EXHIBIT 10.9


 










[ * ] = 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 406 OF THE
SECURITIES EXCHANGE ACT OF 1933, AS AMENDED.


 


ALZA Contract #
20001780


 


INTERIM
DEVELOPMENT AGREEMENT


 


This INTERIM
DEVELOPMENT AGREEMENT (“Agreement”) is entered into as of this 8th
day of November, 2000 between ALZA CORPORATION (“ALZA”)
and BIOMEDICINES, INC. (“BioMedicines”).


 


RECITALS


 


A.                                   ALZA
and BioMedicines have entered into discussions with respect to the development
of a product utilizing proprietary technology of ALZA for the controlled
delivery of BioMedicines’ proprietary Interferon Omega recombinant protein and
have signed a Confidentiality Agreement dated May 10, 2000 (the “Confidentiality
Agreement”) in that regard.


 


B.                                     The
parties wish to commence the development of such product while negotiating the
definitive agreement covering the development, manufacture and marketing of
such product.


 


NOW THEREFORE, in
consideration of the mutual covenants and agreements provided herein, the
parties hereby agree as follows:


 


1.                                      DEFINITIONS.  For the purposes of this Agreement, the
following terms shall have the respective meanings set forth below:


 


1.1                               “Confidential
Information” shall mean (i) in the case of BioMedicines, information
disclosed by BioMedicines to ALZA on or after the Effective Date hereof
concerning Drug (as defined herein) as such, or the use or manufacture thereof,
owned by or licensed to BioMedicines prior to the date of the Confidentiality
Agreement or developed by BioMedicines after the date of the Confidentiality
Agreement outside the Program (as defined herein) and without reference to or
use of any Program Information (as defined herein) or ALZA Confidential
Information, and (ii) in the case of ALZA, information disclosed by ALZA to
BioMedicines on or after the Effective Date hereof concerning the System, or
the use or manufacture thereof, or otherwise useful to the Program, owned by or
licensed to ALZA prior to the date of the Confidentiality Agreement or
developed by ALZA after the date of the Confidentiality Agreement outside the
Program and without reference to or use of any Program Information or
BioMedicines Confidential Information. 
Confidential Information will not include any information which is (i)
now in the public domain or subsequently enters the public domain without fault
on the part of the receiving party; (ii) known by the receiving party from its
own sources, as evidenced by the receiving party’s written records made prior
to the date of the Confidentiality Agreement; or (iii) received from any third
party not under any obligation to keep such information confidential.


 


1





















 


1.2                               “Development
Costs” shall mean the costs of the Program incurred by ALZA pursuant to
this Agreement and determined in accordance with Exhibit A hereto.


 


1.3                               “Drug”
shall mean BioMedicines’ proprietary Interferon Omega recombinant protein in
its pure form or in the formulation originally provided to ALZA by BioMedicines
hereunder.


 


1.4                               “Effective
Date” shall mean November 8, 2000.


 


1.5                               “Product”
shall mean the product developed under the Program which combines Drug with
System or another product combining Drug with System that is substantially
identical to the Product.


 


1.6                               “Program”
shall mean all activities undertaken on or after the Effective Date by either
or both parties in accordance with the terms hereof for the development of a
Product, including regulatory and clinical activities.


 


1.7                               “Program
Information” shall mean any Technical Information and Regulatory Data
developed or acquired by either party under or as a result of the Program.


 


1.8                               “Regulatory
Data” shall mean regulatory filings (but not any Program Information owned
by ALZA or any of ALZA’s Confidential Information contained therein, which
shall remain the property of ALZA) resulting from the Program and clinical
study results resulting from activities under the Program.


 


1.9                               “System”
shall mean an implantable osmotic system which is intended to function by
releasing the active agent or agents on a controlled basis. The term “System”
will include anything incorporated in or used in connection with, or which is
an attribute of, the Product, or the development thereof, including anything
which affects or may affect the pharmacodynamics, pharmacokinetics, stability
or absorption of a therapeutic agent or the formulation, stabilization or use
of a therapeutic agent in the System (in each case other than the Drug itself,
any formulation of the Drug itself provided to ALZA by BioMedicines created by
BioMedicines not under or as a result of the Program or any other therapeutic
agent not physically incorporated into or onto the System).


 


1.10                        “Technical
Information” shall mean know-how, ideas, trade secrets, inventions
(including patents covering such inventions), data, technology and information,
including improvements and modifications to any thereof, processes and
analytical methodology used in development, testing, analysis and manufacture,
and medical, clinical, toxicological and other scientific data developed or
acquired by either party under or as a result of the Program.  Notwithstanding the foregoing, Technical
Information will not include trademarks or Regulatory Data.


 


2.                                      PRODUCT
DEVELOPMENT PROGRAM.


 


2.1                               Promptly
after execution of this Agreement and receipt from BioMedicines of Drug and the
materials described in Section 2.3, the parties will commence the
Program.  In connection with the Program,
the parties will make available appropriate scientific,


 










[ * ] = 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 406 OF THE
SECURITIES EXCHANGE ACT OF 1933, AS AMENDED.


 


2





















 


engineering
and other personnel to perform tasks under the Program.  The parties will use diligent efforts to
carry out the Program, will participate in periodic conferences to review its
status and will cooperate in the prompt preparation and review of, and
discussion concerning, work plans and cost estimates and revisions thereto as
further described in Section 2.2.


 


2.2                               The
initial work plan for, and the initial cost estimate for ALZA’s activities
under the Program is attached hereto as Exhibit B.  The parties understand and agree that it is
difficult to accurately predict the activities that will be necessary to
develop the Product, or the cost thereof, and significant uncertainties exist
in any product development effort.  As a
result, any such work plan and cost estimate will be diligently reviewed and
revised from time to time in order that it remain a faithful best-estimate of
work to be done by the parties under the Program and, with regard to ALZA’s
activities, the Development Costs thereof.


 


2.3                               In
connection with the Program, BioMedicines will provide to ALZA, at no charge to
ALZA, such quantities of Drug which ALZA may reasonably require to carry out
its duties hereunder.  BioMedicines will
provide ALZA with a Material Safety Data Sheet for the Drug and will complete
and return ALZA’s Safety and Environmental Evaluation Questionnaire prior to
commencement of the Program.  BioMedicines
will also provide ALZA with all relevant information available and known to
BioMedicines concerning the safety, handling, use, disposal and environmental
effects of the Drug or as may be necessary to conduct the Program.  ALZA will provide BioMedicines with all
relevant information available and known to ALZA concerning the safety,
handling, use, disposal and environmental effects on the System or as may be
necessary to conduct the Program.


 


BioMedicines will
indemnify, defend and hold ALZA harmless from and against all liabilities,
claims, demands, damages, losses, costs, expenses or money judgments (including
reasonable attorneys’ fees) incurred by or rendered against ALZA and resulting
from the use, storage or handling of the Drug under the Program, except to the
extent that ALZA has not complied with written materials provided in advance by
BioMedicines as described above. 
Notwithstanding the foregoing, BioMedicines shall not be required to
indemnify ALZA for actions by ALZA that represent willful misconduct, gross
negligence or a material violation of the law.


