CONFIDENTIAL TREATMENT REQUESTED
UNDER 17 C.F.R. SECTIONS 200.80(b)4, AND 240.24b-2
[ISIS PHARMACEUTICALS LOGO]
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OLIGONUCLEOTIDE MANUFACTURING AND
SUPPLY AGREEMENT
By and between
ISIS PHARMACEUTICALS, INC.
▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
- Hereinafter referred to as ISIS -
and
INTEGRATED DNA TECHNOLOGIES, INC.
▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
- Hereinafter referred to as IDT -
TABLE OF CONTENTS
Recitals.............................................................2
Article 1 Definitions...............................................2
Article 2 Oligonucleotide Supply Period and Deposit.................4
Article 3 Program Oligonucleotide Specifications Committee..........5
Article 4 ▇▇▇▇▇▇▇▇, Pricing and Invoicing...........................6
Article 5 Intellectual Property.....................................8
Article 6 Representations and Warranties ...........................9
Article 7 Confidential Information.................................12
Article 8 Term and Termination.....................................13
Article 9 Indemnification..........................................15
Article 10 General..................................................15
Appendix A.........................................................A-1
Appendix B.........................................................B-1
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RECITALS
WHEREAS, ISIS and its GeneTrove Division have a need for a reliable
supply of quality-controlled oligonucleotides for use in its antisense
functional genomics and target validation program; and
WHEREAS, IDT has the expertise and manufacturing capacity sufficient
to supply ISIS quality controlled oligonucleotides at required volumes; and
WHEREAS, both IDT and ▇▇▇▇ are willing to collaborate in continuous
efforts to refine IDT's oligonucleotides manufacturing, purification and quality
controlled techniques to ensure that ISIS receives optimized oligonucleotides
for use in its functional genomics program;
NOW THEREFORE, IDT and ISIS agree to the following
Oligonucleotide
Manufacturing and Supply Agreement according to the terms and conditions as
stated herein.
ARTICLE 1:
DEFINITIONS
For purposes of this
Oligonucleotide Manufacturing and Supply Agreement, the
following words, phrases, or terms shall have the meanings as herein defined:
1.0 "Agreement" shall mean this
Oligonucleotide Manufacturing and Supply
Agreement, including Appendices A and B, as originally executed and as
properly amended from time to time according to Article 10.
1.1 "Antisense Oligonucleotides" shall mean a polynucleotide,
oligonucleotide or oligonucleotide analog, which hybridizes in a
sequence specific manner under physiological conditions to RNA forming
an RNA-DNA duplex, which duplex acts to modulate the production of a
targeted gene product. An antisense oligonucleotide analog may include
naturally occurring or non-natural heterocycles, sugar and/or backbone
linkages, and may be a molecule in which the sugar may be absent, in
which the backbone linkage may be phosphate based, amide based, or
based on other chemistries and which may or may not include stem loop
or structural units.
1.2 "Assigned Supply Period" shall mean the [***] year period immediately
following the Effective Date.
1.3 "Assigned Systems" shall mean oligonucleotide synthesizers,
purification and analytical instruments, and other supporting equipment
assigned by IDT to support the manufacture and delivery of ISIS's
requirements of Program Oligonucleotides.
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1.4 "Business Day(s)" shall mean those days from Monday through Friday,
which are not declared as national holidays in the United States, or as
holidays routinely recognized by one or more of the Parties.
1.5 "Calendar Days" shall mean all days Sunday through Saturday, which
appear on the calendar from January 1 through December 31.
1.6 "Customer Deposit" shall mean the credit for dedicated Program
Oligonucleotide supply and Program Oligonucleotide purchases obtained
by ISIS under this Agreement, which will be credited to the benefit of
ISIS against Program Oligonucleotide purchases by ISIS at a rate of
[***] of the monthly Program Oligonucleotide invoice described in
section 4.8 herein.
1.7 "Dedicated Data Management System" shall mean the components of an
integrated hardware and software system designed to support the
isolated processing, tracking and storage of all information related to
ISIS Program Oligonucleotide orders, with access limited to authorized
personnel of IDT and/or ISIS.
1.8 "Effective Date" shall mean the execution date of the last signature on
the signature page of this Agreement.
1.9 "IDT" shall mean Integrated DNA Technologies, Inc., and its affiliates,
if any.
1.10 "IDT List Price" shall mean the then current IDT Catalog price for a
specified product or service as displayed in IDT's World Wide Web
On-line Catalog at (▇▇▇.▇▇▇▇▇▇.▇▇▇) or any successive Internet URL.
1.11 "Intellectual Property" shall mean and includes, but is not limited to,
inventions (whether patentable or unpatentable), trade secrets, all
present improvements thereto and future improvements thereto, and all
United States, and foreign patents, patent applications, patent
disclosures, and patentable inventions, together with all reissuances,
continuations, continuations-in-part, divisionals, revisions,
extensions and reexaminations thereof.
1.12 "ISIS" shall mean ISIS Pharmaceuticals, Inc., its and its divisions,
including specifically GeneTrove-TM-.
1.13 "ISIS Supplied Reagent" shall mean those reagents to be supplied by
ISIS to IDT that are necessary for the specific and limited purpose of
enabling or optimizing IDT's manufacture and supply of MOE
Oligonucleotides or Antisense Oligonucleotides to ISIS.
