter dated August 3, 2011 and
have the following additional comments.  All page numbers below correspond to the marked
version of your filing.

Business, page 36

 Products, page 41

 X-22 Smoking Cessation Aid, page 41

1. Please provide the basis of your belief that X- 22 provides greater relief from withdrawal
symptoms than all FDA-approved nicotine lo zenges and that it reduces cravings more
than all FDA-approved prescription nicotine in halers, or please advise.  Alternatively,
please remove this bullet point.
 Liquidity and Capital Resources, page 61

2. Please include a discussion of your demand bank loan as discussed in Note 4 on page F-
27 and convertible note dated March 31, 2011, note dated date March 30, 2011, and note
dated January 25, 2011 as discussed in No te 6 beginning on page F-29.
 Exhibits and Financial Statement Schedules, page II-3

3. Please file your worldwide exclusive licen se agreements with NCSU and NRC as
exhibits to your next amendment.

Joseph Pandolifino 22nd Century Group, Inc. August 22, 2011 Page 2

 Other

4. The financial statements should be updated, as necessary, to comply with Rule 8-08 of
Regulation S-X.

Please contact Sonia Bednarowski at (202) 551-3666 or me at (202) 551-3859 with any
questions.
Sincerely,
   /s/ John Dana Brown
  John Dana Brown
Attorney-Advisor
cc: Via E-mail

             Patrick G. Quick              Foley & Lardner LLP

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22nd Century Group, Inc.­­­­­­­­

8201 Main Street, Suite 6

Williamsville, NY 14221

Tel.: 716-270-1523

August 5, 2011

Mr. John Dana Brown

Attorney-Advisor

UNITED STATES SECURITIES AND EXCHANGE COMMISSION

100 F Street, N.E.

Washington, D.C. 20549

Re:

22nd Century Group, Inc. (the “Company”)

Amendment No. 3 (“Amendment No. 3”) to Registration Statement on Form S-1 (the “Form S-1”)

Filed July 20, 2011

File No. 333-173420

Dear Mr. Brown:

The Company received your August 3, 2011 letter (the “August 3 Comment Letter”) containing the comments and questions of the Staff of the SEC regarding Amendment No. 3. Accompanying this letter is Amendment No. 4 to the Form S-1 (“Amendment No. 4”), which includes revisions in response to the August 3 Comment Letter. In addition, we discuss the Company’s responses to the August 3 Comment Letter below.  Further, for your convenience, we have restated each of your comments as set forth in the August 3 Comment Letter immediately preceding each of our responses below.

Prospectus Summary, page 1

Our Company, page 1

Overview, page 1

1. Please revise to reconcile your disclosure in the second sentence on page 1 “that you control 90 issued patents” with your disclosure in the same sentence that, of those 90 issued patents, “[you] own 8 issued patents” and “have control of an additional 90 issued patents” and with your disclosure on page 5 that your “proprietary technology is covered by 12 patent families consisting of 98 issued patents.”

RESPONSE: In the second sentence on page 1 of Amendment No. 3 there is a typographical error referring to 90 issued patents.  We control 98 (not 90) issued patents.  We have revised the S-1 accordingly.  Please see page 1 of Amendment No. 4.

2. Please revise to clarify the expiration dates of your two exclusive licenses if none of the patent applications under each license is successful.

1

RESPONSE: The exclusive rights under each of these two license agreements expire on the date on which the last patent covered by the subject license expires in the country or countries where such patents are in effect. The NCSU license relates predominately to issued patents, of which there are dozens to date, and the NCSU license will expire in 2022 when the last patent covered by the NCSU license will expire.  The NRC license currently relates to only patent applications, so if such patent applications result in issued patents, then we expect the NRC license to expire in 2028, which is 20 years from the time when all such patent applications were filed together.  However, in the event that none of the NRC patent applications result in issued patents, then the NRC license would expire upon our receipt of the last formal notice of rejection from the subject patent office of the domestic or foreign jurisdiction relating to the last of the NRC patent applications, which is an unknown date in the future that we cannot calculate.  We have revised Amendment No. 4 to clarify the foregoing. Please see pages 1, 5, 36 and 48 of Amendment No. 4.

It should be noted that we are confident that patents will issue from the pending patent applications that are the subject of our exclusive license with NRC since we are certain that no other entity filed the subject gene sequences including the functions of such genes (the NRC gene sequences were confirmed by the information that later became public from the tobacco genome project).

3. We note your disclosure in the last sentence on page 1 and in the first paragraph on page 36 that your “very low nicotine (VLN) cigarettes made from [your] VLN tobacco have already demonstrated efficacy in previous Phase II trials, specifically the Phase II trial at the University of Minnesota which had a very similar protocol to our upcoming Phase II clinical trial.” Please revise this disclosure to clarify that further research is needed to determine the efficacy of X-22.

RESPONSE: On pages 1 and 36 of Amendment No. 4, we have inserted the following sentence: “Further research may be needed to determine the efficacy of X-22, including our review of the results of our Phase II-B trial and the results of any Phase III trial which may be requested by the FDA.”

4. We note your response to our prior comment one. Please revise the first sentence in the fourth paragraph on page two and the first sentence in the third paragraph on page 36 to clarify that further research is needed to determine the efficacy of X-22.

RESPONSE: On pages 2 and 36 of Amendment No. 4, we have inserted the following sentence: “Further research may be needed to determine the efficacy of X-22, including our review of the results of our Phase II-B trial and the results of any Phase III trial which may be requested by the FDA.”

5. Please refer to the first sentence in the first paragraph on page three. Please explain to us the basis for your belief stated here and elsewhere that BRAND A and BRAND B will qualify as Modified Risk Cigarettes, given that the FDA has not yet issued its regulations and guidance in this regard.

2

RESPONSE: Within the language of the Tobacco Control Act, there are various descriptions of modified risk tobacco products and what will be required, even though the final regulations have not been issued by the FDA.  Please see the language of the Tobacco Control Act:

http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=111_cong_public_laws&docid=f:publ031.111.pdf

For example, it states:

a claim comparing a tobacco product to 1 or more other commercially marketed tobacco products shall compare the tobacco product to a commercially marketed tobacco product that is representative of that type of tobacco product on the market (for example the average value of the top 3 brands of an established regular tobacco product).

I have been involved with “potential reduced exposure tobacco products” or PREPS (the predecessor phrase to modified risk tobacco products) for almost 20 years, my entire professional career.  As conveyed in the S-1 drafts and related letters to the SEC, cigarettes with very low nicotine (approximately 95% reduced) and cigarettes with low tar-to-nicotine ratios (approximately 8 or lower) have reliably resulted in significant reductions in smoke inhalation by smokers due to smoking behavior.  There is no doubt by me and others in the industry that the FDA is going to require human exposure studies comparing potential modified risk cigarettes to the top 3 brands sold in the U.S.  We believe that further exposure studies with BRAND A and BRAND B will have similar results as the studies already cited that are in the public domain.

Nevertheless, on pages 3, 37, 40, 49, 56 and 59 of Amendment No. 4, we have changed the phrase (or similar phrases) from “BRAND A and BRAND B will qualify as Modified Risk Cigarettes” (emphasis added) to “BRAND A and BRAND B may qualify as Modified Risk Cigarettes” (emphasis added).

Furthermore, on pages 3, 37, 42, and 49 of Amendment No. 4 we amended the text to state that “We believe that BRAND A and BRAND B may qualify as Modified Risk Cigarettes because, compared to commercial cigarettes, we believe the tobacco in BRAND A has approximately 95% less nicotine than tobacco in cigarettes previously marketed as “light” cigarettes, and BRAND B’s smoke contains the lowest amount of “tar” per milligram of nicotine.”

Risk Factors, page 9

The FDA requirement regarding graphic health warnings, page 19

6. We note your response to our prior comment eight. Please revise this risk factor and your

Government Regulation disclosure to also address which of your current products or products in development will be subject to these new packaging and advertising regulations.

RESPONSE: On pages 9 and 19 of Amendment No. 4, we have inserted the following sentence: “MAGIC, RED SUN, BRAND A and BRAND B will be subject to these new packaging and advertising regulations. It is unclear at this time whether the FDA may require X-22 and SPECTRUM to be subject to these new packaging and advertising regulations.”

3

Business, page 35

“Tar” Nicotine and Smoking Behavior, page 37

7. We note your response to our prior comment one. We note your disclosure on page 38 that “[s]tudies have shown that smokers do not compensate when smoking cigarettes made with our VLN tobacco, and that smoking VLN cigarettes, such as Brand A, actually assist smokers to smoke fewer cigarettes per day and reduce their exposure to certain tobacco smoke toxins, including nicotine.” Please revise to clarify that further studies are needed to verify the claims made in this statement. In addition, we note that your intent is to sell Brand A as modified risk cigarette and not as a smoking cessation aid. Please revise or advise.

RESPONSE: On page 38 of Amendment No. 4, we have inserted the following sentence: “Further studies are needed to verify these results.”

Yes, our intent is to sell BRAND A as a modified risk cigarette and not as a smoking cessation aid.  The Tobacco Controls Act makes it clear that any product regulated as a smoking cessation aid cannot be regulated as a tobacco product.  On pages 4, 38 and 42 of Amendment No. 4, we amended the text to better clarify our intentions.

8. We note your response to our prior comment one. Please revise the last sentence in this section on page 38 to remove the words “such as Brand B” and revise to clarify that Brand B was not used in these studies and that further studies are needed to verify your statements regarding Brand B.

On page 38 of Amendment No. 4, we have removed the words “such as BRAND B” from the last sentence in this section and added the following: “BRAND B, however, was not used in these studies. Therefore, further studies are needed to verify that smokers inhale less tobacco smoke toxins with BRAND B.”

Market, page 38

Cigarettes and Smoking Cessation Aids, page 38

9. We note your response to our prior comment one. Please revise the last sentence in the first paragraph of this section to clarify that further studies will need to be done in order to determine whether your products can meet the identified needs.

RESPONSE: On page 38 of Amendment No. 4, we have added the following sentence: “However, further studies are needed to determine whether our products can successfully address such unmet needs of smokers.”

10. We note your response to our prior comment nine. Please refer to the third paragraph in this section on page 38. With a view to revised disclosure, please tell us how the information cited earlier in the paragraph provides a basis for your conclusion that X-22 will be attractive to smokers “especially with those who have previously attempted to quit and failed.”

4

RESPONSE: We have deleted the following sentence from page 38 of Amendment No. 4: “Thus, we believe that upon FDA approval, our X-22 smoking cessation aid will be attractive to smokers, especially with those who have previously attempted to quit and failed.”

11. Please remove the word “limited” in the fourth paragraph in this section.

RESPONSE: We have deleted the word “limited” in the fourth paragraph of this section of Amendment No. 4.

Products, page 39

X-22 Smoking Cessation Aid, page 39

12. Please revise the last four bullet points on page 40 given that that further study is needed to demonstrate efficacy.

RESPONSE: On page 40 of Amendment No. 4, we have revised the bullet points given that further studies are needed to demonstrate efficacy. We note that, as currently presented, these bullet points represent our Company’s current belief in the product.

Brand B Cigarettes, page 42

13. We note your response to our prior comment one. Please refer to the first paragraph on page 42. Please revise to clarify that human studies still need to be conducted to determine the level of carbon monoxide exposure and the level of nicotine exposure from smoking BRAND B, or please advise.

RESPONSE: On page 42 of Amendment No. 4, we removed the following sentences: “BRAND B allows the smoker to achieve a satisfactory amount of nicotine per cigarette while inhaling less “tar” and carbon monoxide,” and “At the same time, we do not expect exposure to nicotine from BRAND B to be significantly higher than some full flavor cigarette brands (cigarettes that have relatively higher “tar” and nicotine yields (from smoking machines) and taste more robust than “light” and “ultra lights.”).”  We have also revised this section of Amendment No. 4 on page 42 to clarify that further research and exposure studies, including human exposure studies, are needed.

Research and Development, page 55

14. Please revise to remove the words “highly qualified.”

RESPONSE: On page 55 of Amendment No. 4, we have removed the words, “highly qualified.”

*           *           *

5

In connection with responding to the August 3 Comment Letter, the Company acknowledges that:

·

should the Commission or the staff, acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

·

the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and

·

the Company may not assert staff comments as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

If you have any further comments regarding this letter, the response contained herein or the Registration Statement on Form S-1 referred to above, please contact the undersigned or Patrick G. Quick of the Company’s outside counsel, Foley & Lardner LLP, 777 East Wisconsin Avenue, Milwaukee, WI 53202; Telephone No.: (414) 297-5678, Facsimile No.: (414) 297-4900; email: pgquick@foley.com.

