EXHIBIT 10.215
Portions of this exhibit marked [*] are
requested to be treated confidentially.
AGREEMENT
THIS AGREEMENT
(“ Agreement ”)
is entered into as of July 13, 2005 between Takeda San Diego,
Inc. , a Delaware corporation having its principal place of
business at 10410 Science Center Drive, San Diego, CA 92121,
(formerly known as Syrrx, Inc.) (“ TSD ”),
TAKEDA PHARMACEUTICAL COMPANY LIMITED , a corporation
organized under the laws of Japan, having its principal place of
business at 1-1 Doshomachi 4-chome, Chuo-ku, Osaka, Japan
(hereinafter “ TPC ”), Development Partners,
LLC , a Delaware limited liability company having its principal
place of business at 3151 South 17th Street, Wilmington, NC 28412
(“ PPD ”), and Pharmaceutical Product
Development, Inc. , a North Carolina corporation having its
principal place of business at 3151 South 17th Street, Wilmington,
NC 28412 (“ PPD, Inc. ”). TSD, TPC, and PPD and
PPD, Inc. are sometimes referred to herein individually as a
“ Party ” and collectively as the “
Parties ”.
WHEREAS , TSD, PPD and PPD, Inc. entered into a
Collaboration Agreement (as defined below);
WHEREAS , pursuant to the Collaboration Agreement, PPD
acquired the exclusive worldwide right to co-develop serine
protease dipeptidyl peptidase IV inhibitors with TSD;
WHEREAS , Takeda America Holdings, Inc., a New York
corporation having its principal place of business at New York, NY
(“ Takeda ”), acquired TSD effective March 16,
2005;
WHEREAS , the Parties now desire to, among other things,
(i) terminate the Collaboration Agreement, (ii) reallocate
ownership and responsibilities for the future development and
commercialization of Products (as defined below) and the rights
related thereto; and (iii) provide for up-front and milestone cash
payments and royalty payments based on Net Sales of Products (as
defined below) to PPD by TSD, all in accordance with the terms and
conditions of this Agreement;
NOW, THEREFORE
, in consideration of the foregoing
and the premises and conditions set forth herein, the Parties agree
as follows:
ARTICLE 1
DEFINITIONS
1.1 “Affiliate”
means, (a) with respect to TSD, (i)
TPC; (ii) Takeda or (iii) a particular person, corporation,
partnership, or other entity that controls, is controlled by or is
under common control with TSD, TPC or Takeda; and (b) with respect
to PPD, (i) PPD, Inc. or (ii) a particular person, corporation,
partnership, or other entity that controls, is controlled by or is
under common control with PPD or PPD, Inc. For the purposes
of
the definition in this Section 1.1, the word
“control” (including, with correlative meaning, the
terms “controlled by” or “under the common
control with”) means the actual power, either directly or
indirectly through one or more intermediaries, to direct the
management and policies of such entity, whether by the ownership of
at least fifty percent (50%) of the voting stock of such entity, or
by contract or otherwise.
1.2 “BLA” means a biologics license application with the
FDA as more fully described at 21 CFR § 601.2, or successor
equivalent.
1.3 “Collaboration
Agreement” means
the collaboration agreement entered into among PPD, PPD, Inc. and
TSD (then Syrrx, Inc.) effective as of November 19, 2003 to
discover, develop, and commercialize serine protease dipeptidyl
peptidase IV inhibitors as human drug products.
1.4 “Collaboration
Compound” means any
serine protease dipeptidyl peptidase IV inhibitor [*] that (a) has
[*] as measured internally by TSD using a [*] assay specific for
the Target; or (b) has [*] and has not been shown to have [*] the
Target, a list of which has been delivered to PPD by
TSD.
1.5 “Collaboration Patent
Estate” means (a)
those Patents set forth in Schedule 1.5 and any
continuation, division, continuation-in-part or foreign equivalents
thereof, and (b) any Patents and any continuation, division,
continuation-in-part or foreign equivalents thereof that claim a
Collaboration Compound, regardless of the nature of the claim (i.e.
composition of matter, process, method, etc.).
1.6 “Combination Product”
means a formulation including two or
more active pharmaceutical ingredients, or a package including two
or more different pharmaceutical products, which includes Compound
as one of the active pharmaceutical ingredients but does not
include a Takeda Proprietary Compound as one of the active
pharmaceutical ingredients.
1.7 “Compound”
means (a) any Collaboration
Compound; and (b) any serine protease dipeptidyl peptidase IV
inhibitor discovered by TSD [*] that falls within the scope of the
Collaboration Patent Estate. For sake of clarity, an inhibitor of
the Target is specifically excluded from the definition of a
Compound if such inhibitor (a) has [*] and has been shown to have
[*] the Target, or (b) was Controlled by Takeda or an Affiliate of
Takeda other than TSD [*].