 


2.4                               BioMedicines
will pay to ALZA, on a monthly basis, all Development Costs incurred by ALZA in
connection with the activities carried out under the Program.  ALZA will invoice BioMedicines on or before
the fifteenth day of each month for the preceding month’s Development
Costs.  All payments will be made within
30 days after the date of the invoice. 
Notwithstanding the foregoing, BioMedicines will not be obligated to pay
Development Costs in excess of those provided for in approved work plans and
cost estimates, and ALZA will not be obligated to perform any work which would
result in Development Costs exceeding such approved cost estimates.


 


2.5                               Each
party will, for the term of this Agreement and for [ * ]
after its expiration or termination for any reason, keep confidential and not
disclose to others, and use only as permitted hereunder in connection with the
Program, (a) all clinical study results resulting from activities under the
Program (unless such results fall within the exceptions set forth in
subsections (i), (ii) and (iii) in the last sentence of Section 1.1
above), (b) all of the other 


 










[ * ] = 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 406 OF THE
SECURITIES EXCHANGE ACT OF 1933, AS AMENDED.


 


3





















 


party’s
Confidential Information and (c) all Program Information (other than such
clinical study results) owned by the other party.  Notwithstanding the foregoing, such
information may be (i) disclosed to government and regulatory agencies where
such information may be required to be included in patent applications or
regulatory filings permitted under the terms of this Agreement; (ii) provided
to third parties under agreements including appropriate confidentiality
provisions for consulting, market research, manufacturing, development, and
clinical testing with respect to the Product and similar activities under the
Program; (iii) published if and to the extent such publication has been
approved in writing by each of the parties (provided, however, results of
clinical studies of the Product may be published without the prior written
approval of both parties if and to the extent any such publication has been
reviewed to ensure that no Confidential Information or Program Information
(other than the results of clinical studies of the Product) has been disclosed
and each party has been given at least 60 days to file a patent application to
protect any patentable invention owned by it which would otherwise be disclosed
in such publication); or (iv) disclosed to the extent required by applicable
laws or regulations or as ordered by a court or other regulatory body having
competent jurisdiction.  In each of the
foregoing cases, the other party will use diligent efforts to limit the
disclosure and maintain confidentiality to the extent reasonably possible.


 


2.6                               As
part of the Program, BioMedicines may conduct clinical studies of the Product,
at its sole cost and expense.  In such
instances:


 


(a)                                  ALZA
will have the right to review and comment upon all proposed protocols, forms of
informed consent forms, investigator brochures and all forms of investigator
agreements and contract research organization agreements (other than with
respect to the financial arrangements under such agreements) for any clinical
studies to be conducted by or on behalf of BioMedicines with respect to the
Product.  ALZA agrees to provide its
comments to BioMedicines in writing as soon as reasonably practicable but in
any event within 30 days of receipt of such documents.  BioMedicines will make such changes in any
such documents as may be reasonably requested by ALZA in writing with respect
to the use of the System or any reference to or description of ALZA or to
otherwise protect the rights or intellectual property interests of ALZA as
described herein.


 


(b)                                  Clinical
supplies shall be supplied by ALZA on a Development Cost basis and shall be
manufactured in accordance with current Good Manufacturing Practices as defined
from time to time by the Act (as defined in Section 2.8) or any successor
laws or regulations governing the manufacture of clinical supplies of Product
in the United States (“GMPs”).


 


(c)                                  In
order to assist in obtaining patent protection for the Product outside the
United States, unless otherwise agreed in writing by ALZA, prior to conducting
any clinical study, BioMedicines will obtain from each participating subject or
patient, a confidentiality agreement in the form attached hereto as Exhibit C
and will deliver an executed copy thereof to ALZA.  If ALZA requires BioMedicines to obtain such
an agreement, ALZA shall pay the cost of any translation thereof as required by
applicable law or regulations.


 


(d)                                  Within
a reasonable time after completion or termination of each clinical study,
BioMedicines will deliver a final report concerning the study to ALZA.


 










[ * ] = 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 406 OF THE
SECURITIES EXCHANGE ACT OF 1933, AS AMENDED.


 


4





















 


Publication
of any data or information derived from the study, or any reports thereof, will
be subject to the mutual agreement of the parties, (provided, however, results
of clinical studies of the Product may be published without the prior written
approval of both parties if and to the extent any such publication has been
reviewed to ensure that no Confidential Information or Program Information
(other than the results of clinical studies of the Product) has been disclosed
and each party has been given at least 60 days to file a patent application to
protect any patentable invention owned by it which would otherwise be disclosed
in such publication).


 


(e)                                  If
and to the extent that any clinical studies are undertaken pursuant to this
Agreement, BioMedicines will indemnify, defend and hold ALZA harmless from and
against any and all liabilities, claims, demands, damages, losses, costs,
expenses or money judgments (including reasonable attorneys’ fees) incurred by
or rendered against ALZA, and which arise out of or result from the clinical
studies or the use, design or labeling of the Product in connection therewith,
except as may arise from the gross negligence or willful misconduct of
ALZA.  ALZA will give BioMedicines prompt
notice in writing, in the manner set forth in Section 5.3 below, of any
claim or demand made against ALZA for which ALZA may be entitled to indemnity
under this Section 2.6.


 


(f)                                    If
and to the extent that any clinical studies are undertaken pursuant to this
Agreement, ALZA will indemnify, defend and hold BioMedicines harmless from and
against any and all liabilities, claims, demands, damages, losses, costs,
expenses or money judgments (including reasonable attorneys’ fees) incurred by
or rendered against BioMedicines, which arise out of or result from the gross
negligence or willful misconduct of ALZA or the failure by ALZA to deliver
clinical supplies manufactured in accordance with GMPs as described in Section 2.6(b).  BioMedicines will give ALZA prompt notice in
writing, in the manner set forth in Section 5.3 below, of any claim or
demand made against BioMedicines for which BioMedicines may be entitled to
indemnity under this Section 2.6.


 


2.7                               As
part of the Program, ALZA will have the right, but not the obligation, to
review and comment upon all regulatory filings proposed to be made by
BioMedicines with respect to the Product, and BioMedicines will include any
changes reasonably requested by ALZA with respect to the use of the System or
any reference to or description of ALZA or to otherwise protect the rights or
intellectual property interests of ALZA as described herein.  Such changes must be provided within 10
business days after ALZA’s receipt of the proposed filing from
BioMedicines.  ALZA will have the right,
but not the obligation, to participate in any meetings to be held with
regulatory authorities with respect to the Product, and BioMedicines will
promptly provide ALZA with copies of all correspondence from or to regulatory
authorities concerning the Product.  If
ALZA does elect to participate in any meeting, then ALZA shall promptly inform
BioMedicines of its decision and agrees to coordinate its activities with
BioMedicines in preparation for said meeting(s).  Notwithstanding the foregoing, unless
otherwise agreed subsequently, BioMedicines shall be responsible for the
conduct of all meetings with regulatory authorities regarding the Product.


