EXHIBIT 10.49

 

LICENSE AGREEMENT

 

BY AND BETWEEN

 

AMGEN INC.

 

AND

 

NUVELO, INC.

 

Amgen Contract #200200784

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LICENSE AGREEMENT

 

THIS LICENSE AGREEMENT (the “License Agreement”) is made effective as of
November 3, 2004 (the “Effective Date”) by and between AMGEN INC., a Delaware
corporation having its principal place of business at One Amgen Center Drive,
Thousand Oaks, California 91320-1799 (“Amgen”) and NUVELO, INC., a Nevada
corporation having its principal place of business at 670 Almanor Avenue,
Sunnyvale, California 94085-1710 and formerly known as Hyseq, Inc. (“Nuvelo”).
Amgen and Nuvelo are sometimes referred to herein individually as a “Party” and
collectively as the “Parties”.

 

RECITALS

 

WHEREAS, Amgen and Nuvelo have been collaborating in the joint development and
commercialization of a protein known as Alfimeprase (and other variants of
Alfimeprase) under the terms and conditions of that certain Collaboration
Agreement between the Parties, dated January 8, 2002 (“Collaboration
Agreement”);

 

WHEREAS, pursuant to Article 15 of the Collaboration Agreement, Amgen has
elected to exercise its right to convert its right to jointly develop and
commercialize Alfimeprase (and other variants of Alfimeprase) into the grant to
Nuvelo of an exclusive license under certain Amgen rights to Develop,
manufacture and Commercialize Alfimeprase (and other variants of Alfimeprase);

 

WHEREAS, Nuvelo wishes, to exclusively license such Amgen rights from Amgen in
connection with the Development, manufacture and Commercialization of the
Licensed Product(s) (as hereinafter defined), on the terms and conditions
herein;

 

NOW THEREFORE, based on the foregoing premises and the mutual covenants and
obligations set forth below, the Parties agree as follows:

 

ARTICLE 1

DEFINITIONS

 

Capitalized terms used but not otherwise defined herein have the meanings
provided in Exhibit A hereto.

 

ARTICLE 2

GRANT OF LICENSES AND OTHER RIGHTS

 

2.1 Patent Licenses. Amgen hereby grants to Nuvelo an exclusive license (even as
to Amgen) under Amgen Technology to make, have made, use, sell, lease, offer to
sell or lease, have sold, import, export or otherwise exploit, transfer physical
possession of and transfer title or interest in and to Licensed Products in the
Territory.

 

2.2 Trademark; Copyright Licenses.

 

(a) Amgen hereby grants to Nuvelo an exclusive royalty-free license, with the
right to grant sublicenses (subject to Nuvelo’s compliance with Section 2.3),
under Amgen’s entire right,

 

Amgen Contract #200200784

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title and interest in and to the Product Trademarks, to use and display the
Product Trademarks in connection with Licensed Products in the Territory. For
the avoidance of doubt, Nuvelo shall have the right to select for and use and
display with Licensed Products such Trademarks as it desires.

 

(b) Amgen hereby grants to Nuvelo an exclusive royalty-free license under
Amgen’s entire right, title and interest in any copyrights in and to Promotional
Materials, with the right to grant sublicenses subject to Nuvelo’s compliance
with Section 2.3 of this License Agreement), to reproduce, distribute copies of,
prepare derivative works of and publicly perform and display such Promotional
Materials in connection with Licensed Products in the Territory solely in
compliance with the terms and conditions of this License Agreement.

 

(c) Other than with respect to the rights and licenses granted to Joint Know-How
under this License Agreement, each Party shall have the unrestricted
royalty-free, worldwide right to make, have made, use, sell, lease, offer to
sell or lease, have sold, import, export or otherwise exploit, or transfer
physical possession of or title in, Joint Know-How, without accounting.

 

2.3 Sublicensing.

 

(a) Nuvelo will have the sole right to determine whether to sublicense any of
its rights under Section 2.1 or 2.2. Any such sublicense shall require the
Sublicensee to comply with the obligations of Nuvelo as contained herein
(specifically including without limitation, obligations under Section 6.6,
Article 7, Section 11.2 and Section 14.15), and including an obligation of the
Sublicensee to account for and report its sales of Licensed Products on the same
basis as if such sales were Net Sales by Nuvelo. Any such sublicense shall
provide for the termination of the sublicense, or the conversion to a license
directly between such Sublicensee and Amgen, at the option of Amgen, upon
termination of this License Agreement pursuant to Article 12. Nuvelo shall
forward to Amgen a copy of each fully executed sublicense agreement within sixty
(60) days of the execution of such agreement.

 

(b) Notwithstanding the sublicensing of all or part of Nuvelo’s rights and
obligations hereunder Nuvelo shall remain responsible for the full and complete
performance of all of Nuvelo’s obligations and duties under this License
Agreement. For the avoidance of doubt, Nuvelo shall forward to Amgen and
acknowledges that Amgen shall be entitled to receive Royalties on Net Sales of
Licensed Product(s) sold by Sublicensees hereunder and that Nuvelo shall be
responsible to Amgen for paying Royalties due on Net Sales of Product(s) sold by
Sublicensees.

 

2.4 Assignment to Nuvelo. Pursuant to Section 16.9(c)(ii) of the Collaboration
Agreement, Amgen shall have transferred or is in the process of transferring to
Nuvelo all right, title and interest in all Regulatory Filings and Regulatory
Approvals owned in each case by Amgen and shall have delivered or is in the
process of delivering to Nuvelo all correspondence between Amgen and Regulatory
Authorities relating to all Regulatory Filings and Regulatory Approvals. At
Nuvelo’s request and expense, within seven (7) days after such request Amgen
will provide Nuvelo with access to any pre-clinical and clinical information
(reasonably necessary to the continued Development, manufacturing and
Commercialization of a

 

Amgen Contract #200200784

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Collaboration Product), and Amgen will assist Nuvelo in responding to any
request or inquiry regarding such information by a Regulatory Authority.

 

2.5 Manufacturing License to Nuvelo. Pursuant to Section 4.1, Amgen shall grant
to Nuvelo an exclusive license, with a limited right to sublicense (to Third
Party manufacturers pursuant to Section 4.2), to make, have made and use Amgen
Material and Manufacturing Information solely for the purposes set forth in
Section 3.1 below.

 

2.6 Retained Rights. With respect to the licenses granted under this Article 2,
Amgen expressly reserves for itself and its Affiliates a non-transferable,
non-sublicensable right to make, have made and use (but not to transfer, sell,
have sold, offer to sell or lease, import, export or otherwise exploit or
transfer possession of, title to or interest in) Licensed Products under Amgen
Technology and Amgen Material and Manufacturing Information which are solely for
internal research purposes unrelated to Licensed Products. For the avoidance of
doubt, Amgen shall further retain all rights in Amgen Technology and the Amgen
Material and Manufacturing Information not expressly licensed hereunder,
including the right to make, have made, use, sell, lease, offer to sell or
lease, have sold, import, export or otherwise exploit, transfer physical
possession of and transfer title or interest in and to products, other than
Licensed Products, for any purpose in the Territory.

 

ARTICLE 3

DEVELOPMENT AND COMMERCIALIZATION

 

3.1 Development and Commercialization. At its discretion Nuvelo shall have sole
and full control, authority and responsibility for conducting, funding and
pursuing all aspects of Development and Commercialization of each said Licensed
Product in the Territory.

 

3.2 Regulatory Filings and Regulatory Approvals. With respect to each Licensed
Product, at its discretion Nuvelo will prepare, file and own all right, title
and interest in Regulatory Filings and Regulatory Approvals relating to each
said Licensed Product in the Territory.

 

3.3 Annual Reports. Nuvelo will provide Amgen with detailed written annual
reports concerning their efforts regarding Development and Commercialization
(pursuant to Article 3) and regarding manufacturing (pursuant to Article 4) of
the Licensed Products. At Amgen’s request, Nuvelo shall promptly discuss such
annual report and any progress regarding Development, manufacturing and
Commercialization with Amgen.

 

ARTICLE 4

MANUFACTURE AND SUPPLY

 

4.1 Manufacturing Right. Nuvelo shall be responsible for manufacturing and
supplying Licensed Products for Development and Commercialization in the
Territory and for making all decisions with respect thereto in its sole
discretion, including without limitation, decisions relating to process
development work to support quality assurance, improving manufacturing/cost
efficiency and commercial scale-up manufacturing. For the avoidance of doubt,
Nuvelo shall have final decision making authority to fulfill its regulatory
responsibilities

 

[ * ]  Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

Amgen Contract #200200784

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over all steps of the manufacturing process (including bulk, finish and fill,
labeling and packaging, lot release and management of subcontractors).

 

4.2 Transfer of Manufacturing Responsibilities. Transfer of manufacturing
responsibilities from Amgen to Nuvelo or to a Third Party manufacturer approved
by Amgen pursuant to Section 6.7 of the Collaboration Agreement will take place
according to Section 16.9(c) of the Collaboration Agreement and notwithstanding
any other provision of the Collaboration Agreement, the parties will work
together to establish a manufacturing transition plan within the scope and
bounds set forth in the outline attached to this License Agreement as Exhibit D.

 

4.3 Payment for Transfer Expenses. Within ten (10) days after the Effective Date
Nuvelo shall pay to Amgen the amount of $373,750 (the “Transfer Deposit”), as a
deposit against the 50% share of costs Amgen will incur (based on an FTE rate
of    [*]    in transferring manufacturing responsibilities from Amgen to a
Third Party manufacturer of Nuvelo’s choosing, for which Nuvelo will be
responsible. Within thirty (30) days after the completion of Amgen’s tasks
designated in the manufacturing plan the Parties shall meet and reconcile the
charges recorded by Amgen in transferring manufacturing responsibilities with
the Transfer Deposit. Within thirty (30) days after such reconciliation, Amgen
shall pay to Nuvelo any amount by which the Transfer Deposit exceeded the 50%
share of Amgen’s costs in transferring manufacturing responsibilities or Nuvelo
shall pay to Amgen the amount by which the 50% share of costs in transferring
manufacturing responsibilities exceeds the Transfer Deposit. Pursuant to the
terms of Section 8.3(f) of the Collaboration Agreement, the Parties will meet to
reconcile post-third Calendar Quarter charges to the Operating Profit or Loss
that were incurred prior to the Effective Date of this Opt-Out Agreement
according to the terms of such Section. Failure by Nuvelo to make any such
payment(s) described under this Section 4.3 when due shall be deemed a material
breach of Nuvelo’s obligations under this License Agreement.

 

ARTICLE 5

CONSIDERATION

 

5.1 Clinical Milestones.

 

(a) Within thirty (30) days following the first achievement or occurrence with
the first Licensed Product(s) of each of the following milestone events by
performance of Nuvelo or an Affiliate or Sublicensee of Nuvelo (“Milestone
Event(s)”), Nuvelo shall pay to Amgen the corresponding one-time,
non-creditable, non-refundable milestone payments set forth herein (“Milestone
Payment(s)”):

 

Milestone Event

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Milestone Payment

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(i)   Administration of a Licensed Product to the first patient in a Pivotal
Trial    $5,000,000.00 (ii)   Upon the first BLA filing for a Licensed Product
in the United States, EU or Japan    [ * ] (iii)   Upon the first BLA approval
for a Licensed Product in the United States    [ * ] (iv)   Upon the first BLA
approval for a Licensed Product in the EU    [ * ] (v)   Upon the first BLA
approval for a Licensed Product in Japan    [ * ]         

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    Total    $40,000,000.00

 

[ * ]  Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

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For the purposes of this Section 5.1(a) of the License Agreement, the first
Milestone Event shall be deemed to have occurred upon the earlier of (I) the
administration of a Licensed Product to the first patient in a clinical trial
after the Effective Date or (II)     [ * ]             provided, however that in
the event that Nuvelo has not commenced a clinical trial prior to     [ * ]
        directly due to a decision by FDA that the Licensed Product produced by
Amgen under Process B is not bio-equivalent to the Licensed Product produced by
Amgen under Process A thus requiring further manufacturing be performed before
the start of the next clinical trial, then such     [ * ]     date shall have no
effect and the first Milestone Event shall be deemed to have occurred upon the
administration of a Licensed Product to the first patient in a clinical trial
after the Effective Date.

 

(b) For purposes of clarification, if any of the Milestone Events set forth
above in Sections 5.1(a)(ii)-(v) are achieved prior to or in the absence of the
achievement of the Milestone Event set forth in Section 5.1(a)(i) then,
effective upon achievement of any of such Milestone Events, the previously
unpaid Milestone Payment set forth in Section 5.1(a)(i) shall also become due
and payable. No Milestone Payment shall be payable more than once, no matter how
many times achieved by one or more Licensed Product(s). Each such Milestone
Payment shall be nonrefundable and noncreditable against Royalties payable
pursuant to Section 5.2 and any other fees, other Milestone Payments or other
payments due Amgen with respect to Licensed Product(s) under this License
Agreement.

 

(c) In the event catheter clearance shall be the first indication pursued by
Nuvelo, and the Milestone Event(s) set forth in Sections 5.l(a)(i) or 5.1(a)(ii)
is/are first achieved with respect to the catheter clearance indication. Nuvelo
shall pay to Amgen fifty percent (50%) of the corresponding Milestone Payment
for any such achieved Milestone Event, with the balance of any such
corresponding Milestone Payment being due and payable upon the achievement of
such Milestone Event with respect to any non-catheter clearance indication. In
the event that Nuvelo shall not have obtained Regulatory Approval for the
treatment of peripheral arterial occlusion in the United States, but off-label
gross sales in the United States for the treatment of peripheral arterial
occlusion are or exceed         [ * ]                 Dollars         [ *
]            , (based on data provided by IMS International, or if such data
shall not be available, based on such other data mutually agreed to by Amgen and
Nuvelo), then Nuvelo shall immediately pay the balance of any partially paid
Milestone Payment under this Section 5.3(c).

 

[ * ] Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

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(d) If the Effective Date of this License Agreement is after the date of
achievement of any Milestone Event(s) set forth in Sections 5.1(a)(i) and
5.1(a)(ii), then the corresponding Milestone Payment of such previously achieved
Milestone Event shall be deemed waived and not payable to Amgen.

 

(e) If the Effective Date of this License Agreement is after the date of
achievement of any Milestone Event(s) set forth in Sections 5.1(a)(iii), (iv) or
(v), the corresponding Milestone Payment shall be due within thirty (30) days
after the Effective Date of this License Agreement. Notwithstanding the above
sentence, the     [ * ]         Dollar ($ [ * ]            ) Regulatory Approval
Milestone incurred by Nuvelo under Section 7.2 of the Collaboration Agreement as
a consequence of the achievement of any such Milestone Event shall be creditable
against any Milestone Payments due for the achievement of any Milestone Event(s)
set forth in Sections 5.1(a)(iii), (iv) or (v) prior to or during the Term of
this License Agreement.

 

5.2 Royalties. Subject to Sections 5.3 and 5.4, below, Nuvelo shall pay to Amgen
a Royalty, based on the following Royalty rates, for annual Net Sales of each
Licensed Product (on a Licensed Product-by-Licensed Product basis) by Nuvelo,
its Affiliates, or its Sublicensees in the Territory:

 

(a) a Royalty rate of [*] percent (   [*]  ) of that portion of annual Net Sales
in the Territory of each such Licensed Product that is less than or equal
to        [ * ]            [ * ] (  [ * ]        );

 

(b) a Royalty rate of     [*]     percent (    [ * ]    ) of that portion of
annual Net Sales in the Territory of each such Licensed Product that is greater
than    [ * ]                 Dollars ($ [ * ]            ) and less man or
equal to     [ * ]                 Dollars ($  [ * ]             ); and

 

(c) a Royalty rate of [ * ]     percent (    [ * ]    ) of that portion of
annual Net Sales in the Territory of each such Licensed Product that is greater
than     [ * ]                     Dollars ($ [ * ]        ).

