Exhibit 10.40
[..**..] = Certain Confidential Information Contained
in this Document, Marked by Brackets, Has Been
Omitted and Filed Separately with the Securities
and Exchange Commission Pursuant to rule 24b-2
of the Securities Exchange Act of 1934, as Amended.
Exhibit A-1
LICENSE, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT
     This License, Development and Commercialization Agreement (this
“Agreement”) is made this                      day of                     ,
200___ by and between Myogen, Inc. (“Myogen”), a Delaware corporation with
principal offices at 7575 West 103rd Avenue, Westminster, Colorado 80021, and
Novartis Institutes for BioMedical Research, Inc. (“NIBRI”), a Delaware
corporation with principal offices at 400 Technology Square, Cambridge,
Massachusetts 02139.
     Capitalized terms used but not defined in this Agreement have the meanings
provided in the Collaboration and Option Agreement by and between the parties
dated as of October 8, 2003, as amended and restated on July 7, 2006 (the
“Collaboration Agreement”).
Introduction
     WHEREAS, pursuant to the Collaboration Agreement, Myogen and NIBRI are, or
have been, engaged in discovering and developing compounds having a specific
therapeutic effect on the Myogen Targets or Collaboration Targets (each as
defined in the Collaboration Agreement);
     WHEREAS, NIBRI has exercised its Option under the Collaboration Agreement
to license exclusively one or more of the Development Candidates (as defined
herein) for development and commercialization in the Licensed Field (as defined
herein) and in the Territory;
     NOW THEREFORE, in consideration of the foregoing premises, the parties
agree as follows:
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ARTICLE I
Definitions
     1.1. “Active Compound” shall have the meaning set forth in the
Collaboration Agreement.
     1.2. “Affiliate” shall have the meaning set forth in the Collaboration
Agreement.
     1.3. “Cardiac Field” shall mean the research, treatment, prognosis,
diagnosis, prophylaxis, and monitoring of heart muscle disease.
     1.4. “Collaboration Agreement” shall mean that certain Collaboration and
Option Agreement dated as of October 8, 2003, as amended and restated on July 7,
2006, by and between Myogen and NIBRI, and as amended or restated by Myogen and
NIBRI from time-to-time thereafter.
     1.5. “Collaboration Compound” shall have the meaning set forth in the
Collaboration Agreement.
     1.6. “Collaboration Target” shall have the meaning set forth in the
Collaboration Agreement.
     1.7. “Commencement Date” shall mean, with respect to the application of
this Agreement to a Development Candidate, the date on which NIBRI exercised its
Option under Section 4.4 of the Collaboration Agreement with respect to that
Development Candidate.
     1.8. “Compound” shall have the meaning set forth in the Collaboration
Agreement.
     1.9. “Controlled” shall have the meaning set forth in the Collaboration
Agreement.
     1.10. “Co-Promotion Expenses” shall mean, with respect to each Drug
Product, out-of-pocket costs and other costs (in the case of personnel costs for
personnel directly involved in the marketing or promotional activities,
excluding sales personnel and field service supervisors) which are incurred by a
party or any of its Affiliates solely in connection with marketing or
promotional activities in the Cardiac Field or Expanded Cardiovascular Field, as
the case may be, including, without limitation, costs in the following
categories (in each case to the extent
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incurred in connection with activities in the Cardiac Field or the Expanded
Cardiovascular Field, as the case may be):
     (a) costs incurred in promoting and marketing such Drug Product, including
without limitation, advertising (including agency fees), market research,
patient-oriented promotions, meetings, pre-launch activities and expenses
relating to launch of the Drug Product, and managed markets/health authority
liaisons (but excluding detailing expenses);
     (b) amounts repaid or credited for bad debts;
     (c) costs associated with post-marketing drug safety surveillance;
     (d) medical affairs costs, and costs associated with medical/scientific
liaisons (including regional scientific directors), medical education and
publications, professional symposia, advisory boards, speaker and activity
programs;
     (e) costs of Phase IV Clinical Trials in the Territory and pharmacoeconomic
studies;
     (f) the cost of samples;
     (g) costs of materials and programs for the training of sales force and
marketing management;
     (h) costs of promotional materials, telemarketing, e-marketing, field and
headquarters’ grants, exhibits, direct mail and sample alternative programs;
     (i) all costs associated with the maintenance of Regulatory Approvals;
     (j) costs associated with any sales force training agreed to by NIBRI;
provided, however, that each party will train its own sales force (and that of
its Affiliates) at its own expense;
     (k) amounts paid to a Third Party in order to obtain freedom to operate
with respect to such Drug Product in the Territory; and
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     (l) amounts paid, whether in damages or by a settlement approved by NIBRI,
to a Third Party in the Territory as a result of any allegation of infringement
by any party of a Third Party patent by the manufacture, development or
commercialization of such Drug Product.
     The foregoing shall not include any costs which: (i) are incurred prior to
the Commencement Date; (ii) are incurred in connection with the manufacture of
any Drug Product; or (iii) have been included in Development Costs or Regulatory
Expenses.
     1.11. “Co-Promotion Notice” shall have the meaning set forth in
Section 3.5(a) hereof.
     1.12. “Co-Promotion Response” shall have the meaning set forth in
Section 3.5(a) hereof.
     1.13. “Co-Promotion Share” shall have the meaning set forth in
Section 3.5(a) hereof.
     1.14. “Development Candidate” shall mean the NIBRI Compound, Myogen
Compound or the Collaboration Compound, together with the Myogen Target or
Collaboration Target on which it has therapeutic action, as to which NIBRI
exercised its Option under the Collaboration Agreement and entered into this
Agreement, and any derivatives thereof whether or not they were developed before
or after the execution of this Agreement.
     1.15. “Development Costs” shall mean, with respect to a Development
Candidate and Drug Products derived therefrom, expenses and other costs,
including Regulatory Expenses (except for the maintenance of Regulatory
Approvals), incurred by or on behalf of a party in connection with the worldwide
development of such Development Candidate and Drug Products derived therefrom in
accordance with the Development Program in the Cardiac Field or the Expanded
Cardiovascular Field, as the case may be, including without limitation the costs
of clinical trials, the preparation, collation and/or validation of data from
such clinical trials and the preparation of medical writing as will make the
results of such clinical trials an element of one or more Registration Filings
in the Cardiac Field or Expanded Cardiovascular Field, as applicable; provided,
that Development Costs shall include: (a) the cost of any preclinical or
clinical studies conducted by NIBRI or its Affiliates in connection with a
Development Program outside the
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Cardiac Field or Expanded Cardiovascular Field, as applicable (and not
reimbursed or paid by a Third Party), to the extent the results of such studies
are required to be performed under applicable regulatory guidelines specific to
the indication being studied in the Cardiac Field or Expanded Cardiovascular
Field, as applicable, and incorporated as part of any Registration Filings
submitted to support a Regulatory Approval for an indication in the Cardiac
Field or Expanded Cardiovascular Field, as applicable; and (b) the cost of Phase
IIIB clinical trials and Phase IV clinical trials only if and to the extent they
are intended to support indications in the Cardiac Field or Expanded
Cardiovascular Field, as applicable, beyond the respective initial indications
(as agreed upon by the parties) for the Drug Products, to support expanded
labeling for the Drug Products, or to satisfy requirements imposed by
governmental regulatory authorities in connection with Regulatory Approvals for
the Products in the Cardiac Field or the Expanded Cardiovascular Field, as
applicable. Development Costs consist of:
     (a) all out-of-pocket costs incurred by the parties or their Affiliates,
including payments made to Third Parties with respect to any of the foregoing;
     (b) the fully allocated costs of internal scientific or technical personnel
engaged in such efforts, which costs shall be determined based on the FTE annual
rate or such other basis as may otherwise be agreed by the parties;
     (c) the costs of clinical supplies for such efforts as agreed in the
applicable approved Development Program in the Cardiac Field or the Expanded
Cardiovascular Field, as applicable, including: (i) the fully allocated cost or
out-of-pocket costs, as applicable, incurred in purchasing and/or packaging
comparator drugs; and (ii) disposal of clinical samples;
     (d) the costs and expenses incurred in connection with technical
development and with other manufacturing development activities; and
     (e) any other costs or expenses explicitly included in the Development
Program in the Cardiac Field or the Expanded Cardiovascular Field, as the case
may be.
     1.16. “Development Program” shall mean activities associated with
development of Active Compounds as Development Candidates for sale as Drug
Products in the Cardiac Field or
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the Expanded Cardiovascular Field, as the case may be, in the Territory,
including but not limited to: (a) formulation of Active Compounds as Development
Candidates for use in preparation for preclinical studies; (b) preclinical
animal studies performed in accordance with GLP (or the applicable equivalent)
in preparation for the filing of an IND (or the applicable equivalent); (c)
formulation and manufacture of Active Compounds as Development Candidates for
preclinical and clinical studies; (d) planning, implementation, evaluation and
administration of human clinical trials; (e) manufacturing process development
and scale-up for the manufacture of bulk Active Compound and Drug Product;
(f) preparation and submission of applications for regulatory approval; and
(g) post-market surveillance of approved drug indications, as required or agreed
as part of a marketing approval by any governmental regulatory authority.
     1.17. “Drug Product” shall mean a product prepared from bulk Active
Compound with respect to a Development Candidate, in finished dosage form ready
for administration to the ultimate consumer as a pharmaceutical.
     1.18. “European Co-Promotion Share” shall be equal to: (a) [..**..] of the
Co-Promotion Share for the first year following the commercial launch of the
Drug Product in any of the European Countries; (b) [..**..] of the Co-Promotion
Share for the second year following the commercial launch of the Drug Product in
any of the European Countries; and (c) [..**..] of the Co-Promotion Share for
the third and each successive year following the commercial launch of the Drug
Product in any of the European Countries.
     1.19. “European Countries” shall mean the United Kingdom, Germany, France,
Italy and Spain.
     1.20. “Expanded Cardiovascular Field” shall mean the research, treatment,
prognosis, diagnosis, prophylaxis, and monitoring of cardiovascular disease,
cardio-renal disease and cardio-pulmonary disease.
     1.21. “Expiration Date” shall have the meaning set forth in Section 8.1
hereof.
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     1.22. “First Commercial Sale” shall mean the first shipment of a Drug
Product to a Third Party by NIBRI or an Affiliate or sublicensee of NIBRI in a
country in the Territory following applicable Regulatory Approval of the Drug
Product in such country.
     1.23. “GCP” shall mean the current Good Clinical Practice standards for
clinical trials for pharmaceuticals, as set forth in the Food, Drug and Cosmetic
Act and applicable regulations promulgated thereunder, as amended from time to
time, and such standards of good clinical practice as are required by the
regulatory authorities of the organizations and governmental agencies in
countries in which Drug Products are intended to be sold.
     1.24. “GLP” shall mean the current Good Laboratory Practices regulations
promulgated by the FDA, published at 21 CFR Part 58, as such regulations may be
from time to time amended, and such equivalent regulations or standards of
countries outside the United States as may be applicable to activities conducted
hereunder.
     1.25. “GMP” shall mean the current Good Manufacturing Practice regulations
promulgated by the FDA, published at 21 CFR Part 210 et seq., as such
regulations may be amended, and such equivalent foreign regulations or standards
as may be applicable with respect to bulk Active Compound or a Drug Product
manufactured or sold outside the United States.
     1.26. “Gross Contribution” means, with respect to Drug Products co-promoted
by the parties in accordance with Section 3.5 hereof, [..**..], in the United
States and/or the European Countries (as applicable), less the following:

  (a)   [..**..]; and     (b)   [..**..].

     1.27. “Improvement” means any enhancement in the formulation, ingredients,
preparation, presentation, means of delivery, dosage, packaging of, manufacture,
or any new or expanded therapeutic indication(s) for, an Active Compound, a Drug
Product, or any other metabolite or isomer thereof.
     1.28. “Improvement Patent” means any Patent (except for the formulation
Patent and use Patent with respect to a Development Candidate) containing claims
that cover an Improvement.
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     1.29. “IND” shall mean an application to the Food and Drug Administration,
the filing of which is necessary to commence clinical testing of Compounds in
humans, or the equivalent application to the equivalent agency in any other
country or group of countries.
     1.30. “In Vivo Validation” means, with respect to an Active Compound, the
achievement of physiologically significant activity in an appropriate in vivo
model or models, where the level of physiologically significance and the in vivo
model(s) to be used will be specified by the JSC with respect to High Priority
Targets and Low Priority Targets and by Myogen with respect to
Extra-Collaboration Targets.
     1.31. “Joint Patent” shall mean a Patent which, absent rights thereunder,
would be infringed by the research, development, manufacture, use, importation,
sale, or distribution of the Development Candidate or a Drug Product relating
thereto, and is owned or Controlled jointly by NIBRI or a NIBRI Affiliate, on
the one hand, and Myogen or a Myogen Affiliate, on the other hand.
     1.32. “Joint Know-How” shall mean Know-How that is owned or Controlled
jointly by NIBRI or a NIBRI Affiliate, on the one hand, and Myogen or a Myogen
Affiliate, on the other hand.
     1.33. “Joint Technology” shall mean Joint Patents and Joint Know-How.
     1.34. “Know-How” means all Technology other than inventions that are the
subject of Patents, including, but not limited to, information, technical
information, techniques, data, inventions, discoveries, trade secrets,
processes, practices, methods, materials, compositions, formulas, improvements,
knowledge, know-how, skill, experience, or test data, whether or not patented or
confidential, which is Controlled by a party relating to the Myogen Technology
or the development, manufacture, use, sale, offer for sale, or import of any
Active Compound, Development Candidate, or Drug Product, or any Improvement
thereto, including (but not limited to), pharmacological, toxicological,
pre-clinical and clinical test data, analytical and quality control data,
packaging, marketing, pricing, distribution, sales and manufacturing data or
descriptions, compositions-of-matter, assays and biological materials related
thereto and the content of this Agreement.
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     1.35. “Know-How Period” shall have the meaning set forth in Section 8.1.
     1.36. “Licensed Field” shall mean all human and veterinary health care
applications including, but not limited to, research, prognosis and diagnosis
(subject to Section 2.5), therapeutics, prophylaxis, and monitoring with respect
to any indication, together with all agricultural purposes.
     1.37. “Licensed Patents” shall mean any Myogen Patents that become the
subject of NIBRI’s rights under Article II of this Agreement upon exercise of
its license and development option in accordance with the provisions of
Section 4.4 of the Collaboration Agreement.
     1.38. “Listed Country” shall mean a country listed on Schedule 1.38 hereof,
as Schedule 1.38 may be amended from time to time on mutual written agreement of
the parties.
     1.39. “Live Claim” shall mean a claim of any issued, unexpired Licensed
Patent that shall not have been withdrawn, canceled or disclaimed, nor held
invalid or unenforceable by a court of competent jurisdiction in an unappealed
or unappealable decision.
     1.40. “Myogen Compound” shall have the meaning set forth in the
Collaboration Agreement.
     1.41. “Myogen Know-How” shall have the meaning set forth in the
Collaboration Agreement, as the same shall exist on the Commencement Date and at
any time during the term of this Agreement.
     1.42. “Myogen Patents” shall have the meaning set forth in the
Collaboration Agreement, as in effect on the Commencement Date and at any time
during the term of this Agreement. A list of Myogen Patents is appended hereto
as Schedule 1.42 and will be updated periodically to reflect additions thereto
during the course of this Agreement.
     1.43. “Myogen Target” shall have the meaning set forth in the Collaboration
Agreement.
     1.44. “Myogen Technology” shall mean all Myogen Patents and Myogen
Know-How.
     1.45. “NDA” means a New Drug Application submitted to the Food and Drug
Administration seeking approval to market and sell a Drug Product in the
Licensed Field in the
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United States of America, or a corresponding application filed with any other
regulatory agency seeking approval to market and sell a Drug Product in the
Licensed Field in a country in the Territory.
     1.46. “Net Sales” shall mean, with respect to a Drug Product, the gross
amount invoiced by NIBRI and any NIBRI Affiliate, sublicensee or marketing
partner to Third Party customers for the Drug Product, less:
     (a) Normal and customary trade and quantity discounts and non-affiliated
brokers’ or agents’ commissions actually allowed and taken and not already
reflected in the amount invoiced;
     (b) Amounts repaid or credited by reason of defects, rejections, returns,
recalls, allowances, or retroactive price reductions;
     (c) Third Party cash rebates and chargebacks related to sales of finished
Drug Products, to the extent allowed;
     (d) Retroactive price reductions that are actually allowed or granted;
     (e) Tariffs, duties, excise, sales, value-added, and other consumption
taxes and customs duties to the extent included in the invoice price and paid by
or on behalf of NIBRI;
     (f) Cash discounts for timely payment;
     (g) Delayed ship order credits;
     (h) Discounts pursuant to indigent patient programs and patient discount
programs of any nature;
     (i) A fixed charge of [..**..] to cover warehousing and distribution
expenses; and
     (j) Any other specifically identifiable costs or charges included in the
gross invoiced sales price of such Drug Product falling within categories
substantially equivalent to those listed above;
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provided that:
     (i) In the case of any sale or other disposal of a Drug Product between or
among NIBRI and its Affiliates, sublicensees or marketing partners, for resale,
Net Sales shall be calculated as above only on the value charged or invoiced on
the first arm’s length sale to a Third Party;
     (ii) In the case of any sale or other disposal, such as barter or
counter-trade, of any Drug Product, or part thereof, otherwise than in an arm’s
length transaction exclusively for money, Net Sales shall be calculated as above
on the value of the consideration received or, if higher, on the fair market
price of the Drug Product in the relevant country of sale or disposal; and
     (iii) In the event that a Drug Product is sold as part of a combination
product, Net Sales of the Drug Product, for the purpose of determining royalty
payments, shall be determined by multiplying Net Sales (as defined above) of the
combination product by the fraction A/(A+B), where A is the weighted (by sales
volume) average sales price of the Drug Product when sold separately in finished
form and B is the weighted average sale price of the other product(s) sold
separately in finished form. In the event that such average sales price cannot
be determined for both the Drug Product and the other product(s) in combination,
Net Sales for purposes of determining payments hereunder shall be mutually
agreed by the parties based on the relative value contributed by each component,
and such agreement shall not be unreasonably withheld.
     1.47. “NIBRI Compound” shall have the meaning set forth in the
Collaboration Agreement.
     1.48. “NIBRI Know-How” shall have the meaning set forth in the
Collaboration Agreement, as the same shall exist on the Commencement Date and at
any time during the term of this Agreement with respect to the Development
Candidate, any Drug Product incorporating the same, and their respective use and
manufacture.
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     1.49. “NIBRI Patents” shall have the meaning set forth in the Collaboration
Agreement, as in effect on the Commencement Date and at any time during the term
of this Agreement.
     1.50. “NIBRI Technology” shall mean all NIBRI Patents and NIBRI Know-How.
     1.51. “Patent Period” shall have the meaning set forth in Section 8.1.
     1.52. “Patents” shall mean all existing patents and patent applications and
all patent applications hereafter filed, including any continuation,
continuation-in-part, division, provisional or any substitute applications, any
patent issued with respect to any such patent applications, any reissue,
reexamination, renewal or extension (including any supplementary protection
certificate) of any such patent, and any confirmation patent or registration
patent or patent of addition based on any such patent, and all foreign
counterparts of any of the foregoing.
     1.53. “Person” shall mean any individual, corporation, partnership,
association, limited liability company, trust, unincorporated organization or
government or political subdivision thereof.
     1.54. “Phase I Clinical Trial” shall mean a clinical study, conducted in
accordance with a protocol approved by NIBRI of a Drug Product in human
volunteers with the endpoint of determining initial tolerance, safety and/or
pharmacokinetic information in single dose, single ascending dose, multiple dose
and/or multiple ascending dose regimens.
     1.55. “Phase II Clinical Trial” shall mean a clinical study, conducted in
accordance with a protocol approved by NIBRI, of a Drug Product in patients to
determine initial efficacy and dose range finding.
     1.56. “Phase III Clinical Trial” shall mean a clinical study in patients,
conducted in accordance with a protocol approved by NIBRI, which protocol is
designed to ascertain efficacy and safety of a Drug Product for the purpose of
preparing and submitting a filing for Regulatory Approval in a particular
country in the Territory.
     1.57. “Phase IV Clinical Trial” shall mean a clinical study initiated in a
country after receipt of Regulatory Approval for a Drug Product in such country.
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     1.58. “Registration Filing” shall mean, with respect to each Development
Candidate or related Drug Product, the submission to the relevant governmental
regulatory authority of an appropriate application seeking any Regulatory
Approval, and shall include, without limitation, any marketing authorization
application, supplementary application or variation thereof, or any equivalent
applications.
     1.59. “Regulatory Approval” shall mean, with respect to a country in the
Territory, all authorizations by the appropriate governmental entity or entities
necessary for commercial sale of a Drug Product in that country including,
without limitation and where applicable, approval of labeling, price,
reimbursement and manufacturing.
     1.60. “Regulatory Expenses” shall mean, with respect to a Development
Candidate or related Drug Product, all out-of-pocket costs and fully allocated
costs incurred by or on behalf of a party in connection with the preparation and
filing of Registration Filings and the maintenance of Regulatory Approvals.
     1.61. “Technology” shall mean all data, technical information, know-how,
experience, inventions (whether or not patented), trade secrets, processes and
methods discovered, developed or applied (with the consent of its owner) and
Controlled by either party or its Affiliates, in connection with performance by
either party under the Research Program, or in connection with the conduct of a
Development Program, that relate to the research, development, utilization,
manufacture or use of Targets or Compounds.
     1.62. “Territory” shall mean [..**..].
     1.63. “Third Party” shall mean any Person that is not a party or an
Affiliate of any party to this Agreement.
ARTICLE II
Rights and Licenses
     2.1. NIBRI Rights. Subject to the other provisions of this Agreement,
Myogen grants to NIBRI and its Affiliates a license, exclusive even as to
Myogen, with the right to sublicense, under the Myogen Patents and the Myogen
Know-How and in the Licensed Field, to research
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and have researched, develop and have developed, make and have made, and use and
have used the Development Candidate and to research and have researched, develop
and have developed, make and have made, manufacture and have manufactured, use
and have used, market and have marketed, distribute and have distributed, sell
and have sold, export and import for sale, and have exported or imported for
sale, Drug Products in each country in the Territory. NIBRI understands that the
licenses granted under this Agreement to certain Myogen Technology that has been
licensed by Myogen pursuant to agreements with the University of Texas
Southwestern Medical Center, the University of North Texas Health Sciences
Center and the University Licensing and Equity Holdings, Inc. are subject to the
retained rights of such licensors to use such Myogen Technology for research,
teaching and other educationally-related, non-commercial purposes. Myogen
retains all rights to Myogen Technology except to the extent explicitly granted
to NIBRI hereunder.
2.2. Scope of Exclusivity; Diligence; Development Responsibility.
     (a) As long as NIBRI is using commercially reasonable efforts to diligently
develop and/or commercialize the Development Candidate in the Licensed Field:
     (i) The licenses granted to NIBRI in Section 2.1 shall be effective also
with respect to any other Active Compound which falls under the same Live Claim
as an Active Compound constituting the Development Candidate provided that all
of the terms and conditions of this Agreement (including royalty and milestone
payments) shall apply to all such other Active Compounds; and
     (ii) Myogen shall not develop, make, have made, use, market and sell,
itself or through a Third Party licensee, for use within the Licensed Field, any
other Active Compound which falls under the same Live Claim as an Active
Compound constituting the Development Candidate.
     (b) NIBRI shall be deemed to be using commercially reasonable efforts with
respect to the provisions of Section 2.1 and Section 3.4 if NIBRI or any of its
Affiliates is actively undertaking diligent, commercially reasonable efforts,
similar to those used for other products of NIBRI or its Affiliates that are of
similar commercial potential, for the continuing development and the
commercialization of the Development Candidate in the
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Licensed Field, including, without limitation, the development and/or
optimization and/or further characterization of Active Compounds, initiation and
conduct of clinical trials, submission of regulatory filings and commercial
launch of Drug Products.
     (c) Except as otherwise provided herein, NIBRI will have sole
responsibility for, and bear the cost of conducting, the Development Program
with respect to each Development Candidate and/or seeking Regulatory Approval of
