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                                                                   EXHIBIT 10.53


                          LICENSE AND SUPPLY AGREEMENT

     THIS LICENSE AND SUPPLY AGREEMENT (the "Agreement") is made effective as of
the 31st day of March, 2002 (the "Effective Date") by and between SCIOS, INC., a
Delaware corporation having its principal place of business at 820 West Maude
Avenue, Sunnyvale, CA, USA 94085 ("Scios"), and GLAXO GROUP LTD., a corporation
organized under the laws of England having its principal place of business at
Glaxo Wellcome House, Berkeley Avenue, Greenford, Middlesex UB6 ONN, United
Kingdom ("GSK"). Scios and GSK are sometimes referred to herein individually as
a "Party" and collectively as the "Parties".

                                    RECITALS

     A. GSK and Scios are parties to the Summary of Terms, which contemplates
that the Parties will enter into a more definitive agreement which shall replace
the Summary of Terms.

     B. GSK and Scios wish to enter into this Agreement, which when effective
shall constitute the "Definitive Agreement" contemplated in the Summary of
Terms.

     NOW, THEREFORE, in consideration of the premises and mutual covenants
herein contained, the Parties hereto agree as follows:

                                    ARTICLE 1
                                   DEFINITIONS

     When used in this Summary of Terms, the following terms shall have the
meanings indicated below.

     1.1 "Acceptable Label" means a label for the Original Product satisfying
the criteria set forth on Schedule 1.1.

     1.2 "Active Pharmaceutical Ingredient" or "API" means Natrecor(R) in active
bulk form meeting the API Specifications.

     1.3 "Affiliate" means an individual, trust, business trust, joint venture,
partnership, corporation, association or any other entity which (directly or
indirectly) is controlled by, controls or is under common control with a Party.
For the purposes of this definition, the term "control" (including, with
correlative meanings, the terms "controlled by" and "under common control with")
as used with respect to any Party, shall mean the possession (directly or
indirectly) of at least 50 percent of the outstanding voting securities of a
corporation or comparable equity interest in any other type of entity.

     1.4 "API Specifications" shall mean the specifications for Active
Pharmaceutical Ingredient attached hereto as Schedule 1.4.

     1.5 "Combination Product" means [*****].


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     1.6 "Commercialization" means all activities undertaken relating to the
marketing, promotion, distribution, use, storage, sale and offer for sale of a
Product including, without limitation, advertising and any Phase IV clinical
trials.

     1.7 "Controlled" means possession of the ability to grant a license or
sublicense as provided for herein without violating the terms of any agreement
or other arrangement with a Third Party.

     1.8 "Cost of Goods" means: [*****]

     1.9 "Development" means:

         (a) all activities relating to obtaining and/or maintaining Regulatory
Approval of the Original Product in the Territory with an Acceptable Label
including, without limitation, clinical trials and the preparation, submission,
review and development of data or other information related thereto ("Type 1
Development");

         (b) Phase IV clinical trials supporting pre-launch and
commercialization of the Product but not contributing to obtaining and/or
maintaining Marketing Authorization Applications of the Original Product and any
New Product in the Territory, and excluding the Health Outcomes Study ("Type 2
Development");

         (c) all activities relating to obtaining and/or maintaining Marketing
Authorization of a New Product in the Territory, including Phase III clinical
trials and the preparation, submission, review and development of data or other
information related thereto but excluding pre-clinical, Phase I and Phase II
clinical development ("Type 3 Development"); and

         (d) design and conduct of the Health Outcomes Study.

The term "Development" shall not include process development or final finish or
fill of Product.

     1.10 "Development Expenses" means the expenses incurred by GSK for
Development pursuant to a Development Plan.

     1.11 "Development Plan" means a comprehensive plan for Development of
Products under the direction of GSK, adopted as provided in Article 2, below.

     1.12 "Field" means the development, use, distribution, importation,
storage, marketing, sale and offer for sale of Product for any human
pharmaceutical use other than as a diagnostic reagent.

     1.13 "Final Product Specifications" means the specifications for Product in
final form for commercialization and distribution, labeled in accordance with
local regulatory requirements and custom. The Final Product Specifications are
attached hereto as Schedule 1.13.

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     1.14 "GSK Knowhow" means all Information relating to the Product developed
by GSK as a result of its activities under this Agreement.

     1.15 "GSK Patents" means patent applications, and patents issuing from such
patent applications, which GSK has applied for or owns as a result of its
activities under this Agreement, as well as divisionals, continuations,
continuations-in-part, reissues, reexaminations, renewals, extensions, utility
models, additions and supplementary protection certificates to any such patents
and patent applications which are necessary for development, use, importation,
manufacture, formulation, packaging, sale or offer for sale of Product outside
of the Territory.

     1.16 "Health Outcomes Study" means one or more pharmaco-economic studies
with respect to the Original Product, designed and conducted by GSK pursuant to
Section 2.3, below.

     1.17 "Information" means, whether or not patentable: (i) techniques and
data including inventions, practices, methods, know-how, data (including
pharmacological, toxicological and clinical test data, regulatory submissions
and data and analytical and quality control data), marketing, distribution, and
sales data or descriptions, (ii) compounds, compositions of matter, assays and
biological materials, and (iii) dossiers of information necessary for Regulatory
Approvals.

     1.18 "Launch" means the first commercial sale of a Product in a country in
the Territory by GSK or any of its Affiliates or sub-licensees following receipt
of Regulatory Approval in such country.

     1.19 "Major Market" shall mean each of [*****].

     1.20 "Market Acceptance Criteria" shall mean those objective criteria
regarding market acceptance of Product in each Major Market set forth on
Schedule 1.20.

     1.21 "Marketing Authorization Application" means an application for
Regulatory Approval required before commercial sale or use of the Product in the
Field in a regulatory jurisdiction.

     1.22 "Marketing Plan" means a plan setting forth the basis for
Commercialization of the Product in the Major Markets, as devised by GSK and
approved by the Steering Committee.

     1.23 "Natrecor(R)" means nesiritide or B-type natriuretic peptide (BNP) the
amino acid sequence of which is listed in Schedule 1.23, and any derivatives,
variants, analogs, homologs, fragments, N-terminally or C-terminally extended
forms, conjugates, salts, esters and amides thereof.

     1.24 "New Product" means: (i) a line extension, alternative delivery
system, additional formulation or other modification of the Original Product,
(ii) any modifications to the manufacturing process used for the Original
Product or any New Product which are material, and (iii) any preparation or
product containing Natrecor(R) for treatment of an indication other than label
indications for the Original Product approved as of the Effective Date.

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     1.25 "Net Sales" means, with respect to the Original Product or a New
Product that is not a Combination Product, the amount invoiced by GSK or an
Affiliate or sublicensee of GSK for sales of a Product in the Territory, less
deductions for the following items:

     (i)   reasonable transportation and insurance charges borne by the selling
           party,

     (ii)  sales and excise taxes or customs duties paid by the selling party
           and any other governmental charges imposed upon the sale of the
           Product,

     (iii) rebates or allowances actually granted or allowed, including
           government and managed care rebates,

     (iv)  quantity discounts, cash discounts or chargebacks actually granted,
           allowed or incurred in the ordinary course of business in connection
           with the sale of the Product, and

     (v)   allowances or credits to customers, not in excess of the selling
           price of the Product, on account of governmental requirements,
           rejection, outdating, recalls or return of the Product.

[*****]

     1.26 "Original Product" means the formulation of Natrecor(R) (nesiritide)
intravenous B-type natriuretic peptide (BNP) commercially sold by Scios in the
U.S.A. as of the Effective Date for the treatment of acute decompensated heart
failure. Attached hereto as Schedule 1.26 is the package insert for the Original
Product as of the Effective Date.

     1.27 "Patent Expenses" means [*****]

     1.28 "Product" means the Original Product, any New Product and any
Combination Product.

     1.29 "Quality Assurance Agreement" means a technical and quality assurance
agreement establishing each Party's responsibilities with respect to release and
shipment of API

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to GSK hereunder. The Quality Assurance Agreement shall be negotiated in good
faith by the Parties promptly after the Effective Date and shall be subject to
their mutual agreement independent of the Steering Committee.

     1.30 "Regulatory Approval" means all approvals (including pricing and
reimbursement approvals) and licenses, registrations or authorizations of a
Regulatory Authority, necessary for the use, import, storage, export, transport,
filling, labeling, packaging (to the extent that filling, labeling or packaging
are carried out by GSK or its Affiliates) or sale of a Product in a regulatory
jurisdiction in the Territory. "Regulatory Approval" shall not, however, include
any regulatory approvals related to the manufacture of API and supply of API by
Scios to GSK as contemplated herein.

     1.31 "Regulatory Authority" means a governmental entity with the authority
to grant Regulatory Approvals.

     1.32 "Scios Know-How" means all Information now or hereafter within the
Control of Scios necessary or useful for the Development or Commercialization of
the Product in the Territory, or for the filling, labeling and packaging of the
Product anywhere in the world for use or sale in the Territory.

     1.33 "Scios Patents" means: (i) those patents and patent applications shown
on Schedule 1.33 attached hereto, (ii) all patents issuing from such patent
applications, divisionals, continuations, continuations-in-part, reissues,
reexaminations, renewals, extensions, utility models, additions and
supplementary protection certificates to any such patents and patent
applications, and (iii) all patents and patent applications now or hereafter
owned or Controlled by Scios necessary or useful for the development, use,
importation, formulation, packaging, sale or offer for sale of Product in the
Territory.

     1.34 "Steering Committee" means the entity described in Article 3, below.

     1.35 "Summary of Terms" means an agreement between the Parties titled
"Binding Summary of Terms" and dated as of December 20, 2001.

     1.36 "Territory" means those countries of Western Europe, Central Europe
and Eastern Europe listed in Schedule 1.36.

     1.37 "Third Party" means an entity other than Scios or GSK or their
respective Affiliates.

