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EXHIBIT 10.1
EVALUATION AND LICENSE AGREEMENT
This Evaluation and License Agreement (the "Agreement") is
effective as of this 16th day of December, 1997 (the "Effective Date"), by and
between PHARMACYCLICS, INC., a Delaware corporation, having a principal place of
business at 000 X. Xxxxxx Xxxxxx, Xxxxxxxxx, XX 00000-0000 U.S.A
("Pharmacyclics") and ALCON PHARMACEUTICALS LTD., a Swiss corporation, having
its principal place of business at Xxxxxxxxxxxxx 00, XX-0000 Xxxx, Xxxxxxxxxxx
("Alcon").
WITNESSETH
WHEREAS, Pharmacyclics has developed certain proprietary porphyrin-like,
metal-containing agents, including PCI-0123 (as such term is defined below),
which are potentially useful in ophthalmic applications; and
WHEREAS, Alcon wishes to evaluate PCI-0123 on an exclusive basis during a
certain evaluation period in order to determine its commercial interest therein,
and if it elects to do so, to secure worldwide exclusive rights to develop and
commercialize products based thereon in the field of ophthalmology; and
WHEREAS, Pharmacyclics is willing to xxxxx Xxxxx such exclusive evaluation
rights during the evaluation period and, in the event Alcon makes an election,
such worldwide, exclusive rights to so develop and commercialize products based
thereon in the field of ophthalmology on the terms set forth in this Agreement;
NOW, THEREFORE, the Parties hereto mutually agree as follows:
1. DEFINITIONS. The following definitions will control the
construction of each of the following terms wherever they appear in this
Agreement:
1.1 AFFILIATE shall mean, as to a Party hereto, any person, corporation,
company, partnership, joint venture, firm and/or other entity (a "Person") which
controls, is controlled by or is under common control with such Party. For these
purposes, "control" means direct or indirect ownership or control of at least
fifty percent (50%) of the outstanding voting securities of a corporation or a
comparable equitable interest in any other type of entity.
1.2 ALCON INVENTIONS shall mean all inventions relating to Licensed
Products in the Field made or discovered solely by employees or agents of Alcon,
as well as Alcon's interest in inventions made or discovered jointly by
employees or agents of Alcon and Pharmacyclics, all in the course of the conduct
of the development of Licensed Products under this Agreement.
1.3 ALCON PATENTS shall mean all patent applications claiming any Alcon
Inventions and all patents issued pursuant to any such patent applications, and
all substitutions, divisionals, reexaminations, reissues, renewals,
continuations, continuations-in-part, extensions, supplementary protection
certificates and foreign counterparts thereof.
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
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1.4 COMPETITIVE PRODUCT shall mean any electromagnetic radiation-activated
porphyrin or porphyrin analog product in the Field, other than the Licensed
Product, which directly competes in the indication or indications for which the
Licensed Product is then being developed, marketed or sold by Alcon.
1.5 CONFIDENTIAL INFORMATION shall have the meaning set forth in Section
15.2.
1.6 DETERMINATION shall have the meaning ascribed thereto in Section 2.8.
1.7 DEVICE shall mean any light source and/or light delivery devices and
related items (including, but not limited to diode chips) developed, produced
and/or manufactured by or on behalf of Pharmacyclics for use in the
photoactivation of the Licensed Product in the Field.
1.8 DRUG SUBSTANCE shall mean a composition containing a Licensed Product
in bulk form.
1.9 EMEA shall mean European Medicines Evaluation Agency.
1.10 EXTENDED LUTETIUM TEXAPHYRIN shall mean any Lutetium Texaphyrin owned
or controlled by Pharmacyclics which does not fall within the definition of
Licensed Product.
1.11 EVALUATION PERIOD shall mean the period commencing on the Effective
Date and terminating (*) after the Effective Date.
1.12 EVALUATION PLAN shall have the meaning ascribed thereto in Section
2.1.
1.13 FDA shall mean the United States Food and Drug Administration.
1.14 FD&C ACT shall mean the United States Food, Drug and Cosmetic Act.
1.15 FIELD shall mean the treatment of ophthalmic diseases or disorders.
1.16 FILL AND FINISH shall mean the filling into final container and
finishing of Drug Substance and packaging of finished Licensed Product.
1.17 FIRST COMMERCIAL SALE shall mean the first sale of the Licensed
Product for use, consumption or resale to any third party customer in the Field
and in the Territory after all relevant approvals have been obtained. For
purposes of this definition, Alcon Affiliates shall not be construed as third
party customers.
1.18 GOOD CLINICAL PRACTICES shall mean the clinical practices recognized
by the FDA in its April 30, 1997 Consolidated Guideline on Good Clinical
Practices and includes, but is not limited to, 21 CFR parts 50, 56, 312, and
812, as they may be amended from time to time.
1.19 GOOD LABORATORY PRACTICES shall mean the laboratory practices covered
by FDA regulations in 21 CFR part 58, as it may be amended from time to time.
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
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1.20 GOOD MANUFACTURING PRACTICES shall mean the manufacturing practices
covered by FDA regulations in 21 CFR parts 210-226 and 820, as they may be
amended from time to time.
1.21 HEALTH AUTHORITY means the health regulatory agency of a particular
country in the Territory.
1.22 HC AGREEMENT shall mean that certain Master Process Development and
Supply Agreement between Pharmacyclics and HCC dated September 6, 1996 for the
manufacture and supply of Drug Substance.
1.23 HCC shall mean the Hoechst Celanese Corporation or any successor in
interest to the Hoechst Celanese Corporation under the HC Agreement.
1.24 IND shall mean an Investigational New Drug Application filed with the
FDA and any foreign counterparts thereof.
1.25 LICENSED PRODUCT shall mean any therapeutic agent which contains
PCI-0123 or any other Lutetium Texaphyrin. Notwithstanding anything in this
Agreement, "Licensed Product" shall not include (i) any Lutetium Texaphyrin
which is covalently bound to a biological molecule (e.g., sugars, nucleic acids,
peptides, lipids, proteins, hormones, steroids, polynucleotides, carbohydrates
and amino acids), which substantially enhances, relative to PCI-0123, in vivo
biolocalization to an ophthalmic tissue associated with a specific ophthalmic
disease; or (ii) any Lutetium Texaphyrin that is conjugated to a drug or
biological agent having a mechanism of action that is different from the
photosensitization mechanism of a Lutetium Texaphyrin; or (iii) any Lutetium
Texaphyrin that is bound to a Non-Lutetium Texaphyrin.
1.26 LUTETIUM TEXAPHYRIN shall mean any Texaphyrin owned or controlled by
Pharmacyclics which contains lutetium.
1.27 MA shall mean "Marketing Approval," the approval to market and
commercially distribute a pharmaceutical product or medical device, exclusive of
government price or reimbursement approval where applicable, by the FDA, the
EMEA or by the Health Authority (or other appropriate regulatory agency) of a
country within the Territory.
1.28 MAA shall mean an application for MA submitted to the EMEA or other
Health Authority.
1.29 NDA shall mean a new drug application filed with the FDA.
1.30 NET SALES shall mean the final invoiced selling price of Licensed
Product, reduced by the following (to the extent the following are not already
deducted in calculating the final invoiced selling price):
a) rebates or coupon redemptions;
b) transportation charges invoiced, including air freight and insurance;
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c) sales, use, excise or ad valorem taxes (to the extent borne by Alcon);
d) rebates or discounts given to buying cooperatives;
e) promotional, cash, trade or volume discounts;
f) credits for returns and pricing adjustments; and
g) allowances or credits to customers for spoiled, damaged or out-dated
product.
In calculating Net Sales, goods placed in inventory or on consignment shall not
be deemed sold until paid by customer. For purposes of this Agreement, Alcon's
intracompany transfers or sales to Affiliates shall not be regarded as sales.
Sales shall not include the distribution of complimentary samples.