Sincerely,

/s/ Joseph Pandolfino

Joseph Pandolfino

Chief Executive Officer

22nd Century Group, Inc.

6

August 3, 2011
 Via E-mail

Joseph Pandolifino Chief Executive Officer 22nd Century Group, Inc. 8201 Main Street, Suite 6 Williamsville, NY 14221
Re: 22nd Century Group, Inc.
  Amendment No. 3 to Registra tion Statement on Form S-1
Filed July 20, 2011
  File No. 333-173420

Dear Mr. Pandolifino:
 We have reviewed your responses to the co mments in our letter dated July 14, 2011 and
have the following additional comments.  All page numbers below correspond to the marked
version of your filing.

Prospectus Summary, page 1

 Our Company, page 1

 Overview, page 1

1. Please revise to reconcile your disclosure  in the second sentence on page 1 “that you
control 90 issued patents” with your disclosu re in the same sent ence that, of those 90
issued patents, “[you] own 8 issued patents” and “have control of an additional 90 issued
patents” and with your disclosure on page 5 that your “proprietary technology is covered
by 12 patent families consisting of 98 issued patents.”

2. Please revise to clarify the expiration dates of your two exclusive licenses if none of the
patent applications under each  license is successful.

3. We note your disclosure in the last sentence on page 1 and in the first paragraph on page
36 that your “very low nicotin e (VLN) cigarettes made fr om [your] VLN tobacco have
already demonstrated efficacy in previous Phas e II trials, specifically  the Phase II trial at
the University of Minnesota which had a very  similar protocol to our upcoming Phase II
clinical trial.”  Please revise this disclosure to clarify that further research is needed to
determine the efficacy of X-22.

Joseph Pandolifino 22nd Century Group, Inc. August 3, 2011 Page 2

 4. We note your response to our prior comment one .  Please revise the first sentence in the
fourth paragraph on page two and the first se ntence in the third paragraph on page 36 to
clarify that further research is need ed to determine the efficacy of X-22.

5. Please refer to the first sentence in the first pa ragraph on page three.  Please explain to us
the basis for your belief stated here a nd elsewhere that BRAND A and BRAND B will
qualify as Modified Risk Cigare ttes, given that the FDA has not  yet issued its regulations
and guidance in this regard.

Risk Factors, page 9

 The FDA requirement regarding graphic health warnings, page 19

6. We note your response to our prio r comment eight.  Please revise this risk factor and your
Government Regulation disclosure to also address which of your current products or
products in development will be subject to these new packaging and advertising
regulations.

Business, page 35

“Tar” Nicotine and Smoking Behavior, page 37

7. We note your response to our prior comment one.   We note your disclosure on page 38
that “[s]tudies have shown that smokers do not compensate when smoking cigarettes
made with our VLN tobacco, and that smoking VL N cigarettes, such as Brand A, actually
assist smokers to smoke fewer cigarettes pe r day and reduce their exposure to certain
tobacco smoke toxins, including nicotine.”  Please revise to clarify that further studies are
needed to verify the claims made in this st atement.  In addition, we note that your intent
is to sell Brand A as modified risk cigare tte and not as a smoking cessation aid.  Please
revise or advise.

8. We note your response to our prior comment one.  Please revise the last sentence in this
section on page 38 to remove the words “such as Brand B” and revise to clarify that
Brand B was not used in these studies and that  further studies are needed to verify your
statements regarding Brand B.

Market, page 38
 Cigarettes and Smoking Cessation Aids, page 38

9. We note your response to our prior comment one.  Please revise the last sentence in the
first paragraph of this section to clarify that  further studies will need to be done in order
to determine whether your products can  meet the identified needs.

Joseph Pandolifino 22nd Century Group, Inc. August 3, 2011 Page 3

 10. We note your response to our prior co mment nine.  Please refer to the  third  paragraph in
this section on page 38.  With a view to revised disclo sure, please tell us how the
information cited earlier in  the paragraph provides a basis for your conclusion  that X-22
will be attractive to smokers “especially with  those who have previously attempted to
quit and failed.”

11. Please remove the word “limited” in th e fourth paragraph in this section.
 Products, page 39

 X-22 Smoking Cessation Aid, page 39

12. Please revise the last four bullet points on page  40 given that that further study is needed
to demonstrate efficacy.

Brand B Cigarettes, page 42

13. We note your response to our prior comment one .  Please refer to the first paragraph on
page 42.  Please revise to clarify that huma n studies still need to be conducted to
determine the level of carbon monoxide exposur e and the level of nicotine exposure from
smoking BRAND B, or please advise.

Research and Development, page 55

14. Please revise to remove the words “highly qualified.”

We urge all persons who are responsible for th e accuracy and adequacy of the disclosure
in the filing to be certain that the filing incl udes the information the Securities Act of 1933 and
all applicable Securities Act rules require.  Since the company and its management are in
possession of all facts relating to a company’s disc losure, they are responsible for the accuracy
and adequacy of the disclosures they have made.
Notwithstanding our comments, in the event you request acceleration of  the effective date
of the pending registration statement please pr ovide a written statement from the company
acknowledging that:

 should the Commission or the staff, acting purs uant to delegated authority, declare the
filing effective, it does not foreclose the Co mmission from taking any action with respect
to the filing;

 the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accuracy of the disclosure in the filing; and

Joseph Pandolifino 22nd Century Group, Inc. August 3, 2011 Page 4

  the company may not assert staff comments a nd the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.  Please refer to Rules 460 and 461 regarding re quests for acceleration.  We will consider a
written request for acceleration of  the effective date of the regi stration statement as confirmation
of the fact that those reques ting acceleration are aware of thei r respective responsibilities under
the Securities Act of 1933 and the Securities Excha nge Act of 1934 as they relate to the proposed
public offering of the securities specified in th e above registration stat ement.  Please allow
adequate time for us to review any amendment prior to the requested effective date of the
registration statement.
 Please contact Sonia Bednarowski at (202) 551-3666 or me at (202) 551-3859 with any
questions.
Sincerely,
   /s/ John Dana Brown   John Dana Brown
Attorney-Advisor
cc: Via E-mail

             Patrick G. Quick              Foley & Lardner LLP

CORRESP
1
filename1.htm

    Unassociated Document

22nd Century Group, Inc.

8201 Main Street, Suite 6

Williamsville, NY 14221

Tel.: 716-270-1523

July 20, 2011

Mr. John Dana Brown

Attorney-Advisor

UNITED STATES SECURITIES AND

   EXCHANGE COMMISSION

100 F Street, N.E.

Washington, D.C. 20549

Re:

22nd Century Group, Inc. (the “Company”)

Amendment No. 2 (“Amendment No. 2”) to Registration Statement on Form S-1 (the “Form S-1”)

Filed June 29, 2011

File No. 333-173420

Dear Mr. Brown:

The Company received your July 14, 2011 letter (the “July 14 Comment Letter”) containing the comments and questions of the Staff of the SEC regarding Amendment No. 2.  Accompanying this letter is Amendment No. 3 to the Form S-1 (“Amendment No. 3”), which includes revisions in response to the July 14 Comment Letter. In addition, we discuss the Company’s responses to the July 14 Comment Letter below.  Further, for your convenience, we have restated each of your comments as set forth in the July 14 Comment Letter immediately preceding each of our responses below.

General

1.           We note your response to our prior comment one. Please revise throughout to provide balancing disclosure to clarify that further research of your products is needed to determine efficacy as we note that the abstracts of the reports you provided in response to our prior comment one suggest that results are preliminary and further research is needed. In addition, we note that your conclusions regarding the effectiveness of Brand B are based upon studies that utilized products other than Brand B. We also note that you have not yet completed the FDA approval process. For example, we note the fourth sentence in the second paragraph on page two, statements on pages two and elsewhere that your products do not expose users to any new side effects, the first sentence in the third paragraph on page two, the second sentence in the first paragraph on page three, the first sentence in the second paragraph on page 36, the last two sentences in the first paragraph on page 38, the last sentence of the second paragraph on page 38, the bullet points on page 39, the third sentence in the first paragraph on page 41, the third paragraph on page 41, statements in the first paragraph on page 42, the graph on page 42 and the paragraph preceding the graph, the third sentence of the third paragraph on page 42, the discussion “Clinical Trials with Cigarettes Containing our VLN Tobacco” beginning on page 43, claims regarding Rubisco in the third and fourth paragraph on page 55, and claims regarding Verfola in the fourth and fifth paragraphs on page 55.

RESPONSE:  We have amended the Form S-1 to address the above comments including,

(i)

stating on pages 2 (third paragraph), 36 (second paragraph), 39 (last paragraph), 43 (third paragraph) and 46 (third paragraph) that further research and clinical trials are needed to determine efficacy of X-22;

(ii)

stating on pages 3 (first and last paragraphs), 40 (last paragraph) , 41 (first and third paragraphs), 48 (first paragraph) and 54 (third paragraph) that further research and exposure studies are needed (to validate the findings of previous studies related to Brand A);

1

(iii)

stating on pages 3 (first and last paragraphs), 40 (last paragraph), 42 (first and third paragraph), 48 (first paragraph) and 54 (third paragraph) that further research and exposure studies are needed or that short-term human exposure studies have not been completed on Brand B; and

(iv)

clarifying on pages 2 (third paragraph), 36 (second paragraph) and 40 (first paragraph) what is meant by “does not expose smokers to any new drugs or new side effects” (also see our response below under Comment 3).

Regarding claims for Rubisco and Verfola in the third, fourth and fifth paragraphs on page 55, we deleted these paragraphs because the support for these claims is contained in multiple Company reports and other publications and we are not planning to move forward with our biomass business activities as explained in the Form S-1.

2.           In this regard, we note your disclosure in the second sentence of the “Brand A Cigarettes” section on page 41 that “[c]linical studies have demonstrated” and your disclosure on pages 43 to 46 regarding the results of various clinical trials. Please advise as to whether the reports containing the results of these clinical trials are publicly available. If the reports are not publicly available, please provide a consent of the author under Rule 436 of the Securities Act of 1933.

RESPONSE: Yes, all of the reports containing the results of these clinical trials are publicly available and include the following:

Hatsukami DK, Kotlyar M, Hertsgaard LA, Zhang Y, Carmella SG, Jensen J, Allen SS, Shields PG, Murphy SE, Stepanov I, Hecht SS. 2010. Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation. Addiction 105:343-355.

Becker KM, Rose JE, Albino AP. 2008. A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation. Nicotine Tob Res 10(7):1139-48.

Rezaishiraz H, Hyland A, Mahoney MC, O’Connor RJ, Cummings KM. 2007. Treating smokers before the quit date: Can nicotine patches and denicotinized cigarettes reduce cravings? Nicotine Tob Res. 9:1139-1146.

Barrett BP. 2010. The effects of nicotine, denicotinized tobacco, and nicotine-containing tobacco on cigarette craving, withdrawal, and self-administration in male and female smokers. Behav Pharmacol. Mar; 21(2):144-52.

Donny EC, Houtsmuller E, Stitzer ML. 2007. Smoking in the absence of nicotine: behavioral, subjective and physiological effects over 11 days. Addiction 102:324-34.

Prospectus Summary, page 1

Our Company, page 1

Overview, page 1

3.           Please revise to clarify your disclosure on page two and elsewhere that you believe that your VLN tobacco “does not present any new side effects.” We note that it appears that the tobacco would cause many of the same side effects as smoking a non-VLN tobacco cigarette. In this regard please also note comment one above.

RESPONSE: The phrase “does not present any new side effects” was intended to convey to the reader that there are no side effects other than those side effects from smoking.  It should be noted that in clinical trials and upon FDA approval (as a prescription smoking cessation aid), X-22 is strictly for confirmed smokers.  Most smokers continue to smoke during treatment of FDA-approved smoking cessation aids.  For example, Gonzales et al. 2010 (Immediate versus delayed quitting and rates of relapse among smokers treated successfully with varenicline, bupropion SR or placebo, Addiction, 105, 2002-2013, which is publicly available) report that, in a clinical trial, 76% of subjects using Chantix smoked at some point during the 12-week treatment period.

2

Hatsukami et al.2010 (Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation. Addiction 105:343-355, which is publicly available) report that subjects using VLN cigarettes (containing 22nd Century’s proprietary VLN tobacco) for a six-week treatment period on average significantly reduced cigarettes smoked per day from approximately 19 (baseline) to approximately 12.