1.8 “Confidential
Information” shall
have the meaning set forth in Section 8.1.
1.9 “Control”
means, with respect to an item of
Information, Material or Intellectual Property right that a Party
owns or has a license to, that the Party has the ability to
disclose, assign and/or grant a license or sublicense as provided
for by this Agreement under such Information, Material or
Intellectual Property right without violating the terms of any
agreement or other arrangement with any Third Party.
1.10 “CTM” means a Product that is in a finished
pharmaceutical dosage form that is (a) suitable for administration
and dosing to humans in clinical trials, but (b) not suitable for
commercial sale (for example, without limitation, not in packaged
form such as blister packs or other containers and not including
external packaging and package inserts).
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1.11 “Development Plan”
means the 322 Development Plan and
such other development plans that TSD or its Affiliates may prepare
in the future (for other Compounds), by which TSD or its Affiliates
intend to achieve Regulatory Approval of a Product, including, but
not limited to, a description of the CMC, preclinical, clinical,
and regulatory activities, with estimated timelines necessary to
achieve such approval in the Field in the Territory.
1.12 “322 Development
Plan” means the
Development Plan for SYR110322 as shown in Schedule 1.12
.
1.13 “Diligent Efforts”
means the carrying out by TSD, its
Affiliate or its licensees or subcontractors of obligations or
tasks in a sustained manner consistent with the commercially
reasonable efforts TSD and its Affiliates devote to a research,
development or marketing project for a pharmaceutical product or
products of similar market potential, profit potential or strategic
value resulting from its own research efforts, based on conditions
then prevailing. Diligent Efforts includes, but is not limited to
the requirement that TSD and its Affiliates use commercially
reasonable efforts to carry out its obligations in accordance with
timelines set forth in a Development Plan by: (a) promptly
assigning responsibility for such obligations to specific
employee(s) who are held accountable for progress and monitor such
progress on an on-going basis, (b) setting and consistently seeking
to achieve specific and meaningful objectives for carrying out such
obligations, and (c) consistently making and implementing decisions
and allocating resources designed to advance progress with respect
to such objectives. The Parties understand and agree that delays
outside the control of TSD may occur with regard to the clinical
development of Compounds and that the occurrence of such delays, in
and of themselves, shall not be grounds for PPD to claim that a
material breach of this Agreement has occurred so long as TSD used
Diligent Efforts to avoid the occurrence of such delays, and is
using Diligent Efforts to reduce the impact of such delays
following their occurrence.
1.14 “Drug Substance”
means a Compound together with any
formulation ingredients, that is suitable for administration and
dosing to animals, other than humans.
1.15 “Effective Date”
means the last date on which the
Parties executed this Agreement.
1.16 “EMEA” means the European Medicine Agency.
1.17 “EU” means the European Union established under the
Maastricht Treaty on February 7, 1992, as amended from time to
time.
1.18 “FDA” means the United States Food and Drug
Administration, or a successor federal agency thereto.
1.19 “Field” means all treatments of humans using a
Product.
1.20 “Finished Product”
means a Product in a finished
pharmaceutical dosage form that is suitable for commercial sale
(for example, without limitation, in packaged form such as blister
packs or other containers and including external packaging and
package inserts).
1.21 “First Commercial
Sale” means the
first sale of a Product by TSD, its Affiliates or its licensees for
use, consumption or resale of such Product in a country
where Regulatory Approval of such Product has
been obtained by TSD, its Affiliates or its licensees. Sale of a
Product by TSD to an Affiliate of TSD or a licensee of TSD shall
not constitute a First Commercial Sale unless such Affiliate or
such licensee is the end user of the Product.
1.22 “Good Clinical Practices” or
“GCP” means
current Good Clinical Practices as specified in the United States
Code of Federal Regulations, at the time of testing, and all FDA
and ICH guidelines, including the ICH Consolidated Guidelines on
Good Clinical Practices.
1.23 “Good Laboratory Practices” or
“GLP” means
current Good Laboratory Practices as specified in the United States
Code of Federal Regulations at 21 CFR §58 at the time of
testing and all applicable ICH guidelines.
1.24 “Good Manufacturing Practices”
or “GMP” means current Good Manufacturing Practices and
standards as provided for (and as amended from time to time) in
European Community Directive 91/356/EEC (Principles and Guidelines
of Good Manufacturing Practice for Medicinal Products) and in the
Current Good Manufacturing Practice Regulations of the United
States Code of Federal Regulations Title 21 (21 CFR
§§210-211) in relation to the production of
pharmaceutical intermediates and active pharmaceutical ingredients,
as interpreted by ICH Harmonized Tripartite Guideline, Good
Manufacturing Practice Guide for Active Pharmaceutical Ingredients,
and subject to any arrangements, additions or clarifications agreed
from time to time between the Parties.
