Document:

Exhibit
10.51

 

CERTAIN
CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS
BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION
PURSUANT TO RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.

 

AMENDED
AND RESTATED WORLDWIDE AGREEMENT

 

This Amended and Restated
Worldwide Agreement is entered into as of October 1, 2003 (the “Effective Date”), by and among, on the one
hand, HOFFMANN-LA ROCHE INC., a New Jersey corporation having offices at 340
Kingsland Street, Nutley, New Jersey 07110 (“Roche-Nutley”)
and F. HOFFMANN-LA ROCHE LTD of Basel, Switzerland (“F. Roche”) (Roche-Nutley and F. Roche are hereinafter
individually and collectively referred to as “Roche”)
and, on the other hand, PROTEIN DESIGN LABS, INC., a Delaware corporation
having offices at 34801 Campus Drive, Fremont, California 94555 (“PDL”).

 

RECITALS

 

Roche and PDL
were originally parties to agreements dated January 31, 1989, as amended
(the “1989 Agreements”) pertaining
to humanized and chimeric antibodies against the interleukin-2 receptor (“IL-2R”).

 

Under the 1989
Agreements, PDL exclusively licensed to Roche rights to a humanized antibody
now known as Daclizumab (as defined below).

 

Roche is
currently marketing Daclizumab under the trademark Zenapax® for the prevention
of acute organ rejection in patients receiving kidney transplants.

 

In 1999, Roche
and PDL replaced the 1989 Agreements with two new agreements (as amended, known
separately as the “1999 PDL/Roche Agreement” and
the “F. Roche Agreement,” respectively,
and collectively as the “1999 Agreements”)
which provided PDL with rights to develop and, if successful, promote
Daclizumab in autoimmune indications for increased compensation from the 1989
Agreements.

 

Roche and PDL
now desire to replace the 1999 Agreements with this Amended and Restated
Worldwide Agreement that (1) reverts to PDL all IL-2R antibody rights
licensed to Roche by PDL under the 1999 Agreements, subject to Roche’s
continuing exclusive license to market and sell Daclizumab for Transplant
Indications in the Roche Territory and develop and commercialize products based
on [*] that [*] to the [*] of [*]; (2) grants
to PDL the sole and exclusive worldwide rights under Roche’s relevant
intellectual property to develop, and, if successful, market and sell
Daclizumab for Autoimmune Indications and Other Indications; and (3) grants
PDL the right to purchase all of Roche’s remaining rights to Daclizumab,
subject to Roche’s right to retain its exclusive license from PDL to develop
and commercialize products based on [*]
that [*] to the [*] of [*].

 

1

 

NOW, THEREFORE, in
consideration of the premises and the mutual promises and covenants set forth
below, PDL and Roche mutually agree to amend and restate the 1999 Agreements in
this single Amended and Restated Worldwide Agreement as follows:

 

I.  DEFINITIONS

 

For the purposes of this
Amended and Restated Worldwide Agreement, the following terms, when written
with an initial capital letter, shall have the meaning ascribed to them
below.  All references to particular Appendices, Articles and Sections
shall mean the Appendices to, and Articles and Sections of, this Amended and
Restated Worldwide Agreement, unless otherwise specified.

 

1.1                                 “AAGS” shall mean the average annualized
Roche Adjusted Gross Sales of Daclizumab calculated according to the following:

 

[*]

 

where [*] is the [*]
for the period from [*] through the
most recent [*] ended [*]
the [*] of (i) the date of [*] that [*] the [*]; or (ii) the date of [*]
that [*] the [*];

 

[*] is that portion of [*] that [*], to [*] reasonable satisfaction, to be [*]
to [*] for [*]
in [*] or [*];
and

 

[*] is the [*]
of [*] from (and including) [*] through the end of the [*]
ended [*] to the [*]
of (i) the date of [*] that [*] the [*]; or (ii) the
date of [*] that [*]
the [*].

 

By way of illustration and without limitation, [*]

 

1.2                                 “Acting Party” has the meaning set forth in
Section 12.1(c).

 

1.3                                 “Affiliates” means any corporation or other
business entity controlled by, controlling, or under common control with
another entity, with “control” meaning direct or indirect beneficial ownership
of more than fifty percent (50%) of the voting stock of, or more than a fifty
percent (50%) interest in the income of, such corporation or other business
entity.  Anything to the contrary in this paragraph notwithstanding, [*]

 

1.4                                 “AI Trademarks” means all trademarks used
in connection with the marketing, promotion, and sale of Daclizumab by PDL or
its sublicensee(s) and all trademark registrations and applications therefor,
and all goodwill associated therewith.

 

1.5                                 “Application” means a new application, or a
supplement or an amendment to an existing application, for marketing approval
for an Autoimmune Indication in the Territory.

 

1.6                                 “Autoimmune Indications” or “AI” means all indications that involve
pathogenic consequences, including tissue injury, produced by autoantibodies or
autoreactive T lymphocytes interacting with self epitopes, i.e.,
autoantigens.  Autoimmune Indications shall

 

2

 

include,
without limitation, asthma, psoriasis, rheumatoid arthritis, systemic lupus
erythematosus, scleroderma, juvenile rheumatoid arthritis, polymytosis, Type I
diabetes, sarcoidosis, Sjogrens syndrome, chronic active non-pathogenic
hepatitis, non-infectious uveitis (Behcets), aplastic anemia, regional
non-pathogenic enteritis (including ulcerative colitis, Crohn’s Disease and
inflammatory bowel disease), Kawasaki’s disease, post-infectious encephalitis,
multiple sclerosis, and tropic spastic paraparesis.

 

1.7                                 “Change of Control” means a transaction in
which Roche
either (a) sells, conveys or otherwise disposes of all or substantially
all of its property or business; or (b) either (i) merges or
consolidates with any other entity (other than a wholly-owned subsidiary of Roche); or (ii) effects
any other transaction or series of transactions, in each case of clause (i) or
(ii), such that the voting stockholders of Roche immediately prior thereto, in the
aggregate, no longer own, directly or indirectly, beneficially or legally, at
least fifty percent (50%) of the outstanding voting securities or capital stock
of the surviving entity following the closing of such merger, consolidation,
other transaction or series of transactions.

 

1.8                                 “Combination Product” means any product
containing both an ingredient that causes it to be considered a Licensed
Product and one or more other therapeutically active ingredients.

 

1.9                                 “Commercialization Term” means the period
commencing on the Effective Date and ending on the earliest of (a) the
Reversion Effective Date; (b) the Put Right Effective Date; and (c) if
Roche does not exercise the Roche Put Right and the Exercise Period ends
without PDL exercising the Transplant Reversion, the date Roche ceases to sell
Daclizumab in every country in the Roche Territory, as permitted under this
Amended and Restated Worldwide Agreement.

 

1.10                           “Controlled” means, with respect to any
intellectual property right, that the party has a license to such intellectual
property right and has the ability to grant to the other party a sublicense to
such intellectual property right as provided for herein without violating the
terms of any agreement or other arrangements with any Third Party existing at
the time such party would be first required hereunder to grant the other party
such sublicense.

 

1.11                           “Cost of Goods” means the manufacturing
cost of either (a) unformulated bulk Daclizumab, or (b) finished
Daclizumab product made from unformulated bulk, as the case may be, calculated
in accordance with internal cost accounting methods consistently applied by a
party for its other biologics pharmaceutical products, provided that such
methods comply with [*]. 
Cost of Goods shall include [*]. As used in this Amended and Restated
Worldwide Agreement, the Cost of Goods shall not exceed [*]

 

1.12                           “Cover” (including variations thereof such
as “Covering” or “Covered”), means that the manufacture, use, sale, offer for
sale, or importation of a particular product would infringe a Valid Claim of a
patent in the absence of rights under such patent.  The determination of
whether a particular product is Covered by particular Valid Claims shall be
made on a country-by-country basis.

 

3

 

1.13                           “Daclizumab” means any product that
contains humanized anti-Tac (as defined under “Field”).

 

1.14                           “Daclizumab Assets” means all assets owned by Roche or its
Affiliates and relevant solely to the development or commercialization of
Daclizumab, other than the Trademarks and the Roche Owned Patents. 
Daclizumab Assets include, without limitation:

 

(a)                                  domain
names used in connection with the sale or promotion of Daclizumab;

 

(b)                                 all
then current promotional materials, including brochures, leave-behind
materials, product fact sheets, advertisements in all media;

 

(c)                                  all
then current packaging art copy, and all trade dress rights thereto;

 

(d)                                 rights
to any “look and feel” of any materials referenced in (a) through (c) above
and used in connection with the marketing, sale or promotion of Daclizumab and
any and all copyrights or other intellectual property rights appurtenant
thereto;

 

(e)                                  all
then current sales training materials and medical education materials;

 

(f)                                    copies
of market research surveys, analyses, and reports;

 

(g)                                 then
current customer lists, sales records, lists of distributors;

 

(h)                                 regulatory
filings, INDs, agreements related to physician sponsored INDs (to the extent
assignable), CTXs, BLAs, and foreign equivalents of the foregoing, and all
associated communications with regulatory authorities in the Roche Territory
(excluding manufacturing approvals); and

 

(i)                                     then
current contracts with managed care groups, hospitals, transplant centers,
pharmaceutical benefit managers, distributors and other similar Third Parties.

 

1.15                           “Excluded Field” means [*] that (a) [*] to the [*] of [*], (b) [*] the [*]
of [*], and (c) may also [*]. 
The Parties agree that Daclizumab is not in the Excluded Field.

 

1.16                           “Excluded Product” means any product in the
Excluded Field, including any Combination Product, that contains an [*] that was [*] by [*] on
behalf of [*] pursuant to the [*]. [*]
shall be deemed to be an Excluded Product.

 

1.17                           “Exercise Period” has the meaning set forth
in Section 5.2(a).

 

1.18                           “FDA” means the United States Food and Drug
Administration and any successor agency thereto, and/or any equivalent foreign
governmental agency, depending on the context.

 

4

 

1.19                           “Field” means any humanized or chimeric
antibody that binds to IL-2R, where “humanized” means a genetically engineered
combination of a substantially human framework region and constant region, and
complementarity determining regions from non-human antibodies, and where “chimeric”
means a genetically engineered combination of human constant region and
non-human variable region.  “Antibodies
in the Field” means humanized and chimeric antibodies that bind to
IL-2R.  It is believed that these Antibodies in the Field may be useful
for therapeutic, diagnostic, imaging and similar purposes.  It is
understood that the Field includes, but is not limited to, that certain
humanized murine monoclonal antibody prepared against the p55 component of IL-2R
(“humanized anti-Tac”).
Furthermore, the Field includes, but is not limited to, all improvements
relating to humanized anti-Tac, including without limitation modifications in
structure introduced by genetic engineering, or by chemical or enzymatic
cleavage.  Also included within the Field shall be alternate hosts for
producing humanized anti-Tac, methods for purification, formulations
incorporating humanized anti-Tac, and uses and methods of use for humanized
anti-Tac in human medicine.

 

1.20                           “Joint Inventions” means any inventions in
the Field, whether patented or not, that are jointly made during the period
beginning on January 31, 1989 and continuing until the end of the
Commercialization Term by at least one (1) PDL employee or person
contractually required to assign or license patent rights covering such
inventions to PDL and at least one (1) Roche-Nutley or F. Roche employee
or person contractually required to assign or license patent rights covering
such inventions to Roche-Nutley or F. Roche.

 

1.21                           “Licensed Product” means any product, other
than an Excluded Product, in the Field, including any Combination Product, the
making, importation, use, offer for sale, or sale of which utilizes Roche
Know-How, Roche Patents, or Joint Inventions or would, in the absence of this
Amended and Restated Worldwide Agreement, infringe a Valid Claim of a Roche
Patent.  Daclizumab shall be deemed to be a Licensed Product.

 

1.22                           “Major Country” means the United States,
United Kingdom, France, Italy and Germany.

 

1.23                           “Other Indications” means all indications
other than Transplant Indications and Autoimmune Indications.

 

1.24                           “Other Licensed Products” means all Licensed
Products other than Daclizumab.

 

1.25                           “PDL Adjusted Gross Sales” means the gross
invoice price of Daclizumab sold or otherwise disposed of for consideration in
the Roche Territory by PDL, its Affiliates or sublicensees (other than Roche
and its Affiliates hereunder) to independent Third Parties not an Affiliate of
the seller, reduced by the following amounts: (a) the amounts actually
allowed as volume or quantity discounts, rebates, price reductions, returns
(including withdrawals and recalls); and (b) sales, excise and turnover
taxes imposed directly on and actually paid by PDL, its Affiliates or
sublicensees.

 

5

 

When calculating the PDL
Adjusted Gross Sales, the amount of such sales in foreign currencies shall be
converted into U.S. dollars at the average rate of exchange at the time for the
applicable calendar quarter in accordance with PDL’s then-current standard
practices.

 

In the case of
Combination Products for which Daclizumab and each of the other therapeutically
active ingredients contained in the Combination Product have established market
prices when sold separately, PDL Adjusted Gross Sales shall be determined by
multiplying the PDL Adjusted Gross Sales for each such Combination Product by a
fraction, the numerator of which shall be the established market price for the
form and formulation of Daclizumab contained in the Combination Product, and
the denominator of which shall be the sum of the established market prices for
such form and formulation of Daclizumab plus the other active ingredients
contained in the Combination Product.  When such separate market prices are
not established, then the parties shall negotiate in good faith to determine
the method of calculating PDL Adjusted Gross Sales for Combination Products.

 

If PDL or its Affiliates
or sublicensees receive non-cash consideration for Daclizumab sold or otherwise
transferred to an independent Third Party not an Affiliate of the seller or
transferor, the fair market value of such non-cash consideration on the date of
the transfer as known to PDL, or as reasonably estimated by PDL if unknown,
shall be deemed the PDL Adjusted Gross Sales for such Daclizumab sold or
otherwise transferred.

 

1.26                           PDL Know-How” means, except as otherwise
set forth in this Section 1.26, all inventions, discoveries, trade
secrets, information, experience, data, formulas, procedures and results in the
Field, and improvements thereon, including any information regarding the
physical, chemical, biological, toxicological, pharmacological, clinical, and
veterinary data, dosage regimens, control assays and specifications of
Daclizumab (collectively, “Know-How in the
Field”), that is owned or Controlled by PDL or its Affiliates as of
the Effective Date or that is developed or Controlled by PDL or its Affiliates
during the term of this Amended and Restated Worldwide Agreement, and which
Know-How in the Field is reasonably required or useful for manufacturing, using
or selling Daclizumab; provided, however, that PDL Know-How excludes any
Know-How in the Field of any kind concerning generic methods of manufacturing,
designing, developing or preparing antibodies including, but not limited to,
methods of humanizing antibodies, methods of reducing the immunogenicity of
antibodies, and methods of increasing the affinity of antibodies.

 

1.27                           “PDL Net Sales” means the amount determined
by deducting [*] from PDL Adjusted
Gross Sales to cover all other expenses or discounts, including but not limited
to cash discounts, custom duties, transportation and insurance charges and
other direct expenses, to the extent not already deducted from the amount
invoiced.

 

1.28                           “PDL Patents” means all patent applications
owned or Controlled by PDL alone or with a Third Party (“Sole PDL Patents”) and all patent
applications resulting from Joint Inventions (“Joint
Roche-PDL Patents”) Covering Daclizumab, which are filed prior to or
during the term of the 1989 Agreements, the 1999 Agreements or this Amended and
Restated Worldwide Agreement in the United States or any foreign jurisdiction,
including any addition,

 

6

 

continuation,
continuation-in-part or division thereof or any substitute application
therefor; any patent issued with respect to such patent application, any
reissue, extension or patent term extension of any such patent, and any
confirmation patent or registration patent or patent of addition based on any
such patent; and any other United States or foreign patent or inventor’s
certificate covering products in the Field.

 

1.29                           “PDL Sole Territory” means all countries of
the world, as listed in Appendix C (which the parties may agree to update from
time to time), with respect to which Roche has granted an exclusive license to
PDL, in connection with the previous return or reversion of Roche’s rights
under the 1999 Agreements.

 

1.30                           “Product Operating Committee” or “POC” has the meaning set forth in Section 6.2(a).

 

1.31                           “Put Exercise Fee” has the meaning set
forth in Section 5.3(b).

 

1.32                           “Put Right Effective Date” has the meaning
set forth in Section 5.3(a).

 

1.33                           “Queen et al. Patents” means those Sole PDL
Patents in the Territory claiming priority under 35 USC 120 to U.S. Patent
Application Serial No. 290,975, filed December 28, 1988.

 

1.34                           “Reasonable Diligence” means the same level
of effort used by Roche in developing, registering, marketing and selling its
own protein-based products that must be approved by the FDA before they can be
sold in the Roche Territory.  The parties acknowledge that Roche does not
develop, register, market and sell its own protein-based products in every
country within the Roche Territory, and it is understood that the exercise by
Roche of reasonable diligence shall be determined by judging its efforts in the
Roche Territory taken as a whole.

 

1.35                           “Regulatory Approval” means the granting of
all governmental regulatory approvals required, if any, for the sale of a
Licensed Product in a given country or jurisdiction within the Territory.

 

1.36                           “Reversion Effective Date” has the meaning
set forth in Section 5.2(b).

 

1.37                           “Reversion Exercise Fee” has the meaning
set forth in Section 5.2(c).

 

1.38                           “Roche Adjusted Gross Sales” means the
gross invoice price of Daclizumab sold or otherwise disposed of for
consideration by Roche, its Affiliates or sublicensees (other than PDL and its
Affiliates hereunder) to independent Third Parties not an Affiliate of the
seller, reduced by the following amounts: (a) the amounts actually allowed
as volume or quantity discounts, rebates, price reductions, returns (including
withdrawals and recalls); and (b) sales, excise and turnover taxes imposed
directly on and actually paid by Roche, its Affiliates or sublicensees.

 

7

 

When calculating the
Roche Adjusted Gross Sales, the amount of such sales in foreign currencies
shall be converted into U.S. dollars at the average rate of exchange at the
time for the applicable calendar quarter in accordance with Roche’s
then-current standard practices.

 

In the case of
Combination Products for which Daclizumab and each of the other therapeutically
active ingredients contained in the Combination Product have established market
prices when sold separately, Roche Adjusted Gross Sales shall be determined by
multiplying the Roche Adjusted Gross Sales for each such Combination Product by
a fraction, the numerator of which shall be the established market price for
the form and formulation of Daclizumab contained in the Combination Product,
and the denominator of which shall be the sum of the established market prices
for such form and formulation of Daclizumab plus the other active ingredients contained
in the Combination Product.  When such separate market prices are not
established, then the parties shall negotiate in good faith to determine the
method of calculating Roche Adjusted Gross Sales for Combination Products.

 

If Roche or its Affiliates or sublicensees receive non-cash
consideration for Daclizumab sold or otherwise transferred to an independent
Third Party not an Affiliate of the seller or transferor, the fair market value
of such non-cash consideration on the date of the transfer as known to Roche,
or as reasonably estimated by Roche if unknown, shall be deemed the Roche
Adjusted Gross Sales for such Daclizumab sold or otherwise transferred.

 

1.39                           “Roche Commercialization Activities” has
the meaning set forth in Section 4.1(a).

 

1.40                           “Roche Controlled Patents” means all patent
applications Controlled by Roche or its Affiliates and not Controlled by PDL or
its Affiliates Covering inventions in the Field that are filed prior to or
during the term of this Amended and Restated Worldwide Agreement in the United
States or any foreign jurisdiction, including any addition, continuation,
continuation-in-part or division thereof or any substitute application
therefor; any patent issued with respect to such patent application, any
reissue, extension or patent term extension of any such patent, and any
confirmation patent or registration patent or patent of addition based on any
such patent; and any other United States or foreign patent or inventor’s
certificate covering inventions in the Field. 
Roche Controlled Patents are, specifically, those listed on Schedule 2.8(b).

 

1.41                           “Roche Inventions” means any inventions in
the Field that are made prior to or during the term of this Amended and
Restated Worldwide Agreement by employees of Roche or persons contractually
required to assign or license patent rights covering such inventions to Roche.

 

1.42                           “Roche Know-How” means all Know-How in the
Field that is owned or Controlled by Roche or its Affiliates as of the
Effective Date, or that is developed or Controlled by Roche or its Affiliates
during the Commercialization Term and which Know-How in the Field is reasonably
required or useful for seeking registration of, manufacturing, using or selling
Daclizumab, as the case may be, provided, however, that this portion of Roche
Know-How excludes any Know-How in the Field of any kind concerning generic
methods of manufacturing,

 

8

 

designing,
developing or preparing antibodies including, but not limited to, methods of
humanizing antibodies, methods of reducing the immunogenicity of antibodies,
and methods of increasing the affinity of antibodies.  For clarity, Roche Know-How includes all
Know-How in the Field provided to PDL by Roche or its Affiliates under the 1989
Agreements and 1999 Agreements.

 

1.43                           “Roche Licensed Know-How” means that portion
of Roche Know-How that is reasonably required or useful for seeking
registration of, manufacturing, using or selling Daclizumab for Autoimmune
Indications or any Other Indication, but shall not include [*].

 

1.44                           “Roche Licensed Patents” means those Roche
Patents that Cover in whole or in part the manufacture, importation, offer for
sale or sale of Daclizumab or any Other Licensed Products, or the use of
Daclizumab or any Other Licensed Products in Autoimmune Indications or Other
Indications.

 

1.45                           “Roche Net Sales” means the amount
determined by deducting [*] from
Roche Adjusted Gross Sales to cover all other expenses or discounts, including
but not limited to cash discounts, custom duties, transportation and insurance
charges and other direct expenses, to the extent not already deducted from the
amount invoiced.  Notwithstanding the foregoing, “Roche Net Sales of Excluded Products” shall
be calculated in the same manner as Roche Net Sales, except that for the
purpose of such calculation, Roche Adjusted Gross Sales shall be based on the
gross invoice price of Excluded Products.

 

1.46                           “Roche Owned Patents” means all patent
applications owned by Roche or its Affiliates (“Sole Roche Patents”) alone or with a Third Party, and all
patent applications resulting from Joint Inventions (“Joint Roche-PDL Patents”) covering inventions in the Field
that are filed prior to or during the term of this Amended and Restated
Worldwide Agreement in the United States or any foreign jurisdiction, including
any addition, continuation, continuation-in-part or division thereof or any
substitute application therefor; any patent issued with respect to such patent
application, any reissue, extension or patent term extension of any such
patent, and any confirmation patent or registration patent or patent of
addition based on any such patent; and any other United States or foreign
patent or inventor’s certificate covering inventions in the Field.  Roche
Owned Patents as of the Effective Date are, specifically, those listed on Schedule 2.8(a).

 

1.47                           “Roche Patents” means both the Roche Owned
Patents and the Roche Controlled Patents.

 

1.48                           “Roche Products” means Daclizumab and any
Excluded Products.

 

1.49                           “Roche Put Right” has the meaning set forth
in Section 5.3(a).

 

1.50                           “Roche Territory” means, collectively, (a) the
United States of America (“U.S.”
or “U.S.A.” or “United States”) and its territories and
possessions where the patent laws of the

 

9

 

United
States are in force and (b) all other countries in the Territory,
excluding the PDL Sole Territory (the “Roche
ROW Territory”).

 

1.51                           “Territory” means all the countries of the
world.

 

1.52                           “Third Party” means any person or entity
other than PDL, Roche, and their respective Affiliates.

 

1.53                           “Third Party License” means (a) any of
the license agreements set forth on Appendix B that were entered into by either
party, prior to the Effective Date, in order for Roche or PDL to manufacture,
use, import, offer for sale or sell Daclizumab or (b) any license
agreement entered into with a Third Party by either party in accordance with Section 7.4(b).

 

1.54                           “Trademarks” means the trademark “Zenapax®,”
and all trademark registrations and applications therefor, and all goodwill
associated therewith, and all other trademarks owned by Roche (except for any
Roche housemarks or trade names) and used in connection with the sale or
promotion of Daclizumab in the Roche Territory.

 

1.55                           “Transplant Foreign Filing Expenses” means
ex parte out-of-pocket expenses (a) incurred by PDL after January 31,
1989, but prior to the Effective Date, in connection with the prosecution and
maintenance in the Roche ROW Territory of patent applications and patents
included within the PDL Patents or Joint Roche-PDL Patents and (b) reimbursed
by Roche pursuant to Section 7.2(a) of the 1999 PDL/Roche Agreement
or Section 5.3(a) of the F. Roche Agreement.

 

1.56                           “Transplant Indications” means all
indications that involve the suppression of rejection of transplanted organs,
bone marrow or other tissue, including, without limitation, solid organ
transplantation (including tolerance induction and xenotransplantation), bone
marrow transplantation, graft versus host disease and cell
transplantation.  In any event, if a given indication satisfies the
criteria for both an Autoimmune Indication and a Transplant Indication, such
indication shall be deemed a Transplant Indication and not an Autoimmune
Indication, provided that an Autoimmune Indication shall not be deemed a
Transplant Indication merely because it may cause the need for a transplant
(e.g., Type I diabetes, even if it causes the need for an organ transplant).

 

1.57                           “Transplant Reversion” has the meaning set
forth in Section 5.2(a).

 

1.58                           “Valid Claim” means a claim in any issued
patent that has not been disclaimed or held unenforceable or invalid by a
decision of a court or governmental agency of competent jurisdiction by a
decision beyond right of review.

 

II.  LICENSE GRANTS

 

2.1                                 License
Grant to PDL On Effective Date.

 

10

 

(a)                                  Subject
to the terms and conditions of this Amended and Restated Worldwide Agreement,
Roche grants to PDL and to PDL’s Affiliates the worldwide right and license
under the Roche Licensed Know-How and Roche Licensed Patents, to (i) develop,
use, market, promote, and detail Daclizumab in the Territory solely for use in
Autoimmune Indications and/or the Other Indications, and (ii) sell and
offer for sale Daclizumab in the Territory, under the AI Trademarks.

 

(b)                                 The
licenses set forth in Sections 2.1(a)(i) and 2.1(a)(ii) shall be
exclusive (even as to Roche) with respect to the Roche Licensed Know-How and
Roche Licensed Patents that Roche or its Affiliate solely owns or has an
exclusive license.  With respect to the Roche Licensed Know-How and Roche
Licensed Patents to which Roche or its Affiliate has a non-exclusive license,
such licenses shall be sole, non-exclusive licenses.  With respect to the
Roche Licensed Know-How and Roche Licensed Patents that Roche or its Affiliate
jointly owns, such licenses shall be sole licenses under Roche’s interest in
such Roche Licensed Know-How and Roche Licensed Patents.  As used in
this Section 2.1(b) a “sole” license means that the Roche will not
grant to any Third Party a license that overlaps with the scope of the licenses
granted to PDL under Section 2.1(a).

 

(c)                                  Roche
grants to PDL and to PDL’s Affiliates, the nonexclusive right under the Roche
Licensed Know-How and Roche Licensed Patents to make, have made, and import
Daclizumab.

 

(d)                                 PDL
and its Affiliates may sublicense the rights and licenses granted to them under
Sections 2.1(a) and (c) to any Affiliate or Third Party, with the
right to further sublicense; provided, however, that without Roche’s written
consent, PDL shall not have the right to sublicense, during the
Commercialization Term, any of the [*]
rights or licenses in Section 2.1(a) to any other entity, that is, as
of the time of such sublicensing, [*]
in the [*] (in at least one [*] with [*]),
or [*] in the [*] any [*]
for the [*] of [*] in any [*].  It is expressly
understood and agreed by Roche that PDL shall have the right to sublicense its
rights under Sections 2.1(a) and (c) to [*].  Notwithstanding
the preceding limitation on sublicensing, PDL and its Affiliates may use Third
Party distributors in accordance with their customary practices.