1.31 NON-LUTETIUM TEXAPHYRIN shall mean any Texaphyrin owned or controlled
by Pharmacyclics which contains no lutetium.
1.32 PARTY shall mean either Pharmacyclics or Alcon, as the context may
require.
1.33 PCI-0123 shall mean the Texaphyrin compound incorporating lutetium and
having the structure shown in Appendix A and the IUPAC name as follows: Bis
(acetato-O)[9,10-diethyl-20,21-bis[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]-4,15-
dimethyl-8,11-imino-6,3:16,13-dinitrilo-1,18-benzodiazacycloeicosine-5,14-
dipropanolato-N1,N18, N23, X00, X00] lutetium hydrate.
1.34 PCI-0123 FORMULATION shall mean PCI-0123 in final formulation for
human dosing which meets the specifications set forth in Appendix F.
1.35 PCI-0123 SUBSTANCE shall mean a composition containing PCI-0123 in
bulk form which meets the specifications set forth in Appendix E.
1.36 PHARMACYCLICS INVENTIONS shall mean all inventions relating to the
Licensed Product or Device in the Field made or discovered solely by employees
or agents of Pharmacyclics, as well as Pharmacyclics' interest in inventions
made or discovered jointly by employees or agents of Pharmacyclics and Alcon,
all in the course of the conduct of the development of the Licensed Product
under this Agreement.
1.37 PHARMACYCLICS KNOW-HOW shall mean: all non-patented inventions,
know-how, technology, trade secrets, processes, data, methods and any physical,
chemical or biological material or other information which: (i) Pharmacyclics
owns, controls or has a license to (with a right to sublicense) as of the
Effective Date or during the term of this Agreement; and (ii) relates to the
development, Fill and Finish, use (including photoactivation by the Device),
marketing, sale, importation and distribution of a Licensed Product or Device
for use in the Field and in the Territory.
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1.38 PHARMACYCLICS PATENTS shall mean: (i) all patents and patent
applications owned or controlled by or licensed to Pharmacyclics (with the right
to grant sublicenses) in the Territory as of the Effective Date or during the
term of this Agreement which are necessary or useful in connection with the
development, use or sale of a Licensed Product or Device in the Field,
including, without limitation, the patents and patent applications listed in
Appendix B hereto; (ii) all patents issued pursuant to any such patent
applications; and (iii) all substitutions, divisionals, reexaminations,
reissues, renewals, continuations, continuations-in-part, extensions, and
supplementary protection certificates of the patents described in (i) and (ii)
of this definition.
1.39 PHARMACYCLICS TECHNOLOGY shall mean the Pharmacyclics Inventions,
Pharmacyclics Patents and Pharmacyclics Know-How.
1.40 PHASE II shall mean that phase of clinical development as defined in
the FD&C Act and applicable regulations promulgated thereunder.
1.41 PHASE III shall mean that phase of clinical development as defined in
the FD&C Act and applicable regulations promulgated thereunder.
1.42 PDT OR PHOTODYNAMIC THERAPY shall mean the treatment of diseases of
the eye by the application of light to the eye containing a photosensitizing
therapeutic agent.
1.43 PROGRAM shall mean the evaluation program carried out by Alcon
pursuant to Article 2 focused on the use of PCI-0123 in treating diseases of the
eye.
1.44 PROGRAM INTELLECTUAL PROPERTY shall have the meaning ascribed thereto
in Section 2.6.
1.45 TERM shall have the meaning set forth in Article 13.
1.46 TERRITORY shall mean all the countries and territories of the world.
1.47 TEXAPHYRIN shall mean any molecule which has as its core structure the
structure set forth on Appendix C.
1.48 UT LICENSE shall mean that certain License Agreement, effective as of
May 28, 1992, between Pharmacyclics and the University of Texas, a copy of which
has been provided by Pharmacyclics to Alcon prior to the Effective Date.
2. EVALUATION PROGRAM.
2.1 PREPARATION AND CONDUCT OF EVALUATION PLAN. Attached hereto as
Appendix D is a general plan (the "Evaluation Plan") which outlines the
activities to be carried out by or on behalf of Alcon in the course of the
Program. The Evaluation Plan also includes an initial forecast of Alcon's
expected needs of PCI-0123 Substance and PCI-0123 Formulation for the Program.
During the Evaluation Period, Alcon shall have the exclusive right to evaluate
PCI-0123 for potential commercial development in the Field. Alcon shall
diligently carry out the tasks and
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activities under the Evaluation Plan with the goal of completing the Program
within the Evaluation Period.
2.2 COST OF THE PROGRAM. Alcon shall bear all costs and expenses in
connection with the Program. Within thirty (30) days of receipt of an invoice
therefore, Alcon shall reimburse Pharmacyclics for agreed upon direct expenses
incurred by Pharmacyclics in connection with the Program, including, but not
limited to, Pharmacyclics' direct cost to supply Devices and, as more fully
described in Section 2.4, PCI-0123 Substance and PCI-0123 Formulation.
2.3 COMPLIANCE WITH LAW. Alcon undertakes to comply at all times with the
applicable laws and regulations of the FDA and any other governmental
requirements which apply to activities to be performed pursuant to the
Evaluation Plan, including, but not limited to, safety regulations and
regulations relating to the handling and disposal of animals.
2.4 SUPPLY OF PCI-0123 SUBSTANCE AND PCI-0123 FORMULATION.
(a) Pharmacyclics will supply Alcon with PCI-0123 Substance and
PCI-0123 Formulation in amounts sufficient to carry out the Program.
(b) The price of all PCI-0123 Substance and PCI-0123 Formulation
supplied to Alcon pursuant to Section 2.4(a) shall be equal to (*) for the
respective form of PCI-0123.
(c) Alcon will provide written purchase orders to Pharmacyclics for
the PCI-0123 Substance and PCI-0123 Formulation required for conducting the
Program. With each order, Alcon will provide a forecast of its requirements for
three calendar months thereafter. Pharmacyclics will deliver or cause to be
delivered PCI-0123 Substance and PCI-0123 Formulation within thirty (30) days
from receipt of an order from Alcon or at a later date if so requested in the
order. In the event Pharmacyclics fails to timely deliver the PCI-0123 Substance
and/or PCI-0123 Formulation in accordance with this subsection 2.4(c), Alcon's
sole remedy shall be to extend the Evaluation Period for an amount of time
corresponding to the delay of any such delivery. Delivery is made EXW (Incoterms
1990) Pharmacyclics facility in Sunnyvale.
2.5 ACQUISITION OF DEVICE. Upon reasonable request by Alcon, Pharmacyclics
shall assist Alcon in the acquisition of a Device suitable for pre-clinical and
clinical studies of a Licensed Product in the Field. Alcon shall reimburse
Pharmacyclics for any expenses pre-approved by Alcon which were incurred by
Pharmacyclics in assisting Alcon with the acquisition of the Device.
2.6 INTELLECTUAL PROPERTY DEVELOPED DURING THE EVALUATION PERIOD.
Ownership of any and all patentable and non-patentable inventions, know-how,
technology, data, and analyses of results relating to PCI-0123, PCI-0123
Substance, PCI-0123 Formulation and/or Devices that are developed in the
performance of the Program (the "Program Intellectual Property") that are
developed by employees, agents or others acting on behalf of Pharmacyclics or
Alcon shall be owned by Pharmacyclics without further consideration or royalty
obligation. Alcon shall take all necessary actions to assign, and to have its
employees and agents assign, such Program Intellectual Property to
Pharmacyclics. In the event Alcon makes the Determination, all such
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
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Program Intellectual Property shall be deemed to be part of the Pharmacyclics
Technology. Regardless of whether Alcon makes the Determination, Pharmacyclics
hereby grants a perpetual, worldwide, non-exclusive royalty-free license to
Alcon to practice the Program Intellectual Property that is developed by
employees, agents or others acting on behalf of Alcon for all purposes except to
develop, make, use, sell, offer for sale or import Texaphyrins.