 


2.8                               Each
party will promptly notify the other party of any information that it obtains
or develops regarding the efficacy or safety of the Product or the System but
only insofar as such System-related information bears on the safety or efficacy
of the Product.  ALZA and BioMedicines
also agree to exchange adverse drug reaction reports in a manner and time frame



 










[ * ] = 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 406 OF THE
SECURITIES EXCHANGE ACT OF 1933, AS AMENDED.


 


5





















 


that
will allow compliance with regulatory reporting requirements, including any
requirements of the U.S. Food, Drug and Cosmetic Act, 21 U.S.C. 312 et seq.,
and regulations promulgated thereunder (the “Act”) (and, if applicable, the ICH
guidelines) and ongoing safety review of the Product.  After execution of this Agreement but prior
to the initiation of any clinical trial of the Product, the parties will agree
in writing upon standard operating procedures for reporting adverse events to
regulatory authorities and to each other. 
BioMedicines agrees and acknowledges that ALZA may provide information
it obtains under this Section 2.8 to ALZA’s other clients developing
and/or marketing other products incorporating the System or similar delivery
systems.


 


2.9                               Prior
to [ * ], BioMedicines will not conduct
(by itself or with a third party) any material development or commercialization
activities with respect to any product (other than the Product) which
incorporates any [ * ] into any drug delivery
system for the controlled or sustained release of such [ * ] and
intended for commercialization in any subterritory in which BioMedicines
retains exclusive commercialization rights to the Product (as described in
Exhibit D attached hereto).  Prior to [ * ], ALZA will not conduct (by itself or with any third
party) any material development or commercialization activities with respect to
any product (other than the Product) which incorporates any [ * ]) into any [ * ] drug
delivery system and intended for commercialization in any subterritory in which
BioMedicines retains exclusive commercialization rights to the Product (as
described in Exhibit D attached hereto) so long as BioMedicines is using
diligent efforts to carry out the Program and is not otherwise in material
breach of this Agreement.  Thereafter,
neither party will conduct (by itself or with a third party) any material
development or commercialization activities with respect to any product (other
than the Product) incorporating [ * ] drug delivery
system and intended for commercialization in any subterritory in which
BioMedicines retains exclusive commercialization rights to the Product (as
described in Exhibit D attached hereto).


 


3.                                      OWNERSHIP.


 


3.1                               Technical
Information will be (a) the property of BioMedicines if and to the extent (i) [ * ] or (ii) [ * ], and (b)
the property of ALZA [ * ].  [ * ] will be
the property of BioMedicines, subject to the confidentiality obligations set
forth in Section 2.5.


 


3.2                               Each
party has the right, with respect to Program Information owned by the other
party under Section 3.1, to use such information to carry out the Program
during the term of this Agreement.  Each
party has the right, with respect to Program Information owned by it under Section 3.1,
to disclose and to license such Program Information to third parties; provided,
however, that during the term of this Agreement, no such use will be
inconsistent with the terms of this Agreement.


 


3.3                               In
addition, if BioMedicines terminates this Agreement or determines not to
proceed with the Program for any reasons other than (i) an uncured material
breach of this Agreement by ALZA or (ii) the failure of the parties to enter
into a definitive development and commercialization agreement on the terms in
Exhibit D attached hereto (unless such failure is based on BioMedicines’
failure to negotiate such an agreement in good faith), BioMedicines hereby
grants ALZA a worldwide, royalty-free, nonexclusive license in perpetuity to
use all 


 










[ * ] = 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 406 OF THE
SECURITIES EXCHANGE ACT OF 1933, AS AMENDED.


 


6





















 


Regulatory
Data (including the right to cross-reference the Regulatory Data contained in
the regulatory filings made in connection with the Program).


 


3.4                               Nothing
in this Agreement shall provide or imply under any circumstance (i) the right
of BioMedicines to use or license the System from ALZA; (ii) the right of ALZA
to use or license [ * ] from
BioMedicines; or (iii) the right of either party to otherwise use or license
any intellectual property owned by the other party except as specifically
provided in this Agreement concerning Program Information.


 


3.5                               Each
party agrees to enter promptly into good faith negotiations with the other
party for a definitive development and commercialization agreement, consistent
with the terms set forth on Exhibit D attached hereto, and such additional
terms and conditions as the parties will agree, covering the development and
manufacture by ALZA and marketing by BioMedicines of the Product.


 


4.                                      TERM
AND TERMINATION.


 


4.1                               This
Agreement will remain in effect until such time as work is no longer being
carried out under the Program in accordance with mutually approved work plans
and cost estimates.


 


4.2                               BioMedicines
may terminate this Agreement at any time upon not less than sixty (60) days’
written notice to ALZA.  ALZA may
terminate this Agreement upon not less than thirty (30) days’ written notice to
BioMedicines but only if BioMedicines fails to pay any amounts due to ALZA
under this Agreement within thirty (30) days after the date of invoice or if
BioMedicines is not proceeding diligently with the Program in accordance with Section 2.1
hereof.


 


4.3                               Termination
of this Agreement will be without prejudice to ALZA’s right to receive from
BioMedicines (i) payment of all Development Costs incurred prior to the effective
date of the termination and (ii) all Program Information owned by it.  Termination of this Agreement by BioMedicines
will be without prejudice to BioMedicines’ right to receive from ALZA all
Program Information owned by it.  After
termination of this Agreement by BioMedicines or termination by ALZA due to a
breach of this Agreement by BioMedicines, BioMedicines will reimburse ALZA,
within thirty (30) days after invoice, for any uncancellable obligations and
expenses incurred by ALZA prior to such termination in connection with the
Program and all costs incurred by ALZA in terminating the Program.


 


4.4                               Upon
termination of this Agreement, ALZA will return all unused Drug to
BioMedicines, if requested by BioMedicines in writing within thirty (30) days
after termination, or otherwise will dispose of it at BioMedicines’ expense.


 


5.                                      MISCELLANEOUS.


 


5.1                               This
Agreement will be governed by and construed in accordance with the laws of the
State of California, excluding any choice of law rules which may direct the
application of the laws of another jurisdiction.


 










[ * ] = 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 406 OF THE SECURITIES
EXCHANGE ACT OF 1933, AS AMENDED.


 


7





















 


5.2                               This
Agreement will not be amended or modified except in a writing signed by each of
the parties hereto.


 


5.3                               All
notices, requests and other communications required or permitted to be given
hereunder or with respect hereto will be in writing, and may be given by (i)
personal delivery, (ii) registered first-class United States mail, postage
prepaid by the sender, return receipt requested, (iii) overnight delivery
service, charges prepaid by the sender, or (iv) via facsimile and, in each
case, addressed to the other party at the address for such party as set forth
below, and will be effective upon receipt in the case of (i) (iii) or (iv)
above, and five days after mailing in the case of (ii) above.


 


If to ALZA:                                                                                 ALZA
Corporation


1900 Charleston Road


Mountain View, CA  94043


Fax #: 650-564-7848


Attention:  General Counsel


 


If to BioMedicines:                                          BioMedicines,
Inc.


1301 Marina Village
Parkway


Suite 200


Alameda, CA  94501


Fax #: 510-814-0170


Attention:  Vice President, Chemical Development


 


Any party may
change its address at which notice is to be received by written notice provided
pursuant to this Section 5.3.