                                   ARTICLE 2
                               PRODUCT DEVELOPMENT

     2.1 Scope of Development. Upon the Effective Date, GSK will assume
responsibility for Development throughout the Territory pursuant to a
Development Plan. Scios shall provide GSK with reasonable assistance in the
Development of the Original Product and with respect to

                                      -5-

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New Products which Scios, in its sole discretion, may have developed up to and
including Phase II clinical trials. [*****]

     2.2 Development Plan.

         2.2.1 Timing. [*****]

         2.2.2 Content of the Development Plan. The Development Plan shall,
subject to Section 2.4, below, cover:

               (a) [*****]

               (b) [*****]

     2.3 Health Outcomes Study. Promptly following the Effective Date the
Parties shall in good faith design and thereafter implement, under the direction
of GSK, one or more mutually acceptable Health Outcomes Studies for use as
appropriate in establishing pricing and reimbursement for the Original Product
in the Major Markets. GSK shall regularly report to the Steering Committee on
the progress of each Health Outcomes Study. Within 30 days after completion of
all Health Outcomes Studies and delivery to Scios of a copy of the final report
detailing the results thereof, Scios shall pay to GSK the lesser of: (i) [*****]
and (ii) [*****]. This amount shall be due regardless of the outcome of the
Health Outcomes Studies.

     2.4 Development Effort. GSK shall carry out its responsibilities under the
Development Plan using reasonable efforts consistent with the efforts that GSK
employs for its own products which have substantially the same market potential
in the Territory, and in accordance with all applicable legal and regulatory
requirements including, without limitation, then-current Good Laboratory
Practices, Good Clinical Practices, and Good Manufacturing Practices; [*****].

     2.5 Ownership of Regulatory Approvals. [*****]

     2.6 Communication with Regulatory Authorities. GSK shall have primary
responsibility for dealing with Regulatory Authorities in the Territory,
including filing all supplements and other documents with such authorities with
respect to obtaining Regulatory Approvals, reporting all adverse drug
experiences related to the Product, and handling all Product complaints. GSK
shall promptly furnish Scios with copies of all substantive correspondence it
has had with each Regulatory Authority (including, without limitation, a copy of
the final Marketing Approval Application filed with the EMEA), and with contact
reports concerning substantive conversations or meetings with each such
authority relating to Development or Commercialization. At each meeting of the
Steering Committee, GSK shall provide to the Steering Committee a report
describing the regulatory filing status of each Product throughout the
Territory.

     2.7 Costs of Development. Subject to Section 2.3, above, [*****]


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     2.8 Development of New Products Outside the Territory. Scios shall have the
sole responsibility for development of New Products outside of the Territory.
Scios shall regularly disclose to GSK its plans for New Product development and
afford GSK a reasonable opportunity to comment thereon. Notwithstanding the
foregoing, Scios shall be free, after having considered the suggestions from
GSK, to develop New Products outside of the Territory as it sees fit.

                                   ARTICLE 3
                         MANAGEMENT OF THE COLLABORATION

     3.1 Steering Committee. Within 30 days after the Effective Date, Scios and
GSK shall create a Steering Committee consisting of four qualified
representatives of each Party. A Party may change or replace its representatives
on the Steering Committee as it deems appropriate, by notice to the other Party;
provided, however, that each Party's designees shall be qualified by experience
and training to address the issues anticipated in each meeting of the Steering
Committee in which such member participates. Each member of the Steering
Committee shall devote all time reasonably necessary to participate actively on
the Steering Committee to optimize the development and commercialization of
Products as contemplated herein. Each Party will designate one of its members of
the Steering Committee as co-chairperson. The co-chairperson appointed by each
Party shall be empowered to bind such Party to decisions of the Steering
Committee to the extent contemplated herein.

     The Steering Committee may set up such subcommittees to advise it as it
deems appropriate. It is currently contemplated that the Steering Committee
shall promptly designate a manufacturing subcommittee which shall advise Scios
with respect to its supply and manufacturing obligations (including issues
related to alternative sources of supply and Cost of Goods). Notwithstanding the
foregoing, Scios, after reasonable consideration of GSK's views and the advice
of the Steering Committee (including the manufacturing subcommittee), shall have
sole discretion as to how it manages and satisfies its obligations hereunder
with respect to the manufacture and supply of API.

     3.2 Meetings of the Steering Committee. The Steering Committee shall hold
meetings at such times and places as shall be determined by the co-chairpersons.
The meetings shall be held no less frequently than once every [*****] in the
period from the Effective Date through the third year after the first Launch in
a Major Market, and [*****] thereafter. Steering Committee meetings may be held
in person or by telephone or video conference. The co-chairpersons shall
alternate in keeping written minutes which shall reflect the decisions taken at
the meetings. Such minutes shall be circulated to the Steering Committee for
review and approval within two weeks after each meeting.

     3.3 Function of the Steering Committee. The Steering Committee, directly or
through one or more subcommittees, shall manage the long-range strategy and
planning for Development and Commercialization, coordinate the activities of the
Parties under this Agreement, and perform such other functions as appropriate to
further the purposes of this Agreement as determined by the Parties.

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     3.4 Decision Making. To the extent feasible, the Steering Committee shall
make decisions and take actions by consensus after an open discussion of the
matters as to which decisions are being made. [*****]

     3.5 Limitations of Powers of the Steering Committee. The Steering Committee
shall have only such powers as are expressly delegated to it in this Agreement.
The Steering Committee is not a substitute for the rights or the obligations of
the Parties and, inter alia, shall not have the authority to amend this
Agreement. Except as expressly set forth herein, the Steering Committee shall
not be involved with the day-to-day management of this Agreement.

     3.6 Liaison Manager. Each Party will designate one of its members of the
Steering Committee to act as the liaison manager to the other Party to
facilitate the performance of the rights and satisfaction of the obligations of
the Parties hereunder; provided, however, that designation of liaison managers
shall not restrict the right of the Parties to communicate among themselves as
they see fit.

                                   ARTICLE 4
                                COMMERCIALIZATION

     4.1 General. GSK shall be solely responsible for the Commercialization of
the Products throughout the Territory. It is understood and agreed that GSK
shall have the right not to Commercialize any Product in any country of the
Territory in the event that it would so decide with respect to a product of its
own having substantially the same market potential in such country.

     4.2 Marketing Plan. [*****]

     4.3 Commercialization Efforts.

     [*****]

     4.4 Product Spend. [*****]

     4.5 Advertising and Education

         4.5.1 GSK shall disclose to Scios all promotional platforms, campaign
themes, advertising and educational programs in the Major Markets containing the
Natrecor(R) trademark if such Trademark is available and appropriate for use in
the Territory. Scios shall have not less than 30 days after such disclosure to
review and comment thereon. Such programs shall be consistent with such
reasonable guidelines for the use of the Natrecor(R) trademark as Scios may from
time to time promulgate.

         4.5.2 All written or visual promotional and educational materials,
advertising, Product labeling, and documentary information regarding the Product
in the Territory shall, to

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the extent practical, identify Scios as the supplier and licensor of the
Product.

     4.6 Pricing in the Territory. [*****]

                                    ARTICLE 5
                             MANUFACTURE AND SUPPLY

     5.1 Exclusive Supply and Purchase. [*****]

     5.2 Failure to Supply. [*****]

     5.3 Filling, Labeling and Packaging. [*****]

     5.4 Manufacturing Approvals. Notwithstanding Sections 2.5 and 2.6, above,
Scios will use diligent efforts to make necessary filings to obtain, or to cause
a Third Party manufacturer of API to obtain, the necessary regulatory approvals
for the manufacture of API as contemplated herein. GSK shall be promptly
notified of any proposed change in the process for the manufacture of API which
impacts the Marketing Authorization Applications and Regulatory Approval in the
Territory as well as any proposed change as to the site at which such
manufacture is to occur. Thereafter, the Parties shall in good faith consult as
to the best way of ensuring sufficient supply of API to GSK; provided, however,
that Scios shall in any event ensure a sufficient source of supply of API (as
approved by the relevant Regulatory Authorities) to GSK pending regulatory
approval, if required, to such proposed process changes or site change, and
provided that such supply is consistent with Sections 5.6 and 5.7, below. Except
as required of Scios by law, no API incorporating any such proposed change and
no API manufactured at any proposed new facility shall be supplied by Scios to
GSK hereunder without such changes having first been approved by the appropriate
Regulatory Authorities in the Major Markets or other mutual agreement by the
Parties, which regulatory approvals the Parties agree to pursue diligently
following notice from Scios of such proposed changes.

     5.5 Specifications. Scios warrants that the Active Pharmaceutical
Ingredient it supplies hereunder shall meet the API Specifications, and shall
have been manufactured in accordance with the Quality Assurance Agreement and
with all applicable laws and regulations including, without limitation, the
then-current European Good Manufacturing Practice ("GMP") compliance standards.
The API Specifications and Quality Assurance Agreement may be amended by mutual
agreement (such agreement not to be unreasonably withheld) to the extent
required by Regulatory Authorities. As New Products are developed, the Parties
will by mutual agreement establish appropriate specifications for such New
Products.

     5.6 Forecasts.

         (a) [*****]

         (b) [*****]


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     5.7 Purchase Orders. [*****]

     5.8 Delivery. All orders for deliveries of API to GSK shall be FCA
Incoterms 2000, Scios' contract manufacturing facility in Kundl, Austria (or
such other contract manufacturing facility as Scios may establish during the
term of this Agreement). Risk of loss for the Product passes to GSK upon
delivery to GSK's designated premises. GSK shall arrange and pay for the carrier
and any expenses associated with shipping and insuring Product supplied
hereunder. [*****]

     5.9  Inspection and Rejection.

          5.9.1 [*****]

          5.9.2 [*****]

          5.9.3 [*****]

          5.9.4 [*****]

     5.10 Remedies.

          5.10.1 [*****]

          5.10.2 [*****]

     5.11 Supply Price and Payment Mechanism.

          5.11.1 [*****]

          5.11.2 [*****]

          5.11.3 [*****]

          5.11.4 [*****]

          5.11.5 [*****]

                                    ARTICLE 6
                                 CONFIDENTIALITY

     6.1 Confidentiality; Exceptions. The receiving Party shall keep
confidential and shall not publish or otherwise disclose or use for any purpose
other than as provided for in this Agreement any Information and other
information and materials furnished to it by the other Party pursuant to this
Agreement, or any provision of this Agreement that is the subject of an
effective order of the Securities Exchange Commission granting confidential
treatment pursuant to the Securities Act of 1934, as amended (collectively,
"Confidential Information"), except to the extent that it can be established by
the receiving Party that such Confidential Information:

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               (i)   was already known to the receiving Party at the time of
disclosure by the other Party;

               (ii)  was generally available to the public or otherwise part of
the public domain at the time of its disclosure to the receiving Party;

               (iii) became generally available to the public or otherwise part
of the public domain after its disclosure by the disclosing Party and other than
through any act or omission of the receiving Party in breach of this Agreement;
or

               (iv)  was disclosed to the receiving Party, other than under an
obligation of confidentiality, by a Third Party who had no obligation to the
disclosing Party not to disclose such information to others.

