LICENSE AGREEMENT
Exhibit
10.1
CONFIDENTIAL
TREATMENT REQUESTED. Confidential portions of this document have been redacted
and have been separately filed with the Commission.
This
Agreement made and entered into as of the 29th
day of
September 2006 (the “Effective
Date”)
by and
between Kyowa
Hakko Kogyo Co., Ltd.,
a
Japanese corporation having its principal office at 0-0-0 Xxxxxxxxx, Xxxxxxx-xx,
Xxxxx, 000-0000, Xxxxx (hereinafter referred to as “KYOWA”)
and
KERYX
Biopharmaceuticals, Inc.,
a
Delaware corporation having its principal office at 000 Xxxxxxxxx Xxxxxx,
00xx
Xxxxx,
Xxx Xxxx, Xxx Xxxx 00000, the United States of America (hereinafter referred
to
as “KERYX”).
KYOWA
and KERYX may be individually referred to as a “Party”
or
collectively referred to as “Parties”.
WITNESSETH
WHEREAS,
KYOWA
has developed the Compound, and acquired certain intellectual property rights
relating to such Compound;
WHEREAS,
KYOWA
has entered into a clinical trials agreement with the National Cancer Institute
under which development of the Compound has been conducted;
WHEREAS,
KERYX
wishes to obtain a right and license from KYOWA to such intellectual property
rights in the Field and the KERYX Territory;
WHEREAS,
KYOWA
is
willing to grant such right and license to KERYX, and KERYX is willing to accept
such right and license;
NOW,
THEREFORE,
the
Parties agree as follows:
SECTION
1. DEFINITIONS
In
this
Agreement the following terms shall have the following meanings:
| 1.1. |
“Affiliates”
shall mean, with respect to either Party, any business entity
which
controls, is controlled by, or is under common control with such
Party. A
corporation or non-corporate business entity shall be regarded
as in
control of another corporation if it owns or directly or indirectly
controls more than fifty percent (50%) of the voting stock of
the other
corporation.
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1.2.
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“Annual
Payment” shall
have the meaning set forth in Section
8.6.
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1.3.
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“Approval”
shall mean the technical, medical and scientific license, registrations,
authorizations and approvals of any national, supra-national, regional,
state or local regulatory agency, necessary for the development,
testing,
commercial manufacture, distribution, marketing, promotion, offer
for
sale, use, import, export and sale of a
Product.
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1.4.
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“Authority”
shall mean a governmental authority having jurisdiction over import,
export, development, manufacture, marketing or sales of pharmaceutical
products, not limited to the FDA.
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1.5.
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“Business
Day”
shall mean a day other than a Saturday, Sunday, national or bank
holiday
in Japan or the United States of
America.
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1.6.
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“Combination
Product” shall
mean any pharmaceutical product in finished form which contains the
Compound and one or more active pharmaceutical ingredients other
than the
Compound, which is used in the Field.
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1.7.
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“Combination
Therapy”
shall mean the use of Compound as an active pharmaceutical ingredient
in
the Product, which is used with other pharmaceutical products in
the
Field.
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1.8.
|
“Compound”
shall
mean KW-2401 (UCN-01), the chemical structure of which is specified
in
Exhibit 1 hereof.
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1.9.
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“Control”,
or
“Controlled”
means, with respect to a particular information or intellectual property
right, (i) that the Party owns and has the ability to grant to the
other
Party the licenses to such item provided for herein, without violating
the
terms of any agreement or other arrangement with any Third Party,
and/or
(ii) that the Party has a license to such item and has the ability
to
grant to the other Party the licensees to such item provided for
herein,
without violating the terms of any agreement or other arrangement
with any
Third Party.
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1.10.
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“Data”
shall
mean and include all data relating to the Compound and the Product,
and
all chemistry, manufacturing and control data relating to the development
and manufacture of the Compound and the Product, results of pre-clinical
and clinical studies and all other documentation containing or embodying
any pre-clinical, clinical and chemistry and manufacturing and control
data relating to any application for any Approval for a Product.
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1.11.
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“Development
Plan”
shall mean a written plan to be prepared by KERYX for all activities
that
are reasonably required to obtain MAA and/or NDA for the Product
in the
KERYX Territory. The Development Plan as of the Effective Date is
attached
hereto as Exhibit 5.
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1.12.
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“EMEA”
shall
mean the European Agency for the Evaluation of Medicinal Products
in the
European Union.
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2
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1.13.
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“Expiration”
of
a patent shall mean the expiration, abandonment or cancellation of
all of
the claims of the patent which are being practiced, or, the declaration
of
invalidity or non-enforceability of all the claims of the patent
being
practiced by a court or other governmental authority of competent
jurisdiction (including final rejection in re-examination or re-issue
proceedings) for which the period to file an appeal has expired,
and from
which no further appeal has been taken during the applicable appeal
period
or is not allowed to be taken against such
declaration.
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1.14.
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“FDA”
shall mean the Food and Drug Administration of the United States
Department of Health and Human
Services.
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1.15.
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“Field”
shall mean the treatment and prevention of any diseases in human
beings.
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1.16.
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“Gross
Sales”
of
the Product made by KERYX or the Sublicensees shall mean the aggregate
total amount of the invoice prices charged for such Product in Product
sales, computed in respect of invoice applicable to the transfer
between
parties constituting an arm’s-length sales transaction. Sales, transfer or
other disposition of the Product among KERYX, the Sublicensees and
their
respective Affiliates shall not be considered at-arm’s-length.
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1.17.
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“Improvement”
shall mean any invention and/or Know-How made or developed after
the
Effective Date, whether patentable or not, that improves any
characteristics or use of the Compound and/or the Product, including
but
not be limited to, the use of the Compound in Combination Product
or in
Combination Therapy, or any new Indications of the
Product.
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1.18.
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“Indication”
shall mean a recognized disease or condition, sign or symptom of
a disease
or condition, or symptom associated with the disease and symptom
for which
use of a Product is indicated. For purposes of this Agreement and
the
payment of milestones, all cancer disease, conditions or symptoms
shall
collectively qualify as one
indication.
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1.19.
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“KERYX
Data”
shall mean any Data Controlled by KERYX, which has been developed
or
acquired by KERYX or the Sublicensees during the Term. KERYX Data
shall
include, but not be limited to, the Data regarding KERYX Improvements.
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1.20.
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“KERYX
Improvements”
shall mean any Improvements Controlled by KERYX, which have been
developed
by or otherwise brought under the Control of KERYX or the Sublicensees
during the Term.
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1.21.
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“KERYX
Territory”
shall mean any and all countries of the world other than the KYOWA
Territory.
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1.22.
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“Know-How”
shall mean any technical and other information, whether patentable
or not,
including without limitation technology, experience, formulae, concepts,
discoveries, trade secrets, inventions, modifications, improvements,
data,
results, designs, formulae, ideas, analyses, methods, techniques,
assays,
research plans, procedures, tests, processes (including manufacturing
processes, specifications and techniques), laboratory records, chemical,
pharmacological, toxicological, clinical, analytical and quality
control
data, reports, summaries, and information contained in submissions
to, and
information from, regulatory authorities which are not generally
known.
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3
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1.23.
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“KYOWA
Data”
shall mean any Data in the Field which has been developed or acquired
by
KYOWA and under KYOWA’s Control as of the Effective Date or which has been
developed by or brought under the Control of KYOWA during the Term.
KYOWA
Data shall include, but not limited to, any documents filed with
regulatory agencies and the Data regarding KYOWA Improvements. For
clarity, KYOWA Data shall not include the NCI
Data.
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1.24.
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“KYOWA
Improvements”
shall mean any Improvements in the Field Controlled by KYOWA, which
have
been developed by or otherwise brought under the Control of KYOWA
during
the Term. For clarity, KYOWA Improvements shall not include the NCI
Data.
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1.25.
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“KYOWA
Know-How”
shall mean any Know-How relating to the Compound in the Field Controlled
by KYOWA and KYOWA Data which has been developed or acquired by KYOWA
as
of the Effective Date.
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1.26.
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“KYOWA
Patent Rights A”
shall mean the Patent Rights in the Field owned or Controlled by
KYOWA as
of the Effective Date relating to the Compound as listed in Exhibit
2, and
any additional Patent Rights in the Field to which KYOWA acquires
rights
during the Term , which pertain in any way to the Compound or the
Product.
Exhibit 2 shall be updated from time to time by KYOWA.