any Drug Product.
     2.3. Joint Inventions and Joint Patents. All inventions conceived of and
reduced to practice during the term of, or as a result of, this Agreement,
jointly by employees or agents of Myogen or its Affiliates, on one hand, and
employees or agents of NIBRI or its Affiliates, on the other hand (“Joint
Inventions”) and all Patent applications and Patents claiming Joint Inventions,
shall be owned jointly by Myogen and NIBRI, and such Patent applications and
Patents shall be included within the Joint Patents. The rights of each party
with respect to the Joint Technology shall be determined in accordance with
United States patent law as it applies to issues of joint ownership of
intellectual property as of the Effective Date of the Collaboration Agreement.
     2.4. Inventions Necessary to the License. If Myogen conceives and reduces
to practice during the term of this Agreement any new Technology relating to a
Development Candidate or Drug Product and covered by a Myogen Patent, or
acquires or Controls (either on the Effective Date or at any time during the
term of this Agreement) any Patent on a Technology, and such Technology is
necessary to NIBRI’s exercise of its licensed rights in the Cardiac Field, then
the definition of Myogen Patent will be deemed to include such Patents that are
included within the licenses granted to NIBRI under this Agreement.
     2.5. Diagnostic and Prognostic Products. In the event that NIBRI desires to
develop and commercialize any diagnostic or prognostic products based upon any
Development Candidate, the parties agree to negotiate in good faith the terms
under which NIBRI would be granted rights to develop and commercialize such
products.
     2.6. Right of First Negotiation to Discontinued NIBRI Compounds. In the
event that NIBRI elects to discontinue the Development Program with respect to a
NIBRI Compound or elects to terminate this Agreement for its convenience, and
NIBRI subsequently contemplates collaborating with a Third Party with respect to
development and/or commercialization of such
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NIBRI Compound, NIBRI shall give Myogen written notice of the same. Within
[..**..] of receipt of such notice, Myogen shall inform NIBRI in writing as to
whether it wishes to negotiate in good faith a license to such NIBRI Compound
within the Licensed Field. If Myogen so informs NIBRI, then the parties shall
have [..**..] to negotiate a transaction in good faith. If the parties are
unable to consummate a transaction within such period (or such longer period as
the parties may agree to in writing), then NIBRI may enter into a Third Party
transaction with respect to the NIBRI Compound. All other rights to discontinued
Compounds shall be governed by the terms of the Collaboration Agreement.
ARTICLE III
Development and Commercialization
     3.1. Development and Commercialization Rights. Subject to any
co-funding/co-promotion rights granted to Myogen pursuant to Section 3.5 hereof,
NIBRI, its Affiliates and/or sublicensees, if any, shall have sole rights, even
as to Myogen, in the Licensed Field to develop and manufacture on a commercial
scale the Development Candidate, the related Drug Product, and the active
ingredient in such Drug Product in the Territory, and to commercialize,
manufacture, promote, sell, book sales, and distribute each Drug Product and/or
the active ingredient in such Drug Product in each country in the Territory.
(The foregoing right to manufacture is subject to any applicable United States
statutory requirement that technology the development of which was funded in
part by the United States government must be manufactured domestically, unless
the United States government shall waive such requirement.) NIBRI and its
Affiliates, in their sole discretion, shall select, file, and own all rights to
any and all trademarks and trade dress relating to the Drug Product.
     3.2. Information Transfer. Myogen shall deliver (to the extent not
previously delivered to NIBRI pursuant to the Collaboration Agreement) as
promptly as practicable to NIBRI all information in Myogen’s possession or under
its control (including summaries of raw data from clinical studies conducted by
Myogen of each Active Compound and related Myogen Target or Collaboration Target
comprising the Development Candidate), all scientific reports, and all processes
and procedures that are necessary or useful for further development,
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manufacture and commercial exploitation and distribution of the Development
Candidate in the Territory. Such information shall include a summary of all
material written communications (copies of which Myogen will provide to NIBRI at
NIBRI’s request) between Myogen or (to the extent available to Myogen) its other
licensees and the Food and Drug Administration (or any other similar regulatory
authority) concerning the Development Candidate. This information shall also
include copies of all Patents, copyrights, copyright registrations and
applications therefor and all other manifestations of the intellectual property
embodied in the Development Candidate, whether in human or machine readable
form. Information provided by Myogen will be subject to the provisions of
Article VI hereof.
     3.3. Regulatory Approvals. NIBRI and/or its Affiliates will be responsible
for all required Regulatory Approvals in the Territory. All filings will be made
by NIBRI and/or its Affiliates. All Regulatory Approvals will be held in the
name of NIBRI and/or its Affiliates. NIBRI and its Affiliates shall have the
right to cross-reference information and regulatory filings relating to the
Development Candidate arising out of development work which previously has been
conducted by Myogen and its Affiliates and licensees, for the purpose of
regulatory filings hereunder.
     3.4. Due Diligence. Upon exercise of its Option with respect to a
Development Candidate, NIBRI and its Affiliates shall commence a Development
Program with respect to such Development Candidate and shall use commercially
reasonable efforts (as defined in Section 2.2(b)) to effect introduction of the
Drug Product relating to such Development Candidate into one or more commercial
markets in the Territory. In the normal course of development, any Development
Candidate may be dropped from development for valid scientific or medical
reasons provided to Myogen by NIBRI in writing and may be replaced (at the sole
discretion of NIBRI and/or its Affiliates) with one or more other Development
Candidates having a therapeutic action on the same Myogen Target or
Collaboration Target, and such occurrence shall not constitute a failure of due
diligence.
     3.5. Co-Funding and Co-Promotion Option.
     (a) Following the completion of Phase II Clinical Trials with positive
results leading to NIBRI’s reasonable expectation that it will conduct Phase III
Clinical Trials
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and generation of relevant reports, NIBRI will provide Myogen with a report
containing all relevant pre-clinical data and all relevant clinical data from
the Phase I Clinical Trials and the Phase II Clinical Trials and a preliminary
estimate of anticipated Co-Promotion Expenses (including sales force details)
(the “Co-Promotion Notice”). In the event that Myogen wishes to co-fund and
co-promote such Development Candidate in the Cardiac Field or, solely to the
extent that NIBRI or its Affiliates are no longer pursing a Development Program
with respect to such Development Candidate that was developed from a Myogen
Compound in the Cardiac Field but are pursuing a Development Program with
respect to such Development Candidate in the Expanded Cardiovascular Field, in
the Expanded Cardiovascular Field, either the United States, or the United
States and the European Countries, Myogen shall give NIBRI written notice of the
same no later than [..**..] after its receipt of the Co-Promotion Notice (the
“Co-Promotion Response”). The Co-Promotion Response will specify the level of
financial commitment that Myogen will assume with respect to the co-funding of
such Development Candidate and the co-promotion of such Development Candidate in
the United States in the Cardiac Field or the Expanded Cardiovascular Field, as
the case may be (the “Co-Promotion Share”) and whether Myogen wishes to co-fund
and co-promote such Development Candidate in the European Countries; provided,
that Myogen shall be required to commit to fund no less than [..**..] and no
greater than [..**..] of the Development Costs and Co-Promotion Expenses of such
Development Candidate that are attributable to the development of the
Development Candidate in the Cardiac Field or the Expanded Cardiovascular Field,
as the case may be, in the United States and, if applicable, the European
Countries.
     (b) Along with the Co-Promotion Response, Myogen will provide NIBRI with
certification to NIBRI’s reasonable satisfaction that it has the financial
resources to co-fund the Development Costs and a detailed plan under which
Myogen will have the financial resources to undertake co-promotion of the Drug
Products, including the requisite sales force and sales force infrastructure
required to provide its share of the promotional efforts. NIBRI may require
documentary and other evidence that Myogen has, or will have at the appropriate
time, the requisite resources (including personnel) and expertise to perform
such co-promotion, including satisfying the same percentage level of
Co-Promotion Expenses and promotional effort (including sales force details).
Each Co-
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Promotion Response shall contain a commitment by Myogen that Myogen will be able
to satisfy its portion of the projected levels of Co-Promotion Expenses and
promotional effort, which may be satisfied initially or partially through use of
a contract sales force; provided, however, that oversight of the contract sales
force will be provided by Myogen sales management personnel. NIBRI may reject
the Co-Promotion Response (and the corresponding co-promotion opportunity with
Myogen) only if it has reasonable grounds based on such information that Myogen
will not have such capability at the appropriate time.
     (c) NIBRI and Myogen shall enter into good faith negotiations and will use
reasonable best efforts to conclude a co-funding/co-promotion definitive
agreement (the “Definitive Agreement”). The Definitive Agreement will outline
the overall framework for the co-promotion effort, including roles and
responsibilities, total Co-Promotion Expenses required and Myogen’s co-promotion
funding commitment in the United States and, if applicable, the European
Countries that is at a percentage level identical to the Co-Promotion Share and
the European Co-Promotion Share, respectively. The Definitive Agreement shall
reflect, among other things, the following:
     (i) Given the expertise of NIBRI and its Affiliates in sales and marketing,
NIBRI shall have sole authority to determine the required budget of the
Development Program and the Co-Promotion Expenses and the total levels of
promotional effort (including sales force details) for such Drug Product, with
Myogen’s input taking into account Myogen’s expertise in the heart failure and
cardiovascular market and its Co-Promotion Share.
     (ii) Myogen shall be required under the Definitive Agreement to share a
portion of the Co-Promotion Expenses incurred by both NIBRI and Myogen, taken
together, and to provide the portion of the promotional effort (including sales
force details) in the Cardiac Field or the Expanded Cardiovascular Field, as
applicable, equal to the Co-Promotion Share with respect to the United States,
and the European Co-Promotion Share with respect to the European Countries.
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     (iii) Myogen shall be entitled to receive a portion of the Gross
Contribution derived from sales of the relevant Drug Product in the United
States equal to the Co-Promotion Share, and in [..**..], equal to the [..**..]
Co-Promotion Share, and NIBRI’s royalty obligations to Myogen under this
Agreement shall cease with respect to United States and, if applicable, the
European Countries.
     (iv) In consideration of the rights granted to Myogen under the Definitive
Agreement, Myogen will be required to pay NIBRI: (A) the Development Costs
expended by NIBRI as of the effective date of the Definitive Agreement that are
attributable to the development of the Development Candidate in the Cardiac
Field or the Expanded Cardiovascular Field, as applicable, in the United States
and, if applicable, the European Countries multiplied by the Co-Promotion Share
(the “Expense Reimbursement”); plus (B) a risk premium equal to the Expense
Reimbursement multiplied by [..**..]. These payments will be made in [..**..]
installments on the effective date of the Definitive Agreement and on [..**..]
the Definitive Agreement, regardless of the status of the Development Program.
     (v) If Myogen is unable to satisfy its co-funding and co-promotion
obligations under the Definitive Agreement, or if Myogen elects to terminate its
co-promotion rights during the term of the Definitive Agreement, then Myogen’s
share of the Gross Contribution will be proportionately reduced taking into
account Myogen’s contribution to the co-funding and, if applicable, the
commercialization of the Drug Product, to be more fully specified in the
Definitive Agreement.
     (vi) Additional terms and conditions customary in the industry for an
agreement of this type.
     (d) In no event shall any portion of Myogen’s co-funding commitment be
provided by a Third Party (not including any funding obtained by Myogen through
loans or capital investment by Third Parties) without the consent of NIBRI.
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     (e) Upon exercising its option to co-promote, Myogen will be allowed to
appoint up to [..**..] on NIBRI’s (or its Affiliate’s) International Project
Team for the Development Candidates or Drug Products that are under development
by NIBRI hereunder and will have access to project summaries and other documents
provided by NIBRI to other members of the International Project Team.
ARTICLE IV
Milestone and Royalty Payments
     4.1. Milestone Payments.
     (a) NIBRI shall make milestone payments to Myogen in accordance with this
Section 4.1 with respect to Active Compounds developed as Development Candidates
hereunder. Except as explicitly set forth below, pre-clinical milestone payments
shall be payable on only one Active Compound per Myogen Target or Collaboration
Target, and clinical milestones shall be payable only once on a particular
Active Compound, even though that Active Compound may be subsequently developed
for indications other than those for which Regulatory Approval was initially
sought. In the event that an Active Compound fails in development, any milestone
payments previously paid with respect to such Active Compound shall be fully
creditable toward the same milestone due with respect to another Active Compound
that acts on the same Myogen Target or Collaboration Target. NIBRI may deduct
from any milestone payments otherwise due to Myogen under this Article IV the
amount of any withholding and similar taxes required under applicable law to be
withheld from such payments and paid to applicable tax authorities.
     (b) The following milestone payments shall be payable within [..**..] of
the relevant developmental event:
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                          MILESTONE     DEVELOPMENTAL MILESTONE:   PAYMENT
Pre-Clinical Milestones:    
 