 

5.3 [ * ] Nuvelo acknowledges that Nuvelo may be obligated to pay Third Party
Payments to             [ * ]                                         ”) for
licensing of certain [ * ] [ * ]                     technology with respect to
Licensed Products, in addition to the Milestone Payments set forth in Section
5.1 and the Royalties set forth in Section 5.2 above. Such payments shall be
non-creditable against any payments due to Amgen under this License Agreement.

 

5.4 Third Party Royalty Reduction. Nuvelo shall be responsible for obtaining any
licenses, and for making any Third Party Payments thereunder, or making any
then-due Third Party Payments to Amgen (for forwarding to the licensing Third
Party) under any sublicenses granted by Amgen hereunder, for rights to any Third
Party intellectual property required to make, have made, use, sell, lease, offer
to sell or lease, have sold, import, export or otherwise exploit, or transfer
physical possession of or title in, a Licensed Product in one or more countries
in the Territory. With the exception of any Third Party Payments payable to
[*]     for licensing certain         [ * ]                            
technology, if, and for so long as Nuvelo is required to pay

 

[ * ]  Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

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such Third Party royalties for such license, fifty percent (50%) of the
royalties which are payable by Nuvelo shall be creditable by Nuvelo against any
Royalties due to Amgen under Section 5.2 above for the Net Sales of such
Licensed Product in such country, provided however, that, on a Licensed
Product-by-Licensed Product basis, Nuvelo’s Royalty rate set forth in Section
5.2 in any given year will not be reduced in excess of two percent (2.0%)
(e.g.,[ * ]%, [ * ]% and [ * ]% respectively) as a consequence of any royalties
being creditable against the Royalties to be paid to Amgen by Nuvelo. Nuvelo
shall have sole discretion, authority and right with respect to determining
whether to enter into an agreement for a license or other rights and to incur an
obligation for any Third Party Payments.

 

5.5 Competition Reduction. If, and for so long as one or more Competitive
Product(s) shall be commercially available in a country in the Territory and
shall have in the aggregate a share of more than [ * ] percent ([ * ]%) of the
total market of all Licensed Product(s) in that country as measured by sales
units (based on data provided by IMS International, or if such data shall not be
available, based on such other data mutually agreed to by Amgen and Nuvelo),
Nuvelo shall have the immediate right to reduce the Royalty rates on Net Sales
of each such Licensed Product(s) in such country by [ * ] percent ([ * ]%) of
those set forth in Section 5.2.

 

5.6 Term of Royalties. Amgen’s right to receive Royalties under Section 5.2
shall expire, on a Licensed Product-by-Licensed Product basis and
country-by-country basis, upon the later of: (a) ten (10) years after the date
of First Commercial Sale of each such Licensed Product; or (b) the expiration of
the last-to-expire of the Amgen Patent Rights and (subject to the following
sentence) Joint Patent Rights containing an issued Valid Claim that, but for the
license granted by Amgen to Nuvelo, would be infringed by the use or sale by
Nuvelo, its Affiliates and Sublicensees of such Licensed Product in such
country. Where the Joint Patent Rights described in subparagraph (b) subsist
after expiry of the Amgen Patent Rights, then upon such expiry the Royalties
payable pursuant to Section 5.2 (as reduced by Sections 5.4 and 5.5, as
applicable) shall be further reduced by [ * ] percent [ * ]%) of the amount
payable immediately before expiry of the Amgen Patent Rights, and shall continue
to be payable by Nuvelo if:

 

(i) a mutually acceptable outside patent counsel has provided a written opinion
to both Parties to the effect that but for a license under such subsisting Joint
Patent Rights, the actual or theoretical using (in accordance with a label claim
of, or with published, statistically significant clinical human trial results
regarding, a Licensed Product) or selling by a Third Party of a competing
pharmaceutical product within the meaning of Competitive Product would infringe
an issued Valid Claim under the Joint Patent Rights, or

 

(ii) Nuvelo has elected to continue to retain its exclusive rights to such
subsisting Joint Patent Rights,

 

but failing which Nuvelo’s obligation to pay all Royalties shall expire and each
Party shall thereafter be free to use and exploit their respective interest in
the Joint Patent Rights without the obligation to obtain the consent of, or to
account to, the other Party. Notwithstanding any of the foregoing, after
expiration of Amgen’s right to receive Royalties for at least one Licensed
Product (i.e. the first Licensed Product), Amgen’s right to receive Royalties
for any subsequent Licensed Product shall be determined solely by subparagraph
(b) above and not by subparagraph (a).

 

[ * ]  Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

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5.7 Sublicensing in Asian Countries. In the event of a sublicensing by Nuvelo to
a Third Party of the right to Develop and/or Commercialize Licensed Products in
Asian Countries, Amgen will waive all of Nuvelo’s Milestone Payments described
in Section 5.1(a)(v) above (and the Milestone Payments due under Section
5.1(a)(i) or Section 5.1(a)(ii) shall only apply upon achievement of the
corresponding Milestone Event in a country other than a country within the Asian
Countries), and the Royalty payment described in Section 5.2 above with respect
to Net Sales of Licensed Products in such Asian Countries, and will instead
receive [*] percent ([*]%) of all consideration received by Nuvelo from such
Sublicensee. In all other regions, Nuvelo shall remain responsible for all other
rights and obligations under this License Agreement, including making all
payments to Amgen in accordance with Sections 5.1 and 5.2 and in guaranteeing
the performance of such Sublicensee for all other obligations to Amgen.

 

ARTICLE 6

INTELLECTUAL PROPERTY

 

6.1 Technology Ownership. Ownership of inventions shall be determined in
accordance with the rules of inventorship under United States patent laws.
Subject to the licenses granted in Section 2.1, as between the Parties, Amgen
shall own all right, title and interest in and to Amgen Technology, and any
Confidential Information contained therein shall be considered the Confidential
Information of Amgen. As between the Parties, all right and interest in and to
Joint Know-How (which shall be considered the joint Confidential Information of
the Parties) and Joint Patent Rights shall be owned jointly by Nuvelo and Amgen,
and shall be subject to the license granted to Nuvelo in Section 2.1.

 

6.2 Prosecution.

 

(a) At its sole cost and expense, Nuvelo will be responsible (using mutually
acceptable outside counsel) for the filing, prosecution, defense and maintenance
of Amgen Patent Rights before all patent authorities in the Territory. Amgen
shall have the right to review and comment on such filing, prosecution and
defense of the Amgen Patent Rights by Nuvelo and if such outside counsel
concludes that taking any specific action(s) may likely have an adverse effect
on the scope or validity of any such Amgen Patent Rights, then Nuvelo shall not
take such specific action(s) without the prior express written consent of Amgen
and. if Amgen shall not have given its consent to such action, Nuvelo shall
propose an alternative strategy for Amgen’s consideration. To that end, Nuvelo
shall instruct such outside counsel to furnish Amgen with a reasonably complete
draft of each potential submission to a patent authority regarding Amgen Patent
Rights no later than twenty (20) days (or if given less than twenty (20) days to
respond as soon as practicable) prior to the date such submission is proposed to
be made, and shall reasonably consider any of Amgen’s timely comments thereon.
Additionally, Nuvelo shall instruct such outside counsel to provide Amgen with a
copy of each submission made to and document received from a patent authority
regarding any Amgen Patent Rights reasonably promptly after making such filing
or receiving such document. If Nuvelo determines in its sole discretion to not
file, prosecute, defend or maintain any claim or patent application or patent
within Amgen Patent Rights in any country, then Nuvelo shall provide Amgen with
thirty (30) days prior written notice of such determination to provide Amgen
with the right and opportunity to file, prosecute and maintain such claim or
patent application or patent at Amgen’s sole cost and expense.

 

[ * ]  Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

9

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(b) At its own cost and expense, Nuvelo will be responsible (using mutually
acceptable outside counsel) for the filing, prosecution, defense and maintenance
of Joint Patent Rights before all patent authorities in the Territory. Amgen
shall have the right to review and comment on such filing, prosecution and
defense of the Joint Patent Rights by Nuvelo and if such outside counsel
concludes that taking any specific action(s) may likely have an adverse effect
on the scope or validity of any such Joint Patent Rights, then Nuvelo shall not
take such specific action(s) without the prior express written consent of Amgen
and, if Amgen shall not have given its consent to such action, Nuvelo shall
propose an alternative strategy for Amgen’s consideration. To that end, Nuvelo
shall instruct such outside counsel to furnish Amgen with a reasonably complete
draft of each potential submission to a patent authority regarding Joint Patent
Rights no later than twenty (20) days (or if given less than twenty (20) days to
respond as soon as practicable) prior to the date such submission is proposed to
be made, and shall reasonably consider any of Amgen’s timely comments thereon.
Additionally, Nuvelo shall instruct such outside counsel to provide Amgen with a
copy of each submission made to and document received from a patent authority
regarding any Joint Patent Rights reasonably promptly after making such filing
or receiving such document. If Nuvelo determines in its sole discretion to not
file, prosecute, defend or maintain or any claim or patent application or patent
within Joint Patent Rights in any country, then Nuvelo shall provide Amgen with
thirty (30) days prior written notice of such determination to provide Amgen
with the right and opportunity to file, prosecute, defend and maintain such
claim or patent application or patent on behalf of both Parties (at Amgen’s sole
cost and expense).

 

(c) Amgen and Nuvelo shall each provide to the other any invention disclosures
submitted to its respective outside or in-house patent counsel in the normal
course of its business which disclose an invention within Amgen Know-How and
Joint Know-How, respectively. Amgen and Nuvelo shall cooperate with each other
and render all reasonable assistance in prosecuting and maintaining all
intellectual property licensed under this License Agreement. Amgen and Nuvelo
shall cooperate with each other in any such matters, and shall sign any
necessary legal papers and provide the Party responsible for such prosecution
with data or other information in support thereof (and use their best efforts to
ensure the cooperation of any of their respective personnel and, in the case of
Nuvelo, it’s Affiliates and licensee(s) as might reasonably be requested).

 

(d) Nuvelo shall be responsible (using mutually acceptable outside counsel) for
the filing, prosecution, defense and maintenance of the Product Trademarks
before all trademark authorities in the Territory. For the Product Trademarks
solely or jointly owned by Amgen, Amgen shall have the right to review and
comment on such filing, prosecution and defense of the Product Trademarks by
Nuvelo and if such outside counsel concludes that taking any specific action(s)
may likely have an adverse effect on the scope or validity of any such Product
Trademarks, then Nuvelo shall not take such specific action(s) without the prior
express written consent of Amgen, and Nuvelo shall propose an alternative
strategy for Amgen’s consideration. To that end, Nuvelo shall instruct such
outside counsel to furnish Amgen with a reasonably complete draft of each
submission to a trademark authority regarding the Product Trademarks no later
than twenty (20) days prior to the date such submission is proposed to be made,
or if given less than twenty (20) days to respond as soon as practicable, and
Nuvelo will consider any of Amgen’s reasonably timely comments thereon.
Additionally, Nuvelo shall instruct such outside counsel to provide Amgen with a
copy of each submission made to or document received from a

 

Amgen Contract #200200784

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trademark authority regarding any Product Trademarks reasonably promptly after
making such filing or receiving of such document. If Nuvelo determines in its
sole discretion to not file, prosecute, defend or maintain a Product Trademark
in any country, then Nuvelo shall provide Amgen with thirty (30) days prior
written notice of such determination and shall provide Amgen with the right and
opportunity to file, prosecute, defend and maintain such Product Trademark on
behalf of Nuvelo.

 

6.3 Infringement of Patents and Trademarks by Third Parties.

 

(a) At its sole cost and expense, Nuvelo may, but shall not be obligated to,
elect to enforce Amgen Patent Rights against any actual, alleged or threatened
infringement by Third Parties and to defend the Amgen Patent Rights against any
challenges in the Territory. In the event Nuvelo shall so elect to enforce Amgen
Patent Rights against a Third Party infringement, Nuvelo shall seek and
reasonably consider Amgen’s comments before determining the strategy and Amgen,
at Nuvelo’s reasonable request and sole cost and expense, shall reasonably
assist and cooperate in any such enforcement or defense. If Nuvelo finds it
necessary or desirable to join Amgen as a party, Amgen shall execute all papers
or perform such other acts as may reasonably be requested by Nuvelo, at the sole
expense of Nuvelo. In the event Nuvelo does not commence an enforcement and/or
defense action pursuant to this Section 6.3(a) within forty-five (45) days after
Amgen notifies Nuvelo or is notified by Nuvelo in writing of an actual, alleged
or threatened infringement by a Third Party of the Amgen Patent Rights in the
Territory (or of the filing of a declaratory judgment action), Amgen shall be
entitled to bring and prosecute such an action at its own cost and expense. If
Amgen elects to bring and prosecute such an action, then Nuvelo shall seek and
reasonably consider Amgen’s comments on strategy, and Nuvelo (at Amgen’s request
and sole cost and expense) shall reasonably assist and cooperate in any such
enforcement or defense. If Amgen finds it necessary or desirable to join Nuvelo
as a party, Nuvelo shall execute all papers or perform such other acts as may be
reasonably be required by Amgen, at Amgen’s expense. Amgen shall, at its own
expense, be entitled to participate in and to have counsel selected by it
participate in any action in which Nuvelo is a named party.

 

(b) At its own cost and expense, Nuvelo may, but shall not be obligated to,
elect to enforce Joint Patent Rights against any actual, alleged or threatened
infringement by Third Parties and to defend the Joint Patent Rights against any
challenges in the Territory. In the event Nuvelo shall so elect, Nuvelo shall
seek and reasonably consider Amgen’s comments before determining the strategy,
and Amgen (at Nuvelo’s request and sole cost and expense) shall reasonably
assist and cooperate in any such enforcement or defense. If Nuvelo finds it
necessary or desirable to join Amgen as a party, Amgen shall execute all papers
or perform such other acts as may reasonably be required by Nuvelo, at the
expense of Nuvelo, In the event Nuvelo does not commence an enforcement and/or
defense action pursuant to this Section 6.3(b) within forty-five (45) days after
Amgen notifies Nuvelo or is notified by Nuvelo in writing of an actual, alleged
or threatened infringement by a Third Party of the Joint Patent Rights in the
Territory (or of the filing of a declaratory judgment action), Amgen shall be
entitled to bring and prosecute such an action at its own cost and expense. If
Amgen elects to bring and prosecute such an action, then Amen shall seek and
reasonably consider Nuvelo’s comments on strategy, and Nuvelo (at Amgen’s
request and sole cost and expense) shall reasonably assist and cooperate in any
such enforcement or defense. If Amgen finds it necessary or desirable to join
Nuvelo as a party, Nuvelo shall execute all papers or perform such other acts as
may be reasonably be

 

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required by Amgen, at Amgen’s expense. Nuvelo shall, at its own expense, be
entitled to participate in and to have counsel selected by it participate in any
action in which Nuvelo is a named party.

 

(c) At its own cost and expense, Nuvelo may, but shall not be obligated to,
elect to enforce the Product Trademarks against Third Parties and to defend the
Product Trademarks against any challenges in the Territory. Nuvelo shall seek
and reasonably consider Amgen’s comments before determining the strategy and
Amgen, at Nuvelo’s request and sole cost and expense, shall reasonably assist
and cooperate in any such enforcement or defense. If Nuvelo finds it necessary
or desirable to join Amgen as a party, Amgen shall execute all papers or perform
such other acts as may reasonably be required by Nuvelo, at the expense of
Nuvelo. In the event Nuvelo does not commence an enforcement and/or defense
action pursuant to this Section 6.3(c) within forty-five (45) days after Amgen
notifies or is notified by Nuvelo in writing of an infringement of the Product
Trademarks in the Territory (or of the filing of a declaratory judgment action,
in the case of defense actions), Amgen shall be entitled to bring and prosecute
such an action at its own cost and expense. If Amgen elects to bring and
prosecute such an action, then Amen shall seek and reasonably consider Nuvelo’s
comments on strategy and Nuvelo, at Amgen’s request and sole cost and expense,
shall reasonably assist and cooperate in any such enforcement or defense. If
Amgen finds it necessary or desirable to join Nuvelo as a party, Nuvelo shall
execute all papers or perform such other acts as may be reasonably be required
by Amgen and at Amgen’s expense. Nuvelo shall, at its own expense, be entitled
to participate in and to have counsel selected by it participate in any action
in which Nuvelo is a named party.