2.7 EXCHANGE OF INFORMATION; REPORTS DURING THE EVALUATION PERIOD.
(a) Pharmacyclics shall make available to Alcon such Pharmacyclics
Know-How, regulatory reports, communiques, chemistry, stability and safety data
on PCI-0123, and information on the Device, as Pharmacyclics has in its
possession, subject to any confidentiality agreements between Pharmacyclics and
third parties, as are necessary or useful to accomplishing the goals of the
Evaluation Plan. Pharmacyclics' technical personnel will be reasonably available
to consult with Alcon from time-to-time to assist in the accomplishment of the
Evaluation Plan; provided that Alcon shall reimburse Pharmacyclics for all
expenses which are incurred by Pharmacyclics' employees and consultants under
this Section 2.7(a); provided, however, such expenses are pre-approved by Alcon.
(b) Upon reasonable prior notice, Alcon shall allow technical
personnel and consultants of Pharmacyclics to access all Program data generated
during the Program. Also upon reasonable notice, Alcon personnel involved in the
Program shall be available for discussions with Pharmacyclics personnel
regarding the progress of the Program. Alcon shall make monthly telephonic or
written reports to Pharmacyclics about the status of the Program. In addition,
Alcon shall make detailed quarterly written reports to Pharmacyclics. Such
quarterly reports shall contain detailed summaries of all pertinent information
that was obtained in the course of the Program and Program Intellectual Property
that was developed by Alcon during the period covered by the report. In the
event that, based on such detailed summaries, Pharmacyclics wishes to review any
underlying data arising from the Program and/or Alcon's analyses of the results
of the Program, Alcon shall make such data and analyses available to
Pharmacyclics and, upon the reasonable request of Pharmacyclics, Alcon will
provide copies of such data and/or analyses to Pharmacyclics. Formal status
meetings shall be held quarterly and may be held by teleconference. Within
thirty (30) days from the end of the Evaluation Period, Alcon shall provide to
Pharmacyclics a draft of a final written report and, within sixty (60) days from
the end of the Evaluation Period, a final written report, which shall include
all information, data and analyses of the results that were obtained and Program
Intellectual Property that was developed by Alcon in the course of the Program.
(c) Alcon shall allow clinical personnel and consultants of
Pharmacyclics, at their own expense and without interfering with Alcon personnel
and investigators to visit the clinical trials sites, if any, wherein clinical
trials are being conducted by or on behalf of Alcon in the course of the
Program. In the event Pharmacyclics desires to visit a particular clinical trial
site, it shall notify Alcon of the time and place it desires to visit. Based on
Pharmacyclics request, Alcon shall arrange a visit to the particular trial site,
at a mutually agreed upon time, and shall accompany Pharmacyclics personnel on
their visit to the particular clinical site. Notwithstanding anything in this
Section 2.7(c), Pharmacyclics personnel shall not monitor, direct or attempt to
direct any of the Alcon investigators in carrying out their clinical
responsibilities.
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(d) Pharmacyclics shall also make quarterly written reports to Alcon
regarding the progress of Pharmacyclics and HCC in producing PCI-0123 Substance
which complies with the specifications of Appendix E, part II.
(e) Alcon will be responsible for the administrative handling of all
filings and other communications with Health Authorities during the Evaluation
Period (including, but not limited to, INDs) in all countries of the Territory
for the Licensed Product and the Device in the Field (collectively, the
"Evaluation Period Regulatory Filings"), unless otherwise required by the Device
manufacturer or required by the laws or regulations of the applicable
jurisdiction. Alcon shall use best efforts to give Pharmacyclics the opportunity
to comment upon, prior to filing, all Evaluation Period Regulatory Filings, in
order to advise Alcon of any possible improvements of the proposed filings
Pharmacyclics believes to be necessary or useful, provided, however,
Pharmacyclics shall provide its comments on a given Evaluation Period Regulatory
Filing, if any, to Alcon within three (3) business days of Pharmacyclics'
receipt of such filing. It is understood that Alcon may provide components of
such Evaluation Period Regulatory Filings to Pharmacyclics in a piecemeal
manner, as such components are prepared by Alcon. Alcon shall in good faith
consider Pharmacyclics' opinion and advice when filing the Evaluation Period
Regulatory Filings. Notwithstanding the foregoing, in all events the final
decision as to the content and timing of such filings shall be made by Alcon.
Alcon will pay all fees and expenses related thereto. Alcon shall keep
Pharmacyclics informed of the status of Evaluation Period Regulatory Filings on
an ongoing and timely basis, including, providing copies of all Evaluation
Period Regulatory Filings and any supplements or amendments thereto, to
Pharmacyclics. During the Evaluation Period, Alcon shall be the sole holder of
the Evaluation Period Regulatory Filings, and will at its own expense, be
responsible for all administrative matters necessary to compile and submit the
Evaluation Period Regulatory Filings for the Licensed Product in each country of
the Territory. During the Evaluation Period, Alcon shall also be responsible for
maintaining the Evaluation Period Regulatory Filings and will bear the
registration renewal fees for the Evaluation Period Regulatory Filings of the
Licensed Product in each country of the Territory in which same are filed. In
the event Alcon makes the Determination, the Evaluation Period Regulatory
Filings shall be deemed to be "Regulatory Filings" for purposes of Section 9.1.
2.8 DEVELOPMENT AND COMMERCIALIZATION DETERMINATION. During the Evaluation
Period, Alcon shall evaluate development and commercialization opportunities for
Licensed Products in the Field. Not later than forty-five (45) days after the
end of the Evaluation Period, Alcon shall notify Pharmacyclics in writing
whether or not it desires to go forward and pursue additional development and
commercialization of Licensed Products in the Field. In the event Alcon
determines to so continue such development and commercialization (the
"Determination") it shall provide Pharmacyclics with written notice of its
decision and shall pay Pharmacyclics the license fee pursuant to Section 4.2. In
the event that Alcon chooses not to so continue, (i) this Agreement shall
terminate immediately, (ii) all rights of Alcon created by this Agreement with
regard to Licensed Products shall expire, except as provided in Section 2.6,
(iii) Pharmacyclics shall be free to pursue the development and
commercialization of Licensed Products alone, through or in collaboration with,
a third party, (iv) Alcon shall return any and all remaining quantities of
PCI-0123 Substance, PCI-0123 Formulation, any materials derived from PCI-0123
Substance or PCI-0123 Formulation, all Devices (except for Devices that have
been purchased by Alcon from Pharmacyclics or a third party), all Program
Intellectual Property and data, and all
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other Pharmacyclics Confidential Information and (v) Alcon shall assign or
otherwise transfer to Pharmacyclics all Evaluation Period Regulatory Filings.
3. LICENSE GRANTS; EXCLUSIVITY.
3.1 DEVELOPMENT AND EVALUATION LICENSES. Subject to the terms and
conditions of this Agreement and effective only in the event of a Determination,
Pharmacyclics hereby grants to Alcon an exclusive (even as to Pharmacyclics)
sublicense under the Pharmacyclics Technology governed by the UT License and an
exclusive (even as to Pharmacyclics) license under all other Pharmacyclics
Technology, to conduct clinical development in humans of Licensed Products for
use in the Field and in the Territory. Subject to the terms and conditions of
this Agreement and effective only in the event of a Determination, Pharmacyclics
hereby grants to Alcon an exclusive (except as to Pharmacyclics) sublicense
under the Pharmacyclics Technology governed by the UT License and an exclusive
(except as to Pharmacyclics) license under all other Pharmacyclics Technology,
to evaluate Licensed Products for use in the Field and in the Territory.
