SecProbe.io

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Correspondence

 Pro-Pharmaceuticals, Inc.

7 Wells Avenue

Newton, Massachusetts 02459

 Via
EDGAR and U.S. Mail

 October 5, 2010

Securities and Exchange Commission

 Division of
Corporation Finance

 100 F Street, N.E.

Washington, D.C. 20549-4628 U.S.A.

 Attention:
Jeffrey Riedler. Assistant Director

Re:
Pro-Pharmaceuticals, Inc.

Registration Statement on Form S-I

Filed September 17, 2010

File No. 333-169463

 Dear
Mr. Riedler:

 This letter is submitted on behalf of Pro-Pharmaceuticals, Inc. (the “Company” or “we”)
in response to the comments of the staff of the Division of Corporation Finance of the U.S. Securities and Exchange Commission (the “Staff” or “you”) dated September 27, 2010 (the “Comment Letter”) with respect to
the Company’s Registration Statement on Form S-1 (the “Registration Statement”), which was filed on September 17, 2010.

For reference purposes, the text of the Comment Letter has been reproduced herein with a response below the comments. For your
convenience, we have italicized each comment and have placed in boldface the heading of our response thereto.

 General

1.
We note that you are registering the sale of 52,254,130 shares. Given the size relative to the number of shares outstanding held by non-affiliates, the nature of the
offering and the selling shareholders, the transaction appears that it may be a primary offering. Because you would not be 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) on Form 5-1. As a result, if this offering is deemed to be a primary offering, you must:

•

 file a registration statement for the “resale” offering at the time of each conversion of preferred stock or exercise of warrants because
you are not eligible to conduct the offering on a delayed or continuous basis under Rule 41 5(a)(1)(x);

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•

 identify the selling shareholders as underwriters in the registration statement; and

•

 include the fixed price at which the deemed underwriters will sell the securities.

If you disagree with our analysis, please advise the staff of the company’s basis for determining that the transaction is
appropriately characterized as a transaction that is eligible to be made under Rule 4l5(a)(l)(i). In your analysis, please address the following, among any other relevant factors:

•

 The number of selling shareholders and the percentage of the overall offering made by each shareholder;

•

 The date on which and the manner in which each selling shareholder received the shares and/or the overlying securities;

•

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

•

 Any relationships among the selling shareholders;

•

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

•

 The discount at which the shareholders will purchase the common stock underlying the convertible preferred stock and warrants upon conversion
and exercise, respectively; and

•

 Whether or not any of the selling shareholders is in the business of buying and selling securities.

Response to Comment No. 1

Rule 415 provides that “(a) [s]ecurities may be registered for an offering on a continuous or delayed basis in the future, provided
that (1) the registration statement pertains only to (i) [s]ecurities which are to be offered or sold solely by or on behalf of … persons other than the registrant, …” These are commonly referred to as secondary offerings.
We have reviewed the Staff’s guidance set forth in Securities Act Rules Compliance and Disclosure Interpretations Question 612.09 that identifies certain factors to consider in determining whether “an offering styled as a secondary one is
really on behalf of the issuer” and note its comment that the facts and circumstances of a transaction are critical to the determination. We also are aware that in recent years the Staff has raised concerns, usually with respect to PIPE
transactions, that selling stockholders may be acting as underwriters and that the resale shelf transaction is an indirect primary offering where a significant percentage, such as greater than one third of the public float, is sought to be
registered for resale.

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 The totality of the facts and circumstances demonstrate that in this case the selling
stockholders listed in the Registration Statement are not acting as underwriters or conduits for the Company. Although the number of shares subject to the Registration Statement exceeds one-third of the public float, we respectfully submit that this
should not be the determinative factor. We believe this factor is outweighed by the following:

•

 The Registration Statement names three selling stockholders, the principal one being the 10X Fund, L.P. (“10X Fund”) which owns or has
rights to acquire more than 99% of the shares of the common stock of the Company (the “Common Stock” offered for resale in the Registration Statement (the “Resale Shares”). Of the approximately 52,000,000 Resale
Shares that the 10X Fund is offering to sell, 48,000,000, or more than 92%, of the Resale Shares cannot be sold until the 10X Fund actually acquires the shares of Common Stock (the “Underlying Shares”) by converting its shares of
the Company’s Series B-1 Convertible Preferred Stock and Series B-2 Convertible Preferred Stock (collectively, the “Series B Preferred”) and exercising the related warrants (the “Series B Related Warrants”).