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1.27.
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“KYOWA
Patent Rights B”
shall mean the Patent Rights in the Field owned or Controlled by
KYOWA as
of the Effective Date as listed in Exhibit 3, and any additional
Patent
Rights in the Field to which KYOWA acquires rights during the Term,
which
pertain in any way to the subject matter claimed or disclosed in
the
Patent Rights listed in Exhibit 3. Exhibit 3 shall be updated from
time to
time by KYOWA.
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1.28.
|
“KYOWA
Patent Rights”
shall mean any Patent Rights of KYOWA Patent Rights A and KYOWA Patent
Rights B.
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1.29.
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“KYOWA
Territory” shall
mean Japan.
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1.30.
|
“Launch
Date” shall
mean the date set forth in Section
8.4.
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1.31.
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“Lonza”
shall
mean Lonza Ltd. headquartered at Basel,
Switzerland.
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1.32.
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“MAA”
shall mean the Market Authorization Application to be filed with
the
EMEA.
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1.33.
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“Major
Countries” shall
mean the United Kingdom, Germany, France, Italy, Spain and
Switzerland.
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1.34.
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“NCI”
shall mean National Cancer
Institute.
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1.35.
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“NCI
Agreement”
shall mean the Clinical Trials Agreement executed between KYOWA and
NCI on
September 24, 1999 including its amendments
thereafter.
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1.36.
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“NCI
Data”
shall mean the Data which has been developed or acquired by NCI under
NCI
Agreement.
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1.37.
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“NDA”
shall mean the new drug application to be filed with the
FDA.
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1.38.
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“Net
Sales” shall
mean the Gross Sales of the Product made by KERYX or the Sublicensees,
less the following deductible items to the extent that they are documented
on the applicable invoice or other related document and have in fact
been
paid or credited in relation to sales of such
Product:
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1.
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the
cost of transportation and
insurance;
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2.
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the
cost of rebates, and allowances
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3.
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the
sum of trade, quantity and cash
discounts;
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4.
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the
cost of refunds as cash, credit or free goods supplied due to price
reduction, including retroactive price reduction, or billing
errors;
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5.
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the
cost of refunds as cash, credit or free goods supplied in compensation
for
the Product damaged, rejected, returned or recalled;
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6.
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the
sum of taxes, tariffs, customs duties and other governmental charges
including mandated credits, refunds and rebates paid with respect
to such
sales, however, excluding income or franchise taxes of any kind;
and
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7.
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all
other reasonable and customary allowances and adjustments actually
credited to customers.
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The
Net
Sales shall be calculated according to the generally accepted accounting
principles consistently applied in the United States of America. In the case
the
Product is a Combination Product, the Net Sales of the Combination Product
shall
be the Gross Sales thereof (after the above deductible items) multiplied by
the
fraction which the Parties determine by mutual written agreement, estimating
each relative contribution in value that the Compound and other active
pharmaceutical ingredients contained in such Combination Product would make
to
the total value of such Combination Product, as well as, the cost of
development, the cost of goods and other relevant information with respect
to
such Combination Product, provided that such fraction should not go below one
half (0.5).
The
sale
of a Product between KERYX and any of its Sublicensees solely for the research
and testing of such Product shall be excluded from the computation of Net
Sales.
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1.39.
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“Patent
Rights”
shall mean all issued patents and patent applications, certificates
of
invention, or applications for certificates of invention, together
with
any extensions, registrations, provisionals, divisionals, continuations,
continuations-in-part (to the extent the claims in such
continuation-in-part application are directed to subject matter
specifically described in such prior patent application), and patents
issuing therefrom, reissues, divisions, continuations, or
continuations-in-part, reexaminations, substitutions, renewals,
restorations, additions, registrations, as well as extensions and
supplementary protection certificates based thereon, and any government
Approvals or authorizations relating
thereto.
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1.40.
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“Product”
shall
mean any pharmaceutical product in finished form which contains the
Compound as an active pharmaceutical ingredient. For avoidance of
doubt,
the Combination Product is a
Product.
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| 1.41. |
“Royalty”
or“Royalties”
shall mean the royalties set forth in Sections 8.3, 8.4 and
8.5.
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| 1.42. |
“SPC”
shall mean the supplementary protection certificates in Europe and
any
similar rights elsewhere in the
world.
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| 1.43. |
“Strain”
shall mean the strain which produces the starting material (staurosporine)
for the Compound. The identification of the strain and the quantity
to be
transferred is set forth in Exhibit
4.
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| 1.44. |
“Sublicensee”
shall mean any Third Party to which KERYX grants a sublicense under
the
KYOWA Patent Rights and the KYOWA Know-How according to Section
4.
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| 1.45. |
“Term”
shall
mean the term set forth in Section
27.1.
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| 1.46. |
“Third
Party” shall
mean any entity other than KYOWA, KERYX and their respective Affiliates.
.
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SECTION
2.
INTERPRETATION
In
this
Agreement:
| 2.1. |
Headings
and titles are inserted for convenience only and shall not affect
the
interpretation hereof;
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| 2.2. |
Unless
the context requires otherwise, neither singular nor plural of a
word
shall not affect the interpretation
hereof;
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SECTION
3.
LICENSE
| 3.1. |
KYOWA
hereby grants to KERYX an exclusive right and license, with the right
to
sublicense, under the KYOWA Patent Rights
A
and KYOWA Patent Rights B (subject to Sections 8.6 and 27.3) and
the KYOWA
Know-How to make, have made, use, have used, sell, offer for sale,
have
sold and distribute the Product in the KERYX Territory within the
Field.
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| 3.2. |
KYOWA
hereby grants to KERYX an exclusive right and license, with the right
to
sublicense, under the KYOWA Patent Rights A and KYOWA Patent Rights
B
(subject to Sections 8.6 and 27.3) and the KYOWA Know-How to make
and have
made, use and have used the Compound in the KERYX Territory within
the
Field.
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| 3.3. |
KYOWA
hereby grants to KERYX an exclusive right and license, with the right
to
sublicense, under the KYOWA Improvements to make, have made, use,
have
used, sell, have sold, offer for sale and distribute the Product
in the
KERYX Territory within the Field.
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| 3.4. |
KYOWA
hereby grants to KERYX an exclusive right and license, with the right
to
sublicense, under the KYOWA Improvements to make and have made, use
and
have used the Compound in the KERYX Territory within the Field.
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| 3.5. |
KYOWA
hereby grants to KERYX a non-exclusive right and license, with the
right
to sublicense in the KERYX Territory to use, have used the Strain
in order
to make, or have made the Compound within the
Field.
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| 3.6. |
Notwithstanding
the above Sections 3.1 to 3.5, KYOWA reserves the right to make and
have
made the Compound and/or the Product in the KERYX Territory for the
sole
purpose of developing and marketing the Product in the KYOWA
Territory.
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| 3.7 |
Except
as otherwise expressly provided in this Agreement, KYOWA hereby grants
to
KERYX the right to file with the appropriate Authorities all applications
and other materials needed to obtain the Approvals necessary to implement
this Agreement and protect the respective rights of the Parties,
and KYOWA
shall provide KERYX with reasonable assistance in such
filings.
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SECTION
4.
DILIGENCE
| 4.1 |
KERYX
shall make and shall have Sublicensees make commercially reasonable
efforts to develop, to manufacture, to market, and to sell the Product
within the KERYX Territory. When KERYX makes any changes to the
Development Plan, KERYX shall notify KYOWA and update Exhibit 5
accordingly. By the end of the month immediately following the month
of
the yearly anniversary of the Effective Date, KERYX shall provide
KYOWA
with a written report outlining such efforts made by KERYX and the
Sublicensees during the previous one (1) year period between anniversaries
of the Effective Date.
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| 4.2 |
KERYX
shall immediately notify KYOWA in writing upon commencement of each
phase
in clinical studies conducted by KERYX or, if applicable, by Sublicensees.
KERYX shall provide any relevant documents, upon request from
KYOWA.
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| 4.3 |
Within
ten (10) Business Days after KERYX or the Sublicensee is officially
notified by the Authority that the Approval for sales of the Product
in
the KERYX Territory is granted by such Authority, KERYX shall notify
or
have such Sublicensee notify KYOWA in writing, and shall send or
have such
Sublicensee send to KYOWA a copy of (1) the certificates for such
grant
and (2) any related documentation.
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7
SECTION
5.