3.2 COMMERCIALIZATION LICENSE. Subject to the terms and conditions of this
Agreement, and effective only in the event of a Determination, Pharmacyclics
hereby grants to Alcon an exclusive (even as to Pharmacyclics) sublicense under
the Pharmacyclics Technology governed by the UT License and an exclusive (even
as to Pharmacyclics) license under all other Pharmacyclics Technology, to
import, Fill and Finish, market, sell, offer for sale and distribute Licensed
Products for use in the Field and in the Territory.
3.3 UT LICENSE. Alcon acknowledges and understands that the licenses to the
Pharmacyclics Technology granted to Alcon under Sections 3.1 and 3.2 contemplate
sublicenses of certain of such Pharmacyclics Technology under and pursuant to
the UT License, and that such sublicensed Pharmacyclics Technology is subject to
any rights retained by the University of Texas, including, without limitation,
rights with respect to patent infringement, prosecution and maintenance under
Sections 7 and 13 of the UT License, or retained by the United States government
pursuant to the UT License.
3.4 SUBLICENSE RIGHTS. Alcon shall have the right to sublicense the
licenses granted in Sections 3.1 and 3.2, subject to the prior written approval
of Pharmacyclics, which approval shall not be unreasonably withheld or delayed,
so long as each sublicensee agrees to be bound mutatis mutandis by all of the
terms and conditions of this Agreement, except that no consent of Pharmacyclics
shall be required for sublicenses to Affiliates of Alcon.
3.5 RIGHTS UPON EXPIRATION. Upon the expiration of Alcon's obligations to
pay royalties pursuant to Section 4.5, and provided that this Agreement has not
been terminated early pursuant to Article 14, Alcon's license rights granted
hereunder with respect to Licensed Products then sold by Alcon and/or its
Affiliates shall become paid-up, royalty-free, irrevocable and perpetual.
3.6 EXCLUSIVITY; RIGHT OF FIRST NEGOTIATION.
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(a) EXCHANGE OF INFORMATION; REPORTS DURING POST-EVALUATION PERIOD.
During the post-Evaluation Period of this Agreement, Pharmacyclics and Alcon
personnel shall routinely, but not less than annually, conduct meetings for
purposes of disclosing to Alcon any information Pharmacyclics has in its
possession relative to any Texaphyrins, including Extended Lutetium Texaphyrins
and Non-Lutetium Texaphyrins, or any other chemical entities which Pharmacyclics
believes may have application in the Field. The foregoing sentence: (i) shall
not apply to information which Pharmacyclics is contractually precluded from
disclosing and (ii) shall not apply with respect to Texaphyrins and any other
chemical entities which (x) Alcon has indicated, pursuant to Subsection
3.6(c)(1) or 3.6(c)(2), it is not interested in developing and commercializing
and (y) Pharmacyclics is developing and commercializing, either on its own or
with a third party.
(b) MACULAR DEGENERATION RETINOPATHY. For so long as Alcon is
developing one or more Licensed Products in the field of macular degeneration
retinopathy, Alcon shall have the exclusive right, during the period running
from the Effective Date and ending upon the earlier of (i) Alcon's receipt of
its first MA or NDA approval for a Licensed Product or (ii) (*) year anniversary
of the Effective Date, to evaluate any Extended Lutetium Texaphyrin or
Non-Lutetium Texaphyrin in the field of macular degeneration retinopathy, and
the exclusive right to negotiate a separate agreement with Pharmacyclics for a
license to any Extended Lutetium Texaphyrin or Non-Lutetium Texaphyrin in the
field of macular degeneration retinopathy. For the avoidance of any doubt, for
so long as Alcon is developing one or more Licensed Products in the field of
macular degeneration retinopathy, Pharmacyclics shall not enter into a license
agreement or negotiate a license, covenant or other technology transfer
agreement, including a screening agreement, with any third party relating to an
Extended Lutetium Texaphyrin or Non-Lutetium Texaphyrin for use in the field of
macular degeneration retinopathy prior to the earlier of (i) Alcon's receipt of
its first MA or NDA approval for a Licensed Product, or (ii) (*) year
anniversary of the Effective Date. Following the earlier date of the preceding
sentence, in the event Pharmacyclics obtains bona fide animal or human data
which suggests the likelihood of improved efficacy, safety and/or performance of
an Extended Lutetium Texaphyrin or Non-Lutetium Texaphyrin over a Licensed
Product in the treatment of macular degeneration retinopathy, Pharmacyclics
shall be free to engage in negotiations with third parties for the license of
such Extended Lutetium Texaphyrin or Non-Lutetium Texaphyrin for use in treating
such macular degeneration retinopathy; provided, however, Pharmacyclics first
offers to negotiate with Alcon for a license of such Extended Lutetium
Texaphyrin or Non-Lutetium Texaphyrin for the treatment of such macular
degeneration retinopathy, pursuant to Section 3.6(c).
(c) RIGHT OF FIRST NEGOTIATION.
(1) EXTENDED LUTETIUM TEXAPHYRINS, NON-LUTETIUM TEXAPHYRINS.
Subject to this Section 3.6, in the event Pharmacyclics desires to sell or
license the rights to an Extended Lutetium Texaphyrin or Non-Lutetium Texaphyrin
in the Field and has obtained bona fide animal or human data which suggests the
likelihood that such Extended Lutetium Texaphyrin or Non-Lutetium Texaphyrin has
application in the Field, Pharmacyclics shall provide written notice
("Additional Texaphyrins Notice") to Alcon. The Additional Texaphyrins Notice
shall contain a description of the Extended Lutetium Texaphyrin or Non-Lutetium
Texaphyrin, along with a detailed description of such animal or human data.
Within thirty (30) days of receipt of the
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
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Additional Texaphyrins Notice from Pharmacyclics, Alcon shall provide a written
notice ("Alcon Interest Notice") to Pharmacyclics indicating whether it is
interested in developing and commercializing such Extended Lutetium Texaphyrin
or Non-Lutetium Texaphyrin in the Field. If Alcon is not interested,
Pharmacyclics shall have no obligations to Alcon with respect to such Extended
Lutetium Texaphyrin or Non-Lutetium Texaphyrin. If Alcon is interested in
licensing such Texaphyrin, the parties shall negotiate in good faith an
agreement for the development and commercialization of such Extended Lutetium
Texaphyrin or Non-Lutetium Texaphyrin in the Field. In the event the parties are
unable to reach such an agreement within ninety (90) days of the date of the
Alcon Interest Notice, Pharmacyclics shall be free to develop and commercialize
such Extended Lutetium Texaphyrin or Non-Lutetium Texaphyrin in all fields
and/or enter into an agreement with a third party to do so; provided, however,
that Pharmacyclics shall not enter into such agreement with a third party which
contains terms less favorable to Pharmacyclics than those last offered by Alcon
pursuant to the preceding sentence, without first offering such less favorable
terms to Alcon. As used in the preceding sentence, the term "less favorable
terms" shall be construed to mean the basic financial terms, i.e., licensing
fees, milestone fees, royalty payments and the financial value of any
cross-licensing provision that are, in totality, less favorable than the same
basic financial terms last offered by Alcon under this Section 3.6(c)(1).
(2) OTHER PHARMACYCLICS COMPOUNDS. In the event Pharmacyclics
desires to grant a license to any other compound for use in the Field, other
than an Extended Lutetium Texaphyrin or a Non-Lutetium Texaphyrin (an "Other
Compound"), Pharmacyclics shall provide written notice to Alcon. Within thirty
(30) days of receipt of such notice from Pharmacyclics, Alcon shall provide a
written notice (the "Other Compound Interest Notice") to Pharmacyclics
indicating whether it is interested in developing and commercializing such Other
Compound in the Field under this Subsection 3.6(c)(2). If Alcon is not
interested, Pharmacyclics shall have no obligations to Alcon with respect to
Other Compound. If Alcon is interested in licensing such Other Compound, the
parties shall negotiate in good faith an agreement for the development and
commercialization of such Other Compound in the Field. In the event the parties
are unable to reach such an agreement within ninety (90) days of the Other
Compound Interest Notice, Pharmacyclics shall be free to develop and
commercialize such Other Compound in any field and/or enter into an agreement
with a third party to do so.