 


5.4                               Each
party will be responsible for assuring that all applicable rules, laws and
regulations are met in the performance of its respective duties hereunder.


 


5.5                               This
Agreement, together with the exhibits hereto, sets forth the entire agreement
and understanding between the parties with respect to the subject matter
hereof, and supersedes all prior agreements and understandings between the
parties with respect to the subject matter hereof, whether oral or in writing;
provided, however, that the provisions of the Confidentiality Agreement (other
than with respect to the term of confidentiality which is hereby amended to
extend to the term of this Agreement and for [ * ]
after its expiration or termination for any reason) will remain in full force
and effect with respect to Confidential Information (as such term is defined
therein) disclosed prior to the date hereof.


 


5.6                               Neither
party will originate any publicity, news release or public announcement,
written or oral, whether to the public, the press, stockholders or otherwise,
referring to the existence or terms of this Agreement, including its existence,
the subject matter to which it relates, the performance under it or any of its
specific terms and conditions, except such announcements, as in the opinion of
the counsel for the party making such announcement, are required by law,
including United States securities laws, rules or regulations, without the
prior written consent of the other party, such consent not to be unreasonably
withheld.  If a party decides to make an
announcement it believes to be required by law with respect to this 


 










[ * ] = 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 406 OF THE
SECURITIES EXCHANGE ACT OF 1933, AS AMENDED.


 


8










 










 


Agreement, it will give
the other party such notice as is reasonably practicable and an opportunity to
comment upon the announcement.  In
addition, neither party will disclose the existence of this Agreement, any of the
subject matter hereof, or any of the terms hereof to any third party without
the prior written consent of the other party, except as otherwise provided in
Section 2.5.


 


5.7                               The
provisions of Sections 1, the last sentence of 2.3, 2.5, 2.6(d), (e) and (f),
the first sentence of 2.8, 3.1, the second sentence of Section 3.2, 3.3, 3.4,
4.3, 4.4, 5.1, 5.3, 5.4, 5.5 , 5.6, 5.8, 5.9, 5.10, 5.11 and 5.12 and this
Section 5.7 will survive the termination for any reason of this Agreement.  Except as specifically provided in this
Agreement, neither party will be liable to the other due to the termination of
this Agreement as provided herein, whether in loss of good will, anticipated
profits or otherwise.


 


5.8                               In
the event that any provision of this Agreement (other than any provision
regarding confidentiality of the ownership of intellectual property) shall be
invalid or unenforceable under any controlling body of the law, the validity or
enforceability of the remaining provisions shall remain unaffected.


 


5.9                               This
Agreement may be executed in any number of counterparts, each of which shall be
deemed an original but all of which together shall constitute one and the same
instrument.


 


5.10                        The
failure of either ALZA or BioMedicines to assert a right hereunder or to insist
upon compliance with any term or condition of this Agreement shall not
constitute a waiver of that right or excuse a subsequent failure to perform any
term or condition by BioMedicines or ALZA, respectively.


 


5.11                        The
titles or headings of various numbered or un-numbered Sections in this Agreement
are for reference only and do not limit or modify the substance of the
Agreement in any way.


 


5.12                        Neither
party shall be held liable or responsible to the other party nor be deemed to
have defaulted under or breached this Agreement for failure or delay in
fulfilling nor performing any term of this Agreement, other than an obligation
to make a payment, when such failure or delay is caused by or results from
fire, floods, embargoes, government regulations, prohibitions or interventions,
war, insurrections, riots, civil commotions, lockouts, acts of God or any other
cause beyond the reasonable control of such party.


 


In Witness Whereof, the
parties have executed this Agreement as of the date first set forth above. 


 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 


9





















 


	
  Alza
  Corporation

  	
  Biomedicines,
  Inc.  

  
	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ Robert M. Myers

  	
   

  	
  By:

  	
  /s/ Mark Moran

  	
   

  
	
   

  	
  Robert M. Myers

  	
   

  
	
   

  	
  Title: Senior Vice President,

  	
   

  	
  Title: 

  	
  Chief Executive Officer

  	
   

  
	
   

  	
  Commercial Development

  	
   

  
							



 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 


10





















 


Exhibit
A


 


Development
Costs


 


Development Costs are
equal to the sum of (i) research expenses, (ii) general and administrative
expenses and (iii) capital asset expenditures.


 


(i)                                    Research
expenses include both direct expenses and indirect expenses.


 


(a)                                  Direct
expenses include direct [ * ] in
connection with the Program.


 


(b)                                  Indirect
expenses include [ * ].


 


Examples of items included in direct and indirect
expenses are listed on Exhibit A-1


 


(ii)                                General
and administrative expenses are allocated among the [ * ] organizations.  The portion allocated to the research and
product development organization is then allocated to all [ * ]


 


Examples of items included in general and
administrative expenses are listed on Exhibit A-1.


 


(iii)                            Capital
asset expenditures are the actual costs of new capital assets acquired
specifically for the project.


 










*  This fixed
billing rate will not be changed prior to [ * ] and, if
changed on or after [ * ], such
changes will be limited to not more than [ * ] change
per calendar year and shall be a maximum of [ * ] of
the rate in effect at the time of the increase.


 


[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 





















 


Exhibit
A-1


 


Examples of

Research Expenses


 


Direct Expenses


 


[ * ]


 


Indirect Expenses


 


[ * ]


 


Examples of

General and Administrative 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 406 of the Securities Exchange Act of
1933, as amended.


 





















 


Exhibit
B


 


Work
Plan And Cost Estimates


 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 





















 


Exhibit
C


 


Form of
(Patient) (Subject) Letter of Confidentiality


 


Dear Volunteer:


 


I would like to discuss
with you the possibility of you participating in a clinical study to evaluate
the safety and efficacy of a new product. 
This study is being sponsored by the company that is developing the new
product, and I will be participating in this study as an investigator.  I believe, based on your medical records,
that you would qualify as a participant in this study although a final
determination of your qualification cannot be made until a screening evaluation
is done.


 


At this time, information
about this new product and the study is being kept confidential by the company
sponsoring the study in order to protect the sponsor’s early work in the
development of this product.  I therefore
ask that you confirm by signing this letter that you will respect the sponsor’s
desire to keep any information relating to the new product and the clinical
study confidential until the sponsor releases the information to the public.


 


The sponsor recognizes
that your health and well-being are of primary importance and does not want to
prevent you from discussing information about the study, the product and its
effect on you with your health care providers and other persons involved in the
study.  Instead, what you are agreeing to
do is not to disclose any information about the product or this study to anyone
else.


 


Signing this letter does
not mean that you are required to participate in the study, or that you must
stay in the study if you begin to participate in the study.  It merely means that you will keep
information relating to the product or this study confidential, whether or not
you participate in the study.


 


If you are willing to
agree to maintain the confidentiality of this information, please return this
letter fully signed (including the date and your full name) to me.  I will then be free to discuss this matter in
greater detail with you.