SUBLICENSE
KERYX
shall have the right to grant a sublicense under the license granted hereunder,
provided:
| 5.1. |
that
KERYX shall obtain KYOWA’s prior written approval, which shall not be
unreasonably withheld;
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| 5.2. |
that,
KERYX shall notify KYOWA in writing of (a) the identity of such intended
Sublicensee and (b) the key terms and conditions of such intended
sublicense;
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| 5.3. |
that,
KERYX shall not substantially change the key terms and conditions
of the
sublicense without prior written consent of KYOWA, which shall not
be
unreasonably withheld;
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| 5.4. |
that,
the Sublicensee shall not grant a further sublicense hereunder without
KYOWA’s prior written consent, provided that KYOWA shall not unreasonably
withhold such consent.
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| 5.5. |
that
KERYX shall be responsible for the Sublicensee’s compliance with all the
obligations under this Agreement which apply to such
Sublicensee;
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| 5.6. |
that,
KERYX shall defend and indemnify KYOWA with respect to any claims
arising
out of KERYX’s acts or failure to act relating to such sublicense;
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| 5.7. |
that
such sublicense shall be subject to termination upon expiration or
early
termination of this Agreement for any cause;
and
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| 5.8. |
that
the Royalties shall be payable to KYOWA from KERYX with respect to
the Net
Sales by any Sublicensee, regardless of whether or not the Sublicensee
has
actually paid any royalties due to KERYX.
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SECTION
6.
DATA TRANSFER AND ASSISTANCE
| 6.1. |
KYOWA
shall provide KERYX with KYOWA Data and KYOWA Know-How reasonably
required
for production, development and regulatory approval of the Product
in the
field of the treatment and prevention of cancer (“Cancer-field”), at
KYOWA’s reasonable judgment, within one (1) month of the Effective Date.
KYOWA shall continue providing any KYOWA Data in the Cancer-field
during
the Term. KYOWA shall also provide KERYX with KYOWA Data in the field
other than Cancer-field, if any, when KYOWA completes the preparation
for
clinical studies, at the latest, Provided however, KYOWA has no
obligations to acquire any new KYOWA Data. KERYX agrees that any
KYOWA
Data shall be held in confidence pursuant to Section 15
below.
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| 6.2. |
KYOWA
Data shall be transferred on “as is” basis. Notwithstanding the foregoing,
in the event that KERYX requests KYOWA to translate KYOWA Data from
Japanese to English, and KYOWA accepts such request, such KYOWA Data
may
be transferred to KERYX from KYOWA in English after a reasonable
period
for such translation. KERYX shall bear the costs and expenses of
such
translation.
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| 6.3. |
The
ownership of KYOWA Data transferred to KERYX from KYOWA hereunder
shall
remain with KYOWA. KERYX may utilize such KYOWA Data only for exercise
of
the rights granted to KERYX by KYOWA hereunder and for no other
Purpose.
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| 6.4 |
Within
three (3) months from the Effective Date, at a time mutually agreed
by the
Parties, KYOWA will host a technical review meeting (up to two days)
in
Tokyo to provide KERYX an opportunity to discuss and ask questions
about
the KYOWA Data and KYOWA Know-How with knowledgeable KYOWA staff
to ensure
no misunderstanding or confusion exists. To facilitate the meeting
KERYX
will provide to KYOWA, at least two (2) weeks in advance of the meeting,
a
written summary of questions or areas to be discussed. Each Party
shall
bear their own expenses for the
meeting.
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| 6.5. |
During
the first two (2) years from the Effective Date, KYOWA will answer
by
letter, facsimile or email to the questions which KERYX may have
regarding
the KYOWA Data. KERYX shall notify KYOWA in writing as to whom KERYX
designates among its employees, officers and directors as its contact
person for such assistance.
|
SECTION
7. STRAIN TRANSFER, TECHNICAL ASSISTANCE AND MANUFACTURE
| 7.1. |
KYOWA
shall provide KERYX with technical information concerning the cultivation
of the Strain and instruction for maintenance of Strain purity and
potency
(“Strain Information”) within one (1) month of the Effective
Date.
|
KYOWA
shall provide KERYX or a contract manufacturer designated by KERYX with the
Strain within thirty (30) days after specific site is instructed to KYOWA by
KERYX. Such thirty (30)-day period shall exclude the period of time required
to
obtain permission from the Authorities for the transfer of the Strain, if
necessary. Upon request of KERYX, KYOWA may arrange culture media for the Strain
as set forth in Exhibit 4 for KERYX at KERYX’s cost.
The
Parties acknowledge that the Strain and the Strain Information are a part of
KYOWA Know-How.
KERYX
shall be responsible for maintaining the cell bank of the Strain. In the case
KERYX requests additional supply of the Strain, KYOWA may charge reasonable
costs for such supply.
| 7.2. |
During
the two (2) year period immediately following the Effective Date,
KYOWA
shall, at KERYX’s written request and KYOWA’s reasonable consent as to
timing, duration and the number of employees, KYOWA shall send its
employees to KERYX’s designated premises during KERYX’s normal business
hours, to instruct KERYX’s employees, officers or directors for
cultivation of the Strain and manufacture of the Compound on
non-commercial scale.
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9
*****Confidential
material redacted and filed separately with the Commission.
The
total
working man-hours shall not exceed two hundred (200) working man-hours. At
one
premise, the working man-hours per day per person shall be at least eight (8)
hours.
The
rate
of man-hour is ***** per working man-hour. No charge shall be payable for *****
(other than out-of-pocket disbursements). Travel time shall not be considered
the time for such technical assistance.
KERYX
shall bear KYOWA’s out-of-pocket costs and disbursements including translation
costs for relevant documents incurred in connection with the technical
assistance, including hotel accommodation and business class air transportation.
KERYX
shall make payment for these items specified in this Section 7.2 in US Dollars
within two (2) months of KERYX’s receipt of KYOWA’s invoice
therefor.
| 7.3. |
KYOWA
shall make reasonable efforts to provide the technical assistance
to make
the information understood by KERYX, provided however, KYOWA shall
not
guarantee the manufacture of the Compound by KERYX or its designated
contract manufacturer. KERYX shall be solely responsible for manufacture
of the Compound, and KYOWA will not supply any Compound to KERYX
for the
purposes of conducting clinical trials. KYOWA will supply to KERYX
reasonable quantity of Compound for the purposes of demonstration
of
regulatory equivalency or as analytical standard. KYOWA will charge
KERYX
for such Compound at *****.
|
SECTION
8. CONSIDERATIONS
| 8.1. |
(Initial
Payment)
|
KERYX
shall pay to KYOWA a non-refundable, one-time payment of Six Hundred Thousand
US
Dollars (US$600,000) within fifteen (15) days of the Effective
Date.
| 8.2. |
(Milestone
Payment)
|
In
consideration for the rights and license granted to KERYX by KYOWA with respect
to KYOWA Patent Rights A and related KYOWA Know-How pursuant to Section 3,
KERYX
shall pay to KYOWA the following non-refundable, one-time milestone
payments:
1.
*****
within twenty-four (24) months of the Effective Date;
2.
For
the first Indication:
(i)
*****
within ninety (90) days of KERYX’s or its Sublicensee’s initiation of the Phase
III clinical trial for the Product;
(ii)
***** within ninety (90) days of the earlier to occur of the following: (a)
KERYX’s or its Sublicensee’s filing of NDA for the Product in the USA, or
(b)KERYX’s or its Sublicensee’s filing of MAA for the Product in the EU.
(iii)
***** within ninety (90) days from the day KERYX or its Sublicensee obtains
the
first marketing Approval from FDA for the Product;
10
*****Confidential
material redacted and filed separately with the Commission.
(iv)
***** within ninety (90) days from the day KERYX or its Sublicensee obtains
the
first marketing Approval for the Product in a first country of the Major
Countries.
3.
For
the second Indication:
(i)
*****
within ninety (90) days of KERYX’s or its Sublicensee’s initiation of the Phase
I clinical trial for the Product;
(ii)
***** within ninety (90) days of KERYX’s or its Sublicensee’s initiation of the
Phase III clinical trial for the Product;
(iii)
***** within ninety (90) days of the earlier to occur of the following: (a)
KERYX’s or its Sublicensee’s filing of NDA for the Product in the USA, or
(b)KERYX’s or its Sublicensee’s filing of MAA for the Product in the EU.
