Exhibit 10.1



Amendment No 4



AMENDMENT TO

LICENSE AND COLLABORATION AGREEMENT



THIS AMENDMENT TO LICENSE AND COLLABORATION AGREEMENT (this Amendment), is entered into this 8th day of July, 2009 (the Effective Date) by and between Santaris Pharma A/S, a Danish corporation, having its principal place of business at Hørsholm, Denmark (Santaris), and Enzon Pharmaceuticals, Inc., a Delaware corporation, having its principal place of business at Bridgewater, New Jersey 08807 (Enzon). Santaris and Enzon may be referred to herein individually as a Party or collectively, as the Parties.



BACKGROUND



WHEREAS,
    Enzon and Santaris entered into the License and Collaboration Agreement dated
July 26, 2006 (the Agreement); and



WHEREAS, the Agreement was amended by Amendment No. 1 dated 13th of June 2007, Amendment No. 2 dated 25th of June 2007, and Amendment No. 3 dated 21st of December 2007; and



WHEREAS,
  Enzon and Santaris desire to amend and restate certain provisions of the
  Agreement.



NOW, THEREFORE, in consideration of the covenants and obligations expressed herein and intending to be legally bound, and otherwise bound by proper and reasonable conduct, the Parties agree as follows:



| | 1. | Capitalized terms used herein and not otherwise defined shall have the meanings given to them
| | -- | ---------------------------------------------------------------------------------------------

in the Agreement.



| | 2. | Section 8.1 (c) of the Agreement is hereby amended and restated in its entirety as follows:
| | -- | -------------------------------------------------------------------------------------------



(c) In Respect of all LNA Compound Patents:



(i)          Santaris
and Enzon shall jointly own the right, title and interest in and to all provisional
and other priority LNA Compound Patent applications regardless of inventorship;
and without the need for any further action by a Party and subject to the licenses
granted hereunder.



(ii)          At
    the time of filing of each international patent application filed under the Patent
    Cooperation Treaty (a PCT Application), if not already jointly
    owned, Santaris and Enzon shall jointly own the right, title and interest
    in and to such PCT Application, regardless of inventorship; and without the
    need for any further action by a Party and subject to the licenses granted
    hereunder. Santaris agrees to assign, and herby does assign, such right,
    title and interest in and to any LNA Compound Patents to Enzon so that Santaris
    and Enzon shall jointly own such LNA Compound Patents. For clarity, such
a PCT Application shall be filed in both Santaris and Enzon names.



(iii)At
the time each PCT Application enters the national or regional phase in any



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country or region in the Santaris Territory, Enzon agrees to assign, and hereby does assign, such right, title and interest in and to any such LNA Compound Patent to Santaris so that Santaris shall own the entire right, title and interest in and to such LNA Compound Patent in all countries in the Santaris Territory.



(iv)          At
the time each PCT Application enters the national or regional phase in any country
or region in the Enzon Territory, Santaris and Enzon shall continue to jointly
own such LNA Compound Patent in all countries in the Enzon Territory.



(v)          Promptly
after the Effective Date, Santaris shall assign and hereby does assign, to
Enzon such right, title and interest in and to all existing LNA Compound Patents
listed on Schedule 1.57 that are PCT Applications or have entered the national
phase in any country in the Enzon Territory so that Santaris and Enzon shall
jointly own such LNA Compound Patents, except for those that have already entered
the national or regional phase in any country or region in the Santaris Territory
so that Santaris shall continue to own those LNA Compound Patents in the Santaris
Territory.



(vi)          If
    any given LNA Compound is not selected as a Selected LNA Compound by the
    latest date required by the Agreement, Enzon agrees to assign, and herby
    does assign, such right, title and interest in and to any LNA Compound Patents
covering such LNA Compound to Santaris.



(vii)         Enzon
    discontinues all Development or Commercialization activities of all Selected
LNA Compounds claimed under an LNA Compound Patent jointly owned by the Parties,
Enzon shall then assign its entire, right, title and interest in such LNA Compound
Patent to Santaris.



(viii)        Except
to the extent permitted under Section 2.4 or with the prior written consent of
Santaris, Enzon shall not assign, license, grant, suffer, permit or otherwise
transfer any license, rights, security interest, lien or other encumbrance, or
other interest of any kind in such LNA Compound Patents (except in connection
with an assignment pursuant to Section 14.8).



| | 3. | Section 8.2 (c) of the Agreement is hereby amended and restated in its entirety as follows:
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(c) LNA Compound Patents.
    With respect to inventions made with no inventive contribution by Santaris employees,
    Enzon shall initially file and prosecute all provisional and other priority
    patent applications which at least shall be filed in the United States. The
    parties shall jointly prepare the PCT Applications derived from such provisional
    and other priority patent applications and each of Santaris and Enzon shall
    have the right to approve the initial filing of the PCT Applications. Enzon
    shall file, prosecute and maintain such PCT Applications for the benefit
of both Parties.