This Phase II clinical trial also measured exposure of various smoke compounds in smokers from smoking a VLN cigarette. Smokers significantly reduced their smoking as compared to their usual brand of cigarettes. Carbon monoxide (CO) levels, an indicator of smoke exposure, significantly decreased from 20 parts per million (baseline) to 15 parts per million. Cotinine, a metabolite and biomarker of nicotine, significantly decreased from 4.2 micrograms/mL (baseline) to 0.2 micrograms/mL. All differences were statistically significant (P<0.05).  Furthermore, this Phase II clinical trial also showed significant reductions in the following biomarkers of tobacco toxins:  NNAL, NNN, 1-HOP, 3-HPMA and SPMA.  Our Phase II-B trial and the Phase II reviewed in Hatsukami et al. 2010 have similar protocols, including a 6-week treatment period, and both the VLN cigarettes used (in our Phase II-B trial and the one reviewed in Hatsukami et al.) solely contain 22nd Century’s proprietary VLN tobacco, which has approximately 95% less nicotine compared to tobacco in existing “light” cigarettes.

Therefore, it is plausible that smokers using X-22 for the 6-week treatment period on average are not exposed to any more tobacco smoke than they would be from using other FDA-approved smoking cessation aids, especially those with a longer treatment period than X-22 (6 weeks).

Nevertheless, we have changed the phrase throughout the Form S-1 from “does not expose smokers to any new drugs or new side effects” (and eliminated the phrase “does not present any new side effects”) to “does not expose the smoker to any new drugs or new side effects (other than the exposure and side effects from smoking cigarettes in general) that may occur when a person is exposed to a new drug.”

4.           We note your response to our prior comment 25 and your disclosure on page 1 that you plan to raise approximately $15,000,000 in Fall 2011 to fund Phase III trials, modified risk exposure studies and for your general working capital requirements. Please revise to disclose here how you intend to raise such funds.

RESPONSE: We have revised the S-1 and disclosed on pages 2 (first paragraph), 3 (second paragraph), 10 (third risk factor), 53 (fourth paragraph), and 61 (last paragraph) that we currently plan to seek to raise approximately $15 million in the fourth quarter of 2011 through the sale of common stock and/or securities convertible into common stock to fund Phase III trials, modified risk exposure studies and our general working capital requirements.  As that transaction may proceed on a private placement basis, we are reluctant to provide additional details in the S-1.

5.           We note your response to our prior comments 20 and 22. Please revise the last sentence in the first paragraph of the “Overview” section on page one to indicate that you have not identified any specific countries or developed any timelines or cost estimates for international expansion.

RESPONSE: We have amended the last sentence in the first paragraph of the “Overview” section on page 1 and on page 37 to include that we have not yet identified any specific countries or developed any timelines or cost estimates for international expansion.

Smoking Cessation Aids, page 3

6.           Please remove the words “such as X-22” from the first sentence in this section, as The Tobacco Control Act does not specifically address your product.

RESPONSE: We have removed the words “such as X-22” from all three instances in the S-1 where such words referred to the Tobacco Control Act per your recommendation.

3

Technology Platform and Intellectual Property, page 4

7.           We note your response to our prior comment 16 and reissue in part. Please revise your disclosure on page 5 to clarify what you mean by your “two worldwide exclusive licenses expire upon the last-to-expire patent on a country-by-country basis, which is from 2022 through 2026.”

RESPONSE: We clarified the sentence in which the above phrase appears in all four instances in the S-1: on pages 1 (first paragraph of the Overview section), 5 (first paragraph), 35 (last paragraph) and 47 (second paragraph).  Please note that we changed “2026” to “2028” in such phrase due to a calculation error.

Risk Factors, page 9

8.           Please add a risk factor discussing how FDA requirements requiring graphic health warnings may impact sales of your products, as applicable. Please also revise the Government Regulation section beginning on page 51 as appropriate.

RESPONSE: This risk factor was added on page 19 in the risk factor section and on page 54.

Business, page 35

Market, page 38

Cigarettes and Smoking Cessation Aids, page 38

9.           Please provide a basis for statements in the first three sentences in the third paragraph and the first sentence in the fourth paragraph in this section and the second sentence in the last paragraph on page 40. Additionally, please revise to disclose the date of these statistics.

RESPONSE:  We have provided a basis and/or a reference (all of the papers referenced are publicly available and dated) for each of the first three sentences in the fourth paragraph on page 38, and the first sentence in the following fifth paragraph and the fourth sentence in the last paragraph on page 40.

10.           Please revise the second to the last paragraph on page 38 to clarify that there is no guarantee that, even if approved by the FDA, X-22 will have comparable sales to Chantix, or that the FDA will not require X-22 to have a boxed warning.

RESPONSE: We have revised the second-last paragraph on page 38 to clarify that there is no guarantee that, even if approved by the FDA, X-22 will have comparable sales to Chantix®, or that the FDA will not require X-22 to have a Boxed Warning.

Government Regulation, page 51

Clinical Phase, page 51

11.           We note your disclosure on page 52 that you have designated your upcoming phase II clinical trial as a “Phase II-B trial.” Please revise to clarify whether this is your designation or if the FDA has also designated the trial as a Phase II-B trial, or please advise.

RESPONSE: In the second paragraph on page 52, we already had the following description of our Phase II-B trial:

“Phase II clinical trials involve administering the drug to subjects suffering from the target disease or condition to evaluate the drug’s potential efficacy and appropriate dose. The number of subjects in Phase II trials is typically several hundred subjects or less. Generally, early Phase II or Phase II-A studies look at the absorption, metabolism and pharmacodynamics of a drug rather than at clinical benefit or safety. The second stage of Phase II development, Phase II-B studies look more like Phase III trials because they are looking for clear indications of clinical efficacy and safety in larger groups of patients. The Company has designated its upcoming Phase II clinical trial as a “Phase II-B” clinical trial for the these reasons, plus the fact that VLN cigarettes made from the Company’s VLN tobacco have already demonstrated efficacy in other Phase II trials, specifically the Phase II trial at the University of Minnesota which had a very similar protocol.”

4

However, we have slightly amended the above language on page 52 (second paragraph) to clearly convey that we, and not the FDA, have designated our upcoming trial as a Phase II-B trial.  We have and also conveyed this point and amended this language on pages 1 (last paragraph) and 36 (first paragraph).

*           *           *

In connection with responding to the July 14 Comment Letter, the Company acknowledges that:

·

should the Commission or the staff, acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

·

the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and

·

the Company may not assert staff comments as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

If you have any further comments regarding this letter, the response contained herein or the Registration Statement on Form S-1 referred to above, please contact the undersigned or Patrick G. Quick of the Company’s outside counsel, Foley & Lardner LLP, 777 East Wisconsin Avenue, Milwaukee, WI 53202; Telephone No.: (414) 297-5678, Facsimile No.: (414) 297-4900; email: pgquick@foley.com.

Sincerely,

/s/ Joseph Pa

July 14, 2011
 Via E-mail

Joseph Pandolifino Chief Executive Officer 22nd Century Group, Inc. 8201 Main Street, Suite 6 Williamsville, NY 14221
Re: 22nd Century Group, Inc.
  Amendment No. 2 to Registra tion Statement on Form S-1
Filed June 29, 2011
  File No. 333-173420

Dear Mr. Pandolifino:
 We have reviewed your responses to the co mments in our letter dated June 22, 2011 and
have the following additional comments.  All page numbers below correspond to the marked
version of your filing.

General

1. We note your response to our prior comment one.  Please revise throughout to provide
balancing disclosure to clarify that furthe r research of your products is needed to
determine efficacy as we note that the abstr acts of the reports you pr ovided in response to
our prior comment one suggest th at results are preliminary and further research is needed.
In addition, we note that your conclusions re garding the effectiveness of Brand B are
based upon studies that utilized products other than Brand B.  We also note that you have
not yet completed the FDA approval process.  For example, we note the fourth sentence
in the second paragraph on page two, statem ents on pages two and elsewhere that your
products do not expose users to any new side effects, the fi rst sentence in the third
paragraph on page two, the second sentence in the first paragraph on pa ge three, the first
sentence in the second paragraph on page 36, th e last two sentences in the first paragraph
on page 38, the last sentence of the second paragraph on page 38, the bullet points on
page 39, the third sentence in the first paragraph on page 41, the third paragraph on page
41, statements in the first paragraph on pa ge 42, the graph on page 42 and the paragraph
preceding the graph, the third sentence of th e third paragraph on page 42, the discussion
“Clinical Trials with Cigarettes Cont aining our VLN Tobacco” beginning on page 43,
claims regarding Rubisco in the third and fourth paragraph on page 55, and claims
regarding Verfola in the fourth and fifth paragraphs on page 55.

2. In this regard, we note your di sclosure in the second sentence  of the “Brand A Cigarettes”
section on page 41 that “[c]linical studies have demonstrated” and your disclosure on

Joseph Pandolifino 22nd Century Group, Inc. July 14, 2011 Page 2

 pages 43 to 46 regarding the result s of various clinical trials.  Please advise as to whether
the reports containing the results of these clinic al trials are publicly available.  If the
reports are not publicly available, please provi de a consent of the au thor under Rule 436
of the Securities Act of 1933.
 Prospectus Summary, page 1

 Our Company, page 1

 Overview, page 1

3. Please revise to clarify your disclosure on page two and else where that you believe that
your VLN tobacco “does not present any new side  effects.”  We note that it appears that
the tobacco would cause many of the same side effects as smoking a non-VLN tobacco
cigarette.  In this regard pl ease also note comment one above.

4. We note your response to our prior comment 25 and your disclosure on page 1 that you
plan to raise approximately $15,000,000 in Fall 2011 to fund Phase III trials, modified
risk exposure studies and for your general worki ng capital requirements.  Please revise to
disclose here how you intend to raise such funds.

5. We note your response to our prior comments 20 and 22.  Please revise the last sentence
in the first paragraph of the “Overview” secti on on page one to indicate that you have not
identified any specific countries or devel oped any timelines or cost estimates for
international expansion.

Smoking Cessation Aids, page 3

6. Please remove the words “such as X-22” from the first sentence in this section, as The
Tobacco Control Act does not sp ecifically address your product.

Technology Platform and Inte llectual Property, page 4

7. We note your response to our prior comment 16 and reissue in part.  Please revise your
disclosure on page 5 to clarify what you m ean by your “two worldw ide exclusive licenses
expire upon the last-to-expire patent on a country-by-country basis, which is from 2022
through 2026.”

Risk Factors, page 9

8. Please add a risk factor di scussing how FDA requirements requiring graphic health
warnings may impact sales of your products, as applicable.  Pleas e also revise the
Government Regulation section be ginning on page 51 as appropriate.

Joseph Pandolifino 22nd Century Group, Inc. July 14, 2011 Page 3

 Business, page 35

 Market, page 38

 Cigarettes and Smoking Cessation Aids, page 38

9. Please provide a basis for statements in the fi rst three sentences in the third paragraph and
the first sentence in the fourth paragraph in  this section and the second sentence in the
last paragraph on page 40.  Additionally, pleas e revise to disclose the date of these
statistics.

10. Please revise the second to the last paragr aph on page 38 to clarify that there is no
guarantee that, even if approved by the F DA, X-22 will have comparable sales to
Chantix, or that  the FDA will not re quire X-22 to have a boxed warning.
 Government Regulation, page 51

 Clinical Phase, page 51

11. We note your disclosure on page 52 that you have designated your upcoming phase II
clinical trial as a “Phase II-B  trial.”  Please revise to clarify whether this is your
designation or if the FDA has also designated th e trial as a Phase II-B trial, or please
advise.

We urge all persons who are responsible for th e accuracy and adequacy of the disclosure
in the filing to be certain that the filing incl udes the information the Securities Act of 1933 and
all applicable Securities Act rules require.  Since the company and its management are in
possession of all facts relating to a company’s disc losure, they are responsible for the accuracy
and adequacy of the disclosures they have made.
Notwithstanding our comments, in the event you request acceleration of  the effective date
of the pending registration statement please pr ovide a written statement from the company
acknowledging that:

 should the Commission or the staff, acting purs uant to delegated authority, declare the
filing effective, it does not foreclose the Co mmission from taking any action with respect
to the filing;

 the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accuracy of the disclosure in the filing; and

Joseph Pandolifino 22nd Century Group, Inc. July 14, 2011 Page 4

  the company may not assert staff comments a nd the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.  Please refer to Rules 460 and 461 regarding re quests for acceleration.  We will consider a
written request for acceleration of  the effective date of the regi stration statement as confirmation
of the fact that those reques ting acceleration are aware of thei r respective responsibilities under
the Securities Act of 1933 and the Securities Excha nge Act of 1934 as they relate to the proposed
public offering of the securities specified in th e above registration stat ement.  Please allow
adequate time for us to review any amendment prior to the requested effective date of the
registration statement.
 Please contact Sonia Bednarowski at (202) 551-3666 or me at (202) 551-3859 with any
questions.
Sincerely,
    /s/ John Dana Brown    John Dana Brown
Attorney-Advisor
cc: Via E-mail

             Patrick G. Quick              Foley & Lardner LLP

CORRESP
1
filename1.htm

    Unassociated Document

22nd Century Group, Inc.