1.25 “HSR Act”
means Hart-Scott-Rodino Antitrust
Improvement Act of 1976, as amended.
1.26 “IND” means an Investigational New Drug Application
for a Product filed with the FDA necessary to commence human
clinical trials in conformance with applicable laws and
regulations.
1.27 “Information”
means information, results and data
of any type whatsoever, in any tangible or intangible form
whatsoever, including without limitation, databases, inventions,
practices, methods, techniques, specifications, formulations,
formulae, knowledge, know-how, skill, experience, test data
including pharmacological, biological, chemical, biochemical,
toxicological and clinical test data, analytical and quality
control data, stability data, studies and procedures, and patent
and other legal information or descriptions.
1.28 “Intellectual
Property” means (a)
all Regulatory Documentation, all Regulatory Filings and all
Regulatory Approvals; and (b) any and all inventions, developments,
results, know-how and other Information (including physical,
chemical or biological materials) made, conceived or reduced to
practice by PPD or its Affiliates before the Effective Date or
during the Term of this Agreement, whether alone or jointly with
TSD and its Affiliates or a Third Party that (i) relates to the
composition of matter, manufacture or use of a Compound, or (ii) is
incorporated into any Product or its use, or (iii) is necessary for
the discovery, identification, manufacture, development, or
commercial use or sale of any Product.
1.29 “Joint Development Committee”
or “JDC” means a committee composed as set forth in
Section 4.5 and having the duties set forth in Section
4.6.
1.30 “MAA” means Marketing Authorization Application
submitted to the EMEA.
1.31 “Marketing
Authorization” means any Regulatory Approval required to market
and sell a Product in any country.
1.32 “Marketing Plan”
means an annual marketing plan
prepared by TSD, its Affiliates or licensees or subcontractors,
that includes, but is not limited to, a prospective description of
TSD’s commercial objectives for the upcoming year with
respect to a Product throughout the Territory and the strategy by
which TSD intends to achieve such objectives.
1.33 “Material”
means any tangible material that
comprises, consists of, or incorporates a Collaboration Compound
and any precursor, prodrug, metabolite, ionized form (e.g., salt),
solvate (e.g., hydrate), stereoisomer (e.g., enantiomer,
diastereomer, mixture of isomers), resonant form, or tautomer
thereof.
1.34 “NDA” means a New Drug Application submitted and filed
with the FDA necessary for approval of a Product in conformance
with applicable laws and regulations.
1.35 “Net Sales”
means the total gross amount billed
or invoiced in United States dollars (or converted into US dollars
in accordance with this Agreement) by TSD, its Affiliates, or
licensees for sales of Products to a Third Party less, to the
extent included within the amount invoiced to and paid by the
customer, deductions for: (a) transportation charges, and other
charges, such as insurance, relating thereto, (b) sales and excise
taxes, customs and any other taxes, all to the extent imposed upon
the sale of the Products and paid by the selling party and not
refundable in accordance with applicable law (but not including
taxes assessed against the income derived from such sale), (c)
rebates or allowances actually granted or allowed to group
purchasing organizations, managed health care organizations and to
governments, including their agencies, or to trade customers, in
each case that are not Affiliates or licensees of TSD, (d) quantity
discounts, cash discounts or chargebacks actually granted, allowed
or incurred in the ordinary course of business in connection with
the sale of the Products, and (e) allowances or credits to
customers, not in excess of the selling price of the Products, on
account of governmental requirements, rejection, outdating recalls
or return of the Products. Such amounts shall be determined from
the books and records of TSD maintained in accordance with GAAP or
another generally accepted accounting method agreed by the Parties,
consistently applied. In the event a Product is sold as part of a
Combination Product or a Takeda Combination Product, Net Sales for
purposes of determining royalty and milestone payments hereunder,
shall be as follows:
(i) Net Sales in United States of
Combination Products and Takeda Combination Products
[*]: As long as [*], Net
Sales of a Combination Product or a Takeda Combination Product, as
the case may be, for purposes of determining royalty and milestone
payments hereunder, shall be [*]% of Net Sales of such Combination
Product or Takeda Combination Product, as the case may be. For sake
of clarity, [*] shall not, in and of themselves, cause a
Combination Product or a Takeda Combination Product to be [*]
pursuant to this Subsection 1.35(i).
(ii) Net Sales in United States
of Takeda Combination Products Not Subject to Section 1.35(i)
[*]: In regard to Takeda Combination Products that are not
subject to Section 1.35(i), for the [*] period commencing on [*],
Net
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Sales of such Takeda Combination
Product for purposes of determining royalty and milestone payments
hereunder, shall be [*]% of Net Sales of such Takeda Combination
Product. For sake of clarity, [*] shall not, in and of themselves,
cause a Takeda Combination Product to be [*] pursuant to this
Subsection 1.35(ii).
