Exhibit 10.1

Execution

LICENSE AGREEMENT

This License Agreement (this “Agreement”) is entered into by and between ALNYLAM
PHARMACEUTICALS, INC., a corporation organized under the laws of the State of
Delaware having offices located at 300 Third Street, Cambridge MA 02142 U.S.A.
(“ALNYLAM”), and ARROWHEAD RESEARCH CORPORATION, a corporation organized under
the laws of the State of Delaware having offices located at 225 South Lake
Avenue, Suite 300, Pasadena, CA 91101 and ARROWHEAD MADISON INC., a corporation
organized under the laws of the State of Delaware having offices located at 465
Science Drive, Madison, WI 53711 (collectively “ARROWHEAD”).

INTRODUCTION

ALNYLAM owns or has rights to certain intellectual property covering technology
useful for the discovery, development, manufacture, characterization, or use of
therapeutic products that function through RNA interference (“RNAi”).

ARROWHEAD desires to research and potentially develop and commercialize siRNA
based products that target messenger RNAs encoded by the genome of human
hepatitis B virus (“HBV”), and for such purpose ARROWHEAD desires a license
under certain of the aforementioned intellectual property of ALNYLAM to use the
technology covered by such intellectual property to research, develop and
commercialize any such product.

ALNYLAM is willing to grant ARROWHEAD a license to research, develop and
commercialize products as described above under the terms and conditions of this
Agreement.

In consideration of the mutual covenants contained herein, and other good and
valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, ALNYLAM and ARROWHEAD agree as follows:

 

 

 

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TABLE OF CONTENTS

 

 

Page

ARTICLE I – DEFINITIONS

1

 

 

1.1

Act

1

1.2

Affiliate

1

1.3

ALNYLAM CRT Additional Patent Rights

1

1.4

ALNYLAM Broad RNAi Intellectual Property

1

1.5

ALNYLAM Broad RNAi Know-How

1

1.6

ALNYLAM Broad RNAi Patent Rights

1

1.7

ALNYLAM Intellectual Property

1

1.8

ALNYLAM Patent Rights

1

1.9

ALNYLAM Stanford Additional Patent Rights

1

1.10

ALNYLAM Target-Specific Patent Rights

1

1.11

Approval

2

1.12

Calendar Quarter

2

1.13

Clinical Trial

2

1.14

Commercialize or Commercialization

2

1.15

Confidential Information

2

1.16

Control or Controlled

2

1.17

Cover or Covered

2

1.18

Develop, Developing or Development

2

1.19

Dynamic Polymeric Conjugate Technology or DPC Technology

2

1.20

Effective Date

2

1.21

Executive Officers

2

1.22

Existing ALNYLAM Third Party Agreements

2

1.23

FDA

2

1.24

Field

3

1.25

First Commercial Sale

3

1.26

FTE

3

1.27

FTE Rate

3

1.28

GAAP

3

1.29

GLP Toxicology Study

3

1.30

IND or Investigational New Drug Application

3

1.31

Licensed RNAi Product

3

1.32

Net Sales

3

1.33

Party

4

1.34

Patent Rights

4

1.35

Person

4

1.36

Pivotal Trial

4

1.37

Regulatory Authority

4

1.38

Research or Researching

4

1.39

Research Collaboration Term

4

1.40

siRNA

4

1.41

Sublicensee

5

1.42

Target

5

1.43

Territory

5

1.44

Third Party

5

1.45

Valid Claim

5

 

 

 

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

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ARTICLE II - RESEARCH AND DEVELOPMENT

5

 

 

2.1

Target Selection

5

2.2

Research Collaboration

5

2.3

Research Collaboration FTEs

6

2.4

Status Reports

6

2.5

Research, Development, Manufacture and Commercialization following Research
Collaboration Term

6

 

 

 

ARTICLE III - GOVERNANCE

6

 

 

 

3.1

JRDC

6

3.2

Decision Making; Limits on Authority

6

 

 

 

ARTICLE IV - LICENSE GRANTS

6

 

 

4.1

Licenses

6

4.2

Sublicensing

7

4.3

Retained Rights of ALNYLAM

7

4.4

Additional Patents Option

7

4.5

Exclusivity

7

 

 

 

ARTICLE V - FEES AND ROYALTIES

8

 

 

5.1

FTE Costs

8

5.2

Milestone Payments

8

5.3

Royalties

8

5.4

Sales Milestone Payment

9

5.5

Third Party License Fees

9

 

 

 

ARTICLE VI - REPORTS, TAXES AND PAYMENTS

9

 

 

6.1

Reports

9

6.2

Tax Withholding

9

6.3

Payments

9

6.4

Audits

10

6.5

Late Payments

10

 

 

 

ARTICLE VII - INTELLECTUAL PROPERTY

10

 

 

7.1

Prosecution and Maintenance of Patent Rights

10

7.2

Infringement of ALNYLAM Rights

10

7.3

Claimed Infringement of Third Party Rights, and Third Party Intellectual
Property Obligations

11

 

 

 

ARTICLE VIII - CONFIDENTIAL INFORMATION

11

 

 

8.1

Non-Use and Non-Disclosure of Confidential Information

11

8.2

Permitted Disclosures

12

8.3

Publicity

12

 

 

 

ARTICLE IX - INDEMNIFICATION AND INSURANCE

12

 

 

9.1

ARROWHEAD Indemnification

12

9.2

ALNYLAM Indemnification

12

9.3

Indemnification Procedures

13

 

 

 

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

ii

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ARTICLE X - EXPORT

13

 

 

10.1

General

13

10.2

Delays

13

10.3

Assistance

13

 

 

 

ARTICLE XI - TERM AND TERMINATION

14

 

 

11.1

Term

14

11.2

Material Breach

14

11.3

Termination by ARROWHEAD

14

11.4

Termination Due to Patent Challenge

14

11.5

Consequences of Termination; Survival

14

 

 

 

ARTICLE XII - MISCELLANEOUS

14

 

 

12.1

Representations by ARROWHEAD and ALNYLAM

14

12.2

Mutual Covenants

15

12.3

Dispute Resolution; Arbitration Procedures

15

12.4

Force Majeure

16

12.5

Consequential Damages

16

12.6

Assignment

17

12.7

Notices

17

12.8

Independent Contractors

18

12.9

Governing Law; Jurisdiction

18

12.10

Severability

18

12.11

No Implied Waivers

18

12.12

Entire Agreement

18

12.13

Headings; Construction; Interpretation

19

12.14

Counterparts

19

 

 

 

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

iii

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ARTICLE I - DEFINITIONS

General. When used in this Agreement, each of the following terms, whether used
in the singular or plural, will have the meanings set forth in this Article I.

1.1

Act means the United States Federal Food, Drug, and Cosmetic Act of 1938, 21
U.S.C. §§ 301 et seq., as such may be amended from time to time, and its
implementing regulations.

1.2

Affiliate means with respect to a Person, any other Person which controls, is
controlled by, or is under common control with the applicable Person. For
purposes of this definition, “control” shall mean: (a) in the case of corporate
entities, direct or indirect ownership of more than fifty percent (50%) of the
stock or shares (or such lesser percentage which is the maximum allowed to be
owned by a foreign corporation in a particular jurisdiction) entitled to vote
for the election of directors, or otherwise having the power to control or
direct the affairs of such Person; and (b) in the case of non-corporate
entities, direct or indirect ownership of more than fifty percent (50%) of the
equity interest or the power to direct the management and policies of such
non-corporate entities. For purposes of this Agreement, Regulus Therapeutics,
LLC, 3545 John Hopkins Ct., San Diego, California 92121, shall be deemed not to
be an Affiliate of ALNYLAM.

1.3

ALNYLAM CRT Additional Patent Rights means the patents and patent applications
listed on Exhibit E, and all continuations, continuations-in-part, divisionals,
and other substitute applications with respect thereto; any patents issued with
respect to any of the foregoing; and all reissues, substitutions, confirmations,
re-examinations, supplementary protection certificates, certificates of
invention and patents of addition with respect to any of the foregoing; and all
counterparts to any of the foregoing in any country of the Territory.

1.4

ALNYLAM Broad RNAi Intellectual Property means ALNYLAM Broad RNAi Know-How and
ALNYLAM Broad RNAi Patent Rights.

1.5

ALNYLAM Broad RNAi Know-How means Know-How, Controlled by ALNYLAM as of the
Effective Date or during the Research Collaboration Term to the extent that such
Know-How is necessary or useful for the Research, Development, Commercialization
or manufacture of Licensed RNAi Products.

1.6

ALNYLAM Broad RNAi Patent Rights means Patent Rights that are Controlled by
ALNYLAM as of the Effective Date or during the Research Collaboration Term and
that Cover Alnylam Broad RNAi Know-How, but specifically excluding any ALNYLAM
CRT Additional Patent Rights, ALNYLAM Stanford Additional Patent Rights and
ALNYLAM Target-Specific Patent Rights. The ALNYLAM Broad RNAi Patent Rights as
of the Effective Date are listed in Exhibit A.

1.7

ALNYLAM Intellectual Property means the ALNYLAM Broad RNAi Intellectual Property
and the ALNYLAM Target-Specific Patent Rights.

1.8

ALNYLAM Patent Rights means the ALNYLAM Broad RNAi Patent Rights and the ALNYLAM
Target-Specific Patent Rights.

1.9

ALNYLAM Stanford Additional Patent Rights means the patents and patent
applications listed on Exhibit F, and all continuations, continuations-in-part,
divisionals, and other substitute applications with respect thereto; any patents
issued with respect to any of the foregoing; and all reissues, substitutions,
confirmations, re-examinations, supplementary protection certificates,
certificates of invention and patents of addition with respect to any of the
foregoing; and all counterparts to any of the foregoing in any country of the
Territory.

1.10

ALNYLAM Target-Specific Patent Rights means such claim or claims contained in
Patent Rights Controlled by ALNYLAM as of the Effective Date or during the
Research Collaboration Term and that are specifically directed to particular
sequences of Licensed RNAi Products against the Target. The ALNYLAM
Target-Specific Patent Rights as of the Effective Date are listed in Exhibit A.

 

 

 

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

--------------------------------------------------------------------------------

 

1.11

Approval means, with respect to each Licensed RNAi Product Developed and
Commercialized, the receipt of sufficient authorization from the appropriate
Regulatory Authority to market such Licensed RNAi Product in a country,
including (where legally required in a particular country prior to marketing a
Licensed RNAi Product) all separate pricing and/or reimbursement approvals that
may be required for marketing.

1.12

Calendar Quarter means, in any calendar year, one of the following three-month
calendar quarters: January 1 through March 31, inclusive; April 1 through
June 30, inclusive; July 1 through September 30, inclusive; or October 1 through
December 31, inclusive.

1.13

Clinical Trial means any human clinical trial.

1.14

Commercialize or Commercialization means any and all activities directed to
manufacturing (including, without limitation, by means of contract
manufacturers), marketing, promoting, distributing, importing, exporting and
selling a Licensed RNAi Product, in each case for commercial purposes, and
activities directed to obtaining pricing and reimbursement approvals, as
applicable.

1.15

Confidential Information means all proprietary, confidential information and
materials, patentable or otherwise, of a Party which are disclosed by or on
behalf of such Party to the other Party hereunder, including, without
limitation, chemical substances, formulations, techniques, methodology,
equipment, data, reports, know how, sources of supply, patent positioning,
business plans, and also including without limitation proprietary and
confidential information of Third Parties in possession of such Party under an
obligation of confidentiality, whether or not related to making, using or
selling Licensed RNAi Products.

1.16

Control or Controlled means, with respect to any item of or right under an
intellectual property right, the possession (whether by ownership or license,
other than pursuant to this Agreement) of the ability of a Party to grant access
to, or a license or sublicense of, such items or right as provided for herein
without violating the terms of any agreement or other arrangement with any Third
Party existing at the time such Party would be required hereunder to grant the
other Party such access or license or sublicense; provided that any intellectual
property right that is licensed or acquired by a Party after the Effective Date
and that would otherwise be considered to be under the Control of such Party
shall not be deemed to be under the Control of such Party if the application of
such definition in the context of any licenses or sublicenses granted to the
other Party under this Agreement would require the granting Party to make any
additional payments or royalties to a Third Party in connection with such
license or sublicense grants, unless the other Party agrees to pay the
additional payments or royalties to the Third Party.

1.17

Cover or Covered means with respect to the applicable country, but for the
license granted under a Valid Claim of a Patent Right, the manufacture, use or
sale, or offer for sale in such country of the subject matter at issue would
infringe such Valid Claim, or in the case of a Patent Right that is a patent
application, would infringe a Valid Claim in such patent application if it were
to issue as a patent.

1.18

Develop, Developing or Development means with respect to a Licensed RNAi
Product, preclinical and clinical drug development activities, including without
limitation: test method development and stability testing, toxicology,
formulations, quality assurance/quality control development, statistical
analysis and report writing; clinical studies and regulatory affairs; Approval
and registration.

1.19

Dynamic Polymeric Conjugate Technology or DPC Technology means an siRNA delivery
system including a membrane-active polymer, a masking agent to reversibly mask
the activity of the polymer in vivo, and optionally a targeting agent.

1.20

Effective Date means January 4, 2012.

1.21

Executive Officers means the Chief Executive Officer of ALNYLAM (or a senior
executive officer of ALNYLAM designated by ALNYLAM’s Chief Executive Officer)
and the Chief Executive Officer of ARROWHEAD (or a senior executive officer of
ARROWHEAD as designated by ARROWHEAD’s Chief Executive Officer).

1.22

Existing ALNYLAM Third Party Agreements means the agreements listed on Exhibit B
between ALNYLAM and the listed Third Parties.

1.23

FDA means the United States Food and Drug Administration or any successor agency
thereto.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

2

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1.24

Field means the prevention, treatment and prophylaxis of disease in humans.

1.25

First Commercial Sale means, with respect to each Licensed RNAi Product, the
first commercial sale in a country as part of a nationwide introduction after
receipt by ARROWHEAD or any of its Affiliates or Sublicensees of Approval in
such country, excluding de minimis named patient and compassionate use sales.

1.26

FTE means the number of full-time-equivalent person-years (each consisting of a
total of 1,840 hours) of scientific, technical, regulatory, marketing or
managerial work by each party’s personnel on or directly related to the
applicable activity conducted hereunder.

1.27

FTE Rate means $*** U.S. Dollars per FTE, increased annually beginning on
January 1, 2013 and thereafter on January I of each succeeding year by the
percentage increase in the CPI as of December 31 of the then most recently ended
calendar year over the level of the CPI on December 31, 2011 e., the first such
increase or decrease would occur on January 1, 2013). As used in this
definition, “CPI” shall mean the Consumer Price Index — Urban Wage Earners and
Clerical Workers, U.S. City Average, All Items, 1982-84 = 100, published by the
United States Department of Labor, Bureau of Labor Statistics (or its successor
equivalent index) in the United States.

1.28

GAAP means generally accepted accounting principles as practiced in the United
States.

1.29

GLP Toxicology Study means a toxicology study that is conducted in compliance
with the then-current good laboratory practice standards promulgated or endorsed
by the FDA, as defined in U.S. 21 C.F.R. Part 58 (or such other comparable
regulatory standards in jurisdictions outside the U.S. to the extent applicable
to the relevant toxicology study, as they may be updated from time to time)
(“GLP”) and is required to meet the requirements for filing an IND.

1.30

IND or Investigational New Drug Application means a United States
investigational new drug application or its equivalent or any corresponding
foreign application.

1.31

Licensed RNAi Product means a pharmaceutical product (a) containing, comprised
or based on siRNAs or siRNA derivatives or other moieties effective in gene
function modulation and designed to modulate the function of the Target through
RNA interference and (b) incorporating DPC Technology.

1.32

Net Sales means, with respect to Licensed RNAi Products, the gross amount
invoiced by ARROWHEAD or its Affiliates or Sublicensees, as the case may be, on
sales or other dispositions of such Licensed RNAi Products to Third Parties,
less: (A) portions of invoiced amounts written off by ARROWHEAD, its Affiliates
or Sublicensees as uncollectible, relating to specific invoices and not a
general reserve for uncollectible amounts, in accordance with their normal
accounting practices (provided that if any such written-off amounts are
subsequently collected, such amounts shall be included in Net Sales when
collected); and (B) the following deductions, to the extent standard and
customary and incurred in accordance with ARROWHEAD’S usual practices, as
generally applied across its business (i) rebates, quantity, trade and cash
discounts, and other usual and customary discounts to customers;
(ii) charge-back payments and rebates granted to managed health care
organizations or to national, state or local governments, their respective
agencies, purchasers or reimbursers, adjustments arising from consumer discount
programs or other similar programs; (iii) retroactive price reductions, credits
or allowances granted upon rejections or returns of Licensed RNAi Products,
including for recalls or damaged goods; (iv) compulsory payments and rebates
made or granted to government entities with respect to sales of Licensed RNAi
Products; (v) freight, postage, shipping and insurance charges for delivery of
Licensed RNAi Products; and (viii) sales taxes, excise taxes, use taxes,
value-added taxes, import/export duties or other governmental charges with
respect to Licensed RNAi Products, excluding income taxes.

  

Sales between ARROWHEAD and its Affiliates or Sublicensees for resale shall be
excluded from the computation of Net Sales, but the subsequent resale of such
Product to Third Parties shall be included within the computation of Net Sales.
Sales or other dispositions of Licensed RNAi Products used for promotional or
advertising purposes or used for research or development purposes (including
clinical trials) or for donations, to the extent reasonable and customary and in
accordance with ARROWHEAD’S usual practices, as generally applied across its
business, shall be excluded from Net Sales.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

3

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In the event that a Licensed RNAi Product is sold in any country in the form of
a combination product containing one or more therapeutically active ingredients
in addition to such Licensed RNAi Product in any year, Net Sales of such
combination product will be adjusted by multiplying actual Net Sales of such
combination product in such country by the fraction A/(A+B), where A is the
average Net Sales prices per daily dose during such year of the Licensed RNAi
Product in such country, if sold separately in such country, and B is the
average Net Sales prices per daily dose of any product containing the other
therapeutically active ingredients in the combination product in such country,
if sold separately in such country. If, in a specific country, both the Licensed
RNAi Product and the product containing the other therapeutically active
ingredients in the combination product are not sold separately in such country,
the fraction of actual Net Sales of the combination product that will be deemed
to be Net Sales of the Licensed RNAi Product will be determined based upon the
commercial values of the Licensed RNAi Product and the other therapeutically
active ingredients in such combination product. If the Parties are not able to
agree on any such allocation, the matter may be submitted by either Party for
resolution by arbitration pursuant to Section 12.3.

  

In the event ARROWHEAD or any of its Affiliates or Sublicensees receive
non-monetary consideration in exchange for the sale or other disposition of
Licensed RNAi Products to Third Parties, Net Sales for such sale or other
disposition shall include the fair market value of the non-cash consideration
received as a result of such sale or other disposition. If such sale or other
disposition occurred in a country where ARROWHEAD or such Affiliate or
Sublicensee sold the same Licensed RNAi Product in commercial quantities solely
for monetary consideration, the fair market value of the non-cash consideration
received for such Licensed RNAi Product shall be determined on the basis of the
value received in such solely monetary transactions. If ARROWHEAD or its
Affiliate or Sublicensee did not have sales or other dispositions of Licensed
RNAi Product in such country solely for monetary consideration, then the fair
market value of such Licensed RNAi Product shall be determined on the basis of
all relevant facts and circumstances.

  

Net Sales shall be determined from books and records maintained in accordance
with GAAP, consistently applied throughout the organization and across all
products of the entity whose sales of Licensed RNAi Product are giving rise to
Net Sales.

1.33

Party means either ALNYLAM or ARROWHEAD; Parties means both ALNYLAM and
ARROWHEAD.

1.34

Patent Rights means patents, patent applications and/or provisional patent
applications, utility models and utility model applications, design patents or
registered industrial designs and design applications or applications for
registration of industrial designs, and all substitutions, divisionals,
continuations, continuation-in-part applications, continued prosecution
applications, requests for continued examinations, reissues, reexaminations and
extensions thereof, in any country of the world. For clarity, any Patent Rights
shall include any future Patent Rights that claim priority to or common priority
with such Patent Rights.

1.35

Person shall mean any natural person, corporation, unincorporated organization,
partnership, association, joint stock company, joint venture, limited liability
company, trust or government, or any agency or political subdivision of any
government, or any other entity.

1.36

Pivotal Trial means a prospective, randomized, controlled Clinical Trial that is
designed to confirm or that does confirm with statistical significance the
efficacy and safety of a drug in a given patient population, the results of
which are intended, either alone or with other pivotal human clinical studies,
to form the basis for Approval.

1.37

Regulatory Authority means the FDA in the United States or any health regulatory
authority in another country that is a counterpart to the FDA and holds
responsibility for allowing development of Licensed RNAi Products and/or
granting Approval for a Licensed RNAi Product in such country.

1.38

Research or Researching means identifying, evaluating, validating and optimizing
Licensed RNAi Products.

1.39

Research Collaboration Term means the period commencing on the Effective Date
and ending on the date on which ARROWHEAD or its Affiliates or Sublicensees
initiates the first GLP Toxicology Study for a Licensed RNAi Product.

1.40

siRNA means a double-stranded ribonucleic acid (RNA) composition designed to act
primarily through an RNA interference mechanism that consists of either (a) two
separate oligomers of native or chemically modified RNA that are hybridized to
one another along a substantial portion of their lengths, or (b) a single
oligomer of native or chemically modified RNA that is hybridized to itself by
self-complementary base-pairing along a substantial portion of its length to
form a hairpin.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

4

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1.41

Sublicensee means any Third Party to whom ARROWHEAD, pursuant to a written
agreement, has granted a sublicense of all or a portion of the rights granted
hereunder, provided that such Third Party has the responsibility for the
Commercialization of such Licensed RNAi Product in a licensed territory and has
the right to record sales of such Licensed RNAi Product for its account. For
clarity, “Sublicensee” shall exclude any wholesaler or reseller of Licensed RNAi
Product that purchases Licensed RNAi Product from ARROWHEAD, its Affiliates and
Sublicensees and that is not responsible for marketing or promotion of such
Licensed RNAi Product, any contract manufacturer or service provider (e.g., a
clinical research organization or its equivalent) or other Third Party acting
solely on behalf of ARROWHEAD or its Affiliates and not on its own behalf

1.42

Target means HBV, or a single alternative messenger RNA target selected by
ARROWHEAD and designated in accordance with Section 2.1.

1.43

Territory means worldwide. For clarity, at any time the Territory will not
include any country to which the exportation or re-exportation of materials,
products and related technical data covered by this Agreement is restricted
under U.S. export laws, which restriction has not been removed or waived.

1.44

Third Party means any person, corporation, joint venture or other entity, other
than ALNYLAM, ARROWHEAD and their respective Affiliates.

1.45

Valid Claim shall mean (a) a claim of an issued and unexpired patent within the
ALNYLAM Patent Rights that (i) has not been rejected, cancelled, revoked or held
to be invalid or unenforceable by a court or other authority of competent
jurisdiction, from which decision no appeal can be further taken, and (ii) has
not been finally abandoned, disclaimed or admitted to be invalid or
unenforceable through reissue or disclaimer; or (b) a claim included in a patent
application that has not been pending for more than *** (***) years from the
earliest priority date for such patent application, cancelled, withdrawn or
abandoned or finally determined to be unallowable by the applicable governmental
authority (from which no appeal is or can be taken).

ARTICLE II - RESEARCH AND DEVELOPMENT

2.1

Target Selection. ARROWHEAD has selected HBV as the Target as of the Effective
Date. At any time during the Research Collaboration Term but prior the start of
the first study of a Licensed RNAi Product in a non-rodent efficacy animal
model, ARROWHEAD may provide ALNYLAM written notice designating one
(1) alternative target that ARROWHEAD desires to Research, Develop and
Commercialize in accordance with this Agreement. Within ten (10) business days
of receipt of such alternative target from ARROWHEAD, ALNYLAM shall provide
ARROWHEAD written notice confirming whether such alternative target is available
to be licensed by ALNYLAM to ARROWHEAD hereunder; provided that such alternative
target shall be deemed available unless prior to the date of such request from
ARROWHEAD (a) ALNYLAM has entered into a bona fide collaboration agreement or
license agreement with a Third Party pursuant to which ALNYLAM has granted such
Third Party license rights with respect to such proposed target or (b) ALNYLAM
or its Affiliates have previously initiated a bona fide, active research program
with respect to such proposed target and/or are in active discussions with a
Third Party concerning a research or business collaboration around such target.
In the event that such alternative target is available to be licensed hereunder,
(i) such alternative target shall thereafter be deemed the Target (and HBV shall
thereafter be deemed not to be the Target) and (ii) ARROWHEAD shall thereafter
have no further right to replace the Target with an alternative target except as
mutually agreed by the Parties.

2.2

Research Collaboration.

(a)

Research Collaboration Plan. Within ninety (90) days after the Effective Date,
the ARROWHEAD shall develop a research collaboration plan, which plan if
necessary shall set forth each Party’s obligations and responsibilities during
the Research Collaboration Term in connection with the Research and Development
of Licensed RNAi Products (“Research Collaboration Plan”), which shall be
attached as Exhibit C. Each Party shall use commercially reasonable efforts to
conduct the activities that may be allocated to such Party in the Research
Collaboration Plan.