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1.14 "MOE Oligonucleotides" shall mean oligonucleotides ordered from IDT by
ISIS, which contain one or more of ISIS's proprietary 2'methoxy-ethoxy
modifications (or any combination of an alkyl, alkoxy or thioalkoxy
together with an ether, ester, amino or aminohydroxy substituent). With
the exception of Appendix A and paragraph 4.2 herein, and at ISIS's
sole discretion, ▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇▇▇▇▇ may also mean any Antisense
Oligonucleotide ordered by ISIS from IDT.
1.15 "Parties" shall refer collectively to ISIS and IDT, each individually
referred to as a "Party".
1.16 "Primers" shall refer to unmodified oligonucleotides used to promote
amplification of a targeted sequence.
1.17 "Probes" shall refer to dye-labeled or similarly modified
oligonucleotides used to detect and/or quantify the presence of a
targeted sequence in a sample.
1.18 "Program Oligonucleotide" means a MOE Oligonucleotide and/or a
Quantification Oligonucleotide conforming to the specifications and
criteria set forth in Appendix A (as amended from time to time) for
supply and delivery to ISIS.
1.19 "Quantification Oligonucleotide" shall mean Primers and Probes, either
ordered individually by ISIS, or as 96-well plate combinations referred
to as "Primer-Probes Sets" as defined in Appendix A (as amended from
time to time).
ARTICLE 2
OLIGONUCLEOTIDE SUPPLY PERIOD AND DEPOSIT
2.1 SUPPLY PERIOD. For the duration of the Assigned Supply Period, IDT will
utilize the Assigned Systems to manufacture and sell Program
Oligonucleotides ordered by ISIS according to the terms and conditions
as described in this Agreement. This commitment by IDT includes the
obligations of IDT to individually staff, train, and fully compensate,
the personnel needed to operate the Assigned Systems for ISIS, and to
otherwise fully manage the production and delivery of Program
Oligonucleotides to ISIS.
2.2 SUPPLY DEPOSIT. ISIS shall advance IDT five million dollars
($5 million) to IDT within five (5) Business Days of the effective date
of the Amended and Restated IDT-ISIS Licensing Agreement, in the form
of Customer Deposit.
2.3 ASSIGNMENT OF MANUFACTURING CAPACITY. IDT will utilize the
Customer Deposit to assign within its facility sufficient Program
Oligonucleotide synthesis, processing and purification capacity to
manufacture [***] MOE Oligonucleotides and [***]
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Quantification Oligonucleotides per calendar year for ISIS over the
term of this Agreement.
2.4 DEDICATED DATA MANAGEMENT SYSTEM. IDT will further utilize the
Customer Deposit to design and implement the Dedicated Data Management
System to accommodate the expected ordering parameters of Program
Oligonucleotides and to specifically track the utilization of ISIS's
Customer Deposit.
2.5 SALE OF PROGRAM OLIGONUCLEOTIDES. For the duration of the Assigned
Supply Period, IDT will make and sell Program Oligonucleotides to ISIS
in accordance with the pricing provisions contained in Article 3. IDT
will invoice ISIS at the listed prices less [***] for each Program
Oligonucleotide ordered by ISIS and shipped by IDT, and shall reduce
ISIS's Customer Deposit by the corresponding [***] sum.
ARTICLE 3
PROGRAM OLIGONUCLEOTIDE SPECIFICATIONS COMMITTEE
3.1 COMMITTEE OBJECTIVE. In order to ensure the manufacture and supply to
ISIS of optimized Program Oligonucleotides for the duration of this
Agreement, IDT and ISIS will form a joint committee of their respective
employees to develop, enforce and continuously refine specifications
for the manufacture, supply, and receipt of MOE Oligonucleotides and/or
Quantification Oligonucleotides (the "Program Oligonucleotide
Specifications Committee").
3.2 COMMITTEE FORMATION AND MANAGEMENT. It is contemplated by the Parties
that all decisions affecting or regarding Program Oligonucleotide
specifications (Appendix A) will be the result of informed deliberation
and mutual consent of the Program Oligonucleotide Specifications
Committee (POSC). Each Party shall appoint a Committee Co-Chair, who
will have the joint authority, independent of the POSC, to make any
decision regarding modifications to the Program Oligonucleotide
specifications. The Co-Chairs will appoint additional individuals to
serve on the POSC. The POSC will meet at least once monthly to review
the performance of each Party under the Agreement, to forecast future
supply requirements, and to resolve any Program Oligonucleotide supply,
quality and/or invoicing issues. The POSC will instruct staff members
to direct all related issues or concerns through the POSC and will
distribute minutes of its meetings to the relevant members of their
organizations. IDT hereby appoints ▇▇▇▇ ▇▇▇▇▇▇ and ISIS hereby appoints
▇▇▇▇▇ ▇▇▇▇▇▇ as the acting Committee Co-Chairs for each respective
Party.
3.3 INITIAL OLIGO SPECIFICATION DEVELOPMENT. The specifications listed on
Appendix A will serve as the Program Oligonucleotide Specifications
until amended by POSC. Within ten (10) days of the Effective Date, the
POSC will meet to initiate the controlled development of refined
manufacturing specifications (including yield, purity, quality control
tests and criteria, shipping standards, remake policies, etc.) for both
MOE Oligonucleotides and Quantification Oligonucleotides.
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3.4 SCOPE OF POSC AUTHORITY. The POSC (or the Co-Chairs acting jointly)
has the authority to change the following with respect to Program
Oligonucleotide specifications: synthesis scale; yield guarantees;
chemical compositions; purity requirements; analytical or quality
control tests and/or specifications; and all pricing changes directly
related to such changes, provided that the resulting prices reflect,
whenever possible, the fixed percentage discount rate of paragraph 4.3.