 

(d) Any recovery realized as a result of any such litigation described in this
Section 6.3 (after reimbursement of the Parties’ reasonable attorneys’ fees for
outside counsel and litigation expenses) shall be allocated in proportion to
each Party’s respective profits realized from the Development, manufacturing and
Commercialization of Licensed Products under this License Agreement during the
immediately preceding Calendar year.

 

(e) Neither Party shall enter into any settlement of any suit brought under this
Section 6.3 that affects the other Party’s rights or interests without the other
Party’s written consent, which consent shall not be unreasonably withheld or
delayed.

 

(f) A Party bringing suit under this Section 6.3 shall notify the other Party of
all substantive developments with respect to such enforcement or defensive
actions including, but not limited to, all material filings, court papers and
other related documents, substantive settlement negotiations and offers of
settlement.

 

(g) Each Party shall promptly notify the other upon becoming aware of any Third
Party infringement of the Amgen Patent Rights, Joint Patent Rights, Product
Trademarks, Amgen Know-How or Joint Know-How.

 

6.4 Infringement of Third Party Rights.

 

(a) At its own cost and expense, Nuvelo shall have the first right to defend any
action naming Nuvelo, or both Parties, and claiming the infringement of (i) any
Third Party Patent

 

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Rights or other intellectual property rights through the making, having made,
using, selling, offering to sell or having sold, importing, exporting or
otherwise exploiting, transferring possession of title or interest in, Licensed
Product, or (ii) any Third Party Trademark through the Development,
manufacturing or Commercialization of a Licensed Product. The Parties shall
confer with each other and cooperate during the defense of any such action. At
Nuvelo’s cost and expense, Amgen shall assist and cooperate with Nuvelo in the
defense of any such action. If Nuvelo finds it necessary or desirable to join
Amgen as a party, Amgen shall execute all papers or perform such other acts as
may reasonably be required by Nuvelo, at Nuvelo’s expense. Subject to the
foregoing, Amgen shall, at its own expense, be entitled to participate in and to
have counsel selected by it participate in any action in which Amgen is a named
party.

 

(b) Each Party shall promptly notify the other upon becoming aware of any
actual, alleged or threatened Third Party claim or action against Nuvelo and/or
Amgen for infringement of any Third Party Trademark through the Development,
manufacturing or Commercialization of a Licensed Product; or any Third Party
Patent Rights through the making, having made, using, selling, offering to sell,
and importing, exporting or otherwise transferring physical possession of or
otherwise transferring title in and to Licensed Products in the Territory.

 

(c) Neither Party shall enter into any settlement of any suit referenced under
this Section 6.4 that affects the other Party’s rights or interests without the
other Party’s written consent, which consent shall not be unreasonably withheld
or delayed.

 

(d) A Party defending suit under this Section 6.4 shall notify the other Party
of all substantive developments with respect to such enforcement or defensive
actions including, but not limited to, all material filings, court papers and
other related documents, substantive settlement negotiations and offers of
settlement.

 

6.5 Employee Obligations. Prior to beginning work relating to any aspect of the
subject matter of this License Agreement and/or being given access to Amgen
Know-How or Joint Know-How or the Confidential Information of the other Party,
each employee, consultant or agent of Nuvelo and Amgen shall have signed or
shall be required to sign a non-disclosure and invention assignment agreement
pursuant to which each such person shall agree to comply with all of the
obligations of Nuvelo or Amgen, as appropriate, substantially including: (a)
promptly reporting any invention, discovery, process, software program or other
intellectual property right, as appropriate within Amgen Know-How or Joint
Know-How; (b) assigning to Nuvelo or Amgen, as appropriate, all of his or her
right, title and interest in and to any such invention, discovery, process,
software program or other intellectual property right; (c) cooperating in the
preparation, filing, prosecution, maintenance and enforcement of any Patent
Rights; (d) performing all acts and signing, executing, acknowledging and
delivering any and all papers, documents and instruments required for effecting
the obligations and purposes of this License Agreement; and (e) abiding by the
obligations of confidentiality and non-use set forth in this License Agreement.
It is understood and agreed that any such non-disclosure and invention
assignment agreement need not be specific to this License Agreement.

 

6.6 Patent Marking. Licensed Products marketed and sold by Nuvelo hereunder
shall be marked with appropriate patent numbers or indicia of Amgen Patent
Rights and/or Joint

 

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Patent Rights to the extent permitted by law in those countries of the Territory
in which such markings have notice value as against infringers of patents.

 

6.7 Waiver.

 

(a) Nuvelo, on behalf of itself and its directors, employees, officers,
shareholders, agents, successors and assigns hereby waives any and all actions
and causes of action, claims and demands whatsoever, in law or equity, of any
kind it or they may have against Amgen, its directors, employees, officers,
shareholders, agents, successors and assigns, which may arise in any way, except
as a result of Amgen’s gross negligence, recklessness or willful misconduct in
the performance of its rights or obligations under Sections 6.2, 6.3, 6.4 and
6.5.

 

(b) Amgen, on behalf of itself and its directors, employees, officers,
shareholders, agents, successors and assigns hereby waives any and all actions
and causes of action, claims and demands whatsoever, in law or equity, of any
kind it or they may have against Nuvelo, its directors, employees, officers,
shareholders, agents, successors and assigns, which may arise in any way, except
as a result of Nuvelo’s gross negligence, recklessness or willful misconduct in
the performance of its rights or obligations under Sections 6.2, 6.3, 6.4 and
6.5.

 

ARTICLE 7

PAYMENTS; RECORDS; AUDIT

 

7.1 Payments.

 

(a) U.S. Dollars. All payments to be made under this License Agreement shall be
made in United States Dollars by bank wire transfer in immediately available
funds to a bank account designated from time-to-time by Amgen.

 

(b) Royalty Payments. All Royalties payable to Amgen under this License
Agreement shall be paid within sixty (60) days of the end of each Calendar
Quarter except as otherwise specifically provided herein. Each payment of
Royalties owing to Amgen shall be accompanied by a statement certified by an
executive officer of Nuvelo as accurate to the best of its ability consistent
with Nuvelo’s standard practices in performing such computations and in
accordance with GAAP, (i) on a country-by-country basis, of the amount of gross
sales of Licensed Products, an itemized calculation of Net Sales of each
Licensed Product during such Calendar Quarter, (ii) the amount of aggregate
worldwide gross sales of Licensed Product and Net Sales during such Calendar
Quarter and (iii) on a cumulative basis for the current year and the amount of
Royalty due on Net Sales during such Calendar Quarter.

 

(c) Foreign Exchange. Net Sales received in currencies other than United States
Dollars shall be converted into the United States Dollar equivalent, at the
average rate of exchange for the Calendar Quarter to which such payments relate,
as reported in Bloomberg Professional, a service of Bloomberg L.P., during the
Royalty period of such Net Sales, or in the event Bloomberg Professional is not
available then The Wall Street Journal.

 

(d) Late Payments. Any amounts not paid by Nuvelo when due under this License
Agreement shall be subject to interest from and including the date payment is
due through and including the date upon which Nuvelo has made a wire transfer of
immediately available funds

 

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into an account designated by Amgen of such payment at a rate equal to the
lesser of (i) the sum of three percent (3%) plus the annual prime rate or
successive annual prime rates of interest quoted in the Money Rates section of
the on-line edition, of the Wall Street Journal (at
http://www.interactive.wsj.com) calculated daily on the basis of a 365-day year
or (ii) the highest rate permitted by applicable law.

 

(e) Blocked Currency. If Nuvelo, its Affiliates and/or Sublicensees are unable
to convert a foreign currency into United States Dollars for reasons beyond
their respective control, or are restricted by law or regulation from remitting
Royalties from any country of sale, Nuvelo shall cause such payment to be made
by deposit to the credit and account of Amgen or its designated nominee in any
commercial bank designated by Amgen in the applicable country. Nuvelo shall
deliver to Amgen proper evidence of such deposit.

 

(f) Withholding Taxes. Any taxes, assessments and fees to be withheld by Nuvelo
under the laws, rules or regulations of any foreign country for the account of
Amgen shall be promptly paid by Nuvelo for and on behalf of Amgen to the
appropriate governmental authority, and Nuvelo shall furnish Amgen with a copy
of the original official receipt for the payment of such tax within thirty (30)
days of payment. Any such tax, assessment and fee actually paid on Amgen’s
behalf shall be deducted from any Royalty payments due to Amgen. Nuvelo agrees
to make all lawful and reasonable efforts to minimize such taxes, assessments
and fees to Amgen.

 

7.2 Records; Audit. Nuvelo shall keep or cause to be kept such records as are
required in sufficient detail to track and determine (in a manner consistent
with GAAP) the accuracy of calculations of all sums or credits due under this
License Agreement and to accurately account for the calculations of all
Royalties due for Licensed Products under this License Agreement. Such records
shall be retained for a period of the later of (i) a three (3) year period
following the year in which any payments were made hereunder and/or (ii) the
expiration of the applicable tax statute of limitations (or any extensions
thereof), or such longer period as may be required by law. Once per Calendar
Year, Amgen shall have the option to engage (at its own expense) an independent
certified public accountant, appointed by Amgen and reasonably acceptable to
Nuvelo, to examine in confidence the books and records of Nuvelo as may be
necessary to determine, with respect to any Calendar Year, the correctness or
completeness of any report or payment required to be made under this License
Agreement; provided however, that the books and records for any particular
Calendar Year shall only be subject to one audit. The report of such accountant
shall be limited to a certificate verifying any report made or payment submitted
by Nuvelo during such period but may include, in the event the accountant shall
be unable to verify the correctness of any such payment, information relating to
why such payment is unverifiable. All information contained in any such
certificate shall be deemed the Confidential Information of Nuvelo hereunder. If
any audit performed under this Section 7.2 discloses a variance of more than
five percent (5%) from the amount of the “original report; showing the
calculation of a Royalty under section 5.2 of this License Agreement or
calculation of consideration due to Amgen under section 5.7 of this License
Agreement, Nuvelo shall bear the full cost of the performance of such audit.
Upon the expiration of three (3) years following the end of any Calendar Year,
the calculation of any such amounts payable with respect to such Calendar Year
shall be binding and conclusive upon Amgen, and Nuvelo shall be released from
any liability or accountability with respect to such amounts for such Calendar
Year.

 

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ARTICLE 8

PUBLICATIONS

 

8.1 Procedure. Nuvelo shall determine the overall strategy for and have the
right of publishing and presenting results of pre-clinical and clinical studies
of Licensed Products. However, each Party to this License Agreement recognizes
that the publication of papers regarding results of and other information
involving the activities under this License Agreement (including oral
presentations and abstracts) may be beneficial to both Parties, provided such
publications are subject to reasonable controls to protect Confidential
Information. In particular, it is the intent of the Parties to maintain the
confidentiality of any Confidential Information included in any patent
application until such patent application has been published. Accordingly, Amgen
will have the right to review and approve any paper proposed for publication by
Nuvelo (including oral presentations and abstracts) which utilizes Confidential
Information of Amgen. Before any such paper is submitted for publication or an
oral presentation made, Nuvelo will deliver a complete copy of the paper or
materials and abstracts for oral presentation to Amgen at least sixty (60) days
prior to submitting the paper to a publisher or making the presentation. Amgen
will review any such paper and give its comments to Nuvelo within thirty (30)
days after the delivery of such paper to Amgen. With respect to oral
presentation materials and abstracts, Amgen will make reasonable efforts to
expedite review of such materials and abstracts and will return such items as
soon as practicable to Nuvelo with appropriate comments, if any, but in no event
later than thirty (30) days from the date of delivery to Amgen. Nuvelo will
comply with Amgen’s request to delete references to Amgen’s Confidential
Information in any such paper and agrees to withhold publication of same for an
additional thirty (30) days in order to permit the Parties to obtain patent
protection, if either of the Parties deems it necessary, in accordance with the
terms of this License Agreement. Nuvelo will have the right to review and
approve any paper proposed for publication by Amgen (including oral
presentations and abstracts) which describes Licensed Products or which includes
Confidential Information of Nuvelo. Before any such paper is submitted for
publication or an oral presentation made, Amgen will deliver a complete copy of
the paper or materials and abstracts for oral presentation to Nuvelo at least
sixty (60) days prior to submitting the paper to a publisher or making the
presentation. Nuvelo will review any such paper, materials and abstracts and
give its comments to Amgen within thirty (30) days after the delivery of such
paper to Nuvelo. With respect to oral presentation materials and abstracts,
Nuvelo will make reasonable efforts to expedite review of such materials and
abstracts and will return such items as soon as practicable to Amgen with
appropriate comments, if any, but in no event later than thirty (30) days from
the date of delivery to Nuvelo. Amgen will comply with Nuvelo’s request to
delete references to Nuvelo’s Confidential Information in any such paper and
agrees to withhold publication of same for an additional thirty (30) days in
order to permit the Parties to obtain patent protection, if either of the
Parties deems it necessary, in accordance with the terms of this License
Agreement.

 

8.2 Credit. Any such publication or presentation will include recognition of the
contributions of the other Party according to standard practice for assigning
scientific credit, either through authorship or acknowledgment as may be
appropriate.

 

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ARTICLE 9

CONFIDENTIALITY

 

9.1 Treatment of Confidential Information. The Parties agree that during the
Term, and for a period of five (5) years after this License Agreement expires or
terminates, a Party receiving Confidential Information of the other Party shall
(a) maintain such Confidential Information in confidence to the same extent such
Party maintains its own confidential or proprietary information or trade secrets
of similar kind and value (but at a minimum each Party shall use reasonable best
efforts to maintain such Confidential Information in confidence); (b) not
disclose such Confidential Information to any Third Party without the prior
written consent of the disclosing Party, except for disclosures to its
Affiliates and Sublicensees who agree to be bound by obligations of
non-disclosure and non-use at least as stringent as those contained in this
Article 9; and (c) not use such Confidential Information for any purpose except
those purposes permitted by this License Agreement. Neither Party shall
knowingly disclose to the other Party any Third Party information or know-how
that such Party does not have the legal right to disclose to the other Party
and/or which it has a contractual obligation not to disclose to the other Party.

 

9.2 Authorized Disclosure. Notwithstanding any other provision of this License
Agreement, each Party may disclose Confidential Information of the other Party:

 

(a) to the extent and to the persons and entities as required by an applicable
law, rule, regulation, legal process, court order or the rules of the National
Association of Securities Dealers or of a Regulatory Authority; or

 

(b) as necessary to file, prosecute or defend those patent applications or
patents for which either Party has the right to assume filing, prosecution,
defense or maintenance, pursuant to Section 6.2 of this License Agreement; or

 

(c) to prosecute or defend litigation or otherwise establish rights or enforce
obligations under this License Agreement, but only to the extent that any such
disclosure is necessary.

 

The Party required or intending to disclose the other Party’s Confidential
Information under Sections 9.2(a) or (c) shall first have given prompt notice to
the other Party to enable it to seek any available exemptions from or
limitations on such disclosure requirement and shall reasonably cooperate in
such efforts by the other Party.

 

9.3 Materials. Pursuant to Section 16.9(c) of the Collaboration Agreement, the
Parties anticipate that Amgen may transfer certain of its Amgen Know How and
Amgen Material and Manufacturing Information to Nuvelo; provided however, that
Nuvelo agrees and acknowledges that Amgen may, but shall be under no obligation,
to transfer any Amgen Know How and Amgen Material and Manufacturing Information
characterized, conceived, developed, derived, generated or identified by Amgen
after the Effective Date. Nuvelo agrees that it shall use such Amgen Know How
and Amgen Material and Manufacturing Information only in accordance with the
terms and conditions of this License Agreement and will transfer such Amgen Know
How and Amgen Material and Manufacturing Information only to a Third Party

 

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which has agreed in writing to be bound by obligations of confidentiality and
non-use at least as restrictive as set forth herein and only to use in
accordance with the terms of this License Agreement. Nuvelo will promptly
thereafter provide notice of such transfer to Amgen.