(iii) Net Sales in United States
of Combination Products or Takeda Combination Products Not Subject
to Sections 1.35(i-ii) [*]: In regard to Combination Products
and Takeda Combination Products that are not subject to Sections
1.35(i-ii), for the [*] period commencing on [*], Net Sales of such
Combination Product or Takeda Combination Product, as the case may
be, for purposes of determining royalty and milestone payments
hereunder, shall be [*]% of Net Sales of such Combination Product
or Takeda Combination Product, as the case may be. For sake of
clarity, [*] shall not, in and of themselves, cause a Combination
Product or a Takeda Combination Product to be [*] pursuant to this
Subsection 1.35(iii).
(iv) Net Sales in United States
of Takeda Combination Products Not Subject to Sections 1.35(i-iii)
[*]: In regard to Takeda Combination Products that are not
subject to Sections 1.35(i-iii), for the period commencing on [*],
Net Sales of a Takeda Combination Product for purposes of
determining royalty and milestone payments hereunder, shall be [*]%
of Net Sales of such Takeda Combination Product.
(v) Net Sales in United States of
Combination Products Not Subject to Section 1.35(i) or Section
1.35(iii) [*]: In regard
to Combination Products that are not subject to Section 1.35(i) or
Section 1.35(iii), for the period commencing on [*], Net Sales of
such Combination Product for purposes of determining royalty and
milestone payments hereunder, shall be [*]% of Net Sales of such
Combination Product.
(vi) Net Sales outside of United
States of Takeda Combination Products and Combination
Products: Net Sales
outside of the United States for Takeda Combination Products and
Combination Products, for the purpose of determining royalty and
milestone payments hereunder, shall be determined on a country by
country basis by multiplying the actual Net Sales of the Takeda
Combination Product or Combination Product by the fraction [*],
where A is [*] and B is [*]. Where available in a given country,
the [*] or [*] for the other product(s) in the given country will
be used as [*]. In the event that such [*] cannot be determined for
either the Product or other product(s) in the Combination Product
or the Takeda Combination Product, Net Sales for purposes of
determining royalty payments hereunder shall be calculated by
multiplying the Net Sales of the Combination Product or Takeda
Combination Product by the fraction [*], where C is [*] and D is
[*], determined in accordance with GAAP or another generally
accepted accounting method agreed by the parties, consistently
applied. PPD shall have the right to inspection to verify the
accuracy of the calculation of the Net Sales in accordance with
Section 6.5.
A sale of Product shall be deemed to have
occurred upon the invoicing of such Product to a Third Party; or if
not invoiced, then when delivered, shipped, or paid for,
whichever
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first occurs, provided that there shall be no
double counting of sales if a sale is deemed to have occurred when
Product is delivered to a Third Party. For purposes of
clarification, a sale of a Product shall be deemed to be made in a
particular country when the Product sold is intended for use by
consumers in such country. In the case of a sale or other disposal
of a Product for value other than in an arm’s-length
transaction exclusively for money, such as barter or counter-trade,
the amount of such sale shall be calculated using the fair market
value of such Product (if higher than the stated sales price) in
the country of disposition.
1.36 “Party” or
“Parties” shall have the meaning set forth in the first
paragraph of this Agreement.
1.37 “Patent”
means (a) an unexpired letters
patent (including inventor’s certificates) issued anywhere in
the world which has not been held invalid or unenforceable by a
court of competent jurisdiction from which no appeal can be taken
or has been taken within the required time period, including
without limitation any substitution, extension, registration,
confirmation, reissue, re-examination, renewal or any like filing
thereof, or (b) a pending application for a letters patent pending
anywhere in the world, including without limitation any
continuation, division or continuation-in-part thereof and any
provisional applications.
1.38 “Permitted Seller”
means TSD and any Affiliate,
licensee or sublicensee having the right to sell Product, including
without limitation, TPC and any permitted licensee of
TPC.
1.39 “Phase II Trial”
means a clinical trial of a Product
on patients, including possibly pharmacokinetic and dose ranging
studies, the principal purposes of which are to make a preliminary
determination that such Product is safe for its intended use and to
obtain sufficient information about such Product’s efficacy
to permit the design of further clinical trials, and generally
consistent with 21 CFR §312.21(b).
1.40 “Phase III Trial”
means that portion of the clinical
development program that provides for the pivotal human clinical
trials of a Product, which trial(s) is/are designed to (a)
establish that such Product is safe and efficacious for its
intended use; (b) define warnings, precautions and adverse
reactions that are associated with the Product in the dosage range
to be prescribed; (c) be a pivotal study for submission of a NDA;
and (d) be generally consistent with 21 CFR
§312.21(c).