 

(e)                                  Subject
to the terms and conditions of this Amended and Restated Worldwide Agreement,
Roche grants to PDL and to PDL’s Affiliates a worldwide right and license (or
sublicense, as the case may be) under the Roche Licensed Know-How received by
PDL pursuant to the 1989 Agreements, 1999 Agreements or Section 2.4
hereof, the Roche Controlled Patents and only those Roche Owned Patents listed
in Schedule 2.8(a), to (i) develop, use, market, promote, and detail
Other Licensed Products in the Territory solely for use in Autoimmune
Indications and/or the Other Indications; (ii) sell and offer for sale
Other Licensed Products in the Territory; and (iii) to make, have made,
and import Other Licensed Products in the Territory.

 

(f)                                    The
license set forth in Section 2.1(e) shall be exclusive (even as to
Roche) with respect to the Roche Controlled Patents that Roche or its Affiliate
solely owns or has an exclusive license. 
With respect to the Roche Controlled Patents to which Roche or its
Affiliate has a non-exclusive license, such license shall be a sole,
non-exclusive license.  With respect to

 

11

 

the Roche Owned Patents
that Roche or its Affiliate jointly owns, such license shall be a sole license
under Roche’s interest in such Roche Owned Patents.  PDL and its Affiliates shall have the right
freely to sublicense, through multiple tiers, the rights and licenses granted
to them under Section 2.1(e). 
Notwithstanding anything to the contrary in Section 2.1(e), the
license to Roche Licensed Know-How shall be non-exclusive.  Roche hereby covenants that, until the
termination, pursuant to Section 2.2(a), of the license set forth in Section 2.1(e),
it will not grant to any Third Party any right or license under the
(i) Roche Controlled Patents to which Roche or its Affiliate has a
non-exclusive license or (ii) Roche Owned Patents that Roche or its
Affiliate jointly owns,
to (A) develop, use, market, promote, and detail Other Licensed Products
in the Territory for use in Autoimmune Indications and/or the Other
Indications; (B) sell and offer for sale Other Licensed Products in the
Territory; and (C) make, have made, and import Other Licensed Products in
the Territory.

 

(g)                                 If
PDL wishes to receive a license with respect to Other Licensed Products in
Autoimmune Indications and/or Other Indication, under any Roche Owned Patents
that are not listed in Schedule 2.8(a), it shall [*] and Roche shall [*].

 

2.2                                 License
Grant to PDL On Reversion Effective Date or Put Right Effective Date.

 

(a)                                  Effective
only on the Reversion Effective Date or the Put Right Effective Date, Roche
hereby grants the following license to PDL: subject to the terms and conditions
of this Amended and Restated Worldwide Agreement, Roche grants to PDL and to
PDL’s Affiliates a worldwide right and license under the Roche Know-How and
Roche Patents, to develop, use, manufacture, have manufactured, market,
promote, import, offer for sale, sell and have sold Daclizumab and all Other
Licensed Products in the Field and in the Territory.  On the effectiveness
of the license set forth in this Section 2.2(a), the licenses granted in Section 2.1(a),
(c) and (e) shall terminate. 
PDL and its Affiliates shall have the right freely to sublicense, with
the right to further sublicense, the right and license granted to them under
this Section 2.2(a).

 

(b)                                 For
Daclizumab, the license set forth in Section 2.2(a) shall be
exclusive (even as to Roche) with respect to the Roche Know-How and Roche
Patents that Roche or its Affiliate solely owns or has an exclusive
license.  With respect to the Roche
Know-How and Roche Patents to which Roche or its Affiliate has a non-exclusive
license, the license set forth in Section 2.2(a) shall be a sole,
non-exclusive license.  With respect to
the Roche Know-How and Roche Patents that Roche or its Affiliate jointly owns,
the license set forth in Section 2.2(a) shall be a sole license under
Roche’s interest in such Roche Know-How and Roche Patents.  Roche hereby covenants that it will not grant
to any Third Party any right or license, under (i) the Roche Know-How and
Roche Patents to which Roche or its Affiliate has a non-exclusive license or (ii) the
Roche Know-How and Roche Patents that Roche or its Affiliate jointly owns, to develop, use, manufacture,
have manufactured, market, promote, import, offer for sale and sell Daclizumab
in the Field and in the Territory.

 

(c)                                  For
Other Licensed Products, the license set forth in Section 2.2(a) shall
be non-exclusive.  Notwithstanding the
preceding sentence, Roche hereby covenants that it will not

 

12

 

grant
licenses to any Third Party under the Roche Patents to make, have made, use,
sell, offer for sale or import any Other Licensed Product.

 

2.3                                 Certain
[*] To PDL of [*]
Intellectual Property.  PDL acknowledges and understands that [*] are [*] as to [*] (a) Roche has received, prior to the Effective
Date, a [*] license under certain [*] of [*] that [*] cover the manufacture, use, importation, offer for sale
or sale of humanized antibodies against IL-2R, including Daclizumab and any
Other Licensed Products, and/or (b) [*] Roche has
the right to [*] such licensed [*], to the extent granted to Roche.   In the event that the parties agree that
Roche is [*] such license [*],
PDL shall be deemed to have been [*] pursuant to
the [*], as applicable, and such [*] will be deemed part of the [*]
licensed thereunder.  In the event that the parties agree that Roche [*] such rights, and/or that Roche [*]
such rights to PDL as part of the [*], Roche
agrees to use diligent efforts to itself secure or assist PDL in securing from [*], a license to such [*] from [*], which license rights will be documented under a
separate agreement from this Amended and Restated Worldwide Agreement.  If [*] obtains [*] consent to the terms of such separate agreement, then it
shall be deemed a [*] and [*] shall [*] the costs
of such license rights, in the manner and as set forth in Section 7.4, [*] the [*] the costs
and royalties owed to [*] shall be as
follows: [*] shall bear [*]
of the cost of such license rights and [*] shall bear [*] of the costs of such license rights; and provided,
however, that this addition or offset shall not cause the amount to be paid by
PDL to Roche pursuant to Section 7.2(c), in the aggregate and after
payment to [*], to be less than [*] of [*] in [*].  On either the [*]
or the [*], [*]
shall be [*] responsible for paying the
prospective costs of such license from that date forward, as further detailed
in Section 7.4(e).  If the Exercise
Period expires without [*] or [*], then the parties will proceed as detailed in Section 7.4(f) with
respect to Third Party Licenses.

 

2.4                                 Transfer
of Roche Licensed Know-How to PDL. Promptly after the Effective Date, Roche
shall transfer all Roche Licensed Know-How to PDL in the manner in which and to
the extent to which the parties, prior to the Effective Date, have transferred
know-how under the Joint Development Committee or the Joint Commercialization
Committee under the 1999 Agreements. 
Thereafter, and until the Reversion Effective Date or the Put Right Effective
Date, if Roche develops or gains Control of additional Roche Licensed Know-How,
Roche shall promptly provide such additional Roche Licensed Know-How to PDL
through the parties’ participation in the POC. 
On either the Reversion Effective Date or the Put Right Effective Date,
Roche shall transfer to PDL any Roche Know-How not previously transferred to
PDL, including in particular, any Roche Know-How related to the Transplant
Indications.

 

2.5                                 License
Grants to Roche.

 

(a)                                  Subject
to the terms and conditions of this Amended and Restated Worldwide Agreement,
PDL grants to Roche and to Roche’s Affiliates, during the Commercialization
Term, the exclusive (even as to PDL) right and license under the PDL Know-How
and PDL Patents to (i) market, promote, and detail Daclizumab in the Roche
Territory solely for use in the Transplant Indications, and (ii) to sell
and offer for sale Daclizumab in the Roche Territory under the
Trademarks.   In addition, PDL
grants to Roche and to Roche’s Affiliates, the nonexclusive right under the PDL
Know-How and PDL Patents to make, have made and import

 

13

 

Daclizumab,
but only to the extent reasonably necessary for Roche to carry out its rights
and obligations under this Amended and Restated Worldwide Agreement. 
Roche may sublicense the rights and licenses granted to Roche under this Section 2.5,
subject to PDL’s written consent, which consent PDL may not unreasonably
withhold.  It shall be deemed reasonable for PDL to withhold consent with
respect to sublicense by Roche of any of the rights or licenses to any other
entity that is [*] (in at least
one [*] with [*]), or [*]
in a [*] any [*] for the [*] of any [*]. 
Notwithstanding the preceding sentence, Roche and its Affiliates may use Third
Party distributors in accordance with their customary practices. All
sublicenses granted by Roche or its Affiliates of the licenses set forth in
this Section 2.5(a) shall automatically terminate on the Reversion
Effective Date or Put Right Effective Date.

 

(b)                                 Subject
to the terms and conditions of this Amended and Restated Worldwide Agreement,
in particular the restrictions set forth in Section 3.1(b), PDL grants to
Roche and to Roche’s Affiliates the exclusive (even as to PDL) right and
license, including the right to grant sublicenses, under the PDL Know-How and
PDL Patents to use, develop, make, have made, sell, offer for sale, and import
the Excluded Products in the Roche Territory; provided, however that the
license granted under this Section 2.5(b) under [*] shall be nonexclusive.

 

(c)                                  PDL
hereby covenants that, until the expiration of [*], it will not make, have made, use, sell, offer for sale or
import any product in the Excluded Field Covered by [*] in the Roche Territory, and it will not grant to any Third
Party any right or license under [*]
the right to make, have made, use, sell, offer for sale or import any product
in the Excluded Field in the Roche Territory.

 

(d)                                 If
during the term of this Amended and Restated Worldwide Agreement, Roche or its
Affiliate challenges the validity or enforceability in any jurisdiction of [*], then PDL shall have the right to [*] to Roche under this Amended and Restated Worldwide
Agreement to PDL Patents that include [*].

 

(e)                                  Roche
hereby covenants that it shall not, nor shall it cause any Affiliate or
sublicensee to:

 

(i)                                     knowingly
use or practice, directly or indirectly, any PDL Know-How or PDL Patents for
any other purposes other than those expressly permitted by this Amended and
Restated Worldwide Agreement or any other written agreements in the Field
between the Parties currently in existence and not expressly superceded by this
Amended and Restated Worldwide Agreement, or which may later be entered into by
the Parties;

 

(ii)                                  market,
promote, detail, sell or offer for sale Daclizumab, during the
Commercialization Term, in any manner outside the scope of the licenses set
forth in Section 2.5(a), including, in particular, for any use in the
treatment of Autoimmune Indications or Other Indications; or

 

(iii)                               use,
develop, make, have made, sell, offer for sale or import Excluded Products in
any manner outside the scope of the licenses set forth in Section 2.5(b).

 

14

 

(f)                                    PDL
hereby covenants that it shall not, nor shall it cause any Affiliate or sublicensee
to market, promote, detail, sell or offer for sale Daclizumab, during the
Commercialization Term, in any manner outside the scope of the licenses set
forth in Sections 2.1 and 2.2.

 

2.6                                 Identification
of the Queen et al Patents.  Set forth on Appendix A is a list
identifying patents or patent applications that comprise the Queen et al.
Patents in the Roche Territory as of the Effective Date.   If there
are any changes, PDL shall update this list by delivering a supplement to Roche
no less frequently than once per year during the term of this Amended and
Restated Worldwide Agreement.

 

2.7                                 Cooperation
Regarding Third Party Licenses.   In the event Roche negotiates
and intends to enter into a license agreement with a Third Party with respect
to the right to make, use, sell, import, offer for sale or sale of any [*] under such Third Party’s intellectual property, it shall
so inform PDL and provide PDL the opportunity to participate in such
negotiations and enter into such license agreement or take a sublicense
thereunder with respect to [*], on such
terms as are agreed by the parties.

 

2.8                                 Roche
Representations, Warranties and Covenants.  Roche hereby represents
and warrants as of the Effective Date as follows:

 

(a)                                  To
the best of Roche’s knowledge, Schedule 2.8(a) identifies the Roche
Owned Patents existing as of the Effective Date.  To the extent that it is not prohibited from
doing so, Roche agrees to make available to PDL copies of such Roche Owned
Patents promptly following the Effective Date. Roche covenants that, to the
extent any additional Roche Owned Patents are identified by Roche subsequent to
the Effective Date and to the extent that it is not prohibited from doing so,
it shall promptly inform PDL, and Schedule 2.8(a) shall be revised to
so reflect such additional Roche Owned Patents.

 

(b)                                 Schedule 2.8(b) identifies
all of the license agreements under which Roche has rights to Roche Controlled
Patents existing as of the Effective Date (other than the license rights from
Genentech referred to in Section 2.3). 
Roche agrees to make available to PDL copies of such license agreements
pursuant to which the Roche Controlled Patents were licensed to Roche promptly
following the Effective Date, to the extent not already in PDL’s possession and
to the extent that Roche has a right to do so. 
[*] further covenants that, where it is
not [*] to [*]
to [*] such [*],
it will [*] to [*]
from the [*] its [*]
to do so. Roche shall not, without the prior written consent of PDL, terminate
any agreement that grants Roche a license under a Roche Controlled Patent.  Roche covenants that, to the extent any
additional licenses under which Roche has rights to Roche Controlled Patents
are identified by Roche or come into existence subsequent to the Effective
Date, Roche shall promptly inform PDL, and Schedule 2.8(b) shall be
revised to so reflect such additional licenses; provided, however, that in the
event any royalty or other payment is owed to the licensor of any such Roche
Controlled Patent [*] PDL, [*] shall not be responsible for any such royalty payments,
and [*] shall so notify [*] in writing and [*] shall have
a period of ninety (90) days to evaluate whether it desires that such [*] be included within the [*]

 

15

 

licensed
to [*] under [*]
and if so, the mechanism for payment to the [*]
thereunder.  Where [*]
elects not to [*] to such Roche Controlled
Patent, it agrees to [*]

 

(c)                                  Roche
has not granted any Third Party a license or other right that is currently in
effect under any of the Roche Owned Patents for any purpose.

 

(d)                                 To
Roche’s knowledge, Roche has complied with its obligation under 37 CFR §1.56(a) to
disclose to the United States Patent and Trademark Office, during the pendency
of each United States patent application included in the Roche Owned Patents,
information known to Roche to be material to the patentability of the pending
claims in such application.  None of the Roche Owned Patents is involved
in any interference or opposition proceeding, and, to Roche’s knowledge, no
such proceeding is being threatened with respect to any of the Roche Owned
Patents.

 

(e)                                  [*]

 

(f)                                    [*]

 

(g)                                 Roche
and its Affiliates have not granted to any Third Party in any Major Country,
any sublicense, under the license(s) to the PDL Know-How and PDL Patents that
Roche and its Affiliates received pursuant to the 1999 Agreements, to: (i) promote
and sell Daclizumab generally, and/or for use in Autoimmune Indications or the
Other Indications; or (ii) develop, make, use, import, offer for sale and
sell Other Licensed Products for any indication in the Field.  Roche shall, prior to the [*], disclose in writing to PDL all
sublicenses that Roche or its Affiliate have granted, under the PDL Know-How
and PDL Patents, to develop, make, use, import, promote, offer for sale and
sell Daclizumab and Other Licensed Products for any indication in the
Field.  If any such sublicenses exist at
such time, the parties, through the POC, will work together to [*] (including [*], where practicable) such sublicense.

 

(g)                                 Roche
covenants that, in the event that Roche [*] of the [*] of the [*] of [*], through whatever means, on PDL’s request, Roche will
within [*] days of such request,
meet and discuss with PDL the impact of such event on the relationship between
PDL and Roche at such time, and modify this Amended and Restated Worldwide
Agreement to the extent deemed appropriate by both parties.

 

2.9                                 Termination
of Certain Sublicenses.  If, prior to
the Effective Date, PDL and Roche or an Affiliate of Roche entered into any
agreement(s), other than the 1999 Agreements, wherein PDL granted Roche or such
Affiliate a sublicense with respect to Daclizumab or Other Licensed Product(s),
under any Third Party intellectual property rights licensed by PDL, then such
sublicenses are hereby terminated and replaced by the licenses set forth in Section 2.5.

 

16

 

III.  DEVELOPMENT; REGULATORY ISSUES

 

3.1                                 Development
by Roche.

 

(a)                                  Development
of Daclizumab.  Following the Effective Date, [*] after the Effective Date.  In addition, to the extent Roche receives any
data or other results of any clinical trials pursuant to ongoing physician
sponsored trials, Roche will update the POC with respect to such trial results
and data.  Further, Roche shall promptly
forward to PDL any requests for new [*] studies
involving Daclizumab that Roche receives after the Effective Date.

 

(b)                                 Development
of Excluded Products.  Roche shall be solely responsible, at its sole
cost and expense and at its sole discretion, for the non-clinical, clinical,
and regulatory development of any Excluded Product.  Notwithstanding the foregoing, it is
understood and agreed that [*] for
any indication other than [*]
without the written consent of PDL, such consent not to be unreasonably
withheld.  The Parties recognize that it
may be desirable to develop the Excluded Products for [*],
in which case the POC shall discuss and recommend to the parties whether [*]. 
Following the Effective Date, Roche shall use Reasonable Diligence in
proceeding with the development and registration of Excluded Products in the
Roche Territory, to the extent permitted under this Section 3.1(b).  If Roche fails to exercise such diligence,
PDL may terminate the license granted to Roche under Section 2.5(b), but
shall not be obligated to do so.

 

3.2                                 Development
by PDL.

 

(a)                                  General. 
Following the Effective Date, PDL shall be solely responsible, at its sole cost
and expense and at its sole discretion, for the non-clinical, clinical, and
regulatory development of Daclizumab for all indications in the Territory,
other than those trials referenced in Section 3.1(a), subject to the
restrictions set forth in Section 3.2(b).  All data and information
generated by PDL development activities pursuant to this Section 3.2(a) shall
be PDL Know-How.

 

(b)                                 Restriction
on PDL Development.  During the period commencing on the Effective
Date and ending at the end of the Commercialization Term, PDL agrees not to
pursue the clinical or regulatory development of Daclizumab for use in the [*] in the Roche Territory.

 

3.3                                 Assistance
by Roche.  At no cost to PDL (except as provided in the following
sentence), Roche will allow PDL to cross-reference Roche regulatory filings and
clinical data with respect to Daclizumab and will grant PDL reasonable access
during normal business hours to such regulatory filings and clinical
data.  To the extent Roche is required under applicable law, rule or
regulation, Roche, at PDL’s cost, shall promptly make all filings reasonably
required or useful to permit the use of the clinical materials, if any,
supplied pursuant to Section 4.5(a) (e.g., preparation and filing of
required technical reports, data summaries, or a regulatory dossier).

 

3.4                                 Adverse
Event Reporting.  Each party shall notify the other of all information
coming into its possession concerning any and all side effects, injury,
toxicity, pregnancy or sensitivity event associated with commercial or clinical
uses, studies, investigations or tests with Daclizumab, throughout the world,
whether or not determined to be attributable to Daclizumab (“Adverse Event Reports”).  The parties
shall each identify a person to coordinate the exchange of Adverse Event
Reports (“Report Coordinators”) so
as to enable timely reporting of such Adverse Event Reports to appropriate
governmental and regulatory authorities consistent with all

 

17

 

laws, rules and
regulations. The parties, through their Report Coordinators, have agreed in
writing on formal procedures for such exchange, which are embodied in the
PDL-Roche Procedure for the Exchange of Daclizumab Adverse Event Reports, dated
December 2000 (“Pharmacovigilance
Agreement”).  Promptly after the Effective Date, Roche and PDL
agree to cause their Report Coordinators (a) to review the
Pharmacovigilance Agreement and (b) to negotiate in good faith an
amendment to the Pharmacovigilance Agreement to reflect the terms of this
Amended and Restated Worldwide Agreement, if the Report Coordinators agree that
such an amendment is required.  Such Pharmacoviligance Agreement (as
amended, if applicable) shall survive the end of the Commercialization Term.

 

3.5                                 Copies
of Responses.  Within a reasonable time frame prior to submission of
responses to any regulatory authority on product safety issues regarding
Daclizumab, a copy of a near final draft response will be provided to the other
party for review.  Final copies of responses submitted to any regulatory
authority will be provided to the other party within five (5) business
days of document finalization.

 

3.6                                 Regulatory
Actions.  The party responsible to interact with regulators on a
specific safety issue regarding Daclizumab must communicate action requested by
regulators to the other party without delay.  Such actions may include,
for example, change in label, Dear Doctor letter, trial on hold for clinical
safety reasons and the like.

 

3.7                                 Other
Safety Issues.  Either party may request that specific safety issues
be discussed, and the parties will establish a Joint Safety Committee (“JDSC”), consisting of an equal number of
representatives from each party, for such purpose. JDSC discussion on such
issues will be for the purpose of advising each party concerning the collection
and evaluation of safety data, and responding to any significant safety issues
raised, or requests made, by regulatory authorities.

 

3.8                                 Registration. 
PDL shall notify Roche in writing if PDL determines that clinical trial results
for Daclizumab justify filing an Application.  Roche shall provide cross
reference letters reasonably required or useful to allow PDL to make any such
filing and to allow PDL to carry out without delay any related clinical trial
in the Territory.  PDL shall be responsible for preparing periodic reports
required by the FDA related to any such Applications and for timely filing such
periodic reports with the FDA.  Through the POC, each party shall advise
and consult with the other with respect to any significant issues or questions
raised by any regulatory authorities with respect to Daclizumab.

 

IV.  COMMERCIALIZATION AND MANUFACTURING

 

4.1                                 Commercialization
By Roche.

 

(a)                                  Commercialization
of Daclizumab by Roche.  The parties intend that, following the
Effective Date, Roche will continue to market and sell Daclizumab in the
Transplant Indications in the Roche Territory for the duration of the
Commercialization Term, under the Trademarks.  In particular, and without
limitation, during the Commercialization Term

 

18

 

and in
the Roche Territory, Roche shall be responsible, at its sole cost and as
permitted by applicable law, for (i) the marketing, promotion, and
detailing of Daclizumab for use in the Transplant Indications; (ii) accepting
and filling orders for Daclizumab received by it or its Affiliates, including
the distribution of Daclizumab to fill such orders; (iii) booking all
sales of Daclizumab attributable to such orders; and (iv) any other
activities reasonably related to Daclizumab that are permitted under the
license granted in Section 2.5(a) (the “Roche Commercialization Activities”).  As provided in Article VII,
Roche shall pay royalties to PDL on Roche Net Sales.

 

(b)                                 Commercialization
of Excluded Products by Roche.  Roche, its Affiliates, or sublicensees
shall be solely responsible for, at its or their sole cost and as permitted by
law, all aspects of the commercialization of Excluded Products in the Roche
Territory, including but not limited to the booking of all sales of Excluded
Products in the Roche Territory.  Roche shall use commercially diligent
efforts to develop and commercialize such Excluded Products. Following receipt
of regulatory approval, Roche shall use Reasonable Diligence in proceeding with
the marketing, promotion and sale of Excluded Products in the Roche
Territory.   If Roche fails to exercise such diligence, PDL may
terminate the license granted to Roche under Section 2.5(b), but shall not
be obligated to do so.  As provided in Article VII,
Roche shall pay royalties to PDL on Roche Net Sales of Excluded Products.

 

4.2                                 Commercialization
by PDL.

 

(a)                                  Commercialization
by PDL During Commercialization Term.  In the Roche Territory, PDL,
its Affiliates, or sublicensees shall have the right, but not the obligation,
at its or their sole cost and as permitted by law, to pursue all aspects of the
commercialization of Daclizumab and any Other Licensed Products, excluding the
Roche Commercialization Activities. 
Without limiting the generality of the foregoing, in the Roche Territory
and during the Commercialization Term, PDL, its Affiliates, or sublicensees
shall have the right, but not the obligation, to commercialize Licensed
Products in Autoimmune Indications and Other Indications and to commercialize
Other Licensed Products in any indication. 
In particular, in the Roche Territory, PDL shall be responsible, at its
sole cost and as permitted by applicable law, for (i) the marketing,
promotion, and detailing of Daclizumab for use in the Autoimmune Indications or
Other Indications; (ii) accepting and filling orders for Daclizumab
received by it or its Affiliates, including the distribution of Daclizumab to
fill such orders; (iii) booking all sales of Daclizumab attributable to
such orders; and (iv) any other activities reasonably related to
Daclizumab that are permitted under the license granted in Section 2.1.  As provided in Article VII, PDL shall
pay royalties to Roche on PDL Net Sales during the Commercialization Term.

 

(b)                                 Commercialization
by PDL Following Reversion Effective Date or Put Right Effective Date. 
Following the Reversion Effective Date or the Put Right Effective Date, PDL,
its Affiliates, or sublicensees shall have the right, but not the obligation,
to pursue, at its or their sole cost and as permitted by law, all aspects of
the commercialization of Daclizumab for all indications and for all Other
Licensed Products.  Following the
Reversion Effective Date or the Put Right Effective Date, in no event shall PDL
owe any royalties or any other compensation to

 

19

 

Roche
on sales of Daclizumab under Section 7.2(c) in the Territory, whether
by PDL, its Affiliates, or their sublicensees.

 

4.3                                 Commercialization
in the PDL Sole Territory.  PDL, its Affiliates, or sublicensees shall
have the right, but not the obligation, to pursue, at its or their sole cost
and as permitted by law, all aspects of the commercialization of Licensed
Products in the PDL Sole Territory, including but not limited to the booking of
all sales of Licensed Products in the PDL Sole Territory.

 

4.4                                 Pricing. 
As between the parties, PDL has the sole right to determine the price for
Daclizumab or any Other Licensed Product that it sells and distributes. 
As between the parties, Roche has the sole right to determine the price for any
Excluded Product that it sells and distributes, and the sole right during the
Commercialization Term to determine the price for Daclizumab that it sells and
distributes; provided, however, that until the earlier of (a) [*] or (b) PDL’s receipt of a [*]
from [*] having the power to grant [*], stating that [*] will grant [*] for Daclizumab in [*], Roche
shall provide PDL with [*] of any [*] in the [*] of Daclizumab and shall give [*] to any [*] or
[*] by PDL regarding the [*] of Daclizumab whether [*].  It is expressly understood that
following the date which is the earliest of (i) [*],
(ii) the receipt of [*] for
Daclizumab in [*], or (iii) the Reversion
Effective Date or Put Right Effective Date, the obligations of either party in
the foregoing sentence shall terminate, and PDL shall have sole control
regarding the price of Daclizumab that it sells and distributes.

 

4.5                                 Manufacturing. 
References to Roche in Sections 4.5(a) and 4.5(b) shall include
Roche, its Affiliates [*] and any
sublicensees manufacturing Daclizumab for Roche or its Affiliates.

 

(a)                                  Clinical
Manufacturing.

 

(i)                                     Supply. 
Subject to Section 4.5(a)(ii) and until [*],
Roche shall use commercially reasonable efforts to supply to PDL, [*] Daclizumab and placebo [*] for the development of Daclizumab for AI
in the [*] and [*]
specified by PDL.  Notwithstanding the above, Roche shall not be obligated
to [*] (A) any amount of Daclizumab
or placebo not in accordance with the AI Development plan, (B) a number of
units of placebo in excess of the units of Daclizumab supplied by Roche, or (C) any
form or formulation of Daclizumab [*] for the [*].  In the event PDL requests Daclizumab in a form or
formulation [*] for the [*],
Roche shall be obligated to supply to PDL [*]  All Daclizumab for the development of Daclizumab
for AI, regardless of form or formulation, shall be manufactured in accordance
with cGMPs and any other applicable regulatory or legal requirements. 
Through the POC, the parties shall meet periodically and discuss the
availability and timing of delivery of Daclizumab hereunder.  [*].  At PDL’s cost, PDL shall perform any bridging
studies that are necessary to enable PDL to use PDL-manufactured Daclizumab to
satisfy its clinical development requirements.  On [*],
and any time thereafter, PDL shall have the sole responsibility for the
manufacture of all Daclizumab and placebo required by PDL for the development
of Daclizumab for AI.