 

9.4 Publicity; Terms of Agreement. The Parties agree that the existence of and
the material terms of this License Agreement shall be considered Confidential
Information of both Parties, subject to the special authorized disclosure
provisions set forth below in this Section 9.4 (in lieu of the authorized
disclosure provisions set forth in Section 9.2, to the extent of any conflict)
and without limiting the generality of the definition of Confidential
Information. The Parties will mutually agree upon the text of a press release
announcing the execution of this License Agreement. Thereafter, if either Party
desires to make a public announcement concerning this License Agreement or the
terms hereof that differs from this mutually agreed upon text, such Party shall
give reasonable prior advance notice of the proposed text of such announcement
to the other Party for its prior review and approval, such approval not to be
unreasonably withheld or delayed. A Party shall not be required to seek
permission from the other Party to repeat any information as to the terms of
this License Agreement that have already been publicly disclosed by such Party,
in accordance with the foregoing, or by the other Party. Either Party may
disclose the terms of this License Agreement to potential investors who agree to
be bound by obligations of non-disclosure and non-use at least as stringent as
those contained in this Article 9. The Parties acknowledge that Amgen and/or
Nuvelo may be obligated to file a copy of this License Agreement with the U.S.
Securities and Exchange Commission (the “SEC”) with its next quarterly report on
Form 10-Q, annual report on Form 10-K or current report on Form 8-K or with any
registration statement filed with the U.S. Securities and Exchange Commission
pursuant to the Securities Act of 1933, as amended, and each such Party shall be
entitled to make such filing; provided however, that it requests confidential
treatment of the more sensitive terms hereof to the extent such confidential
treatment is reasonably available to the filing Party under the circumstances
then prevailing. In the event of any such filing, the filing Party will provide
the non-filing Party with an advance copy of the License Agreement marked to
show provisions for which the filing Party intends to seek confidential
treatment and shall reasonably consider the non-filing Party’s timely comments
thereon.

 

9.5 Use of Names, Logos or Symbols. Subject to the licenses granted under
Section 2.2, and further subject to the authorized disclosure provisions under
Sections 9.2(a) and 9.4, no Party hereto shall use the name, Trademarks,
physical likeness, employee names or owner symbol of any other party for any
purpose (including, without limitation, private or public securities placements)
without the prior written consent of the affected Party, such consent not to be
unreasonably withheld or delayed so long as such use of name is limited to
objective statement of fact rather than for endorsement purposes. Nuvelo shall
not use any Trademark either substantially resembling or which is confusingly
similar to any of Amgen’s Trademarks in connection with the subject matter of
this License Agreement.

 

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ARTICLE 10

REPRESENTATIONS AND WARRANTIES

 

10.1 Representations and Warranties of Nuvelo. Nuvelo hereby represents and
warrants to Amgen that as of the Effective Date of the Collaboration Agreement:

 

(a) Corporate Existence, Power and Authority. It is a corporation duly
organized, validly existing and in good standing under the laws of the State of
Nevada and has full corporate power and authority and the legal right to own and
operate its property and assets and to carry on its business as it is now being
conducted and as contemplated in this License Agreement and to perform its
obligations hereunder including, without limitation the right to grant the
licenses granted hereunder. It has taken all necessary corporate action on its
part required to authorize the execution and delivery of this License Agreement
and the performance of its obligations hereunder,

 

(b) Binding Agreement. This License Agreement has been duly executed and
delivered on behalf of Nuvelo and constitutes a legal, valid and binding
obligation of Nuvelo that is enforceable against it in accordance with its
terms.

 

(c) No Conflict. The execution, delivery and performance of this License
Agreement by Nuvelo does not conflict with and would not result in a breach of
any agreement, instrument or understanding, oral or written, to which it is a
party or by which it may be bound, nor does it violate any material law or
regulation of any court, governmental body or administrative or other agency
having jurisdiction over it.

 

(d) Validity. It is aware of no action, suit, inquiry or investigation
instituted by any Third Party which questions or threatens the validity of this
License Agreement.

 

(e) Expertise. In entering into this License Agreement, Nuvelo has relied solely
on its own scientific and commercial experience and its own analysis and
evaluation of both the scientific and commercial value of the Licensed Products.

 

(f) Business Condition. It is not in violation of its charter, bylaws, or any
other organizational document, or in violation of any law, administrative
regulation, ordinance or order of any court or governmental agency, arbitration
panel or authority applicable to it, which violation, individually or in the
aggregate, would reasonably likely have a materially adverse effect on its
business or financial condition. Except as may be set forth in any documents
required to be filed by it under the Securities Act or Exchange Act, as the case
may be, it is not aware of any facts or circumstances, individually or in the
aggregate, which would reasonably likely have a materially adverse effect on its
business or financial condition.

 

10.2 Representations and Warranties of Amgen. Amgen hereby represents and
warrants to Nuvelo that as of the Effective Date of the Collaboration Agreement:

 

(a) Corporate Existence, Power and Authority. It is a corporation duly
organized, validly existing and in good standing under the laws of the State of
Delaware and has full corporate power and authority and the legal right to own
and operate its property and assets and to carry on its business as it is now
being conducted and as contemplated in this License Agreement and to perform its
obligations hereunder including, without limitation, the right to grant the
licenses granted hereunder. It has taken all necessary corporate action on its
part required to authorize the execution and delivery of this License Agreement
and the performance of its obligations hereunder.

 

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(b) Binding Agreement. This License Agreement has been duly executed and
delivered on behalf of Amgen and constitutes a legal, valid and binding
obligation of Amgen that is enforceable against it in accordance with its terms.

 

(c) No Conflict. The execution, delivery and performance of this License
Agreement by Amgen does not conflict with and would not result in a breach of
any agreement, instrument or understanding, oral or written, to which it is a
party or by which it may be bound, nor does it violate any material law or
regulation of any court, governmental body or administrative or other agency
having jurisdiction over it.

 

(d) Validity. It is aware of no action, suit, inquiry or investigation
instituted by any Third Party which questions or threatens the validity of this
License Agreement.

 

(e) Business Condition. It is not in violation of its charter, bylaws, or any
other organizational document, or in violation of any law, administrative
regulation, ordinance or order of any court or governmental agency, arbitration
panel or authority applicable to it, which violation, individually or in the
aggregate, would reasonably likely have a materially adverse effect on its
business or financial condition. Except as may be set forth in any documents
filed with the Securities and Exchange Commission, as required to be filed by it
under the Securities Act or Exchange Act, as the case may be, it is not aware of
any facts or circumstances, individually or in the aggregate, which would
reasonably likely have a materially adverse effect on its business or financial
condition.

 

10.3 Mutual Covenants. Each Party hereby covenants to the other Party as
follows:

 

(a) No Conflict. It shall not during the term of this License Agreement grant
any right, license, consent or privilege to any Third Party(ies) in the
Territory which would conflict with the rights granted to the other Party under
this License Agreement, and shall not take any action that would in any way
prevent it from assuming its obligations or granting the rights granted to the
other Party under this License Agreement or that would otherwise materially
conflict with or adversely affect its obligations or its assumption of the
rights granted to the other Party under this License Agreement.

 

(b) Exclusivity. It shall work exclusively with the other Party with respect to
Licensed Products (subject to Nuvelo’s rights under Sections 2.3 and 4.1 of this
License Agreement to grant sublicenses to Third Parties). It shall not, directly
or indirectly, make, have made, use, sell, offer to sell, import, export or
otherwise transfer physical possession of or otherwise transfer title in (for
purposes of Developing, manufacturing or Commercializing) a Competitive Product
in the Territory, nor license or otherwise enable a Third Party to take such
actions during the Term. If either Party acquires Control of a Competitive
Product as an incident to an otherwise strategic acquisition of or merger with a
Third Party, such Competitive Product shall be deemed a “Licensed Product” and
be subject to the terms and conditions of this License Agreement, with no
additional obligation on the other Party to pay any other consideration,
including any license fee or milestone payment or the like.

 

(c) Regulatory Data. It shall store and provide the other Party access to source
data supporting all Regulatory Filings and Regulatory Approvals for the longer
of (i) ten (10) years or

 

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relating to Licensed Products or relating to requests regarding Licensed
Products from any Regulatory Authority in the Territory.

 

10.4 Covenants of Nuvelo.

 

(a) No Debarment. In the course of the Development, manufacture and
Commercialization of Licensed Products and during the Term, Nuvelo shall not
knowingly use and shall not have knowingly used any employee or consultant who
is or has been debarred by a Regulatory Authority or, to the best of Nuvelo’s
knowledge, is or has been the subject of debarment proceedings by a Regulatory
Authority.

 

(b) Compliance. Nuvelo shall comply with all applicable statutes, regulations
and guidance of Regulatory Authorities in carrying out its activities regarding
the Development, manufacturing and Commercialization of Licensed Products in the
Territory.

 

(c) Diligence. Nuvelo covenants that it shall use Commercially Reasonable
Efforts to carry out its obligations in accordance with the terms of this
License Agreement including, as applicable, the Development, manufacturing and
Commercialization of Licensed Products in the Territory in accordance with the
terms of this License Agreement. Without limiting the generality of the
foregoing obligation, Nuvelo covenants that:

 

(i) Nuvelo shall use Commercially Reasonable Efforts to administer a Licensed
Product to a patient in a government-approved clinical trial within eighteen
(18) months after the Effective Date of the Collaboration Agreement. In the
event Nuvelo fails to administer such Licensed Product in such time period then,
within [*]         ([ * ]) months after the Effective Date, Nuvelo shall either
pay Amgen a [ * ]             Dollar ($ [ * ]         ) maintenance fee or Amgen
may terminate this License Agreement and Nuvelo shall immediately return all
rights to Amgen.

 

(ii) Nuvelo shall use Commercially Reasonable Efforts to administer a Licensed
Product to a patient in a government-approved clinical trial within [ *
]             ([*]) months after the Effective Date of the Collaboration
Agreement. In the event Nuvelo fails to administer such Licensed Product in such
time period then, in addition to any payment that may have been due under
subsection (i) above and within twenty-five (25) months after the Effective
Date, in addition to the payment in subsection (i) above, Nuvelo will either pay
Amgen a[*] [ * ] Dollar ($ [ * ]        ) maintenance fee or Amgen may terminate
this License Agreement and Nuvelo shall immediately return all rights to Amgen.

 

(iii) Nuvelo shall use Commercially Reasonable Efforts to administer a Licensed
Product to a patient in a government approved clinical trial within [*]        
([*]) months after the Effective Date of the Collaboration Agreement. In the
event Nuvelo fails to administer such Licensed Product in such time period, then
Amgen shall have the right to terminate this License Agreement and Nuvelo shall
immediately return all rights to Amgen.

 

(d) No Misappropriation. It shall not knowingly misappropriate the trade secret
of a Third Party in its activities to Develop, manufacture or Commercialize
Licensed Products.

 

[ * ]  Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

21

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(d) No Misappropriation. It shall not knowingly misappropriate the trade secret
of a Third Party in its activities to Develop, manufacture or Commercialize
Licensed Products.

 

10.5 Disclaimers. EXCEPT AS EXPRESSLY PROVIDED HEREIN, THE MATERIALS AND
INFORMATION PROVIDED HEREUNDER ARE BEING PROVIDED “AS IS” AND WITHOUT ANY
REPRESENTATIONS OR WARRANTIES. NEITHER PARTY MAKES ANY REPRESENTATIONS OR
WARRANTIES, EXPRESS OR IMPLIED, OF ANY TYPE WHATSOEVER REGARDING THE MATERIALS
AND INFORMATION. EACH PARTY EXPRESSLY DISCLAIMS ANY WARRANTY OF MERCHANTABILITY,
OF FITNESS FOR A PARTICULAR PURPOSE OR OF NONINFRINGEMENT.

 

ARTICLE 11

INDEMNIFICATION

 

11.1 Indemnification by Amgen. Amgen hereby agrees to defend, hold harmless and
indemnify (collectively “Indemnify” or be “Indemnified”) Nuvelo and its
Affiliates, agents, directors, officers and employees (the “Nuvelo Indemnitees”)
from and against any and all Losses resulting directly or indirectly from any
Third Party claims, suits, actions or demands arising directly or indirectly out
of (a) any of Amgen’s representations and warranties set forth in this License
Agreement being untrue in any material respect when made and/or (b) any material
breach or material default by Amgen of its covenants and obligations under this
License Agreement. Amgen’s indemnification obligation does not include any
responsibility for product liability claims, including but not limited to
negligence, strict liability, and breach of warranty claims, arising out of or
relating to the Licensed Product. To be eligible to be so Indemnified as
described in this Section 11.1, the Nuvelo Indemnitees shall provide Amgen with
prompt notice of any claims, suits, actions or demands (with a description of
the claim and the nature and amount of any such Loss) giving rise to the
indemnification obligation pursuant to this Section 11.1 and the exclusive
ability to defend such claims, suits, actions or demands (with the reasonable
cooperation of Nuvelo Indemnitees); provided however, that Amgen shall be
relieved of its obligations only if any failure by the Nuvelo Indemnitee to
deliver prompt notice shall have been prejudicial to its ability to defend such
claims, suits, actions or demands. Nuvelo shall have the right to retain its own
counsel, at its own expense, if representation of the counsel of Amgen would be
inappropriate due to actual or potential differing interests between the
Parties. Amgen shall not settle or consent to the entry of any judgment with
respect to any claim for Loss for which indemnification is sought, in a manner
that would materially adversely affect Nuvelo, without Nuvelo’s prior written
consent (not to be unreasonably withheld). Amgen’s obligation to Indemnify the
Nuvelo Indemnitees pursuant to this Section 11.1 shall not apply to the extent
of any Losses (i) that arise from the negligence or intentional misconduct of
any Nuvelo Indemnitee; (ii) that arise from Nuvelo’s material breach of any
representation, warranty, covenant or obligation under this License Agreement;
or (iii) for which Nuvelo is obligated to Indemnify the Amgen Indemnitees
pursuant to Section 11.2 of this License Agreement.

 

11.2 Indemnification by Nuvelo. Nuvelo hereby agrees to Indemnify Amgen and its
Affiliates, agents, directors, officers and employees (the “Amgen Indemnitees”)
from and against any and all Losses arising from Third Party claims, suits,
actions or demands resulting directly or indirectly from (a) any of Nuvelo’s
representations and warranties set forth in this License Agreement being untrue
in any material respect when made; (b) the Development, manufacture

 

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and Commercialization of Licensed Products by, on behalf of or under authority
of Nuvelo, its Affiliates or its Sublicensees; and/or (c) any material breach or
material default by Nuvelo of its covenants and obligations under this License
Agreement. Nuvelo is responsible for the defense of any and all product
liability claims, including but not limited to negligence, strict liability, and
breach of warranty claims, arising out of or relating to the Licensed Product.
Nuvelo is also responsible for any settlements or judgments arising from such
product liability claims arising out of or relating to the Licensed Product.
Nuvelo, its sublicensees, its successors and its Affiliates shall be deemed to
bear the obligations under this Section 11.2 jointly and severally. To be
eligible to be Indemnified as described above in this Section 11.2, the Amgen
Indemnitees shall provide Nuvelo with prompt notice of any claims, suits,
actions or demands (with a description of the claim and the nature and amount of
any such Loss) giving rise to the indemnification obligation pursuant to this
Section 11.2 and the exclusive ability to defend such claims, suits, actions or
demands (with the reasonable cooperation of Amgen Indemnitees); provided
however, that Nuvelo shall be relieved of its obligations only if any failure by
the Amgen Indemnitee to deliver prompt notice shall have been prejudicial to its
ability to defend such claims, suits, actions or demands. Amgen shall have the
right to retain its own counsel, at its own expense, if representation of the
counsel of Nuvelo would be inappropriate due to actual or potential differing
interests between the Parties. Nuvelo shall not settle or consent to the entry
of any judgment with respect to any claim for Loss for which indemnification is
sought, in a manner that would materially adversely affect Amgen, without
Amgen’s prior written consent (not to be unreasonably withheld). Nuvelo’s
obligation to Indemnify the Amgen Indemnitees pursuant to this Section 11.2
shall not apply to the extent of any Losses (i) that arise from the negligence
or intentional misconduct of any Amgen Indemnitee (including but not limited to
that arising from the manufacture of Licensed Product by Amgen), (ii) that arise
from any material breach by Amgen of any representation, warranty, covenant or
obligation under this License Agreement or (iii) for which Amgen is obligated to
Indemnify the Nuvelo Indemnitees pursuant to Section 11.1 of this License
Agreement.