(b)

Final Authority. ARROWHEAD shall have the final authority with respect to all
details of the Research Collaboration Plan, except that ARROWHEAD shall not have
any authority either (i) to cause ALNYLAM to conduct any activities other than
with ALNYLAM’s agreement; or (ii) to materially change the scope of ALNYLAM’s
obligations under the Research Collaboration Plan without ALNYLAM’s written
consent.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

5

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2.3

Research Collaboration FTEs. During the Research Collaboration Term, subject to
Section 2.2(b), the Parties shall prepare annual updates to the Research
Collaboration Plan setting forth the number of FTEs each Party will commit to
the activities under the Research Collaboration Plan during the next calendar
year. Such annual updates will be completed and agreed upon at least thirty
(30) days prior to the beginning of the next calendar year. During the Research
Collaboration Term, ALNYLAM shall provide such number of FTEs as may be
specified in the Research Collaboration Plan to perform the activities that may
be allocated to ALNYLAM under the Research Collaboration Plan. ARROWHEAD shall
reimburse ALNYLAM its FTE costs (at the FTE Rate) with respect to the FTEs
provided by ALNYLAM to conduct activities under the Research Collaboration Plan
(“FTE Costs”). ALNYLAM shall invoice ARROWHEAD quarterly for such FTE Costs and
payment shall be due and payable within thirty (30) days after receipt of
invoice.

2.4

Status Reports. ARROWHEAD and ALNYLAM shall each provide the JRDC a semi-annual
written report summarizing in reasonable detail such Party’s activities under
the Research Collaboration Plan. Such semi-annual reports will reflect all
material work done and results achieved in carrying out activities under the
Research Collaboration Plan in the prior six (6) month period.

2.5

Research, Development, Manufacture and Commercialization following Research
Collaboration Term. Following the Research Collaboration Term, ARROWHEAD (or its
Affiliates or Sublicensees, as applicable) shall be solely responsible for the
Research, Development, manufacture and Commercialization of Licensed RNAi
Products in the Field in the Territory, including all costs associated with such
activities. ARROWHEAD shall use commercially reasonable efforts to Research,
Develop, manufacture and Commercialize Licensed RNAi Products in the Field in
the Territory.

ARTICLE III - GOVERNANCE

3.1

JRDC. The Parties shall establish a joint Research and Development committee
(the “JRDC”) as more fully described in this Section 3.1. The JRDC shall
comprise two (2) representatives from each of ALNYLAM and ARROWHEAD. Each Party
may replace its representatives at any time upon written notice to the other
Party. The JRDC shall meet twice per calendar year, or as otherwise mutually
agreed by the Parties. The JRDC shall perform the following functions:

(a)

oversee, review and monitor progress of activities under the Research
Collaboration Plan;

(b)

review the Research Collaboration Plan and any amendments to such plan;

(c)

evaluate reports submitted to the JRDC by the Parties;

(d)

discuss and attempt to resolve any deadlock issues submitted to it by the
Parties; and

(e)

such other responsibilities as may be assigned to the JRDC pursuant to this
Agreement or as may be mutually agreed upon by the Parties from time to time.

3.2

Decision Making; Limits on Authority.

(a)

Subject to Section 2.5, in the event of any disagreement as to a matter within
the JRDC’s responsibilities, ARROWHEAD shall have the final decision-making
authority; provided that ARROWHEAD may not exercise its final decision-making
authority to: (i) impose additional obligations on ALNYLAM without ALNYLAM’s
written consent; or (ii) resolve any dispute between the Parties as to their
respective rights and obligations under this Agreement.

(b)

The JRDC shall not have any authority beyond the specific matters set forth in
this Article III, and in particular shall not have any power to amend or modify
the terms of this Agreement.

ARTICLE IV - LICENSE GRANTS

4.1

Licenses. Subject to the terms and conditions of this Agreement, ALNYLAM hereby
grants to ARROWHEAD:

(a)

A worldwide, non-exclusive, royalty-bearing right and license under the ALNYLAM
Broad RNAi Intellectual Property for the sole and exclusive purposes of
Researching, Developing and Commercializing Licensed RNAi Products in the Field
in the Territory.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

6

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(b)

A worldwide, exclusive, royalty-bearing right and license under the ALNYLAM
Target-Specific Patent Rights for the sole and exclusive purposes of
Researching, Developing, manufacturing and Commercializing Licensed RNAi
Products in the Field in the Territory.

(c)

The licenses granted to ARROWHEAD under Sections 4.1(a) and (b) include the
right to grant sublicenses with respect to Licensed RNAi Products which
ARROWHEAD or its Affiliates have identified in good faith as clinical
candidate(s) and for which they have previously commenced GLP Toxicology Studies
or intend to commence GLP Toxicology Studies within the subsequent six
(6) months.

4.2

Sublicensing.

(a)

In the event that ARROWHEAD sublicenses the rights granted under Section 4.1,
ARROWHEAD will notify ALNYLAM within thirty (30) days after such sublicense
becomes effective and provide a copy of the fully executed sublicense agreement
to ALNYLAM within the same time frame (which copy may be redacted, provided that
information relevant to ARROWHEAD’s obligations to ALNYLAM hereunder shall not
be redacted), which shall be treated as Confidential Information of ARROWHEAD,
provided that ALNYLAM may disclose such sublicense agreement(s) to Third Parties
under confidence if and to the extent required in order to comply with ALNYLAM’s
contractual obligations related to ALNYLAM Patent Rights; and provided, further,
that such Third Parties are bound in writing by confidentiality obligations
consistent with those set forth herein. Should this Agreement or the rights
granted to ARROWHEAD hereunder terminate for any reason, any sublicense(s)
granted by ARROWHEAD to an ARROWHEAD Sublicensee shall survive such termination,
provided that, as to each such ARROWHEAD Sublicensee, the ARROWHEAD Sublicensee
is not then in material breach of the sublicense, all financial obligations to
ALNYLAM under this Agreement through the date of termination with respect to
the, sublicensed rights have been satisfied, all obligations (including without
limitation all financial obligations) to ALNYLAM under this Agreement with
respect to the sublicensed rights continue to be satisfied by or on behalf of
the ARROWHEAD Sublicensee and ALNYLAM shall have no responsibility for
ARROWHEAD’ s obligations to the ARROWHEAD Sublicensee under the sublicense.

(b)

Without limiting the foregoing, all sublicenses granted shall be subject to the
following conditions:

(i)

Such sublicense shall be consistent with the requirements of this Agreement;

(ii)

ARROWHEAD shall be primarily liable for any failure by its sublicensees to
comply with all relevant restrictions, limitations and obligations in this
Agreement;

(iii)

Any such sublicense to a Third Party shall be in writing; and

(iv)

In the event that the Sublicensee initiates any legal action seeking a
determination that any of the ALNYLAM Patent Rights in any country are invalid,
unenforceable, and/or not infringed (including a request for reexamination or
opposition of any such ALNYLAM Patent Rights), ARROWHEAD shall terminate the
sublicense at the request of ALNYLAM.

4.3

Retained Rights of ALNYLAM. Any rights of ALNYLAM not expressly granted to
ARROWHEAD under this Agreement will be retained by ALNYLAM.

4.4

Additional Patents Option. ALNYLAM further grants to ARROWHEAD an option (the
“Additional Patents Option”) to expand the ALNYLAM Broad RNAi Patent Rights to
include either the ALNYLAM CRT Additional Patent Rights or the ALNYLAM Stanford
Additional Patent Rights, or both, for the sole and exclusive purposes of
Researching, Developing, manufacturing and Commercializing Licensed RNAi
Products in the Field in the Territory. The Additional Patents Option shall be
exercisable by ARROWHEAD by written notice to ALNYLAM of such exercise given by
ARROWHEAD anytime during the Term specifying the family or families of
additional patent rights to which such exercise applies. Following exercise of
the Additional Patents Option, the Parties shall negotiate and enter into a
supplemental agreement containing terms and conditions for such license
expansion, which shall include terms that pass through ALNYLAM’s costs of
granting such expansion as well as terms that ALNYLAM is required to impose on
sublicensees under ALNYLAM’s applicable agreement(s) with Third Party(ies), but
which terms shall not impose burdens on ARROWHEAD beyond the foregoing costs and
pass-through terms and the applicable terms of this Agreement.

4.5

Exclusivity. During the Term, neither ALNYLAM nor any of its Affiliates shall,
directly or indirectly, Develop, manufacture commercial quantities of or
Commercialize, any Licensed RNAi Product in the Field in the Territory, or
collaborate with or assist any Third Party with respect to any of the foregoing,
except as provided in this Agreement.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

7

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ARTICLE V - FEES AND ROYALTIES

5.1

FTE Costs. ARROWHEAD shall reimburse ALNYLAM in accordance with Section 2.3 its
FTE Costs with respect to the FTEs provided by ALNYLAM to conduct activities
under Research Collaboration Plan.

5.2

Milestone Payments. Upon the achievement by ARROWHEAD, its Affiliates or
Sublicensees of each of the milestone events in the table below with respect to
a Licensed RNAi Product, ARROWHEAD will provide written notice to ALNYLAM of the
occurrence of such milestone event within five (5) days after such event and
ARROWHEAD will make the indicated milestone payment to ALNYLAM within thirty
(30) days after the occurrence of such event. Milestone payments will be due
only once for the first Licensed RNAi Product to achieve the relevant milestone
event and not for any subsequent Licensed RNAi Product or second generation of
the same.

 

 

Milestone Event

 

Payment

 

Initiation of first Clinical Trial

 

$

***

 

 

 

 

 

 

 

 

 

 

 

Dosing of the first patient in a Pivotal Trial

 

$

***

 

 

 

 

 

 

 

 

 

 

 

First Approval granted by a Regulatory Authority

 

$

***

 

 

 

 

 

 

 

 

 

 

 

First Commercial Sale of a Licensed RNAi Product

 

$

***

In the event one or more milestone events set out above are skipped for any
reason, the payment for such skipped milestone events(s) will be due upon the
earlier of (a) achievement of the next achieved milestone event or (b) First
Commercial Sale of a Licensed RNAi Product. In addition, if a Clinical Trial
becomes a Pivotal Trial after the dosing of the first patient in such Clinical
Trial, the Milestone payment above for dosing of the first patient in a Pivotal
Trial (if not previously paid) shall become payable when such Clinical Trial is
determined to be a Pivotal Trial.

5.3

Royalties.

(a)

Royalties on worldwide Net Sales, whether such sales are made by ARROWHEAD or
through its Affiliates or Sublicensees, will be due and payable by ARROWHEAD to
ALNYLAM on a Licensed RNAi Product-by-Licensed RNAi Product and
country-by-country basis in the Territory commencing on the First Commercial
Sale of such Licensed RNAi Product until the later of (i) ten (10) years
following the First Commercial Sale of such Licensed RNAi Product in such
country; or (ii) the expiration of the last Valid Claim Covering such Licensed
RNAi Product in the country of sale or in the country of manufacture (the
“Royalty Term”).

(b)

Subject to subsection (a) of this Section 5.3, the following royalties will be
payable by ARROWHEAD to ALNYLAM (all references are to U.S. dollars) on
aggregate worldwide Net Sales that fall within the indicated ranges of Net Sales
for each calendar year.

 

 

Royalty Rate for annual worldwide Net Sales of Licensed RNAi Products up to and
including $***

 

 

***

%

 

 

 

 

 

 

 

 

 

 

 

 

 

Royalty Rate for annual worldwide Net Sales of Licensed RNAi Products greater
than $*** up to and including $***

 

 

***

%

 

 

 

 

 

 

 

 

 

 

 

 

 

Royalty Rate for annual worldwide Net Sales of Licensed RNAi Products greater
than $***

 

 

***

%

 

 

 

 

 

 

(c)

If, during any period within the Royalty Term for a given Licensed RNAi Product
in a given country, neither (i) any Valid Claim in such country Covers the
manufacture or Commercialization of the Licensed Product in the country of sale,
nor (ii) any Valid Claim Covers the manufacture of the Licensed RNAi Product in
the country or countries where such Licensed RNAi Product was manufactured, then
the royalty rates applicable to such Licensed RNAi Product in such country shall
be reduced to *** percent (***%) of the rates set forth in Section 5.3(b) for
such portion of the Royalty Term during which such condition exists.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

8

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5.4

Sales Milestone Payment. For the milestone listed in the table below, ARROWHEAD
shall pay, or cause to be paid, to ALNYLAM the following payments concurrently
with ARROWHEAD’s payment of royalties pursuant to Section 6.1 for the Calendar
Quarter during which the achievement of the event set forth below occurs:

 

 

Milestone Event

 

Payment

 

First calendar year in which aggregate annual Net Sales of Licensed RNAi
Products in the Territory exceed $***

 

$

***

 

 

 

 

 

 

 

  

For the avoidance of doubt, the foregoing milestone payment set forth in this
Section 5.4 shall be payable no more than once.

5.5

Third Party License Fees. ARROWHEAD shall be solely responsible for all licensee
fees, milestone payments, royalties, sublicense income and other amounts payable
(a) by ALNYLAM pursuant to the applicable Existing ALNYLAM Third Party Agreement
identified on Exhibit B that become payable as a result of any license granted
by ALNYLAM to ARROWHEAD hereunder with respect to Licensed RNAi Products, and
(b) by ARROWHEAD and its Affiliates and Sublicensees to Third Parties for
licenses or other rights under patents and intellectual property rights of Third
Parties with respect to Licensed RNAi Products Researched, Developed and
Commercialized hereunder. ARROWHEAD shall pay to ALNYLAM the amounts payable by
ALNYLAM to third parties as described in the foregoing clause (a) within thirty
(30) days after any invoice therefor from ALNYLAM to ARROWHEAD. ARROWHEAD shall
be entitled to deduct from royalty payments payable hereunder for a given
Licensed RNAi Product *** percent (***%) of any Third Party License Fees
Payments paid by ARROWHEAD with respect to such Licensed RNAi Product during the
applicable reporting period; provided that in no event shall a deduction under
this Section 5.5 reduce any royalty payment with respect to any such Licensed
RNAi Product payable by ARROWHEAD hereunder to less than *** percent (***%) of
the royalty payment amount otherwise payable pursuant to

  

Section 5.4. In addition, ARROWHEAD shall be entitled to deduct from milestones
payable hereunder for any given Licensed RNAi Product *** percent (***%) of any
milestone payment actually paid by ARROWHEAD to any Third Party for such
Licensed RNAi Product pursuant to an Existing ALNYLAM Third Party Agreement as
set forth in the foregoing clause (a).

ARTICLE VI- REPORTS, TAXES AND PAYMENTS

6.1

Reports. As to each Calendar Quarter commencing with the Calendar Quarter during
which the First Commercial Sale occurs, within seventy five (75) days after the
end of such Calendar Quarter, ARROWHEAD will deliver to ALNYLAM a written report
showing, on a Licensed RNAi Product-by-Licensed RNAi Product and
country-by-country basis, the Net Sales of Licensed RNAi Products calculated
under GAAP and its royalty obligation for such Calendar Quarter with respect to
such Net Sales under this Agreement together with wire transfer of an amount
equal to such royalty obligation. In addition, if the sales milestone set forth
in Section 5.4 is achieved during such Calendar Quarter, ARROWHEAD shall also
pay to ALNYLAM the sales milestone payment set forth in Section 5.4 with such
wire transfer. All Net Sales will be segmented in each such report according to
sales by ARROWHEAD and each Affiliate and Sublicensee, including the rates of
exchange used to convert Net Sales to United States dollars from the currency in
which such sales were made. For the purposes of this Agreement, the rates of
exchange to be used for converting Net Sales to United States dollars will be
the simple average of the selling and buying rates of Dollars published in The
Wall Street Journal East Coast Edition for the last business day of the Calendar
Quarter covered by the report.

6.2

Tax Withholding. ARROWHEAD will use commercially reasonable efforts to reduce
tax withholding with respect to payments to be made to ALNYLAM, provided that
ALNYLAM will reasonably cooperate with ARROWHEAD for said purposes.
Notwithstanding such efforts, if ARROWHEAD concludes that tax withholdings under
the laws of any country are required with respect to payments to ALNYLAM,
ARROWHEAD will, subject to Section 12.6(c), make the full amount of the required
payment to ALNYLAM after any tax withholding. In any such case, ARROWHEAD shall
provide ALNYLAM with a written explanation of such withholding and original
receipts or other evidence reasonably desirable and sufficient to allow ALNYLAM
to document such tax withholdings for purposes of claiming foreign tax credits
and similar benefits.

6.3

Payments. Unless otherwise agreed by the Parties, all payments required to be
made under this Agreement will be made in United States dollars via wire
transfer to an account designated in advance by the receiving Party.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

9

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6.4

Audits. At any given point in time, ARROWHEAD will have on file and will require
its Affiliates and Sublicensees to have on file complete and accurate records
for the last three (3) years of all Net Sales (including associated data).
ALNYLAM will have the right, once during each twelve (12) month period, to
retain at its own expense an independent qualified certified public accountant
reasonably acceptable to ARROWHEAD to review such records upon reasonable
notice, during regular business hours. If the audit demonstrates that the
payments owed under this Agreement have been understated, ARROWHEAD will pay the
balance to ALNYLAM together with interest on such amounts in accordance with
Section 6.5. If the underpayment is greater than five percent (5%) of the amount
owed for any calendar year, then ARROWHEAD will reimburse ALNYLAM for its
reasonable out-of-pocket costs of the audit.

6.5

Late Payments. ARROWHEAD shall pay interest to ALNYLAM on the aggregate amount
of any payments (except for those payments which are the subject of a
reasonable, good faith dispute) that are not paid on or before the date such
payments are due under this Agreement at a rate equal to the then current 30-day
United States dollar LIBOR rate plus two percent per annum.

ARTICLE VII- INTELLECTUAL PROPERTY

7.1

Prosecution and Maintenance of Patent Rights.

(a)

ALNYLAM will have the sole and exclusive right to file, prosecute and maintain
patent protection (or to decline to do so) in the Territory for all ALNYLAM RNAi
Patent Rights in its discretion and the first right to file, prosecute and
maintain patent protection (or to decline to do so) in the Territory for all
ALNYLAM Target-Specific Patent Rights. ALNYLAM covenants that it will not
abandon, sell or exclusively license any portion of the ALNYLAM Patent Rights in
any manner that would adversely affect ARROWHEAD’ s rights hereunder.

(b)

ALNYLAM shall keep ARROWHEAD informed as to material developments with respect
to the filing, prosecution and maintenance of the ALNYLAM Target-Specific Patent
Rights, including by providing copies of all substantive office actions or any
other substantive documents that ALNYLAM receives from any patent office.
ALNYLAM shall provide ARROWHEAD with reasonable opportunities to substantively
comment on the filing, prosecution and maintenance of the ALNYLAM
Target-Specific Patent Rights prior to taking material actions, and will in good
faith consider any actions recommended by ARROWHEAD; provided that ARROWHEAD
provides such comments promptly and consistent with any applicable filing
deadlines. If ALNYLAM decides not to file an ALNYLAM Target-Specific Patent
Right or intends to allow an ALNYLAM Target-Specific Patent Right to lapse or
become abandoned without filing a substitute, ALNYLAM shall, notify and consult
with ARROWHEAD regarding such decision or intention at least thirty (30) days
prior to the date upon which the subject matter of such ALNYLAM Target-Specific
Patent Right shall become unpatentable or such ALNYLAM Target-Specific Patent
Right shall lapse or become abandoned, and ARROWHEAD shall thereupon have the
right, but not the obligation, to assume responsibility for the filing,
prosecution and maintenance thereof at its own expense with counsel of its own
choice.

7.2

Infringement of ALNYLAM Rights.

(a)

Each Party will promptly report in writing to the other Party during the Term
any known or suspected infringement by a Third Party with respect to any ALNYLAM
Patent Right by the Research, Development or Commercialization by such Third
Party of a product that is or would be competitive with a Licensed RNAi Product
being researched, Developed or Commercialized by ARROWHEAD, its Affiliates or
Sublicensees (“Competitive Infringement”) and will provide the other Party with
all available evidence supporting such Competitive Infringement.

(b)

ALNYLAM shall have the sole and exclusive right to initiate and control any
infringement or other appropriate suit in the Territory against any Third Party
who at any time has infringed, or is suspected of infringing, any of the ALNYLAM
RNAi Patent Rights in its discretion.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

10

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(c)

ARROWHEAD shall have the first right to initiate and control any infringement or
other appropriate suit in the Territory with respect to a Competitive
Infringement of an ALNYLAM Target-Specific Patent Right. ALNYLAM shall, at
ARROWHEAD’s expense, cooperate with ARROWHEAD in any such suit and shall have
the right, at its own expense, to be represented in such action by counsel of
its own choice. If ARROWHEAD fails to bring any such action or proceeding within
a period of ninety (90) days after first being notified of a Competitive
Infringement of an ALNYLAM Target-Specific Patent Right, then ALNYLAM shall have
the right to bring and control such an action with respect to such Competitive
Infringement of an ALNYLAM Target-Specific Patent Right by counsel of its own
choice. ARROWHEAD shall, at ALNYLAM’s expense, cooperate with ALNYLAM in any
such suit and have the right to be represented in such action by counsel of its
own choice at its own expense. Any recoveries resulting from such an action
brought in accordance with this clause (c) shall be applied as follows:
(i) first, to reimburse each Party for all out-of-pocket costs incurred in
connection with such proceeding (on a pro rata basis, based on each Party’s
respective litigation costs, to the extent the recovery was less than all such
litigation costs); and (ii) the remainder of any such recovery shall be shared
between the Parties with the Party that initiated such action retaining *** of
the remainder of such recovery and the other Party receiving *** of the
remainder of such recovery.

7.3

Claimed Infringement of Third Party Rights, and Third Party Intellectual
Property Obligations.

(a)

In the event that a Third Party at any time provides written notice of a claim
to, or brings an action, suit or proceeding against, either Party, or any of
their respective Affiliates or Sublicensees, claiming infringement of its patent
rights based upon an assertion or claim arising out of the development, use,
manufacture, distribution, importation or sale of Licensed RNAi Products (“Third
Party Claim”), such Party will promptly notify the other Party of the claim or
the commencement of such action, suit or proceeding, enclosing a copy of the
claim and all papers served. Each Party agrees to make available to the other
Party its advice and counsel regarding the technical merits of any such claim at
no cost to the other Party and, if requested by the other Party, to provide
reasonable assistance to the other Party at no cost to the other Party other
than out-of-pocket expenses incurred in connection with such assistance.

(b)

EACH PARTY DISCLAIMS ALL REPRESENTATIONS AND WARRANTIES, EXPRESS OR IMPLIED, OF
NONINFRINGEMENT WITH RESPECT TO ANY LICENSED RNAi PRODUCT.

ARTICLE VIII - CONFIDENTIAL INFORMATION

8.1

Non-Use and Non-Disclosure of Confidential Information. Each Party agrees that
all Confidential Information of a Party that is disclosed by a Party to the
other Party (a) will not be used by the receiving Party except in connection
with the activities contemplated by this Agreement or in order to further the
purposes of this Agreement, (b) will be maintained in confidence by the
receiving Party and (c) will not be disclosed by the receiving Party to any
Third Party who is not a consultant or advisor under an obligation of
confidentiality to, the receiving Party or an Affiliate or Sublicensee of the
receiving Party, without the prior written consent of the disclosing Party. The
disclosing Party is liable for any breach of the non-disclosure obligation of
its consultants, advisors, Affiliates and Sublicensees as applicable.
Notwithstanding the foregoing, Confidential Information shall not include
information which (i) was known by the receiving Party or its Affiliates prior
to its date of disclosure by the disclosing Party to the receiving Party as
demonstrated by legally admissible evidence available to the receiving Party or
its Affiliates, (ii) either before or after the date of the disclosure such
Confidential Information is lawfully disclosed to the receiving Party or its
Affiliates by sources other than the disclosing Party rightfully in possession
of such Confidential Information or other information and not bound by
confidentiality obligations to the disclosing Party, (iii) either before or
after the date of the disclosure by the disclosing Party to the receiving Party
such Confidential Information becomes published or otherwise part of the public
domain through no fault or omission on the part of the receiving Party or its
Affiliates, or (iv) is independently developed by or for the receiving Party or
its Affiliates without reference to or in reliance upon the Confidential
Information as demonstrated by legally admissible evidence available to the
receiving Party or its Affiliates.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

11

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8.2

Permitted Disclosures. Notwithstanding the foregoing provisions of Section 8.1,
each Party may disclose Confidential Information belonging to the other Party to
the extent: (a) reasonably necessary to Research, Develop, manufacture and
Commercialize Licensed RNAi Products, including to obtain Approval of Licensed
RNAi Products, (b) to its employees, consultants and advisors, and the
employees, consultants and advisors of its Affiliates or Sublicensees as
applicable, who have a legitimate business need to know and an obligation to
maintain in confidence the Confidential Information of the disclosing Party,
(c) reasonably necessary for the prosecution and maintenance of Patent Rights,
(d) reasonably required in order for a Party to obtain financing or conduct
discussions with Development or Commercialization partners so long as such Third
Party recipients are bound by an obligation of confidentiality consistent with
that set forth herein, (e) reasonably necessary in connection with prosecuting
or defending litigation as permitted by this Agreement, (f) reasonably necessary
to enforce its rights under this Agreement or (g) required to be disclosed by
the receiving Party to comply with applicable laws or regulations or legal
process, including without limitation by the rules or regulations of the United
States Securities and Exchange Commission or similar regulatory agency in a
country other than the United States or of any stock exchange or NASDAQ,
provided that the receiving Party provides prior written notice of such
disclosure to the disclosing Party and takes reasonable and lawful actions to
avoid or minimize the extent of such disclosure.