1.41 “Phase III Development
Costs” means all
development costs incurred by either Party with TSD’s prior
approval under the Collaboration Agreement for (a) direct support
of the performance of a Phase III Trial or (b) process development
for a Product in a Phase III Trial. For clarity, Phase III
Development Costs include costs to formulate and manufacture Phase
III Trial CTM.
1.42 “PMDA” means the Pharmaceutical and Medical Devices
Agency in Japan.
1.43 “PPD Product”
means a human therapeutic product
that comprises SYR110322, SYR110619, [*] that PPD develops under
this Agreement by electing to exercise its option as to a PPD
Product pursuant to Article 12.
1.44 “Product”
means a human therapeutic product
that comprises, consists of, or
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incorporates a Compound that has less than [*],
or has [*] and has not been shown to have [*] the Target, including
a prodrug, metabolite, ionized form (e.g., salt), solvate (e.g.,
hydrate), stereoisomer (e.g., enantiomer, diastereomer, mixture of
isomers), resonant form, or tautomer of such Compound together with
any formulation ingredients, regardless of the formulation or mode
of administration of such Product. For sake of clarity, Product
includes Combination Products and Takeda Combination
Products.
1.45 “Regulatory
Approval” means any
and all approvals (including supplements, amendments, pre- and
post-approvals, pricing and reimbursement approvals), licenses,
registrations or authorizations of any national, supra-national
(e.g., the European Commission or the Council of the EU), regional,
state or local regulatory agency, department, bureau, commission,
council or other governmental entity, that are necessary for the
manufacture, distribution, use or sale of a Product in a regulatory
jurisdiction.
1.46 “Regulatory
Documentation” means, with respect to a Product, all regulatory
filings and supporting documents created, submitted to the FDA or
any equivalent agency or government authority outside of the United
States (including any supra-national agency such as in the EU)
relating to such Product, and all data contained therein,
including, without limitation, the contents of any IND(s), NDA(s),
BLA(s), Drug Master File, correspondence to and from the FDA or any
equivalent agency or governmental authority outside of the United
States, minutes from meetings (whether in person or by audio
conference or videoconference) with regulatory authorities,
registrations and licenses, regulatory drug lists, advertising and
promotion documents shared with regulatory authorities, adverse
event files, complaint files and manufacturing records.
1.47 “Regulatory Filing”
means the NDA or BLA or IND or any
foreign counterparts thereof and any other filings required by any
regulatory agency, department, bureau, commission, council or other
governmental entity in a regulatory jurisdiction relating to the
study, development, manufacture or commercialization of any
Product.
1.48 “Serious Adverse
Event” means any
adverse event related to a Product that results in any of the
following outcomes: death, a life-threatening adverse drug
experience, inpatient hospitalization or prolongation of existing
hospitalization, a persistent or significant disability/incapacity,
or a congenital anomaly/birth defect. Important medical events that
may not result in death, be life-threatening, or require
hospitalization may be considered a Serious Adverse Event when,
based upon appropriate medical judgment, they may jeopardize the
patient or subject and may require medical or surgical intervention
to prevent one of the outcomes listed in this
definition.
1.49 “Takeda Combination
Product” means a
formulation including two or more active pharmaceutical
ingredients, or a package including two or more different
pharmaceutical products, which includes a Compound and at least one
Takeda Proprietary Compound.
1.50 “Takeda Proprietary
Compound” means an
active pharmaceutical ingredient that (i) [*], (ii) is not a
Compound, (iii) either (x) is Controlled exclusively or
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semi-exclusively in a country or a region by
TSD, TPC or Takeda or an Affiliate thereof, or (y) TSD, TPC or
Takeda or an Affiliate thereof has or had exclusive or
semi-exclusive rights to commercialize and market such active
pharmaceutical ingredient in a country or a region, and (iv) has
been incorporated into a pharmaceutical product (including a
Product) that was introduced into the commercial market. ACTOS is
one example of a Takeda Proprietary Compound.
1.51 “Target”
means human serine protease
dipeptidyl peptidase IV (DP4).
1.52 “Term” shall have the meaning assigned to it in Section
10.1.
1.53 “Territory”
means throughout the
world.
1.54 “Third Party”
means any individual, corporation,
partnership, limited liability company or other entity other than
(i) TSD, (ii) PPD or (iii) an Affiliate of either of
them.
ARTICLE 2
COLLABORATION
AGREEMENT
2.1 Termination of Collaboration
Agreement.
(a) TSD and PPD agree that the
Collaboration Agreement is hereby terminated in its entirety as of
the Effective Date. As of the Effective Date, the Collaboration
Agreement shall have no further force or effect (including, subject
to Section 2.1(a)(iii), any provisions that would otherwise
survive) and no Party thereto shall have any further right or
obligation thereunder except that:
(i) PPD shall assign, and TSD shall
assume, in an Assignment and Assumption Agreement substantially in
the form of Schedule 2.1(a)(i)(1) , all contracts with Third
Parties under or in connection with the Collaboration Agreement,
including investigator sites, that are in existence as of the
Effective Date, to the extent assignable; provided, that PPD and
TSD shall each use reasonable efforts to obtain any necessary
consents from Third Parties promptly after the Effective Date.