 


 


	
  Very truly yours,

  
	
   

  
	
   

  	
   

  
	
  (Investigator)

  
	
   

  
	
  I agree with the
  confidential treatment of information as discussed above:

  
	
   

  
	
   

  	
   

  
	
  Signature

  
	
   

  
	
   

  	
   

  
	
  (Type in
  Patient/Subject Name)

  



 










[ * ] =
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 406 of the Securities Exchange Act of 1933, as
amended.


 





















 


	
  Date:

  	
   

  	
   

  



 










[ * ] =
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 406 of the Securities Exchange Act of 1933, as
amended.


 


2





















 


Exhibit
C-1a


 


(Alternative
Form for Minor Patients/Subjects)


 


Form of
(Patient) (Subject) Letter of Confidentiality


 


Dear Volunteer:


 


I would like to discuss
with you the possibility of you testing a new type of medicine. The sponsor of
this test has not made any public announcement about this new medicine so I am
asking you and your parent or guardian to agree not to discuss with other
people the information I may give you about the new medicine.


 


If you would like me to
tell you about this new medicine, you should talk with your parents or
guardian.  If you and your parents or
guardian agree that you would like to be a part of this test, please sign this
letter for me.


 


	
  Very truly yours,

  
	
   

  
	
   

  	
   

  
	
  (Investigator)

  
	
   

  
	
  I agree with the
  confidential treatment of information as discussed above:

  
	
   

  
	
   

  	
   

  
	
  Signature

  
	
   

  
	
   

  	
   

  
	
  (Type in
  Patient/Subject Name)

  
	
   

  
	
   

  
	
  Date:

  	
   

  	
   

  
			



 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 


















 


Exhibit
C-1b


 


Form of
Parent or Guardian Letter of Confidentiality


 


Dear Parent or Guardian:


 


I would like to discuss
with you the possibility of your minor child/ward participating as a volunteer
in a clinical study to evaluate the safety and efficacy of a new product.  This study is being sponsored by the company
that is developing the new product, and I will be participating in this study
as an investigator.  I believe, based on
the child’s medical records, that (s)he would qualify as a participant in this
study although a final determination of qualification cannot be made until a
screening evaluation is done.


 


At this time, information
about this new product and the study is being kept confidential by the company
sponsoring the study in order to protect the sponsor’s early work in the
development of this product.  I therefore
ask that you confirm by signing this letter that you will respect the sponsor’s
desire to keep any information relating to the new product and the clinical
study confidential until the sponsor releases the information to the public.


 


The sponsor recognizes
that the health and well-being of the child are of primary importance and does
not want to prevent the discussion of information about the study, the product
and its effect on the child with his/her health care providers and other
persons involved in the study.  Instead,
what you are agreeing to do is not to disclose any information about the
product or this study to anyone else.


 


Signing this letter does
not mean that the child is required to participate in the study, or that (s)he
must stay in the study if (s)he begins to participate in the study.  It merely means that you will keep
information relating to the product or this study confidential as described
above, whether or not the child participates in the study.


 


If you are willing to
agree to maintain the confidentiality of this information, please return this
letter fully signed (including date and your full name) to me. The child has
been asked to sign a separate letter.  
When you sign this letter and the child signs his/her letter, I will be
free to discuss this matter in greater detail with you and the child.


 


	
  Very truly yours,

  
	
   

  
	
   

  	
   

  
	
  (Investigator)

  
	
   

  
	
  I agree with the
  confidential treatment of information as discussed above:

  
	
   

  
	
   

  	
   

  
	
  Signature (Parent or
  Guardian)

  
	
   

  
	
   

  	
   

  
	
  (Type in Name
  of Parent or Guardian)

  



 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 





















 


Exhibit
D


 


Term
Sheet


 










[ * ] =
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 406 of the Securities Exchange Act of 1933, as
amended.


 





















 


Key Terms For

Product Development and Commercialization Agreement


DUROS® Interferon-omega


 


	
  Parties:

  	
   

  	
  ALZA Corporation (together with its affiliates,
  “ALZA”) and BioMedicines, Inc. (“BioMedicines”).

  
	
   

  	
   

  	
   

  
	
  Product:

  	
   

  	
  A product (the “Product”) combining BioMedicines’
  proprietary Interferon-omega (the “Drug”) and ALZA’s proprietary DUROS® drug
  delivery system (the “System”).

  
	
   

  	
   

  	
   

  
	
  Territory:

  	
   

  	
  Worldwide, divided into four Subterritories:

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Subterritory A: [ * ]

  
	
   

  	
   

  	
  Subterritory B: [ * ]

  
	
   

  	
   

  	
  Subterritory C: [ * ]

  
	
   

  	
   

  	
  Subterritory D: [ * ]

  
	
   

  	
   

  	
   

  
	
  Agreement:

  	
   

  	
  Product Development and Commercialization Agreement.

  
	
   

  	
   

  	
   

  
	
  Product Development Program:

  	
   

  	
  ALZA will undertake the development of the Product
  in accordance with work plans and cost estimates approved by BioMedicines.
  BioMedicines will have the right to pre-approve all work plans and cost
  estimates and will reimburse ALZA on a monthly basis for its Development
  Costs. The development program will proceed with diligence through product
  development and regulatory approval of the Product in Major Market Countries*
  in accordance with a reasonable regulatory strategy communicated by
  Biomedicines to ALZA.

  
	
   

  	
   

  	
   

  
	
  Commercialization Rights and Term:

  	
   

  	
  Upon receipt of regulatory approvals, BioMedicines
  will proceed with diligence to commence and continue diligent
  commercialization of the Product during the term of the Agreement as follows:

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Basic Term: BioMedicines will be
  granted the exclusive right to market the Product until (i) in each of
  Subterritories A, B, and C, [ * ] after
  the first commercial sale of the Product in the first Major Market Country of
  such Subterritory, and (ii) in Subterritory D, [ * ]
  after the first commercial sale of the Product in the first Major Market
  Country anywhere in the Territory. BioMedicines shall have the right to
  assign or transfer such right to a third party, subject to ALZA’s approval,
  such approval not to be unreasonably withheld (it being understood that
  reasonable bases for withholding such approval shall include, without
  limitation, a transfer to a competitor of ALZA in the drug delivery business,
  a transfer to a company with whom ALZA is engaged in significant litigation,
  or any other legitimate business reason).

  



 










*France, Germany, Italy,
Japan, United Kingdom and United States.


 


[ * ] = 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 406 of the Securities Exchange Act of 1933, as amended.


 


2





















 


	
   

  	
   

  	
  Extended Term:  At its election, BioMedicines may continue
  its commercialization rights on an exclusive basis, or convert to
  nonexclusive commercialization rights, after the Basic Term, on a
  Subterritory-by-Subterritory basis. 
  Such election will be made on an annual basis, at least 90 days before
  the end of each calendar year (beginning with the last year of the Basic Term).  Once BioMedicines has elected to convert to
  nonexclusive rights for any Subterritory, BioMedicines may not reconvert to
  exclusive rights for such Subterritory.

  
	
   

  	
   

  	
   

  
	
  Upfront Payments:

  	
   

  	
  None.

  
	
   

  	
   

  	
   

  
	
  Milestone Payments:

  	
   

  	
  [ * ], due upon initiation of
  the first [ * ] .