 

20

 

(ii)                                  Limitations. 
From the Effective Date until [*], Roche
shall supply to PDL [*] up to [*] of Daclizumab and an equivalent number of units of
placebo.   For supplies in excess of
such maximum amount [*], PDL shall
pay to Roche for such additional supplies an amount equal to [*] of [*] 
(including for [*]) for such supplies up to [*] of [*] per
gram].  Notwithstanding anything to the contrary herein, from the
Effective Date until [*], the [*] of Daclizumab that Roche shall be obligated to supply to
PDL shall be [*] of Daclizumab.

 

(iii)                               Procedures. 
During the period commencing on the Effective Date and ending on [*], PDL shall provide Roche with [*]
purchase orders, or such other procedures as the POC determines, each setting
forth the amount of Daclizumab and placebo to be supplied by Roche to
PDL.  To the extent that such purchase orders are consistent with the
terms and conditions of this Section 4.5, Roche agrees to honor all such
purchase orders and to deliver to PDL the amount of Daclizumab and placebo
specified therein as soon as practicable but in any event not later than [*] days following Roche’s receipt of each such purchase
order, or under such other procedures as the POC determines.

 

(b)                                 Commercial
Manufacturing.  Effective on the Effective Date and subject to Section 4.5(c) and
this Section 4.5(b), each party shall each be solely responsible for the
manufacturing of all Daclizumab necessary to satisfy the commercial
requirements of itself, its Affiliates and its sublicensees.  [*] shall keep [*] reasonably
informed, via the POC, regarding its progress in [*]
for its [*] to [*]
for [*]. 
As needed, the parties shall discuss and agree upon a plan of action to
address, among other things, [*] that could
arise if [*] progress in [*]
is delayed, which plan could include for [*] to supply
commercial requirements to [*] on a [*] basis.

 

(c)                                  Commercial
Manufacturing Following Exercise of the Roche Put Right.  In the event
that Roche exercises the Roche Put Right, [*] shall [*] to supply [*] for
Daclizumab in the Territory for the period commencing on [*] and ending on [*]
unless PDL has not, despite [*] to [*] for [*] to [*] Daclizumab for sale in the United States, [*] at such time, in which case such period shall end on [*] of such [*].  In
the event that Roche exercises the Roche Put Right, the parties shall negotiate
in good faith a separate supply agreement that shall provide for procedures for
PDL to submit to Roche [*] for
Daclizumab and Roche supplying Daclizumab thereafter at a price equal to [*].  Such procedures shall include PDL providing (i) [*] of [*] and (ii) firm
purchase commitments no less than [*] prior to
the time the order must be delivered to [*] by [*].

 

4.6                                 Roche
Diligence.  Following the Effective Date, Roche shall use Reasonable
Diligence in proceeding with the manufacturing, marketing and sale of Daclizumab
for use in the Transplant Indications in the Territory as contemplated by this
Amended and Restated Worldwide Agreement, and in a manner comparable to its
conduct of the manufacturing, marketing and sale of Daclizumab [*] during the [*] prior to the Effective Date.  If Roche fails to
exercise such diligence, PDL may exercise its rights hereunder pursuant to Section 13.3
below, but shall not be obligated to do so. Roche’s diligence obligations under
this Section 4.6 shall expire on, (i) if PDL exercises the Transplant
Reversion or Roche exercises the Roche Put Right, the completion of all
activities and undertakings set forth in Sections 5.4(b), (c), (e) and
(f), or (ii) if the Exercise Period expires without PDL exercising the
Transplant Reversion.  In the event of a
dispute as to whether Roche has used Reasonable Diligence, the party that loses
on this issue

 

21

 

in an
arbitration brought pursuant to Article XV shall reimburse all of the
other party’s arbitration expenses, including reasonable attorneys’ fees
relating to such arbitration.

 

V.  PDL RIGHT TO ACQUIRE TRANSPLANT BUSINESS FROM
ROCHE

 

5.1                                 General.  The parties intend that, subject to
the terms and conditions of this Amended and Restated Worldwide Agreement, the
commercialization of Daclizumab in the Transplant Indications in the Roche
Territory will continue to be an exclusive Roche responsibility unless and
until PDL decides to undertake commercialization of Daclizumab in the
Transplant Indications under the terms provided in this Article V. 
Subject to the limitations set forth below, PDL shall have the option to
terminate Roche’s rights with respect to Daclizumab, which, if exercised, would
allow PDL to replace Roche as the party responsible for the promotion, sales,
distribution and manufacturing of Daclizumab for use in the Transplant
Indications in the Roche Territory.  In the event that PDL exercises such
option, PDL shall pay an exercise fee as set forth in Section 5.2(c) below. 
In addition, Roche shall have the right to “put” to PDL the rights to
commercialize Daclizumab in the Roche Territory prior to PDL’s exercise of such
option and payment of the exercise fee, as provided in Section 5.3 below.

 

5.2                                 PDL
Transplant Reversion.

 

(a)                                  Grant;
Exercise Period.  PDL is hereby granted the right, subject to the
terms of this Section 5.2(a), to terminate Roche’s license rights under Section 2.5
for Daclizumab (the “Transplant Reversion”). 
Such right may be exercised by PDL in its discretion at any time during the
period commencing [*] and ending [*] (the “Exercise
Period”) by written notice to Roche and payment of the Reversion
Exercise Fee set forth in Section 5.2(c).

 

(b)                                 Effective
Date of Exercise.  If, during the Exercise Period, PDL provides Roche
with written notice that PDL desires to exercise the Transplant Reversion, [*] shall determine the effective date (the
“Reversion Effective Date”) of
such exercise and reversion of rights, which shall be at least [*] after the date of PDL’s written notice
that it desires to exercise the Transplant Reversion, but in no event be later
than [*].

 

(c)                                  Reversion
Exercise Fee.  PDL shall pay to Roche an exercise fee based on the
AAGS, which exercise price shall be calculated as follows (the “Reversion Exercise Fee”):

 

	
  AAGS

  	
   

  	
  Exercise Price

  
	
  [*]
  or more

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  [*]
  or more but not more than [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  [*]
  or more but not more than [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  not more than [*]

  	
   

  	
  [*]

  

 

22

 

(d)                                 Payment
of Reversion Exercise Fee.  Payment of such Reversion Exercise Fee
shall be made in two installments: [*]
of such Reversion Exercise Fee shall be made within [*] of PDL’s written notice that it is exercising the
Transplant Reversion and the remaining [*]
of such Reversion Exercise Fee shall be made on the later of the [*], or the [*]
after completion of all activities and undertakings set forth in Sections [*].

 

5.3                                 Roche
Put Right Regarding Transplant Reversion.

 

(a)                                  If,
at any time from the Effective Date until Roche receives written notice from
PDL pursuant to Section 5.2(a) of PDL’s exercise of the Transplant
Reversion, Roche desires that all of its rights to market, sell, promote and
otherwise commercialize Daclizumab in the Roche Territory should revert to PDL,
Roche shall have such right, on [*]
written notice to PDL (the “Roche Put Right”);
provided, however, that such right shall not be exercisable by Roche before [*] or after [*].  If so exercised, the effective date of such
reversion (the “Put Right Effective Date”)
shall be deemed to be that date [*]
following the date of such written notice.  The Roche Put Right shall
expire on [*] if not previously
exercised.

 

(b)                                 On
receipt from Roche of its notice of exercise of the Roche Put Right, PDL would
pay to Roche an exercise fee based on the AAGS, which exercise price shall be
calculated as follows (the “Put Exercise Fee”):

 

	
  AAGS

  	
   

  	
  Exercise Price

  
	
  [*]
  or more

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  [*]
  or more but not more than [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  [*]
  or more but not more than [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  not more than [*]

  	
   

  	
  [*]

  

 

(c)                                  Payment
of such Put Exercise Fee shall be made in two installments:  [*] of such Put Exercise Fee shall be made
within [*] of Roche’s written
notice that it is exercising the Roche Put Right and the remaining [*] of such Put Exercise Fee shall be made
on the later of the [*], or the [*] after completion of all activities and
undertakings set forth in Sections [*].

 

(d)                                 In
the event of exercise by Roche of the Roche Put Right, PDL agrees to do the
following, until [*]:

 

(i)                                     to
the extent [*], use [*] efforts to maintain [*] in effect as of the Put Right Effective
Date by and between Roche and Third Party [*]
with respect to Daclizumab for use in the Transplant Indications in the US; and

 

(ii)                                  pay
to Roche those payments provided in Section 7.2(d).

 

23

 

5.4                                 Transfer
and Assignment of Daclizumab Assets; Cooperation.  As soon as practicable following PDL’s notice of its
exercise of the Transplant Reversion, or on delivery by Roche of written
exercise of the Roche Put Right, Roche shall take all steps reasonable and
appropriate to facilitate and shall initiate, or to cause its Affiliates to
facilitate or initiate, the assignment to PDL of all of Roche’s and its
Affiliates’ right, title and interest in and to the Daclizumab Assets and the
transfer of Daclizumab commercialization and regulatory responsibilities in the
Roche Territory from Roche to PDL. Such actions shall include, without
limitation:

 

(a)                                  cooperate
and communicate with PDL as PDL may reasonably request in effectuating such
transfer, including responding in a reasonable time frame to all reasonable
inquiries and requests of PDL with respect to the nature or extent of the
Daclizumab Assets, including providing copies of all relevant documents for PDL’s
use [*];

 

(b)                                 assign
and transfer all Regulatory Approvals and other Daclizumab Assets described in Section 1.14(h) from
Roche to PDL (excluding manufacturing approvals);

 

(c)                                  identify
all distributors and other Third Parties involved in the promotion, sale and
distribution of Daclizumab, and as and to the extent possible offering to
assign agreements with such Third Parties to PDL, to the extent not adverse to
the interests of Roche to do so;

 

(d)                                 on
PDL’s request and at PDL’s sole discretion, Roche shall assign and shall cause
its Affiliates to assign, to PDL any contracts (or relevant portions thereof)
then in force between Roche and any Third Parties regarding the marketing,
promotion, and sale of Daclizumab, to the extent assignable, and where not so
assignable, use its reasonably diligent efforts to obtain consent to such
assignment;

 

(e)                                  prepare,
execute and deliver assignments to PDL of the Roche Owned Patents listed on Schedule 2.8(a) and
record, where appropriate with the relevant authorities, such assignments to
PDL of all of Roche’s and its Affiliates’ right, title and interest in and to
the Roche Owned Patents listed on Schedule 2.8(a); and

 

(f)                                    prepare,
execute and deliver assignments to PDL of all of Roche’s and its Affiliates’
right, title, and interest in and to the Trademarks.

 

In such matters, Roche shall bear the [*] of its [*] and associated [*]
but PDL shall [*] for any [*] to [*]
(such as [*]) required in
connection with such transfers, together with any [*] for [*]
requested by PDL and agreed to by Roche.  Roche shall use its commercially
diligent efforts to ensure that all such transfer activities shall be completed
as expeditiously as possible, but in any event by the Reversion Effective Date
or the Put Right Effective Date.  All such
activities shall be coordinated through and overseen by the POC, as provided in
Section 6.2.

 

5.5                                 Effect
of Exercise.  Effective immediately on either the Reversion Effective
Date or the Put Right Effective Date:

 

24

 

(a)                                  the
license granted to Roche under Section 2.5(a) shall terminate and all
such rights shall revert to PDL; except that, following any Put Right Effective
Date, the license granted to Roche to manufacture Daclizumab in the second
sentence of Section 2.5(a) shall survive, to the extent provided in Section 2.5(a);

 

(b)                                 the
license granted to PDL in Section 2.2 shall be in full force and effect;

 

(c)                                  PDL
shall have the right to purchase all or any portion of Roche’s then existing
inventory of bulk and/or finished Daclizumab, and Roche agrees to so sell such
bulk and/or finished Daclizumab, at a price equal to [*], as necessary to meet commercial requirements; and

 

(d)                                 PDL
thereafter shall commence booking all sales of Daclizumab in the Roche Territory,
whether sold under a Trademark or the AI Trademark or any other trademark.

 

5.6                                 No
Effect on Excluded Field and Excluded Products.  Any exercise of
either the Transplant Reversion or the Roche Put Right shall have no effect on
Roche’s rights in and to the Excluded Field and the Excluded Product, or on the
license granted to Roche under Section 2.5(b), except as provided in Section 13.3.

 

5.7                                 No
Assumption of Liabilities.  Except
as specifically assumed by PDL in writing in connection with an assignment
and/or sublicense to PDL of any Third Party contracts comprising the Daclizumab
Assets pursuant to Section 5.4, PDL shall assume no liabilities of Roche
or its Affiliates as a result of either the exercise by PDL of the Transplant
Reversion or the exercise by Roche of the Roche Put Right, including (a) tax
liabilities; (b) any liabilities relating to accounts payable,
indebtedness, accrued liabilities or legal services, accounting services,
financial advisory services or investment banking services or other
professional services; (c) any wages, salaries or benefits or any other
liabilities relating to the employment of any current or former employee; (d) 
any rent, wages or other obligations of any kind payable by Roche; (e) any
environmental liabilities; and (f) any liabilities with respect to Third
Party contracts not expressly assumed by PDL hereunder.  Roche shall remain responsible for all
liabilities associated with its sale, prior to the Reversion Effective Date or
Put Right Effective Date (as applicable), of Daclizumab, and its manufacture of
Daclizumab, including without limitation uncollected amounts, returns, recalls,
and third party royalties (subject to Section 7.4) associated with such
sales.

 

5.8                                 Effect
of [*].  In the event of any [*], the following shall occur:

 

(a)                                  The
Roche Put Right shall immediately terminate;

 

(b)                                 The
exercisability of the Transplant Reversion shall [*] and the Exercise Period shall be deemed to commence on the
date that is [*] after the
effective date of such [*] and shall
extend until [*].  In the
event PDL exercises such Transplant Reversion during such [*] time, PDL would pay to Roche an
exercise fee based on the AAGS, which exercise price shall be calculated as
follows (the “[*] Exercise Fee”):

 

25

 

	
  AAGS

  	
   

  	
  Exercise Price

  
	
   

  	
   

  	
   

  
	
  more than [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  more than [*] but not more
  than [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  more than [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  not more than [*]

  	
   

  	
  [*]

  

 

and

 

(c)                                  Payment
of such [*] Exercise Fee shall be made in two
installments: [*] of such [*] Exercise Fee shall be made within [*] of PDL’s written notice that it is
exercising the Transplant Reversion and the remaining [*] of such [*]
Exercise Fee shall be made on the later of the [*],
or [*] after completion of all
activities and undertakings set forth in Sections [*].

 

VI.  PRODUCT
OPERATING COMMITTEE

 

6.1                                 Dissolution
of Committees under 1999 Agreements.  Effective
as of the Effective Date, the Joint Development Committee and the Joint
Commercialization Committee, as authorized under the 1999 Agreements, shall be
dissolved.

 

6.2                                 Product
Operating Committee.

 

(a)                                  Within
thirty (30) days after the Effective Date, PDL and Roche shall form a Product
Operating Committee (“POC”)
composed of [*] representatives of
each party who shall be appointed (and may be replaced at any time, subject to
the terms of this Section 6.2(a)) by such party with the prior written
consent of the other party in accordance with this Amended and Restated
Worldwide Agreement.  Each POC
representative shall have suitable experience and expertise in the development
and commercialization of biopharmaceutical drugs.  Each party shall each
have the right to replace its representatives from time to time, provided that
such party obtains the written consent of the other party on such replacement
in advance thereof.

 

(b)                                 The
POC shall meet not less than [*]
on such dates and at such times as agreed to by PDL and Roche, alternating
between Fremont, California and Nutley, New Jersey or such other locations as
the POC determines.   On the determination of the POC, any such
meetings may be conducted by teleconference or videoconference.  Other
representatives of the parties and their invitees may also attend the POC
meetings.

 

(c)                                  The
POC shall be responsible for (i) exchanging information regarding the
activities conducted by the parties, their sublicensees or their respective
Affiliates under this Amended and Restated Worldwide Agreement, including
without limitation, [*] of any [*] with respect to [*], (ii) making
recommendations to the parties regarding the [*]
for [*] for the [*]
of the [*], (iii) discussing the [*] for [*] the [*] for [*] and the
potential for a [*] between the [*] to

 

26

 

accomplish
this goal, (iv) coordinating and overseeing the [*]
to PDL of the [*] pursuant to Section [*]; and (vi) such other activities as mutually agreed
by Roche and PDL[*].  If PDL elects to
exercise its Transplant Reversion under Section 5.2, or Roche exercises
its Roche Put Right under Section 5.3, the POC will coordinate transition
of manufacturing and commercialization responsibilities to PDL over the period
specified in this Amended and Restated Worldwide Agreement; the POC shall
dissolve after the completion of such transition [*].  The POC shall have no authority to determine
pricing of Daclizumab by either party in its respective indications nor shall
the POC have any authority to make any decisions regarding Daclizumab that
shall take effect or continue to remain in effect, after the Reversion
Effective Date or Put Right Effective Date.

 

(d)                                 In
general, the POC is not intended to be a decision-making body with respect to
either party’s efforts to develop or commercialize Daclizumab.  However,
all required decision making with respect to matters before the POC shall be
effected [*] of [*]
representatives.  Each party’s representatives shall have a single
vote.  In the event such representatives of each party are unable to
agree, the matter shall be referred to the [*] and to the [*] (or their successors) for resolution in good faith for a
period of [*] days.  In the event such [*] and such [*] are unable
to resolve such dispute in such time frame, [*]
shall have the final say on all such disputes related to the commercialization
of Daclizumab for use in the [*], except for
[*]; and [*]
shall have the final say on all other such disputes, including but not limited
to those disputes related to development of Daclizumab in [*]
or commercialization of Daclizumab for use in [*]

 

VII.  COMPENSATION

 

7.1                                 Payment
to Roche.  In consideration for the rights and licenses granted by
Roche under this Amended and Restated Worldwide Agreement, PDL shall pay to
Roche a non-refundable, non-creditable fee in the sum of Eighty Million U.S.
Dollars (US$80,000,000), due and payable no later than [*] after the Effective Date.

 

7.2                                 Royalties.

 

(a)                                  Royalties
to PDL on Daclizumab Sales.

 

(i)                                     Royalty
Rate.  Roche shall pay PDL royalties on Roche Net Sales commencing as
of the Effective Date, at a royalty rate determined by annual (or annualized,
as the case may be for partial years) Roche Net Sales as follows:

 

	
  Annual
  Roche Net Sales (US$)

  	
   

  	
  Royalty Rate

  
	
   

  	
   

  	
   

  
	
  Up to and
  including [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  Amount in excess
  of [*] but not exceeding [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  Amount in excess
  of [*] but not exceeding [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  Amount in excess
  of [*] but not exceeding [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  Amount in excess
  of [*]

  	
   

  	
  [*]

  

 

27

 

 

No adjustment will
be made to the royalty rates specified in this Section 7.2(a), regardless
of whether the manufacture, use, sale, or importation of Daclizumab by Roche or
its Affiliates in a particular country is covered by a Valid Claim of a PDL
Patent.

 

(ii)                                  Expiration
of Roche’s Royalty Obligations.  Roche’s obligation to pay royalties
to PDL under this Article VII shall expire (A) with respect to sales
of Daclizumab in the [*], on [*], and (B) with respect to sales of
Daclizumab in the [*], on [*].  Notwithstanding the above, Roche’s
obligation to pay royalties to PDL under this Section 7.2(a) shall
expire on the first to occur, if any, of the Reversion Effective Date or the
Put Right Effective Date.

 

(b)                                 Royalties
to PDL on Excluded Product Sales.

 

(i)                                     Royalty
Rate.  Roche shall pay PDL royalties on Roche Net Sales of Excluded
Products at a royalty rate determined by annual Roche Net Sales of Excluded
Products as follows, as measured on a calendar year basis:

 

	
  Annual
  Roche Net Sales of Excluded

  Products (US$)

  	
   

  	
  Royalty Rate

  
	
   

  	
   

  	
   

  
	
  Up to and
  including [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  Amount in excess
  of [*]

  	
   

  	
  [*]

  

 

 

(ii)                                  Term
of Royalty Obligations.  Roche’s obligation to pay royalties to PDL
under Section 7.2(b)(i) with respect to any Excluded Product shall
expire, on a country-by-country basis, on the later of (A) the last date
on which the manufacture, use, sale, or importation in such country in the
Roche Territory, by Roche, its Affiliates, or sublicensees (other than PDL, its
Affiliates, and sublicensees) of such Excluded Product is covered under a Valid
Claim of a PDL Patent (which determination, if not otherwise covered by a Valid
Claim in the country of use, sale, or importation shall be based on whether or
not covered by a Valid Claim in the country of manufacture), or (B) the [*] of the first commercial sale by Roche,
its Affiliates, or sublicensees (other than PDL, its Affiliates, or
sublicensees) of such Excluded Product in such country.

 

28

 

(c)                                  Royalties
to Roche.

 

(i)                                     Royalty
Rate.  PDL shall pay Roche royalties on PDL Net Sales at a royalty
rate determined by annual PDL Net Sales as follows, as measured on a calendar
year basis:

 

	
  Annual
  PDL Net Sales (US$)

  	
   

  	
  Royalty Rate

  
	
   

  	
   

  	
   

  
	
  Up to and
  including [*]

  	
   

  	
  [*]

  
	
   

  	
   

  	
   

  
	
  Amount in excess
  of [*]

  	
   

  	
  [*]

  

 

(ii)                                  Term
of PDL’s Royalty Obligations Where Transplant Reversion Exercised. 
PDL’s obligation to pay royalties pursuant to Section 7.2(c)(i) shall
expire on the earlier of the Put Right Effective Date or the Reversion
Effective Date.

 

(iii)                               Term
of PDL’s Royalty Obligations Where No Transplant Reversion Exercised. 
In the event PDL does not exercise the Transplant Reversion and Roche does not
exercise the Roche Put Right, PDL’s obligation to pay royalties to Roche under Section 7.2(c)(i) shall
expire, on a country-by-country basis, on the later of (A) the last date
on which the manufacture, use, sale, or importation in such country in the
Roche Territory, by PDL, its Affiliates, or sublicensees (other than Roche, its
Affiliates, and sublicensees) of Daclizumab is covered under a Valid Claim of a
Roche Patent (which determination, if not otherwise covered by a Valid Claim in
the country of use, sale or importation, shall be based on whether or not
covered by a Valid Claim in the country of manufacture), or (B) the [*] of the first commercial sale by PDL,
its Affiliates, or sublicensees (other than Roche, its Affiliates, or
sublicensees) of Daclizumab in such country.

 

(d)                                 Payment
to Roche in Event of Roche Put Right Exercise.  In the event Roche
exercises the Roche Put Right, following the Put Right Effective Date, and
until [*], PDL shall pay Roche
(i) for commercial supply of finished and packaged Daclizumab from Roche
as set forth in Section 4.5(c), a transfer price equal to the [*] and (ii) an amount determined by
the parties in good faith to be equal to [*]
for its [*] and [*] efforts that are [*]; provided that, PDL’s payment
obligation under this Section 7.2(d) for any given calendar quarter
shall in no event exceed a maximum (the “Payment Ceiling”) calculated as follows:

 

Payment Ceiling = [*]

 

7.3                                 Foreign
Filing Expenses Credited Against Royalties.  Roche shall have the
right to credit [*] of all Transplant Foreign
Filing Expenses actually paid to PDL, less credits already taken under the 1989
and 1999 Agreements, against future royalties due to PDL on sales of Daclizumab
pursuant to this Article VII, provided that such credits, when added to
the offset provided for in Section 7.4 below, may not in the aggregate
reduce the royalties to be paid to PDL to less than [*]
of the amount that would otherwise be due pursuant to Section 7.2(a) hereof.

 

29

 

7.4                                 Offset
for Third Party Licenses.

 

(a)                                  Appendix
B sets forth the allocation
between the parties of the costs associated with each Third Party License
entered into prior to the Effective Date. 
Such costs include license fees and any other fixed costs associated
with the Third Party License as well as any royalties.  After the Effective
Date, the parties shall, within [*]
of the end of each [*], reimburse
each other in accordance with this Section 7.4 to effect the agreed-on
sharing of such license fees and other fixed costs.  Both parties hereby
acknowledge that [*] has obtained a required
license from the [*] to use the [*] in order to carry out the activities anticipated by this
Amended and Restated Worldwide Agreement and that [*]
has reimbursed [*] under the 1989 Agreements so
that the license fees and other fixed costs of the [*]
license have been shared [*]

 

(b)                                 If
PDL and Roche agree in writing, after the Effective Date, that either party
must obtain an additional license from an independent Third Party in order for
Roche or PDL to manufacture, use, import, offer for sale or sell Daclizumab and
if PDL and Roche agree on the terms of such license, then such license shall be
deemed a Third Party License and the parties shall, subject to Sections 2.3,
7.4(c) and 7.4(d), share the cost of such Third Party License [*].  Such cost includes license fees
and any other fixed costs associated with such Third Party License as well as
any royalties.  The parties shall, within [*] of the end of each [*],
reimburse each other in accordance with this Section 7.4 to effect a [*] of such license fees and other fixed
costs.

 

(c)                                  Notwithstanding
anything to the contrary herein, the following mechanism shall apply to the
royalty portion of any Third Party Licenses to the extent such royalties arise
due to sales of Daclizumab by Roche or its Affiliates or sublicensees during
the time that Roche is obligated to pay royalties to PDL pursuant to Section 7.2(a):  (i) PDL’s share of such Third Party
royalties shall be accrued against and deducted from any amounts due to PDL
from Roche pursuant to Section 7.2(a) if Roche pays the royalties due
under the Third Party License to such Third Party, and (ii) Roche’s share
of the royalties portion of the cost of any Third Party License shall be
accrued in favor of and added to any amounts due to PDL from Roche pursuant to Section 7.2(a) if
PDL pays the royalties due under the Third Party License to such Third Party;
provided, however, that the total amounts of all deductions made by Roche
pursuant to clause (i) above (without taking into account any additions
made pursuant to clause (ii)) shall not exceed [*] of the amount that would otherwise be due to PDL, pursuant
to Section 7.2(a), in any calendar quarter if no adjustments were
permitted to account for payments made pursuant to Third Party Licenses;  provided further that the sum of Roche’s
royalty obligations to PDL under Section 7.2(a) in any calendar
quarter, plus Roche’s share of those royalties payable for such calendar
quarter to Third Parties pursuant to Third Party Licenses shall not exceed [*] of the amount that would otherwise be
due to PDL, pursuant to Section 7.2(a), in such calendar quarter if no
adjustments were permitted to account for payments made pursuant to Third Party
Licenses.  Royalty payments made by Roche
or PDL pursuant to Third Party Licenses that, due to the limitations set forth
in the preceding sentence, cannot be deducted from, or added to, the amount to
be paid to PDL by Roche under Section 7.2(a), may be carried forward to
subsequent calendar quarters.  An example
of the foregoing principles is set forth in Appendix D.