               (v)   was developed by the receiving Party's employees without
the use of or access to confidential information of the disclosing Party, as
demonstrated by contemporaneous written records of the receiving Party.

     6.2 Authorized Disclosure. A Party may disclose Confidential Information of
the other Party to the extent such disclosure is reasonably necessary in filing
or prosecuting patent applications, prosecuting or defending litigation,
complying with applicable governmental regulations or conducting preclinical or
clinical trials, provided that if a Party is required by law to make any such
disclosure it will, to the extent practicable, give reasonable advance notice to
the other Party of such disclosure requirement and, except to the extent
inappropriate in the case of patent applications, use reasonable efforts to
secure confidential treatment of such Confidential Information required to be
disclosed. In addition, each Party shall be entitled to disclose Confidential
Information, under a binder of confidentiality containing provisions as
protective as those of this Article 6, to a Third Party for the purpose of
carrying out activities authorized under this Agreement, including disclosures
to authorized or potential sub-licensees. [*****]

     6.3 Survival. This Article 6 shall survive the expiration or termination of
this Agreement for a period of [*****]; provided, however, that Confidential
Information regarding Scios' manufacturing process for API shall be kept
confidential by GSK during the term of this Agreement and for a further period
of [*****] after the expiration or termination of this Agreement, subject to the
exceptions in Section 6.1, above.

                                    ARTICLE 7
                             INFORMATION AND REPORTS

     7.1 Information and Reports During Development and Commercialization.

         7.1.1 To the extent necessary or useful to enable the Parties to
perform their respective obligations or exercise their respective rights
hereunder, GSK and Scios will each regularly disclose and make available to the
other without charge all Information (including, without limitation, copies of
all preclinical and clinical reports) known to them. Without limiting

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the foregoing, promptly following the Effective Date, and at reasonable
intervals thereafter, Scios shall disclose and transfer to GSK all Scios
Know-how as is necessary or useful for the exercise by GSK of its rights
hereunder.

          7.1.2 [*****]

          7.1.3 [*****]

          7.1.4 [*****]

     7.2  Publicity Review.

          7.2.1 On or about January 7, 2002, the Parties announced the
establishment of an alliance for the marketing and development of Products in
the Territory and its key terms in a mutually agreed press release issued
simultaneously by both Parties. Following the Effective Date, neither Party
shall originate any publicity, news release, or other announcement relating to
this Agreement or to performance hereunder (collectively, "Disclosure"), without
the prior prompt review and written approval of the other, which approval shall
not be unreasonably withheld. Once specific information has been approved for
disclosure, that information may be reiterated in any subsequent Disclosure
without further approval; provided, however, that the Parties shall, to the
extent lawful, maintain the confidentiality of financial information contained
in this Agreement and resulting from the activities contemplated hereunder.

          7.2.2 Notwithstanding Section 7.2.1, a Party may make any Disclosure
it believes in good faith based upon the advice of its counsel or its auditors
is required by applicable law and without the prior approval of the other Party
may make such disclosures as are required by the rules or regulations of the
U.S. Securities and Exchange Commission or its UK counterpart. With respect to
disclosures other than those required under such rules or regulations, prior to
making such Disclosure, the disclosing Party shall provide the other Party with
a written copy or rendition of the materials proposed to be disclosed and
provide the receiving Party with an opportunity to promptly review the proposed
Disclosure.

     7.3  Use of Names. Except as required by law or in furtherance of the
exercise of its rights hereunder, neither Party shall use the name of the other
in any public announcement, press release or other public document related to
this Agreement or the understanding reflected herein without the written consent
of such other Party, which consent shall not be unreasonably withheld or
delayed. No such approval shall be required to republish a disclosure previously
made or otherwise in the public domain.

     7.4  Adverse Drug Events. Each Party shall, in a timely fashion in
accordance with the Data Safety Exchange Agreement attached as Schedule 7.4
attached hereto, report to the other Party any adverse event observed during any
use of a Product.

     7.5  Recall

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          7.5.1 Any necessary recall of Product or any batch of Product from the
market in the Territory shall be effected by GSK at GSK's reasonable discretion
following, to the extent practicable, consultation with Scios.

          7.5.2 [*****]

          7.5.3 [*****]

          7.5.4 [*****]

          7.5.5 In the event of a recall of Products, each Party shall
immediately notify the other Party and cooperate in a manner which is
appropriate and reasonable under the circumstances.

     7.6  GSK shall be entitled to discontinue its Development, distribution
and/or sale of any Product if new toxicity, safety findings or side effects
shall occur that are so severe as to justify such discontinuation. In such event
the Parties shall in good faith attempt to find a mutually agreeable solution.
If the Parties are unable to agree on a mutually agreeable solution and GSK has
ceased marketing any Product for more than 60 days in any country, then Scios
shall have the right to terminate this Agreement with respect to such Product
and such country.

     7.7  [*****]

                                    ARTICLE 8
                                  PATENT RIGHTS

     8.1 Scios Patents. [*****]

     8.2 GSK Patents. [*****]

     8.3 Abandonment. [*****]

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     8.4 Infringement. [*****]

     8.5 Third Party Claims. [*****]

                                    ARTICLE 9
                                    LICENSES

     9.1 License Grant by Scios. Subject to the terms and conditions of this
Agreement, Scios hereby grants to GSK and GSK hereby accepts from Scios a sole
and exclusive license under the Scios Patents and Scios Know-How and the
Natrecor(R) trademark to develop, use, import, formulate, package, sell and
offer for sale Products within the Field in the Territory.

     9.2 License Grant by GSK. Subject to the terms and conditions of this
Agreement, GSK hereby grants to Scios and Scios hereby accepts from GSK a sole
and exclusive royalty-free license under the GSK Patents and GSK Know-How to
manufacture, develop, use, import, formulate, package, sell and offer for sale
Products outside of the Territory.

     9.3 Sub-licensing. GSK may sub-license in any country in the Territory the
license granted to it on notice to and with the consent of Scios, which consent
shall not be unreasonably withheld or delayed. No such consent shall be required
in the event of a sub-license by GSK to an Affiliate of GSK. Scios may
sub-license the license granted to it with respect to GSK Patents to any Scios
licensee outside of the Territory which in turn agrees to permit Scios to
sublicense to GSK, at no cost, patent rights related to any Product owned or
controlled by such sub-licensee. Scios may sub-license the license granted to it
with respect to GSK Knowhow only upon prior agreement of GSK, which may be
withheld or granted in GSK's sole discretion. No such GSK consent shall be
required, however, in the event of a sub-license by Scios to an Affiliate of
Scios.

     9.4 Use of Licenses. Neither Party shall use or disseminate the Patents or
Know-How of the other Party other than as expressly provided under this
Agreement.

                                   ARTICLE 10
                                PAYMENTS TO SCIOS

     10.1 License Fee. The Parties acknowledge that prior to the Effective Date
GSK has paid to Scios a nonrefundable license fee of [*****].

     10.2 Milestone Payments. GSK shall notify Scios immediately upon the
achievement of each of the milestones set forth below, whereupon Scios shall
immediately invoice GSK for the amount due. Within [*****] after the achievement
of each such milestone (and subject to Scios having previously provided such
invoice at least [*****] prior to the due date), GSK shall make a non-refundable
milestone payment to Scios in the amount set forth below. Each milestone payment
shall be due only once, notwithstanding the number of Products actually
developed or commercialized by GSK hereunder.

       -------------------------------------- ---------------------
        Milestone                              Payment
       -------------------------------------- ---------------------


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                                      -14-

<PAGE>


       -------------------------------------- ---------------------
        [*****]                                [*****]
       -------------------------------------- ---------------------
        [*****]                                [*****]
       -------------------------------------- ---------------------
        [*****]                                [*****]
       -------------------------------------- ---------------------

     10.3 Royalty Payments. In addition to the foregoing license fee and
milestone payments, GSK shall pay to Scios royalties on Net Sales in each
calendar year at the following rates:

          [*****]

     10.4 Term of Royalty Obligations. [*****]

     10.5 Royalty Reductions.

                [*****]

     10.6 Royalties Payable Only Once; Sales to Affiliates and Sub-Licensees.
[*****]

     10.7 Reports. [*****]

     10.8 Accounting and Audits.

          (a) GSK shall keep, and shall require its Affiliates and sub-licensees
to keep, complete and accurate records of the latest [*****] of sales of
Products on which royalties are due hereunder and of Development and
Commercialization expenditures for purposes of Section 4.4, above. For the
purpose of verifying royalties due to Scios hereunder and expenditures claimed
by GSK hereunder for purposes of Section 4.4, Scios shall have the right
annually, at Scios's expense, to retain an independent certified public
accountant selected by Scios and reasonably acceptable to GSK, to review such
records in the location(s) where such records are maintained by GSK, its
Affiliates or its sub-licensees upon reasonable notice and during regular
business hours and under obligations of confidence. Results of such review shall
be made available to both Scios and GSK. If the review reflects an underpayment
of royalties to Scios such underpayment shall be promptly remitted to Scios,
together with interest at LIBOR plus two percent. If the underpayment of
royalties, or any over reporting of expenditures by GSK is equal to or greater
than [*****], then GSK pay all of the costs of such review. If the review
reflects an overpayment to Scios, Scios shall promptly refund the amount of the
overpayment to GSK, together with interest calculated at LIBOR plus two percent.