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [ * ] , due upon submission of
  first application for regulatory approval to market the Product in the [ * ].

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [ * ] , due upon first
  regulatory approval to market the Product in the [ * ].

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [ * ], due upon the first
  commercial sale of the Product in a Major Market Country.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [ * ], due when cumulative
  worldwide Net Sales** in four consecutive calendar quarters first exceed [ * ].

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [ * ], due when cumulative
  worldwide Net Sales in four consecutive calendar quarters first exceed [ * ]; provided, however, that if such milestone is
  reached within 12 months of the prior milestone being reached, such milestone
  shall not be due until 12 months after the prior milestone payment of [ * ] became due.

  



 










**        “Net Sales” will mean the total
amount billed or invoiced in United States dollars (or converted thereto in
accordance with the Definitive Agreement) on sales of the Product by
BioMedicines or any of its affiliates, assignees, transferees, distributors or
marketing partners (or their affiliates) to independent, unrelated third
parties such as wholesalers, hospitals, and others, in bona fide arm’s length
transactions, less the following deductions, in each case related specifically
to the Product and actually allowed and taken by such third parties and not
otherwise recovered by or reimbursed to BioMedicines or any of its affiliates,
assignees, transferees, distributors or marketing partners (or their
affiliates):  (i) trade, cash and
quantity discounts; (ii) taxes on sales (such as sales or use taxes) to the
extent added to the sale price and set forth separately as such in the total
amount invoiced; (iii) freight, insurance and other transportation charges to
the extent added to the sale price and set forth separately as such in the
total amount invoiced; and (iv) amounts repaid or credited by reason of
rejections, defects, recalls or returns or because of retroactive price
reductions or wholesaler chargebacks. Net Sales will also include the fair
market value of all other consideration received by BioMedicines in respect of
the Product or by any of its affiliates, assignees, transferees, 


 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 


3





















 


distributors or marketing partners (or their
affiliates) with respect to the Product, in each case whether such
consideration is in cash, payment in kind, exchange or other form.


 


	
   

  	
   

  	
  [ * ], due when cumulative
  worldwide Net Sales in four consecutive calendar quarters first exceed [ * ]; provided, however, that if such milestone is
  reached within 12 months of the prior milestone being reached, such milestone
  shall not be due until 12 months after the prior milestone payment of [ * ] became due.

  
	
   

  	
   

  	
   

  
	
  Exclusivity:

  	
   

  	
  Prior to [ * ],
  BioMedicines will not conduct (by itself or with a third party) any material
  development or commercialization activities with respect to any product
  (other than the Product) which incorporates any [ * ]
  into any [ * ] for the controlled or
  sustained release of such [ * ] and
  intended for commercialization in any Subterritory in which BioMedicines
  retains exclusive commercialization rights to the Product.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Prior to [ * ] , ALZA
  will not conduct (by itself or with a third party) any material development
  or commercialization activities with respect to any product (other than the
  Product) which incorporates any [ * ] into
  any [ * ] and intended for
  commercialization in any Subterritory in which BioMedicines retains exclusive
  commercialization rights to the Product so long as BioMedicines is not in
  material breach of this Agreement. In negotiations for the Agreement, the
  parties will discuss, without obligation on either side, incentives for ALZA
  to extend the foregoing exclusivity period.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Thereafter, neither party will [ * ] with
  respect to any product (other than the Product) incorporating [ * ] and intended for commercialization in any
  Subterritory in which BioMedicines retains exclusive commercialization rights
  to the Product.

  
	
   

  	
   

  	
   

  
	
  Product Payments:

  	
   

  	
  During the Basic Term: In addition
  to the supply price for the Product described below, BioMedicines will make
  quarterly payments (“Product Payments”) to ALZA in each calendar year based
  on Net Sales of the Product, at a percentage rate, determined as provided
  below, of the aggregate worldwide Net Sales of the Product for the
  immediately preceding calendar year:

  



 


	
  If Worldwide Net Sales 

  of the Product in 

  Year X are ($ U.S. million):

  	
   

  	
  The Payment Rate 

  For Year X + 1 will 

  be the following% of Net Sales:

  
	
   

  	
   

  	
   

  
	
  Less than [ * ]

  	
   

  	
  [ * ]

  
	
  [ * ]

  	
   

  	
  [ * ]

  
	
  [ * ]

  	
   

  	
  [ * ]

  
	
  [ * ]

  	
   

  	
  [ * ]

  
	
  [ * ] or more

  	
   

  	
  [ * ]

  



 










[ * ] = 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 406 of the Securities Exchange Act of 1933, as amended.


 


4





















 


	
   

  	
   

  	
  For clarification, for the calendar year in which
  the Product is first sold commercially, the payment rate will be [ * ] of Net Sales.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  During the Extended Term:  For any Subterritory for which BioMedicines
  elects to maintain exclusive commercialization rights after the Basic Term,
  Product Payments will continue to be determined in the same manner as during
  the Basic Term.  For any Subterritory
  for which BioMedicines elects to convert to nonexclusive commercialization
  rights after the Basic Term, Product Payments will be reduced by [ * ] of the rates for the Basic Term.  For example, assuming worldwide Net Sales
  in Year X were less than [ * ],
  the payment rate would be [ * ] of
  Net Sales in Year X + 1 for any Subterritory as to which BioMedicines elects
  nonexclusive rights.

  
	
   

  	
   

  	
   

  
	
  Minimum Payments:

  	
   

  	
  On a Subterritory by Subterritory basis,
  BioMedicines will make quarterly Minimum Payments to ALZA equal to [ * ] of projected quarterly Net Sales of Product in each
  of Subterritories A, B, and C (such projected Net Sales to be based on
  reasonably anticipated timing of regulatory approvals and sales
  projections).  Such quarterly Minimum
  Payments will be established no later than the date of submission of the
  first application for regulatory approval to market the Product, and will be
  fully creditable against quarterly Product Payments due for the quarter in
  which the Minimum Payments are made. 
  No minimum payments will be due for Subterritory D.

  
	
   

  	
   

  	
   

  
	
  Manufacture and Supply:

  	
   

  	
  ALZA will manufacture BioMedicines’ requirements of
  the Product.  The parties will begin to
  negotiate in good faith fixed supply prices (which may include annual price
  increases in accordance with the U.S. Producers’ Price Index) promptly after
  the manufacture and acceptance by BioMedicines of three batches of the
  Product which meet the then-current guidelines of the International Committee
  on Harmonization (“ICH”), or successor organization, or regulatory
  requirements of the U.S. Food and Drug Administration, whichever are more
  stringent.  Until the parties agree
  upon a supply price, the supply price will be [ * ] of
  ALZA’s standard manufacturing cost. BioMedicines will supply Drug to ALZA at [ * ].

  
	
   

  	
   

  	
   

  
	
  Proprietary Rights:

  	
   

  	
  The provisions regarding ownership of Program
  Information will be identical to those in Article 3 of the Interim
  Development Agreement between the parties, including a license to Regulatory
  Data for ALZA under the terms set forth in Section 3.3 of the Interim
  Development Agreement in each Subterritory in which BioMedicines no longer
  retains exclusive commercialization rights to the Product.

