SecProbe.io

September 27, 2010

Theodore D. Zucconi, Ph.D.  Chief Executive Officer and President  Pro-Pharmaceuticals, Inc.  7 Wells Avenue
Newton, Massachusetts 02459

Re: Pro-Pharmaceuticals, Inc.
  Registration Statement on Form S-1
Filed September 17, 2010
  File No. 333-169463

Dear Dr. Zucconi:
 We have limited our review of your registra tion statement to those issues we have
addressed in our comments.
 Please respond to this letter by providing the requested information, with a view toward
disclosure in the prospectus.  Where you do not believe our co mments apply to your facts and
circumstances, please tell us  why in your response.
 After reviewing the information you provide in response to these comments, we may
have additional comments.

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 S-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 415(a)(1)(x);
• identify the selling shareholders  as underwriters in the registration statement; and
• include the fixed price at which the deem ed 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

Theodore D. Zucconi, Ph.D.
Pro-Pharmaceuticals, Inc.
September 27, 2010
Page 2

under Rule 415(a)(1)(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 th e securities, excluding amounts of proceeds
that were returned (or will be returned) to the selling shareholders and/or 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.

Dollar value of underlying securities

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

Payments to the investor and affiliates

3. Please provide us, with a view toward disc losure in the prospectus, with tabular
disclosure of the dollar amount of each paymen t (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 shareholde r has a contractual re lationship regarding
the transaction (including any interest paym ents, liquidated damages, payments made to
“finders” or “placement agents,” and any othe r payments or potential payments). Please
provide footnote disclosure of the terms of each such payment. Please do not include any
repayment of the convertible prefe rred stock in this disclosure.

Further, please provide us, with a view to ward 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.

Theodore D. Zucconi, Ph.D.
Pro-Pharmaceuticals, Inc.
September 27, 2010
Page 3

Potential profits on conversion
 4. Please provide us, with a view toward disc losure in the prospectus, with tabular
disclosure of:
• the total possible profit the selling share holders 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 securi ties underlying the convertible preferred
stock on the date of the sale of the convertible preferred stock;
• the conversion price per share of the underl ying securities on the date of the sale
of the convertible preferred st ock, calculated as follows:
-  if the conversion price per share is set at a fixed price, use the price per
share established by the convert ible preferred stock; and
-  if the conversion price per share is no t 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 convertib le preferred stock and determine the
conversion price per shar e as of that date;
• the total possible shares underlying the convertible preferre d stock (assuming no
interest payments and complete conversi on throughout the term of the convertible
preferred stock);
• the combined market price of the total number of shares underlying the
convertible preferred stock, calculated by using the market price per share on the
date of the sale of the convertible pref erred stock and the total possible shares
underlying the convertible  preferred stock;
• the total possible shares the selling shar eholders may receive and the combined
conversion price of the total number of  shares underlying the convertible
preferred stock calculated by using the conve rsion price on the date  of the sale of
the convertible preferred stock and the to tal possible number of shares the selling
shareholders may receive; and
• the total possible discount to  the market price as of th e date of the sale of the
convertible preferred stock, calculated by subtracting the total conversion price on
the date of the sale of the convertible preferred stock from the combined market
price of the total number of shares unde rlying the convertible preferred stock on
that date.
If there are provisions in the c onvertible preferred stock that could result in a change in
the price per share upon the occurrence of cer tain events, please provide additional
tabular disclosure as appropriate. For example,  if the conversion pric e per share is fixed
unless and until the market price falls below a stated price, at whic h point the conversion
price per share drops to a lower price,  please provide additional disclosure.

Theodore D. Zucconi, Ph.D.
Pro-Pharmaceuticals, Inc.
September 27, 2010
Page 4

 Total potential profit from other securities

 5. Please provide us, with a view toward disc losure in the prospectus, with tabular
disclosure of:
• the total possible profit to be  realized as a result of any conversion discounts for
securities underlying any other warrants, options, notes, or othe r securities of the
issuer that are held by the selling shareholders or any affiliates of the selling
shareholders, presented in a table with the following information disclosed separately:
• market price per share of the underlying secu rities on the date of  the sale of that
other security;
• the conversion/exercise price per share as of the date of the sale of that other
security, calculated as follows:
- if the conversion/exercise price per share is set at a fixed price, use the price
per share on the date of the sale  of that other security; and
- if the conversion/exercise price per sh are is not set at a fixed price and,
instead, is set at a floating rate in re lationship to the market price of the
underlying security, use the conversion/ex ercise discount rate and the market
rate per share on the date of the sale of  that other security  and determine the
conversion price per shar e as of that date;
• the total possible shares to  be received under the partic ular securities (assuming
complete conversion/exercise);
• the combined market price of the total number of underlying shares, calculated by
using the market price per share on the date of the sale of that other security and
the total possible shares  to be received;
• the total possible shares to  be received and the combin ed conversion price of the
total number of shares underlying that other security calculated by using the
conversion price on the date of the sale of that other security and the total possible
number of underl ying shares; and
• the total possible discount to the market price as of the date of the sale of that
other security, calculated by subtracting th e total conversion/exercise price on the
date of the sale of that other security from the combined market price of the total
number of underlying sh ares on that date.

