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Mail Stop 4720          October 8, 2009   Harry S. Palmin President and Chief Executive Officer Novelos Therapeutics, Inc. One Gateway Center, Suite 504 Newton, Massachusetts 02458
 Re: Novelos Therapeutics, Inc.
  Registration Statement on Form S-1
  Filed September 15, 2009
  File No. 333-161922

Dear Mr. Palmin:

We have limited our review of the above referenced registration statement to only
the issues identified herein.  Where indicated, we think you should revise your document in response to these comments.  If you disagr ee, we will consider your explanation as to
why our comment is inapplicable or a revisi on is unnecessary.  Please be as detailed as
necessary in your explanation.   Please understand that the purpose of our re view 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 S-1

1. We note that you are registering the sale of 58,745,592 shares of common stock.
Given the size relative to the number of shares outstanding held by non-affiliates,
the nature of the offering and the selli ng security holders, th e 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).

If you disagree with our analysis, please advise the staff of the company’s basis
for determining that the transaction is a ppropriately characterized as a transaction

Harry S. Palmin
Novelos Therapeutics, Inc.
October 8, 2009 Page 2
that is eligible to be made under Ru le 415(a)(1)(i). In your analysis, please
address the following among any other relevant factors:

• The number of selling shareholders and th e 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 sharehol der is an affiliate of the company;

• Any relationships among th e selling shareholders;
 • The dollar value of the shares registered in relation to the proceeds that the
company received from the selling share holders for the 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 Series E Preferred Stock( or any related security, such as a
warrant or option) upon conve rsion or exercise; and

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

2. Please provide us, with a view toward disc losure in the prospectus, with the total
dollar value of the securi ties underlying the Series E Preferred Stock that you
have registered for resale (using the number of underl ying securities that you have
registered for resale and the market pri ce per share for those securities on the date
of the sale and issuance of th e Series E Preferred Stock).

3. Please provide us, with a view toward disc losure 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 ma ke to any selling shareholder, any
affiliate of a selling shareholder, or any person with whom any selling shareholder
has a contractual relationsh ip regarding the transacti on (including any interest
payments, liquidated damages, payments  made to “finders” or “placement
agents,” and any other payments or poten tial payments).  Please provide footnote
disclosure of the terms of each such payment.

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 Series E Preferred

Harry S. Palmin
Novelos Therapeutics, Inc.
October 8, 2009 Page 3
Stock and the total possible payments to all selling shareholders and any of their affiliates in the first year following the sale of Series E Preferred Stock.

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 unde rlying the Series E Preferred Stock,
presented in a table with the following  information disclosed separately:

• the market price per share of the securities underlying the Series E
Preferred Stock on the date of the sale  of the Series E Preferred Stock;

• the conversion price per share of the underlying securities on the date
of the sale of the Series E Prefe rred Stock, calculate d as follows:

− if the conversion price per share is  set at a fixed price, use the
price per share established in the Series E 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 Series E Preferred Stock and determine the conversion price per share as of that date;

• the total possible shares underlyi ng Series E Preferred Stock;

• the combined market price of the total number of shares underlying the
Series E Preferred Stock, calcula ted by using the market price per
share on the date of the sale of th e Series E Preferred Stock and the
total possible shares underlying the Series E Preferred Stock;

• the total possible shares the selling shareholders may receive and the
combined conversion price of the total number of shares underlying
the Series E Preferred Stock calculated by using the conversion price on the date of the sale of the Series E Preferred Stock and the total possible number of shares the selling shareholders may receive; and

•  the total possible discount to the market price as of the date of the sale
of the Series E Preferred Stock, calculated by subtr acting the total
conversion price on the date of the sa le of the Series E Preferred Stock
from the combined market price of the total number of shares
underlying the Series E Preferred Stock on that date.

Harry S. Palmin
Novelos Therapeutics, Inc.
October 8, 2009 Page 4
If there are terms of the Series E Preferred Stock that could result in a change in the price per share upon th e occurrence of certain events, please provide
additional tabular disclosure as appropriate. For example, if the conversion price
per share is fixed unless and until the market price falls below a stated price, at
which point the conversion price per share drops to a lower price, please provide
additional disclosure.