•

 The 10X Fund and the Company entered into definitive agreements dated February 12, 2009 (the “Sale Date”) for the issuance and
sale of the Series B Preferred and Series B Related Warrants (collectively, the “Purchased Securities”), which were acquired in a series of tranches. The Company was actively pursuing other financing opportunities in the first
quarter of 2009, including a rights offering, and the principals of the 10X Fund were not then directors of the Company; accordingly, it conducted the negotiations with the 10X Fund at arms’ length. The terms of the acquisition of the Purchased
Securities, including purchase price, were “fixed” in the transaction documents as of the Sale Date (which specified $0.50 as the conversion price for the Series B Preferred and as the exercise price for the Series B Related Warrants when
the trading price of the Underlying Shares was $0.20) notwithstanding that the 10X Fund elected to complete its acquisition in tranches.

•

 The three selling stockholders named in the Registration Statement are not a “group” within the meaning of Section 13(d)(3) of the
Securities Exchange Act of 1934. David Platt, Ph.D., although a founding stockholder and former chief executive officer resigned from the Company on the Sale Date and since then has had no relation with the Company other than as a stockholder. He
and the third selling stockholder acquired their securities (described in Response No. 7 below) in a transaction separate from and prior to that of the 10X Fund.

•

 The intention of 10X Fund to be a long-term investor in the Company, rather than a purchaser who could be deemed an underwriter by virtue of seeking an
immediate resale “exit” from its investment, is apparent from several factors:

•

 First, during the approximately 18-month period since the Sale Date, the 10X Fund has neither converted nor exercised any of the Purchased Securities
to acquire Underlying Shares, nor during such period has it sold under Rule 144 any shares of Common Stock that it received as stock dividends on the Series B Preferred. Not until May 2010 (and after nearly all tranches of the Purchased Securities)
has the trading price of the Common Stock consistently exceeded $0.50

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•

 Second, as a condition to the investment, the 10X Fund required the replacement of four of the nine members of the Company’s Board of Directors,
of which two of the four Board positions are nominated and elected by the 10X Fund as sole holder of the Series B Preferred which votes as a separate class on this matter. Although one or more of the new Board members may also be limited partners of
the 10X Fund, they were selected primarily because they are public company veteran executives or well-known for their expertise in drug and business development and related regulatory matters. Following their appointment to fill vacancies created by
the resignations of four former members of the Board, the new Board members were elected at the 2009 and 2010 annual stockholders meetings.

•

 Third, 10X Fund negotiated to structure the Purchased Securities to create a long-term investment incentive. For example, each share of Series B
Preferred, purchased for $2.00, converts at a fixed ratio to four Underlying Shares (1:4) rather than at a floating rate discounted relative to the then-trading price of the Common Stock. In addition, the exercise price for the Series B Related
Warrants was fixed at $0.50 per share (250% of the $0.20 Common Stock trading price on the Sale Date) so as to avoid triggering full-ratchet anti-dilution exercise price protection of warrants previously sold by the Company. Two classes of the
Series B Related Warrants contain a mandatory exercise “window” that starts when the Company’s Common Stock trading price reaches certain levels such that, if exercised, the Company receives cash proceeds or, if declined the warrants
expire, thus preventing further stockholder dilution. These factors make clear that 10X Fund acquired the Purchased Securities with an intent to “restart” the Company and without any certainty or contractual assurances that it would ever
be economic to convert or exercise these securities.

•

 Although the 10X Fund would likely be deemed an affiliate of the Company by virtue of its rights contained in the certificate of designation for the
Series B Preferred and percentage of its stock ownership, the limited trading volume and relatively low trading price of the Common Stock prevent 10X Fund, as a practical matter, from aggressively exiting its investment for the foreseeable future.