          (b) Scios shall keep complete and accurate records of the latest
[*****] of supply hereunder sufficient to enable GSK to confirm Scios' Cost of
Goods. For the purpose of verifying Cost of Goods, GSK shall have the right
[*****] to retain an independent certified public accountant selected by GSK and
reasonably acceptable to Scios, to review such records in the location(s) where
such records are maintained, upon reasonable notice and during regular business
hours and under obligations of confidentiality. Results of such review shall be
made available to both Scios and GSK. If the review reflects an overcharge by
Scios, such overcharge

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                                      -15-

<PAGE>

shall be promptly remitted to GSK, together with interest calculated in the
manner provided in Section 10.9, below. If the amount of such overcharge is
equal to or greater than [*****], then Scios pay all of the costs of such
review. If the review reflects an undercharge by Scios, GSK shall promptly
refund the amount of the overpayment to Scios, together with interest calculated
at LIBOR plus two percent.

     10.9 Currency and Method of Payment. Except as expressly provided herein
(e.g. with respect to API supplied by Scios), all payments due or payable
hereunder shall be made in Pounds Sterling delivered by wire transfer to such
account as Scios may identify from time to time on notice to GSK. Royalty
payments due hereunder with respect to sales not denominated in Pounds Sterling
shall be converted using the applicable conversion rates for buying Pounds
Sterling used in GSK Group's financial reporting systems for the last business
day of the calendar quarter for which such royalties are payable. GSK shall pay
interest to Scios on the amount of any payments that are not paid on or before
the date such payments are due under this Agreement at a rate of LIBOR plus two
percent for the applicable period, calculated on the number of days such payment
is delinquent.

     10.10 Tax Withholding. The Parties shall use all reasonable and legal
efforts to reduce tax withholding on payments made to Scios hereunder.
Notwithstanding such efforts, if GSK concludes that tax withholdings under the
laws of any country are required with respect to payments due to Scios, GSK
shall withhold the required amount and pay it to the appropriate governmental
authority. In such a case, GSK will promptly provide Scios with original
receipts or other evidence reasonably desirable and sufficient to allow Scios to
document such tax withholdings adequately for purposes of claiming foreign tax
credits and similar benefits. No withholding deduction shall be made if Scios
furnishes lawful documentation demonstrating that the payment due is exempt from
withholding according to the applicable convention for the avoidance of double
taxation between the United States and Great Britain or other applicable law or
treaty.

     10.11 Blocked Payments. If, by reason of applicable laws or regulations in
any country, it becomes impossible or illegal for GSK or its Affiliates or
sub-licensees to transfer, or have transferred on its behalf, royalties or other
payments due hereunder to Scios, such royalties or other payments shall be
deposited in local currency in the relevant country to the credit of Scios in a
recognized banking institution designated by Scios or, if none is designated by
Scios within a period of 30 days after inquiry from GSK, in a recognized banking
institution selected by GSK and identified by notice to Scios.

     10.12 Invoice Address. Scios invoices for payments due from GSK hereunder
shall be sent (in the manner in which notice is to be sent as provided in
Section 16.4, below) to:

           Corporate Accounting
           GSK House
           980 Great West Road
           Brentfort
           Middlesex TW8 9GS


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                                      -16-


<PAGE>

           United Kingdom

                                   ARTICLE 11
                                   TRADEMARKS

     11.1 Use of Trademark. Absent mutual agreement or as provided in Section
11.2, below, GSK shall market, advertise, sell or distribute Products only under
the trademark Natrecor(R).

     11.2 Responsible Party. GSK, in consultation with Scios, shall be
responsible for maintaining the trademark Natrecor(R) in all countries in the
Territory in which such mark is registered as of the Effective Date if such
trademark is available and appropriate for use in the Territory and, in Scios'
name, for establishing and maintaining such trademark in other countries in the
Territory in which GSK intends to Commercialize the Products, all at GSK's
expense. In the event that GSK reasonably determines that the trademark
Natrecor(R) is unavailable or inappropriate in any country in the Territory, GSK
shall have the right, at its sole expense, in consultation with Scios, and in
GSK's name, to establish an alternative trademark under which it shall
Commercialize Product in such country.

     11.3 Infringement. [*****]

     11.4 End of Agreement. [*****]

                                   ARTICLE 12
              REPRESENTATIONS AND WARRANTIES; COMPETITIVE PRODUCTS

     12.1 Joint Representations and Warranties. [*****]

     12.2 Representations and Warranties by Scios. Scios represents and warrants
to GSK that, as of the Effective Date, to the actual knowledge of the executive
officers and directors of Scios:

          [*****]

     12.3 Performance by Affiliates and Sub-licensees. The Parties recognize
that each may perform some or all of its obligations under this Agreement
through Affiliates or, to the extent permitted, by sub-licensees. Nonetheless,
each Party shall remain responsible and shall be the guarantor of the
performance by its Affiliates and sub-licensees and shall cause its Affiliates
and sub-licensees to comply with the provisions of this Agreement in connection
with such performance. In the event of a dispute arising out of the actions of
an Affiliate or sub-licensee under this Agreement, each of GSK and Scios may
proceed directly against the other Party, without any obligation to first
proceed against the Affiliate or sub-licensee.

     12.4 Competing Product Development. [*****]

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                                      -17-

<PAGE>

                                   ARTICLE 13
                              TERM AND TERMINATION

     13.1 Term. The term of this Agreement shall commence on the Effective Date
and shall expire upon the termination or expiration in all of the countries of
the Territory of the royalty obligations set forth in Section 10.4, above.

     13.2 Termination for Material Breach. If either Party materially breaches
this Agreement at any time, which breach is not cured within 30 days of notice
thereof from the non-breaching Party, the non-breaching Party shall have the
right to terminate this Agreement on notice to the Party in breach following the
expiration of such cure period; provided, however, that if the Party alleged to
be in breach shall have invoked the dispute resolution mechanism of Article 15
prior to the expiration of such cure period then termination shall not be
effective until the sooner of abandonment of such proceedings by the Party
alleged to be in breach or completion of the dispute resolution proceedings and
a non-appealable finding in arbitration in favor of the non-breaching Party.

     13.3 Termination for Challenge to Patent Rights. [*****]

     13.4 Unilateral Termination by GSK. GSK may, at any time by delivery of 90
days' prior notice to Scios, elect to abandon its rights and obligations with
respect to any country in the Territory, or to terminate this Agreement in toto;
provided, however, that GSK shall not have the right to terminate as to any one
country in the European Union without terminating as to all such countries. Upon
notice by GSK pursuant to this Section 13.4, this Agreement and all obligations
of Scios and GSK hereunder with respect to the country or countries in question
shall terminate. In the event that GSK terminates its rights with respect to one
or more countries but not the entire Territory, then this Agreement shall remain
in effect with respect to the countries not subject to such termination which
countries shall, thereafter, be considered the "Territory."

     13.5 Bankruptcy. All rights granted to GSK hereunder are, and shall
otherwise be deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy
Code (the "Code") licenses of rights to "intellectual property" as defined in
Section 101(52) of the Code. GSK, as a licensee of such rights under this
Agreement shall retain and may fully exercise all of its rights and elections
under the Code, subject to performance by GSK of its obligations under this
Agreement. Scios further agrees that, in the event of the commencement of a
bankruptcy proceeding by or against Scios under the Code, GSK shall be entitled
to a complete duplicate of (or complete access to, as appropriate) any such
intellectual property and all embodiments thereof, which shall promptly be
delivered to GSK, at its sole expense: (i) upon written request from GSK
following commencement of a bankruptcy proceeding by or against Scios, or (ii)
if not delivered pursuant to subsection (i), above, upon written request from
GSK following the rejection in bankruptcy of this Agreement by or on behalf of
Scios. In the event of a filing for bankruptcy or insolvency by Scios, Scios
shall confirm to the receiver, trustee or liquidator that GSK Knowhow and GSK
Patents are the sole property of GSK and may not be disposed of by Scios except
as expressly provided herein. To the extent that Scios hereafter renegotiates
its supply agreement with Biochemie GmbH, Scios shall in good faith endeavor to
obtain assurance

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                                      -18-


<PAGE>

that, in the event that such agreement is subject to termination because of
bankruptcy or insolvency on the part of Scios, GSK shall have the right to
assume Scios' rights and obligations thereunder without interruption.

     13.6 Effect of Termination

          13.6.1 Termination of this Agreement shall not relieve the Parties of
any liability, including any obligation to make payments hereunder, which
accrued hereunder prior to the effective date of such termination, nor preclude
a Party from pursuing all rights and remedies it may have hereunder or at law or
in equity with respect to any breach of this Agreement nor prejudice a Party's
right to obtain performance of any obligation which accrued hereunder prior to
the effective date of such termination. Upon termination (but not expiration of
the term of this Agreement), all licenses and rights to Patents and Know-How
granted hereunder shall terminate.

          13.6.2 Upon termination of this Agreement (but not expiration of its
term), all Confidential Information supplied by one Party shall be returned by
the other Party except for one copy of such information retained solely for
legal archival or regulatory purposes;

          13.6.3 Upon termination of this Agreement (but not expiration of its
term), GSK shall cooperate in the prompt transfer to Scios of all Marketing
Authorization Applications and Regulatory Approvals related to the Products in
the Territory, and shall diligently take such other actions and execute such
other instruments, assignments and documents as may be necessary to effect the
transfer or reconveyance of rights hereunder to Scios and the relinquishment of
such rights by GSK.

          13.6.4 Following termination of this Agreement, GSK shall have [*****]
to sell any Product in its possession as of the effective date of termination,
subject to its obligation to pay royalties to Scios as provided hereinabove with
respect to such sales.

     13.7 Surviving Rights. [*****]

                                   ARTICLE 14
                                 INDEMNIFICATION

     14.1 Indemnification by GSK. [*****]

     14.2 Indemnification by Scios. [*****]

     14.3 Procedure. A Party seeking indemnification under Section 14.1 or
Section 14.2, shall inform the other Party of a claim as soon as reasonably
practicable after it receives notice of the Third Party claim, permit the
indemnifying Party to assume direction and control of the defense of the Third
Party claim (including the right to settle the claim solely for monetary
consideration), and cooperate as requested (at the expense of the indemnifying
Party) in the defense of the Third Party claim.