(d) DILIGENCE. In the event Alcon licenses an Extended Lutetium
Texaphyrin or a Non-Lutetium Texaphyrin (a "Second Generation Product") from
Pharmacyclics, pursuant to a separate license agreement entered into as provided
for in Section 3.6(b) or (c) (a "Second License Agreement"), for use in treating
the same pathology as the pathology for which a Licensed Product, at the time,
is being developed or commercialized by Alcon (the "Common Pathology"), and if,
in the course of developing such Second Generation Product, Alcon makes a good
faith determination that the Second Generation Product demonstrates improved
efficacy, safety and/or performance over Licensed Product for treatment of the
Common Pathology and therefore Alcon ceases all development and
commercialization of Licensed Product for the Common Pathology, then the
diligence requirements of Sections 8.2 and 8.3 of this Agreement will be waived
for the Licensed Product for the Common Pathology and, as will be set forth in
the Second License Agreement, diligence obligations similar to those set forth
in Sections 8.2 and 8.3 of this Agreement will be apply with respect to the
Second Generation Product for the Common Pathology.
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3.7 COVENANTS OF ALCON. Subject to the terms of this Agreement, and during
the Term of this Agreement, Alcon covenants that it shall not, nor shall it
permit any Affiliate to, use or practice directly or indirectly any
Pharmacyclics Know-How, and, until expiration of the applicable patent, any
inventions claimed in any Pharmacyclics Patents, for any purposes other than
those explicitly contemplated by this Agreement. Alcon shall ensure that any
permitted sublicense under this Agreement shall contain terms with the same
effect as this Section 3.7, and agrees that it will, at Pharmacyclics' request,
take all measures necessary to enforce the pertinent terms of such sublicense
against the sublicensee.
3.8 COMPETITIVE PRODUCTS.
(a) Following the Determination and during the Term of this Agreement
in the event that Alcon (i) initiates human clinical trials of a Competitive
Product with the intention of commercializing such Competitive Product during
the Term of this Agreement; (ii) initiates commercial sale of a Competitive
Product; or (iii) enters into an agreement pursuant to which it acquires rights
to a Competitive Product (whether by assignment, license or otherwise) with the
intention of commercializing such Competitive Product during the Term of this
Agreement, other than an agreement described in Section 3.8(b), then
Pharmacyclics shall have the right to immediately terminate this Agreement.
Alcon shall promptly notify Pharmacyclics if it undertakes any of the above
activities.
(b) In the event Alcon acquires a third party entity and such third
party entity was, at the time of such acquisition, developing or commercializing
a Competitive Product (an "Acquired Company Competitive Product"), Alcon shall
provide written notice of such acquisition and a description of the Acquired
Company Competitive Product to Pharmacyclics and the following shall apply:
(i) if, at the time of such acquisition, the Acquired Company
Competitive Product has received MA anywhere in the Territory and the Licensed
Product has not yet received MA anywhere in the Territory, Alcon shall continue
with development of the Licensed Product as set forth in this Agreement
(including, but not limited to, in accordance with Sections 8.1 and 8.2). Within
thirty (30) days of the date upon which the Licensed Product receives MA
anywhere in the Territory, Alcon shall elect whether to (x) continue
commercializing the Acquired Company Competitive Product in the Territory or (y)
commence commercializing Licensed Product in the Territory and shall provide
written notice to Pharmacyclics indicating which option it has elected. In the
event Alcon elects to continue commercializing the Acquired Company Competitive
Product in the Territory, then Pharmacyclics shall have the right to immediately
terminate this Agreement. In the event Alcon elects to commence commercializing
Licensed Product in the Territory, then Alcon shall, within (*) of such
election, cease marketing and selling (and enabling third parties to market and
sell) Acquired Company Competitive Product in the Territory.
(ii) if, at the time of such acquisition, the Acquired Company
Competitive Product has not yet received MA anywhere in the Territory and the
Licensed Product has received MA anywhere in the Territory, Alcon may continue
with development of the Acquired Company Competitive Product. Within thirty (30)
days of the date upon which the
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
12.
13
Acquired Company Competitive Product receives MA anywhere in the Territory,
Alcon shall elect whether to (x) continue commercializing the Licensed Product
in the Territory or (y) commence commercializing Acquired Company Competitive
Product in the Territory and shall provide written notice to Pharmacyclics
indicating which option it has elected. In the event Alcon elects to commence
commercializing the Acquired Company Competitive Product in the Territory, then
Pharmacyclics shall have the right to immediately terminate this Agreement. In
the event Alcon elects to continue commercializing Licensed Product in the
Territory, then Alcon shall not market or sell (or enable third parties to
market or sell) Acquired Company Competitive Product in the Territory.
(iii) if, at the time of such acquisition, the Acquired Company
Competitive Product has not yet received MA anywhere in the Territory and the
Licensed Product has not yet received MA anywhere in the Territory, Alcon shall
continue with development of the Licensed Product as set forth in this Agreement
(including, but not limited to, in accordance with Sections 8.1 and 8.2) and may
also elect to develop the Acquired Company Competitive Product. Within thirty
(30) days of the later of (m) the date upon which the Licensed Product receives
MA anywhere in the Territory and (n) the date upon which the Acquired Company
Competitive Product receives MA anywhere in the Territory, Alcon shall elect
whether it wishes to (x) commercialize the Acquired Company Competitive Product
in the Territory or (y) commercialize Licensed Product in the Territory and
shall provide written notice to Pharmacyclics indicating which option it has
elected. In the event Alcon elects to commercialize the Acquired Company
Competitive Product in the Territory, then Pharmacyclics shall have the right to
immediately terminate this Agreement. In the event Alcon elects to commercialize
Licensed Product in the Territory, then Alcon shall either (p) commencing on the
date of such election, not market or sell (or enable third parties to market or
sell) Acquired Company Competitive Product in the Territory (in the event the
Licensed Product received MA first) or (q) within (*) of such election, cease
marketing and selling (and enabling third parties to market and sell) Acquired
Company Competitive Product in the Territory (in the event the Acquired Company
Competitive Product received MA first).
(iv) if, at the time of such acquisition, the Acquired Company
Competitive Product has received MA anywhere in the Territory and the Licensed
Product has received MA anywhere in the Territory, Alcon shall, within thirty
(30) days of such acquisition, elect whether it wishes to (x) continue
commercializing the Acquired Company Competitive Product in the Territory or (y)
continue commercializing Licensed Product in the Territory and shall provide
written notice to Pharmacyclics indicating which option it has elected. In the
event Alcon elects to continue commercializing the Acquired Company Competitive
Product in the Territory, then Pharmacyclics shall have the right to immediately
terminate this Agreement. In the event Alcon elects to continue commercializing
Licensed Product in the Territory, then Alcon shall, within (*) of such
election, cease marketing and selling (and enabling third parties to market and
sell) Acquired Company Competitive Product in the Territory.
For purposes of Subsections 3.8(b)(i), (ii), (iii) and (iv), inclusion of the
phrases "enabling third parties to market and sell" and "enable third parties to
market or sell" shall not be deemed to preclude Alcon from selling outright to a
third party all rights to the Acquired Company
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
13.
14
Competitive Product (including applicable patent rights, MAs and trademarks),
thereby enabling such third party to market and sell the Acquired Company
Competitive Product.