All price changes require the signed written agreement of both
Co-Chairs prior to their use in an invoice issued to ISIS pursuant to
paragraph 4.8 hereunder. The POSC shall not have the authority to apply
Customer Deposit to oligonucleotides or other products other than to
Program Oligonucleotides.
ARTICLE 4
ORDERING, PRICING AND INVOICING
4.1 PROGRAM OLIGONUCLEOTIDE ORDERING. ISIS shall place all orders for
Program Oligonucleotides over the Dedicated Data Management System,
using the customer order entry software developed by IDT for ISIS
pursuant to paragraph 2.5.
4.2 MOE OLIGONUCLEOTIDE PRICING. Subject to the provisions contained in
paragraphs 2.4, 4.4, and 4.5 hereunder, the invoice price for MOE
Oligonucleotides prior to the application of Customer Deposit will be:
(i) [***] for each MOE Oligonucleotide manufactured on
the [***] scale that meets the MOE specifications;
(ii) [***] for each MOE Oligonucleotide manufactured on
the [***] scale that meets the MOE specifications.
4.3 QUANTIFICATION OLIGONUCLEOTIDE PRICING/FIXED PERCENTAGE DISCOUNT.
Subject to the provisions contained in paragraphs in 2.4, 4.4 and 4.5
hereunder, the invoice price for Quantification Oligonucleotides
(and/or Antisense Oligonucleotide) prior to application of Customer
Deposit shall be [***] of the IDT List Price for corresponding
oligonucleotide Primers and/or Probes and the associated purification,
analytical and/or set-up fees. This fixed percentage discount is also
to be used by the POSC to guide its pricing decisions relevant to
changes to MOE Oligonucleotide specifications, including specifically
changes to purification, analytical, loading, shipping or handling
specifications. Appendix B illustrates the application of this fixed
percentage discount to Primer-Probe Sets and MOE Oligonucleotides using
IDT List Prices.
4.4 EXTERNAL FACTORS & PRICE INCREASES. IDT warrants that it has performed
adequate manufacturing cost-forecasting to ensure that IDT can supply
Program Oligonucleotides in commercially viable fashion at the above
quoted per base prices or at the established [***] discount. However,
should unforeseeable events beyond the control of IDT cause the
manufacturing costs of IDT to increase by [***] then IDT shall have the
right to
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increase the per [***] price to reflect the increased manufacturing
cost. The term "unforeseeable events" as used in this paragraph
includes, but is not limited to:
(i) new and substantial regulatory or legal restrictions imposed
on the manufacture of oligonucleotides or related
manufacturing processes;
(ii) substantial increase(s) in the cost of necessary
oligonucleotide manufacturing amidites, reagents, solvents, or
quality control components, necessary to manufacture Program
Oligonucleotides;
Should IDT rely upon "unforeseeable events" beyond the control of IDT
as a basis for a price increase, IDT shall immediately as is practical
disclose in writing to ISIS through the POSC the cause of the price
increase, and IDT's relevant manufacturing costs in sufficient detail
to allow for confirmation of the costs by ▇▇▇▇.
4.5 PRICE DECREASES/MOST FAVORED PRICING. If there are substantial
decreases in the market cost of commercial amidites, reagents,
solvents, or quality control components necessary to manufacture
Program Oligonucleotides that result in [***] or greater reduction in
the average cost [***] to IDT, then IDT shall reduce the [***] price
charges to ISIS by the amount greater than the [***] cost per base
threshold.
4.6 TURNAROUND. The specifications and requirements for delivery of
manufacture of Program Oligonucleotides will be those specifications
and turnaround requirements identified in Appendix A, as amended from
time-to-time by the POSC.
4.7 SUPPLY FORECASTS/ISIS SUPPLIED REAGENT INVENTORY. On or before the
[***] of each month during the Assigned Supply Period, ISIS will supply
IDT with a forecast of its intended Program Oligonucleotide orders for
the following month. IDT will advise ISIS within [***] Days of receipt
of its ability to meet the forecast. IDT will specifically advise ISIS
of its then current inventory of ISIS Supplied Reagents and of its need
for additional ISIS Supplied Reagents to meet the forecast for the
following month. It is the expectation of both Parties that IDT will:
(i) maintain on-site, a constant minimum [***] inventory
of quality-controlled ISIS Supplied Reagents;
(ii) maintain available manufacturing capacity to meet any
forecast that requires a monthly MOE Oligonucleotide
supply of [***] MOE Oligonucleotides or less, and a
monthly Quantification Oligonucleotide supply of
[***] Primer-Probe Sets or less;
(iii) make reasonable efforts to meet forecasts that exceed
those limits in (ii) above. In the event that an ISIS
forecast is for volumes of Program Oligonucleotides,
which volumes are [***] greater than the prior month,
then IDT's ability to meet such a forecast may
require a scale-up period.
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4.8 INVOICING. During the Assigned Supply Period, IDT will invoice ISIS
following the close of each month in accordance with 2.5 herein, for
Program Oligonucleotides delivered that meet the specifications
established by the POSC. Payment of the invoice by ISIS will be due
within [***] Days from receipt of the invoice by ISIS, and payment will
be made by electronic wire transfer into an account as designated by
IDT. Should ISIS fail to pay the full invoice within [***] Days, IDT
will have the right to suspend Program Oligonucleotide manufacturing
until the invoice is paid in full.