 

30

 

(d)                                 Notwithstanding
anything to the contrary herein, the following mechanism shall apply to the
royalty portion of any Third Party Licenses to the extent such royalties arise
due to sales of Daclizumab by PDL or its Affiliates or sublicensees during the
time that PDL is obligated to pay royalties to Roche, pursuant to Section 7.2(c):  (i) Roche’s share of such Third Party
royalties shall be accrued against and deducted from any amounts due to Roche
from PDL pursuant to Section 7.2(c) if PDL pays the royalties due
under the Third Party License to such Third Party, and (ii) PDL’s share of
such Third Party royalties shall be accrued in favor of and added to any
amounts due to Roche from PDL pursuant to Section 7.2(c) if Roche
pays the royalties due under the Third Party License to such Third Party;
provided, however, that the royalty payments made by PDL to Roche pursuant to Section 7.2(c) shall
not, as a result of the adjustments set forth in this Section 7.4(d), be
reduced to less than [*] of PDL
Net Sales.  Royalty payments made by
Roche or PDL pursuant to Third Party Licenses that, due to the maximum royalty
rate set forth in the preceding sentence, cannot be deducted from, or added to,
the amount to be paid to PDL by Roche under Section 7.2(c), may be carried
forward to subsequent calendar years.

 

(e)                                  If
PDL exercises the Transplant Reversion or Roche exercises the Roche Put Right,
then commencing on the Reversion Effective Date or the Put Right Effective Date
(as applicable): (i) Roche shall not have any further obligation pursuant
to this Section 7.4 to share the costs of, or pay directly, any royalties
pursuant to any Third Party Licenses on account of sales of Daclizumab by PDL
or its Affiliates or sublicensees, and (ii) PDL shall thereafter have sole
responsibility for paying such royalties.

 

(f)                                    If
the Exercise Period expires without PDL exercising the Transplant Reversion or
Roche exercising the Roche Put Right, then:

 

(i)                                     commencing
on [*], with respect to sales of
Daclizumab in the [*] by Roche and
its Affiliates and sublicensees, or [*],
with respect to sales of Daclizumab in the [*]
by Roche and its Affiliates and sublicensees, (A) PDL shall not have any
further obligation pursuant to this Section 7.4 to share the costs of, or
pay directly, any royalties pursuant to any Third Party Licenses on account of
sales of Daclizumab by Roche or its Affiliates or sublicensees, and
(B) Roche shall thereafter have sole responsibility for paying such
royalties.

 

(ii)                                  commencing
on, a country-by-country basis, with the expiration of PDL’s obligations to pay
royalties to Roche, pursuant to Section 7.2(c), in such country with
respect to the sale of Daclizumab by PDL and its Affiliates and sublicensees,
(A) Roche shall not have any further obligation pursuant to this Section 7.4
to share the costs of, or pay directly, any royalties pursuant to any Third
Party Licenses on account of sales of Daclizumab by PDL or its Affiliates or
sublicensees, and (B) PDL shall thereafter have sole responsibility for
paying such royalties.

 

7.5                                 Royalties
on Termination.  If this Amended and Restated Worldwide Agreement is
terminated pursuant to Sections 13.2, 13.3 or 13.4, then Roche shall continue
to pay PDL, and PDL shall continue to pay Roche, as the case may be, any
royalties earned pursuant to this Article VII prior to the date of
termination.

 

31

 

7.6                                 Sublicenses.

 

(a)                                  Any
Roche Net Sales or Roche Net Sales of Excluded Products by a Roche sublicensee
shall be treated as Roche Net Sales or Roche Net Sales of Excluded Products of
Roche, as the case may be, for the purposes of payments under Article VII.  If Roche, in accordance with Section 2.5(a) or
(b), shall grant any sublicenses under this Amended and Restated Worldwide
Agreement, then Roche shall obtain the written commitment of such sublicensees
to abide by all applicable terms and conditions of this Amended and Restated
Worldwide Agreement and Roche shall remain responsible to PDL for the performance
by such sublicensee of any and all terms. 
All such sublicenses to any Excluded Products shall provide that such
license terminates on any termination of the license granted pursuant to Section 2.5(b).  Any sublicense granted under the license in Section 2.5(a) shall
expire as set forth in that Section 2.5(a).

 

(b)                                 Any
PDL Net Sales by a PDL sublicensee shall be treated as PDL Net Sales of PDL for
the purposes of payments under Article VII.  If PDL, in accordance with Section 2.1,
shall grant any sublicenses under this Amended and Restated Worldwide
Agreement, then PDL shall obtain the written commitment of such sublicensees to
abide by all applicable terms and conditions of this Amended and Restated
Worldwide Agreement and PDL shall remain responsible to Roche for the
performance by such sublicensee of any and all terms.

 

VIII.  PAYMENTS, REPORTS, AND ACCOUNTING

 

8.1                                 Roche
Quarterly Royalty Payments and Reports.

 

(a)                                  Promptly after the Effective Date, the parties shall work
in good faith to establish procedures for (a) compiling a final
accounting, pursuant to the 1999 Agreements, for all sales of Daclizumab made
during 2003 prior to the Effective Date and (b) Roche to make all royalty
payments owed to PDL, pursuant to the 1999 Agreements, with respect to such
sales.

 

(b)                                 Beginning
with the report for the last calendar quarter of 2003 and for each calendar
quarter thereafter, Roche agrees to make payments and written reports to PDL
within [*] after the end of each
calendar quarter covering all sales of the Roche Products in the Roche
Territory by Roche, its Affiliates or sublicensees (except PDL, its Affiliates
and sublicensees) for which invoices were sent during such calendar quarter,
each such written report stating for the period in question:

 

(i)                                     for
Roche Products disposed of by sale, the quantity and description of Roche
Products and the calculation of Roche Net Sales or Roche Net Sales of Excluded
Products,

 

(ii)                                  for
Roche Products disposed of other than by sale, the quantity, description, and nature
of the disposition, and

 

(iii)                               the
calculation of the amount due to PDL for such quarter pursuant to Article VII.

 

32

 

(c)                                  The
information contained in each report under Section 8.1(b) shall be
considered confidential and PDL agrees not to disclose such information to any
Third Party, other than its Affiliates and sublicensees or except as may be
required by law, rule or regulation.  Concurrent with the making of
each quarterly report, Roche shall include payment due PDL hereunder for the
calendar quarter covered by such report.

 

(d)                                 It
is understood that only one royalty payment under Article VII shall be
payable on a given unit of Roche Product disposed of under this Amended and
Restated Worldwide Agreement.  In the case of transfers or sales of any
Roche Product between Roche and an Affiliate or sublicensee of Roche, only one
royalty payment under Article VII shall be due, and such royalty shall be
payable with respect to, the sale of such Roche Product to (i) an
independent Third Party not an Affiliate of the seller or (ii) if the end
user is an Affiliate of the seller, then such end user.

 

8.2                                 PDL
Quarterly Royalty Payments and Reports.

 

(a)                                  Until
the expiration of PDL’s royalty obligations under Section 7.2(c), PDL
agrees to make payments and written reports to Roche within [*] after the end of each calendar quarter
covering all sales of Daclizumab in the Roche Territory by PDL for which
invoices were sent during such calendar quarter, or, in the case of royalties
from the PDL Net Sales of PDL’s Affiliates or sublicensees (except Roche, its
Affiliates and sublicensees), within [*]
following the end of the quarter in which PDL receives the royalty report from
the Affiliate or sublicensee.  Each report shall state for the period in
question:

 

(i)                                     for
Daclizumab disposed of by sale, the gross sales by PDL of Daclizumab and PDL
Adjusted Gross Sales and the calculation of PDL Net Sales,

 

(ii)                                  for
Daclizumab disposed of other than by sale, the quantity, description, and
nature of the disposition, and

 

(iii)                               the
calculation of the amount due to Roche for such quarter pursuant to Article VII.

 

(b)                                 The
information contained in each report under Section 8.2(a) shall be
considered confidential and Roche agrees not to disclose such information to
any Third Party, other than its Affiliates and sublicensees or except as may be
required by law, rule or regulation.  Concurrent with the making of
each quarterly report, PDL shall include payment due Roche hereunder for the calendar
quarter covered by such report.

 

(c)                                  It
is understood that only one royalty payment under Article VII shall be
payable on a given unit of Licensed Product disposed of under this Amended and
Restated Worldwide Agreement.  In the case of transfers or sales of any
Licensed Product between PDL and an Affiliate or sublicensee of PDL, only one
royalty payment under Article VII shall be due, and such royalty shall be
payable with respect to the sale of such Licensed Product to (i) an

 

33

 

independent
Third Party not an Affiliate of the seller or (ii) if the end user is an
Affiliate of the seller, then such end user.

 

8.3                                 Termination
Report.  Roche agrees to make a written report to PDL within [*] after the date on which Roche, or its
Affiliates or sublicensees last sell Daclizumab, stating in each such report
the same information called for in each quarterly report by Section 8.1(b) for
all Daclizumab made, sold or otherwise disposed of and which was not previously
reported to PDL.  Roche further agrees to make a written report to PDL
within [*] after the date on which
Roche, or its Affiliates or sublicensees last sell all Excluded Products,
stating in each such report the same information called for in each quarterly
report by Section 8.1(b) for all Excluded Product made, sold or
otherwise disposed of and which was not previously reported to PDL.  PDL
agrees to make a written report to Roche within [*] after the date on which PDL, or its Affiliates or
sublicensees last sell Daclizumab, stating in such report the same information
called for in each quarterly report by Section 8.2(a) for all
Daclizumab made, sold or otherwise disposed of and which was not previously
reported to Roche; provided, however, that PDL need not file such report if
such date of last sale of Daclizumab occurs after the expiration of PDL’s
royalty under Section 7.2(c)).

 

8.4                                 Accounting. 
Each Party (the “Royalty Paying Party”)
agrees to keep full, clear and accurate records for a period of at least [*], setting forth the manufacturing, sales
and other disposition of Daclizumab, Roche Products (as the case may be), and
Combination Products sold or otherwise disposed of under the license herein
granted in sufficient detail to enable royalties and compensation payable to
the other Party (the “Royalty Receiving Party”)
hereunder to be determined.  Each Royalty Paying Party further agrees to
permit its books and records to be examined by an independent accounting firm
selected by the Royalty Receiving Party to verify reports provided for in this Article VIII. 
Unless the Royalty Receiving Party obtains the prior written consent of the
Royalty Paying Party, such accounting firms must be selected from among the
four largest U.S. accounting firms.  Such audit shall not be performed
more frequently that [*] per
calendar year nor more frequently than [*]
with respect to records covering any specific period of time.  Such
examination is to be made at the expense of the Royalty Receiving Party, except
in the event that the results of the audit reveal a discrepancy in favor of the
Royalty Paying Party of [*] or
more over the period being audited, in which case reasonable audit fees for
such examination shall be paid by the Royalty Paying Party.

 

8.5                                 Methods
of Payments.  All payments due to either PDL or Roche under this
Amended and Restated Worldwide Agreement shall be paid in United States dollars
by wire transfer to a bank in the United States designated in writing by the
party to which the payment is due.

 

8.6                                 Taxes. 
If provision is made in law or regulation of any country of the Roche Territory
or the Territory (as applicable) for withholding of taxes of any type, levies
or other charges with respect to the any amounts payable hereunder to a party,
the other party (“Withholding Party”)
shall promptly pay such tax, levy or charge for and on behalf of the party to
the proper governmental authority, and shall promptly furnish the party with
receipt of such payment.  The Withholding Party shall have the right to
deduct any such tax, levy or charge

 

34

 

actually
paid from payment due the party or be promptly reimbursed by the party if no
further payments are due the party.  Each Withholding Party agrees to
assist the other party in claiming exemption from such deductions or
withholdings under double taxation or similar agreement or treaty from time to
time in force and in minimizing the amount required to be so withheld or
deducted.

 

IX.  CELL LINES

 

9.1                                 Cell
Lines.

 

(a)                                  The
parties acknowledge that PDL has delivered all cell lines to Roche as required
under the 1989 Agreements.  Roche agrees to deliver back to PDL viable
samples of such cell lines as may be requested by PDL.

 

(b)                                 Ownership
of any cell lines developed under Article VI of the 1989 Agreements or
delivered to Roche under Milestone #1 of Section 3.1 of the 1989
Agreements, together with their progeny and derivatives, shall remain vested at
all times in PDL.

 

(c)                                  Roche
may use the cell lines delivered to it under the 1989 Agreements, or their
progeny or derivatives or the plasmids contained therein (the “Cell Line Derivatives”) solely to perform
the Roche Commercialization Activities.  Furthermore, the Cell Line
Derivatives may be used by Roche solely in connection with the genes encoding
antibodies developed or provided by PDL.

 

(d)                                 On
the earliest to occur of [*] in
the Roche Territory as permitted under this Amended and Restated Worldwide
Agreement, Roche shall, on request by PDL, promptly return to PDL all cell
lines provided by PDL under the 1989 Agreements and all Cell Line Derivatives.

 

(e)                                  PDL
MAKES NO REPRESENTATIONS AND EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS
OR IMPLIED, WITH RESPECT TO ANY CELL LINES DELIVERED UNDER THE 1989 AGREEMENTS
OR CELL LINE DERIVATIVES USED HEREUNDER, INCLUDING WITHOUT LIMITATION, ANY
EXPRESS OR IMPLIED WARRANTY OF MERCHANTABILITY, FITNESS FOR A PARTICULAR
PURPOSE OR NONINFRINGEMENT.  FOR CLARITY,
PDL MAKES NO REPRESENTATIONS AND EXTENDS NO WARRANTIES OF ANY KIND THAT THE USE
OF THE CELL LINES DELIVERED TO ROCHE OR THE CELL LINE DERIVATIVES WILL NOT
INFRINGE ANY PATENT OR OTHER RIGHTS OF ANY THIRD PARTY.

 

X.  OWNERSHIP OF TECHNOLOGY AND INTELLECTUAL
PROPERTY

 

10.1                           PDL
Technology.  Ownership of the PDL Know-How and PDL Patents shall
remain vested at all times in PDL.  PDL expressly reserves under this
Amended and Restated Worldwide Agreement (i) all rights to use the PDL
Know-How, PDL’s rights under any Joint Roche-PDL Patents, and PDL Patents to
make, have made, use, import, offer to sell and sell anywhere in the world all
products within the Field that are other than Daclizumab for use in the
Transplant Indications (unless and until the Roche Put Right or the Transplant
Reversion is

 

35

 

exercised)
and other than any Excluded Product or any other product in the Excluded Field;
and (ii) for all uses outside of the Field.  Following exercise of
the Transplant Reversion or the Roche Put Right, PDL shall have the right to use
such technology for any and all purposes other than products in the Excluded
Field, which right shall be exclusive to Roche except as provided in Section 10.2.

 

10.2                           Joint
Inventions and Joint Roche-PDL Patents.  Subject to Article XI,
ownership of Joint Inventions and Joint Roche-PDL Patents shall be vested
jointly in PDL and Roche. Both parties shall at all times have the co-exclusive
right within the Territory to practice, or to make, have made, use, import,
offer for sale or sell any Joint Invention outside the Field under any Joint
Roche-PDL Patent, and neither party shall be obligated to account to the
other.  On the earlier of (i) the Reversion Effective Date, or (ii) the Put
Right Effective Date, the following shall occur: (a) PDL shall have the exclusive
right to practice, and to make, have made, use, import, offer for sale or sell
any Joint Invention in the Field (but not in the Excluded Field) under any
Joint Roche-PDL Patent, and (b) Roche shall have the exclusive right to
practice, and to make, have made, use, import, offer for sale or sell any Joint
Invention solely in the Excluded Field, in each case, without restriction and
without any obligation to account to the other party.  As used herein, a
right to practice any Joint Roche-PDL Patent for a particular purpose without
any obligation to account shall include the right to grant licenses for such
purpose without the consent of the other party.  To the extent either
party needs the consent of the other party to exploit its co-exclusive or exclusive
rights with respect to Joint Roche-PDL Patents, including the right to
sublicense or enforce such Joint Roche-PDL Patents, the other party shall
cooperate with the party making such a request and promptly supply all needed
consents, signatures and the like.  In the event the Roche Put Right and
the Transplant Reversion both expire unexercised, each party shall have the
co-exclusive right to practice, and to make, have made, use, import, offer for
sale or sell any Joint Invention in the Field under any Joint Roche-PDL Patent,
subject to the license grants set forth in Article II.

 

10.3                           Roche
Technology.  PDL hereby acknowledges that, except as expressly
provided herein, this Amended and Restated Worldwide Agreement does not grant
PDL any ownership rights in the Roche Inventions, Roche Patents and Roche
Know-How.  Roche hereby confirms the rights of PDL to certain license
grants to Roche Patents and Roche Know-How as provided in Section 2.1 of
this Amended and Restated Worldwide Agreement.

 

10.4                           Trademarks.

 

(a)                                  Until
the Reversion Effective Date or Put Right Effective Date, Roche shall
exclusively own all Trademarks, and the exclusive right to use them in the
Roche Territory in connection with the marketing and promotion of
Daclizumab.  Roche shall have no right to use the Trademarks, or any other
marks confusingly similar to the Trademarks, in connection with the promotion,
sale or marketing of any other product, including any Excluded Product.

 

(b)                                 PDL
shall have the right to select any and all AI Trademarks; provided such AI
Trademarks are not confusingly similar to the Trademarks (unless otherwise
agreed), and PDL

 

36

 

shall
retain ownership of the AI Trademarks and the exclusive right to use them in
connection with the promotion, marketing and sale of Daclizumab for AI or any
Other Indications.

 

(c)                                  Each
party shall be responsible for selection, prosecution, maintenance and
enforcement of its own trademarks, and shall indemnify and defend the other
from any Third Party claims arising from the indemnifying party’s use of such
marks.  At the request [*] of PDL, Roche shall file trademark registration
applications for, and procure and maintain registration of, the trademark “Zenapax®”
in any country in the Territory in which Roche, as of the Effective Date, has
not made such application or procured such registration.  All such applications and registrations shall
be deemed to be Trademarks.

 

(d)                                 Roche
shall assign the Trademarks to PDL upon exercise of either the Transplant
Reversion or the Roche Put Right, as provided for in Section 5.4(f).

 

XI.  PATENT PROSECUTION

 

11.1                           Sole
PDL Patents and Roche Owned Patents.

 

(a)                                  PDL
agrees to prosecute and reasonably maintain all of the patents and applications
included within the Sole PDL Patents, to the extent it has the rights to do so,
and Roche agrees to prosecute and reasonably maintain the Roche Owned Patents,
to the extent it has the rights to do so from any co-owner of such Roche Owned
Patents.  The parties agree and acknowledge that the Roche Owned Patents
listed on Schedule 2.8(a) are co-owned by Roche and a Third Party,
and are governed by the [*] (the “Joint
Patent Agreement”) which provides, among other things, that Roche undertake
certain obligations in order to continue to maintain its [*]
in the Roche Owned Patent.  Promptly after the Effective Date, to the
extent that Roche is permitted to do so, Roche shall provide to PDL a copy of
the Joint Patent Agreement, and the Roche Owned Patent for PDL’s review such
that PDL may determine whether and to what extent, it intends that such Joint
Patent Agreement and Roche Owned Patent be assigned to PDL in the event of the
Transplant Reversion or the exercise of the Roche Put Right.

 

(b)                                 The
party responsible for such patent (“Responsible
Party”) shall bear all costs and expenses for such prosecution and
maintenance. On the reasonable request of the Responsible Party, the other
party shall cooperate, in all reasonable ways, in connection with the
prosecution of all patent applications included within the Sole PDL Patents or
Roche Owned Patents, as the case may be.  Should the Responsible Party
decide that it is no longer interested in maintaining or prosecuting a Sole PDL
Patent or Roche Owned Patent, as the case may be, it shall promptly advise the
other party thereof and, at the request of such other party, PDL and Roche
shall negotiate in good faith to determine an appropriate course of action in
the interests of both parties.  If any Sole PDL Patents are assigned to Roche,
Roche will thereafter prosecute and reasonably maintain such Sole PDL Patents
at Roche’s own cost to the extent that Roche desires to do so, provided that to
the extent such Sole PDL Patent contains claims outside the Field (or,
following either the Reversion Effective Date or the Put Right Effective Date,
outside the Excluded Field only), PDL and its Affiliates shall have a worldwide
immunity from suit thereunder.  If Roche’s interest in any Roche Owned
Patents is assigned to PDL, PDL will

 

37

 

thereafter
prosecute and reasonably maintain such Roche Owned Patent at PDL’s own cost to
the extent that PDL desires to do so, provided that to the extent such Roche
Owned Patent contains claims outside the Field (or following either the
Reversion Effective Date or the Put Right Effective Date, outside the Excluded
Field only), Roche and its Affiliates shall have a worldwide immunity from suit
thereunder.   In the
event Roche’s interest in the Roche Owned Patents is assigned to PDL pursuant
to Section 5.4(e), Roche shall have no further rights with respect thereto
under this Section 11.1 except those set forth in the penultimate sentence
of this Section 11.1.

 

11.2                           Joint
Inventions.

 

(a)                                  PDL
will have the first right of election to file priority patent applications for
Joint Inventions in any country in the world.  If PDL declines to file
such applications then Roche may do so.

 

(b)                                 The
party not performing the priority patent filings for Joint Inventions pursuant
to this Section 11.2 undertakes without cost to the filing party to obtain
all necessary assignment documents for the filing party, to render all
signatures that shall be necessary for such patent filings and to assist the
filing party in all other reasonable ways that are necessary for the issuance
of the patents involved as well as for the maintenance and prosecution of such
patents.  The party not performing the patent filings shall on request be
authorized by the other party to have access to the files concerning such
patents in any patent offices in the world.

 

(c)                                  The
party performing the priority patent filings for Joint Inventions pursuant to
this Section 11.2 undertakes to perform, at its cost and expense, the
corresponding convention filings from case to case, after having discussed the
countries for foreign filings with the other party.

 

(d)                                 Should
the Responsible Party decide that it is no longer interested in maintaining or
prosecuting a Joint Roche-PDL Patent, it shall promptly advise the other party
thereof.  On the written request of such other party, such Joint Roche-PDL
Patent shall be assigned to the other party at no cost to the assignee. 
If any such patents or patent applications are assigned to Roche, they shall
then be deemed to be a Sole Roche Patent and, to the extent such Joint
Roche-PDL Patent contains claims outside the Field (or, following the Reversion
Effective Date or the Put Right Effective Date, outside the Excluded Field),
PDL and its Affiliates shall have a worldwide immunity from suit
thereunder.  If any such patents or patent applications are assigned to
PDL, they shall then be deemed to be a Sole PDL Patent and, to the extent such
Joint Roche-PDL Patents contain claims outside the Field, Roche and its
Affiliates shall have a worldwide immunity from suit thereunder.

 

11.3                           General
Procedures.  Until the Reversion Effective Date, the Put Right
Effective Date or the expiration of the Exercise Period without PDL exercising
the Transplant Reversion, the parties shall observe the following procedures
for patent applications for inventions arising from this Amended and Restated
Worldwide Agreement:

 

38

 

(a)                                  As
soon as one of the parties concludes that it wishes to file a patent application
covering an invention in the Field, it shall immediately inform the other party
thereof and consult about the filing procedures concerning such patent
application.  For this purpose, such party will provide the other party
with the determination of inventors and scope of claims as early as
possible.  Should a party be faced with possible loss of rights, such
communications may take place promptly after filing a convention application.

 

(b)                                 The
party performing any priority patent filings as described above shall be
obliged to prosecute and reasonably maintain such applications and any patents
resulting therefrom and will have to bear the costs associated therewith. 
On request of the party performing the filing, the other party will cooperate,
in all reasonable ways, in connection with the prosecution of all such patent
applications relating to inventions.  The party performing the filing
shall advise the other party of any substantial action or development in the
prosecution of its patent applications and patents, in particular of the
question of scope, the issuance of, or the rejection of, an interference
involving or an opposition to any respective patent application or patent.

 

(c)                                  Inventions
and other intellectual property made by either party outside the Field shall be
excluded from the provisions of this Amended and Restated Worldwide Agreement
and shall belong solely to the party having made the invention or other
intellectual property.

 

11.4                           Reimbursement
for Costs of Patent Applications for Transplant Indications.

 

(a)                                  No Reimbursement.  As of the Effective
Date, PDL shall be responsible for all ex parte out-of-pocket expenses incurred
by PDL after the Effective Date in connection with the prosecution and
maintenance in the Territory of patent applications and patents included within
the PDL Patents or Joint Roche-PDL Patents for which PDL makes filings with
respect to Transplant Indications pursuant to Article XI of this Amended
and Restated Worldwide Agreement.

 

(b)                                 PDL Control.  After
either the Reversion Effective Date or the Put Right Effective Date, PDL shall
have full control over the strategy and decisions with respect to the filing of
any patent applications and patents related to Transplant Indications in the
Territory.  Roche agrees to cooperate
with and reasonably assist PDL in the preparation of any patent applications
and the maintenance of any patents. 
Prior to the Reversion Effective Date or the Put Right Effective Date,
PDL shall consult Roche with respect to its patent prosecution strategy and
decisions, as follows:  Prior to the
filing of a patent application in the Territory for Transplant Indications, PDL
shall inform Roche concerning such proposed filing and shall consult with Roche
concerning the proposed filing procedures, including specifically the
determination of scope of any such patent and countries in which such
application is to be filed.  PDL shall
regularly advise Roche of any substantial action or development in the
prosecution of its patent applications and patents in the Territory related to
the Transplant Indications, in particular of the question of scope of, the
issuance of, the rejection of, or an opposition to any respective patent
application or patent.

 

39

 

(c)                                  Accrued Transplant Foreign Filing Expenses. 
Transplant Foreign Filing Expenses accrued prior to [*]
shall remain creditable against royalties payable by Roche to PDL in the
Territory (excluding the U.S., including its territories and possessions), as
provided in Section 7.3 of this Amended and Restated Worldwide Agreement.

 

11.5                           Reimbursement
for Costs of Patent Applications for Autoimmune Indications.

 

(a)                                  No Reimbursement.  PDL shall be
responsible for all ex parte out-of-pocket expenses incurred by PDL after the
Effective Date in connection with the prosecution and maintenance in the
Territory of patent applications and patents included within the PDL Patents or
Joint Roche-PDL Patents for which PDL makes filings with respect to Autoimmune
Indications pursuant to Article XI of this Amended and Restated Worldwide
Agreement.

 

(b)                                 PDL Control.  PDL shall have full control over the
strategy and decisions with respect to the filing of any patent applications
and patents related to Autoimmune Indications in the Territory.  Roche
agrees to cooperate with and reasonably assist PDL in the preparation of any
patent applications and the maintenance of any patents.

 

11.6                           No
Reimbursement for Roche’s Costs of Patent Applications.  Roche shall be responsible for all ex parte
out-of-pocket expenses incurred by Roche after the Effective Date in connection
with the prosecution and maintenance in the Territory of patent applications
and patents included within the Roche Owned Patents or Joint Roche-PDL Patents
for which Roche makes filings pursuant to this Article XI of this Amended
and Restated Worldwide Agreement.

 

XII.   ENFORCEMENT
AND DEFENSE OF PATENTS

 

12.1                           Sole
Patents.

 

(a)                                  Except
for enforcement or revocation actions involving Sole PDL Patents or Roche Owned
Patents outside the Field, in the event of any action against a Third Party for
infringement of any claim in any issued patent within the Sole PDL Patents or
Roche Owned Patents, as the case may be, or the institution by a Third Party of
any proceedings for the revocation of any such claim, each party will notify
the other promptly and, following such notification, the parties shall
confer.  [*] shall have the right, but not
the obligation, to prosecute such actions or to defend such proceedings
involving the Sole PDL Patents at its own expense, in its own name and entirely
under its own direction and control.  [*] shall have the right, but not the obligation, to
prosecute such actions or to defend such proceedings involving the Roche Owned
Patents at its own expense, in its own name and entirely under its own
direction and control.

