Exhibit
10.5


Execution Copy


AMENDMENT
NO. 1 TO COLLABORATION,

DISTRIBUTION AND LICENSE AGREEMENT


This Amendment No. 1 to Collaboration, Distribution
and License Agreement (“Amendment No. 1”) is made and effective as of July 15,
2004 by and between Millennium Pharmaceuticals, Inc., a Delaware corporation,
with offices at 40 Landsdowne Street, Cambridge, Massachusetts 02139-4815,
U.S.A. (“Millennium”) and Ortho Biotech Products, L.P., a New Jersey limited
partnership, with offices at Route 22 East, Bridgewater, New Jersey 08807-0914,
U.S.A. (“OBI”).


INTRODUCTION


A.            The Parties entered into that certain Collaboration,
Distribution and License Agreement effective as of June 30, 2003 (the “Agreement”);


B.            On and subject to the terms and conditions set forth in
this Amendment No. 1 and the Agreement (as amended), Millennium and OBI
therefore desire to amend the Agreement on the terms and conditions set forth
below.


NOW, THEREFORE, for and
in consideration of the mutual convenants contained herein, Millennium and OBI
hereby agree as follows:


1.             Definitions and Cross References.  Unless otherwise specified herein, each
capitalized term shall have the meaning assigned to it in the Agreement and
each reference to a Section or Article shall refer to the corresponding Section
or Article in the Agreement.


2.             New Sections 1.98 and 1.99.  Section 1.98 shall be renumbered as Section
1.100.  The following new Sections 1.98
and 1.99 shall be inserted immediately following Section 1.97:


                “Section
1.98  “Millennium Marker Know-How” shall
mean any Millennium Know-How pertaining to (a) markers that (i) relate to the
safety or efficacy of any drug (including combinations of drugs) and (ii) are
derived from, developed or first discovered by Millennium or on behalf of
Millennium by an academic collaborator, in each case, using patient clinical
samples obtained under the Development Plan, or any Millennium Know-How related
to such patient clinical samples or their use, or any OBI Know-How related to
such patient clinical samples or their use, or (b) any use of such markers.


Section 1.99  “OBI Marker Know-How” shall mean any OBI
Know-How pertaining to (a) markers that (i) relate to the safety or efficacy of
any drug (including combinations of drugs) and (ii) are derived from, developed
or first discovered by OBI or on behalf of OBI by an academic collaborator, in
each case, using patient clinical samples obtained under the Development Plan,
or any Millennium Know-How related to such 



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clinical samples or their
use, or any OBI Know-How related to such clinical samples or their use, or (b)
any use of such markers.”


3.             Section 3.1(a). 
Section 3.1(a) shall be amended by deleting it in its entirety and
replacing it with the following:


“3.1(a)    Development License.  Millennium hereby grants to OBI (i) a
co-exclusive (with Millennium) right and license, with right to grant
sublicenses, under Millennium Intellectual Property, to Develop the Product in
the Field in the License Territory,  (ii)
a non-exclusive right and license, with the right to grant sublicenses, under
Millennium Intellectual Property, to Develop the Product in the Field in the
U.S, and (iii) a non-exclusive, fully paid-up right and license, with the right
to grant sublicenses under Millennium Marker Know-How and Millennium Patent Rights
pertaining thereto, to use and exploit Millennium Marker Know-How for any
purpose.”


4.             Sections 3.1(d) and 3.1(e).  Sections 3.1(d) and 3.1(e) are amended by
inserting “(i), (ii)” immediately following “3.1(a)” each time such term is
used in Section 3.1(d) and 3.1(e) respectively.


5.             New Section 3.2(d).  The following new Section 3.2(d) shall be
inserted immediately following Section 3.2(c):


“(d)         OBI Marker Know-How and Related OBI
Patent Rights.  OBI hereby grants to
Millennium, a non-exclusive, fully paid-up right and license, with the right to
grant sublicenses under OBI Marker Know-How and OBI Patent Rights pertaining
thereto, to use and exploit OBI Marker Know-How for any purpose.”