8.3

Publicity. No disclosure of the existence of, or the terms of, this Agreement
may be made by either Party, and no Party shall use the name, trademark, trade
name or logo of the other Party or its employees in any publicity, news release
or disclosure relating to this Agreement or its subject matter, without the
prior express written permission of the other Party, except as may be required
by law or as set forth in this Section 8.3. The Parties acknowledge and agree
that, upon and following the Effective Date, the Parties shall jointly issue a
press release announcing the execution of this Agreement in form and substance
substantially as attached hereto as Exhibit D. Either Party may issue such other
press releases or otherwise make such public statements or disclosures (such as
in annual reports to stockholders or filings with the Securities and Exchange
Commission) as it determines, based on advice of counsel, are reasonably
necessary to comply with applicable laws and regulations. In addition, following
any initial press release(s) announcing this Agreement or other public
disclosure approved by both Parties, either Party shall be free to disclose,
without the other Party’s prior written consent, the existence of this
Agreement, the identity of the other Party and those terms of the Agreement
which have already been publicly disclosed in accordance herewith.

ARTICLE IX - INDEMNIFICATION AND INSURANCE

9.1

ARROWHEAD Indemnification. ARROWHEAD agrees to indemnify and hold harmless
ALNYLAM and its Affiliates, and their respective agents, directors, officers and
employees and their respective successors and assigns (the “ALNYLAM
Indemnitees”) from and against any and all losses, costs, damages, fees or
expenses (“Losses”) incurred by an ALNYLAM Indemnitee arising out of or in
connection with any claim, suit, demand, investigation or proceeding brought by
a Third Party (“Claim”) based on (a) the development, use, manufacture,
distribution or sale of any Licensed RNAi Product by ARROWHEAD or any of its
Affiliates or Sublicensees, including, but not limited to, any claims made
against ALNYLAM by Third Parties alleging infringement, injury, damage, death or
other consequence occurring to any person claimed to result, directly or
indirectly, from the possession, use or consumption of, or treatment with, any
Licensed RNAi Product, whether claimed by reason of breach of warranty,
negligence, product defect or otherwise, and regardless of the form or forum in
which any such claim is made, (b) any breach of any representation, warranty or
covenant of ARROWHEAD in this Agreement, or (c) any act or omission by ARROWHEAD
or an ARROWHEAD Indemnitee, which constitutes recklessness, gross negligence, or
willful misconduct on the part of ARROWHEAD or an ARROWHEAD Indemnitee in
connection with this Agreement. The above indemnification shall not apply to the
extent that any Losses are due to (i) a material breach of any of ALNYLAM’s
representations, warranties, covenants and/or obligations under this Agreement;
or (ii) any act or omission by ALNYLAM, or an ALNYLAM Indemnitee, which
constitutes recklessness, gross negligence, or willful misconduct on the part of
ALNYLAM, or an ALNYLAM Indemnitee.

9.2

ALNYLAM Indemnification. ALNYLAM agrees to indemnify and hold harmless ARROWHEAD
and its Affiliates, and their respective agents, directors, officers and
employees and their respective successors and assigns (the “ARROWHEAD
Indemnitees”) from and against any and all Losses incurred by an ARROWHEAD
Indemnitee arising out of or in connection with any Claim based on (a) any
breach of any representation, warranty or covenant of ALNYLAM in this Agreement,
or (b) any act or omission by ALNYLAM or an ALNYLAM Indemnitee, which
constitutes recklessness, gross negligence, or willful misconduct on the part of
ALNYLAM or an ALNYLAM Indemnitee in connection with this Agreement. The above
indemnification shall not apply to the extent that any Losses are due to (i) a
material breach of any of ARROWHEAD’ s representations, warranties, covenants
and/or obligations under this Agreement, or (ii) any act or omission by
ARROWHEAD, or an ARROWHEAD Indemnitee, which constitutes recklessness, gross
negligence, or willful misconduct on the part of ARROWHEAD, or an ARROWHEAD
Indemnitee.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

12

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9.3

Indemnification Procedures.

(a)

Each indemnified party shall notify the indemnifying party in writing (and in
reasonable detail) of the Claim within ten (10) business days after receipt by
such indemnified party of notice of a Claim or otherwise becoming aware of the
existence or threatened existence thereof. Failure to give such notice shall not
constitute a defense, in whole or in part, to any claim by an indemnified party
hereunder except to the extent the rights of the indemnifying party are
materially prejudiced by such failure to give notice. The indemnifying party
shall notify the indemnified party of its intentions as to defense of the Claim
or potential Claim in writing within ten (10) business days after receipt of
notice of the Claim. If the indemnifying party assumes the defense of a Claim
against an indemnified party, an indemnifying party shall have no obligation or
liability under this Article IX as to any Claim for which settlement or
compromise of such Claim or an offer of settlement or compromise of such Claim
is made by an indemnified party without the prior written consent of the
indemnifying party, which consent shall not be unreasonably withheld,
conditioned or delayed.

(b)

The indemnifying party shall assume exclusive control of the defense and
settlement (including all decisions relating to litigation, defense and appeal)
of any such Claim (so long as it has confirmed its indemnification obligation
responsibility to such indemnified party under this Section 9.3(b) with respect
to a given Claim); provided, however, that the indemnifying party may not settle
such Claim in any manner that would require payment by the indemnified party, or
would materially adversely affect the rights granted to the indemnified party
hereunder, or would materially conflict with the terms of this Agreement, or
adversely affect other products of the indemnified party, without first
obtaining the indemnified party’s prior written consent, which consent shall not
be unreasonably withheld, conditioned or delayed.

(c)

The indemnified party shall reasonably cooperate with the indemnifying party in
its defense of the Claim (including making documents and records available for
review and copying and making persons within its control available for pertinent
testimony in accordance with the confidentiality provisions of Article VII, and
neither party shall be required to divulge privileged material to the other) at
the indemnifying party’s expense. If the indemnifying party assumes defense of
the Claim, an indemnified party may participate in, but not control, the defense
of such Claim using attorneys of its choice and at its sole cost and expense,
with such cost and expense not being covered by the indemnifying party. If an
indemnifying party does not agree to assume the defense of the Claim asserted
against the indemnified party (or does not give notice that it is assuming such
defense), or if the indemnifying party assumes the defense of the Claim in
accordance with Section 9.3(b) yet fails to defend or take other reasonable,
timely action, in response to such Claim asserted against the indemnified party,
the indemnified party shall have the right to defend or take other reasonable
action to defend its interests in such proceedings, and shall have the right to
litigate, settle or otherwise dispose of any such Claim; provided, however, that
the indemnified party shall not have the right to settle such Claim in any
manner that would adversely affect the rights granted to the other party
hereunder, or would materially conflict with this Agreement, or would require a
payment by the other party, or adversely affect the products of the other party,
without the prior written consent of the other party, which consent shall not be
unreasonably withheld, conditioned or delayed.

ARTICLE X - EXPORT

10.1

General. The Parties acknowledge that the exportation from the United States of
materials, products and related technical data (and the re-export from elsewhere
of United States origin items) may be subject to compliance with United States
export laws, including without limitation the United States Bureau of Export
Administration’s Export Administration Regulations, the Act and regulations of
the FDA issued thereunder, and the United States Department of State’s
International Traffic and Arms Regulations which restrict export, re-export, and
release of materials, products and their related technical data, and the direct
products of such technical data. The Parties agree to comply with all applicable
exports laws and to commit no act that, directly or indirectly, would violate
any United States law, regulation, or treaty, or any other international treaty
or agreement, relating to the export, re-export, or release of any materials,
products or their related technical data to which the United States adheres or
with which the United States complies.

10.2

Delays. The Parties acknowledge that they cannot be responsible for any delays
attributable to export controls which are beyond the reasonable control of
either Party.

10.3

Assistance. The Parties agree to provide assistance to one another in connection
with each Party’s efforts to fulfill its obligations under this Article X.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

13

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ARTICLE XI - TERM AND TERMINATION

11.1

Term. This Agreement will remain in effect until the end of the last-to-expire
Royalty Term with respect to all Licensed RNAi Products (the “Term”) unless
terminated in accordance with this Article XI.

11.2

Material Breach. Either Party (the “Non-Breaching Party”) will have the right to
terminate this Agreement, upon written notice to the other Party (the “Breaching
Party”), in the event the latter materially breaches its obligations under this
Agreement and does not remedy such breach within sixty (60) days (thirty
(30) days for payment breaches) after receipt of written notice from the
Non-Breaching Party specifically identifying the breach and stating it intends
to terminate the Agreement if the Breaching Party fails to remedy the breach
within the sixty (60)-day (or thirty (30)-day for payment breaches) notice
period.

11.3

Termination by ARROWHEAD. ARROWHEAD will have the right to terminate this
Agreement for any reason upon thirty (30) days’ prior written notice to ALNYLAM.

11.4

Termination Due to Patent Challenge. If ARROWHEAD or any of its Affiliates or
Sublicensees initiates, or assists any Third Party in initiating, any legal
action seeking a determination that any of the ALNYLAM Patent Rights in any
country are invalid, unenforceable, and/or not infringed (including a request
for reexamination or opposition of any such ALNYLAM Patent Rights), to the
extent permitted by the applicable law of such country, ALNYLAM may terminate
this Agreement upon thirty (30) days’ prior written notice to ARROWHEAD,
provided, however, that if, prior to the end of such thirty (30)-day period
ARROWHEAD is able to obtain a full and complete withdrawal of such action and
ARROWHEAD shall pay all of ALNYLAM’s costs associated therewith, the termination
shall not become effective and this Agreement shall remain in full force and
effect.

11.5

Consequences of Termination; Survival.

(a)

In the event this Agreement is terminated under Section 11.2, 11.3 or 11.4, all
licenses and other rights granted by ALNYLAM to ARROWHEAD under this Agreement
will terminate.

(b)

Expiration or termination of this Agreement shall not relieve the Parties of any
obligation accruing prior to such expiration or termination or any rights of the
Parties that accrued prior to such expiration or termination. Termination of
this Agreement, for whatever reason in accordance with the provisions hereof,
shall not limit remedies that may be otherwise available in law or equity.

(c)

The provisions of Article VIII shall survive the expiration or termination of
this Agreement for any cause and shall continue in effect as applicable for ten
(10) years from the date of initial disclosure. In addition, the provisions of
Articles V, VI, IX and XII (other than 12.1 and 12.2), and this Section 11.5
shall survive any expiration or termination of this Agreement.

ARTICLE XII - MISCELLANEOUS

12.1

Representations by ARROWHEAD and ALNYLAM.

(a)

Each Party hereby represents and warrants to the other Party, as of the
Effective Date, that:

(i)

Such Party is duly organized under the laws of the state or country of its
formation, and has all necessary power and authority to conduct its business in
the manner in which it is currently being conducted, to own and use its assets
in the manner in which its assets are currently owned and used, and to enter
into and perform its obligations under this Agreement.

(ii)

The execution, delivery and performance of this Agreement (A) has been duly
authorized by all necessary action on the part of such Party and its Board of
Directors (or comparable governance body) and (B) does not and will not conflict
with, or constitute a default under, any agreement, instrument or understanding,
oral or written, to which such Party is a party or by which it is bound.
Further, no consent, approval, order or authorization of, or registration,
declaration or filing with any Third Party or governmental authority is
necessary for the execution, delivery or performance of this Agreement.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

14

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(iii)

This Agreement constitutes the legal, valid and binding obligation of such
Party, enforceable against it in accordance with its terms, subject to (A) laws
of general application relating to bankruptcy, insolvency and the relief of
debtors, and (B) rules of law governing specific performance, injunctive relief
and other equitable remedies.

(iv)

Neither such Party nor any of its Affiliates has been found in breach of any
laws or regulations governing the production of medicinal products in the United
States or any other jurisdiction within the Territory.

(v)

Neither such Party nor any of its Affiliates has been debarred (nor is such
Party or any of its Affiliates using in any capacity in connection with its
activities under this Agreement any person who has been debarred) by the FDA
from working for or providing services to any pharmaceutical or biotechnology
company under Section 306 of the Act.

(vi)

Such Party has never approved or commenced any proceeding, or made any election
contemplating, the winding up or cessation of such Party’s business or affairs
or the assignment of such Party’s material assets for the benefit of creditors.
To such Party’s knowledge, no such proceeding is pending or threatened.

(b)

ALNYLAM represents and warrants to ARROWHEAD that as of the Effective Date:

(i)

ALNYLAM has the right to grant ARROWHEAD the licenses granted hereunder and has
not granted any conflicting rights to any other person or entity.

(ii)

ALNYLAM has not previously granted any right, license or interest in or to the
ALNYLAM Patent Rights, or any portion thereof, that is in conflict with the
rights or licenses granted to ARROWHEAD under this Agreement.

(iii)

ALNYLAM and its Affiliates have taken reasonable measures to protect the ALNYLAM
Intellectual Property, consistent with prudent commercial practices in the
biotechnology industry.

(c)

EXCEPT AS OTHERWISE EXPRESSLY SET FORTH IN THIS ARTICLE XII, NEITHER PARTY MAKES
ANY REPRESENTATION OR EXTENDS ANY WARRANTIES OF ANY KIND, EITHER EXPRESS OR
IMPLIED, TO THE OTHER PARTY, INCLUDING ANY WARRANTIES OF MERCHANTABILITY OR
FITNESS FOR A PARTICULAR PURPOSE.

12.2

Mutual Covenants. Each Party hereby covenants to the other Party that:

(a)

Such Party shall comply with all applicable laws, rules and regulations in
connection with this Agreement and the transactions contemplated hereby and will
perform its activities pursuant to this Agreement in compliance in all material
respects with GLP and GCP; and

(b)

All employees of such Party or its Affiliates working under this Agreement will
be under the obligation to assign all right, title and interest in and to their
inventions and discoveries, whether or not patentable, to such Party as the sole
owner thereof

12.3

Dispute Resolution; Arbitration Procedures.

(a)

In the event of any dispute, controversy or claim arising out of or relating to
this Agreement or the breach thereof, the Parties will try to settle such
dispute, controversy or claim amicably between themselves, including referring
such dispute, controversy or claim to the Executive Officers. In the event that
after forty-five (45) days the designated officers of both Parties fail to
resolve the matter, either Party may submit such dispute, controversy or claim
that is not an “Excluded Claim” for resolution by binding arbitration under the
Rules of Arbitration of the American Arbitration Association. Judgment on the
arbitration award may be entered in any court of competent jurisdiction. The
arbitration will be conducted in New York, New York and the language of all
communications and proceedings relating to the arbitration will be English.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

15

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(b)

The arbitration shall be conducted by a panel of three persons experienced in
the pharmaceutical business. Within thirty (30) days after initiation of
arbitration, each Party shall select one person to act as arbitrator and the two
Party-selected arbitrators shall select a third arbitrator within thirty
(30) days of their appointment. If the arbitrators selected by the Parties are
unable or fail to agree upon the third arbitrator, the Parties shall select two
replacement arbitrators to replace the arbitrators originally selected, which
replacement arbitrators shall select a third arbitrator within thirty (30) days
of their appointment. The Parties agree (a) to meet with the arbitrator(s)
within thirty (30) days of selection and (b) to agree at that meeting or before
as to the conduct of the hearing which will result in the hearing being
concluded within no more than six (6) months after selection of the
arbitrator(s) and in the award being rendered within thirty (30) days of any
post-hearing briefing, which briefing will be completed by both sides within
thirty (30) days after the conclusion of the hearings, or within sixty (60) days
of the conclusion of the hearings if there is no post-hearing briefing. In no
event will the arbitrator(s), absent agreement of the Parties, allow more than
three (3) days per side for the hearing or more than a total of six (6) days for
the hearing. Multiple hearing days will be scheduled consecutively to the
greatest extent possible.

(c)

Either Party may apply to the arbitrators for interim injunctive relief until
the arbitration award is rendered or the controversy is otherwise resolved.
Either Party also may, without waiving any remedy under this Agreement, seek
from any court having jurisdiction any injunctive or provisional relief
necessary to protect the rights or property of that Party pending the
arbitration award. The arbitrators shall have no authority to award punitive or
any other type of damages not measured by a Party’s compensatory damages. The
costs, expenses, attorneys’ fees and arbitrators’ fees and any administrative
fees of arbitration of both Parties shall be borne by the Parties as determined
by the arbitrators, who shall take into account the nature of the dispute and
reasonableness of the Parties’ positions with respect to the dispute in making
such determination.

(d)

Except to the extent necessary to confirm an award or as may be required by law,
neither a Party nor an arbitrator may disclose the existence, content, or
results of an arbitration without the prior written consent of both Parties. In
no event shall an arbitration be initiated after the date when commencement of a
legal or equitable proceeding based on the dispute, controversy or claim would
be barred by the applicable Massachusetts statute of limitations.

(e)

Notwithstanding anything in this Agreement to the contrary, a Party may seek a
temporary restraining order or a preliminary injunction from any court of
competent jurisdiction in order to prevent immediate and irreparable injury,
loss, or damage on a provisional basis, pending an award of the arbitrators on
the ultimate merits of any dispute.

(f)

As used in this Section 12.3, the term “Excluded Claim” shall mean a dispute,
controversy or claim that concerns (i) the validity or infringement of a patent,
trademark or copyright; or (ii) any antitrust, anti-monopoly or competition law
or regulation, whether or not statutory. Excluded Claims shall be resolved in a
court of competent jurisdiction.

12.4

Force Majeure. No failure or omission by the Parties in the performance of any
obligation of this Agreement will be deemed a breach of this Agreement or create
any liability if the same will arise from any cause or causes beyond the control
of the Parties, 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; flood; storm; earthquake; accident; war; rebellion; insurrection;
riot; and invasion. The affected Party shall notify the other Party of such
force majeure circumstances as soon as reasonably practical, and shall promptly
undertake all reasonable efforts necessary to cure such force majeure
circumstances.

12.5

Consequential Damages. NEITHER PARTY (INCLUDING ITS AFFILIATES AND SUBLICENSEES)
SHALL BE LIABLE UNDER THIS AGREEMENT FOR ANY SPECIAL, INDIRECT, INCIDENTAL, OR
CONSEQUENTIAL DAMAGES OR FOR LOSS OF PROFIT OR LOST REVENUE, EVEN IF SUCH PARTY
HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES. NOTWITHSTANDING THE
FOREGOING, NOTHING IN THIS SECTION 12.5 IS INTENDED TO OR SHALL LIMIT OR
RESTRICT THE INDEMNIFICATION RIGHTS OF A PARTY OR DAMAGES AVAILABLE FOR A
PARTY’S BREACH OF CONFIDENTIALITY OBLIGATIONS IN ARTICLE VIII.

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

16

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12.6

Assignment.

(a)

This Agreement and any of its rights and obligations may not be assigned or
otherwise transferred by either Party without the prior written consent of the
other Party, which consent may not be unreasonably withheld, delayed or
conditioned; provided, however, that either Party may assign this Agreement,
without the consent of the other Party, in connection with such Party’s merger,
consolidation or transfer or sale of all or substantially all of the business or
assets of such Party relating to the subject matter of this Agreement; provided
further that the successor, surviving entity, purchaser of assets, or
transferee, as applicable, expressly assumes in writing such Party’s obligations
under this Agreement. Any purported assignment in contravention of this
Section 12.6 shall, at the option of the non-assigning Party, be null and void
and of no effect.

(b)

Each Party agrees that, notwithstanding any provisions of this Agreement to the
contrary, if this Agreement is assigned by a Party in connection with such
Party’s merger, consolidation or transfer or sale of all or substantially all of
the business or assets of such Party relating to the subject matter of this
Agreement, such assignment shall not provide the non-assigning Party with rights
or access to any intellectual property or technology of the acquirer of the
assigning Party.

(c)

If ARROWHEAD assigns its rights and obligations hereunder to an Affiliate or
Third Party outside the United States pursuant to this Section 12.6, and if such
Affiliate or Third Party shall be required by applicable Law to withhold any
additional taxes from or in respect of any amount payable under this Agreement
as a result of such assignment, then any such amount payable under this
Agreement shall be increased to take into account the additional taxes withheld
as may be necessary so that, after making all required withholdings, ALNYLAM
receives an amount equal to the sum it would have received had no such
assignment been made.

(d)

This Agreement will be binding upon and inure to the benefit of the Parties and
their permitted successors and assigns.

12.7

Notices.

Notices to ALNYLAM will be addressed to:

Alnylam Pharmaceuticals, Inc.

300 Third Street

Cambridge, Massachusetts 02142

U.S.A.

Attention: Chief Business Officer

Facsimile No.: (617) 551-8101

With copy to:

Wilmer Cutler Pickering Hale and Don LLP

60 State Street

Boston, Massachusetts 02109

U.S.A.

Attention: Steven D. Barrett, Esq.

Facsimile No.: (617) 526-5000

Notices to ARROWHEAD will be addressed to:

Attention:

Brendan Rae, Ph.D., J.D.

 

Arrowhead Research Corporation

 

225 South Lake Avenue, 3rd Floor

 

Pasadena, CA 91101

 

Telephone: (626) 304-3400

 

Fax: (626) 304-3401

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

17

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With copy to:

Attention:

Thomas Haag, Ph.D., Esq.

 

Fanelli Haag PLLC

 

1909 K St. NW, Suite 1120

 

Washington, DC 20006

 

Telephone: 202.706.7910

 

Fax: 202.706.7920

Any Party may change its address by giving notice to the other Party in the
manner provided in this Section 12.7. Any notice required or provided for by the
terms of this Agreement will be in writing and will be (a) sent by certified
mail, return receipt requested, postage prepaid, (b) sent via a reputable
national express courier service, or (c) sent by facsimile transmission, with a
copy by regular mail. The effective date of the notice will be the actual date
of receipt by the receiving Party.

12.8

Independent Contractors. It is understood and agreed that the relationship
between the Parties is that of independent contractors and that nothing in this
Agreement will be construed as authorization for either Party to act as the
agent for the other Party.

12.9

Governing Law; Jurisdiction. This Agreement will be governed and interpreted in
accordance with the substantive laws of the State of New York of the U.S.A.,
notwithstanding the provisions governing conflict of laws under such law of the
State of New York to the contrary, provided that matters of intellectual
property law will be determined in accordance with the national intellectual
property laws relevant to the intellectual property in question.

12.10

Severability. In the event that any provision of this Agreement is held by a
court of competent jurisdiction to be unenforceable because it is invalid or in
conflict with any law of the relevant jurisdiction, the validity of the
remaining provisions will not be affected and the rights and obligations of the
Parties will be construed and enforced as if the Agreement did not contain the
particular provisions held to be unenforceable, provided that the Parties will
negotiate in good faith a modification of this Agreement with a view to revising
this Agreement in a manner which reflects, as closely as is reasonably
practicable, the commercial terms of this Agreement as originally signed.

12.11

No Implied Waivers. The waiver by either Party of a breach or default of any
provision of this Agreement by the other Party will not be construed as a waiver
of any succeeding breach of the same or any other provision, nor will any delay
or omission on the part of either Party to exercise or avail itself of any
right, power or privilege that it has or may have hereunder operate as a waiver
of any right, power or privilege by such Party.

12.12

Entire Agreement. This Agreement, along with that certain Confidential
Disclosure Agreement by and between the Parties dated as of October 28, 2011,
constitutes the entire agreement between the Parties with respect to its subject
matter and supersedes all previous written or oral representations, agreements
and understandings between the Parties. This Agreement may be amended only in a
writing signed by both Parties.

 

 

 

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

18

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12.13

Headings; Construction; Interpretation. Headings used herein are for convenience
only and shall not in any way affect the construction of or be taken into
consideration in interpreting this Agreement. The terms of this Agreement
represent the results of negotiations between the Parties and their
representatives, each of which has been represented by counsel of its own
choosing, and neither of which has acted under duress or compulsion, whether
legal, economic or otherwise. Accordingly, the terms of this Agreement shall be
interpreted and construed in accordance with their usual and customary meanings,
and each of the Parties hereto hereby waives the application in connection with
the interpretation and construction of this Agreement of any rule of law to the
effect that ambiguous or conflicting terms or provisions contained in this
Agreement shall be interpreted or construed against the Party whose attorney
prepared the executed draft or any earlier draft of this Agreement. Any
reference in this Agreement to an Article, Section, subsection, paragraph,
clause, Schedule or Exhibit shall be deemed to be a reference to any Article,
Section, subsection, paragraph, clause, Schedule or Exhibit, of or to, as the
case may be, this Agreement. Except where the context otherwise requires,
(a) any definition of or reference to any agreement, instrument or other
document refers to such agreement, instrument other document as from time to
time amended, supplemented or otherwise modified (subject to any restrictions on
such amendments, supplements or modifications set forth herein or therein),
(b) any reference to any law, rule or regulation refers to such law, rule or
regulation as from time to time enacted, repealed or amended, (c) the words
“herein,” “hereof’ and “hereunder,” and words of similar import, refer to this
Agreement in its entirety and not to any particular provision hereof, (d) the
words “include,” “includes,” “including,” “exclude,” “excludes,” and
“excluding,” shall be deemed to be followed by the phrase “but not limited to,”
“without limitation” or words of similar import, (e) except where the context
otherwise requires, the word “or” is used in the inclusive sense, and (f) all
references to “dollars” or “$” herein shall mean US Dollars.