3.9 DEVELOPMENT OF LICENSED PRODUCTS OUTSIDE THE FIELD.
(a) In the event that Pharmacyclics enters into an agreement with any
third party for the development, marketing and sale of a Licensed Product which
has the same chemical structure as a Licensed Product then under development or
commercialized by Alcon (a "Third Party Compound") for indications outside the
Field, but for sale in the Territory (a "Third Party Agreement"), it will ensure
that:
(i) The proposed Third Party Compound differs in its formulation
in such a manner that prescribing physicians could not reasonably be expected to
substitute in the marketplace such Third Party Compound for the Licensed
Product(s) then being developed or commercialized by Alcon in the Field; or
(ii) The proposed development program differs in such other
respects from the Alcon development program hereunder or its anticipated
commercialized Licensed Product then under development so as to otherwise ensure
that the substitution referred to in (i) above could not reasonably be expected
to occur.
It is expressly acknowledged that, as of the Effective Date, Pharmacyclics has
entered into a Third Party Agreement with Nycomed Imaging AS ("Nycomed"),
whereby Nycomed has been granted a license to develop, market and sell PCI-0123
and/or other Lutetium Texaphyrins outside the Field in certain countries in the
Territory. In addition, it is expressly acknowledged that Pharmacyclics may
enter into other Third Party Agreements in the future.
(b) From and after the date Pharmacyclics enters into such Third Party
Agreement, each Party agrees and understands that Alcon will not be permitted to
modify any Licensed Product, whether with respect to its formulation or
otherwise, where such modification would materially increase the likelihood that
prescribing physicians reasonably would substitute in the marketplace such
Licensed Product for one or more Third Party Compounds then being developed
and/or sold for use outside the Field but for sale in the Territory. Alcon will
ensure that any permitted sublicense under this Agreement contains terms with
the same effect as this Section 3.9. Upon entering into any such Third Party
Agreement, Pharmacyclics agrees to disclose to Alcon in confidence those
portions of such Third Party Agreement that are reasonably necessary to
demonstrate compliance with this Section 3.9.
(c) Pharmacyclics agrees to keep Alcon reasonably informed as to the
development programs under any Third Party Agreements, subject to the
confidentiality provisions of Article 15, in order to allow Alcon to monitor
Pharmacyclics' compliance with its obligations under this Section 3.9. Alcon
agrees to inform Pharmacyclics promptly of any adverse implications of such
third party development programs anticipated by Alcon and Pharmacyclics agrees
to meet with Alcon in good faith to address such adverse implications.
14.
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(d) In the event that, despite the Parties' compliance with their
obligations under Subsections (a), (b) and (c) above, (x) a Third Party Compound
which is marketed or sold for use outside the Field and in the Territory is
nonetheless substituted in the marketplace for a Licensed Product marketed and
sold by Alcon, its Affiliates or sublicensees hereunder and/or (y) a Licensed
Product which is marketed and sold by Alcon, its Affiliates or sublicensees for
use in the Field and in the Territory but is nonetheless substituted in the
marketplace for Third Party Compound for use outside the Field and in the
Territory, the following shall apply:
(i) Alcon shall provide to Pharmacyclics any and all audit data
collected by Alcon in its normal course of business with respect to (a) Alcon's
sales of Licensed Product used in the Field and in the Territory, (b) Alcon's
sales of Licensed Products used outside the Field in the Territory, (c) sales of
Third Party Compounds used in the Field and the Territory, and (d) sales of
Third Party Compounds used outside the Field in the Territory;
(ii) Pharmacyclics shall require that any and all third party
licensees under all Third Party Agreements provide to Pharmacyclics all audit
data collected by such third party with respect to the sales referenced in
Subsection (i) above and, subject to Article 15, Pharmacyclics shall provide
such data to Alcon;
(iii) Alcon shall analyze all data developed by Alcon and
provided by Pharmacyclics' third party licensees and shall first develop a
methodology for determining the extent and nature of sales of Licensed Products
by Alcon outside the Field and by such third party licensees within the Field,
in the Territory (the "Audit Methodology") which shall be subject to the
approval of Pharmacyclics and the third party licensee(s). Upon such approval,
Alcon shall then determine the sales for each party using the agreed to Audit
Methodology and all audit data developed by Alcon and provided by Pharmacyclics
under Subsection (i) and (ii) above. In the event data is required to determine
Alcon's sales of Licensed Product used outside the Field, in addition to that
provided by Pharmacyclics under Subsection (ii), Alcon will reimburse
Pharmacyclics for all reasonable costs associated with Pharmacyclics', or the
third party licensees' collection of such additional data. In the event data is
required to determine sales of Third Party Compounds used in the Field, in
addition to that provided by Alcon under Subsection (i), Pharmacyclics will
reimburse Alcon for all reasonable costs associated with Alcon's collection of
such additional data. Alcon will be responsible for collecting all data outside
the scope of normal business of Pharmacyclics or its third party licensee(s)
relating to the sale of Licensed Product used outside the Field. The Audit
Methodology shall be the sole mechanism for reconciling the appropriate net
profit to each of Alcon and such third party licensees, as well as the royalty
owed Pharmacyclics for sales of such Licensed Product, in the Territory.
3.10 MODIFICATIONS TO LICENSED PRODUCT. Alcon agrees that it shall not make
any changes to the chemical structure of any Licensed Product except upon the
prior written approval of Pharmacyclics. In the event Alcon wishes to make a
change to the formulation of a Licensed Product, it will provide written notice
of such proposed change to Pharmacyclics, so that Pharmacyclics can comply with
its obligations under Section 3.9(a) (as well as with similar obligations in
Third Party Agreements) and Alcon can comply with its obligations under Section
3.9(b).
15.
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3.11 ADDITIONAL LICENSED PRODUCTS. The parties acknowledge and agree that
nothing contained in this agreement shall obligate Pharmacyclics to develop or
supply to Alcon any Licensed Product other than PCI-0123. In the event the
parties agree that Pharmacyclics should develop and/or supply any additional
Licensed Products to Alcon for use in the Field, such development shall be
undertaken pursuant to a separate development agreement between the parties;
provided, however, such separate development agreement shall only financially
obligate Alcon to reimburse Pharmacyclics for its reasonable development costs
and supply of any such additional Licensed Products, and shall not contain any
other financial terms, including, but not limited to, licensing fees or
milestone payments provided further, however, subject to Section 4.3(d), the
milestone payments and royalties set forth in Sections 4.3 and 4.4 shall apply
to the development and commercialization of such additional Licensed Products.
4. LICENSE FEE, MILESTONE PAYMENTS AND ROYALTIES.
4.1 TECHNOLOGY ACCESS FEE. In consideration of the rights granted by
Pharmacyclics to Alcon hereunder and the access to and use of Pharmacyclics
Technology during the Program, Alcon shall pay or cause to be paid to
Pharmacyclics a non-refundable technology access fee equal to (*) within ten
(10) days of the Effective Date.
4.2 LICENSE FEE. A non-refundable license fee of (*) shall be due upon the
Determination.
4.3 MILESTONE PAYMENTS. In consideration of the licenses granted by
Pharmacyclics under Sections 3.1 and 3.2, following the Determination, Alcon
shall make non-refundable payments to Pharmacyclics, as follows:
(a) upon the completion of Phase II or the beginning of Phase III for
the Licensed Product, whichever is earlier, (*);
(b) upon the filing of the first NDA or MAA for the Licensed Product,
(*); and
(c) upon the first NDA Approval or receipt of the first MA for the
Licensed Product, (*) of such amount shall be credited against amounts due
pursuant to Section 4.4, provided, however, in each calendar year, such credit
shall not exceed the lesser of (*) of the royalty otherwise due to Pharmacyclics
under Section 4.4(a) for such year.
(d) After a given milestone payment has been made under this Section
4.3, the same milestone payment shall not be due again for the subsequent
development of any Licensed Product (including for any Licensed Products
developed pursuant to a separate development agreement as described in Section
3.11). For the avoidance of any doubt, once Alcon pays Pharmacyclics (*) in
Milestone Payments required under this Section 4.3 for the development of a
Licensed Product, no other Milestone Payments shall ever be due by Alcon for the
subsequent development of any other Licensed Product.