8201 Main Street, Suite 6

Williamsville, NY 14221

Tel.: 716-270-1523

June 29, 2011

Mr. John Dana Brown

Attorney-Advisor

UNITED STATES SECURITIES AND

  EXCHANGE COMMISSION

100 F Street, N.E.

Washington. D.C. 20549

Re:

22nd Century Group, Inc. (the “Company”)

Amendment No. 1 (“Amendment No. 1”) to Registration Statement on Form S-1 (the “Form S-1”)

Filed June 7, 2011

File No. 333-173420

Dear Mr. Brown:

The Company received your June 22, 2011 letter (the “June 22 Comment Letter”) containing the comments and questions of the Staff of the SEC regarding Amendment No. 1.  Accompanying this letter is Amendment No. 2 to the Form S-1 (“Amendment No. 2”), which includes revisions in response to the June 22 Comment Letter.  In addition, we discuss the Company’s responses to the June 22 Comment Letter below.  Further, for your convenience, we have restated each of your comments as set forth in the June 22 Comment Letter immediately preceding each of our responses below.

General

1.           We note statements throughout regarding the effectiveness of the products you are developing. Please tell us whether such statements are appropriate given that you have not yet completed the FDA approval process. Additionally please tell us your basis for statements throughout regarding the limited effectiveness or side-effects of competing products.

RESPONSE:  We consider the statements as to the effectiveness of the products we are developing are appropriate, notwithstanding that we have not yet completed the FDA approval process.  We further consider that statements as to the limited effectiveness or side-effects of competing products are likewise appropriate.  Below we describe several trials, studies and articles that substantiate our statements.  Nonetheless, we have removed reference in the Form S-1 to the limited effectiveness of existing FDA-approved smoking cessation products. Please see Prospectus Summary – Our Company – Overview, Page 2 of Amendment No. 2; and Business – Overview, Page 36 of Amendment No. 2.

With respect to the effectiveness of X-22, in comparison to the effectiveness of other products:

The following three smoking cessation Phase II trials, each with different protocols, have been carried out with cigarettes containing our very low nicotine (“VLN”) tobacco:

Hatsukami DK, Kotlyar M, Hertsgaard LA, Zhang Y, Carmella SG, Jensen J, Allen SS, Shields PG, Murphy SE, Stepanov I, Hecht SS. 2010. Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation. Addiction 105:343-355. (Referred to herein as “Hatsukami et al.” and a copy of which is available upon request.)  Please see http://www.ncbi.nlm.nih.gov/pubmed/20078491.

Becker KM, Rose JE, Albino AP. 2008. A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation. Nicotine Tob Res 10(7):1139-48.   (Referred to herein as “Becker et al.,” and a copy of which is available upon request.)    Please see http://www.ncbi.nlm.nih.gov/pubmed/18629723.

Rezaishiraz H, Hyland A, Mahoney MC, O’Connor RJ, Cummings KM, 2007. Treating smokers before the quit date: Can nicotine patches and denicotinized cigarettes reduce cravings? Nicotine Tob Res. 9:1139-1146. (Referred to herein as “Rezaishiraz et al.,” and a copy of which is available upon request.)  Please see http://www.ncbi.nlm.nih.gov/pubmed?term=17978987

All three of these studies demonstrated increased quit rates whether VLN cigarettes were used alone (Hatsukami et al.) or used in combination with nicotine replacement therapy, or “NRT” (Becker et al. and Rezaishiraz et al.).  The protocol of the VLN cigarette in the Phase II clinical trial reviewed in Hatsukami et al. is very similar to 22nd Century’s Phase II-B trial.  The treatment consists of six weeks of smoking VLN cigarettes ad libitum (as many as desired) and quitting by the end of treatment period.  The VLN cigarette used in the three clinical trials referred to above and the VLN cigarette being used in 22nd Century’s Phase II-B trial all solely contain 22nd Century’s proprietary VLN tobacco, which has approximately 95% less nicotine compared to tobacco in existing “light” cigarettes.

Dr. Hatsukami, Director of the National Transdisciplinary Tobacco Use Research Center at the University of Minnesota Masonic Comprehensive Cancer Center and one of the nine voting members of the 12-person Tobacco Products Scientific Advisory Committee (TPSAC) at the FDA’s Center for Tobacco Products, has dozens of peer-reviewed publications on smoking cessation/tobacco harm reduction and has received millions of dollars in grants from the U.S. government to conduct smoking cessation and exposure studies. For Dr. Hatsukami’s Curriculum Vitae and more information on TPSAC, please see

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProductsScientificAdvisoryCommittee/ucm180906.htm

Dr. Hatsukami is currently conducting a follow-up phase II clinical trial with VLN cigarettes supplied by 22nd Century (the results of which are not yet published), entitled “Innovative Interventions for Smoking Cessation.”  There are three arms to the Innovative Interventions for Smoking Cessation clinical trial:  (i) a VLN cigarette by itself, (ii) a nicotine patch (21 mg) by itself, and (iii) both the patch and a VLN cigarette used together. For more information, please see http://clinicaltrials.gov/ct2/show/NCT01050569?term=NCT01050569&rank=1.

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Regarding the limited effectiveness of competing products, the Institute of Medicine (the health arm of the National Academy of Sciences), which some consider the highest medical authority in the U.S., in a 2007 report, titled “Ending the Tobacco Problem: A Blueprint for the Nation,” concluded as follows:

The limitations of the pharmacotherapies are that their effectiveness is moderate (achieving cessation rates of 10 to 20%, depending on the population of smokers and whether concomitant behavioral therapies are used) and the fact that many dependent smokers have already tried these therapies and failed to quit smoking when they have used them.  Most studies of re-treatment with the same medication find that cessation rates are very low.

Piper ME, et al also reported (See Table 2 of Piper ME, et al.) point-prevalence abstinence rates during the 8th week of treatment, while the subjects were still on medication, for the three individual treatments (monotherapies) as follows:

40% for the nicotine lozenge,

45% for the nicotine patch, and

40% for Zyban (buproprion), versus 30% for the placebo controls.

Because absolute abstinence rates in smoking cessation trials vary between studies due to a variety of factors, the odds ratios for treatment versus control are usually considered more useful for comparisons. Piper ME et al. shows in Table 3 of that study that for point prevalence abstinence at the 8th week of treatment, odds ratios versus placebos were as follows:

1.57 for the nicotine lozenge,

1.87 for the nicotine patch, and

1.55 for Zyban (buproprion).

An odds ratio of 1 implies that the event is equally likely in both groups. An odds of 1.5 implies than the treatment group has a 50% greater probability to quit versus the placebo group.

In the University of Minnesota study (Hatsukami et al.), the point prevalence abstinence rates at 6 weeks after treatment (patients ceased taking medication 6 weeks previous), were as follows:

47.2% for the very low nicotine (VLN) cigarette (0.05 mg nicotine cigarette),

36.7% for the 4 mg nicotine lozenge, and

23.1% for the intermediate nicotine cigarette (0.3 mg nicotine cigarette).

This corresponds to abstinence odds ratios as follows, showing higher abstinence odds ratios in VLN cigarettes as compared to the nicotine lozenge (both vs. the 0.3 mg cigarette control):

3

2.98 for the VLN cigarette, and

1.93 for the nicotine lozenge.

“Varenicline, an ά4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Sustained-Release Bupropion and Placebo for Smoking Cessation, A Randomized Controlled Trial,” by David Gonzales, PhD, et. al., Journal of American Medicine, July 5, 2006—Vol 296, No. 1 (a copy of which is available upon request), details a clinical trial of Chantix (varenicline) and Zyban (bupropion), which showed a 44% quit rate of Chantix and 29.5% quit rate of Zyban (both 4-week of continuous abstinence rates) measured during weeks 9 through 12 of the trial, while the subjects were still on medication.  See http://www.ncbi.nlm.nih.gov/pubmed/16820546.

To illustrate relapse rates of patients after stopping Chantix use, “Effect of Maintenance Therapy With Varenicline on Smoking Cessation, A Randomized Controlled Trial,” by Serena Tonstad, MD, PhD et al., Journal of American Medicine, July 5, 2006—Vol 296, No. 1 (a copy of which is available upon request), reported on a study in which subjects initially received 12 weeks of open-label Chantix treatment. In this study, subjects that were abstinent at the end of treatment were randomized to double-blind additional 12 weeks of Chantix or placebo. The study demonstrated that when Chantix was terminated, abstinence declined rapidly (double blind placebo group). For example, at 4 weeks after the end of the initial 12-week Chantix treatment period (week 16), only 68% of those abstinent at week 12 were still abstinent, and at 8 weeks post treatment (week 20), only 55% were still abstinent.  See http://www.ncbi.nlm.nih.gov/pubmed/16820548.

Regarding the side effects of other FDA-approved smoking cessation products, both Chantix® and Zyban® were required by the FDA on July 1, 2009 to add boxed warnings (the most serious warning in prescription drug labeling) to their package inserts.  These warnings highlight that serious neuropsychiatric events, including but not limited to depression, suicidal ideation, suicide attempt and completed suicide, have been reported in patients taking Chantix® and Zyban®.

o

Please see FDA July 1, 2009 news release: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm170100.htm

o

Please see boxed warning on page 1 of Chantix® label:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021928s012s013lbl.pdf

o

Please see boxed warning on page 1 of Zyban® label: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020711s032s033lbl.pdf

With respect to the effectiveness of Brand A:

The Hatsukami et al. study also measured exposure of various smoke compounds in smokers from smoking a VLN cigarette containing our proprietary tobacco over a six-week period. Smokers significantly reduced their smoking as compared to their usual brand of cigarettes. Carbon monoxide (CO) levels, an indicator of smoke exposure, significantly decreased from 20 parts per million (baseline) to 15 parts per million. Cotinine, a metabolite and biomarker of nicotine, significantly decreased from 4.2 micrograms/mL (baseline) to 0.2 micrograms/mL. All differences were statistically significant (P<0.05).

4

Furthermore, Hatsukami et al., showed significant reductions in the following biomarkers of tobacco toxins NNAL, NNN, 1-HOP, 3-HPMA and S-PMA. The Brand A cigarette and the VLN cigarette used in Hatsukami et al. solely contain 22nd Century’s proprietary VLN tobacco, which has approximately 95% less nicotine compared to tobacco in existing “light” cigarettes.

With respect to the effectiveness of Brand B:

In the following studies (copies of which are available upon request), nicotine was added to cigarettes by researchers to produce low tar-to-nicotine ratio cigarettes:

o

“Evaluation of a low to middle tar/medium nicotine cigarette designed to maintain nicotine delivery to smoker,” by A.K. Armitage, et al., Psychopharmacology (1988), 6: 447-453. Please see http://www.ncbi.nlm.nih.gov/pubmed/3149764;

o

“Effects of a Nicotine-Enriched Cigarette on Nicotine Titration, Daily Cigarette Consumption, and Levels of Carbon Monoxide, Cotinine, and Nicotine,” by Karl-Olov Fagerstrom, Psychopharmacology (1982) 77: 164-167. Please see http://www.ncbi.nlm.nih.gov/pubmed/6812134; and

o

“The separate effects of tar and nicotine on the cigarette smoking manoeuvre,” by G. Woodman, S. P. Newman, D. Pavia & S. W. Clarke, Eur J Respir Dis (1987) 70, 316-321. Please see http://www.ncbi.nlm.nih.gov/pubmed/3609190.

We are not aware of any study that contradicts the findings of these studies that smokers inhale less smoke, including tar and/or carbon monoxide (CO), with low tar-to-nicotine ratio (≤ 8) cigarettes than they do with conventional cigarettes.  See presentation Joseph Pandolfino gave to the Life Science Research Office (LSRO) regarding this subject: www.xxiicentury.com/news/2005-archive/.

Based on the foregoing and other relevant studies, we do consider our statements in the Form S-1 as to the effectiveness of our products vis-à-vis the effectiveness of other very similar products to be appropriate, notwithstanding that our products have not yet received FDA approval/authorization.

Registration Statement Cover Page

2.           Please revise to indicate the Primary Standard Industrial Classification Code as 2111 or advise.

RESPONSE:  We believe that Primary Standard Industrial Classification Code (“SIC Code”) 5194, which we have consistently used in the past and which relates to tobacco and tobacco products, better describes our business than SIC Code 2111, which is limited to cigarettes only.  As we are engaged in modifying the content of nicotinic alkaloids in tobacco plants and the development of modified risk tobacco products, our products and services are broader than those represented by SIC Code 2111.  Therefore, we have not revised the Form S-1 to indicate the SIC Code that you suggested.