 

(b)                                 If
a party with the first right hereunder elects not to prosecute any action for
infringement or to defend any proceeding for revocation of any claims in any
issued patent within the Sole PDL Patents (other than those Sole PDL Patents
for which PDL [*]) or Roche Owned Patents (other
than those Roche Owned Patents [*]), as the
case may be, within [*] of being
requested by the other party to do so, the other party may prosecute such action
or defend such

 

40

 

proceeding
at its own expense, in its own name and entirely under its own direction and
control.  This Section 12.1(b) shall
expire on the Reversion Effective Date or the Put Right Effective Date.

 

(c)                                  In
any event, the party bringing an action (“Acting
Party”) pursuant to this Section 12.1 shall solicit, and
seriously consider in good faith the non-acting party’s input with respect to
all material aspects of such action, including without limitation, the
development of the litigation strategy and the execution thereof.  In
furtherance and not in limitation of the foregoing, the Acting Party shall keep
the other party promptly and fully informed of the status of any such action,
and the non-acting party shall have the right to review and comment on the
Acting Party’s activities related thereto. The obligations of this Section 12.1(c) shall
not apply to PDL as the Acting Party after either the Reversion Effective Date
or the Put Right Effective Date.

 

(d)                                 Each
party will reasonably assist the Acting Party in any such action or proceeding
being prosecuted or defended by the Acting Party, if so requested by the Acting
Party or required by law.  Without limiting the generality of the
foregoing, the non-acting party agrees to join such action or proceeding if
required by law to maintain such action or proceeding.  The Acting Party
will pay or reimburse the assisting party for all costs, expenses and
liabilities that the assisting party may incur or suffer in affording
assistance to such actions or proceedings.  No settlement of any such
action or defense that restricts the scope or affects the enforceability of PDL
Know-How or Sole PDL Patents may be entered into by either PDL (if it would affect
Roche’s rights under this Agreement) or Roche without the prior consent of the
other party hereto, [*].  No
settlement of any such action or defense that restricts the scope or affects
the enforceability of Roche Know-How or Roche Owned Patents may be entered into
by either PDL or Roche without the prior consent of the other party hereto (if
it would affect the other party’s rights under this Agreement)[*].  The consent obligations of this Section 12.1(d) shall
not apply to PDL as the Acting Party after either the Reversion Effective Date
or the Put Right Effective Date.

 

(e)                                  If
either party elects to prosecute an action for infringement or to defend any
proceedings for revocation of any claims pursuant to this Section 12.1 and
subsequently ceases to continue or withdraws from such action or defense, it
shall forthwith so notify the other party in writing and the other party may
substitute itself for the withdrawing party and the parties’ respective rights
and obligations under this Section 12.1 shall be reversed. The obligations
of this Section 12.1(e) shall not apply to PDL as the Acting Party
after either the Reversion Effective Date or the Put Right Effective Date.

 

12.2                           Joint
Roche-PDL Patents.  In the event of any action against a Third Party
for infringement of any claim in any issued patent within the Joint Roche-PDL
Patents, or the institution by a Third Party of any proceedings for the
revocation of any such claim, each party will notify the other promptly and,
following such notification, the parties shall confer to determine whether
either or both parties shall control the prosecution or defense of such action
or proceeding and who shall bear the costs thereof.  If both parties wish
to control the prosecution or defense of such action or proceeding and the
parties are unable to reach agreement within [*]
of the notification referred to above, then (a) with respect to alleged
infringement in the [*], [*] shall have the exclusive right to bring such action or
defend such proceeding at its own expense, in its own name and entirely under
its own direction, (b) with respect to alleged infringement in

 

41

 

the [*], [*] shall have
the exclusive right to bring such action or defend such proceeding at its own
expense, in its own name and entirely under its own direction; and
(c) with respect to alleged infringement [*],
[*] shall have the right to bring such
action or defend such proceeding at its own expense, in its own name and
entirely under its own direction and control; provided, however, that if both
parties elect to prosecute or defend, each party shall bear its own expenses
but both parties shall have equal control over such prosecution or
defense.  No settlement of any action or defense that restricts the scope
or affects the enforceability of Joint Roche-PDL Patents may be entered into by
either PDL or Roche without the prior consent of the other party hereto, which
consent shall not be unreasonably withheld.  In any event, the Acting
Party pursuant to this Section 12.2 shall solicit, and seriously consider
in good faith the other party’s input with respect to all material aspects of
such action, including without limitation, the development of the litigation
strategy and the execution thereof.  In furtherance and not in limitation
of the foregoing, the Acting Party shall keep the other party promptly and
fully informed of the status of any such action, and the other party shall have
the right to review and comment on the Acting Party’s activities related thereto.

 

12.3                           Distribution
of Proceeds.  In the event either party exercises the rights conferred
in Section 12.1 or 12.2 hereof, and recovers any damages or other sums in
such action, suit or proceeding or in settlement thereof, such damages or other
sums recovered shall first be applied to reimburse the parties for all costs
and expenses incurred in connection therewith, including reasonable attorneys’
fees necessarily involved in the prosecution and/or defense of any suit or
proceeding and, if after such reimbursement any funds shall remain from such
damages or other sums recovered, said remaining recovery shall belong to [*]; provided, however, that any remaining recovery by the
party exercising its rights for a Joint Roche-PDL Patent with respect to alleged
infringement outside the Field shall be shared, with [*] of such remaining recovery to Roche and [*] of such remaining recovery to PDL.

 

12.4                           Defense
of Infringement Actions.

 

(a)                                  Roche
shall defend at its own cost any infringement suit that may be brought against
PDL or Roche on account of the development, manufacture, production, use,
importation, offer for sale, or sale of Daclizumab or Excluded Products by
Roche, and shall indemnify and hold PDL
harmless against any such patent or other infringement suits, and any claims,
losses, damages, liabilities, expenses, including reasonable attorneys’ fees
and cost, that may be incurred by PDL therein or in settlement thereof. 
Any and all settlements that restrict the scope or enforceability of PDL
Know-How or PDL Patents must be approved by PDL, in its sole and absolute
discretion, before execution by Roche.  Any and all settlements that
restrict the scope or enforceability of Joint Roche-PDL Patents or Sole Roche
Patents (other than those Sole Roche Patents co-owned by a Third Party) must be
approved by PDL before execution by Roche, such approval not to be unreasonably
withheld.  PDL shall not be required to
approve any settlement that does not include as a condition thereof the
granting to PDL of a full and unconditional release of claims.

 

(b)                                 PDL
shall defend at its own cost any infringement suit that may be brought against
Roche or PDL on account of the development, manufacture, production, use,
importation,

 

42

 

offer
for sale, or sale of Licensed Products by PDL, and shall indemnify and hold Roche harmless against any
such patent or other infringement suits, and any claims, losses, damages,
liabilities, expenses, including reasonable attorneys’ fees and cost, that may
be incurred by Roche therein or in settlement thereof.  Any and all
settlements that restrict the scope or enforceability of Roche Know-How or
Roche Patents must be approved by Roche, in its sole and absolute discretion,
before execution by PDL.  Any and all settlements that restrict the scope
or enforceability of Joint Roche-PDL Patents must be approved by Roche before
execution by PDL, such approval not to be unreasonably withheld.  Roche
shall not be required to approve any settlement that does not include as a
condition thereof the granting to Roche of a full and unconditional release of
claims.  [*]

 

12.5                           Right
to Counsel.  Each party to this Amended and Restated Worldwide
Agreement shall always have the right to be represented by counsel of its own
selection and its own expense in any suit or other action instituted by the
other for infringement, under the terms of this Amended and Restated Worldwide
Agreement.

 

XIII.  TERM
AND TERMINATION

 

13.1                           Term. 
Unless earlier terminated pursuant to the terms of this Article XIII, this
Amended and Restated Worldwide Agreement shall go into effect on the Effective
Date and shall remain in effect until the latest of (i) expiration of the
last to expire PDL Patents; (ii) expiration of the last to expire Roche
Patents; (iii) expiration of PDL’s payment obligations hereunder; or
(iv) expiration of Roche’s payment obligations hereunder.  On expiration of this Amended and Restated
Worldwide Agreement, any exclusive licenses then in effect under any Roche
Know-How or PDL Know-How will convert to fully paid, non-exclusive licenses.

 

13.2                           Termination
by Mutual Agreement.  This Amended and Restated Worldwide Agreement
may be terminated by the written agreement of both parties.

 

13.3                           Termination
by PDL on Roche Default.  If, during the period commencing on the
Effective Date and terminating on the earlier of Reversion Effective Date or
the Put Right Effective Date, Roche defaults in the performance of, or fails to
be in compliance with, any material agreement, condition or covenant of this
Amended and Restated Worldwide Agreement with respect to either (a) the
rights PDL grants to Roche under Article II of this Amended and Restated
Worldwide Agreement, including royalties and consideration due from Roche to
PDL under Article VII, or (b) the Transplant Reversion granted under Article V,
then PDL may terminate any or all of the rights and licenses granted to Roche
under Section 2.5 of this Amended and Restated Worldwide Agreement at its
option, at which time Roche’s right to promote, distribute and sell Daclizumab
in the Roche Territory shall terminate as though PDL had exercised its
Transplant Reversion, with all the same effect as though that were the case,
but without the need for any payment of the Reversion Exercise Fee.  PDL
shall have such right to so terminate Roche’s rights under this Section 13.3
only if such default or noncompliance shall not have been remedied, or steps
initiated to remedy the same to PDL’s reasonable satisfaction, within [*] after receipt by Roche of a written
notice thereof from PDL.  It is expressly understood that PDL’s rights to
terminate under this Section 13.3 are in effect only until the earlier of
the

 

43

 

Reversion
Effective Date or the Put Right Effective Date, and that such rights expire
with the expiration, without exercise,
of the Transplant Reversion and the Roche Put Right.

 

13.4                           Voluntary
Termination Of License by Roche.

 

(a)                                  Roche
shall have the right, in the event the Transplant Reversion and the Roche Put
Right expire unexercised, to voluntarily terminate its licenses under Section 2.5(a),
on six (6) months written notice.  On notice of such voluntary
termination, Roche shall notify PDL of the amount of Daclizumab that Roche, its
Affiliates, sublicensees and distributors then have on hand (“Inventory”).  Roche and its
Affiliates, sublicensees and distributors shall thereupon be permitted to sell
the Inventory, provided that PDL shall have the first option for a period not
to exceed [*] to purchase all or
part of the Inventory at [*]. 
If PDL fails to exercise its option to purchase all of the Inventory or for
that part of the Inventory with respect to which the option is not exercised,
then Roche will be free to sell such Inventory to Third Parties for a period
not to exceed [*] from the
termination of PDL’s option.  In any event, Roche shall pay the royalties
or other consideration due, if any, on the sale of such Inventory in the
amounts and manner provided for in Articles VII and VIII.

 

(b)                                 Roche
shall have the right at any time during the term of this Amended and Restated
Worldwide Agreement, to voluntarily terminate its license granted under Section 2.5(b),
on [*] written notice to PDL.  In the event of such unilateral termination,
Roche agrees to negotiate with PDL, on PDL’s request, for the transfer and/or
license of any Roche owned or licensed intellectual property or technology
relevant to the development and/or commercialization of the Excluded Products,
in return for [*].

 

13.5                           Return
of Materials.  On termination of this Amended and Restated Worldwide
Agreement in whole by both parties pursuant to Section 13.2, by PDL
pursuant to Section 13.3, or by Roche pursuant to Section 13.4, Roche
forthwith shall (a) return to PDL all cell lines and their progeny,
antibodies and other biological materials provided by PDL under the 1989
Agreements; and (b) subject to Section 13.4, at PDL’s cost, shall
deliver to PDL then available supplies of Daclizumab.

 

13.6                           Rights
and Obligations on Termination or Expiration.  Unless expressly
provided to the contrary, the provisions of Sections 2.1(g), 2.3, 2.7, 3.4,
5.7, 7.4, 7.5, 9.1(c), 9.1(e), 13.4, 13.5, 13.6, 13.7, 17.4, 17.5, 17.6, 17.8,
and 17.11, and Articles VIII, X, XI, XII, XIV and XV shall survive the
termination of this Amended and Restated Worldwide Agreement and shall expire
on their own terms, or if no expiration is expressly indicated therein, shall
continue indefinitely.

 

XIV.  CONFIDENTIALITY,
DISCLOSURE AND PUBLICATIONS

 

14.1                           Confidentiality.

 

(a)                                  Generally. 
During the term of this Amended and Restated Worldwide Agreement and for a
period of [*] following expiration
or termination of this Amended and

 

44

 

Restated
Worldwide Agreement, each party shall maintain in confidence all information
and materials including, but not limited to, cell lines, their progeny, and
antibodies, disclosed by the other party hereto that such party knows or has
reason to know are or contain trade secrets or other proprietary information of
the other, including, without limitation, information relating to the PDL
Know-How, PDL Patents, Roche Know-How, Roche Patents, Joint Roche-PDL Patents,
Joint Inventions and inventions of the other party, and the business plans of
the other party, including, without limitation, information provided by either
party to the other party hereto prior to the Effective Date, and shall not use
such trade secrets or proprietary information for any purpose, including,
without limitation, for the purpose of developing products in the Field except
as permitted by this Amended and Restated Worldwide Agreement or disclose the
same to anyone other than those of its Affiliates, sublicensees, prospective
sublicensees, employees, consultants, agents or subcontractors as are necessary
in connection with such party’s activities as contemplated in this Amended and
Restated Worldwide Agreement.  Each party shall be responsible for
ensuring compliance with these obligations by such party’s Affiliates,
sublicensees, prospective sublicensees, employees, consultants, agents and
subcontractors.  Each party shall use a similar effort to that which it
uses to protect its own [*] trade
secrets or proprietary information to ensure that its Affiliates, sublicensees,
employees, consultants, agents and subcontractors do not disclose or make any
unauthorized use of trade secrets or proprietary information of the other party
hereto.  Each party shall notify the other promptly on discovery of any
unauthorized use or disclosure of the other’s trade secrets or proprietary
information.

 

(b)                                 Additional
Roche Obligations.  During the period commencing on the Effective Date
and terminating on the earlier of Reversion Effective Date or the Put Right
Effective Date, Roche agrees to maintain in confidence the Roche Know-How
related to Daclizumab in a manner consistent with Roche’s maintenance of
confidentiality with respect to know-how and trade secrets related to its other
products and technologies and consistent with Roche’s past practices with
respect to such Roche Know-How.

 

14.2                           Exceptions. 
The obligation of confidentiality contained in this Amended and Restated
Worldwide Agreement shall not apply to the extent that (a) either party
(the “Recipient”) is required to
disclose information by order or regulation of a governmental agency or a court
of competent jurisdiction or (b) the Recipient can demonstrate that
(i) the disclosed information was at the time of such disclosure by the
Recipient already in the public domain other than as a result of actions of the
Recipient, its Affiliates, employees, licensees, agents or subcontractors, in
violation hereof; (ii) the disclosed information was rightfully known by
the Recipient or its Affiliates (as shown by its written records) prior to the
date of disclosure to the Recipient in connection with the negotiation,
execution or performance of this Amended and Restated Worldwide Agreement; or
(iii) the disclosed information was received by the Recipient or its
Affiliates on an unrestricted basis from a source unrelated to any party to
this Amended and Restated Worldwide Agreement and not under a duty of
confidentiality to the other party, or (c) the Recipient can demonstrate
that disclosure to a regulatory authority is required by its product license
approval process.

 

45

 

14.3                           Publications.

 

(a)                                  Scientific
Publications.  Prior to public disclosure or submission for
publication of a manuscript describing the results of any scientific activity
or collaboration between PDL and Roche in the Field, the party disclosing or
submitting such a manuscript (“Disclosing
Party”) shall send the other party (“Responding Party”) by expedited delivery a copy of the
manuscript to be submitted and shall allow the Responding Party a reasonable
time period (not to exceed forty-five (45) days from the date of confirmed receipt) in which to determine
whether the manuscript contains subject matter of which patent protection
should be sought (prior to publication of such manuscript) for the purpose of
protecting an invention, or whether the manuscript contains confidential
information belonging to the Responding Party.  After the expiration of
forty-five (45) days from the date of confirmed receipt of such manuscript, the
Disclosing Party shall be free to submit such manuscript for publication and
publish or otherwise disclose to the public such research results.  Should
the Responding Party believe the subject matter of the manuscript contains
confidential information or a patentable invention of substantial commercial
value to the Responding Party, then prior to the expiration of forty-five (45)
days from the date of confirmed receipt of such manuscript by the Responding
Party, the Responding Party shall notify the Disclosing Party in writing of its
determination that such manuscript contains such information or subject matter
for which patent protection should be sought.  On receipt of such written
notice from the Responding Party, the Disclosing Party shall delay public
disclosure of such information or submission of the manuscript for an
additional period of sixty (60) days to permit preparation and filing of a
patent application on the disclosed subject matter.  The Disclosing Party
shall thereafter be free to publish or disclose such information, except that
the Disclosing Party may not disclose any confidential information of the
Responding Party in violation of Sections 14.1 and 14.2 hereof. 
Determination of authorship for any paper or patent shall be in accordance with
accepted scientific practice.  Should any questions on authorship arise,
this will be determined by good faith consultation between the respective heads
of research for each of the parties.

 

(b)                                 Clinical
Studies.  At any time prior to PDL’s exercise of the Transplant
Reversion or Roche’s exercise of the Roche Put Right, if a party intends to
publicly disclose or submit for publication a manuscript describing the results
of any permitted scientific, preclinical or clinical study involving Daclizumab
conducted by or on behalf of such party (the “Publishing
Party”) or its Affiliates, the Publishing Party shall send the other
party by expedited delivery a copy of the manuscript to be submitted and shall
allow the other party a reasonable time period (such period to be stated in the
transmittal and not to exceed forty-five (45) days from the date of confirmed
receipt by the other party) to review the manuscript, including for the purpose
of determining whether the manuscript contains information which is reasonably
likely to have a material adverse impact on Daclizumab for either Transplant
Indications or Autoimmune Indications, as the case may be, in the Territory or
confidential information belonging to the other party.  After the
expiration of such stated reasonable period from the date of confirmed receipt
by the other party of such manuscript, the Publishing Party shall be free to
submit such manuscript for publication and publish or otherwise disclose to the
public such research results.  During such stated reasonable period, if
the other party believes the manuscript contains information that is reasonably
likely to have a material adverse impact on Daclizumab for Transplant
Indications or Autoimmune Indications, as the case may be, in the Territory,
then prior to the expiration of the

 

46

 

stated
period above, the other party shall notify the Publishing Party in writing of
its determination and the reasons therefor.  On receipt of such written
notice from the other party, the Publishing Party shall confer with the other
party and shall attempt in good faith to resolve such concerns before the
Publishing Party makes any public disclosure of such information or submission
of the manuscript.   After the Reversion Effective Date or the Put
Right Effective Date, PDL shall have the sole right to publish or otherwise
publicly disclose, without the consent of Roche, the results of any scientific,
preclinical and clinical data involving Daclizumab conducted by or on behalf of
PDL or Roche or their Affiliates.

 

XV.  DISPUTE
RESOLUTION

 

15.1                           Arbitration. 
Except as expressly provided herein, any claim, dispute or controversy arising
out of or in connection with or relating to this Amended and Restated Worldwide
Agreement or the breach or alleged breach thereof shall be submitted by the
parties to arbitration by the American Arbitration Association (“AAA”) in Santa
Clara County, California,
under the commercial rules then in effect for that AAA except as provided
herein.  All proceedings shall be held in English and a transcribed record
prepared in English.  The parties shall choose, by mutual agreement, one
arbitrator within thirty (30) days of receipt of notice of the intent to
arbitrate.  If no arbitrator is appointed within the times herein provided
or any extension of time that is mutually agreed on, the AAA shall make such
appointment within thirty (30) days of such failure.  The award
rendered by the arbitrator shall include costs of arbitration, reasonable
attorneys’ fees and reasonable costs for expert and other witnesses, and
judgment on such award may be entered in any court having jurisdiction
thereof.  The parties shall be entitled to discovery as provided in
Sections 1283.05 and 1283.1 of the Code of Civil Procedure of the State of
California, whether or not the California Arbitration Act is deemed to apply to
said arbitration.  Nothing in this Amended and Restated Worldwide
Agreement shall be deemed as preventing either party from seeking injunctive relief
(or any other provisional remedy) from any court having jurisdiction over the
parties and the subject matter of the dispute as necessary to protect either
party’s name, proprietary information, trade secrets, know-how or any other
proprietary right.  If the issues in dispute involve scientific or
technical matters, any arbitrator chosen hereunder shall have educational
training and/or experience sufficient to demonstrate a reasonable level of
knowledge in the field of biotechnology.  Judgment on the award rendered
by the arbitrator may be entered in any court having jurisdiction thereof.

 

XVI.  FORCE
MAJEURE

 

16.1                           No
Control.  If either party shall be delayed, interrupted in or
prevented from the performance of any obligation hereunder by reason of force
majeure including an act of God, fire, flood, earthquake, war (declared or
undeclared), public disaster, act of terrorism, strike or labor differences,
governmental enactment, rule or regulation, or any other cause beyond such
party’s control, such party shall not be liable to the other therefor; and the
time for performance of such obligation shall be extended for a period equal to
the duration of the force majeure which occasioned the delay, interruption or
prevention.  The party invoking such force majeure rights of this Section 16.1
must notify the other party by courier or overnight dispatch (e.g., Federal
Express) within a period of fifteen (15) days of both the first and last
day of the force majeure

 

47

 

unless
the force majeure renders such notification impossible in which case
notification will be made as soon as possible.  If the delay resulting
from the force majeure exceeds six (6) months, both parties shall
consult together to find an appropriate solution.

 

XVII.  MISCELLANEOUS

 

17.1                           Representations. 
Each party represents and warrants to the other party hereto that, except as
may otherwise be disclosed in writing to such party:

 

(a)                                  each
party has the full right and authority to enter into this Amended and Restated
Worldwide Agreement; and

 

(b)                                 to
the best knowledge of the party after reasonable investigation, no Third Party
has any right, title or interest in the PDL Patents or PDL Know-How, Roche
Know-How or Roche Patents, as the case may be, or in the Joint PDL-Roche
Patents, as the result of such Third Party’s former employment of any employee
of that party.

 

17.2                           Assignment. 
Either party may assign this Amended and Restated Worldwide Agreement and the
licenses herein granted (a) to any Affiliate of such party without the
consent of the other party, provided that such party remains fully liable for
the performance of such party’s obligations hereunder by such Affiliate, or
(b) to any Third Party, on the prior written consent of the other party,
not to be unreasonably withheld; and (c) without the consent of the other
party, to any Third Party purchaser of all or substantially all of the business
unit to which this Amended and Restated Worldwide Agreement relates, which in
the case of PDL, shall mean the Daclizumab business, and in the case of Roche,
shall mean Roche’s therapeutic antibody business or transplant therapeutic
business.  The parties agree that it would be reasonable for a party to
withhold consent to the other party’s proposed assignment of this Amended and
Restated Worldwide Agreement to an entity, that is, as of the time of such
proposed assignment, [*] (in at
least one [*] with [*]), or [*]
in any [*] any [*] for the [*] of [*] in any
[*].  This Amended and Restated Worldwide Agreement
shall be binding on and shall inure to the benefit of the permitted successors
and assigns of the parties hereto.

 

17.3                           Entire
Agreement.  This Amended and Restated Worldwide Agreement, the
Reversion Agreement between F. Roche and PDL dated March 4, 2002 (“Japan Reversion Agreement”), the
Pharmacovigilance Agreement, and the Joint Defense Agreement dated June 20,
2000, constitute the entire agreement between the parties hereto with respect
to the subject matter herein and, effective on the Effective Date, supersede
all previous agreements (including the 1999 Agreements), whether written or
oral, such superseding resulting in, among other things, the licenses granted
thereunder having no further force or effect and being replaced by the licenses
set forth in Article II of this Amended and Restated Worldwide
Agreement.  Notwithstanding the
foregoing, (a) certain provisions of the 1999 Agreements shall remain in
force and effect, to the extent this Amended and Restated Worldwide Agreement
so indicates by specific reference, and (b) any royalties or other
payments accruing under the 1999 Agreements prior to the Effective Date shall
remain due and payable.  This Amended and Restated 

 

48

 

Worldwide Agreement shall
not be changed or modified orally, but only by an instrument in writing signed
by both parties.

 

17.4                           Releases. 
The parties hereby confirm the releases contained in Section 15.4 of the
1999 PDL/Roche Agreement and in Section 11.4 of the F. Roche
Agreement.

 

17.5                           Severability. 
If any provision of this Amended and Restated Worldwide Agreement is declared
invalid by an arbitrator pursuant to Section 15.1 or by a court of last
resort or by any court or other governmental body from the decision of which an
appeal is not taken within the time provided by law, then and in such event,
this Amended and Restated Worldwide Agreement will be deemed to have been
terminated only as to the portion thereof that relates to the provision
invalidated by that decision and only in the relevant jurisdiction, but this
Amended and Restated Worldwide Agreement, in all other respects and all other
jurisdictions, will remain in force; provided, however, that if the provision
so invalidated is essential to the Amended and Restated Worldwide Agreement as
a whole, then the parties shall negotiate in good faith to amend the terms
hereof as nearly as practical to carry out the original intent of the parties,
and, failing such amendment, either party may submit the matter to arbitration
for resolution pursuant to Section 15.1.

 

17.6                           Indemnification.

 

(a)                                  Roche
agrees to defend, indemnify and hold harmless PDL, its trustees, officers,
agents and employees from and against any and all Third Party suits, claims,
acts, liabilities, demands, damages, expenses, and losses of any kind,
including those resulting from death, personal injury, illness or property
damage arising (i) out of the manufacture, distribution, use, testing,
promotion, marketing or sale or other disposition, by Roche, an Affiliate of
Roche, or any distributor, customer, sublicensee or representative of Roche or
anyone in privity therewith (other than PDL), of (A) any Licensed Product, as
defined in the 1999 Agreements, prior to the Effective Date, (B) Daclizumab or
any Excluded Product on or after the Effective Date, or (C) any cell lines,
their progeny, or other biological materials, method, process, device or
apparatus licensed or provided by PDL pursuant to the 1989 Agreements, the 1999
Agreements or this Amended and Restated Worldwide Agreement; (ii) as a result
of practicing a Joint Invention, or using PDL Know-How or PDL Patents licensed
to Roche under this Amended and Restated Worldwide Agreement, except where such
claim is based on the negligent acts of commission or omission of PDL; (iii)
out of any breach by Roche of any representation, warranty or covenant of this
Amended and Restated Worldwide Agreement; (iv) out of any violation of
applicable law by an action, policy or procedure of Roche or its Affiliates; or
(v) out of any negligence or willful misconduct of Roche or its Affiliates.

