**Exhibit10.5**

Execution Copy

**AMENDMENTNO. 1 TO COLLABORATION,****DISTRIBUTION AND LICENSE AGREEMENT**

This Amendment No. 1 to Collaboration, Distributionand 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 limitedpartnership, 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 inthis Amendment No. 1 and the Agreement (as amended), Millennium and OBItherefore desire to amend the Agreement on the terms and conditions set forthbelow.

NOW, THEREFORE, for andin consideration of the mutual convenants contained herein, Millennium and OBIhereby agree as follows:

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

2.             New Sections 1.98 and 1.99.  Section 1.98 shall be renumbered as Section1.100.  The following new Sections 1.98and 1.99 shall be inserted immediately following Section 1.97:

                “Section1.98  “Millennium Marker Know-How” shallmean any Millennium Know-How pertaining to (a) markers that (i) relate to thesafety or efficacy of any drug (including combinations of drugs) and (ii) arederived from, developed or first discovered by Millennium or on behalf ofMillennium by an academic collaborator, in each case, using patient clinicalsamples obtained under the Development Plan, or any Millennium Know-How relatedto such patient clinical samples or their use, or any OBI Know-How related tosuch patient clinical samples or their use, or (b) any use of such markers.

Section 1.99  “OBI Marker Know-How” shall mean any OBIKnow-How pertaining to (a) markers that (i) relate to the safety or efficacy ofany drug (including combinations of drugs) and (ii) are derived from, developedor first discovered by OBI or on behalf of OBI by an academic collaborator, ineach 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 theiruse, 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 andreplacing it with the following:

“3.1(a)    Development License.  Millennium hereby grants to OBI (i) aco-exclusive (with Millennium) right and license, with right to grantsublicenses, under Millennium Intellectual Property, to Develop the Product inthe Field in the License Territory,  (ii)a non-exclusive right and license, with the right to grant sublicenses, underMillennium Intellectual Property, to Develop the Product in the Field in theU.S, and (iii) a non-exclusive, fully paid-up right and license, with the rightto grant sublicenses under Millennium Marker Know-How and Millennium Patent Rightspertaining thereto, to use and exploit Millennium Marker Know-How for anypurpose.”

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

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

“(d)         OBI Marker Know-How and Related OBIPatent Rights.  OBI hereby grants toMillennium, a non-exclusive, fully paid-up right and license, with the right togrant sublicenses under OBI Marker Know-How and OBI Patent Rights pertainingthereto, 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 insertedimmediately following Section 4.2(e):

“(f)          With respect to each clinical studyunder the Development Plan where a Party is responsible for assuming theoperational lead for the Development activities of such study in a particularcountry or countries (as set forth in Part I of Exhibit D or as otherwiseagreed by the GPT and approved by the JSC), as appropriate, that Party mayrequest the other Party to transfer certain of its obligations under an INDthat such other Party owns in the applicable countries for the purpose ofassisting the lead operational Party in performing such responsibilities.  Subject to the agreement of the Party owningthe applicable IND (the “Transferring Party”), the operational lead Party (“DelegatedSponsor”) will be responsible for the obligations transferred to it (each, a “DelegatedResponsibility” or collectively, “Delegated Responsibilities”), if any, by theTransferring Party in the Delegated Sponsor’s role as the designated contractresearch organization and as described in a document titled “The Transfer ofObligations of Client Under 21 CFR Subpart D,” or its equivalent foreigncounterpart, which in each case the Parties shall execute and will be appendedto this Agreement as Exhibit L.   Anysuch transfer of such obligations in the United States will be construed as atransfer of those obligations described therein in accordance with 21CFR§312.52.  With respect to anyobligation of 

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sponsors under 21 CFRSubpart D or its foreign equivalent that is not expressly transferred to theDelegated Sponsor in accordance with this Section 4.2(f), the TransferringParty shall retain responsibility for such non-transferred obligation(s) in theapplicable country or countries in accordance with its responsibility as asponsor under the applicable IND and the terms of this Agreement.  Furthermore, with respect to each clinicalstudy for which the Parties intend to designate a Delegated Sponsor, as acondition precedent to the transfer of any Delegated Responsibility to suchDelegated Sponsor, the Delegated Sponsor agrees to the following:

(i)            itwill only use informed consents, investigator brochures and clinical trialagreements that are substantially in the form of the Delegated Sponsoredtemplates of such documents which have been furnished to the Transferring Partyand approved in advance in writing by the Transferring Party;

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

(iii)          itwill perform the Delegated Responsibilities in accordance with the terms andconditions of this Agreement, including, without limitation, in compliance withapplicable Law, Good Clinical Practice and Good Laboratory Practice; and

(iv)          itwill permit the Transferring Party and its representatives and representativesof regulatory agencies, during normal business hours, to review the DelegatedSponsor’s standard operating procedures and records pertaining to the DelegatedResponsibilities and to inspect the facilities used to perform thoseresponsibilities.”

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

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

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

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

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

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

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

11.           Prior to the effective date of thisAmendment No. 1, Millennium expressly delegated to OBI pursuant to a letteragreement, certain of its sponsor obligations under its clinical trialapplication filed in the United Kingdom with respect to Protocol26866138-MMY-3001; Phase 3b, entitled, “An International Single-Arm Protocol toProvide Expanded Access to VELCADE® for Patients With Multiple Myeloma Who HaveReceived at Least Two Previous Lines of Therapy and are Refractory to orHave Relapsed After Their Last Therapy for Multiple Myeloma” to be conducted byOBI in the License Territory.  TheParties agree that with respect this clinical study and any other clinicalstudy pursuant to which Millennium expressly delegated certain of its sponsorresponsibilities 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 shallapply as of the date such responsibilities were so delegated to OBI.  The Parties will use Diligent Efforts toexecute any necessary documents to bring the delegation of suchresponsibilities for such clinical studies into compliance with the terms ofthis Section 11.

12.           Millennium shall provide to OBI, foruse under the Development Plan, data Controlled by Millennium related topharmacogenomic studies which were generated prior to the Effective Date underthe 025 VELCADE clinical trial.  Any OBIKnow-How generated through use of such data shall be deemed “OBI MarkerKnow-How”.  Any Millennium Know-Howpertaining 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 firstdiscovered by Millennium or on behalf of Millennium by an academiccollaborator, in each case, in connection with a research study that commencedin accordance with the Development Plan after the effective date of thisAmendment No. 1 and involves the use of patient samples obtained under the 025VELCADE clinical trial, shall be deemed “Millennium Marker Know-How”.

13.           Miscellaneous.

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

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

IN WITNESS WHEREOF, Millenniumand OBI have caused this Amendment No. 1 to be duly executed by theirauthorized representatives under seal, in duplicate on the dates written hereinbelow.

MILLENNIUMPHARMACEUTICALS, 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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