12.14

Counterparts. This Agreement may be signed in counterparts, each and every one
of which shall be deemed an original, notwithstanding variations in format or
file designation which may result from the electronic transmission, storage and
printing of copies from separate computers or printers. Facsimile signatures and
signatures transmitted via portable document format (PDF) shall be treated as
original signatures.

IN WITNESS WHEREOF, the Parties hereto have set their hand as of the Effective
Date.

 

ALNYLAM PHARMACEUTICALS, INC.

 

By:

/s/ Laurence E. Reid

 

Name: L.E. Reid

 

Title: CBO

 

ARROWHEAD RESEARCH CORPORATION

 

By:

/s/ Chris Anzalone

 

Name: Chris Anzalone

 

Title: President & CEO

 

ARROWHEAD MADISON INC.

 

By:

/s/ Chris Anzalone

 

Name: Chris Anzalone

 

Title: President & CEO

 

 

 

 

*** Certain information in this document has been omitted and filed separately
with the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions.

 

Signature Page to License Agreement

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EXHIBIT A

ALNYLAM Patent Rights

 

 

 

--------------------------------------------------------------------------------

 

 

Our Ref. No.

Country

Application No.

Patent No.

Status

Application Title

RIB-001.3AT1

Austria

EP 02003683

E297.463

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3AT2

Austria

05002454.6-2107

E418.60

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3AU

Australia

2000032713

778474

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3AU1

Australia

2005201044

2005201044

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3AUD2

Australia

2008202208

 

Opposed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CA

Canada

2,359,180

2,359,180

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CH1

Switzerland

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CH2

Switzerland

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CY1

Cyprus

EP 02003683

CY05/1101016

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CY2

Cyprus

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE0

Germany

50000414.5-08

1144623

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE1

Belgium

EP 02003683

EP 1214945 B1

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE1

Germany

50010528.6-08

1214945

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE2

Belgium

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE2

Germany

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DED1

Germany

10066235.8

10066235.8

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DED2

Germany

10066344.3

 

Pending

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DED3

Germany

10066382.6

 

Pending

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DEUTM

Germany

20023125.1

DE20023125 U1

RegUtilMode

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DK1

Denmark

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DK2

Denmark

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

 

--------------------------------------------------------------------------------

 

RIB-001.3EPD1

Europe

02003683.6

1214945

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3EPD2

Europe

05002454.6

1550719

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3EPD3

Europe

06025389.5

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3EPD4

Europe

10011217.6

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3ES1

Spain

EP 02003683

ES2243608

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3ES2

Spain

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3FI1

Finland

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3FI2

Finland

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3FR1

France

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3FR2

France

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3GB1

United Kingdom

EP 02003683

EP1214945

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3GB2

United Kingdom

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3GR1

Greece

EP 02003683

3054579

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3GR2

Greece

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IE

Ireland

EP 00910510

1144623 B9

Revoked

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IE1

Ireland

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IE2

Ireland

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IT1

Italy

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IT2

Italy

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD10

Japan

2009-285706

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD3

Japan

2007-186341

 

Appealed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD4

Japan

2007-186340

 

Appealed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

 

--------------------------------------------------------------------------------

 

RIB-001.3JPD5

Japan

2007-186339

 

ExamReq

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD7

Japan

2009-002825

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD9

Japan

2009-285705

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3LI1

Liechtenstein

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3LI2

Liechtenstein

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3LU1

Luxembourg

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3LU2

Luxembourg

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3MC1

Monaco

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3MC2

Monaco

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3NL1

Netherlands

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3NL2

Netherlands

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3PT1

Portugal

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3PT2

Portugal

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3SE1

Sweden

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3SE2

Sweden

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON1

US

11/982325

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON2

US

11/982305

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON3

US

11/982425

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON4

US

11/982441

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON5

US

11/982345

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON6

US

11/982434

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USD1

US

10/382395

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

 

--------------------------------------------------------------------------------

 

RIB-001.3USD2

US

10/383099

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USD3

US

10/382768

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USD4

US

10/612179

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3WO

PCT

PCT/DE00/00244

 

CompletedNt

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3ZA

South Africa

ZA 20015909

2001/5909

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-002.1DE

Germany

10100586.5-09

DE10100586 C1

Granted

INHIBITING GENE EXPRESSION IN CELLS, USEFUL FOR e.g., TREATING TUMORS, BY
INTRODUCING DOUBLE-STRANDED COMPLEMENTARY OLIGORNA HAVING

RIB-002.4

US

12/894018

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4AT

Austria

02710786.1

E328.075

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4AU

Australia

2002229701

2002229701

Granted

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4CH

Switzerland

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4CY

Cyprus

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4DE

Germany

50206993.7-08

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4EP

Europe

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4GB

United Kingdom

EP 02710786

EP 1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4IE

Ireland

02710786.1

1352061

Granted

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4JP

Japan

2002-556740

4210116

Granted

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4JPD1

Japan

2002-556739

4209678

Granted

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4LI

Liechtenstein

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4LU

Luxembourg

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4TR

Turkey

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4US

US

10/384,339

7,829,693

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

 

--------------------------------------------------------------------------------

 

RIB-002.4WO

PCT

PCT/EP02/00152

 

CompletedNt

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-006.1DE

Germany

02702247.4-2405/1349

50214866.9-08

Allowed

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1EP

Europe

02702247.4

EP1349927

GrantedInOp

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1EPD1

Europe

10002422.3

 

Pending

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1EPD2

Europe

10011812.4

 

Published

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1ES

Spain

02702247

ES2204360

Granted

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1FR

France

EP 02702247

EP1349927

Granted

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1GB

United Kingdom

02702247.4-2405/1349

EP1349927

Granted

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1HKD1

Hong Kong

11100629.6

 

Published

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1HKD2

Hong Kong

11111936.1

 

Pending

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1NL

Netherlands

EP 02702247

EP1349927

Granted

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1WO

PCT

PCT/EP02/00151

 

CompletedNt

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.2US

US

10/384,260

7,473,525

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.2US

US

12/276,270

 

Pending

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4AU

Australia

2005284729

 

Allowed

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4CA

Canada

2580560

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4EP

Europe

05797892.6

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4EPD1

Europe

11004902.0

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4HK

Hong Kong

07114036.0

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4US

US

10/941663

7767802

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4USCIP2

US

11/229183

7423142

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4USCON2

US

12/961337

 

Allowed

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

 

--------------------------------------------------------------------------------

 

RIB-006.4USD1

US

12/175,938

7,868,160

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4WO

PCT

PCT/US2005/033 309

 

CompletedNt

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-008.2DE

Germany

DE 10163098

DE10163098

Granted

METHOD FOR INHIBITING THE REPLICATION OF VIRUSES

RIB-008.3USCIP

US

10/384,512

7,348,314

Issued

METHOD TO INHIBIT THE REPLICATION OF VIRUSES

RIB-008.3USCON

US

11/959,936

7,745,418

Issued

METHOD TO INHIBIT THE REPLICATION OF VIRUSES

RIB-008.3USCON1

US

12/631689

 

Published

METHOD TO INHIBIT THE REPLICATION OF VIRUSES

RIB-011.2WO

PCT

PCT/EP02/11973

 

CompletedNt

USE OF DOUBLE STRAND RIBONUCLEIC ACID FOR TREATING AN INFECTION WITH A
POSTIVE-STRAND RNA-VIRUS

RIB-012.2EP

Europe

02779511.1

 

Appealed

USE OF A DOUBLE-STRANDED RIBONUCLEIC ACID FOR SPECIFICALLY INHIBITING THE
EXPRESSION OF A GIVEN TARGET GENE

RIB-012.2EPD1

Europe

10011813.2

 

Published

USE OF A DOUBLE-STRANDED RIBONUCLEIC ACID FOR SPECIFICALLY INHIBITING THE
EXPRESSION OF A GIVEN TARGET GENE

RIB-012.2WO

PCT

PCT/EP02/11969

 

CompletedNt

USE OF A DOUBLE-STRANDED RIBONUCLEIC ACID FOR SPECIFICALLY INHIBITING THE
EXPRESSION OF A GIVEN TARGET GENE

RIB-012.3US

US

10/384,463

7,763,590

Issued

COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF A MUTANT GENE

RIB-012.3USCON1

US

13/177316

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF A MUTANT GENE

RIB-012.3USD1

US

12/817009

7994309

Allowed

COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF A MUTANT GENE

RIB-013.1WO

PCT

PCT/EP02/11972

 

CompletedNt

DRUG FOR TREATING A FIBROTIC DISEASE THROUGH RNA INTERFERENCE

RIB-014.1WO

PCT

PCT/EP02/12221

 

Expired

SMAD7 INHIBITORS FOR THE TREATMENT OF CNS DISEASES

RIB-015.2US

US

10/349,320

7,196,184

Issued

DOUBLE-STRANDED RNA (dsRNA) AND METHOD FOR USE FOR INHIBITING EXPRESSION OF A
FUSION GENE

RIB-015.2USCON1

US

12/912616

 

Published

DOUBLE-STRANDED RNA (dsRNA) AND METHOD FOR USE FOR INHIBITING EXPRESSION OF A
FUSION GENE

RIB-015.2USD1

US

11/656,349

7,846,907

Allowed

DOUBLE-STRANDED RNA (dsRNA) AND METHOD FOR USE FOR INHIBITING EXPRESSION OF A
FUSION GENE

RIB-015.3WO

PCT

PCT/EP03/00604

 

Expired

METHOD FOR INCREASING THE EFFICIENCY OF AN INHIBITOR OF TYROSINE KINASE ACTIVITY

RIB-016.1DE

Germany

10302421.2-41

 

Published

DOUBLE-STRANDED RIBONUCLEIC ACID WITH IMPROVED ACTIVITY

RIB-016.2AT

Austria

E367441

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2AU

Australia

2004206255

2004206255

Issued

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2AUD1

Australia

2008203538

 

Pending

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

 

--------------------------------------------------------------------------------

 

RIB-016.2BE

Belgium

04704041.5

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2CA

Canada

2513809

2513809

Allowed

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2CH

Switzerland

04704041.5

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2CY

Cyprus

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2DE

Germany

602004007620.1- 08

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2DK

Denmark

04704041.5

DK/EP 1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2EP

Europe

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2EPD1

Europe

07010839.4

 

Published

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2ES

Spain

04704041.5-1521

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2FR

France

04704041.5-1521

EP1587926B1

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2GB

United Kingdom

04704041.5-1521

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2HK

Hong Kong

08105048.3

 

Published

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2HU

Hungary

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2IE

Ireland

04704041.5

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2IT

Italy

04704041.5-1521

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2LI

Liechtenstein

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2LU

Luxembourg

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2NL

Netherlands

04704041.5-1521

EP1587926B1

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2PT

Portugal

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2SE

Sweden

04704041.5-1521

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2SI

Slovenia

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2TR

Turkey

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

 

--------------------------------------------------------------------------------

 

RIB-016.2US

US

10/543048

 

Appealed

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2WO

PCT

PCT/US2004/001 461

 

CompletedNt

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-017.1EPUS

US

60/479,354

 

Converted

SiRNA WITH INCREASED STABILITY IN SERUM

 

 

 

 

--------------------------------------------------------------------------------

 

 

Isis Docket No.

Country

Status

Patent No.

Title

GLIS-0129

AT

Granted

ATE190981T1

2’ MODIFIED NUCEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0130

CH

Granted

497875

2’ MODIFIED NUCEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0131

DE

Granted

690 33 495.8

2’ MODIFIED NUCEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0132

DK

Granted

497875

2’ MODIFIED NUCEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0133

FR

Granted

497875

2’ MODIFIED NUCEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0134

GB

Granted

497875

2’ MODIFIED NUCEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0135

LX

Granted

497875

2’ MODIFIED NUCEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0136

SE

Granted

497875

2’ MODIFIED NUCEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0041

AU

Granted

658562

2’ MODIFIED NUCLEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0042

CA

Pending

 

2’ MODIFIED NUCLEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0043

EP

Granted

497875

2’ MODIFIED NUCLEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0045

US

Granted

5792847

2’ MODIFIED NUCLEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0047

US

Granted

5466786

2’ MODIFIED NUCLEOSIDE AND NUCLEOTIDE COMPOUNDS

GLIS-0046

US

Granted

6476205

2’ MODIFIED OLIGONUCLEOTIDES

GLIS-0126

EP

Pending

 

2’ MODIFIED OLIGONUCLEOTIDES

GLIS-0148

US

Pending

 

2’ MODIFIED OLIGONUCLEOTIDES

ISIS-4178

JP

Pending

 

2’-O-ALKYLATED GUANOSINE 3’o-PHOSPHORAMIDITES

GLIS-0146

US

Pending

 

2-AMINOPYRIDINE AND 2-PYRIDONE C-NUCLEOSIDES

GLIS-0113

US

Granted

6447998

2-AMINOPYRIDINE AND 2-PYRIDONE C-NUCLEOSIDES

ISIS-5017

JP

Pending

 

2’-GUANIDINYL-SUBSTITUTED OLIGONUCLEOTIDES AND GENE EXPRESSION MODULATION
THEREWITH

ISIS-4997

EP

Pending

 

2’-GUANIDINYL-SUBSTITUTED OLIGONUCLEOTIDES AND GENE EXPRESSION MODULATION
THEREWITH

ISIS-2004

US

Granted

5859221

2’-MODIFIED OLIGONUCLEOTIDES

ISIS-2826

US

Granted

6005087

2’-MODIFIED OLIGONUCLEOTIDES

ISIS-4099

US

Granted

6531584

2’-MODIFIED OLIGONUCLEOTIDES

ISIS-5137

US

Pending

 

2’-MODIFIED OLIGONUCLEOTIDES

ISIS-4071

US

Granted

6147200

2’-O-ACETAMIDO MODIFIED MONOMERS AND OLIGOMERS

ISIS-4477

EP

Pending

 

2’-O-ACETAMIDO MODIFIED MONOMERS AND OLIGOMERS

ISIS-4496

JP

Pending

 

2’-O-ACETAMIDO MODIFIED MONOMERS AND OLIGOMERS

ISIS-4044

US

Granted

6600032

2’-O-AMINOETHYLOXYETHYL-MODIFIED OLIGONUCLEOTIDES

ISIS-5036

US

Granted

6673912

2’-O-AMINOETHYLOXYETHYL-MODIFIED OLIGONUCLEOTIDES

ISIS-2824

US

Granted

6127533

2’-O-AMINOOXY-MODIFIED OLIGONUCLEOTIDES (as amended)

ISIS-3156

US

Granted

6043352

2’-O-DIMETHYLAMINOETHYLOXYETHYL-MODIFIED OLIGONUCLEOTIDES

ISIS-4047

AU

Granted

750469

2’-O-DIMETHYLAMINOETHYLOXYETHYL-MODIFIED OLIGONUCLEOTIDES

ISIS-4048

CA

Pending

 

2’-O-DIMETHYLAMINOETHYLOXYETHYL-MODIFIED OLIGONUCLEOTIDES

ISIS-4049

EP

Pending

 

2’-O-DIMETHYLAMINOETHYLOXYETHYL-MODIFIED OLIGONUCLEOTIDES

ISIS-4068

JP

Pending

 

2’-O-DIMETHYLAMINOETHYLOXYETHYL-MODIFIED OLIGONUCLEOTIDES

ISIS-5018

US

Pending

 

2’-O-DIMETHYLAMINOETHYLOXYETHYL-MODIFIED OLIGONUCLEOTIDES

ISIS-1082

US

Granted

5914396

2’-O-MODIFIED NUCLEOSIDES AND PHOSPHORAMIDITES

ISIS-2005

US

Granted

5872232

2’-O-MODIFIED OLIGONUCLEOTIDES

ISIS-0780

US

Granted

5457191

3-DEAZAPURINES

 

--------------------------------------------------------------------------------

 

ISIS-2044

US

Granted

5587470

3-DEAZAPURINES

ISIS-0002

US

Granted

5223618

4’-DESMETHYL NUCLEOSIDE ANALOG COMPOUNDS

ISIS-4260

US

Granted

6320040

4’-DESMETHYL NUCLEOSIDE ANALOGS, AND OLIGOMERS THEREOF

ISIS-2090

US

Granted

5998603

4’-DESMETHYL NUCLEOSIDE ANALOGS, AND OLIGOMERS THEREOF

HYBN-221.0US

US

Granted

5912332

AFFINITY-BASED PURIFICATION OF OLIGONUCLEOTIDES USING SOLUBLE MULTIMERIC
OLIGONUCLEOTIDES

ISIS-1692

AU

Granted

679566

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1693

CA

Granted

2170869

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1694

EP

Granted

694 33 036.1

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1698

FR

Granted

728139

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1699

GB

Granted

728139

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1700

DE

Granted

728139

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1702

IE

Granted

728139

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1710

CH

Granted

728139

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1711

JP

Granted

3484197

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1712

US

Pending

 

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-2000

US

Pending

 

AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1788

US

Granted

5834607

AMINES AND METHODS OF MAKING AND USING THE SAME

ISIS-3508

US

Granted

6576752

AMINOOXY FUNCTIONALIZED OLIGOMERS

ISIS-5089

US

Pending

 

AMINOOXY FUNCTIONALIZED OLIGOMERS, OLIGOMER ARRAYS AND METHODS OF USING THEM

ISIS-3993

US

Granted

6639062

AMINOOXY-MODIFIED NUCLEOSIDIC COMPOUNDS AND OLIGOMERIC COMPOUNDS PREPARED
THEREFROM

ISIS-2829

AU

Granted

740799

AMINOOXY-MODIFIED OLIGONUCLEOTIDES

ISIS-2830

CA

Pending

 

AMINOOXY-MODIFIED OLIGONUCLEOTIDES

ISIS-2831

EP

Pending

 

AMINOOXY-MODIFIED OLIGONUCLEOTIDES

ISIS-2849

JP

Pending

 

AMINOOXY-MODIFIED OLIGONUCLEOTIDES

ISIS-2850

KR

Granted

399743

AMINOOXY-MODIFIED OLIGONUCLEOTIDES

ISIS-2955

US

Granted

6172209

AMINOOXY-MODIFIED OLIGONUCLEOTIDES AND METHODS FOR MAKING SAME

ISIS-3996

AU

Granted

752878

AMINOOXY-MODIFIED OLIGONUCLEOTIDES AND METHODS FOR MAKING SAME

ISIS-3997

CA

Pending

 

AMINOOXY-MODIFIED OLIGONUCLEOTIDES AND METHODS FOR MAKING SAME

ISIS-3998

EP

Pending

 

AMINOOXY-MODIFIED OLIGONUCLEOTIDES AND METHODS FOR MAKING SAME

ISIS-4017

JP

Pending

 

AMINOOXY-MODIFIED OLIGONUCLEOTIDES AND METHODS FOR MAKING SAME

ISIS-4309

US

Granted

6194598

AMINOOXY-MODIFIED OLIGONUCLEOTIDES SYNTHETIC INTERMDIATES

GLIS-0054

US

Granted

5214136

ANTHRAQUINONE-DERIVATIVES OLIGONUCLEOTIDES

HYBN-116.0USC1

US

Granted

5929226

ANTISENSE OLIGONUCLEOTIDE ALKYLPHOSPHONOTHIOATES AND ARYLPOSPOHONOTHIOATES

ISIS-0718

US

Granted

5386023

BACKBONE MODIFIED OLIGNUCLEOTIDE ANALOGS AND PREPARATION THEREOF THROUGH
REDUCTIVE COUPLING

 

--------------------------------------------------------------------------------

 

ISIS-0031

US

Granted

5378825

BACKBONE MODIFIED OLIGONUCLEOTIDE ANALOGS

NVIS-0026

US

Granted

5602240

BACKBONE MODIFIED OLIGONUCLEOTIDE ANALOGS

ISIS-3293

US

Granted

6025482

BACKBONE MODIFIED OLIGONUCLEOTIDE ANALOGS AND PERPARATION THEREOF THROUGH
REDUCTIVE COUPLING

ISIS-2420

US

Granted

5969118

BACKBONE MODIFIED OLIGONUCLEOTIDE ANALOGS AND PREPARATION THEREOF THROUGH
RADICAL COUPLING

ISIS-0716

US

Granted

5541307

BACKBONE MODIFIED OLIGONUCLEOTIDE ANALOGS AND SOLID PHASE SYNTHESIS THEREOF

ISIS-0543

AU

Granted

666121

BACKBONE MODIFIED OLIGONUCLEOTIDES

ISIS-0545

CA

Pending

 

BACKBONE MODIFIED OLIGONUCLEOTIDES

ISIS-0550

FR

Granted

586570

BACKBONE MODIFIED OLIGONUCLEOTIDES

ISIS-0551

DE

Granted

692 31 441.5

BACKBONE MODIFIED OLIGONUCLEOTIDES

ISIS-0552

GB

Granted

586570

BACKBONE MODIFIED OLIGONUCLEOTIDES

ISIS-0560

CH

Granted

586570

BACKBONE MODIFIED OLIGONUCLEOTIDES

ISIS-0564

JP

Granted

2711180

BACKBONE MODIFIED OLIGONUCLEOTIDES

ISIS-0565

KR

Granted

155574

BACKBONE MODIFIED OLIGONUCLEOTIDES

ISIS-4293

EP

Pending

 

BACKBONE MODIFIED OLIGONUCLEOTIDES

ISIS-0567

US

Granted

5610289

BACKBONE MODIFIED OLIGONUCLEOTIDES ANALOGS

ISIS-0546

EP

Granted

586570

BACKBONE MODIFIED OLIGONUCLEOTIDES ANALOGUES

ISIS-2404

US

Granted

5965721

BACKBONE MODIFIED OLIGONUCLEOTIDES ANALOGUES

ISIS-5061

US

Pending

 

BACKBONE-MODIFIED OLIGONUCLEOTIDE ANALOGS

ISIS-1713

US

Granted

5618704

BACKBONE-MODIFIED OLIGONUCLEOTIDE ANALOGS AND PREPARATION TH EREOF THROUGH
RADICAL COUPLING

GLIS-0097

EP

Granted

643720

BINDING COMPETENT OLIGOMERS CONTAINING 2’, 5’ LINKAGES

GLIS-0122

GB

Granted

643720

BINDING COMPETENT OLIGOMERS CONTAINING 2’, 5’ LINKAGES

GLIS-0123

DE

Granted

693 22 640

BINDING COMPETENT OLIGOMERS CONTAINING 2’, 5’ LINKAGES

GLIS-0124

FR

Granted

643720

BINDING COMPETENT OLIGOMERS CONTAINING 2’, 5’ LINKAGES

GLIS-0125

CH

Granted

643720

BINDING COMPETENT OLIGOMERS CONTAINING 2’, 5’ LINKAGES

GLIS-0099

US

Granted

5434257

BINDING COMPETENT OLIGOMERS CONTAINING UNSATURATED 3’,5’ AND 2’,5’ LINKAGES

HYBN-132.0AT

AT

Granted

763050

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0AU

AU

Granted

2604995

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0BE

BE

Granted

763050

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0CA

CA

Pending

 

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0CH

CH

Granted

763050

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0CN

CN

Pending

 

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0DE

DE

Granted

69514351

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0EP

EP

Granted

763050

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0FR

FR

Granted

763050

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0GB

GB

Granted

763050

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0IE

IE

Granted

763050

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0JP

JP

Pending

 

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0NL

NL

Granted

763050

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0SE

SE

Granted

763050

BRANCHED OLIGONUCLEOTIDE AS PATHOGEN-INHIBITORY AGENTS

 

--------------------------------------------------------------------------------

 

HYBN-132.0US

US

Pending

 

BRANCHED OLIGONUCLEOTIDES AS PATHOGEN-INHIBITORY AGENTS

HYBN-132.0USC1

US

Granted

6489464

BRANCHED OLIGONUCLEOTIDES AS PATHOGEN-INHIBITORY AGENTS

HYBN-128.0US

US

Pending

 

BUILDING BLOCKS WITH CARBAMATE INTERNUCLEOSIDE LINKAGES AND NOVEL
OLIGONUCLEOTIDES DERIVED THEREFROM

ISIS-2350

US

Granted

6111085

CARBAMATE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-4070

US

Granted

6166188

CARBAMATE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-4507

US

Granted

6322987

CARBAMATE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-4802

US

Pending

 

CARBAMATE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-5239

US

Pending

 

CARBAMATE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-2951

US

Granted

6277967

CARBOHYDRATE OR 2’-MODIFIED OLIGONUCLEOTIDES HAVING ALTERNATING INTERNUCLEOSIDE
LINKAGES

ISIS-3863

US

Granted

6326358

CARBOHYDRATE OR 2’-MODIFIED OLIGONUCLEOTIDES HAVING ALTERNATING INTERNUCLEOSIDE
LINKAGES

ISIS-3868

EP

Pending

 