5

Prospectus Summary, page 1

Our Company, page 1

Overview, page 1

3. We note your response to our prior comment 33. Please revise to state here that you are currently in default pursuant to the terms of your exclusive world-wide license agreement with North Carolina State University. Please indicate that if NCSU chooses to invoke any right it may have to terminate the License Agreement and you are unable to cure the default, your business would be materially and adversely affected. Please additionally state that if NCSU does not agree to continue to defer payment of the balance, you may not have sufficient funds to pay for the Phase II-B clinical trial for X-22 in full.

RESPONSE:  We have amended the Form S-1 to include the suggested disclosure. Please see Prospectus Summary – Our Company – Overview, Page 1 of Amendment No. 2.

4. We note your response to our prior comment four and reissue in part. Please revise to include your net loss from your most recent interim stub and audited period.

RESPONSE:  We have amended the Form S-1 to include the suggested disclosure. Please see Prospectus Summary – Our Company – Overview, Page 2 of Amendment No. 2.

5. We note your response to our prior comment eight and reissue in part. Please provide support to us for your statement on page 2 that X-22 is the only smoking cessation product that functions exactly like a regular cigarette.

RESPONSE:  We have amended the Form S-1 to remove the statement that X-22 is the only smoking cessation product that functions exactly like a regular cigarette.  Please see Prospectus Summary – Our Company – Overview, Page 2 of Amendment No. 2; and Business – Overview, Page 36 of Amendment No. 2.

6. Please provide support to us that every FDA-approved smoking cessation aid since the establishment of the Fast Track program in 1997 has received the Fast Track designation. Alternatively, please remove this statement.

RESPONSE:  We have amended the Form S-1 to remove the statement that since the establishment of the Fast Track program in 1997 every FDA-approved smoking cessation aid has received the Fast Track designation.

7. Please revise the la

June 22, 2011
Joseph Pandolifino
Chief Executive Officer
22nd Century Group, Inc.
8201 Main Street, Suite 6 Williamsville, NY 14221

Re: 22nd  Century  Group, Inc.
  Amendment No. 1 to Registration Statement on Form S -1
Filed  June 7 , 2011
  File No.  333-173420
 Dear Mr. Pandolifino:
 We have reviewed your responses to the comments in our letter dated May 6, 2011 and
have the following additional comments.  All page numbers below correspond to the marked
version of your filing.

General

1. We note statements throughout regarding the effectiveness of the products you are developing.  Please tell us whether such statements are appropriate given that you have not yet completed the FDA approval process. Additionally please tell us your basis for statements throughout regarding the limited effectiveness or side -effects of competing
products.

Registration Statement Cover Page

2. Please revise to indicate the Primary Standard Industrial Classification Code as 2111 or
advise.

Prospectus Summary, page 1

Our Company, page 1

Overview, page 1

3. We note your response to our prior comment 33.  Please revise to state here that you are
currently in default pursuant to the terms of your exclusive worldwide license agreement with North Carolina State University.  P lease indicate that if NCSU chooses to invoke
any right it may have to terminate the License Agreement and you ar e unable to cure the
default, your business would be materially and adversely affected.  Please additionally

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 2

state that if NCSU does not agree to continue to defer payment of the balance, you may not have sufficient funds to pay for the Phase II -B clinical  trial for X -22 in full.

4. We note your response to our prior comment four and reissue in part.  Please revise to include your net loss from your most recent interim stub and audited period.

5. We note your response to our prior comment eight and reissue in part.  Please provide support to us for your statement on page 2 that X -22 is the only smoking cessation
product that functions exactly like a regular cigarette.

6. Please provide support to us  that every FDA -approved smoking cessation aid since the
establishment of the Fast Track program in 1997 has received the Fast Track designation.  Alternatively, please remove this statement.

7. Please revise the last sentence in the second paragraph on page  4 to clarify that you do
not have an agreement with RTI or other researchers to purchase additional SPECTRUM cigarettes.

8. Please provide support to us for your statement on page 4 that your tobacco contains the lowest nicotine content of any tobacco ever commercialized.  Alternatively, state this as a belief.

9. We note your statement on page 4 that “ analyses by an independent accredited laboratory
found that the levels of certain compounds in the tobacco leaf of the genetically engineered variety were not substantially different than that of conventional tobacco,
except for reduction in nicotine and related compounds.”  Please state as to whether the report containing these analyses is publicly available.
In addition, if this report was not
available for f ree or for a nominal fee, please provide a consent of the author to be named in
the registration statement under Rule 436 of the Securities Act of 1933.

10. We note your disclosure in the fourth paragraph on page 4 that you expect your patent applications to  cover your products until 2024 to 2026.  Please revise to clarify that there
is no guarantee that the patent applications will cover your products.

11. We note your response to our prior comment 11.  Please revise the statement on page F -
16 regarding  “each such PPO Security consisting of one (1) Unit and a five -year warrant
to purchase one -half of one (1/2) Unit at an exercise price of $1.50 per whole Unit”
accordingly.

Risk Factors, page 8

12. We note your response to our prior comment 12 and reissue.  P lease remove the words
“although there may be other risks th at could arise or may prove to be more significant
than expected, that may affect our operation or financial results ” from the third  sentence

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 3

of the introductory paragraph of this section, and ple ase remove the fourth  sentence from
the introductory paragraph of this section .  If risks are not deemed material then they
should not be mentioned.

13. We note your response to our prior comment 13.  Please tell us what consideration you have given to providing a risk factor addressing that this product when marketed previously resulted in “relatively low” sales volume.

We will incur increased costs and demands upon management as a result of complying, page 22

14. Please revise to disclose the costs associated with complying with the laws and
regulation s affecting public companies.

Business, page 33

Overview, page 33

15. We note your response to our prior comment 20.  Please further provide us a basis for
your belief that you “will enable us to capture a significant share of the global market for
approved smoking cessation aids and the emerging market for modified risk tobacco products .”  Additionally , please revise the second paragraph on page two to indicate that
there is no guarantee that you will  be ab le to “take sales and market share from existing
smoking cessation products” and “expand the smoking cessation market.”

16. We note your response to our prior comment 21 and reissue.  Please revise to clarify the number of patents that you own and the num ber of patents that you license.  In addition,
please revise to clarify what you mean on page 33 that your “two worldwide exclusive licenses expire upon the last -to-expire patent on a country -by-country basis.”

Market, page 36

17. We note your response to our prior comment 22 and reissue in part.  Please tell us why the 2008 Datamonitor forecast in the second paragraph on page 36 is still reliable.

Products, page 37

X-22 Smoking Cessation Aid, page 37

18. Please revise the second to the last sentence in the second paragraph on page 38 to clarify that you have not taken any steps to obtain approval for X -22 outside of the United
States.

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 4

Brand B Cigarettes, page 39

19. Please revise the statement in the seco nd paragraph on page 40 that “[w]e believe that
evaluation of BRAND B in short -term human exposure studies will confirm…” given
that these studies have not been completed.

Sales and Marketing, page 45

X-22 Smoking Cessation Aid, page 45

20. We note your disclosure on page 45 that you intend to enter into arrangements in both the U.S. and international markets with pharmaceutical companies to market X -22 before
completion of the Phase III clinical trials.  P lease revise to disclose whether you have
identified any  countries where you intend to attempt to have X -22 approved for
commercial sale.  Additionally , please include timelines and costs  for this international
expansion.

21. Please revise to clarify what you mean by “measured approach” in th e first paragraph of
this section.  In addition, please revise the references  to “wherewithal” on page 45 to
indicate more clearly what resources licensing parties will be required to have.

Brand A and Brand B, page 45

22. We note that you expect to begin marketing your Brand A and Brand B cigarettes internationally in approximately 2 years.  P lease revise to disclose where you intend to
sell your products  and advise as to whether you will need to go through an approval
process to sell your Brand A and Brand B cigarettes  in such countries .  To the extent that
you will need to obtain approval, please disclose.

Government Research Cigarettes, page 46

23. We note your response to our prior comment 27 and reissue in part.  Please revise here and in the second paragraph on page four  to clarify that there is no guarantee that you
will receive  additional orders from RTI or from other researchers or advise.

Potential Smoking Cessation Aids, page 47

24. Please provide support to us for your disclosure in the third par agraph on page 47
regarding the vaccine treatment tests.  In addition, please tell us why Dr. Fiore’s estimate regarding the approval of a nicotine vaccine in 2009 is reliable.

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 5

X-22 Clinical Trials, page 51

25. We note your response to our prior comment 30 and reissue in part.  Please revise to disclose whether you have any plans for raising the additional funding you will need for the Phase III clinical trials.

Biomass Products, page 52

26. Please revise to disclo se a brief description of your biomass business plan, including a
timeline and costs.

Exhibit Index, page E -1

27. Please revise to include all of the exhibits that are included in your registration statement here.

Exhibit 5.1

28. Please have counsel revise the last paragraph of the opinion letter by removing the first sentence as it is inappropriate to limit reliance.

We urge all persons who are responsible for the accuracy and adequacy of the disclosure
in the filing to be certain that the filing includes the  information the Securities Act of 1933 and
all applicable Securities  Act rules require.   Since the company and its management are in
possession of all facts relating to a company’s disclosure, they are responsible for the accuracy and adequacy of the disc losures they have made.

Notwithstanding our comments, in the event you request acceleration of the effective date
of the pending registration statement please provide a written statement from the company acknowledging that:

• should the Commission or the  staff, acting pursuant to delegated authority, declare the
filing effective, it does not foreclose the Commission from taking any action with respect to the filing;

• the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accuracy of the disclosure in the filing; and

• the company may not assert staff comments and the declaration of effectiveness as a defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.

Joseph Pandolifino
22nd Century Group, Inc. June 22, 2011
Page 6

Please refer to Rules 460 and 461 regarding requests for  acceleration .  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation of the fact that those requesting acceleration are aware of their respective responsibilities under the Securities Act of 1933 and the Securities Exchange Act of 1934 as they relate to the proposed public offer ing of the securities specified in the above registration statement.  Please allow
adequate time for us to review any amendment prior to the requested effective date of the registration statement.
 Please contact Sonia Bednarowski at (202) 551 -3666 or  me at (202) 551 -3859 with any
questions.
Sincerely,

  John Dana Brown
Attorney -Advisor

cc: Via facsimile: (414) 297 -4900
             Patrick G. Quick
             Foley & Lardner LLP

CORRESP
1
filename1.htm

22nd Century Group, Inc.

8201 Main Street, Suite 6

Williamsville, NY 14221

Tel.: 716-270-1523

June 7, 2011

Mr. John Dana Brown

Attorney-Advisor

UNITED STATES SECURITIES AND

  EXCHANGE COMMISSION

100 F Street, N.E.

Washington. D.C. 20549

Re:

22nd Century Group, Inc. (the “Company”)

Registration Statement on Form S-1 (the “Form S-1”)

Filed April 11, 2011

File No. 333-173420

Dear Mr. Brown:

The Company received your May 6, 2011 letter (the “May 6 Comment Letter”) containing the comments and questions of the Staff of the SEC regarding the Form S-1.  Accompanying this letter is Amendment No. 1 to the Form S-1 (“Amendment No. 1”), which includes revisions in response to the May 6 Comment Letter. In addition, we discuss the Company’s responses to the May 6 Comment Letter below.  Further, for your convenience, we have restated each of your comments as set forth in the May 6 Comment Letter immediately preceding each of our responses below.

General

1.           Given that there is no guarantee that X-22 or Brand A and Brand B will obtain the necessary approval from the FDA, please revise significantly throughout to clarify this and to provide more balanced disclosure regarding your potential products. Please also revise to clarify that there is no guarantee that you will qualify for "Fast Track" designation.  In addition, please clarify throughout that the FDA has yet to release its regulations regarding modified risk cigarettes and that, as of June 2010, all cigarette companies were required to cease the use of the terms "low tar," "light" and "ultra light."

RESPONSE:  We have amended the Form S-1 to include more disclosure that there is no guarantee that X-22 or Brand A and Brand B will obtain the necessary approvals from the FDA and to provide more balanced disclosure regarding the Company’s potential products.  Please see Prospectus Summary – Our Company – Overview, pages 1, 2 (first and last paragraphs) and 3; Risk Factors, page 14; Business – Overview, pages 34 and 35; and Business- Products, page 38 of Amendment  No. 1.