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                                      -19-

<PAGE>

     14.4 Insurance. [*****]

                                   ARTICLE 15
                               DISPUTE RESOLUTION

     15.1 Disputes. All disputes arising between the Parties hereunder or with
respect to this Agreement shall be resolved solely as provided in this Article
15. Any such dispute which the Parties are unable to resolve directly may be
referred by either Party to the Steering Committee for resolution. If the
Steering Committee is unable to resolve such dispute within 30 days after
referral, either Party may, on notice to the other, have such dispute referred
to the CEO of Scios and the European Chairman of GSK for attempted resolution by
good faith negotiation. If such individuals are unable to resolve such dispute
within 30 days after referral, then either Party may thereafter seek to resolve
the dispute through arbitration in accordance with the Rules of Arbitration of
the International Chamber of Commerce by one or more arbitrators appointed in
accordance with such rules, in English. The place of arbitration shall be
London, England, if arbitration is requested by Scios and shall be San
Francisco, California, if arbitration is requested by GSK.

     15.2 Applicable Law. This Agreement shall be governed by and construed
under the substantive laws of the State of New York, without regard to conflicts
of law principles.

                                   ARTICLE 16
                                  MISCELLANEOUS

     16.1 Assignment.

          16.1.1 [*****]

          16.1.2 [*****]

          16.1.3 [*****]

     16.2 Force Majeure. Except as otherwise expressly provided herein, neither
Party shall lose any rights hereunder or be liable to the other Party for
damages or losses on account of failure of performance by the defaulting Party
if the failure is occasioned by government action, war, acts of gods, or any
other similar or dissimilar cause beyond the control of the defaulting Party,
provided that the Party claiming force majeure has exerted all reasonable
efforts to avoid or remedy such force majeure.

     16.3 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 Agreement.

     16.4 Notices. All notices hereunder shall be in writing and shall be deemed
given if delivered personally or by facsimile transmission with confirmed
answer-back, mailed by registered mail (return receipt requested), postage
prepaid, or sent by internationally recognized

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                                      -20-

<PAGE>

express courier service, to the Parties at the addresses set forth below (or at
such other address for a Party as shall be specified by like notice; provided,
that notices of a change of address shall be effective only upon receipt
thereof). Notice by personal delivery shall be deemed effective upon receipt.
Notice by courier or registered mail shall be deemed effective three business
dates after the date sent. Notice by fax shall be deemed effective upon receipt
by the sending Party of confirmation of receipt of the fax by the receiving
Party.

     If to Scios:          749 North Mary Avenue
                           Sunnyvale, CA 94085
                           Fax: 408-616-8319
                           Attn:  General Counsel

     If to GSK:            Glaxo Wellcome House
                           Berkeley Avenue
                           Greenford, Middlesex
                           UB6 ONN, United Kingdom
                           Fax:  01144 2080 47 69 04
                           Attn:  Company Secretary

     16.5 Waiver. The waiver from time to time by either of the Parties of any
of their rights or their failure to exercise any remedy shall not operate or be
construed as a continuing waiver of same or of any other of such Party's rights
or remedies provided in this Agreement.

     16.6 Severability. If any term, covenant or condition of this Agreement or
the application thereof to any Party or circumstance shall, to any extent, be
held to be invalid or unenforceable, then the remainder of this Agreement, or
the application of such term, covenant or condition to Parties or circumstances
other than those as to which it is held invalid or unenforceable, shall not be
affected thereby and each term, covenant or condition of this Agreement shall be
valid and be enforced to the fullest extent permitted by law. In such event the
Parties shall in good faith attempt to reform this Agreement to reflect the
intent and anticipated consequences of the invalidated or unenforcable
provision, to the extent possible in a way that is lawful.

     16.7 Ambiguities. Ambiguities, if any, in this Agreement shall not be
construed against either Party, irrespective of which Party may be deemed to
have authored the ambiguous provision.

     16.8 Headings. The section and article headings contained herein are for
the purposes of convenience only and are not intended to define or limit the
contents of said sections or articles.

     16.9 Counterparts. This Agreement may be executed in two counterparts, each
of which shall be deemed an original, but which together shall constitute one
and the same instrument.

                                      -21-

<PAGE>

     16.10 Entire Agreement. This Agreement (including all Schedules hereto)
sets forth 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. Upon the
Effective Date, the Summary of Terms shall be deemed to have been terminated.

     16.11 Limitation of Liability. IN NO EVENT SHALL EITHER PARTY BE LIABLE TO
THE OTHER HEREUNDER FOR ANY SPECIAL, INDIRECT, INCIDENTAL OR CONSEQUENTIAL
DAMAGES, WHETHER IN CONTRACT, WARRANTY, TORT, STRICT LIABILITY OR OTHERWISE.

IN WITNESS WHEREOF, the Parties have executed this Agreement in duplicate
originals by their proper officers as of the Effective Date.

SCIOS INC.                               GLAXO GROUP LTD.

By:  Matthew R. Hooper                   By:   S. Bicknell
   ------------------------------------      -----------------------------------

Its: Vice President & General Counsel    Its:  Secretary
    ------------------------------------      ----------------------------------






                                      -22-

<PAGE>


                                  Schedule 1.1

                                Acceptable Label



<PAGE>

                                  SCHEDULE 1.1

                               ACCEPTABLE LABELING

Acceptable Labeling will be achieved provided the following criteria are met:


1. [*****]

2. [*****]

3. [*****]

4. [*****]

5. [*****]


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<PAGE>

                                  SCHEDULE 1.4

                               API Specifications



<PAGE>


[*****]



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<PAGE>

                                  Schedule 1.13

                          Final Product Specifications



<PAGE>


[*****]


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<PAGE>

                                  Schedule 1.20

                           Market Acceptance Criteria


<PAGE>

                                  Schedule 1.20

                           Market Acceptance Criteria

[*****]




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<PAGE>

                                  SCHEDULE 1.23

                         AMINO ACID SEQUENCE OF NATRECOR





<PAGE>



                                  SCHEDULE 1.23

                        AMINO ACID SEQUENCE FOR NATRECOR

                        SER-PRO-LYS-MET-VAL-GLN-GLY-SER-
                        GLY-CYS-PHE-GLY-ARG-LYS-MET-ASP-
                      ARG-ILE-SER-SER-SER-SER-GLY-LEU-GLY-
                           CYS-LYS-VAL-LEU-ARG-ARG-HIS

<PAGE>

                                  Schedule 1.26

                                 Package Insert



<PAGE>

                                                                        Item 2-A
                                                                  Package Insert

NATRECOR(R) (NESIRITIDE)
FOR INJECTION
FOR INTRAVENOUS INFUSION ONLY

DESCRIPTION

Natrecor(R) (nesiritide) is a sterile, purified preparation of a new drug class,
human B-type natriuretic peptide (hBNP), and is manufactured from E. coli using
recombinant DNA technology. Nesiritide has a molecular weight of 3464 g/mol and
an empirical formula of C143H244N50O42S4. Nesiritide has the same 32 amino acid
sequence as the endogenous peptide, which is produced by the ventricular
myocardium.


            [GRAPHIC: Picture of amino acid sequence for Nesiritide]



Natrecor is formulated as the citrate salt of rhBNP, and is provided in a
sterile, single-use vial. Each 1.5 mg vial contains a white- to off-white
lyophilized powder for intravenous (IV) administration after reconstitution. The
quantitative composition of the lyophilized drug per vial is: nesiritide 1.58
mg, mannitol 20.0 mg, citric acid monohydrate 2.1 mg, and sodium citrate
dihydrate 2.94 mg.

Mechanism of Action

Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth
muscle and endothelial cells, leading to increased intracellular concentrations
of guanosine 3'5'-cyclic monophosphate (cGMP) and smooth muscle cell relaxation.
Cyclic GMP serves as a second messenger to dilate veins and arteries. Nesiritide
has been shown to relax isolated human arterial and venous tissue preparations
that were preconstracted with either endothelin-1 or the alpha-adrenergic
agonist, phenylephrine.

In human studies, nesiritide produced dose-dependent reductions in pulmonary
capillary wedge pressure (PCWP) and systemic arterial pressure in patients with
heart failure.

In animals, nesiritide had no effects on cardiac contractility or on measures of
cardiac electrophysiology such as atrial and ventricular effective refractory
times or atrioventricular node conduction.

Naturally occurring atrial natriuretic peptide (ANP), a related peptide,
increases vascular permeability in animals and humans and may reduce
intravascular volume. The effect of nesiritide on vascular permeability has not
been studied.

Pharmacokinetics

In patients with congestive heart failure (CHF), Natrecor administered
intravenously by infusion or bolus exhibits biphasic disposition from the
plasma. The mean terminal elimination half-life (t1/2) of Natrecor is
approximately 18 minutes and was associated with approximately 2/3 of the
area-under-the-curve (AUC). The mean initial elimination phase was estimated to
be approximately 2 minutes. In these patients, the mean



<PAGE>

volume of distribution of the central compartment (Vc) of Natrecor was estimated
to be 0.073 L/kg, the mean steady-state volume of distribution (Vss) was 0.19
L/kg, and the mean clearance (CL) was approximately 9.2 mL/min/kg. At steady
state, plasma BNP levels increase from baseline endogenous levels by
approximately 3-fold to 6-fold with Natrecor infusion doses ranging from 0.01 to
0.03 (micro)g/kg/min.

Elimination

Human BNP is cleared from the circulation via the following three independent
mechanisms, in order of decreasing importance: 1) binding to cell surface
clearance receptors with subsequent cellular internalization and lysosomal
proteolysis; 2) proteolytic cleavage of the peptide by endopeptidases, such as
neutral endopeptidase, which are present on the vascular lumenal surface; and 3)
renal filtration.