Schedule 2.1(a)(i)(2) lists all Third Party contracts in existence
as of the Effective Date. PPD confirms that it has provided TSD
with true and correct copies of all Third Party contracts in
existence as of the Effective Date and as listed in Schedule
2.1(a)(i)(2) .
(ii) TSD shall have the obligations
of payment for services to be performed by PPD pursuant to the
Collaboration Agreement as set forth in Section 5.4 of this
Agreement; and
(iii) Articles 12, 14, 15, 16, and
17 and Sections 3.4(e)(ii) and 11.1 of the Collaboration Agreement
shall survive termination.
(b) Without limiting the generality
of the foregoing, following the Effective Date, and except as
specifically set forth herein, PPD shall not, directly or
indirectly, have any liability or obligation for any cost or
expense related to any Compound or Product, including but not
limited to costs or expenses for research, development,
manufacturing, or commercialization of any Compound or any
Product.
2.2 Reversion of License Rights in the
Collaboration Agreement .
Except as otherwise provided in Section 2.1(a) of this Agreement,
as of the Effective Date, (a) all
rights and licenses granted by TSD to PPD under
the Collaboration Agreement shall terminate and revert to TSD, and
(b) all rights and licenses granted by PPD to TSD under the
Collaboration Agreement shall terminate and revert to
PPD.
2.3 End of Collaboration Agreement
Report . As soon as
possible, but no later than thirty (30) days from the Effective
Date, PPD shall provide to TSD a written report summarizing the
status of SYR110322 Phase II Trial and API production for Phase III
through the Effective Date. The provision of such report shall not
relieve PPD from its obligations under Section 3.3. Such report
shall identify any and all material written Information related to
the API and Phase II Trial known to PPD as of the Effective Date.
PPD shall also provide to TSD a final report for the SYR110619
Phase I trial on or about July 31, 2005. Following delivery of such
reports, TSD shall have a right to reasonably request through the
JDC additional information from PPD relating to the SYR110322 and
SYR110619 development programs and results, and PPD shall provide
such information.
2.4 Mutual Release From Claims Arising Under the
Collaboration Agreement .
Each Party, on behalf of itself and its predecessors, successors,
parents, subsidiaries, Affiliates, segments or divisions, and
present and former shareholders, officers, directors, employees,
agents, assigns and representatives and their heirs, family members
and executors, hereby releases the other Party and its
predecessors, successors, parents, subsidiaries, Affiliates,
segments or divisions, and present and former members,
shareholders, officers, directors, agents, employees,
representatives, attorneys, and assigns from any and all claims,
demands, obligations, or liability of whatever kind, that it has,
had, or may have against the other Party, whether asserted or
otherwise and whether known or unknown, for any claims, actions, or
matters of any kind arising through the Effective Date in relation
to the Collaboration Agreement, provided however, that such release
shall not extend to any claims, demands, obligations, or liability
of whatever kind, that it may have against the other Party either
under this Agreement or under the Collaboration Agreement arising
after the Effective Date, or claims for indemnity under Article 15
of the Collaboration Agreement for matters covered under such
indemnification provisions that arose before the Effective
Date.
2.5 California Civil Code Section
1542 . The Parties
represent that they are not aware of any claims other than the
claims that are released by this Agreement. The Parties also
acknowledge that they have been advised by legal counsel and each
Party hereby waives the provisions of California Civil Code Section
1542, which provides as follows:
A GENERAL RELEASE DOES NOT EXTEND TO
CLAIMS WHICH THE CREDITOR DOES NOT KNOW OR SUSPECT TO EXIST IN HIS
FAVOR AT THE TIME OF EXECUTING THE RELEASE, WHICH IF KNOWN BY HIM
MUST HAVE MATERIALLY AFFECTED HIS SETTLEMENT WITH THE
DEBTOR.
ARTICLE 3
ASSIGNMENT and
LICENSE
3.1 Assignment . Subject to all of the terms and conditions of
this Agreement, PPD hereby irrevocably sells, assigns, delivers,
conveys, transfers and sets over to TSD, its successors and assigns
the entire right, title and interest to Intellectual Property that
PPD or an Affiliate of PPD Controls as of the Effective Date or
during the Term of this Agreement.
3.2 License. To the extent that PPD is unable to assign any
Intellectual Property Controlled by PPD or an Affiliate of PPD as
of the Effective Date or during the Term of this Agreement, PPD
hereby grants and shall grant to TSD a perpetual, worldwide,
exclusive license (even as to PPD), with the right to grant
sublicenses as is reasonably necessary for TSD to achieve Rgulatory
Approval and commercialize Products, to such Intellectual Property.