 

(b)                                 PDL
agrees to defend, indemnify and hold harmless Roche, its trustees, officers,
agents and employees harmless from and against any and all Third Party suits,
claims, actions, liabilities, demands, damages, expenses, and losses of any
kind, including those resulting from death, personal injury, illness or
property damage arising (i) out of the manufacture, distribution, use,
testing, promotion, marketing or sale or other disposition, by PDL, an
Affiliate of PDL, or any distributor, customer, sublicensee or representative
of PDL or anyone in privity

 

49

 

therewith
(other than Roche), of (A) Daclizumab prior to the Effective Date, or (B) Daclizumab
or any Other Licensed Product on or after the Effective Date, or (C) any
biological materials, method, process, device or apparatus licensed or provided
by Roche pursuant to this Amended and Restated Worldwide Agreement;
(ii) as a result of practicing a Joint Invention, or using Roche Know-How
or Roche Patents licensed to PDL under this Amended and Restated Worldwide
Agreement, except where such claim is based on the negligent acts of commission
or omission of Roche; (iii) out of any breach by PDL of any representation,
warranty or covenant of this Amended and Restated Worldwide Agreement; (iv) out
of any violation of applicable law by an action, policy or procedure of PDL or
its Affiliates; (v) out of any negligence or willful misconduct of PDL or its
Affiliates; or (vi) from any claim for failure to pay any license fee, royalty
or other payment due on sales of Daclizumab or any Other Licensed Product by
PDL or its Affiliates or sublicensees under any license agreement for any Roche
Controlled Patents between Roche and any Third Party licensor that PDL elected
not to take a sublicense under as provided in Section 2.8(b).

 

(c)                                  Procedure. 
In the event of a claim by a Third Party against a party entitled to
indemnification under this Amended and Restated Worldwide Agreement (“Indemnified Party”), the Indemnified Party
shall promptly notify the other party (“Indemnifying
Party”) in writing of the claim and the Indemnifying Party shall
undertake and solely manage and control, at its sole expense, the defense of
the claim and its settlement.  The Indemnified Party shall cooperate with
the Indemnifying Party, including, as requested by the Indemnifying Party and
at the Indemnifying Party’s cost, entering into a joint defense
agreement.   The Indemnified Party may, at its option and expense, be
represented in any such action or proceeding by counsel of its choice. 
The Indemnifying Party shall not be liable for any litigation costs or expenses
incurred by the Indemnified Party without the Indemnifying Party’s written
consent.  The Indemnifying Party shall not settle any such claim unless
such settlement fully and unconditionally releases the Indemnified Party from
all liability relating thereto, unless the Indemnified Party otherwise agrees
in writing.

 

17.7                           Notices. 
Any notice or report required or permitted to be given under this Amended and
Restated Worldwide Agreement shall be in writing and shall be mailed by
certified or registered mail, or telexed or telecopied and confirmed by
mailing, as follows and shall be effective five (5) days after such
mailing:

 

	
  If to PDL:

  	
  Protein Design
  Labs, Inc.

  
	
   

  	
  34801 Campus
  Drive

  
	
   

  	
  Fremont,
  California U.S.A. 94555

  
	
   

  	
  Attention: Chief
  Executive Officer

  
	
   

  	
   

  
	
  and

  	
  Protein Design
  Labs, Inc.

  
	
   

  	
  34801 Campus
  Drive

  
	
   

  	
  Fremont,
  California U.S.A. 94555

  
	
   

  	
  Attention:
  General Counsel

  

 

50

 

	
  If to Roche:

  	
  Hoffmann-La Roche
  Inc.

  
	
   

  	
  340 Kingsland
  Street

  
	
   

  	
  Nutley, New
  Jersey 07110

  
	
   

  	
  Attention:
  Corporate Secretary

  
	
   

  	
   

  
	
   

  	
   

  
	
  and

  	
  F. Hoffmann-La
  Roche Ltd

  
	
   

  	
  Grenzacherstrasse
  124

  
	
   

  	
  CH-4002 Basel,
  Switzerland

  
	
   

  	
  Attention: Law
  Department

  

 

17.8                           Choice
of Law.  The validity, performance, construction, and effect of this
Amended and Restated Worldwide Agreement shall be governed by the laws of the
State of California, U.S.A, without regard to conflicts of law principles that
would provide for application of the law of a jurisdiction outside California
and excluding the United Nations Convention on Contracts for the International
Sales of Goods.

 

17.9                           Publicity. 
The parties agree to issue press releases in an agreed-on form and format
concerning their entry into this Amended and Restated Worldwide Agreement, with
the content of such releases to be approved in advance by the
parties.    In all other respects, no party to this Amended and
Restated Worldwide Agreement shall use the name of the other parties in any
publicity release without the prior written permission of such other party,
which shall not be unreasonably withheld.  The other party shall have a
reasonable opportunity to review and comment on any such proposed publicity
release.  Except as required by law, no party hereto shall publicly
disclose the terms of this Amended and Restated Worldwide Agreement, the 1989
Agreements, the 1999 Agreements, the Japan Reversion Agreement, or their terms
and conditions unless expressly authorized to do so by the other party which
authorization shall not be unreasonably withheld.  In the event that
disclosure is authorized, the parties will work together to develop a mutually
acceptable disclosure.  Notwithstanding anything to the contrary herein,
if not otherwise disclosed by Roche, PDL shall not disclose to any Third Party
the amount of sales of Roche, or royalties or consideration paid by Roche with
respect to, Daclizumab or Excluded Products without the prior written consent
of Roche, except that PDL shall have the right to disclose the terms of this
Amended and Restated Worldwide Agreement to any bona fide investors, advisors,
investment banking representatives, or prospective strategic partners or
collaborators, under binder of confidentiality.  If not otherwise
disclosed by PDL, Roche shall not disclose to any Third Party the amount of
sales of PDL, or royalties or consideration paid by PDL with respect to, Daclizumab
without the prior written consent of PDL, which consent shall not be
unreasonably withheld.

 

17.10                     Further
Assurances.  The parties agree to reasonably cooperate with each other
in connection with any actions required to be taken as part of their respective
obligations under this Amended and Restated Worldwide Agreement, and shall (a)
furnish to each other such further information; (b) execute and deliver to each
other such other documents; and (c) do such other acts and things (including
working collaboratively to correct any clerical, typographical, or other
similar errors in this Amended and Restated Worldwide Agreement), all as the
other party may reasonably request for the purpose of carrying out the intent
of this Amended and Restated Worldwide Agreement.

 

51

 

17.11                     Tax
Treatment and Tax Structure Disclosure. 
Notwithstanding anything herein to the contrary, any party to this
Amended and Restated Worldwide Agreement (and any employee, representative, or
other agent of any party to this Amended and Restated Worldwide Agreement) may
disclose to any and all persons, without limitation of any kind, the tax
treatment and tax structure of the transactions contemplated by this Amended
and Restated Worldwide Agreement and all materials of any kind (including
opinions or other tax analyses) that are provided to it relating to such tax
treatment and tax structure; provided
however, that such disclosure may not be made to the extent a lack
of disclosure is reasonably necessary to comply with any applicable federal or
state securities laws.  For the purposes
of the foregoing sentence, (a) the “tax treatment” of a transaction means the
purported or claimed federal income tax treatment of the transaction, and (b)
the “tax structure” of a transaction means any fact that may be relevant to
understanding the purported or claimed federal income tax treatment of the
transaction.

 

17.12                     Agency. 
Neither party is, nor will be deemed to be an employee, agent or representative
of the other party for any purpose.  Each party is an independent
contractor, not an employee or partner of the other party.  Neither party
shall have the authority to speak for, represent or obligate the other party in
any way without prior written authority from the other party.

 

17.13                     No
Waiver.  Any omission or delay by
either party at any time to enforce any right or remedy reserved to it, or to
require performance of any of the terms, covenants or provisions hereof, by the
other party, shall not constitute a waiver of such party’s rights to the future
enforcement of its rights under this Amended and Restated Worldwide
Agreement.  Any waiver by a party of a
particular breach or default by the other party shall not operate or be
construed as a waiver of any subsequent breach or default by the other party.

 

17.14                     No
Strict Construction.  This Amended
and Restated Worldwide Agreement has been prepared jointly by the parties and
shall not be strictly construed against either party.

 

17.15                     Headings. 
The captions used herein are inserted for convenience of reference only and
shall not be construed to create obligations, benefits, or limitations.

 

17.16                     Counterparts. 
This Amended and Restated Worldwide Agreement may be executed in counterparts,
all of which taken together shall be regarded as one and the same instrument.

 

52

 

IN WITNESS
WHEREOF, the parties have executed this Amended and Restated Worldwide
Agreement through their duly authorized representatives to be effective as of
the Effective Date.

 

	
  PROTEIN DESIGN LABS,
  INC.

  	
  HOFFMANN-LA
  ROCHE INC.

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
   

  	
   

  	
  By:

  	
   

  	
   

  
	
  Title: 

  	
  Chief Executive
  Officer

  	
   

  	
  Title:

  	
   

  	
   

  
	
  Date:

  	
   

  	
   

  	
  Date:

  	
   

  	
   

  
	
   

  	
   

  
	
   

  	
  F. HOFFMANN-LA
  ROCHE LTD

  
	
   

  	
   

  
	
   

  	
  By:

  	
   

  	
   

  
	
   

  	
  Title:

  	
   

  	
   

  
	
   

  	
  Date:

  	
   

  	
   

  
	
   

  	
   

  
	
   

  	
  By:

  	
   

  	
   

  
	
   

  	
  Title:

  	
   

  	
   

  
	
   

  	
  Date:

  	
   

  	
   

  
													

 

53

 

Appendix
A

 

PDL
Patent Rights

 

The following are patents
and patent applications (also known as the “Queen et al. patents”) issued and
filed in certain countries in the world and licensed as part of the PDL Patent
Rights under the Agreement. (As of: March 5, 2003)

 

1.  The following issued U.S. patents and pending
U.S. patent applications:

 

Patent No. 5,585,089, “Humanized
Immunoglobulins,” issued December 17, 1996.

 

Patent No. 5,693,761, “Polynucleotides
Encoding Improved Humanized Immunoglobulins,” issued December 2, 1997.

 

Patent No. 5,693,762, “Humanized
Immunoglobulins,” issued December 2, 1997.

 

Patent No. 6,180,370 “Humanized
Immunoglobulins and Method of Making the Same”, issued January 30, 2001.

 

[*]

 

2.  The following patents and patent applications
outside the U.S.:

 

	
   

  	
   

  	
   

  	
   

  	
  Patent No.

  	
   

  	
  Country

  	
   

  	
  Title*

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Issued

  	
   

  	
  9/29/00

  	
   

  	
  AR 254487 V1

  	
   

  	
  Argentina

  	
   

  	
  “Novel
  Immunoglobulins, Their Production and Use”

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  AT 0451216

  	
   

  	
  Austria

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  0451216

  	
   

  	
  Belgium

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  0682040

  	
   

  	
  Belgium

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/14/03

  	
   

  	
  1101125-4

  	
   

  	
  Brazil

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  10/27/97

  	
   

  	
  61095

  	
   

  	
  Bulgaria

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/13/02

  	
   

  	
  2328851

  	
   

  	
  Canada

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/20/02

  	
   

  	
  2006865

  	
   

  	
  Canada

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  4/11/00

  	
   

  	
  40279

  	
   

  	
  Chile

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  7/21/00

  	
   

  	
  58770

  	
   

  	
  China

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  11/4/99

  	
   

  	
  P920500A

  	
   

  	
  Croatia

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  12/02/02

  	
   

  	
  174317

  	
   

  	
  Denmark

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  0451216B1

  	
   

  	
  Europe(1)

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  0682040 B1

  	
   

  	
  Europe(1)

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  3/28/02

  	
   

  	
  108797

  	
   

  	
  Finland

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  FR0451216

  	
   

  	
  France

  	
   

  	
  “

  	
   

  

 

54

 

	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  FR0682040

  	
   

  	
  France

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  DE 68925536.5

  	
   

  	
  Germany

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  DE 68929061.6

  	
   

  	
  Germany

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  DD 296 964

  	
   

  	
  East Germany

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  GB 0451216

  	
   

  	
  Great Britain

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  GB 0682040

  	
   

  	
  Great Britain

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/5/93

  	
   

  	
  1001050

  	
   

  	
  Greece

  	
   

  	
  “

  	
   

  
	
  Regist.

  	
   

  	
  7/14/00

  	
   

  	
  0682040

  	
   

  	
  Hong Kong

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  3/22/96

  	
   

  	
  211174

  	
   

  	
  Hungary

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  2/3/03

  	
   

  	
  82755

  	
   

  	
  Ireland

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  IT 0451216

  	
   

  	
  Italy

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  IT 0682040

  	
   

  	
  Italy

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  LU 0451216

  	
   

  	
  Luxembourg

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  LU 0682040

  	
   

  	
  Luxembourg

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  2/18/92

  	
   

  	
  92.2146

  	
   

  	
  Monaco

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  NL 0451216

  	
   

  	
  Netherlands

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  NL 0682040

  	
   

  	
  Netherlands

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  10/20/97

  	
   

  	
  231984

  	
   

  	
  New Zealand

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  6/8/00

  	
   

  	
  314793

  	
   

  	
  New Zealand

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  7/9/01

  	
   

  	
  19912385

  	
   

  	
  Norway(3)

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  12/26/91

  	
   

  	
  132068

  	
   

  	
  Pakistan

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  5/17/96

  	
   

  	
  29729

  	
   

  	
  Philippines

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  10/20/95

  	
   

  	
  92758

  	
   

  	
  Portugal

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  2/10/99

  	
   

  	
  2126046

  	
   

  	
  Russia

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  SG 0451216

  	
   

  	
  Singapore

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  5/22/01

  	
   

  	
  78258

  	
   

  	
  Singapore

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  2/28/99

  	
   

  	
  8912489

  	
   

  	
  Slovenia

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  10/31/90

  	
   

  	
  89/9956

  	
   

  	
  South Africa

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  11/23/98

  	
   

  	
  178385

  	
   

  	
  South Korea

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  2081974 T3

  	
   

  	
  Spain

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  0682040

  	
   

  	
  Spain

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  SE 0451216

  	
   

  	
  Sweden

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  SE 0682040

  	
   

  	
  Sweden

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  1/24/96

  	
   

  	
  CH 0451216

  	
   

  	
  Switzerland

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  8/25/99

  	
   

  	
  CH 0682040

  	
   

  	
  Switzerland

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  12/2/91

  	
   

  	
  50034

  	
   

  	
  Taiwan

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  5/19/93

  	
   

  	
  13349

  	
   

  	
  Uruguay

  	
   

  	
  “

  	
   

  
	
  Issued

  	
   

  	
  2/9/96

  	
   

  	
  56455

  	
   

  	
  Venezuela

  	
   

  	
  “

  	
   

  

 

55

 

[*]

 

* Exact titles may differ
in different countries.

(1) and corresponding
European national patents issued therefrom.

(2) registration date

[*]

 

56

 

Appendix
B

 

Third
Party Licenses as of the Effective Date

 

[*]

 

57

 

Appendix
C

 

PDL
Sole Territory:  Countries or Jurisdictions in which All Rights Have
Reverted to PDL

 

[*]

 

58

 

Appendix
D

 

Example
of Section 7.4(c) Royalty Adjustments

 

[*]

 

59

 

Schedule 2.8(a)

 

Certain
Roche Owned Patents

 

[*]

 

60

 

Schedule 2.8(b)

 

Certain
Roche Controlled Patents

 

All patents and patent applications licensed to Roche
in the following agreements:

 

[*]

 

61

 

Schedule 2.8(e)

 

Notices
of Third Party IP Rights

 

[*]

 

62

 

Schedule 2.8(f)

 

Third
Party Licenses

 

[*]

 

63Exhibit 10.52

 

CERTAIN
CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS
BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION
PURSUANT TO RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED

 

ICOS CORPORATION

MANUFACTURING AGREEMENT

 

THIS
MANUFACTURING AGREEMENT (this “Agreement”) between ICOS Corporation, a
Washington corporation, having its principal offices at 22021 20th
Avenue, Bothell, WA 98021 (“ICOS”), and Protein Design Labs, Inc., a Delaware
corporation, having its principal offices at34801 Campus Drive, Fremont, CA
94555 (“PDL”), is effective as of August 29, 2003.

 

RECITALS

 

A.                                   PDL
is engaged in the discovery, development, and commercialization of new
pharmaceutical candidates;

 

B.                                     ICOS
is in the business of providing biological development and manufacturing
services; and

 

C.                                     PDL
has discussed certain of its areas of interest with ICOS and is familiar with
ICOS’s facilities and expertise and, as a result, wishes to retain ICOS to
provide certain services associated with manufacturing and/or supplying certain
quantities of specific product(s) for use in clinical trials, as more fully set
forth in various Work and Quality Statements (as defined herein) to be attached
to this Agreement, and ICOS is willing to so perform, all in accordance with
the applicable Work and Quality Statements and subject to the terms of this
Agreement.

 

NOW,
THEREFORE, the parties agree as follows:

 

AGREEMENT

 

1.                                      Definitions

 

1.1                                 “Acceptance
Criteria” means the composition, quality, purity, identity and strength of
a Product to be set forth in Work and Quality Statements and which must be met
by ICOS in Processing the Product.

 

1.2                                 “Affiliate”
means any entity that controls, is controlled by, or is under common control
with a party.  A corporation or other
entity shall be deemed to control a corporation or entity if it directly or
indirectly owns or controls at least fifty percent (50%) of the voting stock or
other ownership interest of that corporation or entity.

 

1.3                                 “CMC”
means Chemistry Manufacturing and Control information required by the FDA for
the filing of an IND, as set forth in 21 CFR 312.23(a)(7), et. seq.,
as amended or any successor information.

 

1.4                                 “Confidential
Information” means any business or
technical information, trade secrets, know-how, techniques, data or other
information, disclosed by the disclosing party to the receiving party in
writing and marked “confidential” or that is disclosed orally and confirmed in

 

 

writing
as confidential within thirty (30) days following such disclosure.  Confidential Information shall not include
any information that is: (a) already known to the receiving party at the
time of disclosure hereunder (other than from the other party hereto) as
demonstrated by its written records; (b) now or hereafter becomes publicly
known other than through acts or omissions of the receiving party, or anyone to
whom the receiving party disclosed such information; (c) disclosed to the
receiving party on a nonconfidential basis by a third party under no obligation
of confidentiality to the disclosing party; or (d) independently developed by
the receiving party without reliance on the Confidential Information of the
disclosing party as shown by its written records.  All PDL Materials, PDL Trade Secrets, and all
results of the services shall be deemed Confidential Information of PDL, except
to the extent any such information falls within any of the categories described
in clauses (a) through (d) above.

 

1.5                                 “cGMP”
means the current Good Manufacturing Practices and General Biologics Products
Standards as promulgated under each of the following as in effect on the date
of this Agreement and as amended or revised after the date of this Agreement:

 

(a)                                  the
U.S. Food, Drug & Cosmetics Act (21 U.S.C. Sect. 301 et seq.)
and related U.S. regulations, including 21 Code of Federal Regulations
(Chapters 210, 211, 600 and 610) and other FDA regulations, policies, or
guidelines in effect at a particular time for the manufacture, testing and
quality control of investigational drugs; and

 

(b)                                 the
ICH guide Q7a, “ICH Good Manufacturing Practice Guide for Active Pharmaceutical
Ingredients,” as applied to investigational drugs (Section 19).

 

1.6                                 “PDL
Materials” means those materials supplied by PDL to ICOS (if any) pursuant
to this Agreement or a particular Work or Quality Statement, except those
materials provided by PDL to ICOS that are both (a) not proprietary to PDL and
(b) paid for by ICOS.

 

1.7                                 “PDL
Patent Rights” means patents and patent applications owned by PDL, and all
divisions, continuations, continuations-in-part, and substitutions thereof; all
foreign patent applications corresponding to the preceding applications; and
all U.S. and foreign patents issuing on any of the preceding applications, including
extensions, reissues and re-examinations (including, without limitation, all
claims and causes of action for infringement, misappropriation or violation
thereof).

 

1.8                                 “PDL
Trade Secrets” means unpatented and/or unpatentable trade-secret
information and proprietary technology of any kind or nature owned by PDL
(including, without limitation, all claims and causes of action for
infringement, misappropriation or violation thereof), which is disclosed by or
on behalf of PDL for purposes of assisting ICOS in performing the Services.

 

1.9                                 “FDA”
means the United States Food and Drug Administration, or its successor agency,
and or its European counterpart(s) (currently, the European Medicines
Evaluation Agency, or “EMEA”), as the case may be.

 

2

 

1.10                           “IND”
means an Investigational New Drug application to begin studies of a new drug or biologic for humans that is filed with
the FDA, as set forth in 21 CFR 312.22, et. seq., as amended, or its European
counterpart(s) (currently, EMEA), as the case may be, or any successor
application.

 

1.11                           “Intellectual
Property Rights” means any patent, copyright, trademark, trade secret or
other intellectual or industrial property rights or proprietary rights arising
under the laws of any jurisdiction (including, without limitation, all claims
and causes of action for infringement, misappropriation or violation thereof
and all rights in any registrations and renewals).

 

1.12                           “Manufacture
and Release Requirements” means those specifications, methodologies,
analytical tests, process parameters, acceptance criteria, and cGMP
requirements necessary to manufacture and release to PDL the Product in
conformity with a particular set of agreed on Acceptance Criteria.  All Manufacture and Release Requirements are
set forth in the Work and Quality Statements.

 

1.13                           “Price
and Payment Terms” means the amounts, as stated in a Work Statement, that
are payable by PDL to ICOS in consideration for ICOS performing the Services
pursuant to such Work Statement.

 

1.14                           “Process,”
“Processed” or “Processing” means those activities associated with the
Product as described in the Work and Quality Statements, which ICOS will
perform for and on behalf of PDL in accordance with this Agreement.

 

1.15                           “Product”
means the Product defined in the Work and Quality Statements.

 

1.16                           “Quality
Statement” means the Quality Statement executed by the parties and attached
hereto as Appendix E, and incorporated hereing by this reference, as revised by
the written agreement of the parties from time to time, which shall describe
the regulatory and compliance roles and responsibilities of both PDL and ICOS.

 

1.17                           “Schedule”
means the estimated, target or required timeline for Processing the Product as
agreed on by the parties and set forth in a Work Statement.

 

1.18                           “Services”
means the services to be provided by ICOS for the benefit of PDL, including
Processing specific Product, pursuant to the particular Work and Quality
Statements, which services shall be performed subject to the terms and
conditions of this Agreement.

 

1.19                           “Work
Statement” means each Work Statement executed by the parties and attached
hereto as an Exhibit (including the Quality Statement described above), and
incorporated herein by this reference, as revised by the written agreement of
the parties from time to time, which shall contain at a minimum (a) a
description of all the Services to be performed, (b) a description of the
Product, Acceptance Criteria, Process, and the Manufacture and Release
Requirements, (c) the Price and Payment Terms, (d) the quantity of Product to
be delivered, and (e) an estimated Schedule.

 

3

 

2.                                      Work
and Quality Statements

 

Except
as provided in Section 3.3, ICOS shall have no obligation to perform any
services except in accordance with any Work and Quality Statements.  From time to time with respect to the
manufacture, analysis and/or supply of the M200 Product, they will execute and
attach to this Agreement Work and Quality Statements describing the Services to
be performed and related information. 
This Agreement and each specific Work or Quality Statement, as the same
shall be completed, shall collectively, independent from any other Work or Quality
Statement, constitute the entire agreement for the specific Services identified
in such Work or Quality Statement.  No
Work or Quality Statement shall be binding unless executed by both parties.

 

Subject
to Section 3.2C, by unanimous written decision of the Project Leaders (as
defined in Section 3.5), the parties may revise the Work or Quality
Statements at any time.

 

With
respect to all services provided by ICOS from time to time that are agreed on
by the parties but are outside the scope of the Services (“Additional Services”),
PDL shall pay to ICOS [*] as
described in the Work Statement.  Such
Additional Services and PDL’s payment obligations will be governed by the terms
of this Agreement.  ICOS will invoice PDL
monthly for all Additional Services performed, with each such invoice containing
a reference to the services performed and the personnel used.  All such invoices will be payable under the
terms described in Section 7. 
Notwithstanding the foregoing, and subject to the terms of this
Agreement, ICOS must complete all the tasks necessary to complete the Services
that are within the scope of the Work and Quality Statements to ensure that the
Product is Processed in compliance with the applicable Manufacturing and
Release Requirements in all material respects, and PDL shall compensate ICOS in
performing such Services at the rate specified in the Work Statement.

 

Promptly
following conclusion of the Services, if PDL reasonably determines that further
services are required beyond the Services (as described in the Work and Quality
Statements) to permit PDL to complete the CMC section of documents
necessary to file an IND or IND Amendment with the FDA with respect to the
Product, ICOS shall consider performing any such further services provided that
(i) such further services are within ICOS’s then current manufacturing services
offerings, and (ii) ICOS has resources available (during normal working hours)
to provide such further services.  ICOS
reserves the right to request further compensation prior to agreeing to perform
such further services, considering other commercial opportunities.  Such written description of supplemental
services and compensation shall be an amendment to the pertinent Work and
Quality Statements and shall be governed by the terms of this Agreement.

 

3.                                      Scope
of Services

 

3.1                               Processing
Services

 

Subject
to the terms of this Agreement and pursuant to each Work or Quality Statement,
ICOS will perform the Services as set forth in each Work or Quality Statement
and, as applicable, use commercially reasonable best efforts (based on
biologics manufacturing industry

 

4

 

standards) to (a) Process
the Product in accordance with the related Manufacture and Release
Requirements, including without limitation cGMP, so that when released to PDL
the Product will conform in all material respects with the applicable
Acceptance Criteria, (b) maintain all records regarding the Process and the
Product as agreed to from time to time by the parties and in conformity with
cGMP, (c) subject to the last paragraph of Section 2, provide suitable CMC
support documentation to allow PDL to file an IND or IND Amendment with the FDA
and (d) supply the Product to PDL in accordance with the applicable
Schedule.

 

The
parties agree that the Services, as described in the Work and Quality
Statements, may not be changed without both parties’ prior written
agreement.  PDL acknowledges that ICOS is
given flexibility to conduct such activities, although not expressly stated in
the Work and Quality Statements, at the time and in the manner that ICOS deems
necessary as an independent contractor to fulfill its obligations in completing
the Services.

 

3.2                               Changes
to Schedules and Specifications

 

A.                                   Due
to the unpredictable nature of the biological processes, the Schedules set down
for the performance of the Services (including without limitation the dates for
production and delivery of Product) set out in the Work Statement are best
current estimates only.  ICOS [*] shall keep PDL regularly informed of any changes to the
Schedules.  ICOS understands that any
such changes to the Schedules may have a material impact on PDL’s business and
agrees that the effect on the Schedules caused by any changes to the Schedules
will be made to the minimum extent reasonably necessary.

 

B.                                     The
Acceptance Criteria and the Manufacturing and Release Requirements may be
amended from time to time only as described in Section 3.2C or as dictated
by the FDA and applicable laws.

 

C.                                     ICOS
will not implement any Material Changes relating to any agreed on Acceptance
Criteria or Manufacture and Release Requirements without PDL’s prior written
approval of such changes.  ICOS may,
however, make non-Material Changes without PDL’s prior written approval, but
with timely notification to PDL.  For
purposes of this Section 3.2C, a “Material Change” is defined as any
variation in the written procedures currently in place that (i) impacts the
regulatory commitments for the Product, (ii) may affect the quality, purity,
identity or strength of the Product, or (iii) would necessarily result in
changing, altering or modifying the Acceptance Criteria and/or the Manufacture
and Release Requirements.