Special Populations

Although Natrecor is eliminated, in part, through renal clearance, clinical data
suggest that dose adjustment is not required in patients with renal
insufficiency. The effects of Natrecor on PCWP, cardiac index (CI), and systolic
blood pressure (SBP) were not significantly different in patients with chronic
renal insufficiency (baseline serum creatinine ranging from 2 mg/dL to 4.3
mg/dL), and patients with normal renal function. The population pharmacokinetic
(PK) analyses carried out to determine the effects of demographics and clinical
variables on PK parameters showed that clearance of Natrecor is proportional to
body weight, supporting the administration of weight-adjusted dosing of Natrecor
(i.e., administration on a (micro)g/kg/min basis). Clearance was not influenced
significantly by age, gender, race/ethnicity, baseline endogenous hBNP
concentration, severity of CHP (as indicated by baseline PCWP, baseline CI, or
New York Heart Association [NYHA] classification), or concomitant administration
of an ACE inhibitor.

Effects of Concomitant Medications

The co-administration of Natrecor with enalapril did not have significant
effects on the PK of Natrecor. The PK effect of co-administration of Natrecor
with other IV vasodilators such as nitroglycerin, nitroprusside, milrinone, or
IV ACE inhibitors has not been evaluated. During clinical studies, Natrecor was
administered concomitantly with other medications, including: diuretics,
digoxin, oral ACE inhibitors, anticoagulants, oral nitrates, statins, class III
antiarrhythmic agents, beta-blockers, dobutamine, calcium channel blockers,
angiotensin II receptor antagonists, and dopamine. Although no PK interactions
were specifically assessed, there did not appear to be evidence suggesting any
clinically significant PK interaction.

Pharmacodynamics

The recommended dosing regimen of Natrecor is a 2 (micro)g/kg IV bolus followed
by an intravenous infusion dose of 0.01 (micro)g/kg/min. With this dosing
regimen, 60% of the 3-hour effect on PCWP reduction is achieved within 15
minutes after the bolus, reaching 95% of the 3-hour effect within 1 hour.
Approximately seventy percent of the 3-hour effect on SBP reduction is reached
within 15 minutes. The pharmacodynamic (PD) half-life of the onset and offset of
the hemodynamic effect of Natrecor is longer than what the PK half-life of 18
minutes would predict. For example, in patients who developed symptomatic
hypotension in the VMAC (Vasodilation in the Management of Acute Congestive
Heart Failure) trial, half of the recovery of SBP toward the baseline value
after discontinuation of reduction of the dose of Natrecor was observed in about
60 minutes. When higher doses of Natrecor were infused, the duration of
hypotension was sometimes several hours.

Clinical Trials

Natrecor has been studied in 10 clinical trial including 941 patients with CHF
(NYHA class II-III 61%, NYHA class IV 36%; mean age 60 years, women 28%). There
were five randomized, multi-center, placebo- or active


<PAGE>

controlled studies (comparative agents included nitroglycerin, dobutamine,
milrinone, nitroprusside, or dopamine) in which 772 patients with decompensated
CHF received continuous infusions of Natrecor at doses ranging from 0.01 to 0.03
(micro)g/kg/min. (See the ADVERSE REACTION section for relative frequency of
adverse events at doses ranging from the recommended dose up to 0.03
(micro)g/kg/min). Of these patients, the majority (n = 541, 70%) received the
Natrecor infusion for at least 24 hours; 371 (48%) received Natrecor for 24-48
hours, and 170 (22%) received Natrecor for greater than 48 hours.

In controlled trials, Natrecor has been used alone or in conjunction with other
standard therapies, including diuretics (79%), digoxin (62%), oral ACE
inhibitors (55%), anticoagulants (38%), oral nitrates (32%), statins (18%),
class III antiarrhythmic agents (16%), beta-blockers (15%), dobutamine (15%),
calcium channel blockers (11%), angiotensin II receptor antagonists (6%), and
dopamine (4%). Natrecor has been studied in a broad range of patients, including
the elderly (42% > 65 years of age), women (30%), minorities (26% black), and
patients with a history of significant morbidities such as hypertension (67%),
previous myocardial infarction (50%), diabetes (44%), atrial
fibrillation/flutter (34%), nonsustained ventricular tachycardia (25%),
ventricular tachycardia/fibrillation (12%), preserved systolic function (9%),
and acute coronary syndromes less than 7 days before the start of Natrecor (4%).

The VMAC (Vasodilation in the Management of Acute Congestive Heart Failure)
trial was a randomized, double-blind study of 489 patients (246 patients
requiring a right heart catheter, 243 patients without a right heart catheter)
who required hospitalization for management of shortness of breath at rest due
to acutely decompensated CHF. The study compared the effects of Natrecor,
placebo, and IV nitroglycerin when added to background therapy (IV and oral
diuretics, non-IV cardiac medications, dobutamine, and dopamine). Patients with
acute coronary syndrome, preserved systolic function, arrhythmia, and renal
insufficiency were not excluded. The primary endpoints of the study were the
change from baseline in PCWP and the change from baseline in patients' dyspnea,
evaluated after three hours. Close attention was also paid to the occurrence and
persistence of hypotension, given nesiritide's relatively long (compared to
nitroglycerin) PK and PD half-life.

Natrecor was administered as a 2 (micro)g/kg bolus over approximately 60
seconds, followed by a continuous fixed dose infusion of 0.01 (micro)g/kg/min.
After the 3-hour placebo-controlled period, patients receiving placebo crossed
over to double-blinded active therapy with either Natrecor or nitroglycerin. The
nitroglycerin dose was titrated at the physician's discretion. A subset of
patients in the VMAC trial with central hemodynamic monitoring who were treated
with Natrecor (62 of 124 patients) were allowed dose increases of Natrecor after
the first 3 hours of treatment if the PCWP was 20 mm Hg and the SBP was 100 mm
Hg. Dose increases of a 1 (micro)g/kg bolus followed by an increase of the
infusion dose by 0.005 (micro)g/kg/min were allowed every 3 hours, up to a
maximum dose of 0.03 (micro)g/kg/min. Overall, 23 patients in this subset had
the dose of Natrecor increased in the VMAC trial.

In a second double-blind study, 127 patients requiring hospitalization for
symptomatic CHF were randomized to placebo or to one of two doses of Natrecor
(0.015 (micro)g/kg/min preceded by an IV bolus of 0.3 (micro)g/kg, and 0.03
(micro)g/kg/min preceded by an IV bolus of 0.6 (micro)g/kg). The primary
endpoint of the trial was the change in PCWP from baseline to 6 hours, but the
effect on symptoms also was examined.

Effects on Symptoms

In the VMAC study, patients receiving Natrecor reported greater improvement in
their dyspnea at 3 hours than patients receiving placebo (p = 0.034).

In the dose-response study, patients receiving both doses of Natrecor reported
greater improvement in dyspnea at 6 hours than patients receiving placebo.

Effects on Hemodynamics


<PAGE>

The PCWP, right atrial pressure (RAP), CI, and other hemodynamic variables were
monitored in 246 of the patients in the VMAC trial. There was a reduction in
mean PCWP within 15 minutes of starting the Natrecor infusion, with most of the
effect seen at 3 hours being achieved within the first 60 minutes of the
infusion (see Pharmacodynamics).

In several studies, hemodynamic parameters were measured after Natrecor
withdrawal. Following discontinuation of Natrecor, PCWP returns to within 10% of
baseline within 2 hours, but no rebound increase to levels above baseline state
was observed. There was also no evidence of tachyphylaxis to the hemodynamic
effects of Natrecor in the clinical trials.

The following table and graph summarize the changes in the VMAC trial in PCWP
and other measures during the first 3 hours.

                      MEAN HEMODYNAMIC CHANGE FROM BASELINE
<TABLE>
<CAPTION>

-------------------------------------------------------------------------------------------------------------------
                                                            Placebo           Nitroglycerin            Natrecor
Effects at 3 Hours                                         (n = 62)              (n = 60)             (n = 124)
-------------------------------------------------------------------------------------------------------------------
<S>                                                        <C>                <C>                     <C>
Pulmonary capillary wedge pressure (mm Hg)                   -2.0                 -3.8                  -5.8(2)
-------------------------------------------------------------------------------------------------------------------
Right atrial pressure (mm Hg)                                 0.0                 -2.6                  -3.1(2)
-------------------------------------------------------------------------------------------------------------------
Cardiac index (L/min/M2)                                      0.0                  0.2                   0.1
-------------------------------------------------------------------------------------------------------------------
Mean pulmonary artery pressure (mm Hg)                       -1.1                 -2.5                  -5.4(2)
-------------------------------------------------------------------------------------------------------------------
Systemic vascular resistance (dynes*sec*cm-5)                -44                  -105                  -144
-------------------------------------------------------------------------------------------------------------------
Systolic blood pressure(1) (mm Hg)                           -2.5                 -5.7(2)               -5.6(2)
-------------------------------------------------------------------------------------------------------------------
</TABLE>

(1) Based on all treated subjects: Placebo n=142, nitroglycerin n=143, Natrecor
    n=204
(2) p less than 0.05 compared to placebo







       [GRAPHIC: GRAPH COMPARING MEAN CHANGES IN PCWP OVER A 3 HOUR PERIOD
                    FOR PLACEBO, NITROGLYCERIN and NATRECOR]




<PAGE>

The VMAC study does not constitute an adequate effectiveness comparison with
nitroglycerin. In this trial, the nitroglycerin group provides a rough landmark
using a familiar therapy and regimen.

Effect on Urine Output

In the VMAC trial, in which the use of diuretics was not restricted, the mean
change in volume status (output minus input) during the first 24 hours in the
nitroglycerin and Natrecor groups was similar: 1279 + 1455 mL and 1257 + 1657
mL, respectively.

INDICATIONS AND USAGE

Natrecor is indicated for the intravenous treatment of patients with acutely
decompensated congestive heart failure who have dyspnea at rest or with minimal
activity. In this population, the use of Natrecor reduced pulmonary capillary
wedge pressure and improved dyspnea.

CONTRAINDICATIONS

Natrecor is contraindicated in patients who are hypersensitive to any of its
components. Natrecor should not be used as primary therapy for patients with
cardiogenic shock or in patients with a systolic blood pressure  90 mm Hg.

WARNINGS

Administration of Natrecor should be avoided in patients suspected of having, or
known to have, low cardiac filling pressures.

PRECAUTIONS

General: Parenteral administration of protein pharmaceuticals of E. coli-derived
products should be attended by appropriate precautions in case of an allergic or
untoward reaction. No serious allergic or anaphylactic reactions have been
reported with Natrecor.