           
 
  •   Validation of high-throughput assays*   [..**..]
 
           
 
  •   In vitro validation of lead compound*   [..**..]
 
           
 
  •   In Vivo Validation of lead compound or use of the lead compound as a
starting point for medicinal chemistry and/or SAR exploration*   [..**..]
 
           
 
  •   Completion of Tox/ADME screening and preclinical candidate determination*
  [..**..]
 
            Clinical Milestones:    
 
           
 
  •   IND filing   [..**..]
 
           
 
  •   Initiation of Phase II clinical evaluation   [..**..]
 
           
 
  •   Initiation of Phase III clinical studies   [..**..]
 
           
 
  •   Regulatory filing in the U.S.   [..**..]
 
           
 
  •   First regulatory filing in the E.U.   [..**..]
 
           
 
  •   Regulatory Approval in the U.S.   [..**..]
 
           
 
  •   First Regulatory Approval in the E.U.   [..**..]

 

*   Criteria for determining the achievement of any Milestone have been
established by the JSC and distributed to the parties under separate cover.

     4.2. Royalty Payments During the Patent Period. During the Patent Period
(as defined in Section 8.1 hereof), NIBRI shall make the following royalty
payments to Myogen on total annual Net Sales to unaffiliated Third Parties of
each Drug Product incorporating an Active Compound that is developed as a
Development Candidate hereunder: [..**..] of Net Sales, plus: (a) compensation
for Third Party royalties owed by Myogen to the University of Texas Southwestern
Medical Center and the University of North Texas Health Sciences Center of up to
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[..**..] of Net Sales; and (b) compensation for Third Party royalties owed by
Myogen to University Licensing and Equity Holdings, Inc. of up to [..**..] of
Net Sales, only to the extent that such royalty obligations are incurred in
connection with such Development Candidate.
     4.3. Royalty Payments During a Know-How Period. During a Know-How Period
(as defined in Section 8.1 hereof), and in consideration for NIBRI’s license of
the Myogen Know-How related to the Development Candidate, NIBRI shall pay a
[..**..] royalty to Myogen on total annual Net Sales to unaffiliated Third
Parties of each Drug Product incorporating an Active Compound that is developed
as a Development Candidate hereunder; provided, however, that no period during
which a Licensed Patent covers such Active Compound shall be deemed to be a
Know-How Period, in which case no royalty pursuant to this Section 4.3 shall be
due to Myogen at any time. Subsequent to the Expiration Date, the license of
such Myogen Know-How shall be considered to be perpetual and fully paid.
     4.4. Responsibility for Myogen’s Third Party Royalty Obligations. Myogen
shall have sole responsibility for payment of all its Third Party royalty
obligations.
     4.5. Reduced Royalty Obligations. The obligation of NIBRI to pay royalties
to Myogen under this Agreement shall be reduced upon the occurrence of the
following events:
     (a) In the event of Myogen’s material breach of this Agreement, which shall
remain uncured one hundred eighty (180) days after written notice by NIBRI to
Myogen of the same, NIBRI may, at its election, pay [..**..] of the royalties
thereafter owed to Myogen under this Article IV into a third party escrow
account to be held pending resolution of the dispute between NIBRI and Myogen by
a court of competent jurisdiction. NIBRI may satisfy any final, non-appealable
judgment awarded by such court from the then-current balance of the escrow
account, and any excess of some or all of the escrow account will be promptly
refunded to Myogen; provided that this Section 4.5(a) will not limit any
compensatory or punitive damages that are recoverable at law or equity by NIBRI
for Myogen’s breach hereof.
     (b) In the event that no Live Claim in a particular country exists covering
the Development Candidate NIBRI’s royalty payment obligations under this
Agreement in
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such jurisdiction shall be reduced to [..**..] should a Third Party generic
compound enter the market in such particular jurisdiction with respect to a such
Development Candidate.
     (c) All Third Party royalties and license fees owed by Myogen to any Myogen
licensors under agreements with such Third Party or Third Parties with respect
to a Development Candidate licensed hereunder shall be Myogen’s responsibility,
subject to the provisions of Section 9.3(b) hereof. In the event that NIBRI or
an Affiliate thereof is required to pay Third Party royalties or license fees in
order to practice the License Patents for applications in the Cardiac Field,
NIBRI’s obligation to pay royalties to Myogen shall be reduced by [..**..] of
the amounts actually paid by NIBRI or its Affiliate to such Third Party;
provided, however, that NIBRI’s payment obligation shall in any case not be
reduced more than [..**..] of what otherwise would be owed to Myogen hereunder.
     4.6. Certain Understandings Regarding Royalty Payments. The parties
expressly agree that the royalties and milestones hereunder are in consideration
of the use of Myogen Technology to identify, synthesize, select or find useful
the Development Candidate as having a desired therapeutic effect on any Myogen
Target or Collaboration Target. Therefore, notwithstanding any earlier
expiration of the Licensed Patents, the term of payment of royalties hereunder
is required to compensate Myogen from revenues NIBRI or its Affiliates may in
the future derive from such use of the Myogen Technology and for the convenience
of accounting.
ARTICLE V
Reporting Obligations
     5.1. Development Reports. NIBRI shall prepare and submit to Myogen, on a
quarterly basis, reports which set forth in reasonable detail the progress of
the Development Program with respect to Development Candidates and the results
of work performed thereunder during the preceding quarter.
     5.2. Sales Reports and Records. During the term of this Agreement, but only
after the First Commercial Sale of a Drug Product, NIBRI shall deliver to Myogen
within forty-
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five (45) days after the end of each calendar quarter a written report showing
actual Net Sales of Drug Products by NIBRI, its Affiliates and sublicensees in
each country in the Territory during such calendar quarter. All Net Sales shall
be stated in United States dollars, and shall convert the amounts into United
States dollars from the currency in which such amounts are received by NIBRI
using NIBRI’s then-current standard exchange rate methodology applied in its
external reporting for the translation of foreign currency sales into United
States dollars. NIBRI will keep complete, true and accurate books of account and
records for the purpose of showing the derivation of Net Sales and all amounts
payable to Myogen under this Agreement. Such books and records will be kept by
NIBRI or an Affiliate of NIBRI for at least three (3) years following the end of
the calendar quarter to which they pertain. Such books and records, or copies
thereof, will be made available at NIBRI’s principal place of business, upon
request of Myogen, for inspection and copying by an independent auditor
appointed by Myogen for the purpose of verifying NIBRI’s sales reports or
NIBRI’s compliance in other respects with this Agreement. Such inspections shall
be at the expense of Myogen, unless a variation or error exceeding five percent
(5%) of the amount reported is discovered in the course of any such inspection,
whereupon the costs relating thereto shall be for the account of NIBRI.
ARTICLE VI
Confidentiality
     6.1. Undertaking. During the term of this Agreement, each party (a
“Receiving Party”) shall keep confidential, and other than as provided herein
shall not use or disclose, directly or indirectly, any trade secrets,
confidential or proprietary information, or any other knowledge, information,
documents or materials, owned, developed or possessed by the other party (the
“Proprietary Party”), whether in tangible or intangible form, the
confidentiality of which such other party takes reasonable measures to protect,
including but not limited to Collaboration Technology.
     (a) Each Receiving Party shall take any and all lawful measures to prevent
the unauthorized use and disclosure of such information, and to prevent
unauthorized persons or entities from obtaining or using such information.
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     (b) Each Receiving Party further agrees to refrain from directly or
indirectly taking any action that would constitute or facilitate the
unauthorized use or disclosure of such information. Each Receiving Party may
disclose such information to its Affiliates and to its or their respective
officers, employees and agents, to authorized licensees and sublicensees, and to
subcontractors in connection with the development or manufacture of Development
Candidate or Drug Products, to the extent necessary to enable such parties to
perform their obligations hereunder or under the applicable license, sublicense
or subcontract, as the case may be; provided, that such officers, employees,
agents, licensees, sublicensees and subcontractors have entered into appropriate
confidentiality agreements for secrecy and non-use of such information which by
their terms shall be enforceable by injunctive relief at the instance of the
Proprietary Party.
     (c) Each Receiving Party shall be liable for any unauthorized use and
disclosure of such information by its Affiliates or its or their respective
officers, employees and agents and any such sublicensees and subcontractors.
     6.2. Exceptions. Notwithstanding the foregoing, the provisions of
Section 6.1 hereof shall not apply to knowledge, information, documents or
materials which the Receiving Party can conclusively establish:
     (a) have entered the public domain without the Receiving Party’s breach of
any obligation owed to the Proprietary Party;
     (b) have become known to the Receiving Party from a source other than the
Proprietary Party, other than by breach of an obligation of confidentiality owed
to the Proprietary Party;
     (c) are independently developed by the Receiving Party without breach of
this Agreement, without reference to or reliance upon knowledge, information, or
materials of the Proprietary Party as established by written records; or
     6.3. In addition, a Receiving Party may, notwithstanding the obligations of
Section 6.1, disclose knowledge, information, documents or materials that the
Receiving Party can conclusively establish:
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     (a) are permitted to be disclosed by the prior written consent of the
Proprietary Party;
     (b) are required to be disclosed by the Receiving Party to comply with
applicable laws or regulations, to defend or prosecute litigation or to comply
with governmental regulations, provided that the Receiving Party provides prior
written notice of such disclosure to the Proprietary Party and takes reasonable
and lawful actions to avoid or minimize the degree of such disclosure.
     6.4. Publicity. The timing and content of any press releases or other
public communications relating to this Agreement and the transactions
contemplated herein will, except as otherwise required by law, be determined
jointly by Myogen and NIBRI.
     6.5. Survival. The provisions of this Article VI shall survive the
termination of this Agreement.
ARTICLE VII
Patents
     7.1. Preparation. NIBRI shall take responsibility and pay for the
preparation, filing, prosecution and maintenance of: (a) any and all Patents in
the Territory included in NIBRI Patents, including without limitation any such
patents and patent applications claiming NIBRI Compounds or NIBRI Improvements
under the Collaboration Agreement; (b) subsequent to the Commencement Date with
respect to Development Candidate, any and all Patents covering a Development
Candidate and any uses, formulations and formulation process inventions with
respect thereto; and (c) all Joint Patents. Myogen and NIBRI shall each furnish
to the other party copies of significant documents relevant to any such
preparation, filing, prosecution or maintenance of Patents covered by
subsections (b) and (c) above. Myogen and NIBRI shall cooperate fully in the
preparation, filing, prosecution and maintenance of all Myogen Patents, NIBRI
Patents, and Joint Patents, executing all papers and instruments so as to enable
the responsible party to apply for, to prosecute and to maintain patent
applications and patents in its name in any country in the Territory. The
parties acknowledge the importance of maintaining
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the confidentiality of any inventions or other information relating to potential
patent claims prior to the filing of patent applications with respect hereto.
NIBRI shall provide Myogen prompt notice as to any decision to abandon a Myogen
Patent or a Joint Patent in a Listed Country.
     7.2. Infringement. Each party shall notify the other promptly of any
possible infringements, imitations or unauthorized possession, knowledge or use
of the intellectual property embodied in any of the Development Candidate and
Myogen Know-How related to the manufacture or use of a Development Candidate or
Drug Products by Third Parties in any country in the Territory, of which such
party becomes aware. Each party shall promptly furnish the other party with full
details of such infringements, imitations or unauthorized possession, knowledge
or use, and shall assist in preventing any recurrence thereof. NIBRI or its
Affiliates shall be initially responsible, at its expense, for bringing any
action on account of any such infringements, imitations or possession, knowledge
or use, and Myogen shall cooperate with NIBRI, as NIBRI may reasonably request,
in connection with any such action. If, within sixty (60) days after receipt by
NIBRI of a written request from Myogen that it bring such an action, NIBRI does
not do so, Myogen shall have the right, at its expense and in its own name or in
the name of NIBRI, to do so on behalf of NIBRI, and NIBRI shall cooperate with
Myogen, as Myogen may reasonably request, in connection with such action,
including becoming a party to such suit. Such suit may not be settled by either
party without the other party’s written consent, which shall not be unreasonably
withheld. Damages recovered in any actions referenced hereunder shall be
apportioned in accordance with the royalty schedules contained in this
Agreement, after reimbursement to each party of their respective expenses in
prosecuting such actions as provided hereunder.
ARTICLE VIII
Term and Termination
     8.1. Term. The patent period with respect to any Development Candidate or
Drug Product incorporating that Development Candidate (each, a “Patent Period”)
shall extend in each country of the Territory until the later of the last to
expire of any Licensed Patents in that country covering the Development
Candidate or Drug Product incorporating that Development
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Candidate, the use thereof and/or the Myogen Target or the Collaboration Target
on which the Active Compound for the Development Candidate acts, or in the case
of the European Countries, on a country-by-country basis, the later of: (a) ten
(10) years from the date of First Commercial Sale of the Drug Product in that
country; or (b) the last to expire of any Licensed Patents in that country
covering the Development Candidate or Drug Product. The know-how period with
respect to any Development Candidate or Drug Product incorporating that
Development Candidate shall extend after the First Commercial Sale in each
country of the Territory for any period or periods not to exceed five (5) years
in the aggregate during which no Live Claim exists covering the Development
Candidate in such country (each a “Know-How Period”). Unless terminated earlier
in accordance with the provisions herein, this Agreement will expire, on a
country-by-country basis, upon the completion of the Patent Period and the
Know-How Period (the “Expiration Date”).
     8.2. Material Breach by NIBRI. Upon any material breach of the provisions
of this Agreement or of the Collaboration Agreement by NIBRI, which material
breach remains uncured by NIBRI one hundred eighty (180) days after receipt of
written notice of the same from Myogen, NIBRI’s exclusive rights within the
Territory shall become non-exclusive, and upon Myogen’s written request, NIBRI
shall thereupon render any reasonably necessary assistance to Myogen or its
designee to exercise Myogen’s rights within the Territory. The foregoing remedy
shall not be exclusive, and Myogen shall retain all other rights and remedies at
law or equity for any such breach.
     8.3. Termination. Either Party may terminate this Agreement upon the
bankruptcy or financial insolvency of the other Party. NIBRI may terminate this
Agreement without cause at any time upon ninety (90) days written notice to
Myogen.
     8.4. Effect of Termination. Termination of this Agreement for any reason,
or expiration of this Agreement, will terminate all rights and obligations of
each of the Parties, and all license rights granted to NIBRI and its Affiliates
will terminate and revert exclusively to Myogen except as otherwise provided
below, and except that such termination or expiration will not affect: (a)
obligations, including the payment of any milestones or royalties, which have
accrued as of the date of termination or expiration; and (b) rights and
obligations under the following provisions of this Agreement, which shall
survive termination or expiration of this
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Agreement: Article VI, Sections 9.1, 9.2, and 9.3. Following termination of this
Agreement under Section 8.1 hereof with respect to a particular country, NIBRI
shall have a fully paid license under the Myogen Technology to make, have made,
use, sell, have sold and import for sale Drug Product in that country in the
Territory; provided however that NIBRI’s obligation to pay royalties and
milestone payments under Article IV shall continue after any termination of this
Agreement for the time periods specified in Section 8.1. NIBRI covenants that,
upon and after termination of this Agreement for any reason (other than
expiration under Section 8.1), NIBRI and its Affiliates and sublicensees shall
not practice any of the Myogen Technology for any purpose relating to any
Development Compound (except as may otherwise expressly be permitted in a
separate agreement still in force between the Parties).
ARTICLE IX
Miscellaneous Provisions
     9.1. Governing Law, and Jurisdiction. This Agreement shall be governed and
construed in accordance with the internal laws of the Commonwealth of
Massachusetts. Both parties hereto agree to submit to personal jurisdiction in
the Commonwealth of Massachusetts and to accept and agree to venue in that
Commonwealth.
     9.2. No Warranty. Myogen makes no warranty of any kind whatsoever, either
express or implied, to NIBRI, or any customer of NIBRI, as to the ability of
NIBRI to understand and utilize the Myogen Technology. NIBRI makes no warranty
of any kind whatsoever, either express or implied, to Myogen, or to any customer
of Myogen, as to the ability of Myogen to understand and utilize the NIBRI
Technology. NIBRI shall indemnify and shall hold Myogen harmless against and
from any and all claims of Third Parties for damages due to personal injury
arising out of the actions of NIBRI, its Affiliates, agents, employees,
sublicensees or subcontractors, including but not limited to claims arising in
connection with the development, manufacturing, assembly, or sale of Development
Candidates and Drug Products by NIBRI. Myogen shall indemnify and hold NIBRI
harmless against and from any and all claims of Third Parties for damages due to
personal injury arising out of the actions of Myogen, its Affiliates, agents,
employees, sublicensees or subcontractors pursuant to this Agreement, including
but not
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limited to claims arising in connection with the Development Program in the
Cardiac Field or the Expanded Cardiovascular Field, as applicable. During the
term of this Agreement, the Parties shall keep each other promptly and fully
informed and will promptly notify appropriate authorities in accordance with
applicable law, after receipt of information with respect to any serious adverse
event (as defined by the ICH Harmonized Tripartite Guideline on Clinical Safety
Data Management), directly or indirectly attributable to the use or application
of Development Candidate or Drug Product.
     9.3. Third Party Actions.
     (a) To Myogen’s knowledge, the exercise of the rights by NIBRI hereunder
will not result in the infringement of valid patents of Third Parties.
Nevertheless, each party will promptly notify the other in the event any
relevant Third Party patents come to its notice. Neither party gives a warranty
to the other regarding the infringement of Third Party rights by the
development, manufacture, use or sale of the Development Candidate or the