4.9 MOST-FAVORED QUANTIFICATION OLIGONUCLEOTIDE PRICING. In addition to
IDT's commitment to maintain a fixed [***] discount for Quantification
Oligonucleotides and Antisense Oligonucleotides, IDT agrees not to
extend more favorable pricing to third-parties with comparable orders
for Antisense Oligonucleotides and/or Probes, whether ordered
individually or as part of a Primer-Probe Set. For purposes of this
provision, "comparable orders" shall mean orders for oligonucleotides
in equal or lesser volumes, on the same or substantially similar scale,
with the same or substantially similar modifications, purification or
purity requirements, analytical specifications, and loading
requirements. This provision shall not apply to more favorable prices
extended to third-parties by IDT for Primers ordered without
corresponding orders for Probes, nor shall it apply to Probes, Primers,
or Antisense Oligonucleotides when sold or transferred in any of the
following non-limiting circumstances: as part of a bona-fide research
collaboration; as a component of a kit; as part of a defined promotion;
as a test-order; or as a remake.
4.10 CUSTOMER DEPOSIT DEPLETION. Unless IDT and ISIS agree in writing to
extend the Agreement and the Assigned Supply Period, any unused
portions of the Customer Deposit at the end of the Assigned Supply
Period will be forfeited by ISIS and will become the exclusive property
of IDT.
ARTICLE 5
INTELLECTUAL PROPERTY
5.1 INVENTIONS AND DISCOVERIES. The Parties do not anticipate but do
acknowledge that Intellectual Property may be developed through the
joint efforts of the Parties and their employees under this Agreement.
If Intellectual Property is developed by an individual Party, or by or
through the joint efforts of the Parties, the ownership of the
Intellectual Property, whether joint or separate, will be determined by
the relevant applicable United States patent laws. In the event that an
invention or know-how is developed through the joint or collaborative
efforts of the Parties and their employees, IDT and ISIS agree to
instruct their respective employees to report the invention or the
development in a thorough and prudent manner to the management of the
respective Parties, and each Party and agrees to notify the other Party
of the invention or the development as soon as commercially practical
following internal reporting. The Parties thereafter agree to initiate
good faith negotiations directed toward the completion of a separate
written agreement directed to licensing and/or assignment of such
Intellectual Property.
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5.2 TRADENAMES AND TRADEMARKS. IDT acknowledges that GeneTrove-TM- and
ISIS, among others, are trademarks and tradenames of ISIS, and that
nothing in this Agreement is intended as a grant to IDT, express,
implied, or otherwise, to use any trademark, tradename or trade dress
of ISIS unless expressly agreed to in writing by ISIS.
5.3 PROGRAM OLIGONUCLEOTIDES AND OLIGONUCLEOTIDE MANUFACTURING METHODS.
Notwithstanding the provisions of paragraph 5.1, ISIS shall be the sole
owner of the Program Oligonucleotides, which are or contain the
Confidential Information of ISIS and subject to the provisions of
Article 7. Except with respect to patents and patent applications
exclusively licensed to IDT in the field of antisense technology, IDT
hereby assigns its entire worldwide right, title, and interest, if any,
in any Program Oligonucleotide to ISIS, and IDT agrees to take all
necessary action to effect any such transfer, and to cooperate with and
assist ISIS, at ISIS's expense, in the pursuit, enforcement, and
defense of any Intellectual Property rights in any Program
Oligonucleotide. IDT shall be the sole owner of the oligonucleotide
manufacturing and tracking methods developed by IDT prior to and/or
during the term of this Agreement, including, but not limited to, IDT's
proprietary technology in the following fields: oligo reagent
preparation methods; oligo synthesis methods; oligo processing and
automation protocols; oligo mass order entry software; oligo tracking
software; and oligo quality control systems; excluding, however, the
aforementioned IDT manufacturing and tracking methods pertaining
specifically and/or exclusively to ISIS Supplied Reagents.
ARTICLE 6
REPRESENTATIONS AND WARRANTIES
6.1 REPRESENTATIONS AND WARRANTIES BY IDT:
IDT represents and warrants as follows:
(i) IDT is a corporation duly organized, validly existing and in
corporate good standing under the laws of the State of Iowa;
(ii) IDT has the legal right, authority and power to enter into
this Agreement;
(iii) IDT has taken all necessary action to authorize the execution,
delivery and performance of this Agreement;
(iv) upon the execution and delivery of this Agreement, this
Agreement shall constitute valid and binding obligations
against IDT enforceable in accordance with its terms, except
as enforceability may be limited by applicable bankruptcy,
insolvency, reorganization, moratorium or similar laws
affecting creditors' and contracting parties' rights
generally;
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(v) the performance of its obligations under this Agreement will
not conflict with its charter documents or result in a breach
of any agreements, contracts or other arrangements to which it
is a Party;
(vi) IDT will not during the term of this Agreement enter into any
agreements, contracts or other arrangements that would be
inconsistent with its obligations under this Agreement;
(vii) IDT has obtained, or will obtain, all governmental permits,
licenses, agreements, contracts, and other enabling documents
to fully implement and fulfill its duties hereunder; and
(viii) IDT represents and warrants that all employees or others
acting on its behalf pursuant to this Agreement are and shall
be obligated under a binding written agreement to assign to
IDT all inventions made or conceived by such employee or other
person.