  
	
   

  	
   

  	
   

  
	
  Indemnification:

  	
   

  	
  BioMedicines will indemnify ALZA for claims arising
  from the use or sale of the Product, except to the extent due to ALZA’s gross
  negligence or intentional misconduct, illegal act or failure to manufacture
  Product in accordance with cGMP.  ALZA
  will warrant that, at the time of shipment, Product manufactured by ALZA will
  meet the NDA or BLA

  



 










[ * ] = 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 406 of the Securities Exchange Act of 1933, as amended.


 


5





















 


	
   

  	
   

  	
  specifications, will be manufactured in accordance
  with cGMP, and will not be adulterated or misbranded due to any action, or
  failure to act, of ALZA.  ALZA will
  indemnify BioMedicines for breach of this warranty, subject to certain
  limitations to be negotiated in good faith and included in the Agreement.
  BioMedicines will make parallel warranties with respect to Drug and will
  indemnify ALZA for breach of these warranties, subject to certain limitations
  to be negotiated in good faith and included in the Agreement.

  
	
   

  	
   

  	
   

  
	
  Termination:

  	
   

  	
  BioMedicines may terminate the Agreement at any time
  upon [ * ] written notice to ALZA.

  



 


THIS DOCUMENT OUTLINES THE GENERAL BUSINESS TERMS FOR THE
AGREEMENT.  OTHER TERMS AND CONDITIONS
WILL APPLY.


 










[ * ] = 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 406 of the Securities Exchange Act of 1933, as amended.


 


6





















 


COMPANY
LETTERHEAD


 


 


May 10, 2002


 


BioMedicines, Inc.


2000 Powell Street, Suite
1640


Emeryville, CA 94608


 


Re:          Amendment
No. 1 to lnterim Development Agreement Effective November 8, 2000

ALZA Contract # 20001780-1


 


Ladies and Gentlemen:


 


ALZA Corporation (“ALZA”)
and BioMedicines, Inc. (“BioMedicines”) desire to amend the Interim Development
Agreement between the parties effective November 8, 2000 (the “Agreement”).  Accordingly, effective immediately, Section
2.5 of the Agreement is hereby amended by adding the following sentence at the
end of that section: “Additionally, ALZA may disclose Confidential Information
to affiliated companies controlling, under the control of, or under common
control with ALZA, if such companies are bound by obligations of
confidentiality at least as stringent as those set forth herein.”


 


Capitalized terms used
but not otherwise defined herein shall have the meanings ascribed to them in
the Agreement. Except as expressly amended herein, the Agreement shall remain
unchanged and in full force and effect.


 


If the foregoing is
acceptable, please have both copies of this Amendment executed and dated by an
authorized corporate officer and return one fully executed original to ALZA.


 


	
  Very truly yours,

  	
   

  
	
   

  	
   

  
	
  ALZA Corporation

  	
   

  
	
   

  	
   

  
	
  /s/ Erik Wiberg

  	
   

  	
   

  
	
   

  	
   

  
	
  Erik D. Wiberg

  	
   

  
	
  Vice President,
  Business Development

  	
   

  
	
   

  	
   

  
	
  AGREED TO AND ACCEPTED
  THIS 20th DAY OF May , 2002

  	
   

  
	
   

  	
   

  
	
  BioMedicines, Inc.

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ S. M. Moran

  	
   

  
	
   

  
	
  Title:

  	
  CEO

  	
   

  
					



 


















 


COMPANY
LETTERHEAD


 


August 6, 2002


 


BioMedicines, Inc.


2000 Powell Street, Suite
1640


Emeryville, CA 94608


 


Re:          Amendment
No. 2 to lnterim Development Agreement Effective November 8, 2000

ALZA Contract # 20001780-2


 


Ladies and Gentlemen:


 


ALZA Corporation (“ALZA”)
and BioMedicines, Inc. (“BioMedicines”) desire to amend the Interim Development
Agreement dated November 8, 2000 between the parties (as amended, the “Agreement”)
to revise the description of “Development Costs” in Exhibit A, to extend the
period of expanded exclusivity and to provide for a milestone payment.
Accordingly, effective immediately, the Agreement is hereby amended as follows:


 


1.             Beginning
on the first full monthly invoicing cycle following ALZA’s receipt of this
fully executed Amendment No. 2, Exhibits A and A-1 will be replaced with
Schedule A attached hereto, and all references to “Exhibit A” in the Agreement
will be to Schedule A.


 


2.             Section
2.9 of the Agreement is deleted in its entirety and replaced with the
following:


 


“2.9         Until the
first to occur of: (i) ALZA’s first shipment of Product for the [ * ] of the Product, (ii) the [ * ]
of the [ * ] of a [ * ]
for the Product by [ * ] or (iii) [ * ], BioMedicines will not conduct (by itself or with a
third party) any material development or commercialization activities with
respect to any product (other than the Product) which incorporates any [ * ] into any drug delivery system for the controlled or
sustained release of such [ * ] and
intended for commercialization in any subterritory in which BioMedicines
retains exclusive commercialization rights to the Product (as described in
Exhibit D attached to the Agreement).


 


Until the first to occur of: (i) ALZA’s first shipment
of Product for the [ * ] of the
Product, (ii) the [ * ] of the [ * ] of [ * ] for the
Product by [ * ] or (iii) [ * ], ALZA will not conduct (by itself or with any third
party) any material development or commercialization activities with respect to
any product (other than the Product) which incorporates any [ * ] into any [ * ] drug
delivery system and intended for commercialization in any subterritory in which
BioMedicines retains exclusive commercialization rights to the Product (as
described in Exhibit D attached to the Agreement) so long as BioMedicines is
using diligent efforts to carry out the Program and is not otherwise in
material breach of this Agreement.


 










[ * ] =
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 406 of the Securities Exchange Act of 1933, as
amended.


 


 





















 


Thereafter, neither party will conduct (by itself or
with a third party) any material development or commercialization activities
with respect to any product (other than the Product) incorporating [ * ] drug delivery system and intended for
commercialization in any subterritory in which BioMedicines retains exclusive
commercialization rights to the Product (as described in Exhibit D attached to
the Agreement).”


 


3.             The “Exclusivity”
section of Exhibit D of the Agreement is deleted in its entirety and replaced
with the following:


 


“Exclusivity: Until
the first to occur of: (i) ALZA’s first shipment of Product for the [ * ] of the Product, (ii) the [ * ]
of the [ * ] of [ * ]
for the Product by [ * ] or (iii) [ * ],
BioMedicines will not conduct (by itself or with a third party) any material
development or commercialization activities with respect to any product (other
than the Product) which incorporates any [ * ] into any
drug delivery system for the controlled or sustained release of such [ * ] and intended for commercialization in any Subterritory
in which BioMedicines retains exclusive commercialization rights to the
Product.