 

11.3 Insurance. Within thirty (30) days of the Effective Date, Nuvelo shall at
its own expense procure and maintain an insurance policy/policies, including
product liability insurance (but excluding clinical trial insurance policies
which shall be required only while trials are ongoing), adequate to cover its
obligations hereunder and which is/are consistent with normal business practices
of prudent companies similarly situated. Nuvelo may self-insure all or part of
any such obligation consistent with pharmaceutical industry practices but Nuvelo
shall at all times maintain the following minimum Third Party insurance
coverage:

 

Type of Coverage

--------------------------------------------------------------------------------

   Amount

--------------------------------------------------------------------------------

Commercial General Liability Insurance

   $ 2,000,000.00

Product Liability Insurance

   $ 1,000,000.00

Excess Liability Insurance

   $ 1,000,000.00

Clinical Trial Liability Insurance

   $ 3,000,000.00

Workman’s Compensation

     Statutory Limits

 

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Each insurance policy required by and procured by Nuvelo under this Section 11.3
shall name Amgen as an additional insured. Such insurance shall not be construed
to create a limit of Nuvelo’s liability with respect to its indemnification
obligations under this Article 11. Nuvelo shall provide Amgen with a copy of the
certificate of insurance or other evidence of such insurance and/or
self-insurance, upon request. Nuvelo shall provide Amgen with written notice at
least thirty (30) days prior to the cancellation, non-renewal or material change
in such insurance or self-insurance which materially adversely affects the
rights of Amgen hereunder. In addition to the foregoing requirements under this
Section 11.3 of the License Agreement, prior to the First Commercial Sale,
Nuvelo shall secure product liability insurance with limits no less than
$15,000,000.00 per claim and $15,000,000.00 in aggregate.

 

11.4 Pre-Effective Date Losses. In accordance with Section 16.12 of the
Collaboration Agreement, each Party shall retain its obligations for Losses
accrued under the Collaboration Agreement and this License Agreement shall not
release, waive, alter or otherwise modify the Parties’ respective obligations
thereunder. Other than with respect to its obligation for Losses due under and
prior to the termination of the Collaboration Agreement, Nuvelo shall not assume
or be liable for (pursuant to this License Agreement) any Losses for which Amgen
is previously responsible, resulting from or arising in connection with the
Development, manufacture or Commercialization of Licensed Product on or prior to
the Effective Date.

 

11.5 Limitation of Liability. NEITHER PARTY NOR ITS RESPECTIVE AFFILIATES SHALL
BE LIABLE FOR SPECIAL, EXEMPLARY, CONSEQUENTIAL OR PUNITIVE DAMAGES, WHETHER IN
CONTRACT, WARRANTY, TORT, STRICT LIABILITY OR OTHERWISE INCURRED BY THE OTHER
PARTY IN CONNECTION WITH THIS LICENSE AGREEMENT, INCLUDING BUT NOT LIMITED TO
DAMAGES MEASURING LOST PROFITS OR BUSINESS OPPORTUNITIES.

 

ARTICLE 12

TERM AND TERMINATION

 

12.1. Term. This License Agreement shall become effective on the Effective Date
and shall remain in full force and effect, unless earlier terminated pursuant to
this Article 12, on a country-by-country basis until there is no remaining
Royalty payment obligation in any country. Upon the expiry of Nuvelo’s
obligation to pay “Royalties under this License Agreement for a given Licensed
Product in a country, Nuvelo shall have a fully paid, royalty free, unrestricted
license under the Amgen Technology and the Amgen Material and Manufacturing
Information to make, have made, use, sell, offer to sell, have sold, import,
export and otherwise exploit, transfer physical possession of and transfer title
or interest in or to such given Licensed Product in such country.

 

12.2 Termination for Convenience. Nuvelo may terminate this License Agreement at
any time by providing ninety (90) days prior written notice of termination to
Amgen.

 

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12.3 Termination by Amgen. In the event Nuvelo shall not timely pay any
maintenance fees due pursuant to either Section 10.4(c)(i) or 10.4(c)(ii) or
shall not timely administer a Licensed Product to a patient pursuant to Section
10.4(c)(iii), Amgen shall have the sole right to terminate this License
Agreement by providing thirty (30) days prior written notification of
termination to Nuvelo.

 

12.4 Termination for Default.

 

(a) In the event any material representation or warranty made hereunder or under
the Warrant Purchase Agreement by either Party shall have been untrue in any
material respect (“Representation Default”), or upon any material breach or
material default of a material obligation of this License Agreement or the
Warrant Purchase Agreement (as defined in the Collaboration Agreement) by a
Party (“Performance Default”), the Party not in default (“Non-Defaulting Party”)
must first give the other Party (“Defaulting Party”) written notice thereof
(“Notice of Default”), which notice must state the nature of the Representation
Default or Performance Default in reasonable detail and must request the
Defaulting Party cure such Representation Default or Performance Default within
sixty (60) days. During any such 60-day period after receipt or delivery of a
Notice of Default under this Section 12.4(a) for which termination of this
License Agreement, in whole or in part is a remedy, all of the Party’s
respective rights and obligations under the affected parts of this License
Agreement, including but not limited to Development, manufacturing and
Commercialization, shall (to the extent applicable) remain in force and effect.
If the Defaulting Party shall dispute the existence, extent or nature of any
default set forth in a Notice of Default, the Parties shall use good faith
efforts to resolve the dispute.

 

(b) Nuvelo. In the event of a Representation Default or a Performance Default by
Nuvelo that shall not have been cured within the period set forth in Section
12.4(a) above after receipt of a Notice of Default (or Nuvelo shall not have
presented a reasonably achievable plan to cure such Default as promptly as is
reasonably practicable under the circumstances), Amgen, at its option, may
terminate this License Agreement upon sixty (60) days prior written notice,
unless such Representation Default is an unintentional Representation Default of
the Warranty Agreement and Amgen did not provide Notice of Default within one
(1) year after the Effective Date. In addition, in the event of termination
pursuant to such uncured Representation Default as provided in the foregoing
sentence, Amgen will be entitled to receive a refund of all money paid.

 

(c) Amgen. In the event of a Representation Default or a Performance Default by
Amgen that shall not have been cured within the period set forth in Section
12.4(a) after receipt of a Notice of Default (or Amgen shall not have presented
a reasonably achievable plan to cure such Default as promptly as is reasonably
practicable under the circumstances), Nuvelo, at its option, may terminate this
License Agreement upon sixty (60) days prior written notice. In addition, in the
event of termination pursuant to such uncured Representation Default as provided
in the foregoing sentence, Nuvelo will be entitled to receive a refund of all
money paid.

 

12.5 Bankruptcy.

 

(a) Amgen may terminate this License Agreement if, during the term of the
Research Program, Nuvelo shall file in any court or agency pursuant to any
statute or regulation of any

 

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state or country, a petition in bankruptcy or insolvency or for reorganization
or for an arrangement or for the appointment of a receiver or trustee of Nuvelo
or of its assets, or if Nuvelo proposes a written agreement of composition or
extension of its debts, or if Nuvelo shall be served with an involuntary
petition in bankruptcy or seeking reorganization, liquidation, dissolution,
winding-up arrangement, composition or readjustment of its debts or any other
relief under any bankruptcy, insolvency, reorganization or other similar act or
law of any jurisdiction now or hereafter in effect, or there shall have been
issued a warrant of attachment, execution, distraint or similar process against
it, filed in any insolvency proceeding, and such petition shall not be dismissed
within ninety (90) days after the filing thereof, or if Nuvelo shall propose or
be a party to any dissolution or liquidation, or if Nuvelo shall make an
assignment for the benefit of creditors.

 

(b) All rights and licenses granted under or pursuant to this License Agreement
by Amgen or Nuvelo are and shall otherwise be deemed to be for purposes of
Section 365(n) of the U.S. Bankruptcy Code, licenses of rights to “intellectual
property” as defined under Section 101 of the U.S. Bankruptcy Code. The Parties
agree that each Party shall retain and may fully exercise all of its rights and
elections under the U.S. Bankruptcy Code. The Parties further agree that, in
event of the commencement of a bankruptcy proceeding by or against a bankrupt
Party under the U.S. Bankruptcy Code, the other Party shall be entitled to a
complete duplicate of (or complete access to, as appropriate) any intellectual
property and all embodiments of such intellectual property, and same, if not
already in the other Party’s possession, shall be promptly delivered to the
other Party (a) upon any such commencement of a bankruptcy proceeding, upon the
other Party’s written request therefor, unless the non-bankrupt Party (or a
trustee on behalf of the non-bankrupt Party) elects to continue to perform all
of its obligations under this License Agreement or (b) if not delivered under
(a) above, upon the rejection of this License Agreement by or on behalf of the
non-bankrupt Party, upon written request therefor by the other Party. In the
event of the commencement of a bankruptcy proceeding by or against Nuvelo, Amgen
shall have no responsibility for any product liability claims arising out of or
relating to Licensed Products.

 

12.6 Effects of Termination. In addition to any other remedies which may be
available at law or equity upon termination of this License Agreement the rights
and obligations of the Parties shall be as set forth in this Section 12.6.

 

(a) The following provisions shall remain in full force and effect after the
expiration or termination of this License Agreement: Section 6.5 (solely with
respect to any ongoing possession or exchange of the other Party’s Confidential
Information); Section 6.7; Article 7 (only with respect to accrued rights and
obligations pursuant to Section 12.7); Article 9 (Confidentiality); Section
10.3(c), 10.5 (Disclaimers); Article 11 (Indemnification); Article 12 (Term and
Termination); and Article 14 (General).

 

(b) The Parties shall retain their respective ownership rights as set forth in
Section 6.l(a) Amgen shall have the right, mutatis mutandis, to file, prosecute,
defend and maintain Joint Patent Rights under Section 6.2(b) (with Nuvelo having
the right mutatis mutandis to comment with respects to the claims of Joint
Patent Rights not relating to products which may in any way affect the rights
conferred to Amgen to Develop, manufacture and Commercialize Licensed Products)
and Product Trademarks under Section 6.2(d), enforce Joint Patent Rights

 

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under Section 6.3(b) (with Nuvelo having the right mutatis mutandis to assume
any enforcement and/or defense action not taken by Amgen with respect to the
claims of Joint Patent Rights not relating to products which may in any way
affect the rights conferred to Amgen to Develop, manufacture and Commercialize
Licensed Products) and Product Trademarks under Section 6.3(c); and defend any
action claiming the infringement of any Third Party Patent Rights or any Third
Party Trademark under Section 6.4(a) and to publish under Article 8.

 

(c) Nuvelo shall within thirty (30) days (other than with respect to Amgen
Material and Manufacturing Information, in which case by no later than
completion of its obligations, if any under Section 12.6(g) below) destroy, or
at Amgen’s request return, all Amgen Confidential Information, Amgen Know-How
and Amgen Material and Manufacturing Information (other than with respect to
maintaining one (1) archival copy of Confidential Information related thereto
for its legal files, for the sole purpose of determining its obligations
hereunder) and shall provide Amgen with certification by an officer of Nuvelo
that all such materials have been returned to Amgen.

 

(d) Nuvelo shall promptly transfer to Amgen ownership of all Regulatory Filings
and Regulatory Approvals then in its name for all Licensed Products and shall
notify the appropriate Regulatory Authorities and take any other action
reasonably necessary to effect such transfer of ownership. Nuvelo shall assign
to Amgen Nuvelo’s right, title and interest in the Product Trademarks.

 

(e) Amgen shall have the right to use Nuvelo’s Trademarks in the selling of any
existing inventory of Licensed Product(s) and to use Promotional Materials it
then has on hand, provided however, that Amgen promptly creates new Promotional
Materials (which do not use Nuvelo’s corporate name and/or logo), with no
obligation of accounting to Nuvelo.

 

(f) Nuvelo shall within thirty (30) days (other than with respect to Third Party
agreements entered into pursuant to Section 6.8, in which case by no later than
completion of its obligations if any under Section 12.6(g) below), at the
request of Amgen, assign (if assignable under its terms) to Amgen all of
Nuvelo’s rights and obligations under any then-existing Third Party licenses
having a license grant limited specifically to Licensed Products, regarding the
making, having made, use, selling, offering to sell, and importing, exporting or
otherwise transferring physical possession of or otherwise transferring title in
or to Licensed Products and shall not (until receiving notice of whether or not
Amgen desires such an assignment) terminate or amend any such Third Party
license. Otherwise, Nuvelo shall, at the request of Amgen, sublicense (if
sublicensable under its terms) to Amgen all of Nuvelo’s rights and obligations
under any then-existing Third Party licenses regarding the making, having made,
use, selling, offering to sell, and importing, exporting or otherwise
transferring physical possession of or otherwise transferring title in or to
Licensed Products and shall not (until receiving notice of whether or not Amgen
desires such a sublicense) terminate or amend any such Third Party license. Such
assignment or sublicense shall be made for no additional consideration and be
under the same terms and conditions as the underlying agreement.

 

(g) In the event Nuvelo shall (i) have been using a Third Party contract
manufacturer(s) to manufacture Licensed Products, it shall only be obligated
with respect to the manufacture and supply of Licensed Products under this
License Agreement to assign its

 

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agreement with each such Third Party contract manufacturer to Amgen or (ii) have
been manufacturing Licensed Products at its own facilities, it shall remain
responsible for supplying the reasonable amounts of Licensed Products for such
reasonable period of time as to allow Amgen to obtain an alternate source of
supply, if necessary, while ensuring an uninterrupted supply of Licensed Product
of suitable quality and quantity required for the Development and
Commercialization to proceed. Once manufacturing responsibility has been
successfully transferred, Nuvelo shall no longer be responsible for the
manufacture and supply of Licensed Products to Amgen for the Development and
Commercialization of Licensed Products in the Territory and for making any
decision with respect thereto and shall no longer be responsible for any
obligations pursuant to Article 4. In the event Nuvelo is obligated to continue
to supply Licensed Products under this Section 12.6(g), Amgen shall use
Commercially Reasonable Efforts to identify one or more viable Third Party
manufacturers in order to transfer manufacturing operations as soon as
commercially reasonable.

 

(h) Amgen hereby agrees to Indemnify the Nuvelo Indemnitees from and against any
and all Losses resulting from any Third Party claims, suits, actions or demands
resulting directly or indirectly from the Development, manufacture or
Commercialization of Licensed Products (including a claim that a Licensed
Product caused death or personal injury of any land). To be eligible to be
Indemnified as described above in this Section 12.6(h), the Nuvelo Indemnitees
shall provide Amgen with prompt notice of any claim (with a description of the
claim and the nature and amount of any such Loss) giving rise to the
indemnification obligation pursuant to this Section 12.6(h) and the exclusive
ability to defend such claim (with the reasonable cooperation of Nuvelo
Indemnitees); provided however, that Amgen shall be relieved of its obligations
only if any failure by the Nuvelo Indemnitee to deliver prompt notice shall have
been prejudicial to its ability to defend such action. Nuvelo shall have the
right to retain its own counsel, at its own expense, if representation of the
counsel of Amgen would be inappropriate due to actual or potential differing
interests between the Parties. Neither Party shall settle or consent to the
entry of any judgment with respect to any claim for Loss for which
indemnification is sought, without the prior written consent of the other Party
(not to be unreasonably withheld). Amgen’s obligation to Indemnify the Nuvelo
Indemnitees pursuant to this Section 12.6(h) shall not apply to the extent of
any Losses (i) that arise from the negligence or intentional misconduct of any
Nuvelo Indemnitee (including but not limited to that arising from the
Development of Collaboration Product by Nuvelo); (ii) that arise from Nuvelo’s
breach of any representation, warranty, covenant or obligation under this
License Agreement; or (iii) for which Nuvelo is obligated to Indemnify the Amgen
Indemnitees pursuant to Section 11.2 of this License Agreement.