Natrecor is not recommended for patients for whom vasodilating agents are not
appropriate, such as patients with significant valvular stenosis, restrictive or
obstructive cardiomyopathy, constrictive pericarditis, pericardial tamponade, or
other conditions in which cardiac output is dependent upon venous return, or for
patients suspected to have low cardiac filling pressures. (See
CONTRAINDICATIONS.)

Renal: Natrecor may affect renal function in susceptible individuals. In
patients with severe heart failure whose renal function may depend on the
activity of the renin-angiotensin-aldosterone system, treatment with Natrecor
may be associated with azotemia. When Natrecor was initiated at doses higher
than 0.01 (micro)g/kg/min (0.015 and 0.03 (micro)g/kg/min), there was an
increased rate of elevated serum creatinine over baseline compared with standard
therapies, although the rate of acute renal failure and need for dialysis was
not increased. In the 30-day follow-up period in the VMAC trial, 5 patients in
the nitroglycerin group (2%) and 9 patients in the Natrecor group (3%) required
first-time dialysis.

Cardiovascular: Natrecor may cause hypotension. In the VMAC trial, in patients
given the recommended dose (2 (micro)g/kg bolus followed by a 0.01
(micro)g/kg/min infusion) or the adjustable dose, the incidence of symptomatic
hypotension in the first 24 hour was similar for Natrecor (4%) and IV
nitroglycerin (5%). When hypotension occurred, however, the duration of
symptomatic hypotension was longer with Natrecor (mean duration was 2.2 hours)
than with nitroglycerin (mean duration was 0.7 hours). In earlier trials, when
Natrecor


<PAGE>

was initiated at doses higher than the 2-(micro)g/kg bolus followed by a
0.01-(micro)g/kg/min infusion (i.e., 0.015 and 0.030 (micro)g/kg/min preceded by
a small bolus), there were more hypotensive episodes and these episodes were of
greater intensity and duration. They were also more often symptomatic and/or
more likely to require medical intervention (see ADVERSE REACTIONS). Natrecor
should be administered only in setting where blood pressure can be monitored
closely, and the dose of Natrecor should be reduced or the drug discontinued in
patients who develop hypotension (see Dosing Instructions). The rate of
symptomatic hypotension may be increased in patients with a blood pressure 100
mm Hg at baseline, and Natrecor should be used cautiously in these patients. The
potential for hypotension may be increased by combining Natrecor with other
drugs that may cause hypotension. For example, in the VMAC trial in patients
treated with either Natrecor or nitroglycerin therapy, the frequency of
symptomatic hypotension in patients who received an oral ACE inhibitor was 6%,
compared to a frequency of symptomatic hypotension of 1% in patients who did not
receive an oral ACE inhibitor.

Drug Interactions: No trials specifically examining potential drug interactions
with Natrecor were conducted, although many concomitant drugs were used in
clinical trials. No drug interactions were detected except for an increase in
symptomatic hypotension in patients receiving oral ACE inhibitors (see
PRECAUTIONS, Cardiovascular).

The co-administration of Natrecor with IV vasodilators such as nitroglycerin,
nitroprusside, milrinone, or IV ACE inhibitors has not been evaluated (these
drugs were not co-administered with Natrecor in clinical trials).

Carcinogensis, Mutagenesis, Impairment of Fertility: Long-term studies in
animals have not been performed to evaluate the carcinogenic potential or the
effect on fertility of nesiritide.

Nesiritide did not increase the frequency of mutations when used in an in vitro
bacterial cell assay (Ames test). No other genotoxicity studies were performed.

Pregnancy; Category C: Animal developmental and reproductive toxicity studies
have not been conducted with nesiritide. It is also not known whether Natrecor
can cause fetal harm when administered to pregnant women or can affect
reproductive capacity. Natrecor should be used during pregnancy only if the
potential benefit justifies any possible risk to the fetus.

Nursing Mothers: It is not known whether this drug is excreted in human milk.
Therefore, caution should be exercised when Natrecor is administered to a
nursing woman.

Pediatric Use: The safety and effectiveness of Natrecor in pediatric patients
has not been established.

Geriatric Use: Of the total number of subjects in clinical trials treated with
Natrecor (n = 941), 38% were 65 years or older and 16% were 75 years or older.
No overall differences in effectiveness were observed between these subjects and
younger subjects, and other reported clinical experience has not identified
differences in responses between the elderly and younger patients. Some older
individuals may be more sensitive to the effect of Natrecor than younger
individuals.

<PAGE>

ADVERSE REACTIONS

Adverse events that occurred with at least a 3% frequency during the first 24
hours of Natrecor infusion are shown in the following table.


<TABLE>
<CAPTION>

---------------------------------------------------------------------------------------------------------------------------
                                        VMAC Trial                              Other Long Infusion Trials
---------------------------------------------------------------------------------------------------------------------------
                                                                                             Natrecor (micro)g/kg/min
                                                           Natrecor                         -------------------------------
                                        Nitroglycerin      Recommended Dose     Control*     0.015           0.03
Adverse Event                           (n = 216)          (n = 273)            (n = 256)    (n = 253)       (n = 246)
---------------------------------------------------------------------------------------------------------------------------
<S>                                     <C>                 <C>                 <C>          <C>             <C>
Cardiovascular
---------------------------------------------------------------------------------------------------------------------------
Hypotension                                 25(12%)           31(11%)           20(8%)         56(22%)        87(35%)
---------------------------------------------------------------------------------------------------------------------------
  Symptomatic Hypotension                   10(5%)            12(4%)             8(3%)         28(11%)        42(17%)
---------------------------------------------------------------------------------------------------------------------------
  Asymptomatic Hypotension                  17(8%)            23(8%)            13(5%)         31(12%)        49(20%)
---------------------------------------------------------------------------------------------------------------------------
Ventricular Tachycardia (VT)                11(5%)             9(3%)            25(10%)        25(10%)        10(4%)
---------------------------------------------------------------------------------------------------------------------------
  Non-sustained VT                          11(5%)             9(3%)            23(9%)         24(9%)          9(4%)
---------------------------------------------------------------------------------------------------------------------------
Ventricular Extrasystoles                    2(1%)             7(3%)            15(6%)         10(4%)          9(4%)
---------------------------------------------------------------------------------------------------------------------------
Angina Pectoris                              5(2%)             5(2%)             6(2%)         14(6%)          6(2%)
---------------------------------------------------------------------------------------------------------------------------
Bradycardia                             1(less than 1%)        3(1%)        1(less than 1%)     8(3%)         13(5%)
---------------------------------------------------------------------------------------------------------------------------
Body as a Whole
---------------------------------------------------------------------------------------------------------------------------
Headache                                    44(20%)           21(8%)            23(9%)         23(9%)         17(7%)
---------------------------------------------------------------------------------------------------------------------------
Abdominal Pain                              11(5%)             4(1%)            10(4%)          6(2%)          8(3%)
---------------------------------------------------------------------------------------------------------------------------
Back Pain                                    7(3%)            10(4%)             4(2%)          5(2%)          3(1%)
---------------------------------------------------------------------------------------------------------------------------
Nervous
---------------------------------------------------------------------------------------------------------------------------
Insomnia                                     9(4%)             6(2%)             7(3%)         15(6%)         15(6%)
---------------------------------------------------------------------------------------------------------------------------
Dizziness                                    4(2%)             7(3%)             7(3%)         16(6%)         12(5%)
---------------------------------------------------------------------------------------------------------------------------
Anxiety                                      6(3%)             8(3%)             2(1%)          8(3%)          4(2%)
---------------------------------------------------------------------------------------------------------------------------
Digestive
---------------------------------------------------------------------------------------------------------------------------
Nausea                                      13(6%)            10(4%)            12(5%)         24(9%)         33(13%)
---------------------------------------------------------------------------------------------------------------------------
Vomiting                                     4(2%)             4(1%)             2(1%)         6(2%)          10(4%)
---------------------------------------------------------------------------------------------------------------------------

</TABLE>

* Includes dobutamine, milrinone, nitroglycerin, placebo,
  dopamine, nitroprusside, or amrinone

Adverse events that are not listed in the above table that occurred in at least
1% of patients who received any of the above Natrecor doses included:
Tachycardia, atrial fibrillation, AV node conduction abnormalities, catheter
pain, fever, injection site reaction, confusion, paresthesia, somnolence,
tremor, increased cough, hemoptysis, apnea, increased creatinine, sweating,
pruritis, rash, leg cramps, amblyopia, anemia. All reported events (at least 1%)
are included except those already listed, those too general to be informative,
and those not reasonably associated with the use of the drug because they were
associated with the condition being treated or are very common in the treated
population.

In placebo and active-controlled clinical trials, Natrecor has not been
associated with an increase in atrial or ventricular tachyarrhythmias. In
placebo-controlled trials, the incidence of VT in both Natrecor and placebo
patients was 2%. In the PRECEDENT (Prospective Randomized Evaluation of Cardiac
Ectopy with Dobutamine or Natrecor Therapy) trial, the effects of Natrecor (n =
163) and dobutamine (n = 83) on the provocation or aggravation of existing
ventricular arrhythmias in patients with decompensated CHF was


<PAGE>

compared using Holter monitoring. Treatment with Natrecor (0.015 and 0.03
(micro)g/kg/min without an initial bolus) for 24 hours did not aggravate
pre-existing VT or the frequency of premature ventricular beats, compared to a
baseline 24-hour Holter tape.

Clinical Laboratory

In the PRECEDENT trial, the incidence of elevations in serum creatinine to > 0.5
mg/dL above baseline through day 14 was higher in the Natrecor 0.015
(micro)g/kg/min group (17%) and the Natrecor 0.03 (micro)g/kg/min group (19%)
than with standard therapy (11%). In the VMAC trial, through day 30, the
incidence of elevations in creatinine to > 0.5 mg/dL above baseline was 28% and
21% in the Natrecor (2 (micro)g/kg bolus followed by 0.010 (micro)g/kg/min) and
nitroglycerin groups, respectively.