To the extent that PPD is unable to grant an exclusive license to
any Intellectual Property Controlled by PPD or an Affiliate of PPD
as of the Effective Date or during the Term of this Agreement, PPD
hereby grants and shall grant to TSD a perpetual, worldwide,
non-exclusive license, with the right to grant sublicenses as is
reasonably necessary for TSD to achieve Rgulatory Approval and
commercialize Products, to such Intellectual Property. TSD agrees
to perform under and abide by the terms and conditions of any
underlying licenses to such Intellectual Property.
3.3 Delivery of Documents and
Materials . Promptly
following the Effective Date, PPD shall deliver to TSD any and all
data and documentation in PPD’s Control related to the
development of a Compound or Product, and not in the possession of
TSD, on the Effective Date. Following the Effective Date, PPD shall
promptly notify TSD if it later discovers any data or documentation
in PPD’s Control related to the development of a Compound or
Product that was not previously delivered to TSD and shall promptly
deliver such to TSD. Promptly following the Effective Date, PPD
shall transfer to TSD the legal title to the associated INDs
presently on file and any comparable filings in other countries of
the Territory for SYR110322 and SYR110619. PPD shall transfer to
TSD ownership of all Drug Substance, CTM and Finished Product of
SYR110322 and SYR110619 and any other Material in its possession as
of the Effective Date of this Agreement, the amounts of which are
listed on Schedule 3.3 .
3.4 Notice of New Intellectual Property
Developed by PPD After the Effective Date . PPD shall promptly provide TSD with notice of
any Intellectual Property that PPD develops following the Effective
Date. PPD will promptly provide to TSD information and access to
personnel reasonably requested by TSD that is necessary for seeking
protection of such Intellectual Property. All expenses incurred by
TSD associated with seeking protection of Intellectual Property
shall be paid by TSD.
ARTICLE 4
DEVELOPMENT
4.1 Control over Development
. Subject to Section 4.3 and its
obligations to use Diligent Efforts, TSD shall, directly or through
its Affiliates or licensees or subcontractors, have full control
over implementation of all aspects of a Product’s
development, marketing and commercialization throughout the Term of
this Agreement, and shall be solely responsible for all costs and
expense associated therewith.
4.2 Design and Modifications to the Development
Plan . Except as set
forth in Section 4.3, TSD shall consult PPD with regard to the
design and implementation of a Development Plan as well as
modifications to a Development Plan and take PPD’s
suggestions into consideration. Except as set forth in this Section
4.2 and Section 4.3, TSD shall have the right, in its sole
reasonable discretion, to modify a Development Plan after TSD
consults with PPD about any proposed material changes to a
Development Plan and TSD shall give full consideration to any
reasonable comments or suggestions by PPD. TSD shall at all times
exercise Diligent Efforts in the design, development,
implementation, and modification of a Development Plan.
4.3 Development and Commercialization of
SYR110322 . During the
term of this Agreement, TSD shall be responsible for the remainder
of clinical and non-clinical development of SYR110322 in accordance
with the 322 Development Plan, and TSD shall be solely responsible
for all costs and expenses associated therewith. TSD shall have the
right to modify the 322 Development Plan from time to time as
reasonably necessary, [*]. TSD will use Diligent Efforts to submit
applications for regulatory approval to market a Product comprising
SYR110322 in the United States, EU and Japan, and will use Diligent
Efforts to file an MAA in the European Union for a Product
comprising SYR110322 with the EMEA within [*] of acceptance of an
NDA filing for a Product comprising SYR110322. Upon approval in a
country, TSD shall use Diligent Efforts to market such Product in
such country. TSD shall promptly notify PPD in writing of the First
Commercial Sale of a Product in each country. TSD shall use
Diligent Efforts to exploit the lifecycle of the Product including,
where appropriate, carrying out clinical trials and/or other
studies on the Product and obtaining Marketing Authorizations. TSD
shall use Diligent Efforts to commercialize Product, including
deploying sales personnel as necessary to promote the Product,
taking into account the sales volume of the Product, the number of
competitors, the regulatory environment, and the potential for
sales in a geographic area. TSD shall use Diligent Efforts to
maximize the Net Sales of Products.