4.4 ROYALTIES.
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
16.
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(a) Subject to Sections 4.4(c) and (d), in exchange for the Licenses
granted under Section 3.1 and 3.2, Alcon shall also pay to Pharmacyclics a
marginal royalty on annual, aggregate Net Sales of all Licensed Products in all
countries of the Territory (the "Net Sales Base"), as set forth below:
(*) of all Net Sales up to (*); and
(*) of all Net Sales in the range of (*); and
(*) of all Net Sales in excess of (*).
(b) Subject to Section 4.4(c), in addition to the royalties paid to
Pharmacyclics under Section 4.4(a), and in consideration for the rights
sublicensed to Alcon through the UT License, Alcon shall also pay to
Pharmacyclics a royalty, on annual, aggregate Net Sales of all Licensed Products
in all countries of the Territory, as follows:
(*) of all Net Sales in the range of (*); and
(*) of all Net Sales in excess (*).
In the event amounts due the University of Texas by Pharmacyclics on sales of
Licensed Product are to be reduced pursuant to Section 5.4 of the UT License,
Alcon will provide Pharmacyclics with any data obtained by Alcon in Alcon's
normal course of business which is necessary or useful for Pharmacyclics to
calculate the reduced amount due from Pharmacyclics to the University of Texas.
For the avoidance of any doubt, the above royalty rates of Subsections 4.4(a)
and 4.4(b) are based on Net Sales accrued during each annual period ending
December 31st. As such, the royalty rates are based on each new calendar year,
and are not cumulative across years (i.e., successive years' Net Sales are not
added together in calculating Net Sales for royalty rate determination).
(c)
(i) COMBINATION PRODUCTS. In the event a Licensed Product is
combined with other pharmaceutical agents for sales to third parties, for
purposes of calculating Net Sales for Sections 4.4(a) and 4.4(b), the Net Sales
attributable to sales of the Licensed Product will be a pro rata share of the
Net Sales attributable to the combined product, based on the ratio P1/(P1 + P2),
where
P1 = the fair market value of the Licensed Product;
P2= the fair market value of the other pharmaceutical agents (the
"Other Agents").
If the Licensed Product is sold as a stand-alone product, the "fair market
value" of P1 will be the selling price of the stand-alone Licensed Product. If
the Other Components are sold as stand-alone products, the "fair market value"
of P2 will be the sum of the selling prices of the Other Agents as stand-alone
products. If the Licensed Product and/or the Other Agents are not sold as
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
17.
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stand-alone products, then the ratio P1/(P1 + P2) shall be determined by Alcon
and Pharmacyclics in good faith based on the relative fair market values of the
Licensed Product and the Other Agents as determined by mutual agreement of the
parties or, if the parties cannot agree on such ratio, the ratio P1/(P1 + P2)
shall be determined by a third party expert in such matters. Such third party
expert shall be jointly selected by the parties.
(ii) KITS, SYSTEMS. In the event that a Licensed Product is sold
in combination with or as part of a kit, package or system, for purposes of
calculating Net Sales for Sections 4.4(a) and 4.4(b), the Net Sales attributable
to sales of the Licensed Product will be based on Alcon's average selling price
for the stand alone Licensed Product as represented in Alcon's price catalogue.
(d) Notwithstanding anything in this Section 4.4, in any country of
the Territory in which:
(x) a Competitive Product consisting of a Lutetium Texaphyrin is
marketed by a third party for the same indication in the Field for which Alcon
or an Alcon Affiliate or an Alcon sublicensee is marketing Licensed Product; and
(y) the sales of such Competitive Product are having a material
adverse effect on the sales of Licensed Product; and
(z) either (i) no Pharmacyclics Patents exist to protect Alcon's
exclusive sale of a Licensed Product in the Field or (ii) the Pharmacyclics
Patents have expired, have been invalidated or have otherwise held
unenforceable, then, for purposes of calculating Net Sales for Section 4.4(a),
Net Sales shall be reduced (*), by multiplying Net Sales by the factor (*). In
all other countries where there is no such Competitive Product, Net Sales shall
not be reduced.
4.5 DURATION OF ROYALTY PAYMENTS. Pursuant to Section 4.4, Alcon shall pay
to Pharmacyclics the royalties set forth in Section 4.4 on the Net Sales of each
Licensed Product in the Territory on a country-by-country basis, for the longer
of: (i) the last to expire of the Pharmacyclics Patent(s) which protect Alcon's
exclusive sale of a Licensed Product in that country; or (ii) 10 years after the
First Commercial Sale of the Licensed Product.
5. PAYMENTS, REPORTS AND RECORDS.
5.1 PAYMENTS. Royalties accruing in any calendar quarter shall be paid by
Alcon, Alcon Affiliates and/or Alcon sublicensees, as the case may be, within
thirty (30) days after the end of such quarter. Simultaneously with the delivery
of each such royalty payment, Alcon, Alcon Affiliates and/or Alcon sublicensees,
as the case may be, shall deliver to Pharmacyclics a report indicating, on a
country-by-country basis: (i) Net Sales for each Licensed Product, (ii) all
deductions taken under Section 1.29, by category, where available to Alcon in
Alcon's normal course of business, in arriving at Net Sales, and (iii) the
calculations used in determining any reductions in Net Sales pursuant to
Subsection 4.4(c) or (d). Alcon, Alcon Affiliates and Alcon sublicensees, will
keep records in sufficient detail to enable the royalties to be determined, and
an
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
18.
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independent certified public accountant selected by Pharmacyclics shall have
access to the records of Alcon, Alcon Affiliates and Alcon sublicensees during
reasonable business hours for the purpose of verifying for Pharmacyclics, in
respect of any calendar quarter ending not more than three calendar years prior
to the date of such request, the correctness of any report and/or payment made
under this Agreement. Such accountant shall be bound by a confidentiality
agreement and shall not disclose any information other than information relating
solely to the accuracy of the reports and payments made under this Agreement.
Any such audit shall be at Pharmacyclics' expense, unless such audit reveals an
underpayment by Alcon of (*), in which case Alcon shall bear such expense.
5.2 LATE PAYMENTS. Any amount not paid when due under this Agreement shall
bear interest at the prevailing prime rate for commercial loans at the time of
such underpayment.
5.3 EXCHANGE RATES; BLOCKED CURRENCY. Royalties due on Net Sales by Alcon,
Alcon Affiliates or Alcon sublicensees to third party customers shall be
calculated and paid by Alcon in United States Dollars using an exchange rate in
accordance with Alcon corporate guidelines consistent with how Alcon calculates
exchange rates for its own internal accounting purposes. In the event that, by
reason of regulations or taxes of any kind, it becomes impossible or illegal for
Alcon, an Alcon Affiliate or an Alcon sublicensee as to any country to transfer,
or have transferred on its behalf, royalty or other payments to Pharmacyclics in
the United States, such royalties or other payments shall be deposited in local
currency in the relevant country to the credit of Pharmacyclics in a recognized
banking institution designated by Pharmacyclics or, if none is designated by
Pharmacyclics within a period of thirty (30) days, in a recognized banking
institution selected by Alcon, an Alcon Affiliate or an Alcon sublicensee, as
the case may be, and identified in a notice in writing given to Pharmacyclics.
5.4 TAX CONSEQUENCES. All witholding or other taxes or fees levied by Swiss
governmental entities on any payments due under the Agreement to Pharmacyclics,
including but not limited to, the Determination Fee, License Fees, Milestone
Payments, royalties and expense reimbursements shall be borne in their entirety
by Alcon and shall not reduce the amount of any payment made to Pharmacyclics.
To the extent Pharmacyclics claims a credit for such Swiss taxes against its
U.S. tax liability, Pharmacyclics agrees to reimburse that amount to Alcon.