CARBOHYDRATE OR 2’-MODIFIED OLIGONUCLEOTIDES HAVING ALTERNATING INTERNUCLEOSIDE
LINKAGES

ISIS-4847

US

Pending

 

CARBOHYDRATE OR 2’-MODIFIED OLIGONUCLEOTIDES HAVING ALTERNATING INTERNUCLEOSIDE
LINKAGES

ISIS-5300

US

Pending

 

CHIMERIC OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

ISIS-0060

AU

Granted

651569

COMPOSITIONS AND METHODS FOR DETECTING AND MODULATING RNA ACTIVITY AND GENE
EXPRESSION

ISIS-0062

CA

Pending

 

COMPOSITIONS AND METHODS FOR DETECTING AND MODULATING RNA ACTIVITY AND GENE
EXPRESSION

ISIS-0063

EP

Pending

 

COMPOSITIONS AND METHODS FOR DETECTING AND MODULATING RNA ACTIVITY AND GENE
EXPRESSION

ISIS-0079

JP

Granted

2580091

COMPOSITIONS AND METHODS FOR DETECTING AND MODULATING RNA ACTIVITY AND GENE
EXPRESSION

ISIS-0080

KR

Pending

 

COMPOSITIONS AND METHODS FOR DETECTING AND MODULATING RNA ACTIVITY AND GENE
EXPRESSION

ISIS-5093

EP

Pending

 

COMPOSITIONS AND METHODS FOR DETECTING AND MODULATION RNA ACTIVITY AND GENE
EXPRESSION

ISIS-0979

US

Granted

6358931

COMPOSITIONS AND METHODS FOR MODULATING RNA

ISIS-4919

US

Granted

6610663

COMPOSITIONS AND METHODS FOR MODULATING RNA

ISIS-0707

US

Granted

5514786

COMPOSITIONS FOR INHIBITING RNA ACTIVITY

ISIS-1787

US

Granted

6262241

COMPOUND FOR DETECTING AND MODULATING RNA ACTIVITY AND GENE EXPRESSION

ISIS-5055

US

Pending

 

COMPOUNDS AND OLIGOMERIC COMPOUNDS COMPRISING NOVEL NUCLEOBASES

ISIS-0282

US

Granted

5359051

COMPOUNDS USEFUL IN THE SYNTHESIS OF NUCLEIC ACIDS CAPABLE OF CLEAVING RNA

ISIS-4319

EP

Pending

 

COMPOUNDS, PROCESSES AND INTERMEDIATES FOR SYNTHESIS OF MIXED BACKBONE
OLIGOMERIC COMPOUNDS

ISIS-4338

JP

Pending

 

COMPOUNDS, PROCESSES AND INTERMEDIATES FOR SYNTHESIS OF MIXED BACKBONE
OLIGOMERIC COMPOUNDS

 

--------------------------------------------------------------------------------

 

ISIS-3299

US

Granted

6207819

COMPOUNDS, PROCESSES AND INTERMEDIATES FOR SYNTHESIS OF MIXED BACKBONE
OLIGOMERIC COMPOUNDS

ISIS-4528

US

Granted

6462184

COMPOUNDS, PROCESSES AND INTERMEDIATES FOR SYNTHESIS OF MIXED BACKBONE
OLIGOMERIC COMPOUNDS

ISIS-5039

US

Pending

 

COMPOUNDS, PROCESSES AND INTERMEDIATES FOR SYNTHESIS OF MIXED BACKBONE
OLIGOMERIC COMPOUNDS

ISIS-1715

US

Granted

5608046

CONJUGATED 4’-DESMETHYL NUCLEOSIDE ANALOG COMPOUNDS

HYBN-175.0US

US

Granted

6372427

COOPERATIVE OLIGONUCLEOTIDES

HYBN-175.1US

US

Pending

 

COOPERATIVE OLIGONUCLEOTIDES

HYBN-175.1WO

WO

Pending

 

COOPERATIVE OLIGONUCLEOTIDES

ISIS-0984

CA

Pending

 

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-0985

EP

Granted

635023

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-0989

FR

Granted

635023

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-0990

GB

Granted

635023

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-0991

DE

Granted

693 31 543.1

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-0993

IE

Granted

635023

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-1000

CH

Granted

635023

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-1003

JP

Pending

 

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-1006

US

Granted

5719271

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-1007

IL

Granted

104965

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-1304

US

Granted

5543507

COVALENTLY CROSS-LINKED OLIGONUCLEOTIDES

ISIS-0462

US

Granted

5359044

CYCLOBUTYL OLIGONUCLEOTIDE SURROGATES

ISIS-1450

US

Granted

6001841

CYCLOBUTYL OLIGONUCLEOTIDE SURROGATES

ISIS-0628

CA

Granted

2122030

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-0646

JP

Granted

2823959

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-0629

EP

Granted

724447

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-0633

FR

Granted

724447

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-0634

DE

Granted

692 33 046.1

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-0635

GB

Granted

724447

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-0643

CH

Granted

724447

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-0649

US

Granted

6153737

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-4470

US

Granted

6395492

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-5024

US

Pending

 

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

 

--------------------------------------------------------------------------------

 

ISIS-5060

US

Pending

 

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-5109

US

Pending

 

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-5166

EP

Pending

 

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-5425

US

Pending

 

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

ISIS-5426

US

Pending

 

DERIVATIZED OLIGONUCLEOTIDES HAVING IMPROVED UPTAKE AND OTHER PROPERTIES

GLIS-0073

US

Granted

5484908

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION DIRECTED BY OLIGONUCLEOTIDES
CONTAINING MODIFIED PYRIMIDINES

GLIS-0077

US

Granted

6235887

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION DIRECTED BY OLIGONUCLEOTIDES
CONTAINING MODIFIED PYRIMIDINES

GLIS-0080

CA

Pending

 

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0121

DE

Granted

692 32 816.5

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0072

US

Granted

5594121

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PURINES

GLIS-0076

US

Granted

5645985

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0082

JP

Pending

 

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0084

US

Granted

5830653

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0085-CPA2

US

Granted

6380368

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0079

AU

Granted

679508

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0081

EP

Granted

637965

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0083

Taiwan

Granted

116354

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0120

FR

Granted

637965

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0143

US

Pending

 

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0145

EP

Pending

 

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0152

GB

Granted

637965

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

GLIS-0153

CH

Granted

637965

ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING
MODIFIED PYRIMIDINES

 

--------------------------------------------------------------------------------

 

GLIS-0016

CA

Pending

 

EXONUCLEASE-RESISTANT OLIGONUCLEOTIDES AND METHODS FOR PREPARING THE SAME

GLIS-0029

US

Granted

5264564

FORMACETAL / KETAL LINKED OLIGONUCLEOTIDE ANALOGS

GLIS-0031

AU

Granted

653504

FORMACETAL / KETAL LINKED OLIGONUCLEOTIDE ANALOGS

GLIS-0033

EP

Granted

498843

FORMACETAL / KETAL LINKED OLIGONUCLEOTIDE ANALOGS

GLIS-0034

DE

Granted

69027443

FORMACETAL / KETAL LINKED OLIGONUCLEOTIDE ANALOGS

GLIS-0035

FR

Granted

498843

FORMACETAL / KETAL LINKED OLIGONUCLEOTIDE ANALOGS

GLIS-0036

GB

Granted

498843

FORMACETAL / KETAL LINKED OLIGONUCLEOTIDE ANALOGS

GLIS-0037

US

Granted

5264562

FORMACETAL / KETAL LINKED OLIGONUCLEOTIDE ANALOGS

ISIS-3811

US

Granted

6593466

FUNCTIONALIZED OLIGOMERS

ISIS-0816

AU

Granted

669353

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-0841

US

Granted

5623065

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-2002

US

Granted

5955589

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-2454

US

Granted

5856455

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-4387

EP

Pending

 

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-4852

US

Pending

 

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-5213

US

Pending

 

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-0818

CA

Granted

2126691

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-0819

EP

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0821

BE

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0822

DK

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0823

FR

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0824

GB

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0825

DE

Granted

69232032

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0827

IE

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0831

NL

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0834

SE

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0835

CH

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0838

JP

Granted

3131222

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-4383

JP

Pending

 

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0839

KR

Pending

 

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-2825

KR

Granted

188858

GAPPED 2’-MODIFIED MACROMOLECULES

ISIS-4288

US

Pending

 

GAPPED OLIGOMERS HAVING SITE SPECIFIC PHOSPHOROTHIOATE INTERNUCLEOSIDE LINKAGES

ISIS-2003

US

Pending

 

GAPPED OLIGONUCLEOTIDES

ISIS-5090

US

Pending

 

GUANIDINIUM FUNCTIONALIZED OLIGOMERS AND METHODS

ISIS-4406

US

Granted

6534639

GUANIDINIUM FUNCTIONALIZED OLIGOMERS AND METHODS OF SYNTHESIS

ISIS-1058

CA

Pending

 

HETEROATOMIC OLIGONUCLEOSIDE LINKAGES

ISIS-1059

EP

Pending

 

HETEROATOMIC OLIGONUCLEOSIDE LINKAGES

ISIS-1078

JP

Granted

2879973

HETEROATOMIC OLIGONUCLEOSIDE LINKAGES

ISIS-1245

US

Granted

6087482

HETEROATOMIC OLIGONUCLEOSIDE LINKAGES

ISIS-1960

US

Granted

5623070

HETEROATOMIC OLIGONUCLEOSIDE LINKAGES

ISIS-2421

US

Granted

5777092

HETEROATOMIC OLIGONUCLEOSIDE LINKAGES

 

--------------------------------------------------------------------------------

 

ISIS-1959

US

Granted

5677437

HETEROATOMIC OLIGONUCLEOTIDE LINKAGES

HYBN-118.0AT

AT

Granted

198073

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0AU

AU

Granted

674158

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0BE

BE

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0CA

CA

Pending

 

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0CH

CH

Granted

9500143

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0CZ

CZ

Pending

 

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0DE

DE

Granted

69329755

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0DK

DK

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0EP

EP

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0ES

ES

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0FR

FR

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0GB

GB

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0IE

IE

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0IT

IT

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0NL

NL

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0SE

SE

Granted

650493

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0US

US

Granted

5652355

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.0USD1

US

Granted

6143881

HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES

HYBN-118.1US

US

Granted

6346614

HYBRID OLIGONUCLEOTIDES PHOSPHOROTHIOATES

HYBN-118.1USC1

US

Pending

 

HYBRID OLIGONUCLEOTIDES PHOSPHOROTHIOATES

HYBN-224.1US

US

Pending

 

IMPROVED REAGENTS AND PROCESS FOR SYNTHESIS OF OLIGONUCLEOTIDES CONTAINING
PHOSPHORODITHIOATE INTERNUCLEOSIDE LINKAGES

HYBN-123.0USC2

US

Granted

5739308

INTEGRATED OLIGONUCLEOTIDES

ISIS-4723

US

Pending

 

LABELED OLIGONUCLEOTIDES, METHODS FOR MAKING SAME, AND COMPOUNDS USEFUL THEREFOR

ISIS-5272

AU

Pending

 

LABELED OLIGONUCLEOTIDES, METHODS FOR MAKING SAME, AND COMPOUNDS USEFUL THEREFOR

ISIS-5273

CA

Pending

 

LABELED OLIGONUCLEOTIDES, METHODS FOR MAKING SAME, AND COMPOUNDS USEFUL THEREFOR

ISIS-5274

EP

Pending

 

LABELED OLIGONUCLEOTIDES, METHODS FOR MAKING SAME, AND COMPOUNDS USEFUL THEREFOR

ISIS-1164

US

 

5554746

LACTAM NUCLEIC ACIDS

ISIS-4390

US

Pending

 

LIGAND-CONJUGATED OLIGOMERIC COMPOUNDS

GLIS-0061

EP

Pending

 

LIPOPHILIC OLIGONUCLEOTIDE ANALOGS

HYBN-191.0BE

BE

Granted

850300

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0CA

CA

Pending

 

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0DE

DE

Granted

96904686

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0DK

DK

Granted

850300

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

 

--------------------------------------------------------------------------------

 

HYBN-191.0EP

EP

Granted

850300

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0ES

ES

Granted

850300

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0FI

FI

Granted

850300

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0GR

GR

Granted

850300

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0JP

JP

Pending

 

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0LU

LX

Granted

850300

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0PT

PT

Granted

850300

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0SE

SE

Granted

850300

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-191.0US

US

Granted

5968909

METHOD OF MODULATING GENE EXPRESSION WITH REDUCED IMMUNOSTIMULATORY RESPONSE

HYBN-146.0US

US

Granted

5847104

METHOD OF TRITIUM LABELING OLIGONUCLEOTIDE

HYBN-146.0USD1

US

Pending

 

METHOD OF TRITIUM LABELING OLIGONUCLEOTIDE

HYBN-146.0USD2

US

Granted

5668262

METHOD OF TRITIUM LABELING OLIGONUCLEOTIDE

HYBN-152.0CA

CA

Pending

 

METHODS AND COMPOUNDS FOR THE STEREOSELECTIVE ENRICHMENT OF OLIGONUCLEOTIDE
DIASTEREOMERS AND OLIGONUCLEOTIDES THEREBY PRODUCED

HYBN-152.0EP

EP

Pending

 

METHODS AND COMPOUNDS FOR THE STEREOSELECTIVE ENRICHMENT OF OLIGONUCLEOTIDE
DIASTEREOMERS AND OLIGONUCLEOTIDES THEREBY PRODUCED

HYBN-152.0JP

JP

Pending

 

METHODS AND COMPOUNDS FOR THE STEREOSELECTIVE ENRICHMENT OF OLIGONUCLEOTIDE
DIASTEREOMERS AND OLIGONUCLEOTIDES THEREBY PRODUCED

HYBN-152.0US

US

Granted

5750674

METHODS AND COMPOUNDS FOR THE STEREOSELECTIVE ENRICHMENT OF OLIGONUCLEOTIDE
DIASTEREOMERS AND OLIGONUCLEOTIDES THEREBY PRODUCED

ISIS-3073

US

Granted

6335437

METHODS FOR THE PREPARATION OF CONJUGATED OLIGOMERS

ISIS-4101

WO

Pending

 

METHODS FOR THE PREPARATION OF CONJUGATED OLIGOMERS

ISIS-4105

EP

Pending

 

METHODS FOR THE PREPARATION OF CONJUGATED OLIGOMERS

HYBN-227.0AT

AT

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0BE

BE

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0CH

CH

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0DE

DE

Granted

697 20 481.2

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

 

--------------------------------------------------------------------------------

 

HYBN-227.0DK

DK

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0EP

EP

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0ES

ES

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0FI

FI

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0FR

FR

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0GB

GB

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0GR

GR

Granted

3043738

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0IE

IE

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0IT

IT

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0LU

LX

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0MC

MC

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0NL

NL

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0PT

PT

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0SE

SE

Granted

928335

METHODS FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

ISIS-4853

US

Pending

 

METHODS OF MODULATING PHARMACOKINETICS OF OLIGONUCLEOTIDES

ISIS-5400

AU

Pending

 

METHODS OF MODULATING PHARMACOKINETICS OF OLIGONUCLEOTIDES

ISIS-5401

CA

Pending

 

METHODS OF MODULATING PHARMACOKINETICS OF OLIGONUCLEOTIDES

ISIS-5402

EP

Pending

 

METHODS OF MODULATING PHARMACOKINETICS OF OLIGONUCLEOTIDES

HYBN-226.0US

US

Granted

5886165

MIXED BACKBONE ANTISENSE OLIGONUCLEOTIDES CONTAINING 2’-5’-RIBONUCLEOTIDE- AND
3’-5’-DEOXYRIBONUCLEOTIDES SEGMENTS

HYBN-259.0US

US

Pending

 

MIXED-BACKBONE OLIGONUCLEOTIDES CONTAINING POPS BLOCKS TO OBTAIN REDUCED
PHOSPHOROTHIOATE CONTENT

HYBN-259.0USC1

US

Pending

 

MIXED-BACKBONE OLIGONUCLEOTIDES CONTAINING POPS BLOCKS TO OBTAIN REDUCED
PHOSPHOROTHIOATE CONTENT

GLIS-0095

US

Granted

5817781

MODIFIED INTERNUCLEOSIDE LINKAGES (H)

GLIS-0098

US

Granted

6410702

MODIFIED INTERNUCLEOSIDE LINKAGES (II)

 

--------------------------------------------------------------------------------

 

GLIS-0150

US

Granted

6683166

MODIFIED INTERNUCLEOSIDE LINKAGES (II)

GLIS-0056

US

Granted

5596086

MODIFIED INTERNUCLEOSIDE LINKAGES HAVING ONE NITROGEN AND TWO CARBON ATOMS

ISIS-1724

US

Granted

5808023

MODIFIED OLIGNUCLEOTIDES INCORPORATING THIOL-DERIVATIZED NUC LEOSIDES

ISIS-4289

US

Granted

6653458

MODIFIED OLIGONUCLEOTIDES

ISIS-5110

US

Pending

 

MODIFIED OLIGONUCLEOTIDES FOR USE IN RNA INTERFERENCE

HYBN-227.2US

US

Granted

6476000

MODULATION OF OLIGONUCLEOTIDE CPG-MEDIATED IMMUNE STIMULATION BY POSITIONAL
MODIFICATION OF NUCLEOSIDES

ISIS-5054

US

Pending

 

MONOMERIC AND OLIGOMERIC COMPOUNDS COMPRISING BICYCLIC SUGAR MOIETIES

ISIS-1832

CA

Pending

 

MONOMERIC DIOLS AND PHOSPHATE LINKED OLIGOMERS FORMED THEREF ROM

ISIS-1850

JP

Granted

3072127

MONOMERIC DIOLS AND PHOSPHATE LINKED OLIGOMERS FORMED THEREF ROM

ISIS-1833

EP

Granted

739351

MONOMERIC DIOLS AND PHOSPHATE LINKED OLIGOMERS FORMED THEREFROM

ISIS-1837

FR

Granted

739351

MONOMERIC DIOLS AND PHOSPHATE LINKED OLIGOMERS FORMED THEREFROM

ISIS-1838

GB

Granted

739351

MONOMERIC DIOLS AND PHOSPHATE LINKED OLIGOMERS FORMED THEREFROM

ISIS-1839

DE

Granted

695 26 331.5

MONOMERIC DIOLS AND PHOSPHATE LINKED OLIGOMERS FORMED THEREFROM

ISIS-1841

IE

Granted

739351

MONOMERIC DIOLS AND PHOSPHATE LINKED OLIGOMERS FORMED THEREFROM

ISIS-1849

CH

Granted

739351

MONOMERIC DIOLS AND PHOSPHATE LINKED OLIGOMERS FORMED THEREFROM

ISIS-5046

US

Pending

 

MONOMERIC DIOLS AND PHOSPHATE LINKED OLIGOMERS FORMED THEREFROM AND PROCESSES
FOR PREPARING

ISIS-0284

US

Granted

5212295

MONOMERS FOR PREPARATION OF OLIGONUCLEOTIDES WITH CHIRALPHOSPHORUS LINKAGES

ISIS-1051

US

Granted

5459255

N2 SUBSTITUTED PURINES

ISIS-1767

EP

Granted

731807

N2 SUBSTITUTED PURINES

ISIS-1784

JP

Pending

 

N-2 SUBSTITUTED PURINES

ISIS-3151

US

Granted

6166199

N-2 SUBSTITUTED PURINES

ISIS-2407

US

Granted

5808027

N-2 SUBSTITUTED PURINES IN OLIGONUCLEOTIDES (as amended)

GLIS-0053

US

Granted

5414077

NON-NUCLEOSIDE LINKERS FOR CONVENIENT ATTACHMENT OF LABELS TO OLIGONUCLEOTIDES
USING STANDARD SYNTHETIC METHODS

ISIS-1085

CA

Granted

2140428

NOVEL 2’-O-ALKYL NUCLEOSIDES & PHOSPHORAMIDITES PROCESSES FOR THE PREPARATION &
USES THEREOF

ISIS-1086

EP

Granted

651759

NOVEL 2’-O-ALKYL NUCLEOSIDES & PHOSPHORAMIDITES PROCESSES FOR THE PREPARATION &
USES THEREOF

ISIS-1090

FR

Granted

651759

NOVEL 2’-O-ALKYL NUCLEOSIDES & PHOSPHORAMIDITES PROCESSES FOR THE PREPARATION &
USES THEREOF

 

--------------------------------------------------------------------------------

 

ISIS-1091

GB

Granted

651759

NOVEL 2’-O-ALKYL NUCLEOSIDES & PHOSPHORAMIDITES PROCESSES FOR THE PREPARATION &
USES THEREOF

ISIS-1092

DE

Granted

693 33 344.8

NOVEL 2’-O-ALKYL NUCLEOSIDES & PHOSPHORAMIDITES PROCESSES FOR THE PREPARATION &
USES THEREOF

ISIS-1102

CH

Granted

651759

NOVEL 2’-O-ALKYL NUCLEOSIDES & PHOSPHORAMIDITES PROCESSES FOR THE PREPARATION &
USES THEREOF

ISIS-4806

EP

Pending

 

NOVEL 2’-O-ALKYL NUCLEOSIDES & PHOSPHORAMIDITES PROCESSES FOR THE PREPARATION &
USES THEREOF

ISIS-1105

JP

Granted

3015464

NOVEL 2’-O-ALKYL NUCLEOSIDES & PHOSPHORAMIDITES PROCESSES FOR THE PREPARATION &
USES THEREOF

GLIS-0002

US

Granted

5194599

NOVEL HYDROGEN PHOSPHONODITHIOATE COMPOSITIONS

GLIS-0003

AU

Granted

622930

NOVEL HYDROGEN PHOSPHONODITHIOATE COMPOSITIONS

GLIS-0005

US

Granted

5565555

NOVEL HYDROGEN PHOSPHONODITHIOATE COMPOSITIONS

ISIS-2347

US

6000000

5866691

NOVEL LACTAM NUCLEIC ACIDS

ISIS-3297

US

Granted

6084082

NOVEL LACTAM NUCLEIC ACIDS

ISIS-0134

AU

Granted

655937

NOVEL NUCLEOSIDE ANALOGS

ISIS-0136

CA

Granted

2089377

NOVEL NUCLEOSIDE ANALOGS

ISIS-0137

EP

Granted

544792

NOVEL NUCLEOSIDE ANALOGS

ISIS-0141

FR

Granted

544792

NOVEL NUCLEOSIDE ANALOGS

ISIS-0142

DE

Granted

69128250

NOVEL NUCLEOSIDE ANALOGS

ISIS-0143

GB

Granted

544792

NOVEL NUCLEOSIDE ANALOGS

ISIS-5052

US

Pending

 

NOVEL PEPTIDE-CONJUGATED OLIGOMERIC COMPOUNDS

ISIS-5052WO

WO

Pending

 

NOVEL PEPTIDE-CONJUGATED OLIGOMERIC COMPOUNDS

ISIS-1917

CA

Granted

2184005

NOVEL PHOSPHORAMIDATE AND PHOSPHOROTHIOAMIDATE OLIGOMERIC CO MPOUNDS

ISIS-1918

EP

Granted

751948

NOVEL PHOSPHORAMIDATE AND PHOSPHOROTHIOAMIDATE OLIGOMERIC COMPOUNDS

ISIS-1923

GB

Granted

751948

NOVEL PHOSPHORAMIDATE AND PHOSPHOROTHIOAMIDATE OLIGOMERIC COMPOUNDS

ISIS-0024

US

Granted

5138045

NOVEL POLYAMINE CONJUGATED OLIGONUCLEOTIDES

ISIS-0290

EP

Granted

544757

NOVEL POLYAMINE CONJUGATED OLIGONUCLEOTIDES

ISIS-0510

US

Granted

5218105

NOVEL POLYAMINE CONJUGATED OLIGONUCLEOTIDES

ISIS-4804

US

Pending

 

NUCLEASE RESISTANT CHIMERIC OLIGONUCLEOTIDES

ISIS-4948

US

Pending

 

NUCLEASE RESISTANT CHIMERIC OLIGONUCLEOTIDES

ISIS-5377

AU

Pending

 

NUCLEASE RESISTANT CHIMERIC OLIGONUCLEOTIDES

ISIS-5378

CA

Pending

 

NUCLEASE RESISTANT CHIMERIC OLIGONUCLEOTIDES

ISIS-5379

EP

Pending

 

NUCLEASE RESISTANT CHIMERIC OLIGONUCLEOTIDES

ISIS-5399

JP

Docketed

 

NUCLEASE RESISTANT CHIMERIC OLIGONUCLEOTIDES

ISIS-0311

AU

Granted

641565

NUCLEASE RESISTANT PYRIMIDINE MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE
GENE EXPRESSION

ISIS-0314

EP

Granted

544824

NUCLEASE RESISTANT PYRIMIDINE MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE
GENE EXPRESSION

ISIS-0318

FR

Granted

544824

NUCLEASE RESISTANT PYRIMIDINE MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE
GENE EXPRESSION

 

--------------------------------------------------------------------------------

 