4.4 Development and Commercialization of Backup
Product . Should TSD
cease to develop and commercialize a Product comprising SYR110322
despite using Diligent Efforts, then TSD shall use Diligent Efforts
(and shall cause any Affiliates, licensees or subcontractors
participating in the subject matter of this Agreement to use
Diligent Efforts) to develop and introduce a Product comprising one
of SYR110619 [*] to the commercial market and to market such
Product. Should TSD cease to develop and commercialize such Product
despite using Diligent Efforts, then TSD shall use Diligent Efforts
(and shall cause any licensees or subcontractors participating in
the subject matter of this Agreement to use Diligent Efforts) to
develop and introduce a Product comprising [*] SYR110619 [*] to the
commercial market and to market such Product. With respect to this
Section 4.4, TSD will use Diligent Efforts to submit applications
for regulatory approval to market the SYR110619 [*] Product in the
United States, EU and Japan. Should TSD cease to develop and
commercialize such Product despite using Diligent Efforts, then TSD
shall not have any further obligation to develop alternative
Compound(s) under this Agreement.
4.5 Joint Development Committee
. Within thirty (30) days of the
Effective Date, PPD and TSD shall assemble a JDC. Initially, the
JDC will be composed of at least two, but no more than six,
representatives, with an equal number appointed by each of PPD and
TSD, or their Affiliates. A list shall be provided to the other
Party within thirty (30) days after the Effective Date. Each Party
will promptly notify the other Party in writing of any change in
its appointed representatives. The chairperson of the JDC will be
one of TSD’s or its Affiliate’s
representatives.
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4.6 Duties of JDC . The duties of the JDC shall include, but not
be limited to, (a) reporting the progress of all Development and
Marketing Plans; (b) providing updates describing the progress made
in designing and implementing new Development or Marketing Plan(s);
(c) discussing potential modifications to any Development Plan; (d)
reporting the results of any efforts, if any, to evaluate potential
therapeutic applications for Compounds other than type II diabetes;
and (e) providing updates on discovery, non-clinical and
preclinical, clinical development or marketing of Compounds other
than SYR110322. TSD shall promptly provide PPD with copies, through
the JDC, of all Development Plans and Marketing Plans. TSD shall
also provide PPD with copies through the JDC of all Regulatory
Filings, Regulatory Documentation and communications with
regulatory agencies within ten (10) days of mailing or receipt of
Regulatory Filings, Regulatory Documentation or communications, as
the case may be, with a regulatory agency. TSD shall provide to PPD
copies of all final clinical study reports. A PPD JDC member shall
have the right to consult with the JDC if the PPD JDC member
reasonably believes information is needed from TSD in order to
protect PPD’s interests, as the case may be, in the subject
matter of this Agreement, and TSD through the JDC shall reasonably
cooperate in connection therewith. To accomplish its objectives,
the JDC will meet quarterly, or more often if mutually agreed upon
by the Parties, during the term of any Development Plan or during
any period of post-marketing regulatory activity, and will meet at
least annually thereafter. The JDC may meet in person or by
telephone or video conference. In-person JDC meetings will be held
in Chicago, IL or such other sites that the Parties may mutually
agree upon. Each Party will bear all expenses of its personnel
arising from attending such meetings. Among other duties, one of
TSD’s JDC members shall prepare and promptly circulate to the
other JDC members written minutes of each such meeting, which
minutes will, without limitation, record the updates given at the
meetings describing the progress made in discovery, development,
and commercialization of a Product. Both Parties acknowledge and
agree that they intend to be as transparent as reasonably possible
with each other on all material issues relating to development and
commercialization of Product, and that the forum for achieving such
transparency shall be the JDC.
4.7 Decision Making By the JDC
. TSD shall have a sole and final
vote on any issue and matter in the JDC after taking into account
TSD’s obligation to use Diligent Efforts as set forth in
Article 4.
4.8 Serious Adverse Event
. TSD shall immediately inform PPD
in writing of the occurrence of any Serious Adverse Event with
regard to a Product.
4.9 Clinical Development
Collaboration . TSD
agrees to utilize PPD exclusively for clinical and bioanalytical
CRO services related to the Phase II and Phase III Trials of
Products that are conducted in support of obtaining Regulatory
Approval in the U.S. and in the EU, in all cases, under terms and
conditions mutually acceptable to the Parties; provided that (a)
PPD provides such services at [*] rates which are applied between
PPD, Takeda Global Research and Development Center, Inc.
(“TGRD”) and Takeda Europe Research & Development
Centre Ltd. (“TeuR&D), and (b) PPD demonstrates that it
has and is maintaining the requisite technical expertise and
capacity to reliably provide such services in a professional and
competent manner. TSD will consider in good faith using PPD for CRO
services related to Phase IV trials
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of the Products and biostatistics and data
management services related to Phase II-IV trials of the Products.
CRO services performed by PPD pursuant to this Section 4.9 shall be
governed by that certain Global Master Agreement, Clinical Research
Management Services (Phase II-IV) dated July 1, 2004, that certain
Global Master Agreement, Bioanalytical Laboratory Services dated
September 1, 2004 and that certain Global Master Agreement,
Biostatistics and Data Management Services (Phase II-IV) dated July
13, 2005, each of which is