 


Until the first to occur of: (i) ALZA’s first shipment
of Product for the [ * ] of the
Product, (ii) the [ * ] of the [ * ] of [ * ] for the
Product by [ * ] or (iii) [ * ], ALZA will not conduct (by itself or with any third
party) any material development or commercialization activities with respect to
any product (other than the Product) which incorporates any [ * ] into any [ * ] drug
delivery system and intended for commercialization in any Subterritory in which
BioMedicines retains exclusive commercialization rights to the Product, so long
as BioMedicines is not in material breach of this Agreement.


 


Thereafter, neither party will conduct (by itself or
with a third party) any material development or commercialization activities
with respect to any product (other than the Product) incorporating [ * ] drug delivery system and intended for
commercialization in any Subterritory in which BioMedicines retains exclusive
commercialization rights to the Product.”


 


4.             A new
Section 6 is added to the Agreement to read as follows:


 


“6.           Milestone
Payment. BioMedicines will make a one-time, noncreditable, nonrefundable
milestone payment to ALZA of $1,500,000 (One Million, Five Hundred Thousand
Dollars) within 30 days of BioMedicines first entering into an agreement with
any third party under which such third party obtains the right to market the
Product in any one or more of the following major market countries:   [ * ].”


 


Except as expressly
amended hereinabove, the Agreement shall remain unchanged and in full force and
effect.


 


If the foregoing is acceptable,
please have both copies of this Amendment No. 2 executed and dated by an
authorized corporate officer and return one fully executed original to ALZA.


 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 


2





















 


	
  Very truly yours,

  	
   

  
	
   

  	
   

  
	
  ALZA Corporation

  	
   

  
	
   

  	
   

  
	
  /s/ Erik Wiberg

  	
   

  	
   

  
	
   

  	
   

  
	
  Erik D. Wiberg

  	
   

  
	
  Vice President, Business
  Development

  	
   

  
	
   

  	
   

  
	
  APPROVED AND ACCEPTED
  THIS  8 th DAY OF August , 2002

  	
   

  
	
   

  	
   

  
	
  BioMedicines, Inc.

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ S. M. Moran

  	
   

  
	
   

  	
   

  
	
  Title:

  	
  CEO

  	
   

  
					



 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 


3





















 


SCHEDULE A


 


DEVELOPMENT COSTS


 


Development Costs are
equal to the sum of (i) direct labor and overhead costs and (ii) out-of-pocket
expenses and (iii) capital asset expenditures.


 


(i) Direct labor and overhead costs include [ * ]. Direct labor and overhead costs are billed using an
all inclusive FTE rate as follows:


 


The annual rate will be based upon a fixed rate* of [ * ].


 


(ii) Out-of-pocket expenses include [ * ].


 


(iii) Capital asset expenditures are the actual costs
of new capital assets acquired specifically for the Program.


 










* This fixed billing rate
will not be changed prior to [ * ] and, if
changed on or after [ * ], such
changes will be limited to not more than [ * ] per
calendar year and shall be a maximum of [ * ] of the
rate in effect at the time of the increase.


 


[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 





















 


COMPANY
LETTERHEAD


 


 


December 30, 2002


 


BioMedicines, Inc.


2000 Powell Street, Suite
1640


Emeryville, CA 94608


 


Re:          Amendment
No. 3 to Interim Development Agreement


Effective November 8, 2000


ALZA Contract # 20001780-3


 


Ladies and Gentlemen:


 


ALZA Corporation (“ALZA”)
and BioMedicines, Inc. (“BioMedicines”) desire to amend the Interim Development
Agreement effective November 8, 2000 between the parties (as amended, the “Agreement”).
Accordingly, effective immediately, the Agreement is hereby amended as follows:


 


5.             (a)           Notwithstanding
Section 2.4 of the Agreement, beginning on [ * ] and
continuing until the end of the month in which the first subject is dosed in
the first [ * ] human clinical study of the
Product, but in any event no later than [ * ],
BioMedicines shall pay to ALZA, on a monthly basis, [ * ] of
the Development Costs invoiced consisting of [ * ] and
[ * ] of the Development Costs invoiced
consisting of [ * ] .


 


(b)           After
the end of the month in which the first subject is dosed in the first     [ * ] human
clinical study of the Product, but in any event no later than [ * ], BioMedicines will again pay to ALZA, on a monthly
basis, [ * ] of all Development Costs
invoiced, as described in Section 2.4 of the Agreement.


 


6.             A new
Section 7 is added to the Agreement to read as follows:


 


“7.           Milestone
Payment.  BioMedicines will make a
one-time, noncreditable, nonrefundable milestone payment to ALZA equal to [ * ] of the Development Costs consisting of [ * ] invoiced for the period described in Section 1(a) of
Amendment No. 3 within thirty days of the first to occur of (i) ALZA’s first
shipment of Product meeting the specifications agreed to by the parties for the
[ * ] of the Product or (ii) the [ * ] of the [ * ] of [ * ] for the Product by [ * ].”


 


Except as expressly
amended hereinabove, the Agreement shall remain unchanged and in full force and
effect.


 


If the foregoing is
acceptable, please have both copies of this Amendment No. 3 executed and dated
by an authorized corporate officer and return one fully executed original to
ALZA.


 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 


 





















 


	
  Very truly yours,

  	
   

  
	
   

  	
   

  
	
  /s/ Erick Wiberg

  	
   

  	
   

  
	
   

  	
   

  
	
  Erik D. Wiberg

  	
   

  
	
  Vice President,
  Business Development

  	
   

  
	
   

  	
   

  
	
  APPROVED AND ACCEPTED
  THIS  30 DAY OF December , 2002.

  	
   

  
	
   

  	
   

  
	
  BioMedicines, Inc.

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ S. M. Moran

  	
   

  
	
   

  	
   

  
	
  Title:

  	
  CEO

  	
   

  
					



 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.


 


2





















 


Amendment No. 4 to
Interim Development Agreement


 


ALZA
Corporation (“ALZA”) and BioMedicines, Inc. (“BioMedicines”) desire to amend
the Interim Development Agreement dated November 8, 2000 between the parties
(as amended the “Agreement”). 
Accordingly, effective immediately, the Agreement is hereby amended as
follows:


 


1.             The
references in Section 2.9 and in Exhibit D of the Agreement to “[ * ]”, describing the periods during which the parties will
deal with each other exclusively in certain defined areas, are deleted and
replaced with “[ * ].”


 


2.             Section
7 of the Agreement, providing for a milestone payment from BioMedicines to
ALZA, is deleted in its entirety.


 


Except as expressly amended herein above, the
Agreement shall remain unchanged and in full force and effect.


 


ALZA Corporation


 


 


	
  /s/ Erick. D.
  Wiberg

  	
   

  	
  Dated: 

  	
  May 19, 2004

  
	
  Erick D. Wiberg

  	
   

  	
   

  
	
  Vice President,
  Pharmaceutical Group

  	
   

  	
   

  
	
  Business
  Development

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  BioMedicines,
  Inc.

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ K. Alice
  Leung

  	
   

  	
  Dated:

  	
   May 26, 2004

  
	
   

  	
   

  	
   

  
	
  Title:

  	
  K. Alice Leung,
  President & CEO

  	
   

  	
   

  	
   

  
						



 










[ * ] =
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 406 of the Securities Exchange Act of
1933, as amended.