(iv)
***** within ninety (90) days from the day KERYX or its Sublicensee obtains
the
first marketing Approval from FDA for the Product;
(v)
*****
within ninety (90) days from the day KERYX or its Sublicensee obtains the first
marketing Approval for the Product in a first country of the Major
Countries.
| 8.3 |
(Royalty
Payment)
|
In
consideration for the rights and license granted to KERYX by KYOWA with
respect
to KYOWA Patent Rights A and related KYOWA Know-How pursuant to Section
3, KERYX
shall pay to KYOWA a royalty fee of ***** the annual Net Sales in each
country.
| 8.4 |
The payment set forth in
8.3 shall begin
from the first commercial sales of the Product in each country
(“Launch
Date”)
and continue with respect to each Product until the later to
occur of the
following: *****.
|
|
8.5
|
Upon
occurrence of (a) or (b) set forth in Section 8.4, and for additional
***** from such date, KERYX shall pay to KYOWA a royalty fee of *****
the
annual Net Sales of the Product in such
country.
|
| 8.6 |
(Annual
Payment)
|
KERYX
shall pay to KYOWA a non-refundable, annual payment of ***** each year in
consideration for the rights and license granted to KERYX by KYOWA pursuant
to
Section 3 with respect to KYOWA Patent Rights B and related KYOWA Know-How
(“Annual
Payment”).
The
first payment shall be made within fifteen (15) days of the Effective Date,
and
thereafter to be made within fifteen (15) days of each anniversary date of
the
Effective Date during the Term of this Agreement, unless earlier terminated
in
accordance with Section 27.3.
| 8.7 |
(Mode
of Payment)
|
All
payments to KYOWA hereunder shall be made in US Dollars in the stated amount
by
wire transfer or such other mode agreed upon between the Parties. KERYX shall
bear the transfer costs or other fees arising from such transaction. Each
Royalty payment shall be accompanied by a report summarizing in reasonable
detail the total Net Sales for each Product during the relevant calendar year
and the calculation of Royalties, if any, due thereon. For purposes of computing
Royalty payments for Net Sales made outside of the US, such Royalty shall be
converted into US Dollars, by applying the rate of exchange quoted in the New
York edition of The Wall Street Journal on the last Business Day of the
applicable payment period, or such other conversion rate approved by KYOWA.
11
*****Confidential
material redacted and filed separately with the Commission.
| 8.8 |
(Records
and Audit)
|
With
respect to any Product for which Royalties are due pursuant to this Agreement,
KERYX shall keep and shall have the Sublicensees keep, for five (5) years after
the end of the calendar year when the Net Sales for Royalty occur, records
of
quantities, sales and deductions, in sufficient detail to confirm the accuracy
of the Royalty calculations hereunder. During the Term and for three (3) years
thereafter, upon written notice from KYOWA, KERYX shall permit either KYOWA
representatives or an independent certified public accountant of
nationally-recognized standing, appointed and paid by KYOWA, at reasonable
times
during normal business hours to enter KERYX’s offices or other facilities to
examine these records solely to the extent necessary to verify such
calculations. Such examination shall occur only once per year. Such KYOWA
representatives or public accountant shall be permitted to make copies of such
records only if a discrepancy is discovered and only to the extent necessary
to
explain and pursue the discrepancy. Such investigation shall be at the expense
of KYOWA, unless it reveals a discrepancy in KERYX’s favor of more than *****,
in which event KERYX shall pay all reasonable expenses related thereto.
| 8.9 |
(Tax
Withholding)
|
The
Parties shall use all reasonable and legal efforts to reduce tax withholding
on
payments made to KYOWA hereunder. The Parties shall cooperate in good faith
to
provide each other with such documents and certificates as are reasonably
necessary so as to minimize any withholding tax obligations. KERYX shall provide
to KYOWA documentation of the payment of any withholding taxes that cannot
be
avoided and have therefore been paid so that KYOWA can obtain credit.
| 8.10 |
(Blocked
Payments)
|
In
the
event that, by reason of applicable law or regulations in any country, and
KERYX
or Sublicensees are unable to pay KYOWA Royalties or other payments shall be
deposited in local currency in the relevant country to the credit of KYOWA
in a
recognized banking institution designated by KYOWA or, if none is designated
by
KYOWA within a period of thirty (30) days, the deposit to the credit of KYOWA
shall be made in a recognized banking institution selected by KERYX or
Sublicensees, as the case may be, and identified in a notice in writing given
to
KYOWA.
12
SECTION
9. PATENT PROSECUTION
| 9.1 |
KYOWA
shall, at its own cost and discretion, use its commercially reasonable
efforts to prosecute and to maintain the KYOWA Patent Rights, subject
to
Section 9.2.
|
| 9.2 |
Concerning
the patent application Xxxx.Xx. EP0850646A1 listed in the Exhibit
2, KYOWA
shall, at the request and expense of KERYX, take commercially reasonable
steps required to prosecute and to maintain in certain countries
in Europe
selected by KERYX, other than the Major
Countries.
|
| 9.3 |
KYOWA
shall give notice to KERYX of the grant (allowance), registration
(issuance), revocation, invalidation, opposition or abandonment of
any
KYOWA Patent Rights. In the event that KYOWA desires to discontinue
maintenance or prosecution of the KYOWA Patent Rights A, KYOWA shall
upon
request and confirmation of KERYX’s willingness to pay transfer costs,
assign such KYOWA Patent Rights A to KERYX at no consideration. Attorney’s
fees and cost of the assignment of such rights, and the prosecution
and
maintenance shall thereafter be borne by KERYX. If requested, KYOWA
shall
reasonably assist KERYX in such maintenance and prosecution. KYOWA
shall
update any relevant exhibits hereto in writing to include any additional
KYOWA Patent Rights.
|
| 9.4 |
In
the event KYOWA is notified in writing by patent offices that any
interference, revocation, opposition or similar proceedings are instituted
against the Patent Rights by a Third Party, KYOWA shall immediately
inform
KERYX in writing. KYOWA shall retain the right to take any necessary
actions in its own discretion and expense. Notwithstanding the above,
in
the event that KYOWA advises KERYX that KYOWA declines to defend
or
contest such challenge to the Patent Rights and KERYX in writing
requests
KYOWA, within ten (10) Business Days after being so informed, to
undertake
such defense or contest, the cost of such defense or contest ( “Defense
Cost”) should be borne by KERYX. KERYX shall pay to KYOWA the Defense
Cost
within one (1) month after KERYX’s receipt of KYOWA’s invoice therefor. In
such case, KYOWA shall not enter into any agreement that would impose
any
monetary or other responsibilities or liabilities on KERYX or limit
or
reduce KERYX’s rights hereunder without KERYX’s prior written consent
thereto.
|
SECTION
10. PATENT INFRINGEMENT
| 10.1. |
Either
Party shall immediately notify the other Party in writing of any
infringement or possible infringement on the KYOWA Patent Rights,
by a
Third Party, of which they become aware of, and shall simultaneously
provide the other Party with relevant information. KYOWA is under
no
obligation to take any action against such infringement or to bear
the
cost of such prevention. KERYX may take legal action against such
infringement in the KERYX Territory at KERYX’s expense, provided that
KERYX shall notify KYOWA in writing of such intent in advance and
regarding developments of the proceedings thereafter. KYOWA shall
provide
reasonable assistance to KERYX at KERYX’s written request and expense.
Notwithstanding the foregoing, KYOWA shall retain the right to take
any
necessary actions in its own discretion and expense. Any damages
or other
compensation which KERYX may obtain from the Third Party as a result
of
such proceedings in the KERYX Territory shall be first allocated
proportionally to reimbursement for the Parties respective costs
if any,
and the remainder shall inure to the benefit of KERYX.
|
13
| 10.2. |
Either
Party shall immediately notify the other Party in writing of any
allegation that the Product may infringe any Third Party patents
or patent
applications in the KERYX Territory, of which they become aware of,
and
shall simultaneously provide the other Party with relevant information.
Neither Party shall be obligated to defend the other Party or such
Product
against or to contest such allegation, nor shall either Party bear
the
cost of the other Party for such defense or contest. However, each
Party
may, at their own cost defend itself or such Product against such
allegation. Either Party may settle such case, provided that such
settlement shall not impose any monetary or other responsibilities
or
liabilities upon the other Party.
|
SECTION
11. PATENT
TERM EXTENSION
KERYX
agrees to apply for and to exercise due diligence in obtaining an extension
of
the term of any patent included in the KYOWA Patent Rights under the applicable
laws of any country where such extensions are available, including but not
limited to, the Drug Price Competition and Patent Term Restoration Act in the
United States. KYOWA agrees to execute such documents and take such additional
actions as KERYX reasonably request in connection therewith. Each Party shall
bear its own expenses in connection with the application for such patent term
extensions.