ISIS-0319

DE

Granted

691 26 530.5

NUCLEASE RESISTANT PYRIMIDINE MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE
GENE EXPRESSION

ISIS-0320

GB

Granted

544824

NUCLEASE RESISTANT PYRIMIDINE MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE
GENE EXPRESSION

ISIS-0327

CH

Granted

544824

NUCLEASE RESISTANT PYRIMIDINE MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE
GENE EXPRESSION

ISIS-0333

US

Granted

5614617

NUCLEASE RESISTANT PYRIMIDINE MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE
GENE EXPRESSION

ISIS-0330

JP

Granted

2089377

NUCLEASE RESISTANT PYRIMIDINE MODIFIED OLIGONUCLEOTIDES THAT DETECT AND MODULATE
GENE EXPRESSION

ISIS-0313

CA

Pending

 

NUCLEASE RESISTANT PYRIMIDINE MODIFIED OLIGONUCLEOTIDES THAT DETECT AND MODULATE
GENE EXPRESSION

GLIS-0094

US

Granted

5792608

NUCLEASE STABLE AND BINDING COMPETENT OLIGOMERS AND METHODS FOR THEIR USE

GLIS-0128

US

Pending

 

NUCLEOSIDE 5’-METHYLENE PHOSPHONATES

GLIS-0007

US

Pending

 

NUCLEOSIDE HYDROGEN PHOSPHONODITHIOATE DIESTERS AND ACTIVATED PHOSPHONODITHIOATE
ANALOGUES

ISIS-4803

US

Pending

 

NUCLEOSIDIC AND NON-NUCLEOSIDIC FOLATE CONJUGATES

ISIS-3453

US

Granted

6335434

NUCLEOSIDIC AND NON-NUCLEOSIDIC FOLATE CONJUGATES

ISIS-4732

US

Granted

6500945

NUCLEOTIDES HAVING CHIRAL PHOSPHORUS LINKAGES

ISIS-1872

US

Granted

6121433

OLIGOMERIC COMPOUNDS HAVING NITROGEN-CONTAINING LINKAGES

ISIS-5214

WO

Pending

 

OLIGOMERIC COMPOUNDS THAT INCLUDE CARBOCYCLIC NUCLEOSIDES AND THEIR USE IN GENE
MODULATION

ISIS-1720

US

Granted

5792844

OLIGONUCLEOSIDE LINKAGES CONTAINING ADJACENT NITROGEN ATOMS

ISIS-3141

US

Granted

6214551

OLIGONUCLEOSIDE LINKAGES CONTAINING ADJACENT NITROGEN ATOMS

ISIS-0713

US

Granted

5489677

OLIGONUCLEOSIDE LINKAGES CONTAINING ADJACENT OXYGEN AND NITR OGEN ATOMS

ISIS-1968

US

Pending

 

OLIGONUCLEOSIDE LINKAGES CONTAINING ADJACENT OXYGEN AND NITROGEN ATOMS

ISIS-2906

US

Granted

6420549

OLIGONUCLEOTIDE ANALOGS HAVING MODIFIED DIMERS

ISIS-5081

US

Pending

 

OLIGONUCLEOTIDE ANALOGS HAVING MODIFIED DIMERS

GLIS-0032

CA

Granted

2071483

OLIGONUCLEOTIDE ANALOGS WITH NOVEL LINKAGES

ISIS-1198

US

Granted

6235886

OLIGONUCLEOTIDE AND NUCLEOTIDE AMINE ANALOGS

ISIS-4508

US

Granted

6495671

OLIGONUCLEOTIDE AND NUCLEOTIDE AMINE ANALOGS, METHODS OF SYNTHESIS AND USE

ISIS-5025

US

Pending

 

OLIGONUCLEOTIDE AND NUCLEOTIDE AMINE ANALOGS, METHODS OF SYNTHESIS AND USE

GLIS-0049

US

Granted

5486603

OLIGONUCLEOTIDE HAVING ENHANCED BINDING AFFINITY

ISIS-1014

US

Granted

5783682

OLIGONUCLEOTIDE MIMICS HAVING NITROGEN-CONTAINING LINKAGES

ISIS-3138

US

Granted

6271357

OLIGONUCLEOTIDE MIMICS HAVING NITROGEN-CONTAINING LINKAGES

ISIS-4729

US

Granted

5023243

OLIGONUCLEOTIDE THERAPEUTIC AGENT AND METHOD OF MAKING

ISIS-2954

US

Granted

6528631

OLIGONUCLEOTIDE-FOLATE CONJUGATES

 

--------------------------------------------------------------------------------

 

GLIS-0063

US

Pending

 

OLIGONUCLEOTIDES AND THEIR ANALOGS CAPABLE OF PASSIVE CELL MEMBRANE PERMEATION

ISIS-1169

US

Pending

 

OLIGONUCLEOTIDES BEARING ALKYLAMINO AND ALKYLENEGLYCOL SUBSTITUENTS

ISIS-3758

US

Granted

6656730

OLIGONUCLEOTIDES CONJUGATED TO PROTEIN-BINDING DRUGS

ISIS-4921

AU

Granted

763518

OLIGONUCLEOTIDES CONJUGATED TO PROTEIN-BINDING DRUGS

ISIS-4922

CA

Pending

 

OLIGONUCLEOTIDES CONJUGATED TO PROTEIN-BINDING DRUGS

ISIS-4923

EP

Pending

 

OLIGONUCLEOTIDES CONJUGATED TO PROTEIN-BINDING DRUGS

ISIS-4942

JP

Pending

 

OLIGONUCLEOTIDES CONJUGATED TO PROTEIN-BINDING DRUGS

ISIS-5246

US

Pending

 

OLIGONUCLEOTIDES CONTAINING 2’-O-MODIFIED PURINES

ISIS-5426

 

 

 

OLIGONUCLEOTIDES CONTAINING 2’-O-MODIFIED PURINES

ISIS-2014

US

Granted

5587469

OLIGONUCLEOTIDES CONTAINING N-2 SUBSTITUTED PURINES

ISIS-3310

US

Granted

6369209

OLIGONUCLEOTIDES HAVING A-DNA FORM AND B-DNA FORM CONFORMATIONAL GEOMETRY

ISIS-4877

AU

Granted

762212

OLIGONUCLEOTIDES HAVING A-DNA FORM AND B-DNA FORM CONFORMATIONAL GEOMETRY

ISIS-4878

CA

Pending

 

OLIGONUCLEOTIDES HAVING A-DNA FORM AND B-DNA FORM CONFORMATIONAL GEOMETRY

ISIS-4879

EP

Pending

 

OLIGONUCLEOTIDES HAVING A-DNA FORM AND B-DNA FORM CONFORMATIONAL GEOMETRY

ISIS-4898

JP

Pending

 

OLIGONUCLEOTIDES HAVING A-DNA FORM AND B-DNA FORM CONFORMATIONAL GEOMETRY

ISIS-4949

US

Pending

 

OLIGONUCLEOTIDES HAVING A-DNA FORM AND B-DNA FORM CONFORMATIONAL GEOMETRY

ISIS-0727

CA

Granted

2121144

OLIGONUCLEOTIDES HAVING CHIRAL PHOSPHORUS LINKAGES

ISIS-2260

US

Granted

5852188

OLIGONUCLEOTIDES HAVING CHIRAL PHOSPHORUS LINKAGES

ISIS-3306

US

Granted

6239265

OLIGONUCLEOTIDES HAVING CHIRAL PHOSPHORUS LINKAGES

ISIS-5033

US

Pending

 

OLIGONUCLEOTIDES HAVING CHIRAL PHOSPHORUS LINKAGES

HYBN-227.0CA

CA

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0JP

JP

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.0US

US

Granted

5856462

OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

HYBN-227.1US

US

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

ISIS-5067

US

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS

ISIS-5067US

US

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS

ISIS-5067WO

WO

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS

ISIS-5068

US

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS

ISIS-5068US

US

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS

ISIS-5068WO

WO

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS

ISIS-2012

US

Granted

5587361

OLIGONUCLEOTIDES HAVING PHOSPHOROTHIOATE LINKAGES OF HIGH CH IRAL PURITY

ISIS-2298A

KR

Granted

257972

OLIGONUCLEOTIDES HAVING PHOSPHOROTHIOATE LINKAGES OF HIGH CH IRAL PURITY

ISIS-2299

AU

Granted

698739

OLIGONUCLEOTIDES HAVING PHOSPHOROTHIOATE LINKAGES OF HIGH CH IRAL PURITY

 

--------------------------------------------------------------------------------

 

ISIS-2301

EP

Pending

 

OLIGONUCLEOTIDES HAVING PHOSPHOROTHIOATE LINKAGES OF HIGH CH IRAL PURITY

ISIS-2319

JP

Pending

 

OLIGONUCLEOTIDES HAVING PHOSPHOROTHIOATE LINKAGES OF HIGH CH IRAL PURITY

ISIS-4499

JP

Pending

 

OLIGONUCLEOTIDES HAVING PHOSPHOROTHIOATE LINKAGES OF HIGH CH IRAL PURITY

ISIS-4500

JP

Pending

 

OLIGONUCLEOTIDES HAVING PHOSPHOROTHIOATE LINKAGES OF HIGH CH IRAL PURITY

ISIS-2300

CA

Pending

 

OLIGONUCLEOTIDES HAVING PHOSPHOROTHIOATE LINKAGES OF HIGH CHIRAL PURITY

ISIS-3890

US

Granted

6440943

OLIGONUCLEOTIDES HAVING SITE SPECIFIC CHIRAL PHOSPHOROTHIOATE INTERNUCLEOSIDE
LINKAGES

ISIS-3895

EP

Pending

 

OLIGONUCLEOTIDES HAVING SITE SPECIFIC CHIRAL PHOSPHOROTHIOATE INTERNUCLEOSIDE
LINKAGES

ISIS-3914

JP

Pending

 

OLIGONUCLEOTIDES HAVING SITE SPECIFIC CHIRAL PHOSPHOROTHIOATE INTERNUCLEOSIDE
LINKAGES

ISIS-0746

JP

Granted

2693643

OLIGONUCLEOTIDES HAVING SUBSTANTIALLY CHIRALLY PURE PHOPHORO THIOATE LINKAGES

ISIS-0728

EP

Granted

655088

OLIGONUCLEOTIDES HAVING SUBSTANTIALLY CHIRALLY PURE PHOSPHOROTHIOATE LINKAGES

ISIS-0732

FR

Granted

655088

OLIGONUCLEOTIDES HAVING SUBSTANTIALLY CHIRALLY PURE PHOSPHOROTHIOATE LINKAGES

ISIS-0733

GB

Granted

655088

OLIGONUCLEOTIDES HAVING SUBSTANTIALLY CHIRALLY PURE PHOSPHOROTHIOATE LINKAGES

ISIS-0734

DE

Granted

692 32 699.5

OLIGONUCLEOTIDES HAVING SUBSTANTIALLY CHIRALLY PURE PHOSPHOROTHIOATE LINKAGES

ISIS-0743

CH

Granted

655088

OLIGONUCLEOTIDES HAVING SUBSTANTIALLY CHIRALLY PURE PHOSPHOROTHIOATE LINKAGES

GLIS-0142

US

Granted

6495672

OLIGONUCLEOTIDES INCLUDING 2-AMINOPYRIDINE AND 2-PYRIDONE C-NUCLEOSIDES UNITS

ISIS-3889

US

Pending

 

OLIGONUCLEOTIDES INCORPORATING BOTH 2-AMINOADENINE AND 5-SUBSTITUTED PYRIMIDINES

ISIS-4977

EP

Pending

 

OLIGONUCLEOTIDES INCORPORATING BOTH 2-AMINOADENINE AND 5-SUBSTITUTED PYRIMIDINES

NVIS-0005

EP

Granted

586520

OLIGONUCLEOTIDES MODIFIED WITH AMIDE BACKBONES

NVIS-0009

FR

Granted

586520

OLIGONUCLEOTIDES MODIFIED WITH AMIDE BACKBONES

NVIS-0010

DE

Granted

692 30 935.7

OLIGONUCLEOTIDES MODIFIED WITH AMIDE BACKBONES

NVIS-0011

GB

Granted

586520

OLIGONUCLEOTIDES MODIFIED WITH AMIDE BACKBONES

NVIS-0019

CH

Granted

586520

OLIGONUCLEOTIDES MODIFIED WITH AMIDE BACKBONES

NVIS-0021

HU

Granted

221806

OLIGONUCLEOTIDES MODIFIED WITH AMIDE BACKBONES

NVIS-0022

IE

Pending

 

OLIGONUCLEOTIDES MODIFIED WITH AMIDE BACKBONES

ISIS-1669

US

Granted

5506212

OLIGONUCLEOTIDES WITH SUBSTANTIALLY CHIRALLY PURE PHOSPHOROT HIOATE LINKAGES

 

--------------------------------------------------------------------------------

 

ISIS-0868

US

Granted

6448373

PHOSPHATE LINKED OLIGOMERS FORMED OF MONOMERIC DIOLS AND PROCESSES FOR PREPARING
SAME

ISIS-1010

US

Granted

5637684

PHOSPHORAMIDATE AND PHOSPHOROTHIOAMIDATE OLIGOMERIC COMPOUNDS

ISIS-1935

JP

Granted

2972344

PHOSPHORAMIDATE AND PHOSPHOROTHIOAMIDATE OLIGOMERIC COMPOUNDS

ISIS-4790

US

Pending

 

PHOSPHOROTHIOATE MONOESTER MODIFIED OLIGOMERS

ISIS-5192

WO

Pending

 

PHOSPHOROTHIOATE MONOESTER MODIFIED OLIGOMERS

ISIS-2953

US

Granted

6242589

PHOSPHOROTHIOATE OLIGONUCLEOTIDES HAVING MODIFIED INTERNUCLEOSIDE LINKAGES

ISIS-4718

US

Pending

 

PHOSPHOROTHIOATE OLIGONUCLEOTIDES HAVING MODIFIED INTERNUCLEOSIDE LINKAGES

ISIS-5059

US

Pending

 

POLYALKYLENEAMINE-CONTAINING OLIGOMERS

GLIS-0019

US

Granted

5399676

PREPARATION OF OLIGONUCLEOTIDES WITH INVERTED POLARITY AND USES THEREOF

GLIS-0020

US

Granted

5527899

PREPARATION OF OLIGONUCLEOTIDES WITH INVERTED POLARITY AND USES THEREOF

GLIS-0022

US

Granted

5721218

PREPARATION OF OLIGONUCLEOTIDES WITH INVERTED POLARITY AND USES THEREOF

GLIS-0024

AU

Granted

641219

PREPARATION OF OLIGONUCLEOTIDES WITH INVERTED POLARITY AND USES THEREOF

GLIS-0026

EP

Pending

 

PREPARATION OF OLIGONUCLEOTIDES WITH INVERTED POLARITY AND USES THEREOF

ISIS-5139

US

Pending

 

PREPARATION OF PHOSPHOROTHIOATE OLIGOMERS

HYBN-199.0US

US

Granted

6140482

PRIMARY PHOSPHORAMIDATEINTERNUCLEOSIDE LINKAGES AND OLIGONUCLEOTIDES CONTAINING
SAME

GLIS-0105

US

Granted

6005096

PYRIMIDINE DERIVATIVES (as amended)

GLIS-0144

US

Pending

 

PYRIMIDINE DERIVATIVES AND OLIGONUCLEOTIDES CONTAINING SAME

GLIS-0114

US

Granted

6028183

PYRIMIDINE DERIVATIVES AND OLIGONUCLEOTIDES CONTAINING SAME

GLIS-0100

US

Granted

5502177

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0102

EP

Granted

719272

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0103

JP

Pending

 

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0104

US

Granted

5763588

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0116

US

Granted

6007992

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0127

US

Granted

6414127

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0137

US

Granted

6617437

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0139

CA

Pending

 

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0140

JP

Pending

 

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0141

EP

Pending

 

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0147

US

Pending

 

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0157

FR

Granted

719272

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0158

DE

Granted

719272

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0159

GB

Granted

719272

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0160

CH

Granted

719272

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

 

--------------------------------------------------------------------------------

 

ISIS-1325

US

Granted

6060592

PYRIMIDINE NUCLEOSIDE COMPOUNDS AND OLIGONUCLEOSIDE COMPOUNDS CONTAINING SAME

ISIS-1874

CA

Granted

2180978

PYRROLIDINE-CONTAINING MONOMERS AND OLIGOMERS

ISIS-3147

US

Granted

6271358

RNA-TARGETED 2’MODIFIED OLIGONUCLEOTIDES THAT ARE CONFORMATIONALLY PREORGANIZED

ISIS-3972

EP

Pending

 

RNA-TARGETED 2’MODIFIED OLIGONUCLEOTIDES THAT ARE CONFORMATIONALLY PREORGANIZED

ISIS-0460

US

Granted

5681941

SUBSTITUTED PURINES AND OLIGONUCLEOTIDE CROSS-LINKING

ISIS-1897

EP

Pending

 

SUBSTITUTED PURINES AND OLIGONUCLEOTIDE CROSS-LINKING

ISIS-2536

US

Granted

5811534

SUBSTITUTED PURINES AND OLIGONUCLEOTIDE CROSS-LINKING

ISIS-3152

US

Granted

6232463

SUBSTITUTED PURINES AND OLIGONUCLEOTIDE CROSS-LINKING

ISIS-4943

US

Pending

 

SUGAR MODIFIED OLIGONUCLEOTIDES

ISIS-3154

US

Granted

6399754

SUGAR MODIFIED OLIGONUCLEOTIDES (as amended)

ISIS-0385

AU

Granted

661662

SUGAR MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE GENE EXPRESSION

ISIS-0404

JP

Granted

2104052

SUGAR MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE GENE EXPRESSION

ISIS-0407

US

Granted

5670633

SUGAR MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE GENE EXPRESSION

ISIS-2042

JP

Pending

 

SUGAR MODIFIED OLIGONUCLEOTIDES THAT DETECT & MODULATE GENE EXPRESSION

ISIS-0387

CA

Pending

 

SUGAR MODIFIED OLIGONUCLEOTIDES THAT DETECT AND MODULATE GEN E EXPRESSION

ISIS-0388

EP

Pending

 

SUGAR MODIFIED OLIGONUCLEOTIDES THAT DETECT AND MODULATE GENE EXPRESSION

ISIS-2708

US

Granted

6307040

SUGAR MODIFIED OLIGONUCLEOTIDES THAT DETECT AND MODULATE GENE EXPRESSION

ISIS-4789

US

Pending

 

SUGAR MODIFIED OLIGONUCLEOTIDES THAT DETECT AND MODULATE GENE EXPRESSION

ISIS-5207

 

 

 

SUGAR SURROGATE-CONTAINING OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE
MODULATION

ISIS-3454

US

Granted

6093807

SUGAR-MODIFIED 7 - DEAZA 7 - SUBSTITUTED OLIGONUCLEOTIDES

ISIS-3683

US

Pending

 

SYNTHETIC METHODS AND INTERMEDIATES FOR TRIESTER OLIGONUCLEOTIDES

ISIS-3103

US

Granted

6300319

TARGETED OLIGONUCLEOTIDE CONJUGATES

ISIS-4799

US

Granted

6525031

TARGETED OLIGONUCLEOTIDE CONJUGATES

ISIS-5092

US

Granted

6660720

TARGETED OLIGONUCLEOTIDE CONJUGATES

ISIS-0784

US

Granted

5578718

THIOL-DERIVATIZED NUCLEOSIDE

ISIS-1673

EP

Pending

 

THIOL-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1690

JP

Granted

3256236

THIOL-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-4100

US

Granted

6265558

THIOL-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES

ISIS-1992

US

Granted

5852182

THIOL-DERIVATIZED OLIGONUCLEOSIDES

ISIS-2661

US

Granted

6114513

THIOL-DERIVATIZED OLIGONUCLEOSIDES

GLIS-0025

CA

Granted

2071536

TRIPLE HELIX FORMATION IN OLIGONUCLEOTIDE THERAPY

 

--------------------------------------------------------------------------------

 

HYBN-151.0US

US

Granted

5693773

TRIPLEX-FORMING ANTISENSE OLIGONUCLEOTIDES HAVING ABASIC LINKERS THAT TARGET
NUCLEIC ACIDS COMPRISING MIXED SEQUENCES OF PURINES

ISIS-1163

US

6000000

5629152

TRISUBSTITUTED BATA-LACTAMS AND OLIGO BETA-LACTAMAMIDES

HYBN-178.0AT

AT

Granted

187645

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0AU

AU

Granted

3893095

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0BE

BE

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0CA

CA

Granted

2203652

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0CH

CH

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0CN

CN

Granted

1170367

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0DE

DE

Granted

69513998

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0DK

DK

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0EP

EP

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0ES

ES

Granted

2141393

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0FR

FR

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0GB

GB

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0GR

GR

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0IE

IE

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0IT

IT

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0JP

JP

Pending

 

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0LU

LX

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0MC

MC

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0NL

NL

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0NO

Norway

Granted

971905

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

 

--------------------------------------------------------------------------------

 

HYBN-178.0PT

PT

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

HYBN-178.0SE

SE

Granted

788366

USE OF 2’-SUBSTITUTED OLIGONUCLEOTIDES TO DOWN-REGULATING GENE EXPRESSION

 

Isis Current Chemistry Patents (June 2007 Updates)

 

 

 

Isis Docket Number

Country

Status

Application Number

Title

CORE0030US.P1

US

FILED

11/679,159

BACKBONE MODIFICATIONS TO MODULATE OLIOGONUCLEOTIDE TARGETING IN VIVO

ISIS-5772

US

FILED

11/283,119

OLIGONUCLEOTIDES HAVING A-DNA FORM AND B-DNA FORM CONFORMATIONAL GEOMETRY

 

Isis Future Chemistry Patents (as at June 27, 2007)

 

 

Isis Docket Number

Country

Status

Application Number

Title

CHEM0019AU

AU

FILED

2004270741

GAPPED OLIGOMERIC COMPOUNDS HAVING LINKED BICYCLIC SUGAR MOIETIES AT THE TERMINI

CHEM0019CA

CA

FILED

2538174

GAPPED OLIGOMERIC COMPOUNDS HAVING LINKED BICYCLIC SUGAR MOIETIES AT THE TERMINI

CHEM0019EP

EP

FILED

4788694

GAPPED OLIGOMERIC COMPOUNDS HAVING LINKED BICYCLIC SUGAR MOIETIES AT THE TERMINI

CHEM0019JP

JP

FILED

2006-526330

GAPPED OLIGOMERIC COMPOUNDS HAVING LINKED BICYCLIC SUGAR MOIETIES AT THE TERMINI

CHEM0019WO

WO

INACTIVE

PCT/US2004/029650

GAPPED OLIGOMERIC COMPOUNDS HAVING LINKED BICYCLIC SUGAR MOIETIES AT THE TERMINI

CHEM0020AU

AU

FILED

2004320622

CHIMERIC GAPPED OLIGOMERIC COMPOUNDS

CHEM0020CA

CA

FILED

TBD

CHIMERIC GAPPED OLIGOMERIC COMPOUNDS

CHEM0020EP

EP

FILED

4754188.3

CHIMERIC GAPPED OLIGOMERIC COMPOUNDS

CHEM0020JP

JP

FILED

2007-515019

CHIMERIC GAPPED OLIGOMERIC COMPOUNDS

CHEM0020USA

US

FILED

11/569,941

CHIMERIC GAPPED OLIGOMERIC COMPOUNDS

CHEM0020WO

WO

INACTIVE

PCT/US2004/017522

CHIMERIC GAPPED OLIGOMERIC COMPOUNDS

CHEM0022EP

EP

FILED

4754153.7

POSITIONALLY MODIFIED SIRNA CONSTRUCTS

CHEM0022USA

US

FILED

11/569,939

POSITIONALLY MODIFIED SIRNA CONSTRUCTS

CHEM0022WO

WO

INACTIVE

PCT/US2004/017485

POSITIONALLY MODIFIED SIRNA CONSTRUCTS

CHEM0023US

US

FILED

11/251,564

OLIGOMERIC COMPOSITIONS AND METHODS

CHEM0026US.L

US

FILED

 

PYRROLIDINYL GROUPS FOR ATTACHING CONJUGATES TO OLIGOMERIC COMPOUNDS

CHEM0026USA

US

FILED

11/574,396

PYRROLIDINYL GROUPS FOR ATTACHING CONJUGATES TO OLIGOMERIC COMPOUNDS

CHEM0026WO

WO

INACTIVE

PCT/US2005/031269

PYRROLIDINYL GROUPS FOR ATTACHING CONJUGATES TO OLIGOMERIC COMPOUNDS

CHEM0027US

US

FILED

11/627,964

6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS

CHEM0027US.P1

US

FILED

11/747,042

COMPOUNDS AND METHODS FOR SYNTHESIS OF BICYCLIC NUCLEIC ACID ANALOGS

CHEM0027WO

WO

INACTIVE

PCT/US2007/061183

6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS

CHEM0029US

US

FILED

11/747,057

5’-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS

 

--------------------------------------------------------------------------------

 

Isis Docket Number

Country

Status

Application Number

Title

CHEM0029US.L

US

EXPIRED

60/747,059

5’-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS

CHEM0029WO

WO

FILED

PCT/US2007/68690

5’-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS

CHEM0030US.L

US

INACTIVE

60/820,431

BICYCLIC CYCLOHEXOSE NUCLEIC ACID ANALOGS

CHEM0035US.L

US

FILED

60/890,079

5’-SUBSTITUTED-2’-F MODIFIED NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED
THEREFROM