We have amended the Form S-1 to clarify that there is no guarantee X-22 will qualify for “Fast Track” designation.  The Company expects to have FDA’s answer about X-22’s Fast Track Status by July 2011.  Please see Prospectus Summary – Our Company - Overview, page 3; Business - Overview, page 34; and Business – Government Regulation, pages 50 and 51 of Amendment No. 1.

However, where appropriate, Amendment No. 1 also discloses that, since smoking is the number one cause of preventable death in the U.S., to the Company’s knowledge, every FDA-approved smoking cessation aid since the establishment of the Fast Track program in 1997 (and Nabi Biopharmaceuticals’s nicotine vaccine currently in development) has received “Fast Track” designation while the products were going through the FDA-approval process.  Please see Prospectus Summary – Our Company – Overview, page 3; Business – Overview, page 34; Business – Government Regulation, pages 50 and 51 of Amendment No. 1.

We have amended the Form S-1 to clarify that the FDA has yet to release its regulations regarding modified risk cigarettes, and to include where applicable a statement that we believe such regulations will be released over the next year based in part on the timelines contained in the Tobacco Control Act.  Please see Prospectus Summary – Our Company – Overview, page 2; Risk Factors, pages 9 and 10; Business – Products, page 34; Business – Sales and Marketing, page 38; Business – Government Regulation, pages 45 and 52 of Amendment No. 1.

We have amended the Form S-1 to clarify that, as of June 2010, all cigarette companies were required to cease the use of the terms “low tar,” “light” and “ultra light.”  The following phrase (or a very similar one):  “as of June 2010, all cigarette companies were required to cease the use of the terms ‘low tar,’ ‘light’ and ‘ultra light’” appears as follows: Prospectus Summary – Our Company - Overview, pages 2 and 3; Business - Products, pages 34 and 35 (second and last paragraphs); Business – Sales and Marketing, pages 40 and 45; Business – Government Regulation, page 51; and Management’s Discussion and Analysis of Financial Condition and Results of Operations - Overview, page 55 of Amendment No. 1.

2.           Please revise to clarify what you mean by the phrases “super-premium priced cigarette brands,” “specialty cigarette components,” “full flavor cigarette brands,” “reduce smoke exposure,” “biomass products” and “bioconversion.”

RESPONSE:  We have amended the Form S-1 to clarify what we mean by these six phrases.  For the definition of “super-premium priced cigarette brands,” please see Prospectus Summary – Our Company - Overview on page 3 of Amendment No. 1 under “RED SUN and MAGIC Cigarettes.” For the definitions of “specialty cigarette components,” “full flavor cigarette brands” and “reduce smoke exposure,” see Business – Biomass Products on page 39 of Amendment No. 1 under “BRAND B Cigarettes.” For the definitions of “biomass products” and “bioconversion” see page 52 of Amendment No. 1 under “Biomass Products.”

2

Registration Statement Cover Page

3. The registration fee appears to have been calculated pursuant to Rule 457(c) of the Securities Act. Please revise footnote 2 to the Calculation of Registration Fee table or advise.

RESPONSE:  We have amended the footnote on the cover page to Amendment No. 1 to refer to Rule 457(c).

Our Company, page 1

Overview, page 1

4. Please include in one of your introductory paragraphs your revenues, assets, and losses for the most recent audited period and interim stub. This snapshot will help investors evaluate the disclosure as they read the filing. Also, disclose the fact that your independent auditor's report expresses substantial doubt about your ability to continue as a going concern and that you will not receive any proceeds from this offering.

RESPONSE:  We have amended the Form S-1 to include the suggested disclosure. Please see Prospectus Summary – Our Company – Overview, page 1 of Amendment No. 1.

5. Please revise the first paragraph on page one to clarify that you have not attempted to obtain approval or authorization for your products outside of the United States and that there is no guarantee that you will be able to gain approval or authorization for your products outside of the United States.

RESPONSE:  We have amended the Form S-1 to include the suggested disclosure regarding X-22.  Please see the third paragraph of the Prospectus Summary – Our Company – Overview section of Amendment No. 1, on page 1.  Since modified risk tobacco products are not explained until the fourth paragraph on page 2 of Amendment No. 1, we have included the suggested disclosure regarding Brand A and Brand B in the fifth paragraph of page 2 of Amendment No.1. Please note that, in many foreign countries, a product for which a smoking cessation claim is made (e.g., X-22) generally can be sold legally without having to be approved by a regulatory agency – the presence of a smoking cessation claim in many cases does not trigger regulatory approval requirements.  In contrast, the FDA considers tobacco/nicotine addiction a disease, with the result that smoking cessation products are regulated since they cure or mitigate the disease of tobacco/nicotine addiction.  Therefore, given the regulatory landscape of many foreign countries, it is unlikely that the Company would need to seek regulatory approval or authorization for our products in such countries.  The same is generally true in many foreign countries regarding claims for reduced exposure/risk tobacco products (modified risk tobacco products such as Brand A and Brand B).

6. We note your statement on page one that you plan to use a substantial portion of the proceeds of the Private Placement Offering to complete clinical trials for X-22. Please revise to provide quantitative information here regarding the cost of completing these trials, the amount of money raised in the Private Placement Offering. In addition, please either define the term "Private Placement Offering" or include a cross-reference to the definition.

RESPONSE:  We have amended the Form S-1 to include the suggested disclosure.  The Form S-1 defined “Private Placement Offering” in the Prospectus Summary – Our Company – Overview section (second paragraph under Recent Developments, page 5 of Amendment No. 1), and we have amended the Form S-1 to provide a cross reference to this definition in the second paragraph of page 1 under the Prospectus Summary – Our Company – Overview section of Amendment No. 1.

3

7. Please revise your discussion of the clinical trials for X-22 and your plans to produce and sell modified risk cigarettes by adding the disclosure from the last risk factor on page eight that the net proceeds of the Private Placement Offering will not be sufficient to enable you to complete the FDA approval process for X-22 or the FDA authorization process for your Modified Risk Cigarettes and that you will have to seek additional funding to complete your business plans.

RESPONSE:  We have amended the Form S-1 to include the suggested disclosure.  Please see the last paragraph of page 2 (Prospectus Summary – Our Company – Overview) of Amendment No. 1.

8. Please provide support for your statement on page one that X-22 is the only smoking cessation product that functions exactly like a regular cigarette and your statement on page three that the modifications you have made to your proprietary tobacco do not affect the leaf constituents important to a cigarette's characteristics, including taste and aroma.

RESPONSE:  We have amended the Form S-1 to include the suggested disclosure. In the second paragraph of page 2 (Prospectus Summary – Our Company – Overview) of Amendment No. 1,  we have included a cross reference to the amended discussion later in such section, under the heading “Technology Platform and Intellectual Property,” of how we believe our genetic engineering processes result in less nicotine without altering the functionality, taste and aroma of the tobacco – resulting in the X-22 product having what we believe are taste and aroma characteristics within the range of a typical cigarette. Please see page 4 (Technology Platform and Intellectual Property) of Amendment No. 1.

RED SUN and MAGIC Cigarettes, page 2

9. Please provide support to us for your statement that the ban of flavored cigarettes has created a product void in the tobacco channels where you intend to focus your marketing efforts. Alternatively, please revise to state that this is your belief.

RESPONSE:  We have amended the Form S-1 to provide more information regarding the 2009 ban by the FDA of flavored cigarettes, which we believe resulted in a product void where we intend to focus our marketing efforts, and the market share of such cigarettes prior to the ban.  Please see page 3 of the Prospectus Summary – Our Company – Overview section of Amendment No. 1, under the heading “RED SUN and MAGIC Cigarettes”.

Technology Platform and Intellectual Property, page 3

10. Please balance your disclosure regarding your intellectual property on page three with your disclosure in the last risk factor on page 18 and in the second to the last risk factor on page 19 that you have not performed searches for third-party intellectual property rights that may raise freedom-to-operate issues, that you have not obtained legal opinions regarding the commercialization of your potential products and that there may be existing patents that affect your ability to commercialize your potential products.

RESPONSE: We have amended the Form S-1 to balance the disclosures identified above.  Please see the last paragraph of page 4  of Amendment No. 1 (Prospectus Summary – Our Company – Overview) under the heading “Technology Platform and Intellectual Property”; and the first paragraph of the risk factor beginning on page 19 of Amendment No. 1.

4

Recent Developments, page 3

11. Please revise to clarify the manner in which you sold 5,434,446 Private Placement Offering Securities in the Private Placement Offering and how this relates to the shares being offered. Additionally please reconcile the statement on page three regarding “each Unit consisting of one limited liability company membership interest of 22nd Century and a five-year warrant to purchase one half of one (1/2) limited liability company membership interest” with the statement on page 32 regarding “each such PPO Security consisting of one (1) Unit and a five-year warrant to purchase one-half of one (1/2) Unit.”

RESPONSE: We have amended the Form S-1 to make consistent the phrases referred to in your comment above.  The term “PPO Securities” refers to all of the equity securities sold in the private placement offering, and which consist of individual Units sold.  “Units” are comprised of one limited liability company membership interest in 22nd Century and a warrant to purchase one-half limited liability security membership interest in 22nd Century.  Please see the fourth paragraph of page 33 of Amendment No. 1 under the heading “Background.”  With respect to the manner in which the Company sold 5,434,446 Private Placement Offering Securities (PPO Securities) in the Private Placement Offering and how this relates to the shares being offered, 22nd Century Limited, LLC conducted a private placement to raise capital. Immediately after the closing of that Private Placement Offering, 22nd Century Limited, LLC merged with an acquisition company created by 22nd Century Group, Inc. (which was a shell public company at the time). In that merger transaction, 22nd Century Limited, LLC became a wholly-owned subsidiary of 22nd Century Group, Inc. At the closing of the Merger, each limited liability company membership interest of 22nd Century Limited, LLC issued and outstanding immediately prior to the closing of the Merger was exchanged for one (1) share of the 22nd Century Group, Inc’s common stock, and each warrant to purchase limited liability company membership interests of 22nd Century Limited, LLC was exchanged for one warrant of like tenor and term to purchase shares of the 22nd Century Group, Inc’s common stock.  The shares being offered under the 22nd Century Group, Inc. registration statement on Form S-1 prospectus are those shares of the 22nd Century Group, Inc that were issued in connection with the Private Placement Offering.

Risk Factors, page 7

12. Refer to the third sentence in the introductory paragraph to this section. All material risks should be discussed in this section. If risks are not deemed material then they should not be mentioned. Please revise accordingly.

RESPONSE:  The Company believes that all material risks are already discussed in this section and has revised the introductory paragraph of this section to clarify this. Please see page 8 in the Risk Factors section of Amendment No. 1.   We have amended the Form S-1 to remove risks that the Company does not consider material.

5

13. We note your statement in the last paragraph on page 35 that Vector Tobacco had previously marketed Quest cigarettes. Please provide an appropriate risk factor addressing, if true, that at least one of your products was previously marketed unsuccessfully.

RESPONSE:  In fact, it is not the case that “at least one of [our] products was previously marketed unsuccessfully.”  Vector had to stop marketing QUEST, which contained our proprietary tobacco, as a result of a dispute between Vector and 22nd Century that involved Vector’s ceasing FDA activities related to QUEST.  See the Current Report on Form 8-K filed by Vector Group, Inc. (NYSE:VGR) on November 22, 2006. According to a publicly available transcript of a public investor conference call held by Vector Group, Ltd. on November 9, 2007 (approximately 5 years after QUEST was introduced into the market in 2003), distrib

May 6, 2011
Joseph Pandolifino
Chief Executive Officer
22nd Century Group, Inc.
8201 Main Street, Suite 6 Williamsville, NY 14221

Re: 22nd  Century  Group, Inc.
  Registration Statement on Form S -1
Filed  April 11, 2011
  File No.  333-173420
 Dear Mr. Pandolifino:
 We have limited our review of your registration statement to those issues we have
addressed in our comments.  In some of our comments, we may ask you to provide us with information so we may better understand your disclosure.
 Please respond to this letter by amending your registration statement and providing the
requested information.  Where you do not believe our comments apply to your facts and circumstances or do not believe an amendment is appropriate, please tell us why in your response.
 After reviewing any amendment to your registration statement and the information you
provide in response to these comments, we may have additional comments.

General

1. Given that there is no guarantee that X -22 or Brand A and Brand B will obtain the
necessary approval from the FDA , please revise significantly throughout to clarify this
and to provide more balanced disclosure  regarding your potential products.  Please also
revise to clarify that there is no guarantee that you will qualify for “Fast Track” designation.  In addition, please clarify throughout that the FDA h as yet to release its
regulations regarding mo dified risk cigarettes  and that, as of June 2010, all cigarette
companies were required to cease the use of the terms “low tar,” “light” and “ultra light .”