 

D.                                    With
respect to (i) amendments dictated by the FDA or applicable laws and (ii)
Material Changes, as described in this Section 3.2, PDL shall be
responsible for (a) the costs specific to the Product in making such amendments
to the Acceptance Criteria and/or Manufacturing and Release Requirements,
including without limitation capital costs specific to the Product (but excluding
[*]), (b) the costs in validating the
Process after such amendment, and (c) any increases in cost of manufacturing
the Product as a result of such amendment. 
With respect to amendments dictated by the FDA or applicable laws, the
parties will promptly meet to discuss the actions necessary to comply with such
amendments and the costs associated

 

5

 

therewith.  ICOS shall invoice PDL in accordance with Section 7.2
for all cost that PDL is responsible to pay pursuant to this Section 3.2.D.

 

3.3                               Technical
Difficulties

 

If it
becomes apparent to either ICOS or PDL at any stage in the provision of any
Services that, as a result of scientific or technical reasons out of the
reasonable control of either party, it will not be possible to complete the
Services in the manner described in this Agreement or the applicable Work and
Quality Statements, the parties shall [*] to resolve
such problems in a commercially reasonable manner.

 

3.4                               Safety
Procedures

 

ICOS will have
responsibility for adopting and enforcing safety procedures for ICOS’s internal
handling and production of each Product, which procedures will comply in all
material respects with applicable federal, state and local environmental and
occupational safety and health requirements.

 

3.5                               Project
Leaders

 

Each
party will, within ten (10) days of signing this Agreement, select an
individual to serve as its Project Leader (collectively, the “Project Leaders”)
and inform the other party of such selection. 
Each party’s Project Leader will (a) be authorized to manage the
relationship of the parties under this Agreement, (b) oversee the performance
of the Services, (c) take the actions specifically delegated to them under
this Agreement, and (d) be the principal contact of such party for matters
relating to this Agreement.  Each party
may change its Project Leader at any time on written notice to the other
party.  The Project Leaders shall meet on
request of either party, but in any event no less frequently than monthly.  Meetings may be held by telephone conference
call and may be attended by other representatives of each party, in addition to
the Project Leader, as the applicable Project Leader may desire.  Decisions of the Project Leaders must be
unanimous.

 

3.6                               Ownership
of Products; License to Know-How

 

PDL
will own all rights, title and interest to all Products, PDL Materials, PDL
Intellectual Property Rights, PDL Patent Rights and PDL Trade Secrets
including, without limitation, all in process materials used to produce
Products and paid for by PDL, cell lines, cell banks, data, marketing plans,
product lines, product plans and records (except to the extent the data or
records contain ICOS’s Intellectual Property Rights or Confidential
Information) produced pursuant to such Work and Quality Statements and all
Intellectual Property Rights in and to all of the foregoing (collectively, “PDL
Property”); provided, however, that PDL Property will not include any right,
title or interest in or to any Intellectual Property Rights or Confidential
Information owned by ICOS, including without limitation [*].  ICOS grants to PDL a non-exclusive,
non-sublicensable (except to third parties for purposes of manufacturing as
described in the last sentence of this Section 3.6), royalty free license,
to use ICOS’s Intellectual Property Rights developed only as a result of
performing the Services for PDL under the Work and

 

6

 

Quality Statements,
including but not limited to batch records and other such information (the “ICOS
Project Related IP”), solely for the purpose of permitting PDL to perform
clinical trials and file for an IND or an IND Amendment with the FDA.  PDL shall have the right to sublicense its
rights in ICOS Project Related IP granted pursuant to this Section 3.6 for
the sole purpose of permitting the third party sublicensees to perform
manufacturing services that are substantially similar to the Services and
related to such PDL Property, provided that each sublicensee agrees in writing
to be bound by the provisions of Section 10 to the same extent as PDL is
bound.  In the event that PDL’s license
rights granted under this Section 3.6 are terminated at any time for any
reason, all such sublicenses shall terminate. 
PDL shall include in all of its sublicense agreements granted hereunder
provisions for such termination.

 

3.7                               Assistance
with Transfer of PDL Property.

 

ICOS
agrees that during or after the term of this Agreement, PDL, at its option, may
elect to engage a third party to perform the same services or services
substantially similar to the Services at any time during or after the term of
this Agreement.  Subject to both (a) the
availability of ICOS personnel, which shall not be unreasonably or unduly
withheld, and (b) PDL compensating ICOS for its time spent in complying with
its obligations under this paragraph [*] in
connection with such obligations, ICOS agrees to provide all necessary
assistance to PDL in transferring PDL Property to such third parties that PDL
engages to perform such services.  In
addition, ICOS agrees that in connection with such transfer, PDL may [*] that is directly related to the PDL Property and
necessary for such third parties to perform manufacturing services that are
substantially similar to the Services and related to such PDL Property and the
ICOS Project Related IP licensed to PDL under Section 3.6, on behalf of
PDL under a confidentiality agreement containing provisions at least as
protective as those of Article 10, provided that PDL [*].

 

4.                                      PDL
Supply of Information

 

4.1                               Proprietary
Information to Provide Services

 

As
soon as practicable after the parties’ execution of Work and Quality
Statements, PDL shall supply to ICOS all PDL Materials and shall disclose to
ICOS all PDL Trade Secrets necessary for ICOS to perform the Services to be
provided under such Work and Quality Statements.  PDL hereby grants ICOS during the term of the
applicable Work and Quality Statements the non-exclusive right to use such PDL
Patent Rights, PDL Trade Secrets and PDL Materials as are necessary for ICOS to
perform the Services for the sole purpose of providing the related
Services.  ICOS acknowledges it may not
use any such rights, information or materials for any purpose other than as
required to perform the Services.

 

4.2                               Information
Regarding Hazards

 

PDL
shall also provide to ICOS on an ongoing basis throughout the term of this
Agreement prompt notice of any information it receives involving the PDL
Materials or Product that relates to any hazards to the health or safety of any
personnel of ICOS or the possibility of

 

7

 

cross-contamination of
any other products being manufactured or stored by ICOS.  ICOS shall promptly notify PDL of any
information it receives relating to (a) the safety of the PDL Materials or
Product, including any confirmed or unconfirmed information on adverse,
serious, or unexpected events, including health or safety risks, associated
with the use or toxicity of the Product, or (b) the possibility that
cross-contamination has occurred with other Products manufactured or stored by
ICOS.

 

5.                                      Shipping

 

ICOS
agrees to work with PDL to deliver and transfer title to the Product in such
locations and in such a manner as directed by PDL, provided that any such
arrangement shall not materially alter ICOS’s obligations, or expose ICOS to
any additional liabilities, under or arising out of this Agreement.  Notwithstanding, all Product that ICOS
Processes pursuant to this Agreement shall be packaged and shipped FOB ICOS’s
facilities and in accordance with PDL’s written instructions and in compliance
with all applicable shipping regulations. 
The parties acknowledge that, according to the Quality Statement, ICOS
may not ship the Product to PDL until PDL has authorized such shipment.  In the event PDL does not grant such shipping
authorization within [*] following
the date that ICOS has provided notice to PDL that it is prepared to ship the
Product, the Product will be deemed to have been delivered to PDL upon the
expiration of such [*] period for
all purposes under this Agreement (including, without limitation, to determine
whether ICOS has timely delivered the Product to PDL, to begin the evaluation
period of the Product as described in Section 6.1A, and to transfer the
title and risk of loss in the Product to PDL). 
All risk in and title to the Product shall pass to PDL on delivery by
ICOS.  Unless the parties agree otherwise
in the applicable Work Statement, PDL shall designate a shipping company,
coordinate with such shipping company for the shipment of the Product, and be
billed directly by the shipping company for all related shipping costs.  Notwithstanding the foregoing, shipment may,
on agreement of the parties, be arranged by ICOS and at terms and with a
carrier reasonably acceptable to PDL.

 

6.                                      Inspection
and Acceptance

 

6.1                               Evaluation
Period

 

A.                                   All
Product shipped from ICOS to PDL shall comply in all material respects with the
applicable Acceptance Criteria and Manufacture and Release Requirements and shall
be accompanied by a certificate of analysis in a form to be agreed on by the
parties.  PDL shall have[*] from the date the Product is delivered to PDL to
evaluate the Product and reject the acceptance thereof; provided, however, that
PDL may reject any Product only if (i) ICOS fails to deliver a certificate of
analysis, (ii) the Product does not meet the Acceptance Criteria as of the date
of delivery in any material respect, (iii) the Product was not Processed
according to the Manufacture and Release Specifications in any material
respect, or (iv) the Product was not manufactured according to cGMPs in any
material respect.  In the absence of PDL
notifying ICOS of rejection within the above described [*]
period, PDL will be deemed to have accepted the Product as delivered.

 

8

 

B.                                     In
the event that the Schedules in a particular Work Statement are estimates only,
PDL shall not be entitled to cancel any unfulfilled part of the Services or
refuse acceptance of Product related to such Work Statement on grounds of
reasonably late performance of the Services or reasonably late delivery of the
Product, as described in section 3.2.A. 
In such event, and notwithstanding Section 12, ICOS shall not be
liable for any loss, damage, costs or expenses of any nature, whether direct or
consequential, arising out of any delay in performance or delivery howsoever
caused; or arising out of any failure to produce the estimated quantities of
Product for delivery on the estimated schedule.

 

6.2                               Rejection
of Product

 

A.                                   If
PDL rejects any of the Product pursuant to Section 6.1A, PDL shall (i)
immediately provide to ICOS written notice of rejection which shall state in
reasonable detail the reasons for such rejection and (ii) provide ICOS with the
opportunity to conduct its own tests on such rejected Product.  PDL shall return all remaining unused Product
to ICOS and require that ICOS replace such rejected Product; provided, however,
that PDL may retain only that portion of the rejected Product that is then
being used for laboratory testing, and may use such retained portion solely to
complete such tests but in no event may PDL use any of the rejected Product for
any human clinical testing or trials after becoming aware of the basis for such
rejection (and PDL shall indemnify ICOS for all liabilities, costs and damages
incurred by ICOS resulting from PDL’s breach of this limitation on use).  ICOS shall replace the Product (as mutually
agreed) as soon as practicable.  In no
case shall ICOS take more than [*] to replace
such Product.

 

B.                                     Notwithstanding
the foregoing, if PDL rejects the Product for the reasons stated in Section 6.1A(ii)
or (iii) and the parties disagree on whether PDL is entitled to so reject such
Product, then (i) analysts from both parties shall promptly meet to determine
that the methods of analysis are the same and are being executed in the same
manner, (ii) carefully controlled and split samples shall be sent from one site
to another for testing in an attempt to reach agreement, and (iii) the parties
shall use good faith efforts for a period of [*]
after completing such tests to resolve whether PDL is entitled to reject such
Product.  In the event that the parties
cannot resolve their dispute in the manner described, an independent laboratory
acceptable to both parties shall be qualified and shall utilize agreed on test
methods to test the Product in dispute (“Disputed Product”).  The costs of such independent laboratory
shall be borne by the parties equally; provided, however, that the party that
is determined to be incorrect in the dispute shall be responsible for all such
costs and shall reimburse the correct party for its share of such costs
incurred.  The decision of such independent
laboratory shall be in writing and shall be binding on both ICOS and PDL.

 

C.                                     If
PDL properly rejects Product pursuant to Section 6.1A and 6.2B, or if ICOS
breaches its warranty stated in Section 10.1B subject to the time
limitation regarding notice of breach as stated therein, and ICOS cannot
replace the Product with conforming Product within the time period set forth in
Section 6.2A, then ICOS [*]; provided,
however, that ICOS will not wait for the time period in Section 6.2A to
expire before [*] if ICOS has earlier knowledge
that it will be unable to replace the Product [*].  Nothing in this Section shall permit
ICOS to cancel its remaining obligations under the Work and Quality Statements
(e.g., obligations regarding

 

9

 

transfer of PDL Property
and confidentiality) or terminate this Agreement as it relates to other Work
Statements.  The provisions of this Section 6.2
shall be the sole remedies available to PDL with respect to Product that PDL
properly rejects.

 

7.                                      Fees
and Invoices

 

7.1                               Fees

 

In consideration for ICOS
performing the Services, PDL shall pay to ICOS such amounts as described in the
Price and Payment Terms section of the applicable Work Statement.  All fees are exclusive of sales tax or of any
other applicable taxes, levies, duties and fees of whatever nature imposed by
or under the authority of any governmental authority, which shall be paid by
PDL (other than taxes based on ICOS’s income).

 

7.2                               Invoices

 

ICOS shall invoice PDL as
provided in the Price and Payment Terms section of the applicable Work
Statement.  PDL shall pay the total
amount of each invoice within [*] of receipt
of the invoice.  If ICOS has not received
full payment prior to the expiration of such [*]
period, ICOS shall provide written notice to PDL of such non-payment.  In the event PDL fails to make payment within
[*] of the date of such notice, then
(a) all unpaid amounts shall accrue interest from the date of the applicable
invoice at a monthly rate equal to the lower of [*]
percent ([*]%) or the highest rate permitted by
law, and (b) ICOS may terminate this Agreement as set forth in Section 14.2A
upon written notice to PDL (unless PDL’s failure to pay is due to its rejection
of Product pursuant to Section 6.2A and the parties are within the dispute
resolution procedures set forth in Section 6.2B) provided that such
termination will not forgive PDL’s obligation to pay all amounts owing to ICOS.

 

8.                                      Raw
Materials

 

ICOS
will be responsible for procuring, testing, releasing and maintaining
sufficient inventory of all raw materials necessary to Process the Product in
accordance with this Agreement and the applicable Work and Quality Statements;
provided, however, that PDL shall reimburse ICOS for the purchase of unusual or
special raw materials, which are to be identified on the applicable Work
Statement as the “PDL Raw Materials,” in such amount and in the manner as
described in such Work Statement.

 

9.                                      Confidentiality

 

9.1                               Non-disclosure

 

Each
party agrees (a) to take all reasonable precautions and to use its commercially
reasonable efforts (provided such efforts shall be no less than what such party
uses to protect its own confidential information, but in no event less than
reasonable care) to maintain the confidentiality of all Confidential
Information that such party (the “Recipient”) obtains in respect to the other
party (the “Disclosing Party”) and (b) not to use or disclose to any third

 

10

 

parties Confidential
Information of the Disclosing Party other than as permitted by Section 9.2.  The Disclosing Party’s disclosure of
Confidential Information to the Recipient shall not constitute a grant of any
license or any other rights or generate any business arrangements unless
specifically set forth herein or in another written agreement between the
parties.

 

9.2                               Permitted
Disclosures

 

A
Recipient may disclose Confidential Information of the Disclosing Party only
(a) to its employees solely for purposes of performing the Services, (b) with
the prior written consent of the Disclosing Party and subject to any
non-disclosure agreement that the Disclosing Party wishes to execute with the
third party recipient of the Confidential Information, or (c) to appropriate
regulatory authorities, attorneys and accountants and pursuant to any order of
a court, administrative agency or other governmental authority, provided that
the Disclosing Party has been provided with reasonable prior notice so that the
Disclosing Party can take actions to prevent such disclosure or mitigate the
effect of such disclosure on the Disclosing Party, and (d) to its attorneys,
advisors, investors, prospective acquirors and investors, lenders and other
financing sources, and to strategic partners or licensees of the Products,
provided that such disclosure shall be made under terms of confidentiality at
least as protective as those herein.

 

9.3                               Terms
of This Agreement

 

Except
as required by law and disclosure to each party’s respective accountants and
legal counsel, neither party shall disclose to any third party any information
about this Agreement other than the existence of this Agreement, without the
other party’s prior written consent. 
Each party shall give the other at least ten (10) business days advance
written notice, unless such number of days must be shortened to comply with a
legal request, of a disclosure required by applicable law and will cooperate
with the other party to minimize the scope and content of such disclosure.

 

9.4                               Press
Release

 

The
text and timing of any press release or other communication to be published
publicly in any manner by either party concerning the subject matter of this
Agreement shall require the prior written approval of the other party, which
shall not be unreasonably withheld.

 

10.                               Representations
and Warranties; Disclaimers

 

10.1                       ICOS

 

ICOS
represents and warrants to PDL the following:

 

A.                                   As
of the date of this Agreement, ICOS has all requisite corporate power and
authority to enter into and perform all of its obligations under this
Agreement.  The execution and delivery of
this Agreement and the consummation of the transactions contemplated hereby
have been duly and validly authorized by all necessary corporate action in
respect thereof on the part of ICOS.  As
of the date of this Agreement, neither the execution and

 

11

 

delivery of this
Agreement nor the performance of the transactions contemplated hereby, nor
compliance by ICOS with the provisions hereof, shall (i) conflict with or
result in a breach of any provision of the certificate of incorporation or
by-laws of ICOS, (ii)  violate any order, writ, injunction, decree,
statute, rule or regulation applicable to ICOS, or (iii)  conflict with
any obligations or agreements of ICOS to any person, contractual or otherwise;

 

B.                                     The
Product will have been manufactured in all material respects with the
Manufacturing and Release Requirements and cGMP; [*] this [*] is [*]
upon [*] giving [*] of [*]
within [*] and [*] returning all [*] to [*]
(at [*] cost) as soon as [*]; provided, however, that [*] may retain only [*] of the [*] that is then being used [*],
and may use such [*] solely to [*], but in no event may [*] use any of the [*] for [*]
after it becomes aware of [*] (and
[*] shall indemnify [*] for all liabilities, costs and damages
incurred by [*] resulting from [*] of this [*]).  Without
limitation to the foregoing [*],
the parties agree that [*] may not
[*] based on [*] of this [*] unless such [*]
results directly in [*] being
imposed on [*] by a [*] and

 

C.                                     ICOS
is not debarred and has not and, in providing the Services, will not knowingly
use in any capacity the services of any person debarred under subsections
306(a) or (b) of the Generic Drug Enforcement Act of 1992 or any comparable law
of any foreign jurisdiction, as each may be amended from time to time;

 

D.                                    EXCEPT
AS EXPRESSLY WARRANTED IN THIS SECTION 10.1, ICOS MAKES NO REPRESENTATION
OR WARRANTY WITH RESPECT TO THE SERVICES OR PRODUCT, EXPRESS OR IMPLIED, IN ANY
MANNER AND EITHER IN FACT OR BY OPERATION OF LAW, AND SPECIFICALLY DISCLAIMS
ANY AND ALL IMPLIED OR STATUTORY WARRANTIES, INCLUDING, WITHOUT LIMITATION, ANY
WARRANTY OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, COURSE OF
DEALING, COURSE OF PERFORMANCE, USAGE OF TRADE OR NONINFRINGEMENT.  Without limiting the foregoing, PDL
acknowledges that it has not and is not relying upon any implied warranty of
any kind or upon any representation or warranty whatsoever by ICOS as to the
commercial exploitability of the Product, the prospects (financial, regulatory
or otherwise) or likelihood of commercial success of the Product after the date
of this Agreement, or the need for third party licenses to commercialize the
Product.

 

10.2                        PDL

 

PDL
represents and warrants to ICOS the following:

 

A.                                   As
of the date of this Agreement, PDL has all requisite power and authority to
enter into and perform all of its obligations under this Agreement.  The execution and delivery of this Agreement
and the consummation of the transactions contemplated hereby have been duly and
validly authorized by all necessary corporate action in respect thereof on the
part of PDL.  Neither the execution and
delivery of this Agreement nor the performance of the transactions contemplated
hereby, nor compliance by PDL with the provisions hereof, shall (i) conflict
with or result in a breach of any provision of the certificate of incorporation
or by-laws of PDL, (ii) violate any order, writ, injunction, decree,
statute, rule or regulation applicable to

 

12

 

PDL, or
(iii) conflict with any obligations or agreements of PDL to any person,
contractual or otherwise;

 

B.                                     PDL
is entitled to supply the applicable PDL Patent Rights, PDL Trade-Secrets and
PDL Materials to ICOS for the performance of the related Services;

 

C.                                     PDL
shall use all Product supplied by ICOS pursuant to this Agreement solely for
conducting clinical trials (and research and development activities related
thereto) for the purpose of collecting clinical data necessary to meet North
American and European regulatory filing requirements; and

 

D.                                    EXCEPT
AS EXPRESSLY WARRANTED IN THIS SECTION 10.2, PDL MAKES NO REPRESENTATION
OR WARRANTY WITH RESPECT TO THE PDL PATENT RIGHTS, PDL TRADE-SECRETS, PDL
MATERIALS OR THE PRODUCT, EXPRESS OR IMPLIED, IN ANY MANNER AND EITHER IN FACT
OR BY OPERATION OF LAW, AND SPECIFICALLY DISCLAIMS ANY AND ALL IMPLIED OR
STATUTORY WARRANTIES, INCLUDING, WITHOUT LIMITATION, ANY WARRANTY OF
MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, COURSE OF DEALING, COURSE OF
PERFORMANCE, USAGE OF TRADE OR NONINFRINGEMENT.

 

11.                               Limitation
on Liability

 

A.                                   EXCEPT
FOR BREACHES OF SECTION 9, IN NO EVENT SHALL EITHER PARTY BE LIABLE TO THE
OTHER PARTY FOR ANY INCIDENTAL, INDIRECT, PUNITIVE, CONSEQUENTIAL (INCLUDING,
WITHOUT LIMITATION, LOST PROFITS) OR SPECIAL DAMAGES OF ANY TYPE OR AMOUNT
ARISING OUT OF ITS BREACH OF ANY PROVISION IN THIS AGREEMENT (INCLUDING WITHOUT
LIMITATION, THE PERFORMANCE OR FAILURE TO PERFORM HEREUNDER) EVEN IF SUCH
DAMAGES WERE FORESEEABLE AND WHETHER SUCH DAMAGES ARISE IN TORT, IN CONTRACT OR
OTHERWISE.

 

B.                                    ICOS’s
sole liability to PDL for delivering Product that PDL is entitled to reject
pursuant to Section 6.2 or breaching its warranty made in Section 10.1B,
is to perform the obligations in accordance with Section 6.2.

 

C.                                    Without
expanding (i) PDL’s liability as described in Section 7.2 for the failure
to make timely payments as described therein or (ii) ICOSs’ liability as
described in Section 11.B for the happening of the events described
therein, each party’s liability to the other for any loss suffered by such
other party arising as a direct result of a breach of this Agreement or of any
other liability of any kind or nature, including without limitation,
misrepresentation and negligence, arising out of this Agreement shall be
limited to the payment of damages which shall not exceed in US Dollars an
amount equal to [*]; provided, however, if and
only to the extent that such damages are caused by the party’s willful or
intentional misconduct, then [*].

 

13

 

12.                               Indemnification

 

12.1                        Indemnification
of ICOS

 

Except
to the extent any of the following Liabilities (defined as follows) are as a
result of ICOS’s negligence or willful misconduct, PDL shall defend, indemnify
and hold harmless ICOS, its officers, agents, employees and Affiliates from and
against any liabilities, damages, losses, expenses and costs (including
reasonable attorneys’ fees) (collectively “Liabilities”) as a result of any
third party claims or actions arising out of (a) PDL’s breach, violation or
nonfulfillment of any of its covenant, agreements, representations or
warranties under this Agreement, (b) PDL’s gross negligence or willful
misconduct, (c) the handling, possession, marketing and distribution, sale or
use of the Product following delivery by ICOS to PDL, including without
limitation any claim alleging breach of warranty or product liability, (d) any
claims alleging ICOS’s use of the PDL Patent Rights, PDL Trade-Secrets and PDL
Materials infringes any third party’s rights, or (e) any claim of infringement
arising out of the composition of matter of the Product, Processing of the
Product or use of the Product.

 

12.2                        Indemnification
of PDL

 

Except
to the extent any of the following Liabilities are as a result of PDL’s
negligence or willful misconduct, ICOS shall defend, indemnify and hold
harmless PDL, its officers, agents, employees and Affiliates from and against
any Liabilities (as defined in Section 12.1) as a result of any third
party claims or actions arising out of (a) ICOS’s breach, violation or
nonfulfillment of any of its covenant, agreements, representations or
warranties under this Agreement, (b) ICOS’s gross negligence or willful
misconduct, (c) ICOS’s handling, possession, or use of the Product and PDL
Materials (except for claims of infringement based on ICOS’s Processing the
Product) in ICOS’s possession and prior to delivery by ICOS to PDL, and (d)
claims alleging that ICOS’s operations constitute an infringement of third-party
proprietary rights, if infringement arises from technical information and
know-how provided by ICOS, unless developed by ICOS on PDL’s behalf.

 

12.3                        Indemnification
Procedures

 

Each
party agrees it shall give to the party that is obligated to indemnify such
party (a) prompt notice of any claim coming within the purview of the
indemnities contained in this Section 12, (b) all relevant facts in its
possession or control, (c) the right to exclusive control of the defense of any
action unless a conflict of interest exists with respect to defending such
action, and (d) its cooperation in the defense of any such action.  In addition, each party agrees that the
indemnified party will not settle any Liabilities without the prior written
consent of the indemnifying party, not to be unreasonably withheld.

 

12.4                        Product
Liability and Worker’s Compensation Insurance

 

Each
Party shall maintain, during the term of this Agreement and for a period of one
(1) year thereafter, product liability in an amount not less than [*] per occurrence and aggregate and shall maintain worker’s
compensation insurance as required under applicable laws.

 

14

 

13.                               Term
and Termination

 

13.1                        Term

 

Unless
terminated early according to this Agreement (a) this Agreement shall continue
for a period of five (5) years from the date hereof and may be extended by the
parties’ mutual written agreement and (b) each Work or Quality Statement shall
commence on the date of execution by the parties and shall terminate on the
completion of the Services described therein. 
The termination of this Agreement for any reason shall automatically
terminate any and all Work and Quality Statements, unless the parties otherwise
agree in writing.  In any event, each
Work or Quality Statement is and shall remain subject to the terms and
conditions of this Agreement.

 

13.2                        Termination

 

PDL is
entitled to terminate this Agreement at any time and for any reason on sixty
(60) days prior written notice to ICOS, subject to the Effects of Termination
as described in Section 13.3 including, without limitation, the obligation
to make such payments to ICOS as described in Section 13.3C.

 

In
addition to the termination rights stated in foregoing paragraph and in Section 7.2,
either party may terminate this Agreement by written notice to the other party
on the occurrence of any of the following events:

 

A.                                   if
the other commits a material breach of this Agreement which (in the case of a
breach capable of remedy) is not remedied within sixty (60) days of the receipt
by the other of written notice identifying the breach with specificity and
requiring its remedy; provided, however, if the breach is as a result of
non-payment of any amounts owed, following the expiration of any applicable
grace period, the breaching party must remedy the breach within ten (10) days
after receiving such written notice; or

 

B.                                     a
petition is filed against the other party for an involuntary proceeding under
any applicable bankruptcy or other similar law, and (i) such petition has not
been dismissed within sixty (60) days of filing; or (ii) a court having
jurisdiction has appointed a receiver, liquidator, trustee or similar official
of such other party for any substantial portion of its property, or ordered the
winding up or liquidation of its affairs; or

 

C.                                     the
other party commences a voluntary proceeding under applicable bankruptcy or
other similar law, has made any general assignment for the benefit of
creditors, or has failed generally to pay its debts as they become due.

 

D.                                    ICOS
may terminate this Agreement by providing written notice to PDL if (i) PDL or
ICOS is unable to perform or is substantially impaired from performing its
respective obligations in a timely manner under this Agreement and the Work and
Quality Statements due to court rulings related to third-party claims of
intellectual property infringement against PDL covered under Section 12.1(d)
and (ii) the parties cannot reach agreement about how to proceed within twenty
(20) days of ICOS’s written notice to PDL.