 

(i) In the event that Amgen becomes entitled to terminate this License Agreement
at any time after the First Commercial Sale, the Parties will mutually agree
upon the text of a press release announcing the termination of this License
Agreement. After a notice of termination has been delivered pursuant to any one
of Sections 12.2 to 12.4, Nuvelo shall, in no event in excess of ninety (90)
days after the delivery date of such notice (other than with respect to
obligations which explicitly exceed such 90-day period), conduct an orderly
transition of rights and responsibilities from Nuvelo to Amgen or to a Third
Party, as the case may be. Further, each Party shall cooperate and assist the
other Party to effect any such transition of rights and responsibilities in an
orderly, reasonable and businesslike manner. Such assistance shall include, but
not be limited to (i) making its personnel and other resources reasonably
available to Amgen,

 

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as necessary and (ii) transferring copies of all relevant information, files or
data containing Information and all Materials to Amgen.

 

(j) Except as expressly set forth in this Section 12.6, all other rights and
obligations shall terminate.

 

12.7 Accrued Rights. Termination, relinquishment or expiration of any licenses
under this License Agreement or of this License Agreement for any reason in
accordance with this Article 12 shall he without prejudice to any rights which
shall have accrued to the benefit of either Party or any liability incurred by
either Party prior to the effective date of such termination, relinquishment or
expiration nor preclude either Party from pursuing all rights and remedies it
may have hereunder or at law or in equity with respect to any breach of this
License Agreement nor prejudice either Party’s right to obtain performance of
any obligation.

 

ARTICLE 13

DISPUTE RESOLUTION

 

13.1 Disputes. The Parties recognize that disputes as to certain matters may
from time to time arise during the term of this License Agreement which relate
to either Party’s rights and/or obligations hereunder. It is the objective of
the Parties to establish procedures to facilitate the resolution of disputes
arising from, concerning or in any way relating to this License Agreement in an
expedient manner by mutual cooperation and without resort to litigation. To
accomplish this objective, the Parties agree to follow the procedures set forth
in this Section 13.1 if and when a dispute arises under this License Agreement.
The Parties shall undertake good faith efforts to resolve any such dispute in
good faith. In the event the Parties shall be unable to resolve such dispute,
either Party may, by written notice to the other Party, have any dispute between
the Parties referred to their respective executive officers designated below )or
their designees or successors) for attempted resolution by good faith
negotiations within fifteen (15) days after such notice is received. Such
designated officers are as follows:

 

For Nuvelo:

   Nuvelo’s General Counsel

For Amgen:

   Amgen’s General Counsel

 

If the designated officers are not able to resolve such dispute within such
fifteen (15) day period, the dispute will be referred to the respective Chief
Executive Officers of each Party (or their respective Senior Vice President
designee(s)). If the Chief Executive Officers (or their designees) are unable to
resolve such dispute within a further fifteen (15) day period, either Party may
at any time thereafter pursue any legal or equitable remedy available to it.
Notwithstanding the above, either Party shall be entitled at all times and
without delay to seek equitable relief.

 

13.2 Governing Law; Judicial Resolution. Resolution of all disputes arising out
of or related to this License Agreement, or the performance, enforcement, breach
or termination of this License Agreement and any remedies relating thereto,
shall be governed by and construed under the substantive laws of the State of
California as applied to agreements executed and performed entirely in the State
of California by residents of the State of California, without regard to
conflicts of law rules. Any dispute arising under this License Agreement shall
be submitted to a state or federal court of competent jurisdiction in
California; provided however,

 

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that if Amgen is the initiating Party in a dispute, its shall bring such suit in
a state or federal court which has jurisdiction over Sunnyvale, California; and
if Nuvelo is the initiating Party in a dispute, its shall bring such suit in a
state or federal court which has jurisdiction over Thousand Oaks, California.

 

13.3 Patent and Trademark Dispute Resolution. Notwithstanding the above Section
13.2, as between the Parties, any dispute, controversy or claim relating to the
scope, validity, enforceability or infringement of any Amgen Patent Rights or
Joint Patent Rights or of any Product Trademark shall be submitted to a court of
competent jurisdiction in the Territory in which such Patent Rights or Trademark
rights were granted or arose. Notwithstanding the foregoing, any dispute,
controversy or claim relating to the scope, validity, enforceability or
infringement of any United States patent application or patent within Amgen
Patent Rights or Joint Patent Rights shall be submitted to a court of competent
jurisdiction in the State of California.

 

ARTICLE 14

GENERAL

 

14.1 Force Majeure. Both Parties shall be excused from the performance of their
obligations under this License Agreement to the extent that such performance is
prevented by Force Majeure and the nonperforming Party promptly provides notice
of the prevention to the other Party. Such excuse shall be continued so long as
the condition constituting Force Majeure continues and the nonperforming Party
uses reasonable efforts to remove the condition. When such circumstances arise,
the Parties shall discuss what, if any, modification of the terms of this
License Agreement may be required in order to arrive at an equitable solution.

 

14.2 Notices. Any notice required or permitted to be given under this License
Agreement shall be in writing, shall specifically refer to this License
Agreement and shall be deemed to have been sufficiently given for all purposes
if mailed by first class certified or registered mail, postage prepaid, express
delivery service or personally delivered or, if sent by facsimile, electronic
transmission is confirmed. Unless otherwise notified in writing, the mailing
addresses and fax numbers for notice of the Parties shall be as described below.

 

For Nuvelo:

  

Nuvelo, Inc.

670 Almanor Ave.

Sunnyvale, CA 94085-1710

Phone: (408) 524-8100

Facsimile: (408) 524-8415

Attn: General Counsel

     With a copy to: Chief Financial Officer

For Amgen:

  

Amgen Inc.

One Amgen Center Drive

Thousand Oaks, CA 91320-1799

Fax: (805) 499-6058

Attention: Vice President, Licensing

     With a copy to: Corporate Secretary

 

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14.3 Maintenance of Records. Each Party shall keep and maintain all records
required by law or regulation with respect to Licensed Products and shall make
copies of such records available to the other Party upon request.

 

14.4 No Strict Construction. This License Agreement has been prepared jointly
and shall not be strictly construed against either Party.

 

14.5 Assignment. Other than as set forth in Sections 2.3 or 14.6, neither Party
may assign or transfer this License Agreement or any lights or obligations
hereunder without the prior written consent of the other, except that a Party
may make such an assignment without the other Party’s consent to Affiliates or
to an entity that acquires all or substantially all of the business of such
Party, whether in a merger, consolidation, reorganization, acquisition, sale or
otherwise. This License Agreement shall be binding on the successors and assigns
of the assigning Party, and the name of a Party appearing herein shall be deemed
to include the name(s) of such Party’s successors and permitted assigns to the
extent necessary to carry out the intent of this License Agreement. Any
assignment or attempted assignment by either Party in violation of the terms of
this Section 14.5 shall be null and void and of no legal effect. The assigning
Party shall forward to the other Party a copy of those portions of each fully
executed assignment agreement which relate to the assumption of the rights and
responsibilities of the assigning Party, within sixty (60) days of the execution
of such assignment agreement.

 

14.6 Performance by Affiliates. Each of Amgen and Nuvelo acknowledge that
obligations under this License Agreement may be performed by Affiliates of Amgen
and Nuvelo. Each of Amgen and Nuvelo guarantee performance of this License
Agreement by its Affiliates, notwithstanding any assignment to Affiliates in
accordance with Section 14.5 of this License Agreement. Wherever in this License
Agreement the Parties delegate responsibility to Affiliates or local operating
entities, the Parties agree that such affiliates/entities may not make decisions
inconsistent with this License Agreement, nor amend the terms of this License
Agreement or act contrary to its terms in any way. Nuvelo shall forward to Amgen
a copy of each fully executed license or sublicense agreement, within sixty (60)
days of the execution of each such license or sublicense agreement.

 

14.7 Counterparts. This License Agreement may be executed in two (2) or more
counterparts, each. of which shall be deemed an original but all of which
together shall constitute one and the same instrument.

 

14.8 Severability. If any one or more of the provisions of this License
Agreement are held to be invalid or unenforceable by any court of competent
jurisdiction from which no appeal can be or is taken, such provisions shall be
considered severed from this License Agreement and shall not serve to invalidate
any remaining provisions hereof. The Parties shall make a good faith effort to
replace any invalid or unenforceable provision with a valid and enforceable one
such that the objectives contemplated by the Parties when entering this License
Agreement, as

 

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evidenced by the terms of this License Agreement in accordance with Section
14.16, may be realized.

 

14.9 Headings. The headings for each Article and Section in this License
Agreement have been inserted for convenience of reference only and are not
intended to limit or expand on the meaning of the language contained in the
particular Article or Section. Unless otherwise specified, (a) references in
this License Agreement to any Article, Section or Exhibit shall mean references
to such Article, Section or Exhibit of this License Agreement, (b) references in
any Section to any clause are references to such clause of such Section, and (c)
references to any agreement, instrument or other document in this License
Agreement refer to such agreement, instrument or other document as originally
executed or, if subsequently varied, replaced or supplemented from time-to-time,
as so varied, replaced or supplemented and in effect at the relevant time of
reference thereto.

 

14.10 Further Actions. Each Party agrees to execute, acknowledge and deliver
such further instruments, and to do all such other acts, as may be necessary or
appropriate in order to carry out the purposes and intent of this License
Agreement.

 

14.11 Independent Contractors. The relationship between Nuvelo and Amgen created
by this License Agreement is one of independent contractors. This License
Agreement does not create any agency, distributorship, employee-employer,
partnership, joint venture or similar business relationship between the parties.
Neither Party is a legal representative of the other Party, and neither Party
can assume or create any obligation, representation, warranty or guarantee
(express or implied) on behalf of the other Party for any purpose whatsoever.
Each Party shall use its own discretion and shall have complete and
authoritative control over its employees and the details of performing its
obligations under this License Agreement.

 

14.12 No Benefit of Third Parties. The representations, warranties, covenants
and agreements set forth in this License Agreement are for the sole benefit of
the Parties hereto and their successors and permitted assigns, and they shall
not be construed as conferring any rights on any Third Parties.

 

14.13 Use of Name. Except as expressly provided in this License Agreement, no
Party hereto shall use, and no rights are granted in or to, the names or
Trademarks (including the names “Amgen” and “Nuvelo”), physical likeness,
employee names or owner symbol of the other Party for any purpose (including,
without limitation, private or public securities placements) without the prior
written consent of the affected Party, such consent not to be unreasonably
withheld or delayed so long as such use of name is limited to an objective
statement of fact rather than for endorsement purposes, provided, further that
in the event that such use is legally required the required Party shall provide
the affected Party with “reasonable opportunity to comment on such use and the
required Party shall reasonably consider the comments timely provided by such
affected Party. Neither Party shall use any Trademark which either substantially
resembles or is confusingly similar to, misleading or deceptive with respect to,
or which dilutes any of the other Party’s Trademarks in connection with the
subject matter of this License Agreement.

 

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14.14 No Waiver. Any delay in enforcing a Party’s rights under this License
Agreement or any waiver as to a particular default or other matter shall not
constitute a waiver of such Party’s rights to the future enforcement of its
rights under this License Agreement, except with respect to an express written
and signed waiver relating to a particular matter for a particular period of
time.

 

14.15 Export Requirements. It is understood and acknowledged that the transfer
of certain commodities and technical data is subject to United States laws and
regulations controlling the export of such commodities and technical data,
including all Export Administration Regulations of the United States Department
of Commerce. Each Party hereby agrees and by entering into this License
Agreement gives written assurance that it shall comply with all United States
laws and regulations controlling the export of commodities and technical data
within Information and Materials, that it will be solely responsible for any
violation of any such laws and regulations by itself, its Affiliates or its
Sublicensees, and that it will indemnify, defend and hold the other Party
harmless from any liability in the event of any legal action of any nature
occasioned by such violation, pursuant to Section 11.1 (in the case of Amgen) or
Section 11.2 (in the case of Nuvelo).

 

14.16 Entire Agreement; Amendment. This License Agreement (including all
Exhibits); that certain Warrant Purchase Agreement, dated January 8, 2002; and
any rights and obligations surviving, by its terms, termination of that certain
Collaboration Agreement (as defined herein on Page 1) set forth the complete,
final and exclusive agreement and all the covenants, promises, agreements,
warranties, representations, conditions and understandings between the Parties
hereto and supersedes and terminates all prior agreements and understandings
between the Parties. There are no covenants, promises, agreements, warranties,
representations, conditions or understandings (either oral or written) between
the Parties other than as are set forth herein and therein. This License
Agreement may only be modified or supplemented in a writing expressly stated for
such purpose and signed by an authorized officer of each Party (i.e., it may not
be modified by any purchase order, change order, acknowledgment, order
acceptance, standard terms of sale, invoice or the like).

 

14.17 Exhibits. All Exhibits referenced herein and attached hereto are
incorporated in this License Agreement by reference.

 

SIGNATURE PAGE FOLLOWS

 

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IN WITNESS WHEREOF, the Parties have executed this License Agreement in
duplicate originals by their duly authorized representatives as of the Effective
Date.

 

LOGO [g3765810-491.jpg]

 

AMGEN INC.

     

NUVELO, INC.

By:   LOGO [g3765810-492.jpg]       By:   LOGO [g3765810-493.jpg]

Print Name:

 

Roger M. Perlmutter, M.D., Ph.D.

     

Print Name:

 

Ted W. Love

Title:

 

Executive Vice President,

     

Title:

 

Pres & CEO

   

Research and Development

           

 

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EXHIBIT A

 

Defined Terms

 

A.1 “Affiliate” shall mean, except as provided below, an individual, a
partnership, a joint venture, a corporation, a trust, an estate, an
unincorporated organization, a government or any department or agency thereof,
or any other entity or any combination of the aforementioned entities that,
directly or indirectly, through one or more intermediaries, controls, is
controlled by or is under common control with Amgen or Nuvelo. For purposes of
this definition, “control” shall mean the possession, direct or indirect, of the
power to cause the direction of the management and policies of a Party, whether
through ownership of more than fifty percent (50%) of the voting securities of
such Party, by contract or otherwise.

 

A.2 “Alfimeprase” shall mean the polypeptide having the amino acid sequence
which is set forth in Exhibit B.

 

A.3 “Amgen Know-How” shall mean all Information and Material Controlled by Amgen
prior to or on the Effective Date necessary to Develop, manufacture or
Commercialize Licensed Products, including but not limited to the following
information: (1) information disclosed in the IND for Alfimeprase as of the
Effective Date; (2) information disclosed as of the Effective Date in any IND
supplements for Alfimeprase; (3) all Amgen-sponsored collaborator data and
results (subject to any contractual confidentiality obligations of Amgen to
Third Parties regarding such results); (4) any regulatory data which Amgen
provides to Nuvelo; (5) sequence information of other Licensed Products and
information regarding their activity; and (6) such information which Amgen
expressly designates in writing it intends to include as Amgen Know-How under
this License Agreement; provided however, that Amgen Know-How shall exclude
Amgen Material and Manufacturing Information.

 

A.4 “Amgen Material and Manufacturing Information” shall mean the most current
version of (i) the Materials (other than Licensed Products); and (ii) the
Information pertaining to the manufacture of Licensed Products including,
without limitation, Information contained in the CMC section of any applicable
Regulatory Filings or Information regarding Amgen’s manufacturing facility; and
(iii) Information regarding the Materials.

 

A.5 “Amgen Patent Rights” shall mean Amgen’s rights in (a) those Patent Rights
Controlled by Amgen on the Effective Date with respect to the Licensed Products
and listed in Exhibit C and (b) all Patent Rights Controlled by Amgen prior to
or during the term of the License Agreement that claim Amgen Know-How.