2. Please revise to clarify what you mean by the phrases  “super -premium priced cigarette
brands,” “s pecialty cigarette components,” “ful l flavor cigarette brands,” “reduce smoke
exposure ,” “biomass products” and “bioconversion.”

Joseph Pandolifino
22nd Century Group, Inc. May 6, 2011
Page 2

Regist ation Statement Cover Page

3. The registration fee appears to have been calculated pursuant to Rule 457(c) of the
Securities Act.  Please revise footnote 2 to the Calculation of Registration Fee table or advise.

Our Company, page 1
Overview, page 1

4. Please include in one of your introductory paragraphs your revenues, assets, and losses for the most recent audited period and interim stub.  This snapshot will help investors evaluate the disclosure as they read the filing.  Also , disclose the fact that your
independent auditor’s report expresses substantial doubt about your ability to continue as a going concern  and that you will not receive any proceeds from this offering .

5. Please revise the first paragraph on page one to clarify that  you have not attempted to
obtain approval or authorization for your products outside of the United States  and that
there is no guarantee that you will be able to gain approval or authorization for your products outside of the United States .

6. We note your statement  on page one  that you plan to use a substantial portion of the
proceeds of the Private Placem ent Offer ing to complete clinical trials  for X -22.  Please
revise to provide quantitative information here regarding the cost of completing these
trials , the amount of money raised in the Private Placement Offer ing.  In addition, please
either define the term “Private Placement Offer ing” or include a cross -referen ce to the
definition.

7. Please revise your discussion of the clinical tr ials for X -22 and y our plans to produce and
sell modified risk cigarettes by  adding the disclosure from the last risk factor on page
eight that the net proceeds o f the Private Placement Offer ing will not be sufficient to
enable you to complete the FDA approval process for X -22 or the FDA authorization
process  for your Modified Risk Cigarettes and that you will have to seek additional
funding to complete your business plans.

8. Please provide support for your statement on page one that X -22 is the only smoking
cessation product that functions e xactly like a regular cigarette and your statement on
page three tha t the modifications you have made to your proprietary tobacco do not affect
the leaf constituents important to a cigarette’s characteristics, including taste and ar oma.

RED SUN and MAGIC Cigarettes, page 2

9. Please provide support to us for your statement that the ban of flavored cigarettes has
created a product void in the tobacco channels where you intend to focus your marketing efforts.  Alternatively, please revise to state that this is your belief.

Joseph Pandolifino
22nd Century Group, Inc. May 6, 2011
Page 3

Technology Platform and Intellectual Property, page 3

10. Please balance your disclosure regarding your intellectual property on page three with your disclosure in the last risk factor on page 18 and in the second to the last risk factor
on page 19 that you have not performed searches for third- party intellectual property
rights that may raise freedom- to-operate issues, that you have not obtained legal opinions
regarding the commercialization of  your potential products and that there may be existing
patents that affect your ability to commercialize your potential products.

Recent Developments, page 3

11. Please revise to clarify the manner in which  you sold 5,434,446 Private Placement
Offering Sec urities in the Private Placement Offering and how this relates to the shares
being offered.  Additionally please reconcile the statement on page three regarding “each
Unit consisting of one limited liability company membership interest of 22nd Century
and a five -year warrant to purchase one half of one (1/2) limited liability company
membership interest” with the statement on page 32 regarding  “each such PPO Security
consisting of one (1) Unit and a five -year warrant to purchase one- half of one (1/2) Unit.”

Risk Factors, page 7

12. Refer to the third sentence in the introductory paragraph to this section.  All material risks
should be discussed in this section.  If risks are not deemed material then they should not be mentioned.  Please revise accordingly.

13. We note your statement in the last paragraph on page 35 that Vector Tobacco had previously marketed Quest cigarettes.  Please provide an appropriate risk factor addressing, if true, that at least one of your products was previously marketed unsuccessfully.

Risks Related to Our Business and Operations, page 7

The net proceeds of the Private Placement Offering will not be sufficient to enable us to, page 8

14. Please revise to include an estimate of the cost of completing  the FDA  approval process
for X -22 and, if possible, for your modified risk cigarettes .

Risks Related to Ownership of Our Common Stock, page 20

We will incur increased costs and demands upon management as a result of complying, page 21

15. We note your disclosure i n this risk factor that you are currently unable to estimate the
costs of complying with the laws and regulations for public companies.  How ever, you

Joseph Pandolifino
22nd Century Group, Inc. May 6, 2011
Page 4

are currently a reporting  company and must already comply with the laws and regulations
affecting public companies.  Please revise or advise.

An active trading market for our common stock may not develop or be sustained, and, page 21

16. Please reconcile your disclosure here with your disclosure on the cover page of your prospectus that your common stock is cur rently traded on the OTC Bulletin.

A significant portion of the total outstanding shares of common stock may be sold into, page 22

17. Please provide a definition for “PPO Security” and “EIP” here.

18. Please revise the first sentence in the second paragraph of this risk factor to clarify that the shares can be sold in the public market after the effective date of the registration statement.

We are controlled by our current officers, directors and principal stockholders, page 23

19. Please reconcile your disclosure here that your directors and officers own 33.8% of the outstanding shares of your common stock with your disclosure on page 26 that they own 39.50% of the outstanding shares of your common stock or advise .

Business, page 32

Overview, page 32

20. Please provide a b asis for statements such as “a global leader” and “will enable us to
capture a significant share of the global market…” on page 32 and “well -positioned to
capture a significant share of this market” and “expand the smoking cessation marke t” on
page 33.

21. We note your disclosure that you own or exclusively control 98 issued patents.  Please revise to clarify the number of patents that you hold and, to the extent material, please disclose the duration of your patents and licenses.

Market, p age 34

22. Please revise the reference to the Datamonitor  forecast in the last paragraph on page 34 to
indicate the first date covered by  the forecast.  If it is not a recent forecast please tell us
why the forecast is  still reliable .

Joseph Pandolifino
22nd Century Group, Inc. May 6, 2011
Page 5

Modified Risk Tobacco Products, page 35

23. Please revise to provide support for your statement in the last sentence in the first paragraph on page 36.

Products, page 36

X-22 Smoking Cessation Aid, page 36

24. Please balance your statement that you plan to complete the FDA -approval process for
your X -22 smoking cessation aid in the fourth quarter by adding your disclosure from the
first complete risk factor on page 13 that the time required for FDA approval and authorization is lengthy and uncertain.

Brand A Cigarettes, page 37

25. Please refer to the third paragraph.  Given that smokers in the study decreased the number of VLN cigarettes they smoked during the six week period, please address the possibility that this means  smokers might not be interested in smo king the product in the long term.

Sales and Marketing , page 43

26. Please revise to disclose when you intend to begin marketing each product  and the
expected cost .  Additionally we note references elsewhere to foreign markets.  P lease
clarify for investors whether you have current  plans to market internationally, including
timelines and costs as applicable.

Government Research Cigarettes, page 44

27. We note your disclosure on page 44 that “you expect to receive an additional purchase order for an  additional 7.85 million SPECTRU M research cigarettes in 2011.”  Please
disclose here and elsewhere as appropriate that there is no guarantee that you will receive this order or other direct orders from researchers or advise.

Healthcare Reimbursement, page 44

28. Please revise the second to the last sentence on page 44 to state that it is your belief t hat
you will have  latitude in pricing X -22.  In addition, please revise the last sentence on
page 44 to state that it is your belief that the price of X -22 will not only encourage
governmental and private third- party payers to cover X -22 but will also encourage
smokers to attempt to quit X -22.  Alternatively, please remove these statements.

Joseph Pandolifino
22nd Century Group, Inc. May 6, 2011
Page 6

Clinical Phase, page 47

29. Please revise your discussion to explain how the Phase II -B clinical trials fit into the
process described in this section.

X-22 Clinical Trials, page 48

30. Please revise to disclose the amount of additional funding you will need to complete the
Phase III clinical trials and whether you have any plans for raising such funding.

Biomass Products, page 49

31. Please revise to clarify what you mean by “once we have achieved success with X -22 and
our Modified Risk Cigarettes ” on page 49.

32. Please revise the third  paragraph  on page 50 to state that it is your belief that Rubisco will
compete favorably in the markets you list on page 50.  In addition, please revise the last
sentence in the second to the last paragraph of this section to state that it is your belief
that protein concentrates from Verfola will compete fa vorably in animal feed.

Management’s Discussion and Analysis of Financial Condition and Results of Operations, page
52

Net Cash F rom Financing Activities, page 55

33. We note your disclosure on page 1 that you plan to use a substantial portion of the
proceeds from  the Private Placement Offering to complete your Phase II -B cli nical trial.
Please advise as to whether these funds will be sufficient to cover the cost s associated
with your Phase II -B clinical trial if you are unsuccessful with your negotiations for
deferred payment arrangements relating to approximately $1,300,000 owed to NCSU and the two vendors  you disclose on page 55.  To the extent that these funds will be
insufficient to cover your Phase II -B clinical trials if you are unsuccessful in the
negotiations  with NCSU and the vendors , please disclo se on page 1 and add a risk factor
that discloses this risk .  Please also provide ri sk factor disclosure regarding any other
effects of defaulting on y our obligations .

Director Compensation, page 59

34. Please revise this section to include a director compensation table purs uant to Item 402(r)
of Regulation S -K.

Joseph Pandolifino
22nd Century Group, Inc. May 6, 2011
Page 7

Executive Compensation, page 59

35. Please revise to include the compensation of Mr. Rector, Mr. Warman, and Mr. Asirwatham .  For guidance,  refer to Regulation S -K Compliance and Disclosure
Interpretations 217.02 and 217.12, available at www.sec.gov.   Additionally please revise your Summary Compensation Table on page 59 to include Mr. Rider’s compensation.

Director Compensation, page 60

36. Please recon cile your disclosure regarding director compensation on page 60 with your
disclosure regarding director compensation on page 59.

Certain Relationships and Related Transactions, page 61

37. We note your disclosure on page 62 regarding shares of your common stock issued to Dr. Moynihan in lieu of cash due and payable to him as compensation. Please disclose this information as footnotes to your Summary Compensation Table on page 59, as applicable.

Exhibits

38. Please file your agreement with RTI international as  an exhibit to your next amendment,
or please advise.

Other

39. The financial statements should be updated, as necessary, to comply with Rule 3- 12 of
Regulation S -X.
 We urge all persons who are responsible for the accuracy and adequacy of the disclosure
in the filing to be certain that the filing includes the  information the Securities Act of 1933 and
all applicable Securities  Act rules require.   Since the company and its management are in
possession of all facts relating to a company’s disclosure, they are responsible for the accuracy and adequacy of the disclosures they have made.

Notwithstanding our comments, in the event you request accelera tion of the effective date
of the pending registration statement please provide a written statement from the company acknowledging that:

• should the Commission or the staff, acting pursuant to delegated authority, declare the
filing effective, it does not foreclose the Commission from taking any action with respect
to the filing;

Joseph Pandolifino
22nd Century Group, Inc. May 6, 2011
Page 8

• the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility fo r
the adequacy and accuracy of the disclosure in the filing; and

• the company may not assert staff comments and the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.
 Please refer to Rules 460 and 461 regarding reques ts for acceleration .  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation of the fact that those requesting acceleration are aware of their respective responsibilities under the Securities  Act of 1933 and the Securities Exchange Act of 1934 as they relate to the proposed
public offering of the securities speci

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549-4628

DIVISION OF
CORPORATION FINANCE
        June 30, 2009

Mr. Nanuk Warman
President, Principal Executive and Financial Officer  Touchstone Mining Limited 11923 SW 37 Terrace  Miami, Florida 33175
 Re: Touchstone Mining Limited
  Form 10-K for the Fiscal Year Ended September 30, 2008
Filed December 29, 2008
  File No. 333-130696

 Dear Mr. Warman:      We have completed our review of your Form 10-K and related filings and have no further comments at this time.           S i n c e r e l y ,            Karl Hiller,
Branch Chief

CORRESP
1
filename1.htm

    Touchstone
Mining Limited

    11923
SW 37 Terrace

    Miami,
Florida  33175

    June 18,
2009

    VIA
EDGAR

    U.S.
Securities and Exchange Commission

    Washington,
DC 20549-7010

    Attn:  Karl
Hiller and Craig Arakawa

                    Re:

                    Touchstone
      Mining Limited

                    Form
      10-K for the Fiscal Year Ended September 30, 2008

                    Filed
      December 29, 2008

                    Form
      10-Q for the Fiscal Quarter Ended March 31, 2009

                    Filed
      May 20, 2009

                    File
      No.
333-130696

    Gentlemen:

    Touchstone
Mining Limited (the “Company”) is in receipt of your June 9, 2009 letter (the
“Letter”) to Nanuk Warman containing comments to the captioned
filings.  The Company has amended the captioned filings under cover of
Forms 10-K/A and 10-Q/A to address such comments.  Set forth below are
your comments, indicated in bold, together with responses thereto by the
Company.