6.2 REPRESENTATIONS AND WARRANTIES BY ISIS:
ISIS represents and warrants as follows:
(i) ISIS is a corporation duly organized, validly existing and
in corporate good standing under the laws of the State of
Delaware;
(ii) ISIS has the legal right, authority and power to enter into
this Agreement;
(iii) ISIS has taken all necessary action to authorize the
execution, delivery and performance of this Agreement;
(iv) upon the execution and delivery of this Agreement, this
Agreement shall constitute valid and binding obligations
against ISIS enforceable in accordance with its terms, except
as enforceability may be limited by applicable bankruptcy,
insolvency, reorganization, moratorium or similar laws
affecting creditors' and contracting parties' rights
generally;
(v) the performance of its obligations under this Agreement will
not conflict with its charter documents or result in a breach
of any agreements, contracts or other arrangements to which it
is a Party;
(vi) to the best of ISIS's knowledge, IDT's manufacture of
Program Oligonucleotides for use by ISIS does not constitute
contributory infringement with respect to any issued patent of
any third party that has issued prior to the effective date of
this Agreement;
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(vii) ISIS will not during the term of this Agreement enter into any
agreements, contracts or other arrangements that would be
inconsistent with its obligations under this Agreement; and,
(viii) ISIS represents and warrants that all employees or others
acting on its behalf pursuant to this Agreement are and shall
be obligated under a binding written agreement to assign to
ISIS all inventions made or conceived by such employee or
other person.
6.3 LIMITED WARRANTY FOR PROGRAM OLIGONUCLEOTIDES. IDT warrants that
Program Oligonucleotides will meet the specifications as determined in
Appendix A, and as later amended by the POSC if applicable. This
limited warranty represents ISIS's sole and exclusive remedy with
respect to Program Oligonucleotides manufactured for and sold to ISIS
or its Affiliates. IDT does not warrant, guarantee or make any
representations above and beyond the criteria set forth in Appendix A
(as amended from time to time) regarding the use of Program
Oligonucleotides in functional genomics, target validation, or any
other application, or with respect to the correctness, accuracy,
reliability or otherwise of the results of any such use. ISIS ASSUMES
THE ENTIRE RISK AS TO THE RESULTS OBTAINED FROM THE USE OF PROGRAM
OLIGONUCLEOTIDES. ISIS FURTHER ACKNOWLEDGES THAT ISIS, AND NOT IDT, IS
SOLELY RESPONSIBLE FOR ANY WARRANTY OR GUARANTEE MADE TO COLLABORATORS
OF ISIS OR GENETROVE WITH RESPECT TO THE USE OF PROGRAM
OLIGONUCLEOTIDES. THE FOREGOING WARRANTY IS EXCLUSIVE AND IS MADE IN
LIEU AND TO THE EXCLUSION OF ANY OTHER WARRANTIES, WHETHER ORAL OR
WRITTEN, EXPRESS OR IMPLIED, DIRECT OR INDIRECT, BY ESTOPPEL, OR BY
EFFECT OF THE UNIFORM COMMERCIAL CODE, USAGE IN THE INDUSTRY OR THROUGH
COURSE OF DEALINGS OF THE PARTIES, INCLUDING BUT NOT LIMITED TO THOSE
CONCERNING MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE.
6.4 NO CONSEQUENTIAL DAMAGES. NEITHER PARTY HERETO WILL BE LIABLE FOR
SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES ARISING OUT THE
MANUFACTURE, SALE OR USE OF PROGRAM OLIGONUCLEOTIDES UNDER THIS
AGREEMENT, OR ARISING OUT OF THE EXERCISE OF EITHER PARTY'S RIGHTS
HEREUNDER, REGARDLESS OF ANY NOTICE OF SUCH DAMAGES.
ARTICLE 7
CONFIDENTIAL INFORMATION
7.1 CONFIDENTIAL INFORMATION. For the purpose of this Agreement,
Confidential Information means all information, data, and material,
labeled or otherwise designated or identified as confidential by ISIS
or by IDT.
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7.2 DESIGNATED CONFIDENTIAL INFORMATION OF ISIS. All information relating
to Program Oligonucleotides including specifically target sequences
(i.e., the sequence ordered and/or its complementary sequence or
components thereof) ordered by ISIS during the course of this Agreement
are hereby permanently designated as ISIS Confidential Information.
▇▇▇▇ agrees that it will, in writing, clearly identify as confidential,
any and all additional information that it provides to IDT that it
considers to be the Confidential Information of ISIS.
7.3 DESIGNATED CONFIDENTIAL INFORMATION OF IDT. Any and all data generated
by IDT's validation or use of the Assigned Systems and/or the Dedicated
Data Management System, except for the information described in 7.2
herein, are hereby designated as IDT's Confidential Information. IDT
agrees that it will, in writing, clearly identify as confidential, any
and all such information that it provides to ISIS that it considers to
be the Confidential Information of IDT.
7.4 USE OF CONFIDENTIAL INFORMATION. Each Party may use the other Party's
Confidential Information only for the purpose of performing each
Party's duties and obligations under this Agreement.
7.5 OBLIGATIONS OF CONFIDENTIALITY. Except as expressly provided herein,
ISIS and IDT, and their officers, employees, agents, consultants, and
authorized representatives (a) shall hold in strict confidence all
Confidential Information from the other Party or any of its officers,
employees, agents or representatives and (b) shall not distribute,
disclose or disseminate such Confidential Information to any third
party without the prior written approval of the other Party (that is,
the original disclosing Party), provided, however, that such approval
will not be unreasonably withheld where the receiving Party reasonably
believes that disclosure of the other Party's Confidential Information
is reasonably necessary to obtain patents, authorization to conduct
clinical trials, or regulatory approval.