 

A.6 “Amgen Technology” “shall mean all Amgen Patent Rights and Amgen Know-How
and Amgen’s interest in the Joint Patent Rights and Joint Know-How.

 

A.7 “Asian Countries” shall mean one or more of the following: Bangladesh,
Cambodia, India, Indonesia, Japan, Laos, Malaysia, Myanmar, Nepal, North Korea,
Pakistan, Peoples Republic of China (including Hong Kong and Macao),
Philippines, Singapore, South Korea, Sri Lanka, Taiwan, Thailand and Vietnam.

 

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A.8 “Calendar Quarter” shall mean the respective periods of three (3)
consecutive calendar months ending on either March 31, June 30, September 30, or
December 31 for so long as this License Agreement is in effect.

 

A.9 “Calendar Year” means each successive period of twelve (12) months
commencing on January 1 and ending on December 31.

 

A.10 “Commercialize” or “Commercialization” shall mean all activities relating
to the manufacturing, promotion, and other pre-launch and post-launch marketing
and sale activities of Licensed Products and shall include without limitation,
Phase IV clinical trials (as defined in the Collaboration Agreement) or
equivalent clinical trials conducted following Regulatory Approval to market
such Licensed Product.

 

A.11 “Commercially Reasonable Efforts” shall mean the level of efforts and
resources required to Develop, manufacture or Commercialize a Licensed Product
in a sustained manner consistent with the efforts a similarly situated
biopharmaceutical company would typically devote to a product of similar market
potential, profit potential or strategic value resulting from its own research
efforts, based on conditions then prevailing. Commercially Reasonable Efforts
shall be determined on a country-by-country (each country including its
territories) basis for a particular Licensed Product, and it is anticipated that
the level of effort will change over time reflecting changes in the status of
the Licensed Product and the country (including its territories) involved.

 

A.12 “Competitive Product” shall mean any pharmaceutical product, other than a
Licensed Product, that contains (a) Alfimeprase or (b) any fibrinolytic
metalloproteinase product which has, incorporates or contains the following
properties: (i) is directly fibrinolytic, (ii) does not require the involvement
of the plasminogen system, and (iii) is complexed by alpha-2 macroglobulin.

 

A.13 “Confidential Information” shall mean all Information received by either
Party from the other Party pursuant to this License Agreement, other than that
portion of such Information which:

 

  (a) is publicly disclosed by the disclosing Party, either before or after it
becomes known to the receiving Party;

 

  (b) was known to the receiving Party, without obligation to keep it
confidential, prior to when it was received from the disclosing Party;

 

  (c) is subsequently disclosed to the receiving Party, by a Third Party
lawfully in possession thereof without obligation to keep it confidential;

 

  (d) has been publicly disclosed other than by the disclosing Party and without
breach of an obligation of confidentiality with respect thereto; or

 

  (e) has been independently developed by the receiving Party without the aid,
application or use of Confidential Information, as demonstrated by competent
written proof.

 

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A.14 “Control” or “Controlled” shall mean possession of the ability to grant a
license or sublicense as provided for herein under such intellectual property
right without violating the terms of any agreement or other arrangement with any
Third Party.

 

A.15 “Development” or “Develop” shall mean all research, pre-clinical, process
development/manufacturing and clinical activities undertaken for a Licensed
Product required to successfully complete Pivotal Trials in the Territory. For
the avoidance of doubt, these activities shall include clinical drug development
activities, including among other things: test method development and stability
testing, toxicology, formulation, statistical analysis and report writing,
product approval and registration, and regulatory affairs related to the
foregoing. When used as a verb, “Develop” means to engage in Development.

 

A.16 “Dollar” shall mean a United States dollar, and “$” shall be interpreted
accordingly.

 

A.17 “Drug Approval Application” shall mean an application for Regulatory
Approval required before commercial sale or use of a Licensed Product as a drug
or to treat a particular indication in a regulatory jurisdiction, including
without limitation: (a) (i) a Biologics License Application (BLA) pursuant to 21
C.F.R. 601.2, submitted to the FDA, or any successor application or procedure
and (ii) any counterpart of a U.S. BLA in another country in the Territory; and
(b) all supplements and amendments, including supplemental BLAs (and any foreign
counterparts), that may be filed (e.g., to expand the label) with respect to the
foregoing.

 

A.18 “FDA” shall mean the United States Food and Drug Administration, or any
successor thereto.

 

A.19 “First Commercial Sale” shall mean the initial transfer by Nuvelo or its
Affiliates or Sublicensees under this License Agreement of a Licensed Product to
a non-Sublicensee Third Party in exchange for cash or some equivalent to which
value can be assigned for the purpose of determining Net Sales, following
Regulatory Approval to market such Licensed Product.

 

A.20 “Force Majeure” shall mean any occurrence beyond the reasonable control of
a Party that prevents or substantially interferes with the performance by such
Party of any of its obligations hereunder, if such occurs by reason of any act
of God, flood, fire, explosion, earthquake, breakdown of plant, shortage of
critical equipment, loss or unavailability of manufacturing facilities or
material, strike, lockout, labor dispute, casualty or accident, or war,
revolution, civil commotion, acts of public enemies, blockage or embargo, or any
injunction, law, order, proclamation, regulation, ordinance, demand or
requirement of any government or of any subdivision, authority or representative
of any such government, inability to produce or use materials, labor, equipment,
transportation, or energy sufficient to meet manufacturing needs without the
necessity of allocation, or any other cause whatsoever, whether similar or
dissimilar to those above enumerated, beyond the reasonable control of such
Party, if and only if the Party affected shall have used reasonable efforts to
avoid such occurrence and to remedy it promptly if it shall have occurred.

 

A.21 “GAAP” shall mean United States generally accepted accounting principles.

 

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A.22 “IND” shall mean an Investigational New Drug application.

 

A.23 “Information” shall mean all tangible and intangible techniques,
technology, practices, trade secrets, inventions (whether patentable or not),
methods, knowledge, know-how, conclusions, skill, experience, test data and
results (including pharmacological, toxicological and clinical test data and
results), analytical and quality control data, results or descriptions, software
and algorithms.

 

A.24 “Joint Know-How” shall mean Information and Materials characterized,
conceived, developed, derived, generated or identified jointly by employees of
or consultants to Nuvelo and employees of or consultants to Amgen from the
Effective Date through the Term.

 

A.25 “Joint Patent Rights” shall mean all Patent Rights that claim or disclose
Joint Know-How.

 

A.26 “Licensed Product(s)” shall mean (a) Alfimeprase or (b) any fibrinolytic
metalloproteinase product which is owned or Controlled by Amgen and/or Nuvelo
and which has, incorporates or contains the following properties: (i) is
directly fibrinolytic, (ii) does not require the involvement of the plasminogen
system, and (iii) is complexed by alpha-2 macroglobulin.

 

A.27 “Losses” shall mean liabilities, costs, fees, expenses and/or losses,
including without limitation reasonable legal costs and expenses and attorneys’
fees for outside counsel.

 

A.28 “Materials” shall mean certain biological materials including, but not
limited to, Licensed Products, screens, animal models, cell lines, cells,
nucleic acids, receptors and reagents.

 

A.29 “Net Sales” shall mean all revenues recognized in accordance with GAAP from
the sale or other disposition of Licensed Products by Nuvelo or its Affiliates
or Sublicensees to a non-Sublicensee Third Party after deducting returns and
allowances (actually paid or allowed) including, but not limited to, prompt
payment and volume discounts, price reductions, including Medicaid and similar
types of rebates, chargebacks from wholesalers of Licensed Products (whether in
cash or trade), freight, shipping, packing, insurance, rebates, and sales and
other taxes based on sales prices when included in gross sales, but not
including taxes when assessed on income derived from such sales. Amounts
received by Nuvelo or its Affiliates for the sale of Licensed Products among
Nuvelo or its Affiliates for resale or for transfer of Licensed Products to a
Sublicensee for resale shall not be included in the computation of Net Sales
hereunder.

 

A.30 “Patent Rights” shall mean (i) a pending application for a patent,
including without limitation any provisional, converted provisional, continued
prosecution application, continuation, divisional or continuation-in-part
thereof; or (ii) an issued, unexpired patent (with the term “patent” being
deemed to encompass, without limitation, an inventor’s certificate) which has
not been held invalid or unenforceable by a court of competent jurisdiction from
which no appeal can be taken or has been taken within the required time period,
including without limitation any substitution, extension, registration,
confirmation, reissue, re-examination, renewal or any like filing thereof.

 

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A.31 “Pivotal Trial(s)” shall mean those clinical trials on sufficient numbers
of patients that, if the defined end-points are met, are designed (and agreed to
by the FDA, or other Regulatory Authorities in the Territory based upon existing
data in the same patient population) as of the start of the trial to
definitively establish that a drug is safe and efficacious for its intended use,
and to define warnings, precautions and adverse reactions that are associated
with the drug in the dosage range to be prescribed, and provide pivotal data
supporting Regulatory Approval of such drug or label expansion of such drug and
that satisfy the requirements of 21 CFR 321.21(c) (or its successor regulation),
or an equivalent foreign clinical trial.

 

A.32 “Product Trademark” shall mean any trademarks and trade names (and
trademark applications (whether or not registered) together with all goodwill
associated therewith, and any renewals, extensions or modifications thereto in
the Territory), trade dress and packaging which (a) are owned by or Controlled
by either Party and (b) are applied to or used with Licensed Products or any
Promotional Materials. The Parties hereby acknowledge that as of the Effective
Date no such Product Trademarks are owned or have been developed by Amgen.

 

A.33 “Promotional Materials” shall mean all sales representative training
materials and all written, printed, graphic, electronic, audio or video matter
including, but not limited to, journal advertisements, sales visual aids, direct
mail, direct-to-consumer advertising, Internet postings, broadcast
advertisements, and sales reminder aids (e.g., scratch pads, pens and other such
items) intended for use or used by a Party in connection with any Promotion (as
defined herein) or Detailing (as defined in the Collaboration Agreement) of a
Licensed Product, except for (i) the Regulatory Authority-approved full
prescribing information for a Licensed Product, including any required patient
information and (ii) all labels and other written, printed or graphic matter
upon any container, wrapper, or any package insert or outsert utilized with or
for a Licensed Product.

 

A.34 “Regulatory Approval” shall mean any approvals (including supplements,
amendments, pre- and post-approvals and price approvals), licenses,
registrations or authorizations (including designations of a Licensed Product as
an “Orphan Product” under the Orphan Drug Act) of any national, supra-national,
regional, state or local regulatory agency, department, bureau, commission,
council or other governmental entity, including the FDA or equivalent foreign
Regulatory Authorities, necessary for the distribution, use or sale of a
Licensed Product in a regulatory jurisdiction. Regulatory Approval shall not
include any site license for an Amgen manufacturing facility.

 

A.35 “Regulatory Authority” shall mean the FDA or any counterpart of the FDA
outside the United States.

 

A.36 “Regulatory Filings” shall mean collectively, INDs, BLAs, establishment
license applications (ELAs) and drug master files (DMFs), applications for
designation of a Licensed Product as an “Orphan Product” under the Orphan Drug
Act, or any other similar filings (including any foreign equivalents and further
including any related correspondence and discussions), and all data contained
therein, as may be required by the FDA or equivalent foreign Regulatory
Authorities for the Development, manufacture or Commercialization of a Licensed
Product.

 

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A.37 “Royalty” or “Royalties” shall mean those amounts payable as royalties by
Nuvelo to Amgen pursuant to Section 5.2 of this License Agreement.

 

A.38 “Sublicensee” shall mean a Third Party to whom Nuvelo shall have granted a
license or sublicense under Nuvelo’s rights pursuant to Section. 2.3 to make,
have made, use, sell, offer for sale, or import a Licensed Product in one or
more countries in the Territory. Solely for the purpose of any compensation
payable to Amgen hereunder, “Sublicensee” shall include a Third Party to whom
Nuvelo or another Sublicensee shall have granted the right to distribute one or
more Licensed Product(s), wherein such distributor pays to Nuvelo or such
another Sublicensee a royalty based upon the revenues received by the
distributor for the sale of such Licensed Product(s), but shall not include (i)
any Third Party who receives an implied license to use a unit of Licensed
Product(s), arising by operation of law, as a consequence of the purchase of
said unit of Licensed Product(s); or (ii) any Third Party where Nuvelo or such
another Sublicensee merely sells such Licensed Product(s) at a fixed transfer
price to such distributor for resale by such distributor and Nuvelo is not
compensated based on the resale price of such Licensed Product by such
distributor.

 

A.39 “Term” shall have the meaning set forth in Section 12.1.

 

A.40 “Territory” shall mean the world.

 

A.41 “Third Party” shall mean any individual, a partnership, a joint venture, a
corporation, a trust, an estate, an unincorporated organization, a government or
any department or agency thereof, or any other than Amgen or Nuvelo or an
Affiliate of either of them.

 

A.42 “Third Party Payment” shall mean all upfront payments, milestone payments,
license fees, royalties or other payments, payable to any Third Party under any
Third Party license agreement deemed necessary or useful to make, have made,
use, sell, offer to sell, and import, export or otherwise transfer physical
possession of or otherwise transfer title in a Licensed Product.

 

A.43 “Trademark” shall mean any and all corporate names, trade names, service
marks, logos or trademarks and trademark applications (whether or not
registered) together with all good will associated therewith, and any renewals,
extensions or modifications thereto either filed or used.

 

A.44 “Valid Claim” shall mean (i) an unexpired claim of an issued patent within
the Amgen Patent Rights and Joint Patent Rights that has not been found to be
unpatentable, invalid or unenforceable by a court or other authority in the
country of the patent, from which decision no appeal is taken or can be taken;
or (ii) a claim of a pending application within the Amgen Patent Rights and
Joint Patent Rights, wherein such pending application claims a first priority no
more than five (5) years prior to the date upon which pendency is determined.