Comparison of issuer proceeds to potential investor profit

6. Please provide us, with a view toward disc losure in the prospectus, with tabular
disclosure of:
• the gross proceeds paid or payable to the issuer in the convertible preferred stock
transaction;

Theodore D. Zucconi, Ph.D.
Pro-Pharmaceuticals, Inc.
September 27, 2010
Page 5

• all payments that have been made or that  may be required to be made by the issuer
that are disclosed in response to comment 2;
• the resulting net proceeds to the issuer; and
• the combined total possible profit to be realized as a result of any conversion
discounts regarding the securities underlyi ng the convertible preferred stock and any
other warrants, options, notes, or other secu rities of the issuer that are held by the
selling shareholders or any affiliates of the selling shareholders that is disclosed in
response to comments 3 and 4.

Further, please provide us, with a view to ward disclosure in the prospectus, with
disclosure – as a percentage – of the total amount of all possi ble payments as disclosed in
response to comment 2 and the total possible di scount to the market price of the shares
underlying the convertible preferred stock as disclosed in response to comment 3 divided
by the net proceeds to the issuer from the sale  of the convertible preferred stock, as well
as the amount of that resulting percentage averaged over the term of the convertible preferred stock.
Prior transactions between the i ssuer and the selling shareholders

 7. Please provide us, with a view toward disc losure in the prospectus, with tabular
disclosure of all prior securities transact ions between the issuer (or any of its
predecessors) and the selling shareholders, any affiliates of the selling shareholders, or any person with whom any selling shareholde r has a contractual re lationship regarding
the transaction (or any predecessors of thos e persons), with the table including the
following information disclosed sepa rately for each transaction:
• the date of the transaction;
• the number of shares of the class of securi ties subject to the transaction that were
outstanding prior to the transaction;
• the number of shares of the class of securi ties subject to the transaction that were
outstanding prior to the transaction and held by persons other than the selling
shareholders, affiliates of the company, or affiliates of the selling shareholders;
• the number of shares of the class of securi ties subject to the transaction that were
issued or issuable in connection with the transaction;
• the percentage of total issued  and outstanding securities that  were issued or issuable
in the transaction (assuming full issuance), with the percentage calculated by taking
the number of shares issued and outstanding prior to the applicable transaction and
held by persons other than the selling sh areholders, affiliates of the company, or
affiliates of the selling shareholders, and dividing that number by the number of shares issued or issuable in connecti on with the applicable transaction;
• the market price per share of the class of  securities subject to the transaction

Theodore D. Zucconi, Ph.D.
Pro-Pharmaceuticals, Inc.
September 27, 2010
Page 6

immediately prior to the tran saction (reverse split adju sted, if necessary); and
• the current market price per share of the cla ss of securities subject  to the transaction
(reverse split adjusted, if necessary).

Comparison of registered shares to outstanding shares

8. Please provide us, with a view toward disc losure in the prospectus, with tabular
disclosure comparing:
• the number of shares outstanding prior to th e convertible preferred stock transaction
that are held by persons other than the sel ling shareholders, affiliates of the company,
and affiliates of the selling shareholders;
• the number of shares registered for resale by the selling shareholders or affiliates of
the selling shareholders in prior registration statements;
• the number of shares registered for resale by the selling shareholders or affiliates of
the selling shareholders that continue to be held by the selling shareholders or
affiliates of the selling shareholders;
• the number of shares that have been sold in registered resale  transactions by the
selling shareholders or affiliates of the selling shareholders; and
• the number of shares registered for resale on behalf of the selling shareholders or
affiliates of the selling shareholders in the current transaction.

In this analysis, the calculation of the numbe r of outstanding shares should not include
any securities underlying any outstanding conve rtible securities, options, or warrants.

The presence or absence of shor t selling by the selling shareholders

9. Please provide us, with a view toward disclo sure in the prospectus , with the following
information:
• whether – based on information obtained from  the selling shareholders – any of the
selling shareholders have an existing s hort position in the company’s common stock
and, if any of the selling shareholders have an existing short position in the
company’s stock, the following additional information:  • the date on which each such selling share holder entered into that short position;
and
• the relationship of the date on which each such selling shareholder entered into
that short position to the date of the announcement of the convertible preferred
stock transaction and the f iling of the registration stat ement (e.g., before or after
the announcement of the convert ible preferred stock transaction, before the filing
or after the filing of the regi stration statement, etc.).

Theodore D. Zucconi, Ph.D.
Pro-Pharmaceuticals, Inc.
September 27, 2010
Page 7

Relationships between the issu er and selling shareholders

10. Please provide us, with a view toward disclosure in the prospectus, with:
• a materially complete description of the relationships and arrangements that have
existed in the past three years or are to be performed in the futu re between the issuer
(or any of its predecessors) and the selli ng shareholders, any affiliates of the selling
shareholders, or any person with whom any selling shareholder has a contractual relationship regarding the