7.6 OTHER INFORMATION. For purposes of this section, information will not
be considered to be Confidential Information of a Party if the
information:
(i) was lawfully in the receiving Party's possession prior to
disclosure under this Agreement and was not acquired directly
or indirectly from the disclosing Party; or,
(ii) was, at the date of disclosure by the disclosing Party, public
knowledge; or subsequently becomes public knowledge other than
through the failure of the receiving Party to comply with its
obligations of confidentiality under the terms of this
Agreement; or,
(iii) was or is acquired by the receiving Party from any third party
lawfully having possession of such information and who is not
under an obligation of confidentiality to the disclosing
Party; or,
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(iv) was or becomes independently known by the receiving Party
without utilizing information provided by the disclosing Party
and wherein such independent knowledge is supported in
contemporaneously written and dated documentation of the
receiving Party; or,
(v) is required to be disclosed, retained, or maintained by either
Party, by applicable law or regulation or under the rules of
any regulatory or governmental authority, including
specifically federal district courts; provided however that
each Party shall immediately notify the other Party in writing
of such required disclosure and must provide such notice at
least thirty (30) days prior to the date when disclosure is
proposed to take place, and provided that the Party or third
party required to make disclosure shall use its best efforts
to secure confidential treatment of any such information
required to be disclosed.
7.7 ADDITIONAL REMEDIES. The Parties hereto understand and agree that
remedies at law may be inadequate to protect against any breach of any
of the provisions of this Article 7 by either Party or their employees,
agents, officers or directors or any other person acting in concert
with it or on its behalf. Accordingly, each Party shall be entitled to
the granting of injunctive relief by a court of competent jurisdiction
against any action that constitutes any such breach of this Article 7.
7.8 EXTENDED TERM. The provisions of this Article 7 shall survive any
termination or expiration of this Agreement and continue in force for a
period of [***] years.
ARTICLE 8
TERM AND TERMINATION
8.1 TERM. The term of this Agreement will be from the Effective Date and
will continue for a period of eight (8) years from the Effective Date,
unless earlier terminated by a Party or the Parties under one of the
provisions of this Article 8.
8.2 BANKRUPTCY. This Agreement shall terminate upon written notice subject
to paragraph 10. 4, by one Party to the other Party in the event the
other Party shall become insolvent, asks its creditors for a
moratorium, files a bankruptcy petition, or suffers appointment of a
temporary or permanent receiver, trustee, or custodian, for all or a
substantial portion of its assets. In the event of any termination
pursuant to this provision, any unused Customer Deposit shall be
immediately forfeited by ISIS, and shall become the exclusive property
of IDT.
8.3 TERMINATION. Either Party may terminate this Agreement for default by
the other Party in performing any of its material obligations under
this Agreement by notifying the other Party in writing of such default
and allowing the other Party [***] Days within which to cure such
default, unless the default is the failure to pay money, in which case
the defaulting Party shall have only [***] Days to cure such default
after receiving written
13
notice of non-payment. If such default is not cured within [***] Days
from receipt of such notice of default (or [***] Days in the case of
non-payment of money owed), the non-defaulting Party may terminate
this Agreement by written notice, subject to paragraph 10.4, to the
defaulting Party.
8.4 ELECTIVE TERMINATION. ISIS may terminate this Agreement by providing
IDT [***] days written notice if IDT materially fails to comply with
any of the Program Oligonucleotide manufacturing or supply requirements
set forth in Article 4 and in Appendix A, as amended from time to time.
The Parties recognize and acknowledge that the production of Program
Oligonucleotides conforming to the specifications is important to ISIS
and is a material term of this Agreement, and further that time is of
the essence with respect to ISIS's demand for Program Oligonucleotides.
IDT's failure to materially produce and deliver Program
Oligonucleotides to ISIS as set forth in Article 4 and in conformity
with the specifications, is considered a material breach of this
Agreement and must be cured to the satisfaction of ISIS within [***]
Days of notice of the same to IDT by ISIS. Failure by IDT to cure such
a breach within thirty [***] Days is grounds for ISIS's elective
termination of this Agreement. In the event IDT refuses to supply
Program Oligonucleotides to ISIS in accordance with Article 2 herein,
and/or IDT refuses to cure a material breach of this Agreement, such
acts shall constitute an elective termination by IDT, and in such
events ISIS shall be entitled to a refund of its unused and outstanding
Customer Deposit.
8.5 EFFECT OF EXPIRATION OR TERMINATION OF AGREEMENT. Within [***] days
after expiration or termination (the date of termination will be the
date upon which the [***] day notice period lapses) of this Agreement,
each Party shall return to the other Party any and all Confidential
Information (Article 7) provided by the other Party pursuant to this
Agreement. ISIS shall have the right to obtain and use all Program
Oligonucleotides for which ISIS has paid and that are in IDT's
possession, or that are scheduled to be manufactured, at the time of
termination. Except to the extent expressly provided to the contrary,
the rights and obligations of the Parties pursuant to Articles 5,6,7 9,
and 10, shall survive the expiration or termination of this Agreement.
Any and all rights of IDT to payments accrued through expiration or
termination as well as obligations of the Parties under firm orders for
purchase and delivery of Program Oligonucleotides at the time of such
expiration or termination shall remain in effect. IDT will have no
obligation to sell and deliver Program Oligonucleotides to ISIS that
have delivery dates more than thirty (30) Business Days after the date
of termination, and in the case of termination under paragraphs 8.2 or
8.3, the terminating Party has discretion in electing whether firm
orders will remain in effect. Upon expiration of this Agreement, or
termination of this Agreement for reasons other than an IDT elective
termination as defined in 8.4 herein, any unused Customer Deposit shall
be forfeited by ISIS and will default to IDT. Upon termination of this
Agreement under paragraphs 8.2, 8.3, or 8.4, or upon expiration of this
Agreement under 8.1, IDT shall immediately transfer to ISIS possession
of ISIS Supplied Reagents upon notice from ISIS of the final
post-termination receipt of Program Oligonucleotides, if any.