CHEM0036US.L

US

FILED

60/871,397

OLIGOMERIC COMPOUNDS HAVING A MODIFIED HEMIMER MOTIF

CHEM0037US.L

US

FILED

60/895,019

BICYCLIC CYCLOHEXITOL NUCLEIC ACID ANALOGS

CORE0026EP

EP

FILED

4788713.8

CHIMERIC OLIGOMERIC COMPOUNDS COMPRISING ALTERNATING REGIONS OF NORTHERN AND
SOUTHERN CONFORMATIONAL GEOMETRY

CORE0026US

US

FILED

10/936,273

CHIMERIC OLIGOMERIC COMPOUNDS COMPRISING ALTERNATING REGIONS OF NORTHERN AND
SOUTHERN CONFORMATIONAL GEOMETRY

CORE0026WO

WO

INACTIVE

PCT/US2004/029821

CHIMERIC OLIGOMERIC COMPOUNDS COMPRISING ALTERNATING REGIONS OF NORTHERN AND
SOUTHERN CONFORMATIONAL GEOMETRY

CORE0030EP

EP

FILED

4788853.2

ANTISENSE OLIGONUCLEOTIDES OPTIMIZED FOR KIDNEY TARGETING

CORE0030US

US

FILED

10/946,498

ANTISENSE OLIGONUCLEOTIDES OPTIMIZED FOR KIDNEY TARGETING

CORE0030WO

WO

INACTIVE

PCT/US2004/030785

ANTISENSE OLIGONUCLEOTIDES OPTIMIZED FOR KIDNEY TARGETING

CORE0051AU

AU

FILED

2005286738

ENHANCED ANTISENSE OLIGONUCLEOTIDES

CORE0051CA

CA

FILED

2580504

ENHANCED ANTISENSE OLIGONUCLEOTIDES

CORE0051EP

EP

FILED

5798891.7

ENHANCED ANTISENSE OLIGONUCLEOTIDES

CORE0051JP

JP

FILED

TBD

ENHANCED ANTISENSE OLIGONUCLEOTIDES

CORE0051US

US

FILED

11/231,243

ENHANCED ANTISENSE OLIGONUCLEOTIDES

CORE0051WO

WO

INACTIVE

PCT/US2005/033837

ENHANCED ANTISENSE OLIGONUCLEOTIDES

CORE0070US.L

US

FILED

60/852,894

ANTISENSE COMPOUNDS

GLIS-0172

US

FILED

10/921,734

PYRIMIDINE DERIVATIVES FOR LABELED BINDING PARTNERS

GLIS-0173

US

ABANDONED

11/064,374

2’ MODIFIED OLIGONUCLEOTIDES

HYBN-175.1CA

CA

FILED

2473906

COOPERATIVE OLIGONUCLEOTIDES

HYBN-175.1EP

EP

FILED

3732025.6

COOPERATIVE OLIGONUCLEOTIDES

HYBN-175.1JP

JP

ABANDONED

2003-562339

COOPERATIVE OLIGONUCLEOTIDES

ISIS-5213US.C1

US

FILED

11/457,703

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-5213US.C2

US

FILED

11/457,715

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-5475

US

GRANTED (Reissue Patent)

10/925,348

METHODS AND COMPOSTIONS COVERING CHIMERIC OLIOMERS (GAPMERS) HEMIMERS AND
[HAVING (Sp)n-(Rp)m-(Sp)p] WHERE THE CONFIGURATION

ISIS-5481

US

FILED

10/859,825

CHIMERIC OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

ISIS-5553

AU

FILED

2003228477

OLIGOMERIC COMPOUNDS HAVING MODIFIED PHOSPHATE GROUPS

ISIS-5554

CA

FILED

2482440

OLIGOMERIC COMPOUNDS HAVING MODIFIED PHOSPHATE GROUPS

ISIS-5555

EP

FILED

3726231.8

OLIGOMERIC COMPOUNDS HAVING MODIFIED PHOSPHATE GROUPS

ISIS-5582

US

FILED

10/510,667

OLIGOMERIC COMPOUNDS HAVING MODIFIED PHOSPHATE GROUPS

 

 

--------------------------------------------------------------------------------

 

Isis Current Motif and Mechanism Patents (June 2007 Updates)

 

Isis Docket Number

Country

Status

Patent Number

Title

CORE0005US.L

US

Pending

 

OLIGOMERIC COMPOUNDS FOR USE IN GENE MODULATION

CHEM0004US.P1

US

Pending

 

CROSS-LINKED OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

CHEM0004WO

WO

Pending

 

CROSS-LINKED OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

CHEM0005US.P1

US

Pending

 

CONJUGATED OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

CHEM0005WO

WO

Pending

 

CONJUGATED OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

CHEM0008US.P1

US

Pending

 

OLIGOMERIC COMPOUNDS HAVING MODIFIED BASES FOR BINDING TO ADENINE AND GUANINE
AND THEIR USE IN GENE MODULATION

CHEM0009US.P1

US

Pending

 

SUGAR AND BACKBONE-SURROGATE-CONTAINING OLIGOMERIC COMPOUNDS AND COMPOSITIONS
FOR USE IN GENE MODULATION

ISIS0002-108

US

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-5203

US

Pending

 

OLIGOMERIC COMPOUNDS HAVING MODIFIED BASES FOR BINDING TO CYTOSINE AND URACIL OR
THYMINE AND THEIR USE IN GENE MODULATION

ISIS-5301

US

Pending

 

2’-SUBSTITUTED OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE MODULATIONS

ISIS-5312

US

Pending

 

MODIFIED OLIGONUCLEOTIDES FOR USE IN RNA INTERFERENCE

ISIS-5313

US

Pending

 

2’-FLUORO SUBSTITUTED OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE
MODULATIONS

ISIS-5314

US

Pending

 

2’-METHOXY SUBSTITUTED OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE
MODULATIONS

ISIS-5326

US

Pending

 

MODIFIED OLIGONUCLEOTIDES FOR USE IN RNA INTERFERENCE

CHEM0004US

US

Pending

 

CROSS-LINKED OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

CHEM0007US

US

Pending

 

NON-PHOSPHOROUS-LINKED OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

CHEM0007US.P1

US

Pending

 

NON-PHOSPHOROUS-LINKED OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

CHEM0008US

US

Pending

 

OLIGOMERIC COMPOUNDS HAVING MODIFIED BASES FOR BINDING TO ADENINE GUANINE AND
THEIR USE IN GENE MODULATION

CHEM0009US

US

Pending

 

SUGAR AND BACKBONE-SURROGATE-CONTAINING OLIGOMERIC COMPOUNDS AND COMPOSITIONS
FOR USE IN GENE MODULATION

CHEM0012US

US

Pending

 

STRUCTURAL MOTIFS, AND OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE
MODULATION

CHEM0012US.P1

US

Pending

 

STRUCTURAL MOTIFS AND OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

ISIS-2197

US

Granted

5898031

OLIGORIBONUCLEOTIDES FOR CLEAVING RNA

ISIS-2483

JP

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-2484

US

Granted

6107094

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

 

--------------------------------------------------------------------------------

 

ISIS-5207

US

Pending

 

SUGAR SURROGATE-CONTAINING OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE
MODULATION

ISIS-0002-104

US

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-0002-105

US

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-0002-106

US

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-0002-107

US

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS0002-503

WO

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-2465

EP

Granted

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-2465EP.D1

EP

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-2465EP.D2

EP

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-4313

US

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-4313US.C2

US

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-4313US.P2

US

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

ISIS-5027

US

Pending

 

OLIGORIBONUCLEOTIDES AND RIBONUCLEASES FOR CLEAVING RNA

CORE0015US.L

US

Pending

 

PROBE DESIGN FOR THE DETECTION OF RNAs IN CELL EXTRACTS, CELLS, AND TISSUES

CORE0016US.L

US

Pending

 

OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN MODULATION OF SMALL NON-CODING
RNAS

CORE0016US.L2

US

Pending

 

OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN MODULATION OF SMALL NON-CODING
RNAS

CORE0016US.L3

US

Pending

 

OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN MODULATION OF SMALL NON-CODING
RNAS

CORE0016WO

WO

Expired

 

OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN MODULATION OF SMALL NON-CODING
RNAS

CORE0016US

US

Pending

 

OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN MODULATION OF SMALL NON-CODING
RNAS

ISIS0003-500

WO

Pending

 

HUMAN RNASE III AND COMPOSITIONS AND USES THEREOF

ISIS-5030

US

Pending

 

HUMAN RNASE III AND COMPOSITIONS AND USES THEREOF

ISIS-5030.D1

US

Pending

 

HUMAN RNASE III AND COMPOSITIONS AND USES THEREOF

ISIS-5030EP

EP

Pending

 

HUMAN RNASE III AND COMPOSITIONS AND USES THEREOF

ISPH-0522

US

Pending

 

HUMAN RNASE III AND COMPOSITIONS AND USES THEREOF

ISPH-0522.D2

US

Pending

 

HUMAN RNASE III AND COMPOSITIONS AND USES THEREOF

ISIS-0207

AU

Granted

654816

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURES

ISIS-0209

CA

Granted

2082044

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURE

ISIS-0210

EP

Granted

529008

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURE

ISIS-0214

FR

Granted

529008

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURE

ISIS-0215

DE

Granted

69131848

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURES

ISIS-0216

GB

Granted

529008

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURES

 

--------------------------------------------------------------------------------

 

ISIS-0223

CH

Granted

529008

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURES

ISIS-0226

JP

Granted

2800848

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURES

ISIS-1124

IL

Pending

 

PSEUDO-HALF-KNOT FORMATION BY HYBRIDIZATION OF ANTISENSE OLIGONUCLEOTIDE TO
TARGET RNA’S SECONDARY STRUCTURE

ISIS-1130

EP

Pending

 

PSEUDO-HALF-KNOT FORMATION BY HYBRIDIZATION OF ANTISENSE OLIGONUCLEOTIDE TO
TARGET RNA’S SECONDARY STRUCTURE

ISIS-1149

JP

Granted

3113280

PSEUDO-HALF-KNOT FORMATION BY HYBRIDIZATION OF ANTISENSE OLIGONUCLEOTIDE TO
TARGET RNA’S SECONDARY STRUCTURE

ISIS-1241

US

Granted

5512438

INHIBITING RNA EXPRESSION BY FORMING A PSEUDO-HALF-KNOT RNA AT THE TARGET’S RNA
SECONDARY STRUCTURE USING ANTISENSE OLIGONUCLEOTIDES

ISIS-1420

US

Granted

5866698

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURE

ISPH-0270

EP

Pending

 

MODULATION OF GENE EXPRESSION THROUGH INTERFERENCE WITH RNA SECONDARY STRUCTURE

ISIS-5323

WO

Pending

 

2’-FLUORO SUBSTITUTED OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE
MODULATIONS

ISIS-5324

WO

Pending

 

2’ METHOXY SUBSTITUTED OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE
MODULATIONS

CHEM0013US.L

US

Pending

 

2’-SUBSTITUTED OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE MODULATIONS

ISIS-5321

WO

Pending

 

MODIFIED OLIGONUCLEOTIDES FOR USE IN RNA INTERFERENCE

ISIS-5322

WO

Pending

 

COMPOSITIONS COMPRISING ALTERNATING 2’-MODIFIED NUCLEOSIDES FOR USE IN GENE
MODULATION

ISIS-5325

US

Pending

 

COMPOSITIONS COMPRISING ALTERNATING 2’-MODIFIED NUCLEOSIDES FOR USE IN GENE
MODULATION

CORE0001US.L

US

Pending

 

MODULATION OF THE RNA INTERFERENCE PATHWAY

CORE0001US

US

Pending

 

MODULATION OF THE RNA INTERFERENCE PATHWAY

CORE0001WO

WO

Expired

 

MODULATION OF THE RNA INTERFERENCE PATHWAY

CORE0004US

US

Pending

 

ISOFORM-SPECIFIC TARGETING OF SPLICE VARIANTS

CORE0004WO

WO

Expired

 

ISOFORM-SPECIFIC TARGETING OF SPLICE VARIANTS

CORE0027US

US

Pending

 

EFFICIENT REDUCTION OF TARGET RNA’s BY SINGLE- AND DOUBLE-STRANDED OLIGOMERIC
COMPOUNDS

CORE0027WO

WO

Pending

 

EFFICIENT REDUCTION OF TARGET RNA’s BY SINGLE- AND DOUBLE-STRANDED OLIGOMERIC
COMPOUNDS

ISIS-1962

US

Pending

 

CHIMERIC OLIGONUCLEOTIDES FOR MODULATING GENE EXPRESSION

ISPH-0328

CA

Pending

 

COMPOSITIONS AND METHODS FOR ANTISENSE INHIBITION OF PROTEIN TRANSLATION

ISPH-0332

NZ

Granted

332999

COMPOSITIONS AND METHODS FOR ANTISENSE INHIBITION OF PROTEIN TRANSLATION

ISPH-0384

US

Granted

6232296

INHIBITION OF COMPLEMENT ACTIVATION AND COMPLEMENT MODULATION BY USE OF MODIFIED
OLIGONUCLEOTIDES

 

--------------------------------------------------------------------------------

 

ISPH-0760

US

Pending

 

INHIBITION OF COMPLEMENT ACTIVATION AND COMPLEMENT MODULATION BY USE OF MODIFIED
OLIGONUCLEOTIDES

ISPH-0327

AU

Granted

712228

COMPOSITIONS AND METHODS FOR ANTISENSE INHIBITION OF PROTEIN TRANSLATION

CORE0026US.L

US

Pending

 

CHIMERIC OLIGOMERIC COMPOUNDS COMPRISING ALTERNATING REGIONS OF NORTHERN AND
SOUTHERN CONFORMATIONAL GEOMETRY

ISIS-1399

EP

Granted

691853

ANTISENSE OLIGOS WHICH INTERFERE WITH MRNA CAP ACTIVITY AND INHIBIT TRANSLATION

ISIS-1401

BE

Granted

691853

ANTISENSE OLIGOS WHICH INTERFERE WITH MRNA CAP ACTIVITY AND INHIBIT TRANSLATION

ISIS-1403

FR

Granted

691853

ANTISENSE OLIGOS WHICH INTERFERE WITH MRNA CAP ACTIVITY AND INHIBIT TRANSLATION

ISIS-1404

DE

Granted

69430740.8

ANTISENSE OLIGOS WHICH INTERFERE WITH MRNA CAP ACTIVITY AND INHIBIT TRANSLATION

ISIS-1405

GB

Granted

691853

ANTISENSE OLIGOS WHICH INTERFERE WITH MRNA CAP ACTIVITY AND INHIBIT TRANSLATION

ISIS-1415

CH

Granted

691853

ANTISENSE OLIGOS WHICH INTERFERE WITH MRNA CAP ACTIVITY AND INHIBIT TRANSLATION

CORE0030US.L

US

Pending

 

ANTISENSE OLIGONUCLEOTIDES OPTIMIZED FOR KIDNEY TARGETING DEMONSTRATE INCREASED
EFFICACY IN MICE

CHEM0006US

US

Pending

 

POLYCYCLIC SUGAR SURROGATE-CONTAINING OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR
USE IN GENE MODULATION

CORE0029US.L

US

Pending

 

DOUBLE STRANDED COMPOSITIONS COMPRISING A PHOSPHOROTHIOATE RNA REGION AND A
3’-ENDO REGION FOR USE IN GENE MODULATION

CORE0029US.L2

US

Pending

 

DOUBLE STRANDED COMPOSITIONS COMPRISING AN RNA REGION AND A 3’-ENDO REGION FOR
USE IN GENE MODULATION

ISIS-4730

US

Granted

5919619

OLIGONUCLEOTIDE THERAPEUTIC AGENT AND METHODS OF MAKING SAME

ISIS-4502

US

Pending

 

OLIGONUCLEOTIDE THERAPEUTIC AGENT AND METHODS OF MAKING SAME

CHEM0002US.L

US

Pending

 

OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS

CHEM0014US.L

US

Pending

 

CHIMERIC OLIGOMERIC COMPOUNDS AND THEIR USE IN GENE MODULATION

CHEM0001US

US

Pending

 

MODIFIED OLIGONUCLEOTIDES FOR USE IN GENE MODULATION

CHEM0001WO

WO

Pending

 

MODIFIED OLIGONUCLEOTIDES FOR USE IN GENE MODULATION

ISIS-0816

AU

Granted

669353

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-0841

US

Granted

5623065

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-2002

US

Granted

5955589

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-2454

US

Granted

5856455

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-3153

US

Granted

6146829

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-4291

US

Granted

6326199

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-4387

EP

Pending

 

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-4852

US

Pending

 

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-5213

US

Pending

 

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

 

--------------------------------------------------------------------------------

 

ISIS-0818

CA

Granted

2126691

GAPPED 2’ MODIFIED OLIGONUCLEOTIDES

ISIS-0819

EP

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0821

BE

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0822

DK

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0823

FR

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0824

GB

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0825

DE

Granted

69232032

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0827

IE

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0831

NL

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0834

SE

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0835

CH

Granted

618925

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0838

JP

Granted

3131222

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-4383

JP

Pending

 

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-0839

KR

Pending

 

GAPPED 2’ MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES

ISIS-2825

KR

Granted

188858

GAPPED 2’-MODIFIED MACROMOLECULES

ISIS-4288

US

Pending

 

GAPPED OLIGOMERS HAVING SITE SPECIFIC PHOSPHOROTHIOATE INTERNUCLEOSIDE LINKAGES

ISIS-2003

US

Pending

 

GAPPED OLIGONUCLEOTIDES

HYBN-198.0AT

AU

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0BE

BE

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0CA

CA

Pending

 

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0CH

CH

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0DE

DE

Granted

696 28 864.8

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0DK

DK

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0EP

EP

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0EPD1

EP

Pending

 

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0ES

ES

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0FI

FI

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0FR

FR

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0GB

GB

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0GR

GR

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0IE

IE

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0IT

IT

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0JP

JP

Pending

 

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0NL

NL

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0PT

PT

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0SE

SE

Granted

1019428

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.0US

US

Granted

5652356

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.1US

US

Granted

5973136

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

HYBN-198.2US

US

Granted

5773601

INVERTED CHIMERIC AND HYBRID OLIGONUCLEOTIDES

ISIS-1203

NZ

Granted

256787

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

ISIS-1204

AU

Granted

668604

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

ISIS-1207

EP

Granted

672193

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

ISIS-1211

FR

Granted

672193

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

 

--------------------------------------------------------------------------------

 

ISIS-1212

GB

Granted

672193

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

ISIS-1223

CH

Granted

672193

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

ISIS-1206

CA

Granted

2145664

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

ISIS-1226

JP

Granted

2818031

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

ISIS-1229

US

Granted

5952490

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

ISIS-1213

DE

Granted

693 32 206.3

OLIGONUCLEOTIDES HAVING A CONSERVED G4 CORE SEQUENCE

 

 

 

 

--------------------------------------------------------------------------------

 

Isis Current Mechanism and Motif Patents (June 2007 Updates)

Isis Docket Number

 

Country

Status

Filing Date

CORE0005EP

                    

EP

FILED

6/18/2004

CORE0005USA

 

US

FILED

5/5/2006

CHEM0021EP

 

EP

FILED

 

CHEM0021USA

 

US

FILED

 

CHEM0021WO

 

WO

INACTIVE

 

CORE0005WO

 

WO

INACTIVE

 

CORE0026EP

 

EP

FILED

 

CORE0027EP

 

EP

FILED

 

CORE0036US

 

US

FILED

 

CORE0041US

 

US

FILED

 

CORE0043EP

 

EP

FILED

 

CORE0043USA

 

US

FILED

 

CORE0043WO

 

WO

INACTIVE

 

CORE0052US.L

 

US

EXPIRED

 

CORE0052US.L2

 

US

EXPIRED

 

CORE0055AU

 

AU

FILED

 

CORE0055CA

 

CA

FILED

 

CORE0055EP

 

EP

FILED

 

CORE0055JP

 

JP

FILED

 

CORE0055US.C1

 

US

FILED

 

CORE0055US.C10

 

US

FILED

 

CORE0055US.C2

 

US

FILED

 

CORE0055US.C3

 

US

FILED

 

CORE0055US.C4

 

US

FILED

 

CORE0055US.C5

 

US

FILED

 

CORE0055US.C6

 

US

FILED

 

CORE0055US.C7

 

US

FILED

 

CORE0055US.C8

 

US

FILED

 

CORE0055US.C9

 

US

FILED

 

CORE0055USA

 

US

FILED

 

CORE0055WO

 

WO

INACTIVE

 

CORE0056AU

 

AU

FILED

 

CORE0056CA

 

CA

FILED

 

CORE0056EP

 

EP

FILED

 

CORE0056JP

 

JP

FILED

 

CORE0056US.C1

 

US

FILED

 

CORE0056US.C2

 

US

FILED

 

CORE0056US.C3

 

US

FILED

 

CORE0056US.C4

 

US

FILED

 

CORE0056USA

 

US

FILED

 

CORE0056WO

 

WO

INACTIVE

 

CORE0060WO2

 

WO

FILED

 

 

--------------------------------------------------------------------------------

 

CORE0066WO

 

WO

FILED

 

CORE0068WO

 

WO

FILED

 

ISIS-2965EP.D1

 

EP

FILED

 

ISIS-2965EP.D2

 

EP

FILED

 

ISIS-5482

 

US

FILED

 

ISIS-5586

 

US

FILED

 

ISIS-5737

 

AU

FILED

 

ISIS-5738

 

CA

FILED

 

ISIS-5739

 

EP

FILED

 

CORE0054US.L

 

US

EXPIRED

 

CORE0053US.L

 

US

EXPIRED

 

 

 

 

--------------------------------------------------------------------------------

 

 

Our Ref. No.

CaseType

Application No.

Patent No.

Status

Country

Title

NUCL-006

PCT

2004263832

2004263832

Granted

Australia

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

PI0411219.9

 

ExamReq

Brazil

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

2528510

 

Published

Canada

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

200480022894.9

 

Abandoned

China (People’s Republic)

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

04776661.3

 

Pending

European Patent Convention

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

DIV

10180048.0

 

Published

European Patent Convention

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

DIV

10180047.2

 

Published

European Patent Convention

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

5572/DELNP/2005

 

Published

India

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

172268

 

Abandoned

Israel

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

2006-533810

 

ExamReq

Japan

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

DIV

2011-148461

 

Pending

Japan

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

ORD

PCT/US2004/019229

 

Expired

Patent Cooperation Treaty

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

200507781-3

117818

Granted

Singapore

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

DIV

200704437-3

 

Published

Singapore

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

10/560377

 

Published

United States of America

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PRO

60/478,076

 

Expired

United States of America

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

PCT

13/065601

 

Pending

United States of America

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-006

CON

13/234698

 

Pending

United States of America

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

PCT

2005319306

 

Allowed

Australia

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

PCT

2592099

 

Published

Canada

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

PCT

05854816.5

EP1833967

Allowed

European Patent Convention

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

 

--------------------------------------------------------------------------------

 

NUCL-010

DIV

10010655.8

 

Abandoned

European Patent Convention

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

EPP

05854816.5

EP1833967

Allowed

France

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

EPP

05854816.5

EP1833967

Allowed

Germany

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

PCT

2007-548393

 

Abandoned

Japan

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

ORD

PCT/US2005/046162

 

Expired

Patent Cooperation Treaty

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

EPP

05854816.5

EP1833967

Allowed

United Kingdom

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

PRO

60/638,294

 

Expired

United States of America

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

NUCL-010

PCT

 

 

Not Filed

United States of America

CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING

 

 

 

--------------------------------------------------------------------------------

 

 

Our Ref. No.

Country

Application No.

Patent No.