6.             New Section 4.2(f).  The following new Section 4.2(f) shall be inserted
immediately following Section 4.2(e):


“(f)          With respect to each clinical study
under the Development Plan where a Party is responsible for assuming the
operational lead for the Development activities of such study in a particular
country or countries (as set forth in Part I of Exhibit D or as otherwise
agreed by the GPT and approved by the JSC), as appropriate, that Party may
request the other Party to transfer certain of its obligations under an IND
that such other Party owns in the applicable countries for the purpose of
assisting the lead operational Party in performing such responsibilities.  Subject to the agreement of the Party owning
the applicable IND (the “Transferring Party”), the operational lead Party (“Delegated
Sponsor”) will be responsible for the obligations transferred to it (each, a “Delegated
Responsibility” or collectively, “Delegated Responsibilities”), if any, by the
Transferring Party in the Delegated Sponsor’s role as the designated contract
research organization and as described in a document titled “The Transfer of
Obligations of Client Under 21 CFR Subpart D,” or its equivalent foreign
counterpart, which in each case the Parties shall execute and will be appended
to this Agreement as Exhibit L.   Any
such transfer of such obligations in the United States will be construed as a
transfer of those obligations described therein in accordance with 21
CFR§312.52.  With respect to any
obligation of 



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sponsors under 21 CFR
Subpart D or its foreign equivalent that is not expressly transferred to the
Delegated Sponsor in accordance with this Section 4.2(f), the Transferring
Party shall retain responsibility for such non-transferred obligation(s) in the
applicable country or countries in accordance with its responsibility as a
sponsor under the applicable IND and the terms of this Agreement.  Furthermore, with respect to each clinical
study for which the Parties intend to designate a Delegated Sponsor, as a
condition precedent to the transfer of any Delegated Responsibility to such
Delegated Sponsor, the Delegated Sponsor agrees to the following:


(i)            it
will only use informed consents, investigator brochures and clinical trial
agreements that are substantially in the form of the Delegated Sponsored
templates of such documents which have been furnished to the Transferring Party
and approved in advance in writing by the Transferring Party;


(ii)           it
will not subcontract the performance of any of the Delegated Responsibilities
to a Third Party without the Transferring Party’s prior written consent, such
consent to be given upon prompt consideration and not unreasonably withheld;


(iii)          it
will perform the Delegated Responsibilities in accordance with the terms and
conditions of this Agreement, including, without limitation, in compliance with
applicable Law, Good Clinical Practice and Good Laboratory Practice; and


(iv)          it
will permit the Transferring Party and its representatives and representatives
of regulatory agencies, during normal business hours, to review the Delegated
Sponsor’s standard operating procedures and records pertaining to the Delegated
Responsibilities and to inspect the facilities used to perform those
responsibilities.”


7.             Section 4.4(a). 
Section 4.4(a) shall be amended by inserting the following sentences
immediately following the second sentence thereto:


“The Transferring Party
under Section 4.2(f) with respect to any IND it owns shall be solely
responsible for all contacts and communications with the Regulatory Authorities
with respect to such IND, provided, however, that the Transferring Party shall
afford the Delegated Sponsor under Section 4.2(f) active participation in
contacts and communications with such Regulatory Authorities.  In addition, the Delegated Sponsor under such
IND, shall notify the Transferring Party 
immediately, and in no event later than one (1) day, after it receives
any contact or communication from any Regulatory Authority relating in any way
to the Delegated Responsibilities or such IND and will provide the Transferring
Party with copies of such communications within one (1) day of receipt of such
communication by the Delegated Sponsor.”


8.             New Section 4.7. 
The following new Section 4.7 Research Studies shall be inserted
immediately following Section 4.6:



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“Section 4.7  Research Studies.  To the extent that the Development Plan
includes any research study involving the use of clinical samples or clinical
data that, in each case, are obtained, generated or developed thereunder, the
Parties agree that each Party will disclose and transfer to the other Party any
raw data it obtains or generates in performing those research studies (to the
extent that it Controls such data) along with a final report containing key
conclusions from that study.”