 

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EXHIBIT B

 

PROTEIN SEQUENCE OF ALFIMEPRASE

 

RN

   259074-76-5        ZREGISTRY

CN

   3-203-Fibrolase    [3-serine]    (Agkistrodon contortrix contortrix
recombinant)      (9CI)        (CA INDEX NAME)

FS

   PROTEIN SEQUENCE

SQL

   201

NTE

    

 

type

--------------------------------------------------------------------------------

 

location

--------------------------------------------------------------------------------

 

description

--------------------------------------------------------------------------------

bridge

  Cys-116   - Cys-196   disulfide bridge

bridge

  Cys-156   - Cys-180   disulfide bridge

bridge

  Cys-158   - Cys-163   disulfide bridge

 

SEQ

   1    SFPQRYVQLV    IV&DHRMNTK    YNGDSDKIRQ    WVHQIVNTIN    EIYRPLNIQF     
51    TLVGLEIWSN    QDLITVTSVS    HDTLASFGNW    RETDLLRRQR    HDNAQLLTAI     
101    DFDGDTVGLA    YVGGMCQLKH    STGVIQDHSA    INLLVALTMA    HELGHNLGMN     
151    HDGNQCHCGA    NSCVMAAMLS    DQPSKLFSDC    SKKDYQTFLT    VNNPQCILNK     
201    P                    

 

SEQ.3

   1    Ser-Phe-Pro-Gln-Arg-Tyr-Val-Gln-Leu-Val-      11   
Ile-Val-Ala-Asp-His-Arg-Met-Asn-Thr-Lys-      21   
Tyr-Asn-Gly-Asp-Ser-Asp-Lys-Ile-Arg-Gln-      31   
Trp-Val-His-Gln-Ile-Val-Asn-Thr-Ile-Asn-      41   
Glu-Ile-Tyr-Arg-Pro-Leu-Asn-Ile-Gln-Phe-      51   
Thr-Leu-Val-Gly-Leu-Glu-Ile-Trp-Ser-Asn-      61   
Gln-Asp-Leu-Ile-Thr-Val-Thr-Ser-Val-Ser-      71   
His-Asp-Thr-Leu-Ala-Ser-Phe-Gly-Asn-Trp-      81   
Arg-Glu-Thr-Asp-Leu-Leu-Arg-Arg-Gln-Arg-      91   
His-Asp-Asn-Ala-Gln-Leu-Leu-Thr-Ala-Ile-      101   
Asp-Phe-Asp-Gly-Asp-Thr-Val-Gly-Leu-Ala-      111   
Tyr-Val-Gly-Gly-Met-Cys-Gln-Leu-Lys-His-      121   
Ser-Thr-Gly-Val-Ile-Gln-Asp-His-Ser-Ala-      131   
Ile-Asn-Leu-Leu-Val-Ala-Leu-Thr-Met-Ala-      141   
His-Glu-Leu-Gly-His-Asn-Leu-Gly-Met-Asn-      151   
His-Asp-Gly-Asn-Gln-Cys-His-Cys-Gly-Ala-      161   
Asn-Ser-Cys-Val-Met-Ala-Ala-Met-Leu-Ser-      171   
Asp-Gln-Pro-Ser-Lys-Leu-Phe-Ser-Asp-Cys-      181   
Ser-Lys-Lys-Asp-Tyr-Gln-Thr-Phe-Leu-Thr-      191   
Val-Asn-Asn-Pro-Gln-Cys-Ile-Leu-Asn-Lys-      201    Pro

 

Amgen Contract #200200784

  41    

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EXHIBIT C

 

AMGEN PATENT RIGHTS AS OF THE EFFECTIVE DATE

 

PATENTS

 

COUNTRY

--------------------------------------------------------------------------------

 

TITLE

--------------------------------------------------------------------------------

 

PATENT #

--------------------------------------------------------------------------------

ALBANIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 AUSTRIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 BELGIUM  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 BULGARIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 CYPRUS  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 DENMARK  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 EURASIAN PATENT OFFICE  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  4627 EUROPEAN PATENT OFFICE  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 FINLAND  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 FRANCE  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 GERMANY  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 GREAT BRITAIN  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 GREECE  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 IRELAND  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 ITALY  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 LATVIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 LITHUANIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 LUXEMBOURG  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 MACEDONIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 MONACO  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 NETHERLANDS  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 NEW ZEALAND  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  518007 PORTUGAL  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 ROMANIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 SLOVENIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 SOUTH AFRICA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  02002/2400 SPAIN  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 SWEDEN  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 SWITZERLAND  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  1220685 UNITED STATES  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  6440414

 

Amgen Contract #200200784

  42    

--------------------------------------------------------------------------------

PATENTS

 

COUNTRY

--------------------------------------------------------------------------------

 

TITLE

--------------------------------------------------------------------------------

 

PATENT #

--------------------------------------------------------------------------------

UNITED STATES   METHOD FOR LOCALIZED
ADMINISTRATION OF FIBRINOLYTIC
METALLOPROTEINASES   6455269 UNITED STATES   DNA MOLECULES ENCODING
FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   6617145 AUSTRALIA   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   767827 NEW ZEALAND   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   517951 SINGAPORE   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   87654 SOUTH AFRICA   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   02002/2206 UNITED STATES   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   6261820 UNITED STATES   SIZE ENHANCED FIBRINOLYTIC
ENZYMES; LIMITATIONS OF PLASMA
INACTIVATION   6214594

 

PATENT APPLICATIONS

 

COUNTRY

--------------------------------------------------------------------------------

 

TITLE

--------------------------------------------------------------------------------

 

PATENT APPLICATlONS#

--------------------------------------------------------------------------------

UNITED STATES  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  10/226408 PCT  

METHOD FOR TREATMENT OF

INDWELLING CATHETER OCCULSION

USING FIBRINOLYTIC

  US03/19702 UNITED STATES  

METHOD FOR TREATMENT OF

INDWELLING CATHETER OCCULSION

USING FIBRINOLYTIC

  10/177916 AUSTRALIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  77430/00 BRAZIL  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  PI00014420-7 CANADA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  2385966 CHINA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  816379 CZECH REPUBLIC  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  02002-1033 HONG KONG  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  3100282.4 HUNGARY  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  00P0202554 ISRAEL  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  148842 JAPAN  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  2001527816 MEXICO  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  3197 NORWAY  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  20021500 PCT  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  US00/27022 POLAND  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  P-355016 SERBIA AND MONTENEGRO  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  P-233/02 SINGAPORE  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  2002017465 SLOVAKIA  

PHARMACEUTICAL COMPOSITIONS

OF FIBRINOLYTIC AGENT

  42402002

 

Amgen Contract #200200784

  43    

--------------------------------------------------------------------------------

PATENT APPLICATIONS

 

COUNTRY

--------------------------------------------------------------------------------

 

TITLE

--------------------------------------------------------------------------------

 

PATENT APPLICATIONS#

--------------------------------------------------------------------------------

SOUTH KOREA   PHARMACEUTICAL COMPOSITIONS OF FIBRINOLYTIC AGENT   7004128/02
AUSTRALIA   PHARMACEUTICAL COMPOSITIONS OF FIBRINOLYTIC AGENT   2004201694
EUROPEAN PATENT OFFICE   PHARMACEUTICAL COMPOSITIONS OF FIBRINOLYTIC AGENT  
4007657.2 NEW ZEALAND   PHARMACEUTICAL COMPOSITIONS OF FIBRINOLYTIC AGENT  
530959 SINGAPORE   PHARMACEUTICAL COMPOSITIONS OF FIBRINOLYTIC AGENT  
2004005427 AUSTRALIA   METHOD FOR LOCALIZED ADMINISTRATION OF FIBRINOLYTIC
METALLOPROTEINASES   0024346/01 CANADA   METHOD FOR LOCALIZED ADMINISTRATION OF
FIBRINOLYTIC METALLOPROTEINASES   2394613 EUROPEAN PATENT OFFICE   METHOD FOR
LOCALIZED ADMINISTRATION OF FIBRINOLYTIC METALLOPROTEINASES   988099.8 HONG KONG
  METHOD FOR LOCALIZED ADMINISTRATION OF FIBRINOLYTIC METALLOPROTEINASES  
3101990.5 JAPAN   METHOD FOR LOCALIZED ADMINISTRATION OF FIBRINOLYTIC
METALLOPROTEINASES   2001544901 MEXICO   METHOD FOR LOCALIZED ADMINISTRATION OF
FIBRINOLYTIC METALLOPROTEINASES   2002006024 PCT   METHOD FOR LOCALIZED
ADMINISTRATION OF FIBRINOLYTIC METALLOPROTEINASES   US00/34143 UNITED STATES  
METHODS FOR THE TREATMENT OF THROMBOSIS   10/441667 BRAZIL   FIBRINOLYTICALLY
ACTIVE POLYPEPTIDE   00014414-2 BULGARIA   FIBRINOLYTICALLY ACTIVE POLYPEPTIDE  
106578 CANADA   FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   2386185 CHINA  
FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   816321.9 CZECH REPUBLIC   FIBRINOLYTICALLY
ACTIVE POLYPEPTIDE   02002-1034 EURASIAN PATENT OFFICE   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   200200410 EUROPEAN PATENT OFFICE   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   965554.9 HONG KONG   FIBRINOLYTICALLY ACTIVE POLYPEPTIDE  
3100667.9 HUNGARY   FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   00P0202650 ISRAEL  
FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   148787 JAPAN   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   2001528597 MEXICO   FIBRINOLYTICALLY ACTIVE POLYPEPTIDE  
2002003126 NORWAY   FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   20021501 PCT  
FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   US00/27029 POLAND   FIBRINOLYTICALLY
ACTIVE POLYPEPTIDE   00P-355017 SERBIA AND MONTENEGRO   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   00P-225/02

 

Amgen Contract #200200784

  44    

--------------------------------------------------------------------------------

PATENT APPLICATIONS

 

COUNTRY

--------------------------------------------------------------------------------

 

TITLE

--------------------------------------------------------------------------------

 

PATENT APPLICATIONS#

--------------------------------------------------------------------------------

SLOVAKIA   FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   PV4232002S SOUTH KOREA  
FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   7004225 AUSTRALIA   FIBRINOLYTICALLY
ACTIVE POLYPEPTIDE   2004200775 EURASIAN PATENT OFFICE   FIBRINOLYTICALLY ACTIVE
POLYPEPTIDE   1 MEXICO   FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   1 NEW ZEALAND  
FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   530114 SERBIA AND MONTENEGRO  
FIBRINOLYTICALLY ACTIVE POLYPEPTIDE   00P-596/04 SINGAPORE   FIBRINOLYTICALLY
ACTIVE POLYPEPTIDE   2473790 PCT   SIZE ENHANCED FIBRINOLYTIC ENZYMES;
LIMITATION OF PLASMA INACTIVATION   US99/10108

 

Amgen Contract #200200784

  45    

--------------------------------------------------------------------------------

 

EXHIBIT D

 

MANUFACTURING TRANSFER OUTLINE

 

Summary

 

The Tech Transfer of the alfimeprase will occur on two fronts. First, the API
process and fill/finish process will be transferred to Nuvelo and then Nuvelo
will be responsible for transferring the process to the contract manufacturer,
Avecia and the fill/finish contractor of Nuvelo’s choice, which shall be either
[*]            or  [*]        Amgen will provide documentation currently in its
possession necessary for the transfer of manufacturing and to support Nuvelo’s
BLA filing to the extent relating to Amgen’s manufacturing prior of Licensed
Product prior to the Effective Date of the License Agreement. Activities
associated with transfers of analytical methods will be similar for both API and
DP. All transfers would begin as soon as possible after entering into the
License Agreement. Amgen would commit [*]    [*] FTEs for a one-year period to
performing the manufacturing technology transfer, one in Process Development,
one in Drag Product Process Development and one in Quality/Analytics. Amgen’s
manufacturing technology transfer responsibilities will be complete upon
Avecia’s successful completion of the shakedown runs.

 

Transfer of API Process:

 

Time [*]  LAUNCH (  [*]        )

 

  •   Meeting with CMO

 

  •   Review and finalize process fit

 

  •   Review equipment specs and confirm for ordering

 

  •   Prepare activity plan (includes lab-scale, large-scale centrifugation
runs, validation, etc.)

 

  •   Discuss analytical method transfer, and finalize assay validation
responsibilities

 

  •   Outline timeline and activities for harvest development

 

  •   Discuss process characterization plan

 

  •   Discuss training plan for CMO operators

 

  •   Finalize communication process, points of contact, etc. (between CMO
manufacturing operators, CMO tech transfer leads and ATO)

 

  •   Delivery of Technology Transfer Package

 

Time [*]  EQUIPMENT and RAW MATERIALS (  [*]        )

 

  •   Avecia/Nuvelo to order chromatography columns

 

  •   Avecia/Nuvelo to order depth filtration filter housings (6 housings)

 

  •   Avecia/Nuvelo to order delipid filtration filter housing (1 housings)

 

  •   Avecia/Nuvelo to order Stedim jacketed pallet tank for 1000-L bags, and
confirm availability of sterile bags (possible custom bag design with 1” tubing
– order)

 

[ * ]  Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

46

--------------------------------------------------------------------------------

  •   Avecia/Nuvelo to order membrane holders for existing CMO ultrafiltration
skids

 

  •   Avecia/Nuvelo to order trace heating elements for media filtration lines

 

  •   Check on availability of all raw materials, and Avecia/Nuvelo to begin
ordering

 

EQUIPMENT MODIFICATION / COMMISSIONING ( [ * ]      )

 

  •   Avecia/Nuvelo to test and evaluate ammonia gas system in fermentation
suite

 

  •   Avecia/Nuvelo to modify bioreactor controls for mass-flow (for lab-scale
and production scale)

 

  •   Discuss and Avecia/Nuvelo to complete various piping modifications to
support process

 

  •   Discuss and Avecia/Nuvelo to prepare microfiltration skid as possible
alternative to centrifugation

 

VALIDATION PLAN (  [ * ]    )

 

  •   Avecia/Nuvelo to Create validation Master Plan for conformance lots

 

PROCESS CHARACTERIATION ( [ * ]    )

 

  •   Avecia/Nuvelo to Plan for characterization studies

 

Time [*]  LAB SCALE DEMONSTRATION RUNS (  [*]    )

 

  •   Avecia to create batch records for lab scale runs (both upstream and
downstream)

 

  •   Avecia to perform a minimum of two runs

 

  •   Avecia collect and review lab scale data

 

  •   Avecia to develop and test microfiltration strategy for harvest (as
alternative to centrifugation)

 

  •   Avecia to test and finalize analytical assays for process

 

PROCESS CHARACTERIATION ( [ * ]      )

 

  •   Avecia to perform characterization studies

 

CENTRIFUGE CHARACTERIZATION ( [ * ]      )

 

  •   Avecia to write, review and finalize batch records

 

  •   Avecia to perform two large scale centrifugation runs

 

  •   Avecia to collect and review data

 

  •   Avecia to decide on final clarification strategy for harvest
(microfiltration versus centrifugation)

 

[ * ]  Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

47

--------------------------------------------------------------------------------

Time [ * ]  WRITE MANUFACTURING PROCEDURES ( [ * ]        )

 

  •   Avecia to create, review and finalize equipment validation procedures

 

  •   Avecia to create, review and finalize batch records/manufacturing
procedures for “Shake-down” runs

 

  •   Avecia to create process validation protocols

 

Time [ * ]  EQUIPMENT ( [ * ]  )

 

  •   Avecia to perform Factory Acceptance Tests (FAT)

 

  •   Avecia to receive all equipment

 

  •   Avecia to perform IQ/OQ/ PQ equipment validation

 

Time [ * ]  “SHAKE-DOWN” (ENGINEERING) RUNS (  [ * ]    )

 

  •   Avecia to perform two runs at large scale to test equipment, process,
analytical assays, etc.

 

  •   Avecia to collect and review data (compare to clinical GMP data)

 

  •   Avecia to troubleshoot issues, and finalize logistics and process for
preparation of conformance lots (including revision of batch records and
manufacturing procedures)

 

  •   Avecia to finalize acceptance criteria for conformance lots

 

Time [ * ]  CONFORMANCE LOTS (  [ * ]    )

 

  •   Avecia to perform five successful consecutive conformance lots

 

  •   Avecia to perform “blank” run following the five conformance lots

 

  •   Avecia to collect and review data

 

  •   Avecia to complete process validation protocols

 

[ * ]

 

Transfer of Drug Product (Fill/Finish)

 

It was anticipated that a contract manufacturer would be selected [ * ]

 

•   Tech Transfer items

 

  •   Amgen to prepare technical package for CM site

 

  •   Nuvelo to ID and procure equipment for CM site (tanks, change parts, raw
materials, components, freezers if needed, etc)

 

  •   CM to conduct tank characterization

 

  •   CM/Nuvelo to Review Batch record/MP/SOP draft

 

[ * ]  Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities and Exchange Act of 1934, as
amended.

 

48

--------------------------------------------------------------------------------

  •   Nuvelo to Develop validation strategy with CM site

 

  •   Nuvelo to work with CM on validation support of vial wash and
sterilization, stopper processing, etc

 

  •   CM to support WFI runs

 

  •   Nuvelo to support shakedown engineering runs

 

  •   CM to complete Lyo robustness studies (full scale at CM)

 

  •   CM to complete any scale-down work needed based on site parameters

 

  •   Nuvelo to support Validation runs

 

•   Nuvelo to partner with Contract Mfg on site selection for secondary
packaging (may be a post-conformance activity)

 

Transfer of Analytical Methods:

 

  •   Amgen to transfer documentation to contract manufacturer

 

  •   Amgen to review Method Transfer Protocols (MTP) with CM and Nuvelo

 

  •   Amgen to provide support for method troubleshooting

 

  •   Nuvelo and Amgen to review data from CM on MTP execution

 

  •   Nuvelo to review draft of Method Transfer Reports with CM and Amgen

 

  •   Amgen to transfer of stability samples to CM

 

  •   Amgen to transfer of stability database to CM

 

Amgen Contract #200200784

  49