SECTION
12. THIRD
PARTY CONTRACT
| 12.1 |
KERYX
acknowledges the existence of the NCI Agreement under which NCI has
been
conducting certain clinical studies of the Compound in the US. If
KERYX
intends to obtain the NCI Data, KERYX shall be solely responsible
for
negotiation with NCI provided that, if necessary, KYOWA will grant
permission to NCI to release NCI Data to KERYX.
|
14
| 12.2 |
The
NCI Agreement will expire on August 10, 2006. If NCI intends to continue
the agreement, KERYX may be requested to become a party to the NCI
Agreement in the place of KYOWA. In such case, KERYX shall be solely
responsible for negotiation with NCI provided that KYOWA will give
consent
to NCI for KERYX to become a party to the NCI
Agreement.
|
| 12.3 |
Under
the NCI Agreement KYOWA had supplied NCI with the Compound for its
clinical studies. For such supply KYOWA selected Lonza as a contract
manufacturer of the Compound. The agreement between KYOWA and Lonza
has
expired, and if KERYX intends to have Lonza manufacture the Compound,
KERYX shall be solely responsible for negotiation with Lonza provided
that
KYOWA will authorize Lonza to use the technology to manufacture the
Compound as well as to make use of the Drug Master File relating
to the
Compound thereof.
|
| 12.4 |
KERYX
acknowledges that Third Parties may have Patent Rights or Know-How
relevant to the commercialization of a Product containing the Compound.
KERYX agrees that KERYX shall be solely responsible to negotiate
with any
Third Party, (such Third Party including but not be limited to
Xxxxx-Xxxxxxxxx Institute for Cancer Research and Washington State
University) a license under any patents, technology, know-how and/or
data.
|
SECTION
13.
IMPROVEMENTS
| 13.1 |
KYOWA
shall notify KERYX in the event KYOWA makes any Improvements, and
KYOWA
shall grant to KERYX an exclusive, irrevocable, royalty-free license,
with
the right to sublicense, to make, have made, use, have used, sell,
have
sold, offer for sale and distribute the Product under KYOWA Improvements
in the KERYX Territory in the
Field.
|
| 13.2 |
Upon
discovery by KERYX or its Affiliates, or Sublicensees of any Improvements,
including but not be limited to the use of Compound in Product for
Combination Therapy or in Combination Product, KERYX shall immediately
notify KYOWA in writing. All rights to the KERYX Improvements shall
belong
to KERYX, including the right to seek Patent Rights throughout the
world.
|
| 13.3 |
KERYX
shall grant to KYOWA and shall cause its Sublicensees to grant to
KYOWA an
exclusive, irrevocable, royalty-free license, with the right to
sublicense, under KERYX Improvements for any purposes in the KYOWA
Territory.
|
15
*****Confidential
material redacted and filed separately with the Commission.
SECTION
14. KERYX DATA AND SUPPLY
| 14.1 |
Upon
KYOWA’s request, KERYX shall transfer to KYOWA all KERYX Data necessary
for submission to Authorities in the KYOWA Territory. KYOWA agrees
that
such data shall be held in confidence pursuant to Section 15. KYOWA
shall
have an exclusive, paid-up license, with the right to grant sublicenses,
to use such KERYX Data for KYOWA’s development and marketing of the
Product in KYOWA Territory.
|
| 14.2 |
For
KYOWA’s development and marketing in KYOWA Territory, KYOWA reserves the
rights to purchase the Compound or the Product which KERYX manufactures
or
has its contract manufacturer make at
*****.
|
| 14.3 |
In
the event KYOWA chooses to purchase the Compound or the Product from
KERYX
as set forth in 14.2, KERYX shall supply to KYOWA with such Compound
or
the Product as long as KYOWA markets the Product in the KYOWA Territory,
or until KYOWA requests termination of the supply with twelve (12)
months
prior written notice to KERYX, provided that KYOWA shall provide
KERYX
with at least nine (9) month prior notification of its requirement
of
Compound or Product with ±
15% accuracy. If KERYX ceases to manufacture or commission the manufacture
of the Compound, or if, despite KERYX’s good faith efforts to ensure an
adequate supply of the Compound, such supply is not readily obtainable,
KERYX shall have no obligation to provide or obtain Compound to meet
KYOWA’s needs, and KYOWA shall be free to seek alternative sources, but
at
no expense to KERYX.
|
SECTION
15. CONFIDENTIALITY
| 15.1 |
During
the Term and for a period of five (5) years after the expiration
or early
termination of this Agreement, either Party shall not disclose to
any
Third Party any information disclosed by the other Party under this
Agreement, in written or electronic form, that is marked “confidential” or
designated in writing as confidential within thirty (30) Business
Days of
oral or visual disclosure, or is understood by the Parties to be
confidential (“Confidential
Information”).
|
| 15.2 |
Either
Party shall maintain the Confidential Information in strict confidence,
and shall use the Confidential Information solely for the purpose
of this
Agreement. The receiving Party shall prevent unauthorized use or
reproduction of the Confidential Information by taking all necessary
measures, including limiting access to the Confidential Information
to its
directors, officers and employees to whom disclosure is necessary
to
perform or facilitate the purpose of this Agreement, and who shall
be
bound by the confidentiality obligations in this
Section.
|
16
| 15.3 |
The
foregoing obligations of confidentiality and limited use shall not
apply
to information which,
the receiving Party can establish by reasonable proof;
|
| 1. |
is
in the public domain at the time of disclosure;
or
|
| 2. |
becomes
part of the public domain by publication or otherwise after disclosure
not
due to any breach hereof by the receiving Party;
or
|
| 3. |
is
in the possession of the receiving Party at the time of disclosure
without
obligations of confidentiality; or
|
| 4. |
is
provided to the receiving Party by a Third Party legally and without
confidentiality; or
|
| 5. |
is
independently developed by the receiving Party without any knowledge
or
access to the disclosing Party’s Confidential Information; or
|
| 6. |
is
required by judicial or administrative authorities to disclose; provided,
however, that the receiving Party shall promptly notify the other
Party of
such requirement so that the other Party may seek an appropriate
protective order; or
|
| 7. |
is
required by any Authority for the purposes of obtaining Approval;
however
the providing Party shall endeavor to have that Authority treat the
information as confidential.
|
| 15.4 |
Notwithstanding
Section 15.1, 15.2 and 15.3, KERYX may disclose KYOWA’s Confidential
Information to its Sublicensees for the purpose of Section 4, provided
that KERYX shall assure that such Sublicensees comply with the
confidentiality obligations and limited use set forth in this Section
15.
In the event such Sublicensee has ceased to be the Sublicensee after
KYOWA’s Confidential Information has been disclosed, KERYX shall have such
Sublicensee immediately return to KERYX or destroy such Confidential
Information.
|
| 15.5 |
Upon
request from the disclosing Party, or upon expiration or early termination
of this Agreement, the receiving Party shall either return or destroy,
at
the discretion of the disclosing Party, all written or graphic
Confidential Information to the disclosing Party and shall not retain
any
copies thereof, provided, however, one copy may be retained in the
receiving Party’s legal files as a means of determining any continuing
obligations hereunder. Each Party may request a certificate from
the other
Party regarding compliance with this
Section.
|
| 15.6 |
Neither
Party shall make any publications, news release or other public
announcement, visual or oral, relating hereto without the other Party’s
prior written approval thereof, which shall not be unreasonably withheld
or delayed, except as required by law or
regulation.
|
17
SECTION
16. LIMITED WARRANTY AND DISCLAIMER
| 16.1. |
Each
Party represents and warrants:
|
| 1. |
that
such Party has the power and right to enter into this Agreement as
of the
Effective Date and to perform its obligations hereunder;
and
|
| 2. |
that
such Party is not a party to any agreement with a Third Party, whether
written or not, which would prevent such Party from fulfilling any
of its
obligations hereunder.