practice of the Myogen Technology or the NIBRI Technology, and gives no
indemnity against costs, damages, expenses or other losses arising out of
proceedings brought against the other party or any other Person by any Third
Party. In the event NIBRI is sued for infringement of any rights of any Third
Party in the course of its development, manufacture, marketing and sale of
Development Candidate in the Cardiac Field or its use of Myogen Technology in
connection therewith, Myogen shall extend to NIBRI, at no charge, good faith
assistance and support in defending such action, and may participate in the
conduct of the suit at its own expense, but shall otherwise be under no
obligation in respect thereof. Legal expenses and fees arising from such a legal
action shall be paid by NIBRI.
     (b) In the event that the development of Development Candidate or the sale
of a Drug Product for indications within the Cardiac Field in any country
necessarily involves working within the scope of a Third Party’s patent, which
would otherwise be infringed by the practice of a Myogen Patent in connection
with such development or sale, then Myogen will use reasonable efforts to obtain
required licenses under the Third Party’s patents, under terms reasonably
acceptable to both Myogen and NIBRI, and the terms of Section 4.5(c) hereof
shall apply; provided that neither Myogen nor NIBRI shall
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be required to accept any license which carries a financial obligation which is
materially in excess of the range of financial obligations customarily
associated with comparable non-exclusive licenses. If the terms of a required
license under a Third Party patent do not meet the foregoing requirements and
Myogen therefore elects not to assume any financial obligation, NIBRI may
nonetheless elect to obtain the license, to continue sales of Drug Product in
such country and to pay, itself, any amounts due under such license. If the
required license is either unavailable or its terms are unacceptable both to
Myogen and to NIBRI, then NIBRI may elect in its sole discretion to discontinue
sales of the Drug Product in such country or at its sole expense to undertake
the defense of a patent infringement action or the prosecution of a declaratory
judgment action with respect to the Third Party patents.
     9.4. Force Majeure. Neither party will be in breach hereof by reason of its
delay in the performance of or failure to perform any of its obligations
hereunder, if that delay or failure is caused by strikes, acts of God or the
public enemy, riots, incendiaries, interference by civil or military
authorities, compliance with governmental priorities for materials, or any fault
beyond its control or without its fault or negligence.
     9.5. Waiver. Any waiver by either party of the breach of any term or
condition of this Agreement will not be considered as a waiver of any subsequent
breach of the same or any other term or condition hereof.
     9.6. Severability. Should one or more provision of this Agreement be or
become invalid, then the parties hereto shall attempt in good faith to agree
upon valid provisions in substitution for the invalid provisions, which in their
economic effect come so close to the invalid provisions that it can be
reasonably assumed that the parties would have accepted this Agreement with
those new provisions. If the parties are unable to agree on such valid
provisions, the invalidity of such one or more provisions of this Agreement
shall nevertheless not affect the validity of this Agreement as a whole, unless
the invalid provisions are of such essential importance for this Agreement that
it may be reasonably presumed that the parties would not have entered into this
Agreement without the invalid provisions.
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     9.7. Government Acts. In the event that any act, regulation, directive, or
law of a government within the Territory, including its departments, agencies or
courts, should make impossible or prohibit, restrain, modify or limit any
material act or obligation of NIBRI or Myogen under this Agreement, the party,
if any, not so affected, shall have the right, at its option, to suspend or
terminate this Agreement as to such country, if good faith negotiations between
the parties to make such modifications herein as may be necessary to fairly
address the impact thereof, after a reasonable period of time are not successful
in producing mutually acceptable modifications to this Agreement.
     9.8. Government Approvals. NIBRI or its sublicensees will obtain any
government approval required in the Territory to enable this Agreement to become
effective, or to enable any payment hereunder to be made, or any other
obligation hereunder to be observed or performed. NIBRI will keep Myogen
informed of progress in obtaining any such government approval, and Myogen will
cooperate with NIBRI in any such efforts.
     9.9. Export Controls. This Agreement is made subject to any restrictions
concerning the export of Development Candidate or Myogen Technology from the
United States that may be imposed upon or related to either party to this
Agreement from time to time by the Government of the United States. Furthermore,
NIBRI will not export, directly or indirectly, any Myogen Technology or any
Development Candidate utilizing such Myogen Technology to any countries for
which the United States Government or any agency thereof at the time of export
requires an export license or other governmental approval, without first
obtaining the written consent to do so (of which NIBRI will promptly inform
Myogen) from the Department of Commerce or other agency of the United States
Government when required by applicable statute or regulation.
     9.10. Assignment. NIBRI may assign this Agreement, without the consent of
Myogen: (a) to any of its Affiliates; or (b) in connection with the transfer or
sale of all or substantially all of its assets or business or in the event of
its merger or consolidation with another company. Myogen may not assign or
otherwise transfer this Agreement or any of its rights or obligations under this
Agreement without the prior written consent of NIBRI, except, that Myogen may
assign this Agreement to any Person in connection with a transaction which
results in the sale, merger, consolidation, transfer, or other reorganization of
Myogen in which substantially all of the assets of Myogen are transferred or in
which the holders of Myogen’s capital stock
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immediately prior to the transaction hold less than a majority of the capital
stock of the surviving entity after the transaction provided that should NIBRI
demonstrate with reasonable certainty that the proposed assignee is a
significant competitor of NIBRI or its Affiliates and Myogen’s proposed
transaction would cause a material adverse effect on the commercial potential of
the Drug Product, then NIBRI will provide to Myogen written notice of such
determination within [..**..] specifying the reasons for such determination and,
at NIBRI’s election, the option to co-fund and co-promote Drug Products as set
forth in Section 3.5 shall be unavailable to Myogen and such assignee. Any
purported assignment in contravention of this Section 9.10 shall, at the option
of the nonassigning party, be null and void and of no effect. No assignment
shall release either party from responsibility for the performance of any
accrued obligation of such party hereunder. This Agreement shall be binding upon
and enforceable against the successor to or any permitted assignees from either
of the parties hereto.
     9.11. Counterparts. This Agreement may be executed in duplicate, each of
which shall be deemed to be original and both of which shall constitute one and
the same Agreement.
     9.12. No Agency. Nothing in this Agreement shall be deemed to create an
agency, joint venture, amalgamation, partnership or similar relationship between
Myogen and NIBRI Notwithstanding any of the provisions of this Agreement,
neither party to this Agreement shall at any time enter into, incur, or hold
itself out to Third Parties as having authority to enter into or incur, on
behalf of the other party, any commitment, expense, or liability whatsoever, and
all contracts, expenses and liabilities in connection with or relating to the
obligations of each party under this Agreement shall be made, paid, and
undertaken exclusively by such party on its own behalf and not as an agent or
representative of the other.
     9.13. Notice. All communications between the parties with respect to any of
the provisions of this Agreement will be sent to the addresses set out below or
to other addresses as may be designated by one party to the other by notice
pursuant hereto, by prepaid certified mail (which shall be deemed received by
the other party on the seventh business day following deposit in the mails), or
by facsimile transmission or other electronic means of communication (which
shall be deemed received when transmitted), with confirmation by first class
letter, postage pre-paid, given by the close of business on or before the next
following business day:
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if to NIBRI, at:
Novartis Institutes for BioMedical Research, Inc.
400 Technology Square
Cambridge, Massachusetts 02139
Attention: Robert L. Thompson, Vice President and General Counsel
Fax: (617) 871-3354
if to Myogen, at:
Myogen, Inc.
7575 West 103rd Avenue
Westminster, Colorado 80021
Attention: J. William Freytag, President and Chief Executive Officer
Fax: (303) 410-6667
with a copy to:
Myogen, Inc.
7575 W. 103rd Avenue
Westminster, Colorado 80021
Attention: Andrew D. Dickinson, Vice President and General Counsel
Fax: (303) 410-3350
     9.14. Headings. The paragraph headings are for convenience only and will
not be deemed to affect in any way the language of the provisions to which they
refer.
     9.15. Authority. The undersigned represent that they are authorized to sign
this Agreement on behalf of the parties hereto. The parties each represent that
no provision of this Agreement will violate any other agreement that a party may
have with any other person or company. Each party has relied on that
representation in entering into this Agreement.
     9.16. Entire Agreement. This Agreement contains the entire understanding of
the parties relating to the matters referred to herein, and may only be amended
by a written document, duly executed on behalf of the respective parties.
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                      MYOGEN, INC.    
 