 

15

 

E.                                      PDL
may terminate this Agreement by providing written notice to ICOS if (i) PDL or
ICOS is unable to perform or is substantially impaired from performing its
respective obligations in a timely manner under this Agreement and the Work and
Quality Statements due to court rulings related to third-party claims of
intellectual property infringement against ICOS described under Section 12.2(d)
and (ii) the parties cannot reach agreement about how to proceed within twenty
(20) days of PDL’s written notice to ICOS.

 

13.3                        Effect of
Termination

 

A.                                   On
termination of this Agreement for any reason (whether due to breach of either
party or otherwise), ICOS will furnish to PDL a complete inventory of all work
in progress and an inventory of all Processed Product.

 

B.                                     By
no later than the date on which the termination of this Agreement becomes
effective, each party will return to the other all Confidential Information
that it possesses or controls that belongs to the other, except that each may
retain a copy in its law department or with its outside counsel for
record-keeping purposes.  Notwithstanding
the foregoing, the license rights granted to PDL under Sections 3.6 and 3.7
shall survive the termination of this Agreement unless this Agreement is
terminated pursuant to the events described in Section 13.3C.

 

C.                                     In
the event this Agreement is terminated (i) by PDL for any reason other than
pursuant to Section 13.2.A, B, C or E, or Section 15 or (ii) by ICOS
pursuant to Section 13.2.A, B, C or D, PDL will pay ICOS a sum equal to
one hundred percent (100%) of the full Price of all stage(s) of the scheduled
Services less all amounts already paid to ICOS for such Services, the payment
for which shall be due to ICOS on or before the date of termination of this
Agreement.  With respect to the
manufacturing capacity that would have otherwise been used to perform the
Services, in the event ICOS (i) resells any such capacity to any third party
and/or (ii) uses any such capacity for any internal manufacturing projects,
ICOS and PDL shall negotiate in good faith a reasonable refund to PDL.

 

D.                                    If
this Agreement is terminated pursuant to Section 13.2.E, ICOS shall [*].

 

E.                                      On
termination of this Agreement, neither party shall use or exploit in any manner
whatsoever any Intellectual Property Rights of any kind or nature of the other
party, except for the express rights granted in other Agreements between the
parties and in Section 3.6 of this Agreement.  Without limitation to the foregoing, on
termination of this Agreement, ICOS shall not use or exploit the PDL Patent
Rights, PDL Trade-Secrets, PDL Confidential Information or PDL Materials in any
way.

 

F.                                      Termination
of this Agreement for any reason will not relieve the parties of any obligation
accruing prior thereto.

 

G.                                     The
following Sections will survive the termination of this Agreement for whatever
reason:  3.6, 3.7, 6.2, 7, 8, 9 through
13, and 17 through 24.

 

16

 

14.                               Facility
Inspection

 

PDL
has the right on [*] days’ notice and during
business hours to visit ICOS (i.e., person in the plant) to observe the Process
and the progress of the work and to inspect related records and data for the
purpose of making quality control inspections so as to assure compliance with
the applicable Work and Quality Statements; provided, however, that if another
party’s product is being manufactured during the time that PDL intends to
visit, such visit, as mutually agreed, (i) may be reasonably delayed until only
PDL’s Product is being manufactured or (ii) take place subject to the provision
that PDL’s representatives will not enter areas of any ICOS facility at times
when third parties’ products are being manufactured.  The form, participants and procedures of all
such inspections shall be subject to ICOS’s reasonable approval.  PDL representatives will follow such security
and facility access procedures as are reasonably designated by ICOS.  During all such inspections, PDL shall use
good faith efforts to avoid disrupting ICOS’s operations.

 

On no less than [*] days’
notice to ICOS, PDL shall also be entitled to conduct a reasonable annual
multi-day quality assurance site audit, the form, participants and procedure of
which shall be subject to ICOS’s reasonable approval.  When conducting an inspection or audit as
described, each of PDL’s representatives will (a) be subject to a nondisclosure
obligation comparable in scope to Section 9, (b) follow such security and
facility access procedures as are reasonably designated by ICOS, (c) be
accompanied by an ICOS representative, and (d) not enter areas of any ICOS
facility at times when third parties’ products are being manufactured to assure
protection of ICOS’s or a third party’s Confidential Information.

 

15.                               Force
Majeure

 

Neither
party hereto shall be liable to the other party for any delay or default in
such party’s performance hereunder if such delay or default is caused by
conditions beyond such party’s reasonable control including, but not limited
to, delays by the FDA or other governmental agency which are not due to serious
violations of law by ICOS, acts of God, war, insurrection, civil commotion,
destruction of production facilities or materials by earthquake, fire, flood or
storm, labor disturbances including strikes or lockouts or epidemic (“Force
Majeure”).  Each party hereto agrees to
promptly notify the other party of any event of Force Majeure and to employ all
reasonable efforts toward prompt resumption of its performance hereunder when possible
if such performance is delayed or interrupted by reason of such event.  If an event of Force Majeure affecting ICOS
continues for a period of sixty (60) days, ICOS shall notify PDL as to how long
ICOS expects the Force Majeure delay will last. 
If ICOS expects that the Force Majeure delay will last six (6) months or
more, PDL shall have the right to terminate this Agreement.  If ICOS expects that the Force Majeure delay
will last less than six (6) months, and after such six (6) month period ICOS can
still not perform under this Agreement, ICOS shall be in material breach of
this Agreement and PDL shall have the right to terminate this Agreement.

 

17

 

16.                               Assignment

 

This
Agreement will be binding on and will inure to the benefit of the parties
hereto and their respective successors and assigns; provided, however, that
neither party may assign any of its rights or obligations under this Agreement
or the Work and Quality Statements to any third party without the other party’s
prior written consent, which consent will not be unreasonably withheld;
provided, however, that either party may assign its rights and obligations
hereunder without the other party’s consent to a third party that is acquiring
or merging with such party or that is purchasing all or substantially all of
such party’s assets that are the subject matter of this Agreement, provided
that the assignee assumes all of such party’s rights and obligations under this
Agreement.

 

17.                               Use
of Intellectual Property Rights

 

Except
as expressly stated in this Agreement, no Intellectual Property Rights of any
kind or nature are conveyed by this Agreement and neither party shall have any
right, title or interest in or to the other party’s Intellectual Property
Rights for any purpose whatsoever without such other party’s prior written
consent.  Neither party shall use or
disclose the name of the other in any advertising, sales, marketing or other
promotional material, without the prior written consent of the other.

 

18.                               Entire
Agreement; Amendments

 

Unless
otherwise agreed to in a writing signed by both parties, this Agreement and the
applicable Work and Quality Statements represent the entire understanding of
the parties.  There are no promises,
terms or conditions, oral or written, expressed or implied, other than those
contained in this Agreement and/or in a Work or Quality Statement.  The terms of this Agreement shall supersede
all previous and contemporaneous agreements between ICOS and PDL relating to
the subject matter contained herein.  To
the extent any terms of a Work or Quality Statement (or any Appendices attached
thereto) conflict with the terms of this Agreement, the terms of this Agreement
shall control unless the parties expressly state in the Work or Quality
Statement (or in the Appendices) that specific terms contained therein control
over the applicable conflicting terms in this Agreement.  If PDL chooses to issue a purchase order (“PO”)
for the delivery of Product, such PO should reference this Agreement and the
specific Work and Quality Statements and shall be issued solely for the
convenience of PDL and to provide subject matter description.  Except as expressly provided in this
Agreement, this Agreement and each Work or Quality Statement may be modified or
amended only by the parties’ written agreement.

 

19.                               Waiver;
Severability

 

No
delay or waiver (or single or partial exercise) on the part of either party on
any one or more occasions in exercising any right, power or privilege hereunder
will operate as a waiver thereof or of any other right, power or privilege
hereunder.  Any such waiver must be made
in writing.  If any provision of this
Agreement or any Work or Quality Statement is held to be illegal, invalid, or
unenforceable under present or future laws effective while this Agreement

 

18

 

remains in effect, the
legality, validity and enforceability of the remaining provisions will not be
affected thereby.

 

20.                               Construction;
Headings

 

This
Agreement and all Work and Quality Statements will be deemed to have been
drafted by both PDL and ICOS and will not be construed against either party as
the draftsperson hereof.  All section titles
or headings contained in this Agreement and any Work and Quality Statements are
for convenience only, will not be deemed a part hereof or thereof and will not
affect the meaning or interpretation of this Agreement or the Work and Quality
Statements.

 

21.                               Attorneys’
Fees

 

If
either party is reasonably required to initiate legal action to enforce its
rights and the other party’s obligations under this Agreement, the prevailing
party in such action shall be entitled to recover its reasonably attorneys’
fees and costs.

 

22.                               Notices

 

Any
notices, demand, invoices, payments or statements required or permitted to be
given pursuant to this Agreement shall be in writing and shall be deemed to
have been delivered when personally delivered, when sent by fax or email (with
confirmation of delivery), or on the third business day following its mailing
by registered or certified mail (return receipt requested), to the parties at
their respective addresses stated in the opening paragraph of this Agreement,
or to such other address as designated in writing.

 

23.                               Independent
Contractor

 

The
parties hereto are independent contractors and nothing contained in this
Agreement shall be construed to place them in the relationship of partners,
principal and agent, employer/employee or joint venturer.  The parties agree that neither shall have power
or right to bind or obligate the other, nor shall either hold itself out as
having such authority.

 

24.                               Counterparts

 

This
Agreement and any Work or Quality Statements may be executed in counterparts,
each of which will be deemed an original but all of which together will
constitute a single instrument.

 

 

[signatures on following page]

 

19

 

IN
WITNESS WHEREOF, the parties hereto have signed this
Agreement as of the date first written above.

 

 

	
  PROTEIN
  DESIGN LABS, INC.

  	
  ICOS
  CORPORATION

  
	
   

  	
   

  
	
   

  	
   

  
	
  By

  	
   

  	
   

  	
  By 

  	
   

  	
   

  
	
  Name:

  	
   

  	
   

  	
  Name:

  	
   

  	
   

  
	
  Title 

  	
   

  	
   

  	
  Title 

  	
   

  	
   

  
										

 

20

 

EXHIBIT

 

WORK STATEMENT

TO MANUFACTURING AGREEMENT

BETWEEN

ICOS CORPORATION AND PROTEIN DESIGN LABS, INC.

DATED                

 

Date of Work Statement:                            

 

I.                                         Product

 

“Product”
means M200.

 

II.                                     Scope
of Services

 

Attached
as Appendix A

 

III.                                 PDL
Materials

 

 

IV.                                Manufacture
and Release Requirements

 

A.                                   Manufacturing
Procedure and Requirements

 

 

B.                                     QA/QC
Tests

 

 

C.                                     Handling
and Storage Requirements

 

 

D.                                    Packaging
Requirements

 

 

E.                                      Record
Keeping Requirements

 

21

 

V.                                    Acceptance
Criteria

 

Attached as Appendix B.

 

VI.                                Estimated
Timeline

 

Attached as Appendix C.

 

VII.                            Price
and Payment Terms

 

Attached as Appendix D.

 

VIII.                        Quality
Statement

 

Attached
as Appendix E.

 

 

	
  PROTEIN
  DESIGN LABS, INC.

  	
  ICOS
  CORPORATION

  
	
   

  	
   

  
	
   

  	
   

  
	
  By

  	
   

  	
   

  	
  By 

  	
   

  	
   

  
	
  Name:

  	
   

  	
   

  	
  Name:

  	
   

  	
   

  
	
  Title 

  	
   

  	
   

  	
  Title 

  	
   

  	
   

  
	
  Dated:

  	
   

  	
   

  	
  Dated:

  	
   

  	
   

  
											

 

22

 

APPENDIX A

SCOPE OF SERVICE

 

Manufacture
of M200, a Recombinant Antibody

 

Scope of Services

 

A.
Assumptions

 

1.                                       ICOS
has maintained a Master Cell Bank (MCB), produced under prior contract,
suitable for manufacturing clinical trial lots of the M200 Product.

2.                                       The
cell line will be grown in [*]

3.                                       Six
(6) cGMP clinical lots will be manufactured that are suitable for regulatory
filings and human clinical trials.

4.                                       ICOS
will provide (bulk) Formulated Drug Substance to PDL or designee.

5.                                       ICOS
will provide [*]

 

B.
Services

 

Manufacturing
of Clinical (cGMP) Batches

Objectives

Perform six (6) cGMP production runs (six cell
culture and six purification runs). Each run is also referred to as a “lot”
herein.

Carry out in-process and Drug Substance testing to
confirm that the process is in control and that the Product from each lot meets
Product Specifications.

1.                                       Carry
out six cGMP (clinical) production runs based on the process developed
previously by ICOS for this product.

2.                                       Revise
master documents to include process corrections and improvements identified
during the previous clinical production lot.

3.                                       Carry
out manufacturing processes and testing according to approved, written
procedures.  Master documents will be
reviewed and approved by ICOS and PDL according to the Quality Statement.

4.                                       Store
solutions, process intermediates, and Formulated Drug Substance in controlled
access locations under appropriate conditions as specified in the Work
Statement.

5.                                       Test
each lot of Drug Substance by the methods described in Section D and as
specified in the Material Specifications.

6.                                       Save
a sample of EOP cells from each cGMP run.

7.                                       Perform
Lot Disposition according to the Quality Statement.

8.                                       Prepare
for PDL a summary of the results, including items such as key in-process
control data, production titers, process step yields, for the cGMP runs.

 

23

 

9.                                       Within
[*]of delivery of Product, deliver
Product-related Records and Documentation described in Section E needed to
support the CMC section for PDL’s regulatory filings.  Additional detailed data will be provided on
specific request from PDL.

 

C.
Deliverables

 

The
following items will be delivered from ICOS Corporation to PDL.

1.                                       Six
(6) lots of (bulk) Formulated Drug Substance prepared from six cGMP clinical
production runs using the 3000L ICOS bioreactor.

2.                                       Certificates
of Analysis that include all ICOS release testing results and a notice of
disposition from ICOS Quality Assurance, delivered within [*]
following the date of product lot formulation.

3.                                       Documentation
as described in Section E and in the Quality Statement.

4.                                       The
pre-bank and Master Cell Bank(1).

5.                                       EOP
cell samples, if requested by PDL.

 

(1) If
desired, ICOS will retain a number of vials in the event that at some future
date PDL would like to request additional clinical production runs.

 

24

 

D.
In-Process and Drug Substance Testing

 

The test methods in the table below will be performed at the indicated
process stages.

The development or performance of any other assays is out-of-scope
work.

 

	
   

  	
   

  	
  Production Scale (Clinical)

  	
   

  
	
  Method

  	
   

  	
  Harvest fluid

  	
   

  	
  Purification In-

  Process

  	
   

  	
  Formulated

  Drug Substance

  	
   

  
	
  Mycoplasma(1)

  	
   

  	
  X (EOP)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Sterility(1)

  	
   

  	
  X (EOP)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  MMV(1)

  	
   

  	
  X (EOP)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  In-vitro viral –
  14 day(1)

  	
   

  	
  X (EOP)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Product Titer
  (Protein A)

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Bioburden

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Endotoxin

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  Product
  concentration (A280)

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  Size Exclusion
  HPLC

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  SDS-PAGE,
  unreduced

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  SDS-PAGE,
  reduced

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  Isoelectric
  Focusing

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  MALDI-MS

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Silver stain,
  unreduced

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Silver stain,
  reduced

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Appearance

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Osmolality

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  PH

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Insulin

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Residual Protein
  A EIA

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Residual Host
  Cell DNA Content

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Residual Host
  protein Content

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Binding assay

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Potency assay

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Bovine IgG

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  Polysorbate 80
  concentration(2)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  

 

(1) Contracted
to an outside vendor

(2) Protocol
and necessary reagents to be transferred from PDL to ICOS

 

25

 

E.                                      Product-related
Records and Documentation Provided to PDL

 

Drug History Record – provided for each clinical lot

•                  [*]

•                  Lot disposition notice [*]

•                  Certificate of Analysis [*]

•                  Certificate of Compliance

•                  Indented bill of materials [*]

•                  Process flowchart

 

Satellite Files

Informational copies (on request) of:

•                                    Product specific
master manufacturing batch records

•                                    Product specific
test methods

•                                    Product specific
material specifications

 

26

 

APPENDIX B

ACCEPTANCE
CRITERIA

 

[*]

 

 

 

APPENDIX C

ESTIMATED TIMELINE

 

[*]

 

27

 

APPENDIX D

PRICE AND PAYMENT TERMS

 

 

	
  Stage

  	
   

  	
  Terms

  	
   

  	
  Estimated Date of Payment(1)

  	
   

  	
  [*]

  	
   

  
	
  Reservation Fee

  	
   

  	
  [*]

  	
   

  	
  9/1/03

  	
   

  	
  [*]

  	
   

  
	
  Run Initiation Fee

  	
   

  	
  [*]

  	
   

  	
  1/15/04

  	
   

  	
  [*]

  	
   

  
	
  Per Lot Fee(2),(3)

  	
   

  	
  [*]

  	
   

  	
  TBD

  	
   

  	
  [*]

  	
   

  
	
  Additional Services(5)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  

 

(1) The dates listed are
estimates only.  The actual payment date
is the date on which the applicable event occurs as stated in the “Terms”
column.

 

[*]

 

[*]

 

[*]

 

(5) Determined by written
agreement of the Project Leaders.

 

28

 

APPENDIX E

QUALITY STATEMENT

 

1. Purpose

 

This Quality Statement
has been developed to define the regulatory compliance roles and
responsibilities of PDL and ICOS Corporation (ICOS, “Manufacturer”).  The Quality Statement shall constitute part
of the agreement between PDL and ICOS and may be revised from time to time when
mutually agreed in writing by the Quality Assurance contacts listed in Section 2
or their designees.  In the event of a
conflict between the provisions of the Manufacturing Agreement and Quality
Statement, the provisions of the Manufacturing Agreement shall prevail.

 

2. Quality Assurance
Contacts

 

Emergency Quality
Assurance contact names and numbers during and outside working hours at each
company:

 

PDL Quality
Assurance:

[*]

 

ICOS Quality
Assurance:

[*]

 

The PDL and ICOS Quality
Departments will jointly establish a list of Quality contacts in order to
conduct their business.

 

3. Definitions

 

“Agreement” shall mean the
Manufacturing Agreement executed between PDL and ICOS on [*]

 

“cGMP” shall mean Current Good
Manufacturing Practices as promulgated under the US Federal Food Drug and
Cosmetic Act and 21 CFR Sections 210, 211, 600 and 610 and ICH Q7A, cGMPs for
APIs

 

“Critical Deviation” shall mean
deviations where (i) [*]

 

“Party” means either PDL or ICOS

 

“Parties” means both PDL and
ICOS

 

“Products” shall mean PDL drug
products and all intermediate precursors

 

29

 

4. Regulatory Activities

 

4.1 Roles
of the parties

 

PDL will be the holder the IND or equivalent and the
holder of the registration submission and subsequent license.  ICOS will support these submissions as a
contract manufacturer under the direction of PDL.

 

4.2
Regulatory submissions

 

PDL will be responsible for the submission of
documentation to regulatory authorities in support of the Products.  ICOS will provide PDL with the information
necessary to complete regulatory submissions in a timely and effective manner.

 

ICOS and PDL will mutually agree on responses to
questions regarding PDL submissions, which PDL will make, to FDA questions and
requests regarding facilities, production processes and Product testing
relevant to ICOS.

 

4.3
Inspections

 

PDL will inform ICOS in a timely fashion when
regulatory agencies are seeking to schedule inspections concerning the
Product at ICOS’ facilities.

 

PDL will be permitted to have [*]on
site for consultation during a PDL Product inspection but will not participate
during the inspection unless requested by ICOS or a regulatory representative.

 

ICOS will [*]PDL will [*]

 

ICOS will hold daily wrap-up discussions with PDL to
discuss any potential issues identified and corrective action plans.

 

[*]addressing manufacturing,
facility, and compliance observations. 
PDL will receive one copy of any FDA 483 appropriately purged.

 

For regulatory
observations (e.g. FDA 483 observations) that specifically involve the Product,
[*]

 

For regulatory observations (e.g. FDA483 observations)
that involve facility and system-related cGMP issues[*]

 

5. Compliance

 

5.1 Roles
of the parties

 

ICOS, in its activities under the Agreement, is
responsible for compliance with cGMP, other applicable guidelines and ICOS
SOPs.

 

30

 

PDL, in its activities under the Agreement, is
responsible for compliance with cGMP and applicable guidelines and for
confirming ICOS’ compliance with cGMP, other applicable guidelines and ICOS
SOPs.

 

5.2
Audits

 

Upon no less than [*]notice to
ICOS, PDL shall be entitled to perform one audit of ICOS facilities,
laboratories and warehouses each year for the purposes of confirming ICOS
compliance with cGMP, applicable guidelines and ICOS SOPs in the manufacture,
testing and validation of the Product. 
The audit will be limited to [*]to occur on
mutually agreed dates.

 

[*]

 

[*]

 

At the conclusion of each audit, PDL will hold a
wrap-up meeting with ICOS and/or its subcontractors to review all significant
audit observations.

 

Within[*]of each
audit that it performs at ICOS and its subcontractors, PDL will provide ICOS
with a written report of its observations and recommendations.  Within [*]of receipt
of PDL’s audit report, ICOS and/or its subcontractors will provide a written
response to PDL including a response to all PDL observations and details
regarding corrective actions.

 

5.3
Documentation

 

ICOS is responsible for generating and maintaining
records of equipment usage, calibration, cleaning and maintenance.

 

ICOS is responsible for developing documentation to
support the manufacturing, testing and validation of the Product as defined by
the Scope of Services.

 

PDL-QA must approve documents and procedures specific
to the Product prior to implementation as listed below:

 

•                  Master Batch Records specific for the
production of the Product.

 

•                  Test Methods specific for the
production and testing of the Product.

 

•                  Product specific Material
Specifications for materials produced during the manufacture of the Product,
including the Product.

 

ICOS will provide PDL with copies of all
Product-specific documents used in the production, testing and validation of
the Product, upon request.  Documents
that are not specific to the Product are available for onsite review.

 

31

 

Changes to documentation will be implemented according
to the Change Control section of this document.

 

ICOS is responsible for maintaining Product batch
production and testing records for the period of [*].  Written authorization from PDL-QA is required
before the destruction of Product records. 
When ICOS is no longer willing or able to store Product records, PDL may
have the records destroyed, or transferred to an alternate storage location at
PDL’s expense.

 

5.4 Product Release

 

ICOS and PDL will each identify a Quality Assurance
representative who will function as the points of contact between the companies
for the purposes of communication regarding Product release and regulatory
compliance activities.

 

ICOS will source raw materials and components to be
used in the manufacture of the Product and will ensure that approved
specifications are in place.

 

PDL will determine in-process, release and stability
specifications for the Product.  ICOS and
PDL will mutually agree on these testing specifications for the Product.  The parties will mutually agree in writing to
all changes to specification before implementation.  ICOS may subcontract some or all of the
Product testing, subject to prior written approval by PDL.

 

ICOS is responsible for control and monitoring of the
Product manufacturing process and production facility.

 

ICOS is responsible for reviewing Product lot records,
test results against specifications and determining whether to reject the lot
or issue a manufacturer’s release to PDL-QA. 
PDL-QA is responsible for the final release of each Product lot.

 

ICOS will issue a Certificate of Analysis and
Certification of Compliance to PDL for each lot that receives a manufacturer’s
release.  The Certificate of Analysis
will contain a summary of the Product test results, specifications, and date of
manufacture.  The Certificate of
Compliance will contain a statement signed by ICOS’ QA representative stating
that the lot has been manufactured and tested in compliance with cGMPs, ICOS
procedures and applicable guidelines.

 

PDL may request additional documentation to support
its review and release of Product lots, including but not limited to copies of
Batch Production Records, raw data from Product testing and in-process test
results.  Environmental monitoring data
is available for on site review.

 

PDL will make reasonable efforts to release each lot
within [*] of receipt of the Certificate of
Analysis, Certificate of Compliance and documents listed in the scope of
services.

 

32

 

ICOS will store and ship the Product according to
written PDL instructions and in compliance with cGMP.  ICOS will ship Product only upon PDL’s
approval.

 

PDL is
responsible for retaining samples from each lot for testing in accordance with
cGMP.  ICOS will provide retain samples
to PDL as identified in the production batch records.

 

5.5 Product Complaints and Adverse Drug Events

 

PDL shall notify ICOS of all complaints related to the Products that
occur after release and transportation if the complaint is deemed to be
directly related to the manufacture of the Product including, but not limited
to, Product testing, batch record review, procedure assessment or examination
of retention samples. ICOS shall provide the necessary information to assist
any investigations required by PDL as a result of a Product complaint or
adverse event.

 

5.6 Product Recall

 

PDL is responsible for instituting and facilitating a
Product recall.

 

PDL will notify ICOS in a timely fashion when a
Product recall may be due to manufacturing of the Products.

 

In the event that a Product recall may be due to
manufacture of the Products, ICOS will provide PDL [*]ICOS
will provide this information to PDL within [*]of
receipt of the request from PDL.

 

At PDL’s request and under PDL’s direction, ICOS will
support communication with regulatory authorities.

 

5.7 Change Control

 

ICOS and PDL must mutually approve changes to
documents and procedures listed as requiring PDL approval in Section 5.3,
prior to implementation.  Administrative
changes (i.e. correcting typographical errors) do not require PDL approval.

 

5.8 Validation

 

All validation specific to the Product (as specified
in the Scope of Services) must be executed according to protocols approved
before execution by PDL.

 

ICOS will provide PDL with copies of all Product
specific validation reports.  Validation
reports which are Product related but not Product specific are available for on
site review.

 

33

 

5.9 Investigations

 

ICOS will notify PDL of all excursions, critical
deviations, observations and investigations that could impact past, current or
future lots of the Product.

 

Laboratory investigations will be performed when an
out of specification (OOS) result is obtained during Product testing.  Resampling and/or retests may be authorized
by the ICOS Laboratory Manager during the laboratory investigation phase of an
OOS investigation as described in ICOS standard operating procedures.  ICOS will notify PDL of all Product testing
failures within [*], and before initiating
retesting and/or resampling of any sample where the laboratory investigation
did not show laboratory error to be the cause of the OOS result.

 

All critical deviation investigations concerning the
Product and conducted at ICOS will be reviewed and approved by ICOS and
reviewed by PDL after completion.

 

6.
Product Supply

 

6.1 Roles
of the parties

 

ICOS will perform manufacture, testing and validation
of the Products in its facilities as defined in the Scope of Services.

 

PDL is authorized to have [*]
present at ICOS’ manufacturing facilities during Product manufacture, testing and/or
validation.  Additional PDL
representatives may be permitted when mutually agreed with ICOS.

 

7.
Authorization of production

 

Manufacture of the Product at ICOS will be authorized
in accordance with the Agreement.

 

7.1 Lot
numbers

 

ICOS is responsible for assigning and tracking unique
identifier numbers to each lot of raw material, component, product intermediate
and Product.  From this information ICOS
will develop a trace tree for each lot of Product; ICOS will send to PDL the
trace tree for any and all Product lots upon request by PDL.

 

7.2 Dates
of production and expiration

 

The dates of manufacture will be determined by the
date of sterile filtration, and documented in the Batch Production
Records.  PDL will determine the
expiration date of the Product.

 

34

 

8.
Dispute Resolution

 

Disputes concerning the acceptability of Product lots
or general compliance issues will be resolved by the Quality Assurance
representatives of the Parties.  If the
dispute is not resolved after [*], either
Party may upon written notification to the other request that the dispute be
resolved according to the provisions of the Agreement.

 

35

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