|
| 16.2 |
KYOWA
represents and warrants:
|
| 1. |
that
subject to Section 16.3, KYOWA is the owner of the KYOWA Patent Rights
and
KYOWA Know-How;
|
| 2. |
that
subject to Section 16.3, KYOWA is entitled to grant to KERYX the
rights
granted to KERYX by KYOWA hereunder;
and
|
| 3. |
that,
to the best knowledge of KYOWA, as of the Effective Date KYOWA knows
of no
infirmity in the claimed rights and that no claim or challenge is
presently pending with regard to those rights, nor is KYOWA aware
of any
claim that the Compound violates any Third Party rights..
|
| 16.3 |
KYOWA
NEITHER REPRESENTS NOR WARRANTS AND
DISCLAIMS:
|
| 1. |
the
scope, validity and enforceability of the KYOWA Patent Rights and
the
KYOWA Improvements;
|
|
2.
|
future
grant (allowance) and registration (issuance) of the KYOWA Patent
Rights
and the KYOWA Improvements;
|
|
3.
|
future
filing, prosecution and maintenance of the KYOWA
Improvements;
|
|
4.
|
future
development of the KYOWA
Improvements;
|
|
5.
|
accuracy
or completeness of the KYOWA Data or any warranty that the use of
the
KYOWA Data will not infringe or violate any patent or proprietary
rights
of any Third Party;
|
|
6.
|
non-infringement
by any product, material or information on the intellectual property
or
other rights vested in or enforceable by a Third
Party;
|
|
7.
|
successful
development of the Product;
|
|
8.
|
Approval
of the Product by the Authority;
and
|
|
9.
|
merchantability
and fitness for a particular
purpose.
|
| 16.4 |
KERYX
NEITHER REPRESENTS NOR WARRANTS AND
DISCLAIMS:
|
|
1.
|
the
scope, validity and enforceability of the KERYX
Improvements;
|
|
2.
|
future
grant (allowance) and registration (issuance) of the KERYX
Improvements;
|
|
3.
|
future
filing, prosecution and maintenance of the KERYX
Improvements;
|
|
4.
|
future
development of the KERYX Improvements and KERYX
Data;
|
|
5.
|
accuracy
or completeness of the KERYX Data or any warranty that the use of
the
KERYX Data will not infringe or violate any patent or proprietary
rights
of any Third Party;
|
18
|
6.
|
non-infringement
by any product, material or information on the intellectual property
or
other rights vested in or enforceable by a Third
Party;
|
|
7.
|
successful
development of the Product;
|
|
8.
|
Approval
of the Product by the Authority;
and
|
|
9.
|
merchantability
and fitness for a particular
purpose.
|
| 16.5 |
EXCEPT
AS EXPRESSLY PROVIDED FOR HEREIN, NEITHER PARTY MAKES ANY REPRESENTATION
OR WARRANTY, WHETHER IMPLIED, STATUTORY OR OTHERWISE, WITH
RESPECT TO THE SUBJECT MATTER
HEREOF.
|
SECTION
17. LIMITED LIABILITY
Neither
Party shall be liable to the other Party or any Third Party for (1) any
consequential, indirect, incidental, special or exemplary damages and (2) any
losses of goodwill, business, contracts, revenues, profits or savings, which
would be caused in relation hereto, through contract, tort (including
negligence, but not gross negligence), misrepresentation (but not fraudulent
misrepresentation), breach of statutory duties or otherwise, even if such Party
is advised of the possibility of such damages or losses.
SECTION
18. INDEMNIFICATION
| 18.1. |
KERYX
shall defend, indemnify and hold harmless KYOWA, KYOWA’s Affiliates, their
respective directors, officers and employees from and against any
and all
claims, actions, judgments, expenses (including legal expenses and
reasonable attorneys’ fees), losses and damages incurred by them, arising
from any Third Party claim in relation to (1) KERYX exercising the
license
under Section 3, (2) the Sublicensee exercising the sublicense under
Section 5 and (3) KYOWA Data and any related documentation, if any,
which
are supplied to KERYX by KYOWA unless such claims, actions, judgments,
expenses, losses and damages result from gross negligence, wrongful
intentional actions or omissions or fraud on the part of KYOWA, KYOWA’s
Affiliate, their respective directors, officers or employees. Such
claims,
actions, judgments, expenses, losses and damages include those related
to
the products or materials manufactured by or on behalf of KERYX or
its
Sublicensees pursuant to this Agreement, in particular (but not limited
to) those related to the claim that such products or materials have
caused
death or bodily injury or have infringed intellectual property rights
of
any Third Party.
|
19
| 18.2. |
KYOWA
shall defend, indemnify and hold harmless KERYX, KERYX’s Affiliates, the
Sublicensees, their respective directors, officers and employees
from and
against any and all claims, actions, judgments, expenses (including
legal
expenses and reasonable attorneys’ fees), losses and damages incurred by
them, arising from any Third Party claim in relation to (1) KYOWA
exercising the license under Section 13 and (2) a Third Party exercising
the sublicense under the same unless such claims, actions, judgments,
expenses, losses and damages result from gross negligence, wrongful
intentional actions or omissions or fraud on the part of KERYX, KERYX’s
Affiliates, the Sublicensee, their respective directors, officers
or
employees. Such claims, actions, judgments, expenses, losses and
damages
include those related to the products or materials manufactured by
or on
behalf of KYOWA or KYOWA’s sublicensees, in particular (but not limited
to) those related to the claim that such products or materials have
caused
death or bodily injury or have infringed intellectual property rights
of
any Third Party.
|
| 18.3. |
In
the event that a Party is notified of a Third Party claim and seeks
the
indemnification for such claim under Section 18.1 or 18.2, from the
other
Party, the Party shall (1) inform the indemnifying Party in writing
of
such claim as soon as practicable after such notification, (2) permit
the
indemnifying Party to assume the direction and control of the defense
against such claim, (3) cooperate with the indemnifying Party in
such
defense at the indemnifying Party’s written request and expense and (4)
undertake all reasonable steps to mitigate any expenses, losses and
damages arising in relation to such claim. Further, the indemnifying
Party
may settle such claim at its sole discretion, provided that such
settlement should not impose any obligation on or otherwise adversely
affect the indemnified Party.
|
SECTION
19. FORCE MAJEURE
The
failure by either Party to timely perform any obligation under this Agreement
by
reason of a cause beyond its reasonable control shall not be deemed to be a
material breach of this Agreement, but shall be excused to the extent and for
the duration of such cause, provided the duration is not more than six (6)
months, and the affected Party shall use commercially reasonable efforts to
avoid or remove such cause, and shall perform its obligations with the utmost
dispatch when the cause is removed.
SECTION
20. WAIVER
Neither
Party shall be deemed to have waived any of its rights or remedies conferred
to
such Party hereunder unless such waiver is made in writing and signed by a
duly
authorized representative of such Party. In particular, no delay or failure
of
either Party in exercising or enforcing any of its rights or remedies conferred
to such Party hereunder shall operate as waiver of such rights or remedies
or so
as to preclude or to impair the exercise or enforcement of such rights or
remedies. Further, partial exercise or enforcement of such rights or remedies
shall not preclude or impair any other exercise or enforcement of such rights
or
remedies.
20
SECTION
21. ENTIRE AGREEMENT
This
Agreement constitutes the entire agreement and understanding between the Parties
relating to the subject matter hereof and supersedes any and all prior oral
or
written agreement, understanding, representation or warranty between them
relating to the same. The Parties understand and confirm that, as regards the
subject matter hereof, no director, officer, employee or agent of either Party
is authorized to make any representation or warranty to the other Party and
that
neither Party relies on such representation or warranty, whether made orally
or
in writing.
SECTION
22. AMENDMENT
No
amendment, modification or supplement of or to this Agreement shall be valid
unless made in writing and signed by duly authorized representatives of both
Parties.
SECTION
23. INDEPENDENT CONTRACTORS
The
relation between the Parties is that of independent contractors. Nothing herein
is construed to create any other relation, such as partnership or agency,
between the Parties. Neither Party shall have any right or authority to create,
assume or incur any obligations, liabilities or expenses on behalf of the other
Party.
SECTION
24. NO SOLICITATION
For
one
(1) year after and during the Term hereof, KERYX shall not execute or shall
not
have a Third Party execute an employment, consulting or similar Agreement with
KYOWA’s employees sent to KERYX for technical assistance set forth in Section
7.
21
SECTION
25. ASSIGNMENT
Neither
Party shall wholly or partially assign or pledge its rights and obligations
hereunder to any Third Party without the other Party’s prior written consent
thereto, which consent shall not be unreasonably withheld or delayed.