               
 
  By:                          
 
                    Title:                      
 
                    Date of Signature:    
 
               
 
                    NOVARTIS INSTITUTES FOR BIOMEDICAL         RESEARCH, INC.  
 
 
               
 
  By:                          
 
                    Title:                      
 
                    Date of Signature:    
 
               

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Schedule 1.38
Listed Countries
 

         
Albania AL
  Algeria DZ   Antigua and Barbuda AG
Argentina
  Armenia AM   Australia AU
Austria AT
  Azerbaijan AZ   Barbados BB
Belarus BY
  Belgium BE   Belize BZ
Benin BJ
  Bosnia and Herzegovina BA   Botswana BW
Brazil BR
  Bulgaria BG   Burkina Faso BF
Cameroon CM
  Canada CA   Central African Republic CF
Chad TD
  Chile   China CN
Colombia CO
  Congo CG   Costa Rica CR
Côte d’Ivoire CI
  Croatia HR   Cuba CU
Cyprus CY
  Czech Republic CZ   Democratic People’s Republic of Korea KP
Denmark DK
  Dominica DM   Ecuador EC
Egypt EG
  Equatorial Guinea GQ   Estonia EE
Finland FI 2
  France FR   Gabon GA
Gambia GM
  Georgia GE   Germany DE
Ghana GH
  Greece GR   Grenada GD
Guinea GN
  Guinea-Bissau GW   Hong Kong
Hungary HU
  Iceland IS   India IN
Indonesia ID
  Ireland IE   Israel IL
Italy IT
  Japan JP   Kazakhstan KZ 1
Kenya KE
  Kyrgyzstan KG   Latvia LV
Lesotho LS
  Liberia LR   Liechtenstein LI
Lithuania LT
  Luxembourg LU   Madagascar MG
Malawi MW
  Malaysia   Mali ML
Mauritania MR
  Mexico MX   Monaco MC
Mongolia MN
  Morocco MA   Mozambique MZ
Netherlands NL 4
  New Zealand NZ   Nicaragua NI
Niger NE
  Norway NO   Oman OM
Pakistan
  Papua New Guinea PG   Peru
Philippines PH
  Poland PL   Portugal PT
Republic of Korea KR
  Republic of Moldova MD   Romania RO
Russian Federation RU
  Saint Lucia LC   Saint Vincent and the Grenadines VC
Saudi Arabia
  Senegal SN   Serbia and Montenegro CS
Seychelles SC
  Sierra Leone SL   Singapore SG
Slovakia SK
  Slovenia SI   South Africa ZA
Spain ES
  Sri Lanka LK   Sudan SD
Swaziland SZ
  Sweden SE   Switzerland CH
Syrian Arab Republic SY
  Taiwan   Tajikistan TJ
Thailand
  The former Yugoslav Republic of Macedonia MK   Togo TG
Trinidad and Tobago TT
  Tunisia TN   Turkey TR
Turkmenistan TM
  Uganda UG   Ukraine UA
United Arab Emirates AE
  United Kingdom GB   United Republic of Tanzania TZ
United States of America US
  Uruguay   Uzbekistan UZ
Venezuela
  Viet Nam VN   Zambia ZM
Zimbabwe ZW
       

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Schedule 1.42
Myogen Patents

                          Schedule 1.42 Myogen Patents PATENTS   Filing Date  
App. No.   Country   Pat. No.   Issue Date   Subject Matter
MYOG:004-USD1
  4/25/2000   09/558,472   U.S.           Alpha Myosin Heavy Chain Gene Therapy
 
                       
MYOG:004-USD2
  10/1/2001   09/969,086   U.S.   7,049,066   5/23/2006   Alpha Myosin Heavy
Chain Therapeutic/Screening
 
                       
MYOG:004-USD3
  2/25/2005   11/067,502   U.S.           Alpha Myosin Heavy Chain Treatment
 
                       
MYOG:004-WO
  1/30/1998   PCT/US98/01983   PCT           Alpha Myosin Heavy Chain
 
                       
MYOG:004-CA
  7/29/1999   2,278,465   Canada           Alpha Myosin Heavy Chain
 
                       
MYOG:004-EP
  7/30/1999   98906089.2   Europe           Alpha Myosin Heavy Chain
 
                       
MYOG:004-JP
  7/30/1999   10-533182   Japan           Alpha Myosin Heavy Chain
 
                       
MYOG:005-US
  4/1/1998   09/053,293   U.S.   6,218,597   4/17/2001   Transgenic mice
w/cardiac specific promoters
 
                       
MYOG:006-US
  9/26/1997   08/938,105   U.S.   6,353,151   3/5/2002   Transgeneic alpha
myosin
 
                       
MYOG:006-EP
  5/24/1999   97943597.1   Europe           Alpha Myosin Transgenes
 
                       
MYOG:007-US
  5/26/1998   09/047,755   U.S.   6,203,776   3/20/2001   Methods for
identifying adrenergic receptors
 
                       
MYOG:013-US
  6/19/1998   09/100,497   U.S.   5,998,458   12/7/1999   Positive inotrope +
beta adrenergic receptor antagonist
 
                       
MYOG:013-WO
  6/24/1998   PCT/US98/13442   PCT           Positive inotrope + beta adrenergic
receptor antagonist
 
                       
MYOG:013-AU
  1/6/2000   81740/98   Australia   731,656   7/19/2001   Positive inotrope +
beta adrenergic receptor antagonist
 
                       
MYOG:013-CA
  12/23/1999   2,295,094   Canada           Positive inotrope + beta adrenergic
receptor antagonist
 
                       
MYOG:013-EP
  1/25/2000   198,931,687   Europe           Positive inotrope + beta adrenergic
receptor antagonist
 
                       
MYOG:013-JP
  12/27/1999   11-505056   Japan           Positive inotrope + beta adrenergic
receptor antagonist
 