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•

 The 10X Fund purchased, for net proceeds of $5.53 million, 3,000,000 shares of Series B Preferred convertible to 12,000,000 Underlying Shares and
Series B Related Warrants exercisable to purchase 36,000,000 Underlying Shares. Insofar as the closing price of the Common Stock was $0.20 per share on the Sale Date, representing approximately $2,400,000 in market value for 12,000,000 Underlying
Shares issuable had the 10X Fund then converted its shares of Series B Preferred, it is clear the net proceeds of the investment substantially exceeded the then value of the Underlying Shares. Moreover, as long as a registration statement is in
effect with respect to the 36,000,000 Resale Shares issuable upon exercise of the Series B Related Warrants, the warrants are exercisable solely for cash, which if fully exercised would result in an additional $18,000,000 to the Company.

•

 None of the selling stockholders is in the business of buying and selling securities. To our knowledge, the 10X Fund has not invested in any other
company.

 Based on the foregoing facts and circumstances, we believe the transaction subject to the
Registration Statement is a secondary offering eligible to be made under Rule 415(a)(1)(i) and that the selling stockholders should not be deemed underwriters.

Dollar value of underlying securities

2.
Please provide us, with a view toward disclosure in the prospectus, with the total dollar value of the securities underlying the convertible preferred stock that you
have registered for resale (using the number of underlying securities that you have registered for resale and the market price per share for those securities on the date of the sale of the convertible preferred stock).

Response to Comment No. 2

Based on the $0.20 market price of the Underlying Shares on the Sale Date, the total dollar value of 12,000,000 Underlying Shares relative
to the Series B Preferred was $2,400,000, an amount that is substantially less than the $6,000,000 paid for the Purchased Securities.

Payments to the investor and affiliates

3.
Please provide us, with a view toward disclosure in the prospectus, with tabular disclosure of the dollar amount of each payment (including the value of any payments
to be made in common stock) in connection with the transaction that you have made or may be required to make to any selling shareholder, any affiliate of a selling shareholder, or any person with whom any selling shareholder has a contractual
relationship regarding the transaction (including any interest payments, liquidated damages, payments made to “finders” or “replacement agents,” and any other payments or potential payments). Please provide footnote disclosure of
the terms of each such payment. Please do not include any repayment of the convertible preferred stock in this disclosure.

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 Further, please provide us, with a view toward disclosure in the prospectus, with
disclosure of the net proceeds to the issuer from the sale of the convertible preferred stock and the total possible payments to all selling shareholders and any of their affiliates in the first year following the sale of the convertible preferred
stock.

 Response to Comment No. 3

Please see the table below which sets forth payments we made to or on behalf of the 10X Fund as of the first anniversary (February 12,
2010) of the Sale Date and as of the sale of the final tranche of the Purchased Securities (May 10, 2010). We did not pay any amounts to its affiliates. We have no further payment obligations to or on behalf of the 10X Fund in connection with the
sale of the Purchased Securities. The net proceeds to us was $5,532,955.

Paid as of First
Anniversary of Sale Date

Total Paid

 Origination Fee (3%) paid to 10X Fund

$
143,550

$
180,000

 10X Fund counsel fee

130,410

150,285

 Other professional & consulting fees of 10X Fund

84,761

88,661

 Other 10X Fund expenses

47,558

48,099

$
406,279

$
467,045

 Potential profits on conversion

4.
Please provide us, with a view toward disclosure in the prospectus, with tabular disclosure of:

•

 the total possible profit the selling shareholders could ±realize as a result of the conversion discount for the securities underlying the
convertible preferred stock, presented in a table with the following information disclosed separately:

•

 the market price per share of the securities underlying the convertible preferred stock on the date of the sale of the convertible preferred
stock;

•

 the conversion price per share of the underlying securities on the date of the sale of the convertible preferred stock, calculated as follows:

•

 if the conversion price per share is set at a fixed price, use the price per share established by the convertible preferred stock, and

•

 if the conversion price per share is not set at a fixed price and, instead, is set at a floating rate in relationship to the market price of the
underlying security, use the conversion discount rate and the market rate per share on the date of the sale of the convertible preferred stock and determine the conversion price per share as of that date;

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•

 the total possible shares underlying the convertible preferred stock (assuming no interest payments and complete conversion througho