Notwithstanding the foregoing, either Party may assign its rights and
obligations hereunder to a successor of such Party’s whole or substantially
whole business, provided that such Party should timely notify the other Party
in
writing of the fact and its intent to effectuate such assignment.
SECTION
26. SEVERABILITY
In
the
event that any provision of this Agreement has been declared illegal, invalid
or
unenforceable in any jurisdiction either by any laws or regulations or by any
orders or judgments of such competent governmental authorities as
administrations or courts, this Agreement shall continue in full force and
effect without said provision, so long as the Agreement, taking into account
said voided provision(s), continues to provide the Parties with the same
practical benefits as the Agreement containing said voided provision(s) did
on
the Effective Date. If, after taking into account said voided provision(s),
the
Parties are unable to realize the practical benefit contemplated on the
Effective Date, the Parties shall negotiate in good faith to amend this
Agreement to reestablish the practical benefit provided the Parties on the
Effective Date.
SECTION
27. TERM AND TERMINATION
| 27.1. |
This
Agreement shall come into effect as of the Effective Date and, unless
earlier terminated according hereto, continue to be effective until
KERYX
is no longer obligated to pay the Royalties and other considerations
to
KYOWA under this Agreement (“Term”).
|
| 27.2. |
KERYX
may at any time terminate this Agreement upon one hundred eighty
(180)
days prior written notice.
|
| 27.3. |
KERYX
may at any time unilaterally terminate this Agreement only with respect
to
the rights and license granted to KERYX for KYOWA Patent Rights B
and
related KYOWA Know-How upon written notice to KYOWA three (3) months
prior
to an anniversary date of the Effective Date.
|
| 27.4. |
Either
Party may terminate this Agreement by giving written notice to the
other
Party in the following events;
|
| 1. |
the
other Party materially breaches any term or condition of this Agreement
and fails to remedy such breach within ninety (90) days of receipt
of the
written notice requesting to remedy such
breach.
|
22
| 2. |
the
other Party files for itself a petition for bankruptcy, reorganization,
composition, readjustment, receivership or similar procedures under
any
applicable bankruptcy, insolvency, reorganization, moratorium or
similar
law affecting creditors’ rights and interests (hereinafter referred to as
“Petition”) ;
|
| 3. |
the
Petition has been filed against the other Party by a Third Party
and the
court procedures for such Petition have been pending for more than
forty
five (45) days; or
|
| 4. |
the
other Party has been wound up, dissolved or liquidated not for merger
and
acquisition or the procedures therefor have been
started.
|
| 27.5 |
In
the event this Agreement has expired in accordance with Section 27.1:
|
| 1. |
KERYX
shall thereafter be granted a non-exclusive, paid-up right and license,
with the right to sublicense, under the KYOWA Patent Rights , KYOWA
Know-How and KYOWA Improvements to make, have made, use, have used,
sell,
offer for sale, have sold and distribute the Product in the KERYX
Territory within the Field.
|
| 2. |
KERYX
shall immediately return to KYOWA or destroy, under KYOWA’s instruction
and KERYX’s expense, all Confidential Information disclosed to KERYX by
KYOWA, except to the extent such Confidential Information is necessary
for
KERYX to practice and exploit the rights and the license retained
by KERYX
after the expiration.
|
| 3. |
The
license granted by KERYX to KYOWA under Section 13.3 shall survive
the
expiration of this Agreement as an exclusive, irrevocable, perpetual
and
royalty-free license for any purposes in the KYOWA
Territory.
|
| 4. |
KYOWA
shall retain the exclusive, paid-up license, with the right to grant
sublicenses, to use the KERYX Data for KYOWA’s development and marketing
of the Product in KYOWA Territory, pursuant to Section
14.1.
|
| 27.6 |
In
the event this Agreement is terminated by KERYX in accordance with
Section
27.4;
|
| 1. |
Subsections
1 and 2 of Section 27.5 shall
apply.
|
| 2. |
KYOWA
shall immediately return to KERYX or destroy, under KERYX’s instruction
and at KYOWA’s expense, all Confidential Information disclosed to KYOWA,
to KERYX including without limitation any KERYX Data and KERYX
Know-How.
|
| 27.7 |
In
the event this Agreement is terminated by KERYX in accordance with
Sections 27.2 or by
KYOWA in accordance with Section
27.4;
|
| 1. |
The
license granted to KERYX under Section 3 of this Agreement shall
terminate
as of the effective date of termination, and KERYX shall cease any
use of
the KYOWA Patent Rights, KYOWA Know-How and KYOWA
Improvements.
|
| 2. |
KERYX
shall transfer to KYOWA, at KERYX’s expense, within a reasonable time
after the effective date of termination, any and all of KERYX’s Data, any
physical material of the Compound, the Product or the Strain, and
any
patents of KYOWA Patent Rights A assigned to KERYX during the Term
of this
Agreement pursuant to Section 9.3, including without limitation,
any
rights in NDAs, XXXx and other relevant Approvals acquired by KERYX
for
its Product in the KERYX Territory.
|
23
| 3. |
KERYX
shall immediately return to KYOWA or destroy, under KYOWA’s instruction
and at KERYX’s expense, all Strain and all Confidential Information
disclosed to KERYX by KYOWA, including without limitation any KYOWA
Data
and KYOWA Know-How.
|
| 4. |
The
license granted by KERYX to KYOWA under Section 13.3 shall survive
the
termination of this Agreement as an exclusive, irrevocable, perpetual
and
royalty-free license for any purposes in the KYOWA Territory.
|
| 5. |
KYOWA
shall retain the exclusive, paid-up license, with the right to grant
sublicenses, to use the KERYX Data for KYOWA’s development and marketing
of the Product, or Product in KYOWA Territory, pursuant to Section
14.1.
|
| 6. |
KYOWA
shall immediately return to KERYX or destroy, under KERYX’s instruction
and at KERYX’s expense, all Confidential Information, except to the extent
such Confidential Information is necessary for KYOWA to practice
and
exploit the rights and the license retained by KYOWA after the
termination.
|
| 27.8 |
In
the event this Agreement is terminated by KERYX with respect to KYOWA
Patent Rights B and related KYOWA Know-How pursuant to Section
27.3;
|
| 1. |
Subsections
1 to 6 of Section 27.7 shall apply mutatis
mutandis only
with respect to KYOWA Patent Rights B and related KYOWA
Know-How.
|
| 2. |
KERYX
shall no longer be obligated thereafter to pay the Annual Payment,
provided that KERYX shall pay all Annual Payments due before the
effective
date of termination.
|
| 3. |
KYOWA
shall no longer be obligated to perform any intellectual property
obligations set forth in Section 9 and Section 10 with respect to
Patent
Rights B.
|
| 27.9 |
Expiration
or termination of this Agreement shall not relieve the Parties of
any
obligation accruing prior to such expiration or
termination.
|
| 27.10 |
Unless
otherwise expressly stated in this Agreement, Sections 13, 16, 17,
18, 28,
and 29 shall survive the expiration or termination hereof. Section
15
shall survive according to Section
15.1.
|
SECTION
28. ARBITRATION
If
there
is any dispute, controversy, difference or question between the Parties with
respect to any matter arising out of or relating to this Agreement, the Parties
shall first make efforts to solve such issue amicably. If such issue is not
solved through such amicable efforts, the Parties shall finally settle such
issue according to the Rules of Conciliation and Arbitration of the
International Chamber of Commerce. Such arbitration shall be conducted in the
English language in New York, New York if initiated by KYOWA, and in Tokyo,
Japan if initiated by KERYX. The award rendered by the arbitrator(s) shall
be
final and binding upon both Parties concerned.
24
SECTION
29. GOVERNING LAW
| 29.1. |
This
Agreement shall be governed by and construed according to the laws
of
Japan, exclusive of choice of law rules. To the extent that patent
law or
law governing trade secrets, know-how or data must be applied, the
laws of
the country governing such rights shall be utilized.
|
| 29.2. |
The
Parties agree that the arbitration decisions according to Section
28 shall
be enforceable by the courts of competent jurisdiction in Japan,
the
United States of America and any other country covered by this Agreement,
and shall submit to the jurisdictions of such courts solely for such
enforcement.
|
SECTION
30. AFFILIATES
Each
Party may perform its obligations hereunder personally or through one or more
Affiliate and shall be responsible for the performance of such obligations,
and
any liabilities resulting from such performance. Neither Party shall permit
any
of its Affiliates to commit any act (including any act of omission) which such
Party is prohibited hereunder from committing directly.