14
ARTICLE 9
INDEMNIFICATION
9.1 INDEMNIFICATION. Each Party (the "Indemnifying Party") agrees to defend
the other Party and such other Party's Affiliates and their respective
directors, officers, employees and agents (the "Indemnified Parties")
at the Indemnifying Party's cost and expense, and shall hold the
Indemnified Parties harmless from and against any losses, costs,
damages, fees or expenses arising out of any third party claim relating
to (i) any breach by the Indemnifying Party of any of its
representations, warranties or obligations pursuant to this Agreement,
or (ii) product liability or liability stemming from allegations of
contributory infringement resulting from use of a product made, sold or
imported by or for the Indemnifying Party.
9.2 NOTICE/REPRESENTATION. In the event of any claim against the
Indemnified Parties by any third party for which indemnification may be
sought pursuant to this Agreement, the Indemnified Party shall promptly
notify the Indemnifying Party in writing of the claim; provided that
the failure to promptly notify the Indemnifying Party of such claim
shall not result in the loss of rights of indemnification hereunder
except to the extent that the Indemnifying Party was materially
prejudiced by such failure. The Indemnifying Party shall assume, at its
sole expense, the defense of the claim and its settlement. The
Indemnified Parties shall cooperate with the Indemnifying Party and
may, at their option and expense, be represented in any such action or
proceeding. The Indemnifying Party shall not be liable for any
litigation costs or expenses incurred by the Indemnified Parties. In
addition, the Indemnifying Party shall not be responsible for the
indemnification of any Indemnified Party arising from any negligent or
wrongful acts by such Indemnified Party, or as the result of any
settlement or compromise by the Indemnified Parties without the
Indemnifying Party's prior written consent. The Indemnifying Party may
not settle or compromise any matter without the consent of the
Indemnified Parties unless such settlement or compromise imposes no
obligations on the Indemnified Parties and does not restrict the rights
of the Indemnified Parties.
ARTICLE 10
GENERAL
10.1 GOVERNING LAW. This Agreement shall be construed and the respective
rights of the Parties determined according to the laws of the State of
New York (without regard to the conflict of law rules of any
jurisdiction), except as regarding matters of intellectual property
law, which shall be determined in accordance with the national
intellectual property laws relevant of the intellectual property in
question.
10.2 ASSIGNMENT. Neither IDT nor ▇▇▇▇ may assign this Agreement in whole or
in part without the consent of the other Party, except if such
assignment occurs in connection with the sale or transfer of all or
substantially all of the business or assets of the assigning Party to
which the subject matters of this Agreement pertains.
15
10.3 ENTIRE AGREEMENT; AMENDMENTS. This Agreement, together with the
Appendices incorporated herein, constitute the entire agreement between
the Parties with respect to the subject matter hereof, and supersedes
all previous arrangements with respect to the subject matter hereof,
whether written or oral. Any amendment or modification to this
Agreement shall be made in writing signed by both Parties.
10.4 NOTICES. Notices with respect to IDT shall be sent to:
▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇, M.D., Ph.D.
Attn: Legal Department
Integrated DNA Technologies, Inc.
▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇
▇▇▇▇▇▇▇▇▇▇, ▇▇
▇▇▇▇▇-9802;
With a duplicate sent to:
▇▇▇▇ ▇▇▇▇▇▇▇▇, ▇.▇., COO
Corporate Vice President
Integrated DNA Technologies, Inc.
▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇, ▇▇▇▇▇ ▇▇▇
▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇,
▇▇▇▇▇;
and with respect to ISIS:
▇. ▇▇▇▇▇ ▇▇▇▇▇▇▇▇, ▇.▇.
Isis Pharmaceuticals, Inc.
Executive Vice President and CFO
▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇, ▇▇
▇▇▇▇▇
With a duplicate sent to:
President, GeneTrove Division
Isis Pharmaceuticals, Inc.
▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇, ▇▇
▇▇▇▇▇
Any Party may change its address by giving notice to the other Party in
the manner herein provided. Any notice required or provided for by the
terms of this Agreement shall be in writing and shall be (a) delivered
personally, (b) sent by registered or certified mail, return receipt
requested, postage prepaid, (c) sent via a reputable overnight courier
service, or (d)
16
sent by facsimile transmission with an original to be followed the same
day via a reputable overnight courier service, in each case properly
addressed in accordance with the paragraph above. The effective date of
notice shall be the actual date of receipt by the Party receiving the
same.
10.6 FORCE ▇▇▇▇▇▇. No failure or omission by a Party in the performance of
any of its obligations of this Agreement shall be deemed a breach of
this Agreement or create any liability if the same shall arise from any
cause or causes beyond the control of such Party, including, but not
limited to, the following: acts of God; acts or omissions of any
government; any rules, regulations or orders issued by any governmental
authority or by any officer, department, agency or instrumentality
thereof; fire; storm; flood; earthquake; accident; war; rebellion;
insurrection; riot; terrorist activities; and invasion and provided
that such failure or omission resulting from one of the above causes is
cured as soon as is practicable after the occurrence of one or more of
the above-mentioned causes.