With
    respect to inventions made with inventive contribution by Santaris employees,
    Santaris shall initially file and prosecute all provisional and other priority
    patent applications which at least shall be filed in the United States. The
    parties shall jointly prepare the PCT Applications derived from such provisional
    and other priority patent applications and each of Santaris and Enzon shall
have the right to approve the initial



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filing of the PCT Applications. Santaris shall file, prosecute and maintain such PCT Applications for the benefit of both Parties.



At the time each such PCT Application enters the national or regional phase in any country in the Santaris Territory, Santaris shall thereafter direct the filing, prosecution (including any interferences, oppositions, reissuance, and re-examinations) and maintenance of all LNA Compound Patents in countries in the Santaris Territory.



At the time each such PCT Application enters the national or regional phase in any country in the Enzon Territory, Enzon shall thereafter direct the filing, prosecution (including any interferences, oppositions, reissuance, and re-examinations) and maintenance of all LNA Compound Patents in countries in the Enzon Territory.



The
    Party having the right to prosecute in accordance with the foregoing is referred
    to as the Prosecuting Party. Prosecuting Party shall provide
    the other Party promptly with copies of all patent applications, correspondences
    and other communications relating to LNA Compound Patents to and from patent
    offices and provide the other Party at least sixty (60) days to offer comments.
    Prosecuting Party shall consider in good faith any comments the other Party
    may have with regard to the preparation, filing, prosecution and/or maintenance
    of the patent applications and patents related to such LNA Compound Patents.
    Prosecuting Party shall provide the other Party, a reasonable time prior
    to taking or failing to take action that would affect the scope or validity
    of rights under any LNA Compound Patent (including substantially narrowing
    or canceling any claim without reserving the right to file a continuing or
    divisional application, abandoning any patent or not filing or perfecting
    the filing of any patent application in any country), with notice of such
    proposed action or inaction so that the other Party has a reasonable opportunity
    to review and make comments, and take such actions as may be appropriate
    in the circumstances. However, the foregoing three sentences shall not apply
    to the prosecution of national or regional phase applications in the Santaris
    Territory, except that Santaris shall keep Enzon informed of the material
    progress of such prosecution and shall provide such documents and take such
    actions as may be reasonably required to facilitate the prosecution of corresponding
Patents in the Enzon Territory.



The
    Parties and their patent counsel shall establish such procedures as may be
    desired to carry out the mutual review and consultation procedure contemplated
    under this Section 8.2 (c) without imposing unreasonable burdens and delays
    on the prosecution of the LNA Compound Patents. If Enzon, as the Prosecuting
    Party, determines not to file, prosecute, defend or maintain any LNA Compound
    Patent (including failing to defend any interference or opposition proceedings)
    in any country, and providing that no other patent applications or patents
    containing the same claims are pending or issued in that same country, then
    Enzon shall provide Santaris with thirty (30) days prior written notice of
    such determination and Santaris shall have the right and opportunity to file,
    prosecute, defend and/or maintain such patent or patent application at Santaris sole
cost and expense.



| | 4. | Except as set forth in this Amendment, the Agreement shall remain in full force and effect.
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5.   Resolution
of all disputes arising out of or related to this Amendment or the performance, enforcement,
breach or termination of this Amendment and any remedies relating thereto, shall
be governed by and construed under the substantive Laws of the State of New York,
without regard to conflicts of law rules that would provide for application of
the Law of Jurisdiction outside of New York. To the extent there is any such
dispute, such dispute will be handled in accordance with the procedures set forth
in Section 13 of the Agreement.



6.  This
    Amendment may be executed in two or more counterparts (including by facsimile
or pdf file) each of which shall be deemed an original, but all of which together
shall constitute one and the same instrument.



IN
    WITNESS WHEREOF, the
Parties have executed this Amendment in duplicate originals by their proper officers
as of the date and year first above written.



|SANTARIS PHARMA A/S |                         | ENZON PHARMACEUTICALS,
    INC.
|------------------- | ----------------------- | -------------------------------
|                    |                         |                                
|By:                 | /s/ Søren
    Tulstrup  |                                
|                    |                         |                                
|NAME:               | Søren Tulstrup          |                                
|TITLE:              | Chief Executive Officer |                                
|                    |                         |                                
|By:                 | /s/ Maja Bojko          |                                
|                    |                         |                                
|NAME:               | Maja Bojko              |                                
|TITLE:              | Chief Financial Officer |                                
|                    |                         |                                





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