                       
MYOG:020-US
  10/15/1998   09/173,798   U.S.   6,201,165   3/13/2001   CamKIIa,
CaMKIV,p38,MKK6,anf,bnp,beta myosin transgenes
 
                       
MYOG:020-WO
  10/16/1998   PCT/US98/21988   PCT           CamKIIa,
CaMKIV,p38,MKK6,anf,bnp,beta myosin transgenes
 
                       
MYOG:020-AU
  4/16/2000   10992/99   Australia   755428   8/16/2002   CamKIIa,
CaMKIV,p38,MKK6,anf,bnp,beta myosin transgenes
 
                       
MYOG:020-CA
  4/16/2000   2,315,244   Canada           CamKIIa, CaMKIV,p38,MKK6,anf,bnp,beta
myosin transgenes
 
                       
MYOG:020-EP
  4/16/2000   98953672.7   Europe           CamKIIa,
CaMKIV,p38,MKK6,anf,bnp,beta myosin transgenes
 
                       
MYOG:020-JP
  4/16/2000   2000-516026   Japan           CamKIIa,
CaMKIV,p38,MKK6,anf,bnp,beta myosin transgenes
 
                       
MYOG:020-MX
  4/14/2000   0003678   Mexico           CamKIIa, CaMKIV,p38,MKK6,anf,bnp,beta
myosin transgenes
 
                       
MYOG:023-US
  10/15/1998   09/173,795   U.S.   6,673,768   1/6/2004   Calcineurin Therapies
 
                       
MYOG:024-US
  11/10/1999   09/438,075   U.S.   6,372,957   4/16/2002   MEF2 methods of
treatment
 
                       
MYOG:024-USC1
  1/9/2002   10/043,658   U.S.           MEF2 screening methods
 
                       
MYOG:024-WO
  11/10/1999   PCT/US99/26725   PCT           MEF2
 
                       
MYOG:024-CA
  5/7/2001   2,350,086   Canada           MEF2
 
                       
MYOG:024-EP
  5/21/2001   99971848.9   Europe           MEF2
 
                       
MYOG:024-JP
  5/10/2001   2000-581187   Japan           MEF2
 
                       
MYOG:025-US
  10/15/1998   09/173,799   U.S.   6,657,104   12/2/2003   Calcineurin
transgenics
 
                       
MYOG:026-US
  8/20/2000   09/643,206   U.S.   6,632,628   8/20/2000   HDAC screening and
treatment
 
                       
MYOG:026-USD1
  8/20/2003   10/637,403   U.S.           HDAC transgenics
 
                       
MYOG:026-WO
  8/20/2000   PCT/US00/22958   PCT           Class II HDACs
 
                       
MYOG:026-CA
  2/14/2002   2,382,045   Canada           Class II HDACs
 
                       
MYOG:026-EP
  3/13/2002   00955805.7   Europe           Class II HDACs
 
                       
MYOG:026-JP
  2/19/2002   2001-518892   Japan           Class II HDACs
 
                       
 
                       
MYOG:028-US
  7/18/2001   09/908,988   U.S.   6,740,751   5/25/2004   Muscle Ring Finger
Proteins (MURFS) Screening and Treatment
 
                       
MYOG:028-USD1
  2/10/2004   10/775,627   U.S.   7,005,512   2/28/2006   Muscle Ring Finger
Proteins (MURFS) Screening and Treatment
 
                       
MYOG:028-USD2
  2/10/2004   10/775,649   U.S.   issue fee   paid   Muscle Ring Finger Proteins
(MURFS)
 
                       
MYOG:029-US
  4/16/1998   09/061,417   U.S.           NF-AT3 inhibitors
 
                       
MYOG:029-WO
  10/16/1998   PCT/US98/21845   PCT           NF-AT3 inhibitors
 
                       
MYOG:029-AU
  10/15/1998   98058/98   Australia   748334   9/12/2002   NF-AT3 inhibitors
 
                       
MYOG:029-CA
  4/10/2000   2,306,448   Canada           NF-AT3 inhibitors
 
                       
MYOG:029-EP
  5/16/2000   9895233.7   Europe           NF-AT3 inhibitors
 
                       
MYOG:029-JP
  4/17/2000   2000-516024   Japan           NF-AT3 inhibitors

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                          Schedule 1.42 Myogen Patents PATENTS   Filing Date  
App. No.   Country   Pat. No.   Issue Date   Subject Matter
MYOG:034-US
  9/26/2002   10/256,221   U.S.   6,707,686   3/16/2004   HDAC Inhibitors
 
                       
MYOG:034-USC1
  3/16/2004   10/801,985   U.S.   6,946,441   9/20/2005   Inhibiting HDACs
 
                       
MYOG:034-USC2
  7/26/2005   11/190,074   U.S.           Inhibiting HDACs
 
                       
MYOG:034-USC3
  8/30/2005   11/215,844   U.S.           Inhibiting HDACs
 
                       
MYOG:034-EP
  9/27/2001   02/021678.8   Europe   1,297,851   1/26/2005   Inhibiting HDACs
 
                       
MYOG:034-EPD1
  1/25/2005   5001443   Europe           Inhibiting HDACs
 
                       
MYOG:034-JP
  9/27/2001   2002-284313   Japan           Inhibiting HDACs
 
                       
MYOG:035-US
  1/21/2003   10/348,598   U.S.           Hypertrophic Cell Line
 
                       
MYOG:036-US
  2/13/2001   09/782,953   U.S.           MCIP’s screening, treatment,
transgenics, antibodies
 
                       
MYOG:036-WO
  2/13/2001   PCT/US01/21662   PCT           MCIP’s screening, treatment,
transgenics, antibodies
 
                       
MYOG:036-CA
  1/24/2003   2,415,967   Canada           MCIP’s screening, treatment,
transgenics, antibodies
 
                       
MYOG:036-EP
  2/5/2003   1952568.2   Europe           MCIP’s screening, treatment,
transgenics, antibodies
 
                       
MYOG:036-JP
  12/26/2002   2002-509354   Japan           MCIP’s screening, treatment,
transgenics, antibodies
 
                       
MYOG:037-US
  8/20/2003   10/644,659   U.S.           STARS screening, treatment,
transgenics, antibodies
 
                       
MYOG:044-US
  5/21/2003   10/848,820   U.S.           PKD (HDAC Kinase I)
 
                       
MYOG:044-WO
  5/21/2003   PCT/US04/015715   PCT           PKD (HDAC Kinase I)
 
                       
MYOG:044-AU
  5/21/2003   2004249114   Australia           PKD (HDAC Kinase I)
 
                       
MYOG:044-BR
  5/21/2003       Brazil           PKD (HDAC Kinase I)
 
                       
MYOG:044-CA
  5/21/2003       Canada           PKD (HDAC Kinase I)
 
                       
MYOG:044-CN
  5/21/2003       China           PKD (HDAC Kinase I)
 
                       
MYOG:044-EP
  5/21/2003       Europe           PKD (HDAC Kinase I)
 
                       
MYOG:044-IN
  5/21/2003       India           PKD (HDAC Kinase I)
 
                       
MYOG:044-JP
  5/21/2003       Japan           PKD (HDAC Kinase I)
 
                       
MYOG:044-MX
  5/21/2003       Mexico           PKD (HDAC Kinase I)
 
                       
MYOG:045-US
  11/3/2004   10/980,612   U.S.           Alpha myocin modulating compound ‘R’
enatiomer
 
                       
MYOG:045-WO
  11/3/2004   PCT/US04/036569   PCT           Alpha myocin modulating compound
‘R’ enatiomer
 
                       
MYOG:046-US
  11/3/2004   10/980,605   U.S.           Alpha myocin modulating compound ‘S’
enatiomer
 
                       
MYOG:046-US
  11/3/2004   PCT/US04/036568   PCT           Alpha myocin modulating compound
‘S’ enatiomer
 
                       
MYOG:047-US
  11/13/2004   10/988,192   U.S.           TRP Channel
 
                       
MYOG:047-WO
  11/13/2004   PCT/US04/037858   PCT           TRP Channel
 
                       
MYOG:048-US
  12/23/2004   11/018,426   U.S.           5-HT2 receptors
 
                       
MYOG:048-WO
  12/23/2004   PCT/US04/042922   PCT           5-HT2 receptors
 
                       
MYOG:049-US
  12/23/2004   11/018,383   U.S.           5-HT2 receptor binding compounds
 
                       
MYOG:049-WO
  12/23/2004   PCT/US04/042921   PCT           5-HT2 receptor binding compounds
 
                       
MYOG:050-US
  2/2/2005   11/049,630   U.S.           PRK (HDAC kinase II)
 
                       
MYOG:050-WO
  2/2/2005   PCT/US05/002808   PCT           PRK (HDAC kinase II)
 
                       
MYOG:054-US
  4/5/2005   11/099,417   U.S.           Nuclear export
 
                       
MYOG:054-WO
  4/5/2005   PCT/US05/011264   PCT           Nuclear export
 
                       
MYOG:057-WO
  9/19/2005   PCT/US05/033461   PCT           P38 MCIP
 
                       
MYOG:058-US
  8/15/2005   11/203,828   U.S.           Ku
 
                       
MYOG:060-USP1
  7/13/2005   60/699,189   U.S.           Proteasome inhibitors
 
                       
MYOG:062-USP1
  11/18/2005   60/737,952   U.S.           CAMKII/Calpain/HDACs
 
                       
UTSD:803-US
  5/30/2002   10/159,971   U.S.   6,924,415   8/2/2005   MEK5
 
                       
USTD:803-USD1
  4/21/2005   11/089,425   U.S.           MEK5
 
                       
UTSD:803-CA
  5/29/2002   2,384,907   Canada           MEK5
 
                       
UTSD:803-JP
  11/22/2001   2001-358595   Japan           MEK5
 
                       
USTD:1771-USP1
  5/3/2006   not yet assigned   U.S.           CAMTA

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