10.7 DISCLOSURE OF PROVISIONS OF AGREEMENT.
Each Party agrees to hold as confidential the terms of this Agreement,
except that:
(i) IDT may furnish a copy of this Agreement to the
University of Iowa Research Foundation; and,
(ii) Each Party shall have the right to disclose the terms
of this Agreement to investors and other third
parties in connection with financing activities and
to potential collaborators, provided that any such
third party has entered into a written obligation
with the disclosing Party to treat such information
and materials as confidential and to not use the
information materials for any purposes other than the
evaluation of the potential investment or
collaboration and that the disclosing Party shall
enforce against the third party recipient of such
information and materials, for and on behalf of the
other Party, such written obligation; and,
(iii) Each Party may furnish a copy of this Agreement or
disclose the terms of this if such is required to be
disclosed by the receiving Party to comply with
applicable laws, to defend, prosecute or preclude
litigation, or to comply with governmental
regulations, PROVIDED THAT the receiving Party
provides prior written notice of such disclosure to
the disclosing Party and takes reasonable and lawful
actions to avoid and/or minimize the degree of such
disclosure. At the request of the other Party, the
disclosing Party shall use commercially reasonable
efforts to enforce such obligations against such
third parties.
(iv) Each Party may include this Agreement, in any report,
statement or other document filed by such Party with
the United States Securities and Exchange Commission
(the "SEC"). In such event, the disclosing Party
shall use reasonable efforts to obtain, to the extent
permitted by law,
17
confidential treatment from the SEC of any trade
secrets and commercial or financial information of
a privileged or confidential nature, including
without limitation all information on the Exhibits
hereto relating to patent applications of Isis or
IDT, and shall notify the other Party as to such
efforts and all related communications with the
SEC; provided that notwithstanding the foregoing
no Party shall submit a confidentiality request or
include this Agreement without the prior review
and approval of the confidentiality request by the
other Party, which review and approval shall not
be unreasonably withheld or delayed.
(v) The Parties will cooperate in the development of any
public announcement announcements or similar
publicity with respect to the execution of this
Agreement. The content and timing of any such
announcement or publicity shall be agreed upon
between Parties in advance of such announcement.
10.8 INDEPENDENT CONTRACTORS. It is understood and agreed that the
relationship between the Parties hereunder is that of independent
contractors and that nothing in this Agreement shall be construed as
authorization for either Party to act as agent for the other.
10.9 NO STRICT CONSTRUCTION. This Agreement has been prepared jointly and
shall not be strictly construed against any Party.
10.10 HEADINGS. The captions or headings of the Sections or other
subdivisions hereof are inserted only as a matter of convenience or for
reference and shall have no effect on the meaning of the provisions
hereof.
10.11 NO IMPLIED WAIVERS; RIGHTS CUMULATIVE. No failure on the part of either
Party to exercise, and no delay in exercising, any right, power, remedy
or privilege under this Agreement, or provided by statute or at law or
in equity or otherwise, shall impair, prejudice or constitute a waiver
of any such right, power, remedy or privilege or be construed as a
waiver of any breach of this Agreement or as an acquiescence therein,
nor shall any single or partial exercise of any such right, power,
remedy or privilege preclude any other or further exercise thereof or
the exercise of any other right, power, remedy or privilege.
10.12 SEVERABILITY. If any provision hereof should be held invalid, illegal
or unenforceable in any respect in any jurisdiction, then, to the
fullest extent permitted by law, (a) all other provisions hereof shall
remain in full force and effect in such jurisdiction and shall be
liberally construed in order to carry out the intentions of the Parties
as nearly as may be possible and (b) such invalidity, illegality or
unenforceability shall not affect the validity, legality or
enforceability of such provision in any other jurisdiction.
10.13 CURRENCY. All references to prices and/or monies owed in this
Agreement are to United States dollars.
18
10.14 EXECUTION IN COUNTERPARTS. This Agreement may be executed in
counterparts, each of which counterparts, when so executed and
delivered, shall be deemed to be an original, and all of which
counterparts, taken together, shall constitute one and the same
instrument.
REMAINDER OF THIS ▇▇▇▇ LEFT INTENTIONALLY BLANK
SIGNATURE PAGE TO IMMEDIATELY FOLLOW
19
IN WITNESS WHEREOF, the Parties hereto have executed this Agreement by their
duly authorized representatives.
ISIS PHARMACEUTICALS, INC. INTEGRATED DNA TECHNOLOGIES, INC.
By: ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇ By: ▇▇. ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇
Signature: /s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇ Signature: /s/ ▇▇. ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇
---------------------- -------------------------
Title: President, GeneTrove Title: President & CEO
Vice President,
ISIS Pharmaceuticals
Date: 12/04/01 Date: 12/04/01
-------- --------
20
APPENDIX A
PROGRAM OLIGONUCLEOTIDE SPECIFICATIONS AND OTHER CRITERIA
PROGRAM OLIGONUCLEOTIDE TYPE PURITY BY MASS SPEC ABSORBANCE ADDITIONAL
HPLC RATIO ANALYSIS/HANDLING
MOE OLIGOS
[***] To be To be To be
determined* determined determined
[***] To be To be To be
determined determined determined
QUANTIFICATION OLIGOS
Probes To be To be To be
determined determined determined
Primers To be To be To be
determined determined determined
"Primer Probe Sets" To be To be To be
determined determined determined
* POSC to determine test use and test specifications
A-1
APPENDIX B
APPLICATION OF 4.3 PRICING PROVISION
PROGRAM OLIGONUCLEOTIDE TYPE SYNTHESIS SCALE
--------------------------------------------------------------------------------
[***]
* NON-CATALOG ITEM
CONFIDENTIAL TREATMENT REQUESTED UNDER
17 C.F.R. SECTIONS 200.80(b)4, AND 240.24b-2