Effect on Mortality

In the VMAC trial, the mortality rates at six months in the patients receiving
Natrecor and nitroglycerin were 25.1% (95% confidence interval, 20.0% to 30.5%)
and 20.8% (95% confidence interval, 15.5% to 26.5%), respectively. In all
controlled trials combined, the mortality rates for Natrecor and active control
(including nitroglycerin, dobutamine, nitroprusside, milrinone, amrinone and
dopamine) patients were 21.5% and 21.7%, respectively.

OVERDOSAGE

No data are available with respect to overdosage in humans. The expected
reaction would be excessive hypotension, which should be treated with drug
discontinuation or reduction (see PRECAUTIONS) and appropriate measures.

DOSAGE AND ADMINISTRATION

Natrecor (nesiritide) is for intravenous use only. There is limited experience
with administering Natrecor for longer than 48 hours. Blood pressure should be
monitored closely during Natrecor administration. If hypotension occurs during
the administration of Natrecor, the dose should be reduced or discontinued and
other measures to support blood pressure should be started (IV fluids, changes
in body position). In the VMAC trial, when symptomatic hypotension occurred,
Natrecor was discontinued and subsequently could be restarted at a dose that was
reduced by 30% (with no bolus administration) once the patient was stabilized.
Because hypotension caused by Natrecor may be prolonged (up to hours), a period
of observation may be necessary before restarting the drug.

Preparation

1. Reconstitute one 1.5 mg vial of Natrecor by adding 5 mL of diluent removed
   from a pre-filled 250 mL plastic IV bag containing the diluent of choice. The
   following preservative-free diluents are recommended for reconstitution: 5%
   Dextrose Injection (D5W), USP; 0.9% Sodium Chloride Injection, USP; 5%
   Dextrose and 0.45% Sodium Chloride Injection, USP, or 5% Dextrose and 0.2%
   Sodium Chloride Injection, USP.

2. Do not shake the vial. Rock the vial gently so that all surfaces, including
   the stopper, are in contact with the diluent to ensure complete
   reconstitution. Use only a clear, essentially colorless solution.

3. Withdraw the entire contents of the reconstituted Natrecor vial and add to
   the 250 mL plastic IV bag. This will yield a solution with a concentration of
   Natrecor of approximately 6 (micro)g/mL. The IV bag should be inverted
   several times to ensure complete mixing of the solution.

<PAGE>

4. Use the reconstituted solution within 24 hours, as Natrecor contains no
   antimicrobial preservative. Parenteral drug products should be inspected
   visually for particulate matter and discoloration prior to administration,
   whenever solution and container permit. Reconstituted vials of Natrecor may
   be left at Controlled Room Temperature (20 - 25(degree)C; 68 - 77(degree)F)
   as per United States Pharmacopeia (USP) or may be refrigerated (2 -
   8(degree)C; 36 - 46(degree)F) for up to 24 hours.

Dosing Instructions

The recommended dose of Natrecor is an IV bolus of 2 (micro)g/kg followed by a
continuous infusion of 0.01 (micro)g/kg/min. Natrecor should not be initiated at
a dose that is above the recommended dose.

Prime the IV tubing with an infusion of 25 mL prior to connecting to the
patient's vascular access port and prior to administering the bolus or starting
the infusion.

Bolus followed by infusion: After preparation of the infusion bag, as described
previously, withdraw the bolus volume (see table below) from the Natrecor
infusion bag, and administer it over approximately 60 seconds through an IV port
in the tubing. Immediately following the administration of the bolus, infuse
Natrecor at a flow rate of 0.1 mL/kg/hr. This will deliver a Natrecor infusion
dose of 0.01 (micro)g/kg/min.

To calculate the appropriate bolus volume and infusion flow rate to deliver a
0.01 (micro)g/kg/min dose, use the following formulas (or refer to the following
dosing table):

              BOLUS VOLUME (ML) = PATIENT WEIGHT (KG) DIVIDED BY 3

             INFUSION FLOW RATE (ML/HR) = 0.1 X PATIENT WEIGHT (KG)

                      NATRECOR WEIGHT-ADJUSTED BOLUS VOLUME
                             AND INFUSION FLOW RATE

          (2 (MICRO)G/KG BOLUS FOLLOWED BY A 0.01 (MICRO)G/KG/MIN DOSE)
--------------------------------------------------------------------------------
Patient Weight(kg)          Volume of Bolus(mL)           Rate of Infusion(mL/h)
--------------------------------------------------------------------------------
      60                          20.0                            6
--------------------------------------------------------------------------------
      70                          23.3                            7
--------------------------------------------------------------------------------
      80                          26.7                            8
--------------------------------------------------------------------------------
      90                          30.0                            9
--------------------------------------------------------------------------------
     100                          33.3                           10
--------------------------------------------------------------------------------
     110                          36.7                           11
--------------------------------------------------------------------------------

Dose Adjustments: The dose-limiting side effect of Natrecor is hypotension. Do
not initiate Natrecor at a dose that is higher than the recommended dose of a 2
(micro)g/kg bolus followed by an infusion of 0.01 (micro)g/kg/min. In the VMAC
trial there was limited experience with increasing the dose of Natrecor above
the recommended dose (23 patients, all of whom had central hemodynamic
monitoring). In those patients, the infusion dose of Natrecor was increased by
0.005 (micro)g/kg/min (preceded by a bolus of 1 (micro)g/kg), no more frequently
than every 3 hours up to a maximum dose of 0.03 (micro)g/kg/min. Natrecor should
not be titrated at frequent intervals as is done with other IV agents that have
a shorter half-life (see Clinical Trials).

Chemical/Physical Interactions

Natrecor is physically and/or chemically incompatible with injectable
formulations of heparin, insulin, ethacrynate sodium, bumetamide, enalaprilat,
hydralazine, and furosemide. These drugs should not be co-administered as
infusions with Natrecor through the same IV catheter. The preservative sodium
metabisulfite is incompatible with Natrecor. Injectable drugs that contain
sodium metabisulfite should not be administered in


<PAGE>

the same infusion line as Natrecor. The catheter must be flushed between
administration of Natrecor and incompatible drugs. Natrecor binds to heparin and
therefore could bind to the heparin lining of a heparin-coated catheter,
decreasing the amount of Natrecor delivered to the patient for some period of
time. Therefore, Natrecor must not be administered through a central
heparin-coated catheter. Concomitant administration of a heparin infusion
through a separate catheter is acceptable.

Storage

Store Natrecor at controlled room temperature (20 - 25(degree)C; 68 -
77(degree)F); excursions permitted to 15 - 30(degree)C (59 - 86(degree)F; see
USP Controlled Room Temperature), or refrigerated (2 - 8(degree)C; 36 -
46(degree)F). Keep in carton until time of use.

HOW SUPPLIED

Natrecor is provided as a sterile lyophilized powder in 1.5 mg, single-use
vials. Each carton contains one vial and is available in the following package:

1 vial/carton (NDC 65847-205-25)

US patent No. 5,114,923 and 5,674,710.
Distributed by Scios Inc.
820 West Maude Ave
Sunnyvale, CA 94085
Copyright. 2001 Scios Inc.
NA1030.01

                 Revised September 2001

<PAGE>

                                  SCHEDULE 1.33

                                  SCIOS PATENTS

<PAGE>

                                  SCHEDULE 1.33

                                  SCIOS PATENTS

                  [*****]




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          SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION



<PAGE>

                                  Schedule 1.36

                                    Territory



<PAGE>

                                  SCHEDULE 1.36

                                    Territory

                 WESTERN, CENTRAL AND EASTERN EUROPEAN COUNTRIES
                 -----------------------------------------------

 ------------------ ----------------- ---------------- ------------------------
      European         European                           Central and Eastern
      Community     Economic Area        Others                 European
 ------------------ ----------------- ---------------- ------------------------
  Austria            Iceland           Andorra          Albania
 ------------------ ----------------- ---------------- ------------------------
  Belgium            Liechtenstein     Cyprus           Armenia
 ------------------ ----------------- ---------------- ------------------------
  Denmark            Norway            Israel           Azerbaijan
 ------------------ ----------------- ---------------- ------------------------
  Finland                              Malta            Belarus
 ------------------ ----------------- ---------------- ------------------------
  France                               Vatican City     Bosnia & Hertzegovina
 ------------------ ----------------- ---------------- ------------------------
  Germany                              Switzerland      Bulgaria
 ------------------ ----------------- ---------------- ------------------------
  Greece                               San Marino       Croatia
 ------------------ ----------------- ---------------- ------------------------
  Ireland                              Monaco           Czech Republic
 ------------------ ----------------- ---------------- ------------------------
  Italy                                                 Estonia
 ------------------ ----------------- ---------------- ------------------------
  Luxembourg                                            Georgia
 ------------------ ----------------- ---------------- ------------------------
  Netherlands                                           Hungary
 ------------------ ----------------- ---------------- ------------------------
  Portugal                                              Kazakstan
 ------------------ ----------------- ---------------- ------------------------
  Spain                                                 Kyrgyzstan
 ------------------ ----------------- ---------------- ------------------------
  Sweden                                                Latvia
 ------------------ ----------------- ---------------- ------------------------
  United Kingdom                                        Lithuania
 ------------------ ----------------- ---------------- ------------------------
                                                        Macedonia
 ------------------ ----------------- ---------------- ------------------------
                                                        Moldova
 ------------------ ----------------- ---------------- ------------------------
                                                        Poland
 ------------------ ----------------- ---------------- ------------------------
                                                        Romania
 ------------------ ----------------- ---------------- ------------------------
                                                        Russia
 ------------------ ----------------- ---------------- ------------------------
                                                        Slovakia
 ------------------ ----------------- ---------------- ------------------------
                                                        Tajikistan
 ------------------ ----------------- ---------------- ------------------------
                                                        Turkmenistan
 ------------------ ----------------- ---------------- ------------------------
                                                        Ukraine
 ------------------ ----------------- ---------------- ------------------------
                                                        Uzbekistan
 ------------------ ----------------- ---------------- ------------------------
                                                        Yugoslavia
 ------------------ ----------------- ---------------- ------------------------


<PAGE>

                                  Schedule 7.4

                         Safety Data Exchange Agreement


<PAGE>

                              SAFETY DATA EXCHANGE

[*****]




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