25
IN
WITNESS WHEREOF,
the
Parties have caused this Agreement to be executed by their duly authorized
representatives as of the Effective Date.
| KYOWA HAKKO KOGYO CO., LTD. | KERYX BIOPHARMACEUTICALS, INC. | ||
|
By:
/s/ Xxxxxxx
Xxxx
|
By: /s/ Xxxxxxx X. Xxxxx | ||
|
Name: Xxxxxxx Xxxx |
Name: Xxxxxxx X. Xxxxx |
||
| Title: President | Title: CEO | ||
| Pharmaceuticals Business Unit | |||
26
EXHIBIT
1
COMPOUND
CHEMICAL STRUCTURE
26
EXHIBIT
2
KYOWA
PATENT RIGHTS A
|
No.
|
Country
|
Designated
Country in EP
|
Kind
|
Appl.
No.
|
Appl.
Date
|
Publ.
No.
|
Publ.
Date
|
Reg.
No.
|
Reg.
Date
|
Exp.
Date
|
|
1
|
U.S.A.
|
|
Product
|
28201
|
03.20.87
|
|
|
4935415
|
06.19.90
|
06.19.2007
|
|
|
Europe
|
GB,
DE, FR, IT
|
Product
|
87103764
|
03.16.87
|
0238011
|
09.23.87
|
0238011
|
09.25.91
|
03.16.2007
|
|
2
|
U.S.A.
|
|
Process(oxidization)
|
79560
|
06.22.93
|
|
|
5344926
|
09.06.94
|
06.22.2013
|
|
|
Europe
|
GB,
FR, DE, IT, ES
|
Process(oxidization)
|
93109935
|
06.22.93
|
0575955
|
12.29.93
|
0575955
|
09.15.99
|
06.22.2013
|
|
3
|
U.S.A.
|
|
Formulation(liposome)
|
09/025752
|
06.12.97
|
|
|
6045822
|
04.04.00
|
06.12.2017
|
|
|
Europe
|
GB,
FR, DE, IT, ES, CH
|
Formulation(liposome)
|
97926234
|
06.12.97
|
0850646
|
07.01.98
|
|
|
|
|
|
Canada
|
|
Formulation(liposome)
|
2229892
|
06.12.97
|
2229892
|
12.24.97
|
2229892
|
01.07.03
|
06.12.2017
|
|
|
Australia
|
|
Formulation(liposome)
|
31066-97
|
06.12.97
|
3106697
|
01.07.98
|
718856
|
08.03.00
|
06.12.2017
|
|
4
|
U.S.A.
|
|
Process(isomerization)
|
09/466903
|
12.20.99
|
|
|
6197955
|
03.06.01
|
12.20.2019
|
|
|
Europe
|
GB,
FR, DE, IT, CH, LI
|
Process(isomerization)
|
99125341.0
|
12.21.99
|
1020471
|
07.19.00
|
1020471
|
05.28.03
|
12.21.2019
|
|
|
Canada
|
|
Process(isomerization)
|
2293023
|
12.17.99
|
2293023
|
06.22.00
|
|
|
|
EXHIBIT
3
KYOWA
PATENT RIGHTS B
|
No.
|
Country
|
Designated
Country in EP
|
Kind
|
Appl.
No.
|
Appl.
Date
|
Publ.
No.
|
Publ.
Date
|
Reg.
No.
|
Reg.
Date
|
Exp.
Date
|
|
1
|
U.S.A.
|
Leakage
inhibition from liposome
|
10/018349
|
06.23.00
|
|
|
|
|
|
|
|
|
Europe
|
GB,
FR, DE, IT, ES, CH
|
Leakage
inhibition from liposome
|
00939146.7
|
06.23.00
|
1190705
|
03.27.02
|
|
|
|
|
|
Canada
|
Leakage
inhibition from liposome
|
2376849
|
06.23.00
|
2376849
|
01.04.01
|
|
|
|
|
|
|
Australia
|
Leakage
inhibition from liposome
|
54298-00
|
06.23.00
|
5429800
|
01.31.01
|
780194
|
06.23.05
|
06.23.2020
|
*****Confidential material redacted and filed separately
with
the Commission.
EXHIBIT
4
STRAIN
AND MEDIA
| 1. |
Strain:
Streptomyces sp. *****
|
| 2. |
Media:
*****,
|
*****Confidential material redacted and filed separately
with
the Commission.
EXHIBIT
5
DEVELOPMENT
PLAN
The
initial development plan for development of UCN-01 would be pursued through
the
following areas which would be designed to run simultaneously:
|
(a)
|
Pre-clinical
|
KERYX
recognizes that considerable in-vitro
and
in-vivo
experiments have been performed with UCN-01. However, KERYX would make UCN-01
available to collaborators for evaluations that would include but not be limited
to some or all of the following:
|
i.
|
Establishment
of molecular profiles of tumors that are or are not responsive to
UCN-01.
Such profiles might be developed through *****. Results may be derived
from *****. In particular, KERYX would target information related
to
*****.
|
|
ii.
|
Additional
in-vivo
toxicology might be considered to develop additional single agent
or
combination regimens. KERYX recognizes that preclinical opportunities
may
be limited *****
|
|
iii.
|
Evaluation
of novel combinations of UCN-01 with either traditional anti-cancer
agents
or newer targeted agents both in-vitro
and in-vivo.
In particular, studies of UCN-01 ***** are interesting in light of
the new
data *****. UCN-01 *****. Pre-clinical studies ***** suggest that
UCN-01
*****. *****.
|
|
iv.
|
Evaluation
of ***** would be undertaken.
|
KERYX
will accomplish this pre-clinical strategy by soliciting investigator proposals,
placing studies through an NCI research CRADA and by contracting with commercial
laboratories.
|
(b)
|
Clinical
|
KERYX
would immediately undertake additional clinical studies. Results derived from
the pre-clinical studies would be rapidly translated into clinical trials,
and
clinical studies would provide samples for additional pre-clinical studies.
Based
on
the results from the initial phase 1 studies, it appears that *****. KERYX
will
also consider additional treatment schedules.
KERYX
believes that oncology drugs should be developed using multiple simultaneous
strategies that might lead to either FDA subpart H or full
approvals.
|
i.
|
Subpart
H Single Agent Approvals
|
*****Confidential material redacted and filed separately
with
the Commission.
To
determine possible subpart H approval strategies KERYX would consider the
following approaches
|
a.
|
*****.
|
|
b.
|
*****
|
|
c.
|
*****.
|
For
each
subpart H strategy KERYX would also initiate a phase II study. If the FDA
accepts a subpart H strategy and an appropriate comparator exists, *****.
*****.
|
ii.
|
Subpart
H Combination Approvals
|
KERYX
will also consider the development of strategies in which *****. For these
strategies, KERYX will consider randomized phase II studies *****. Given that
UCN-01 is an IV infusion KERYX believes that it will be difficult to conduct
such studies using a placebo. The combination of *****.
|
iii.
|
Full
Approvals
|
KERYX
believes that randomized studies and potentially full approval strategies may
be
required for any strategy involving time to progression as an endpoint. These
strategies would be pursued in areas for which there was no opportunity for
pursuit of an unmet medical need. One example is *****.
Potential
Timelines
(starting from the date that formulated drug is available for clinical
studies)
The
following represent timelines similar to those used for other drugs that KERYX
has in-licensed at a similar stage. Two scenarios are envisaged
(1)
Potential indication for phase II subpart-H strategy can be determined from
data
available prior to in-licensing
Months
1
- 6
*****
*****
*****
*****
*
to
begin as soon as drug in-licensed
Months
7
-18
*****
*****
*****Confidential
material redacted and filed separately with the Commission.
Months
18
-24
*****
Months
24
-36
*****
*****
*****
Months
37
- 48
*****
*****
Months
49
- 60
*****
(2)
Potential indication for phase II subpart-H strategy cannot be determined from
data available prior to in-licensing
Months
1
- 6
*****
*****
*****
*****
*
to
begin as soon as drug in-licensed
Months
7
-18
*****
Months
18
-24
*****
Months
24-36
*****
*****Confidential
material redacted and filed separately with the Commission.
Months
36
-48
*****
*****
*****
Months
49
- 60
*****
*****
Months
60
- 72
*****
*****
Months
72-84
*****