Status

Application Title

RIB-001.3AT1

Austria

EP 02003683

E297.463

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3AT2

Austria

05002454.6-2107

E418.60

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3AU

Australia

2000032713

778474

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3AU1

Australia

2005201044

2005201044

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3AUD2

Australia

2008202208

 

Opposed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CA

Canada

2,359,180

2,359,180

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CH1

Switzerland

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CH2

Switzerland

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CY1

Cyprus

EP 02003683

CY05/1101016

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3CY2

Cyprus

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE0

Germany

50000414.5-08

1144623

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE1

Belgium

EP 02003683

EP 1214945 B1

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE1

Germany

50010528.6-08

1214945

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE2

Belgium

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DE2

Germany

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DED1

Germany

10066235.8

10066235.8

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DED2

Germany

10066344.3

 

Pending

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DED3

Germany

10066382.6

 

Pending

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DEUTM

Germany

20023125.1

DE20023125 U1

RegUtilMode

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DK1

Denmark

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3DK2

Denmark

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

 

--------------------------------------------------------------------------------

 

RIB-001.3EPD1

Europe

02003683.6

1214945

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3EPD2

Europe

05002454.6

1550719

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3EPD3

Europe

06025389.5

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3EPD4

Europe

10011217.6

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3ES1

Spain

EP 02003683

ES2243608

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3ES2

Spain

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3FI1

Finland

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3FI2

Finland

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3FR1

France

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3FR2

France

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3GB1

United Kingdom

EP 02003683

EP1214945

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3GB2

United Kingdom

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3GR1

Greece

EP 02003683

3054579

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3GR2

Greece

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IE

Ireland

EP 00910510

1144623 B9

Revoked

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IE1

Ireland

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IE2

Ireland

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IT1

Italy

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3IT2

Italy

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD10

Japan

2009-285706

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD3

Japan

2007-186341

 

Appealed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD4

Japan

2007-186340

 

Appealed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

 

--------------------------------------------------------------------------------

 

RIB-001.3JPD5

Japan

2007-186339

 

ExamReq

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD7

Japan

2009-002825

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3JPD9

Japan

2009-285705

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3LI1

Liechtenstein

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3LI2

Liechtenstein

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3LU1

Luxembourg

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3LU2

Luxembourg

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3MC1

Monaco

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3MC2

Monaco

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3NL1

Netherlands

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3NL2

Netherlands

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3PT1

Portugal

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3PT2

Portugal

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3SE1

Sweden

EP 02003683

EP 1214945 B1

GrantedInOp

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3SE2

Sweden

05002454.6-2107

EP1550719

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON1

US

11/982325

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON2

US

11/982305

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON3

US

11/982425

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON4

US

11/982441

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON5

US

11/982345

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USCON6

US

11/982434

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USD1

US

10/382395

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

 

--------------------------------------------------------------------------------

 

RIB-001.3USD2

US

10/383099

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USD3

US

10/382768

 

Allowed

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3USD4

US

10/612179

 

Published

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3WO

PCT

PCT/DE00/00244

 

CompletedNt

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-001.3ZA

South Africa

ZA 20015909

2001/5909

Granted

METHOD AND MEDICAMENT FOR INHIBITION THE EXPRESSION OF A DEFINED GENE

RIB-002.1DE

Germany

10100586.5-09

DE10100586 C1

Granted

INHIBITING GENE EXPRESSION IN CELLS, USEFUL FOR e.g., TREATING TUMORS, BY
INTRODUCING DOUBLE-STRANDED COMPLEMENTARY OLIGORNA HAVING

RIB-002.4

US

12/894018

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4AT

Austria

02710786.1

E328.075

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4AU

Australia

2002229701

2002229701

Granted

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4CH

Switzerland

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4CY

Cyprus

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4DE

Germany

50206993.7-08

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4EP

Europe

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4GB

United Kingdom

EP 02710786

EP 1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4IE

Ireland

02710786.1

1352061

Granted

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4JP

Japan

2002-556740

4210116

Granted

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4JPD1

Japan

2002-556739

4209678

Granted

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4LI

Liechtenstein

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4LU

Luxembourg

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4TR

Turkey

02710786.1

1352061

GrantedInOp

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-002.4US

US

10/384,339

7,829,693

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

 

--------------------------------------------------------------------------------

 

RIB-002.4WO

PCT

PCT/EP02/00152

 

CompletedNt

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A TARGET GENE

RIB-006.1DE

Germany

02702247.4- 2405/1349

50214866.9-08

Allowed

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1EP

Europe

02702247.4

EP1349927

GrantedInOp

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1EPD1

Europe

10002422.3

 

Pending

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1EPD2

Europe

10011812.4

 

Published

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1ES

Spain

02702247

ES2204360

Granted

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1FR

France

EP 02702247

EP1349927

Granted

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1GB

United Kingdom

02702247.4- 2405/1349

EP1349927

Granted

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1HKD1

Hong Kong

11100629.6

 

Published

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1HKD2

Hong Kong

11111936.1

 

Pending

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1NL

Netherlands

EP 02702247

EP1349927

Granted

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.1WO

PCT

PCT/EP02/00151

 

CompletedNt

METHOD FOR INHIBITING THE EXPRESSION OF A TARGET GENE AND MEDICAMENT FOR
TREATING A TUMOR DISEASE

RIB-006.2US

US

10/384,260

7,473,525

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.2US

US

12/276,270

 

Pending

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4AU

Australia

2005284729

 

Allowed

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4CA

Canada

2580560

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4EP

Europe

05797892.6

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4EPD1

Europe

11004902.0

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4HK

Hong Kong

07114036.0

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4US

US

10/941663

7767802

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4USCIP2

US

11/229183

7423142

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4USCON2

US

12/961337

 

Allowed

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

 

--------------------------------------------------------------------------------

 

RIB-006.4USD1

US

12/175,938

7,868,160

Issued

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-006.4WO

PCT

PCT/US2005/033 309

 

CompletedNt

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF ANTI- APOPTOTIC GENES

RIB-008.2DE

Germany

DE 10163098

DE10163098

Granted

METHOD FOR INHIBITING THE REPLICATION OF VIRUSES

RIB-008.3USCIP

US

10/384,512

7,348,314

Issued

METHOD TO INHIBIT THE REPLICATION OF VIRUSES

RIB-008.3USCON

US

11/959,936

7,745,418

Issued

METHOD TO INHIBIT THE REPLICATION OF VIRUSES

RIB-008.3USCON1

US

12/631689

 

Published

METHOD TO INHIBIT THE REPLICATION OF VIRUSES

RIB-011.2WO

PCT

PCT/EP02/11973

 

CompletedNt

USE OF DOUBLE STRAND RIBONUCLEIC ACID FOR TREATING AN INFECTION WITH A
POSTIVE-STRAND RNA-VIRUS

RIB-012.2EP

Europe

02779511.1

 

Appealed

USE OF A DOUBLE-STRANDED RIBONUCLEIC ACID FOR SPECIFICALLY INHIBITING THE
EXPRESSION OF A GIVEN TARGET GENE

RIB-012.2EPD1

Europe

10011813.2

 

Published

USE OF A DOUBLE-STRANDED RIBONUCLEIC ACID FOR SPECIFICALLY INHIBITING THE
EXPRESSION OF A GIVEN TARGET GENE

RIB-012.2WO

PCT

PCT/EP02/11969

 

CompletedNt

USE OF A DOUBLE-STRANDED RIBONUCLEIC ACID FOR SPECIFICALLY INHIBITING THE
EXPRESSION OF A GIVEN TARGET GENE

RIB-012.3US

US

10/384,463

7,763,590

Issued

COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF A MUTANT GENE

RIB-012.3USCON1

US

13/177316

 

Published

COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF A MUTANT GENE

RIB-012.3USD1

US

12/817009

7994309

Allowed

COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF A MUTANT GENE

RIB-013.1WO

PCT

PCT/EP02/11972

 

CompletedNt

DRUG FOR TREATING A FIBROTIC DISEASE THROUGH RNA INTERFERENCE

RIB-014.1WO

PCT

PCT/EP02/12221

 

Expired

SMAD7 INHIBITORS FOR THE TREATMENT OF CNS DISEASES

RIB-015.2US

US

10/349,320

7,196,184

Issued

DOUBLE-STRANDED RNA (dsRNA) AND METHOD FOR USE FOR INHIBITING EXPRESSION OF A
FUSION GENE

RIB-015.2USCON1

US

12/912616

 

Published

DOUBLE-STRANDED RNA (dsRNA) AND METHOD FOR USE FOR INHIBITING EXPRESSION OF A
FUSION GENE

RIB-015.2USD1

US

11/656,349

7,846,907

Allowed

DOUBLE-STRANDED RNA (dsRNA) AND METHOD FOR USE FOR INHIBITING EXPRESSION OF A
FUSION GENE

RIB-015.3WO

PCT

PCT/EP03/00604

 

Expired

METHOD FOR INCREASING THE EFFICIENCY OF AN INHIBITOR OF TYROSINE KINASE ACTIVITY

RIB-016.1DE

Germany

10302421.2-41

 

Published

DOUBLE-STRANDED RIBONUCLEIC ACID WITH IMPROVED ACTIVITY

RIB-016.2AT

Austria

E367441

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2AU

Australia

2004206255

2004206255

Issued

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

 

--------------------------------------------------------------------------------

 

RIB-016.2AUD1

Australia

2008203538

 

Pending

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2BE

Belgium

04704041.5

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2CA

Canada

2513809

2513809

Allowed

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2CH

Switzerland

04704041.5

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2CY

Cyprus

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2DE

Germany

602004007620.1-08

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2DK

Denmark

04704041.5

DK/EP 1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2EP

Europe

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2EPD1

Europe

07010839.4

 

Published

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2ES

Spain

04704041.5-1521

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2FR

France

04704041.5-1521

EP1587926B1

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2GB

United Kingdom

04704041.5-1521

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2HK

Hong Kong

08105048.3

 

Published

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2HU

Hungary

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2IE

Ireland

04704041.5

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2IT

Italy

04704041.5-1521

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2LI

Liechtenstein

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2LU

Luxembourg

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2NL

Netherlands

04704041.5-1521

EP1587926B1

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2PT

Portugal

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2SE

Sweden

04704041.5-1521

EP1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2SI

Slovenia

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

 

--------------------------------------------------------------------------------

 

RIB-016.2TR

Turkey

04704041.5-1521

1587926

Granted

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2US

US

10/543048

 

Appealed

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-016.2WO

PCT

PCT/US2004/001 461

 

CompletedNt

LIPOPHILIC DERIVATIVES OF DOUBLE-STRANDED RIBONUCLEIC ACID

RIB-017.1EPUS

US

60/479,354

 

Converted

SiRNA WITH INCREASED STABILITY IN SERUM

 

 

 

 

--------------------------------------------------------------------------------

 

EXHIBIT B

IN-LICENSES COVERING ALNYLAM PATENT RIGHTS

B.1.    In-Licenses Covering Base Alnylam Patent Rights

 

Co-Exclusive License Agreement between Garching Innovation GmbH and Alnylam
Pharmaceuticals, Inc., (effective December 20, 2002) and Amendment (effective
8 July, 2003).

Amended and Restated Strategic Collaboration and License Agreement effective as
of April 28, 2009, between Isis Pharmaceuticals, Inc. and Alnylam
Pharmaceuticals, Inc.

B.2.    In-Licenses Covering Additional Alnylam Patent Rights Stanford

 

Co-Exclusive License Agreement between THE BOARD OF TRUSTEES OF THE LELAND
Stanford JUNIOR UNIVERSITY and Alnylam Pharmaceuticals, Inc., (effective
September 17, 2003)

Cancer Research Technology Limited

 

Exclusive License Agreement between CANCER RESEARCH TECHNOLOGIES LIMITED and
Alnylam Pharmaceuticals, Inc., (effective July 18, 2003)

 

 

 

--------------------------------------------------------------------------------

 

EXHIBIT C

RESEARCH COLLABORATION PLAN

[Reserved.]

 

 

 

--------------------------------------------------------------------------------

 

EXHIBIT D

PRESS RELEASE

 

 

 

 

--------------------------------------------------------------------------------

 

 

Contacts:

 

Alnylam Pharmaceuticals, Inc.

Arrowhead Research Corporation

Cynthia Clayton

Michael Levitan

Vice President, Investor Relations and

The Trout Group, LLC

Corporate Communications

646-378-2920

617-551-8207

ir@arrowres.com

 

 

Amanda Sellers (Media)

 

Spectrum

 

202-955-6222 x2597

 

Alnylam and Arrowhead Form Collaboration and Licensing Agreement

– Arrowhead Receives License from Alnylam to Develop RNAi Therapeutic

Toward Hepatitis B Virus (HBV) –

– Alnylam Gains Access to Arrowhead’s Dynamic Polyconjugate (DPC)

Delivery Technology for “Alnylam 5x15” Target –

Cambridge, Mass. and Pasadena, Calif., January 5, 2012 – Alnylam
Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and
Arrowhead Research Corporation, (Nasdaq: ARWR) a nanomedicine company with
development programs in RNAi and obesity, announced today that they have entered
into a collaboration and joint licensing agreement.

Alnylam has granted Arrowhead a license under its intellectual property that
enables the discovery, development, and commercialization of an RNAi therapeutic
targeting the hepatitis B virus (HBV). Alnylam is eligible to receive from
Arrowhead milestone payments and royalties on sales of product resulting from
the license. In addition, Alnylam has received a license from Arrowhead to
utilize their Dynamic Polyconjugate (DPC) delivery technology for an RNAi
therapeutic product. Alnylam expects to deploy this technology for an
undisclosed target in its “Alnylam 5x15” pipeline which is focused on
genetically defined targets and diseases. Arrowhead is eligible to receive from
Alnylam milestone payments and royalties on sales of product resulting from the
license. No additional financial details were disclosed.

“We view Arrowhead’s DPC technology as a promising emerging delivery approach,
with the potential to complement our existing delivery platform which currently
includes lipid nanoparticles and our siRNA conjugate platform,” said Laurence
Reid, Ph.D., Senior Vice President and Chief Business Officer of Alnylam. “In
addition, by granting Arrowhead a license for their HBV program, we are enabling
their efforts with access to Alnylam intellectual property which we believe is
critical for the development and commercialization of RNAi therapeutics. We look
forward to continuing to work with Arrowhead, who is already a partner and
licensee of Alnylam.”

“This license from Alnylam is an important step for us as we expand our pipeline
to include our first DPC-enabled candidate targeting hepatitis B,” said
Christopher Anzalone, Ph.D., President and CEO of Arrowhead. “With over
350 million carriers world-wide, HBV represents a large underserved medical
need, and one that RNAi and DPCs are well-suited to address. We are also very
pleased to grant Alnylam the first commercial license to our DPC technology for
one of their genetically defined disease targets. We believe DPCs represent one
of the most promising delivery approaches for the systemic delivery of RNAi
therapeutics, and we look forward to a close collaboration to help Alnylam bring
a DPC-enabled candidate to the clinic.”

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough
in understanding how genes are turned on and off in cells, and a completely new
approach to drug discovery and development. Its discovery has been heralded as
“a major scientific breakthrough that happens once every decade or so,” and
represents one of the most promising and rapidly advancing frontiers in biology
and drug discovery today which was awarded the 2006 Nobel Prize for Physiology
or Medicine. RNAi is a natural process of gene silencing that occurs in
organisms ranging from plants to mammals. By harnessing the natural biological
process of RNAi occurring in our cells, the creation of a major new class of
medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs
(siRNAs), the molecules that mediate RNAi and comprise Alnylam’s RNAi
therapeutic platform, target the cause of diseases by potently silencing
specific mRNAs, thereby preventing disease-causing proteins from being made.
RNAi therapeutics have the potential to treat disease and help patients in a
fundamentally new way.

 

--------------------------------------------------------------------------------

 

About DPC Technology

Dynamic Polyconjugate (DPC) technology is a systemic siRNA delivery platform
that enables polymer-based formulation chemistry to efficiently target gene
silencing complexes to specific cells. As the DPCs attach to and enter the
target cells, they respond to the environmental cues provided by the cell to
disassemble and release the active siRNA molecule. This unique chemistry mimics
the natural viral targeting and disassembly process. Pre-clinical studies show
that DPCs are highly efficacious for delivery to the liver.

About “Alnylam 5x15™”

The “Alnylam 5x15” strategy, launched in January 2011, establishes a path for
development and commercialization of novel RNAi therapeutics to address
genetically defined diseases with high unmet medical need. Products arising from
this initiative share several key characteristics including: a genetically
defined target and disease; the potential to have a major impact in a high unmet
need population; the ability to leverage the existing Alnylam RNAi delivery
platform; the opportunity to monitor an early biomarker in Phase I clinical
trials for human proof of concept; and the existence of clinically relevant
endpoints for the filing of a new drug application (NDA) with a focused patient
database and possible accelerated paths for commercialization. This strategy
leverages Alnylam’s clinical progress on siRNA delivery, including definitive
human proof-of-concept data for systemic delivery. By the end of 2015, the
company expects to have five such RNAi therapeutic programs in advanced clinical
development. These include ALN-TTR for the treatment of transthyretin-mediated
amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia,
ALN-HPN for the treatment of refractory anemia, ALN-APC for the treatment of
hemophilia, and one additional program from the company’s ongoing discovery
efforts that will be designated at or around the end of 2011. Alnylam intends to
focus on developing and commercializing certain products arising under the
“Alnylam 5x15” strategy itself in the United States and potentially certain
other countries; the company will seek development and commercial partners for
other core products both in the United States and in other global territories.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on
RNA interference, or RNAi. The company is leading the translation of RNAi as a
new class of innovative medicines with a core focus on RNAi therapeutics for the
treatment of genetically defined diseases, including ALN-TTR for the treatment
of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of
severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, and
ALN-APC for the treatment of hemophilia. As part of its “Alnylam 5x15TM”
strategy, the company expects to have five RNAi therapeutic products for
genetically defined diseases in advanced stages of clinical development by the
end of 2015. Alnylam has additional partner-based programs in clinical or
development stages, including ALN-RSV01 for the treatment of respiratory
syncytial virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and
ALN-HTT for the treatment of Huntington’s disease. The company’s leadership
position on RNAi therapeutics and intellectual property have enabled it to form
major alliances with leading companies including Merck, Medtronic, Novartis,
Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. In addition, Alnylam
and Isis co-founded Regulus Therapeutics Inc., a company focused on discovery,
development, and commercialization of microRNA therapeutics; Regulus has formed
partnerships with GlaxoSmithKline and Sanofi. Alnylam has also formed Alnylam
Biotherapeutics, a division of the company focused on the development of RNAi
technologies for application in biologics manufacturing, including recombinant
proteins and monoclonal antibodies. Alnylam’s VaxiRNA™ platform applies RNAi
technology to improve the manufacturing processes for vaccines; GlaxoSmithKline
is a collaborator in this effort. Alnylam scientists and collaborators have
published their research on RNAi therapeutics in over 100 peer-reviewed papers,
including many in the world’s top scientific journals such as Nature, Nature
Medicine, Nature Biotechnology, and Cell. Founded in 2002, Alnylam maintains
headquarters in Cambridge, Massachusetts. For more information, please visit
www.alnylam.com.

About Arrowhead Research Corporation

Arrowhead Research Corporation is a clinical stage nanomedicine company
developing innovative therapies at the interface of biology and nanoengineering.
Arrowhead’s world-class capabilities and intellectual property covering nucleic
acid delivery, siRNA chemistry, and tissue targeting allow it to design and
develop therapeutic agents for a wide range of diseases. The company’s lead
products include CALAA-01, an oncology drug candidate based on the gene
silencing RNA interference (RNAi) mechanism, and Adipotide™, an anti-obesity
peptide that targets and kills the blood vessels that feed white adipose tissue.
Arrowhead is leveraging its proprietary Dynamic Polyconjugate™ (DPC), Liposomal
Nanoparticle (LNP), and RONDEL™ delivery platforms to support its own pipeline
of preclinical and clinical candidates and to secure external partnerships and
collaborations with biotech and pharmaceutical companies. For more information,
please visit www.arrowheadresearch.com.

 

--------------------------------------------------------------------------------

 

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations,
plans and prospects, including without limitation, statements regarding
Alnylam’s views with respect to the potential for RNAi therapeutics and DPC
technology, and Alnylam’s expectations regarding its “Alnylam 5x15” product
strategy, constitute forward-looking statements for the purposes of the safe
harbor provisions under The Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these
forward-looking statements as a result of various important factors, including,
without limitation, Alnylam’s ability to discover and develop novel drug
candidates, successfully demonstrate the efficacy and safety of its drug
candidates, including those utilizing DPC technology, the pre-clinical and
clinical results for its product candidates, which may not support further
development of product candidates, actions of regulatory agencies, which may
affect the initiation, timing and progress of clinical trials, obtaining,
maintaining and protecting intellectual property, obtaining regulatory approval
for products, competition from others using technology similar to Alnylam’s and
others developing products for similar uses, as well as those risks more fully
discussed in the “Risk Factors” section of its most recent quarterly report on
Form 10-Q on file with the Securities and Exchange Commission. In addition, any
forward-looking statements represent Alnylam’s views only as of today and should
not be relied upon as representing its views as of any subsequent date. Alnylam
does not assume any obligation to update any forward-looking statements.

Arrowhead Forward-Looking Statements

This news release contains forward-looking statements within the meaning of the
“safe harbor” provisions of the Private Securities Litigation Reform Act of
1995. These statements are based upon our current expectations and speak only as
of the date hereof. Our actual results may differ materially and adversely from
those expressed in any forward-looking statements as a result of various factors
and uncertainties, including the future success of our scientific studies, our
ability to successfully develop drug candidates, the timing for starting and
completing clinical trials, rapid technological change in our markets, and the
enforcement of our intellectual property rights. Arrowhead Research
Corporation’s most recent Annual Report on Form 10-K and subsequent Quarterly
Reports on Form 10-Q discuss some of the important risk factors that may affect
our business, results of operations and financial condition. We assume no
obligation to update or revise forward-looking statements to reflect new events
or circumstances.

 

 

 

 

--------------------------------------------------------------------------------

 

EXHIBIT E

ALNYLAM CRT ADDITIONAL PATENT RIGHTS

 

 

 

 

--------------------------------------------------------------------------------

 

 

Our Ref. No.

Country

Application No.

PatNumber

ApplicationStatus

Title

CRT-001AU1

Australia

200114065 B2

774285

Granted

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001AT1

Austria

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001BE1

Belgium

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001CA1

Canada

2391622

 

ExamReq

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001CY1

Cyprus

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001DK1

Denmark

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001EP1

Europe

00976188.3

EP1230375B1

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001FI1

Finland

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001FR1

France

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001DE1

Germany

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001DE1

Greece

00976188.3

1230375

Granted

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001HK1

Hong Kong

03100785.6

1050378

Granted

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001IE1

Ireland

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001IL1

Israel

149666

 

Pending

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001IT1

Italy

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001JP1

Japan

2001-538524

 

Pending

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001JPD1

Japan

 

 

Not Filed

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001LV1

Latvia

00976188.3

EP1230375B1

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001LI1

Liechtenstein

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001LU1

Luxembourg

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001MX1

Mexico

PA/a/2002/005013

 

Allowed

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001MC1

Monaco

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001NL

Netherlands

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001NZ

New Zealand

519325

519325

Granted

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001NZ1

Norway

20022359

 

Pending

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001PL

Poland

P356698

 

Pending

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001PL1

Poland

P388605

 

Pending

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001PT1

Portugal

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001SG1

Singapore

200203380-1

89569

Granted

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001ZA1

South Africa

2002-3816

2002/3816

Granted

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001ES

Spain

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001SE

Sweden

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001CH

Switzerland

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001TR1

Turkey

00976188.3

1230375

Granted

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001GB0

United Kingdom

 

 

Expired

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001GB1

United Kingdom

00976188.3

1230375

GrantedInOp

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001US1

US

10/150426

 

Published

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001USCON1

US

11/933121

 

Published

INHIBITING GENE EXPRESSION WITH DSRNA

CRT-001USCON2

US

11/933,153

 

Published

INHIBITING GENE EXPRESSION WITH DSRNA

 

 

 

 

--------------------------------------------------------------------------------

 

EXHIBIT F

ALNYLAM STANFORD ADDITIONAL PATENT RIGHTS

 

 

 

--------------------------------------------------------------------------------

 

 

Our Ref. No.

Country

Application No.

Patent No.

Status

Title

STN 001.4US1

US

10/259226

 

Published

METHODS AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF VIRAL GENE EXPRESSION
IN MAMMALS

STN 001.4USCON1

US

12/368,082

 

Pending

METHODS AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF VIRAL GENE EXPRESSION
IN MAMMALS

STN 001.4USCON2

US

12/576052

 

Appealed

METHODS AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF VIRAL GENE EXPRESSION
IN MAMMALS

STN-001.1USPRO1

US

60/307,411

 

Expired

METHODS AND COMPOSITIONS FOR IN VIVO DELIVERY OF A NAKED RIBONUCLEIC ACID INTO A
TARGET CELL

STN-001.2USPRO1

US

60/360,664

 

Expired

METHODS AND COMPOSITIONS FOR IN VIVO DELIVERY OF A NAKED RIBONUCLEIC ACID INTO A
TARGET CELL

STN-001.3AU

Australia

2002326410

 

Accepted

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3AUD1

Australia

2009200231

 

Pending

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3CA

Canada

2,454,183

 

Published

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3EP

Europe

02761123.5

 

Published

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3EPD1

Europe

10178509.5

 

Published

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3HK

Hong Kong

04108019.6

 

Published

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3JP

Japan

2003-515539

 

Published

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3JPD1

Japan

2007-511489

 

Pending

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3JPD2

Japan

2010-249697

 

Published

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3WO

PCT

PCT/US02/22869

 

CompletedNt

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-001.3US

US

10/200002

 

Appealed

METHOD AND COMPOSITIONS FOR RNAi MEDIATED INHIBITION OF GENE EXPRESSION IN
MAMMALS

STN-003AU

Australia

2005240118

 

Opposed

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL

STN-003AUD1

Australia

 

 

Pending

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL

STN-003CA

Canada

2564503

 

Pending

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL

STN-003EP

Europe

05749437.9

 

Pending

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL

STN-003IL

Israel

178679

 

Pending

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL

 

--------------------------------------------------------------------------------

 

STN-003WO

PCT

PCT/US2005/015264

 

CompletedNt

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL

STN-003US

US

11/122,328

7,307,067

Allowed

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL

STN-003USCON1

US

12/950672

 

Published

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL

STN-003USCON2

US

11/953,705

7,838,504

Granted

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL

STN-003USPRO1

US

60/568,358

 

Converted

METHODS AND COMPOSITIONS FOR REDUCING VIRAL GENOME AMOUNTS IN A TARGET CELL