    Form 10-K for the Fiscal
Year Ended September 30, 2008

    Controls and Procedures,
page 12

              1.

              Please disclose the conclusions
      of management, regarding the effectiveness of your internal control over
      financial reporting as of September 30, 2008, to comply with Item 308 of
      Regulation S-K.

    Item
9A[T] of the captioned 10-K has been amended to disclose that the Company’s
internal control over financial reporting was effective as of September 30,
2008.

    Financial
Statements

    Report of Independent
Registered Public Accounting Firm, Page F-2

              2.

              We
      note that your auditors have placed reliance on the work of other auditors
      in rendering their audit opinion on the inception-to-date information, for
      that portion of the cumulative period from September 12, 2005 (inception)
      through September 30, 2006. Given this reliance, you will need to include
      the report of the prior auditors upon whom reliance is being placed,
      provided that you are able to obtain their
  permission.

    If
this is not feasible, your present auditors should remove the reference to the
other auditors in their opinion. Under these circumstances, you will need to
obtain a new audit of the inception-to-date information or revise your financial
statements to identify the cumulative activity as “un-audited.”

    The
present auditors have removed the reference to the other auditors in their
opinion.  Further, the financial statements have been revised to
identify the cumulative activity as “un-audited.”

    Exhibits

              3.

              The
      certifications you attached as Exhibits 31 to your September 30, 2008 Form
      10-K and your subsequent interim periodic reports on Form 10-Q, do not
      conform to the requirements of Item 601 (b)(31) of Regulation S-K as you
      have omitted the language pertaining to your responsibility for internal
      control over financial reporting, required in the introductory section of
      paragraph 4. Please revise your annual and interim certifications to
      comply with your reporting
obligations.

    The
Exhibit 31 Certification in the captioned filings have been revised to conform
to the requirements of Item 601 (b)(31) of Regulation S-K.

    In
responding to your comments we acknowledge that:

              ·

              the
      Company is responsible for the adequacy and accuracy of the disclosure in
      the filing;

              ·

              Staff
      comments or changes to disclosure in response to staff comments do not
      foreclose the Commission from taking any action with respect to the
      filing; and

              ·

              the
      Company may not assert staff comments as a defense in any proceeding
      initiated by the Commission or any person under the federal securities
      laws of the United States.

    Sincerely,

    Touchstone
Mining Limited

                  By:

                  /s/ Nanuk Warman

                  Name:  Nanuk
      Warman

                  Title:  President

        2

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549-7010

DIVISION OF
CORPORATION FINANCE
        June 9, 2009

Mr. Nanuk Warman
President, Principal Executive and Financial Officer Touchstone Mining Limited 11923 SW 37 Terrace Miami, Florida 33175
 Re: Touchstone Mining Limited
  Form 10-K for the Fiscal Year Ended September 30, 2008
Filed December 29, 2008
  Form 10-Q for the Fiscal Quarter Ended March 31, 2009
Filed May 20, 2009
  File No. 333-130696

 Dear Mr. Warman:
We have reviewed your filing and have the following comments.  We have
limited our review to only your financial statements and related disclosures and do not intend to expand our review to other portions of your documents. Where indicated, we think you should revise your document in response to these comments.  If you disagree, we will consider your explanation as to why our comment is inapplicable or a revision is unnecessary.  Please be as detailed as necessary in your explanation.  In some of our comments, we may ask you to provide us with information so we may better understand your disclosure.  After reviewing this information, we may raise additional comments.       Please understand that the purpose of our review process is to assist you in your compliance with the applicable disclosure requirements and to enhance the overall disclosure in your filing.  We look forward to working with you in these respects.  We welcome any questions you may have about our comments or any other aspect of our review.  Feel free to call us at the telephone numbers listed at the end of this letter.

Form 10-K for the Fiscal Year Ended September 30, 2008

Controls and Procedures, page 12

1. Please disclose the conclusions of management, regarding the effectiveness of your internal control over financial reporting as of September 30, 2008, to comply with Item 308 of Regulation S-K.

Mr. Nanuk Warman
Touchstone Mining Limited
June 9, 2009 Page 2

Financial Statements
 Report of Independent Registered Public Accounting Firm, Page F-2

 2. We note that your auditors have placed reliance on the work of other auditors in rendering their audit opinion on the inception-to-date information, for that portion of the cumulative period from September 12, 2005 (inception) through September 30, 2006.  Given this reliance, you will need to include the report of the prior auditors upon whom reliance is being placed, provided that you are able to obtain their permission.  If this is not feasible, your present auditors should remove the reference to the other auditors in their opinion. Under these circumstances, you will need to obtain a new audit of the inception-to-date information or revise your financial statements to identify the cumulative activity as “un-audited.”
 Exhibits

 3. The certifications you attached as Exhibits 31 to your September 30, 2008 Form 10-K and your subsequent interim periodi c reports on Form 10-Q, do not conform
to the requirements of Item 601(b)(31) of Regulation S-K as you have omitted the language pertaining to your responsibility for internal control over financial reporting, required in the introductory section of paragraph 4.  Please revise your annual and interim certifications to comply with your reporting obligations.
  Closing Comments

 As appropriate, please amend your filing and respond to these comments within
10 business days or tell us when you will provide us with a response.  You may wish to provide us with marked copies of the amendment to expedite our review.  Please furnish a cover letter with your amendment that keys your responses to our comments and provides any requested information.  Detailed cover letters greatly facilitate our review.  Please understand that we may have additional comments after reviewing your amendment and responses to our comments.    We urge all persons who are responsible for the accuracy and adequacy of the disclosure in the filing to be certain that the filing includes all information required under the Securities Exchange Act of 1934 and that they have provided all information investors require for an informed investment decision.  Since the company and its management are in possession of all facts relating to a company’s disclosure, they are responsible for the accuracy and adequacy of the disclosures they have made.

Mr. Nanuk Warman
Touchstone Mining Limited June 9, 2009 Page 3

 In connection with responding to our comments, please provide, in writing, a statement from the company acknowledging that:  ‚ the company is responsible for the adequacy and accuracy of the disclosure in the filing;
‚ staff comments or changes to disclosure in response to staff comments do not foreclose the Commission from taking any action with respect to the filing; and
‚ the company may not assert staff comments as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

In addition, please be advised that the Division of Enforcement has access to all
information you provide to the staff of the Di vision of Corporation Finance in our review
of your filing or in response to our comments on your filing.
You may contact Craig Arakawa at (202) 551-3650, if you have questions
regarding comments on the financial statements and related matters.  Please contact me at (202) 551-3686 with any other questions.          S i n c e r e l y ,             Karl Hiller         B r a n c h  C h i e f

CORRESP
1
filename1.htm

TOUCHSTONE MINING LIMITED - Request for Accelerated Filing

TOUCHSTONE MINING LIMITED

808 Nelson Street

Suite 2103

Vancouver, British Columbia

Canada V6Z 2H2

January 18, 2006

United States

Securities and Exchange Commission

Division of Corporate Finance

100 F Street, N.E.

Washington, D.C. 20549

Attention:

Mr. John Reynolds

Assistant Director

RE:

Touchstone Mining Limited

Form SB-2 Registration Statement

Registration No. 333-130696

Dear Mr. Reynolds:

Pursuant to the provisions of Rule 461 of Regulation C of the Securities Act of 1933, as amended, Touchstone Mining Limited (the "Company") requests acceleration of the effective date of its Form SB-2 Registration Statement to January 24, 2006, at 10:30 a.m., E.S.T., or as soon thereafter as practicable.

The Company is aware that the filing with the Securities and Exchange Commission (the "Commission") may not be relied upon in any degree to indicate that the registration statement is true, complete or accurate.

Please be advised that the Company has not distributed any preliminary prospectus and the Company is in compliance with Rule 15c2-8 of the Securities Exchange Act of 1934, as amended.

Further, no other documents, reports or memoranda have been prepared for external use by the Company.

The Company acknowledges that should the Commission or the staff, acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any action with respect to the filing; the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and the Company may not assert staff comments and the declaration of effectiveness as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

Securities and Exchange Commission

RE:     Touchstone Mining Limited

Form SB-2 Registration Statement

SEC File 333-130696

January 18, 2006

Page 2

The undersigned is aware of its respective responsibilities under the Securities Act of 1933, as amended, and the Securities Exchange Act of 1934, as amended, as they relate to the proposed transaction specified in the above captioned registration statement.

Thank you for your cooperation.

Yours truly,

TOUCHSTONE MINING LIMITED

BY:

/s/ Douglas Scheving

Douglas Scheving, President, Principal Executive Officer and a member of the Board of Directors

cc: Conrad C. Lysiak

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Mail Stop 3561

							January 4, 2006
Douglas Scheving, President
Touchstone Mining Ltd.
808 Nelson Street, Suite 2103
Vancouver, British Columbia
Canada  V6Z 2H2

Re:	Touchstone Mining Ltd.
	Registration Statement on Form SB-2
	Filed December 27, 2005
	File No. 333-130696

Dear Mr. Scheving:

      We have limited our review of your filing to those issues we
have addressed in our comments.  Where indicated, we think you
should
revise your document in response to these comments.  If you
disagree,
we will consider your explanation as to why our comment is
inapplicable or a revision is unnecessary.  Please be as detailed
as
necessary in your explanation.  In some of our comments, we may
ask
you to provide us with information so we may better understand
your
disclosure.  After reviewing this information, we may raise
additional comments.

      Please understand that the purpose of our review process is
to
assist you in your compliance with the applicable disclosure
requirements and to enhance the overall disclosure in your filing.
We look forward to working with you in these respects.  We welcome
any questions you may have about our comments or any other aspect
of
our review.  Feel free to call us at the telephone numbers listed
at
the end of this letter.

Comment

	Please amend your registration statement to include an
updated
accountants consent which bears only one date.

      As appropriate, please amend your registration statement in
response to these comments.  You may wish to provide us with
marked
copies of the amendment to expedite our review.  Please furnish a
cover letter with your amendment that keys your responses to our
comments and provides any requested information.  Detailed cover
letters greatly facilitate our review.  Please understand that we
may
have additional comments after reviewing your amendment and
responses
to our comments.

      We urge all persons who are responsible for the accuracy and
adequacy of the disclosure in the filing to be certain that the
filing includes all information required under the Securities Act
of
1933 and that they have provided all information investors require
for an informed investment decision.  Since the company and its
management are in possession of all facts relating to a company`s
disclosure, they are responsible for the accuracy and adequacy of
the
disclosures they have made.

      Notwithstanding our comments, in the event the company
requests
acceleration of the effective date of the pending registration
statement, it should furnish a letter, at the time of such
request,
acknowledging that:

?	should the Commission or the staff, acting pursuant to
delegated
authority, declare the filing effective, it does not foreclose the
Commission from taking any action with respect to the filing;

?	the action of the Commission or the staff, acting pursuant to
delegated authority, in declaring the filing effective, does not
relieve the company from its full responsibility for the adequacy
and
accuracy of the disclosure in the filing; and

?	the company may not assert staff comments and the declaration
of
effectiveness as a defense in any proceeding initiated by the
Commission or any person under the federal securities laws of the
United States.

	In addition, please be advised that the Division of
Enforcement
has access to all information you provide to the staff of the
Division of Corporation Finance in connection with our review of
your
filing or in response to our comments on your filing.

      We will consider a written request for acceleration of the
effective date of the registration statement as confirmation of
the
fact that those requesting acceleration are aware of their
respective
responsibilities under the Securities Act of 1933 and the
Securities
Exchange Act of 1934 as they relate to the proposed public
offering
of the securities specified in the above registration statement.
We
will act on the request and, pursuant to delegated authority,
grant
acceleration of the effective date.

      We direct your attention to Rules 460 and 461 regarding
requesting acceleration of a registration statement.  Please allow
adequate time after the filing of any amendment for further review
before submitting a request for acceleration.  Please provide this
request at least two business days in advance of the requested
effective date.

      You may contact Goldie B. Walker, Financial Analyst, at
(202)
551-3234 or me at (202) 551-3790 with any questions.

						Sincerely,

								John D. Reynolds
								Assistant Director

cc:	Corporation Trust Company of Nevada
            6100 Neil Road, Suite 500
            Reno, NV  89511

           Conrad C. Lysiak, Esq.
           601 West First Avenue, Suite 503
           Spokane, WA  99201

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Douglas Scheving, President
Touchstone Mining Ltd.
January 4, 2006
Page 3

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