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 other 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 securities 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 pe r share is set at a fixed price,
use the price per share on the da te of the sale of that other
security; and

− if the conversion/exercise price per share is not set at a fixed
price and, instead, is set at a floa ting rate in relationship to the
market price of the underlying security, use the conversion/exercise discount rate and the market rate per share on the date of the sale of that other security and determine the
conversion price per share as of that date;

• the total possible shares  to be received under the particular securities
(assuming complete conversion/exercise);

• the combined market price of th e total number of underlying shares,
calculated by using the market price pe r 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 combined conversion price
of the total number of shares underlyi ng that other security calculated by
using the conversion price on the date of the sale of that other security and

Harry S. Palmin
Novelos Therapeutics, Inc.
October 8, 2009 Page 5
the total possible number of  underlying shares; and

• the total possible discount to the market price as of the date of the sale of
that other security, calculated by subt racting the 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 shares on that date.

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 Series E Preferred Stock
transaction;

• all payments that have been made or that may be required to be made by the
issuer that are disclosed in response to comment 3 above;

• 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 secu rities underlying the Seri es E Preferred Stock and
any other warrants, options, notes, or other securities of the issuer that are held
by the selling shareholders or any affiliates of the selling shareholders that is disclosed in response to comments 4 and 5 above.

Further, please provide us, with a view to ward disclosure in the prospectus, with
disclosure – as a percentage – of the total amount of all possible payments, as
disclosed in response to comment 3 above , and the total possible discount to the
market price of the shares underlying the Series E Preferred Stock, as disclosed in response to comment 4 above, divided by th e net proceeds to the issuer from the
sale of the Series E Preferred Stock.

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 shareholder has a contractual relationship regarding the transaction (or any predecessors of those persons), with
the table including the following information disclosed separately for each transaction:

• the date of the transaction;

• the number of shares of the class of secu rities subject to the transaction that
were outstanding prior to the transaction;

Harry S. Palmin
Novelos Therapeutics, Inc.
October 8, 2009 Page 6
• the number of shares of the class of secu rities subject to the transaction that
were outstanding prior to the transacti on and held by persons other than the
selling shareholders, affiliates of th e company, or affiliates of the selling
shareholders;

• the number of shares of the class of secu rities subject to the transaction that
were issued or issuable in connection with the transaction;

• the percentage of total is sued and outstanding securiti es that were issued or
issuable in the transaction (assuming full issuance), with the percentage
calculated by taking the number of shar es issued and outstanding prior to the
applicable transaction and held by persons other than the selling shareholders,
affiliates of the company, or affiliates of the selling shareholders, and dividing that number by the number of shares issued  or issuable in connection with the
applicable transaction;

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

8. Please provide us, with a view toward disc losure in the prospectus, with tabular
disclosure comparing:

• the number of shares outstanding prior to the Series E Preferred Stock
transaction that are held by persons other than the selling shareholders,
affiliates of the company, and affiliates of the selling shareholders;

• the number of shares registered for re sale by the selling shareholders or
affiliates of the selling shareholders in prior registration statements;

• the number of shares registered for re sale 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 resa le 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 sharehol ders in the current transaction.

In this analysis, the calculation of the number of outstanding shares should not

Harry S. Palmin
Novelos Therapeutics, Inc.
October 8, 2009 Page 7
include any securities underlying any outst anding convertible securities, options,
or warrants.

9. Please provide us, with a view toward di sclosure in the prospectus, with the
following information:

• whether the issuer has the intention, and a reasonable basis to believe that it
will have the financial ability, to make all payments on the overlying securities; and

• whether – based on information obtained from the selling shareholders – any
of the selling shareholders have an existing short 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 shareholder entered into that short position; and

− the relationship of the date on which each such selling
shareholder entered into that sh ort position to the date of the
announcement of the Series E Preferred Stock transaction and
the filing of the registration stat ement (e.g., before or after the
announcement of the Series E Preferred Stock transaction, before the filing or after the fili ng of the registration statement,
etc.).

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 future
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
shareholder has a contractual relationsh ip regarding the transaction (or any
predecessors of those persons) – the in formation provided should include, in
reasonable detail, a complete descripti on of the rights and obligations of the
parties in connection with the sale of  the Series E Preferred Stock; and

• copies of all agreements 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 share holder has a contractual relationship
regarding the transaction (or any predece ssors of those persons) in connection
with the sale of the Series E Preferred Stock.

If it is your view th at such a description of the relationships and arrangements

Harry S. Palmin
Novelos Therapeutics, Inc.
October 8, 2009 Page 8
between and among those parties already is presented in the prospectus and