9.             Section 11.11(c)(iii).   Section 11.11(c)(iii) shall be amended by
restating the entire subsection (iii) as follows:


“Any Losses involving a
Third Party products liability claim or Action (other than such Losses entitled
to indemnification under subsection (c)(i) or (c)(ii)) shall (a) be borne by
Millennium to the extent such Losses were incurred (x) with respect to the
Development of the Product conducted by Millennium, except to the extent of any
claims related to manufacturing or design defects of OBI, or any Product
Manufactured by Millennium or (y) with respect to the Commercialization of the
Product in the U.S. and (b) be borne by OBI to the extent such Losses were
incurred (x) with respect to the Development of the Product conducted by OBI,
except to the extent of any claims related to manufacturing or design defects
of Millennium, or any Product Manufactured by OBI or (y) with respect to the
Commercialization of the Product in the License Territory.”


10.           Exhibit L.  The Agreement is amended by adding a new
Exhibit L to be attached to the Agreement in accordance with Section 4.2(f).


11.           Prior to the effective date of this
Amendment No. 1, Millennium expressly delegated to OBI pursuant to a letter
agreement, certain of its sponsor obligations under its clinical trial
application filed in the United Kingdom with respect to Protocol
26866138-MMY-3001; Phase 3b, entitled, “An International Single-Arm Protocol to
Provide Expanded Access to VELCADE® for Patients With Multiple Myeloma Who Have
Received at Least Two Previous Lines of Therapy and are Refractory to or
Have Relapsed After Their Last Therapy for Multiple Myeloma” to be conducted by
OBI in the License Territory.  The
Parties agree that with respect this clinical study and any other clinical
study pursuant to which Millennium expressly delegated certain of its sponsor
responsibilities to OBI prior to the effective date of this Amendment No. 1,
the terms set forth in this Amendment No. 1 under Sections 2 through 9 shall
apply as of the date such responsibilities were so delegated to OBI.  The Parties will use Diligent Efforts to
execute any necessary documents to bring the delegation of such
responsibilities for such clinical studies into compliance with the terms of
this Section 11.


12.           Millennium shall provide to OBI, for
use under the Development Plan, data Controlled by Millennium related to
pharmacogenomic studies which were generated prior to the Effective Date under
the 025 VELCADE clinical trial.  Any OBI
Know-How generated through use of such data shall be deemed “OBI Marker
Know-How”.  Any Millennium Know-How
pertaining to markers that (i) relate to the safety or efficacy of any drug
(including combinations of drugs) and (ii) are derived from, 



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developed or first
discovered by Millennium or on behalf of Millennium by an academic
collaborator, in each case, in connection with a research study that commenced
in accordance with the Development Plan after the effective date of this
Amendment No. 1 and involves the use of patient samples obtained under the 025
VELCADE clinical trial, shall be deemed “Millennium Marker Know-How”.


13.           Miscellaneous.


13.1         Continuing Effect.  This Amendment No. 1 shall be effective for
all purposes as of the date first written above.  Except as otherwise expressly modified by
this Amendment No. 1, the Agreement shall remain in full force and effect in
accordance with its terms.


13.2         Counterparts.  This Amendment No. 1 may be executed in
counterparts, each of which shall be deemed to be an original and together
shall be deemed to be one and the same instrument.


IN WITNESS WHEREOF, Millennium
and OBI have caused this Amendment No. 1 to be duly executed by their
authorized representatives under seal, in duplicate on the dates written herein
below.


MILLENNIUM
PHARMACEUTICALS, INC.


	
  By:

  	
  /s/ Kenneth M.
  Bate

  	
   

  	
   

  
	
   

  	
  Title: CFO

  	
   

  	
   

  
	
   

  	
  Date: July 16,
  2004

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  ORTHO BIOTECH PRODUCTS, L.P.

  
	
   

  	
   

  	
   

  
	
  By: Ortho Biotech Inc., its managing general partner

  
	
   

  
	
  By:

  	
  /s/ Joaquin
  Duato

  	
   

  	
   

  
	
   

  	
  Title: President

  	
   

  	
   

  
	
   

  	
  Date: August 13,
  2004

  	
   

  	
   

  
					



 



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