6. MANUFACTURE AND SUPPLY OF LICENSED PRODUCT.
6.1 SUPPLY OF DRUG SUBSTANCE.
(a) PHASE III CLINICAL TRIALS AND COMMERCIAL SUPPLY. Alcon
acknowledges and understands that Pharmacyclics has entered into the HC
Agreement and that, pursuant to the HC Agreement, HCC has the right to supply to
Pharmacyclics all of its worldwide requirements for Drug Substance for Phase III
clinical trials and commercial sale. Pharmacyclics agrees, based on Alcon's
election of one of the following two supply options, to either: (i) cause HCC to
supply to Alcon all of Alcon's requirements of Drug Substance for Phase III
clinical trials and commercial sale during the term of this Agreement; or (ii)
enter into negotiations with Alcon and HCC for the supply by HCC of Drug
Substance directly to Alcon for Phase III clinical trials and commercial sale,
in either case, as Alcon shall determine following the Effective Date. In the
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
19.
20
event Pharmacyclics supplies Drug Substance to Alcon through and under the HC
Agreement, Alcon and Pharmacyclics shall enter into a separate supply agreement
(the "Pharmacyclics Supply Agreement"), which such agreement shall set forth the
terms and conditions of such supply; provided, however, that (a) for commercial
supply, the price to be paid by Alcon for such Drug Substance will be equal to
(*) and (b) for supply for Phase III clinical trials, the price to be paid by
Alcon for such Drug Substance will be (*) therefor. In the event Pharmacyclics
is unable to supply Drug Substance under the Pharmacyclics Supply Agreement,
such agreement will provide that Alcon can draw up to (*) of its requirements of
Drug Substance from amounts inventoried by HCC pursuant to the HC Agreement. In
the event Alcon elects to negotiate with HCC for supply directly by HCC to
Alcon, such supply will be conducted pursuant to a separate supply agreement by
and between Alcon (and, where deemed appropriate, Pharmacyclics) and HCC (the
"HCC/Alcon Supply Agreement"). Pharmacyclics will use good faith efforts to
negotiate an HCC/Alcon Supply Agreement which provides that, in the event HCC is
unable to supply Drug Substance under the HCC/Alcon Supply Agreement, such
agreement will provide that Alcon can draw up to (*) of its requirements of Drug
Substance from amounts inventoried by HCC pursuant to the HCC/Alcon Supply
Agreement.
(b) PRE-PHASE III CLINICAL TRIALS. Pharmacyclics agrees to supply all
of Alcon's requirements of Drug Substance for pre-Phase III clinical trials
during the term of this Agreement, pursuant to a separate supply agreement
(which may be the Pharmacyclics Supply Agreement) to be entered into by the
parties. The price to be paid by Alcon for such Drug Substance will be equal to
(*) therefor. Pharmacyclics understands that it is Alcon's desire to use Drug
Substance supplied by HCC for Phase II and Phase II/III trials and Pharmacyclics
agrees that Alcon will not be deemed to be in breach of Section 8.2 of this
Agreement if any failure of Alcon to perform under Section 8.2 arises as a
result of delays in obtaining Drug Substance from HCC for Phase II trials or
Phase II/III trials.
6.2 FILL AND FINISH OF LICENSED PRODUCTS. Following the Determination date,
Alcon shall inform Pharmacyclics whether Alcon desires to have supplied to it
finished, but not packaged, Licensed Product. In the event Alcon prefers to be
supplied finished Licensed Product, such supply shall be pursuant to the
Pharmacyclics' Supply Agreement referred to in Section 6.1 and shall be supplied
in lieu of or in addition to Drug Substance, and (a) for commercial supply shall
be at a price (*) and (b) for supply for clinical trials shall be at a price
equal (*) therefor. For the avoidance of doubt, the (*) in the preceding
sentence shall include (*). Where Alcon prefers to be supplied Drug Substance,
it shall undertake itself all Fill and Finish activities. In such event and upon
request of Alcon, Pharmacyclics shall transfer to Alcon the Pharmacyclics
Know-How with regard to Fill and Finish. Alcon shall Fill and Finish Licensed
Product in accordance with the applicable MAs and such Fill and Finish shall be
done in accordance with all applicable regulatory requirements, including
current Good Manufacturing Practices.
6.3 FORMULATION WORK. Pharmacyclics shall have no responsibility under this
Agreement for performing any formulation work on the Licensed Product. Subject
to the other terms of this Agreement, Alcon shall arrange for such formulation
work to be done or shall do such formulation work itself, all at the sole
expense of Alcon. In order to allow Pharmacyclics to comply with its obligations
under Section 3.9 of this Agreement and similar obligations in Third Party
Agreements, Alcon hereby covenants that the finished Licensed Product developed,
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
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marketed and sold by Alcon pursuant to this Agreement will have a formulation
which is sufficiently different from the PCI-0123 Formulation that prescribing
physicians could not reasonably be expected to substitute in the marketplace
Alcon's finished Licensed Product for the PCI-0123 Formulation.
6.4 STANDBY LICENSE. The Pharmacyclics Supply Agreement or the HCC/Alcon
Supply Agreement, as applicable, will provide that, under circumstances to be
set forth in such supply agreement, in the event Pharmacyclics or HCC is unable
or unwilling to fill Alcon's orders for Licensed Product or Drug Substance, as
is required under Sections 6.1 and 6.2, Pharmacyclics will xxxxx Xxxxx a
royalty-free, world-wide license to make or have made any Drug Substance.
7. MANUFACTURE AND SUPPLY OF DEVICES.
Pharmacyclics agrees to assist Alcon, upon Alcon's reasonable request, in
determining the specifications for and obtaining sources of supply for the
Device.
8. DILIGENCE IN DEVELOPMENT AND COMMERCIALIZATION.
8.1 DEVELOPMENT STRATEGY. Attached hereto as Appendix G is an initial
timeline and development plan for the regulatory approval in the United States,
Europe and Japan of Licensed Product for the treatment of macular degeneration
retinopathy. Such initial timeline and development plan shall be updated by
Alcon and provided to Pharmacyclics from time to time and no less frequently
than on an annual basis. Alcon agrees that, within sixty (60) days of receipt of
the first MA for the Licensed Product, it shall present Pharmacyclics with a
development plan for the development, regulatory approval and commercialization
of Licensed Product throughout the Territory (the "Development Plan"). Within
thirty (30) days of receipt of the Development Plan, Pharmacyclics shall provide
Alcon with comments on the Development Plan. Alcon shall consider all such
comments in good faith, and shall modify the Development Plan as Alcon deems
necessary. From time to time during the implementation of the Development Plan,
but not less than annually, Alcon shall inform Pharmacyclics of any updates to
its development, regulatory approval and/or commercialization strategy. Alcon
will be responsible for, and shall keep Pharmacyclics reasonably apprised of,
the specific preclinical and clinical activities necessary to obtain MA in
different countries in the Territory. Pharmacyclics' personnel and its
consultants shall continue to be allowed to comment on the Development Plan as
it is revised over time and such comments shall be considered in good faith by
Alcon for implementation in the development, regulatory and commercialization
strategy. In addition, Alcon shall keep Pharmacyclics informed, not less than
annually (and by January 1st of each year), of Alcon's, its Affiliates' and
sublicensees' global marketing strategies for each Licensed Product, including
but not limited to, an annual forecast of sales for Licensed Product.
8.2 DEVELOPMENT OF LICENSED PRODUCT. Alcon shall use best efforts to
develop the Licensed Product for approval in the widest number of geographic
markets consistent with the Development Plan and its overall product development
strategy. Such development shall be pursued at Alcon's own expense. Alcon shall
use its good faith business and scientific judgment as applied to commercial
development projects, to allocate sufficient time, effort, equipment and
facilities to carry out development of the Licensed Product. Alcon shall devote
the same degree
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of attention and diligence to such development efforts as it
devotes to compounds of comparable market potential. Alcon shall conduct its
efforts hereunder in compliance with all current Good Laboratory Practices,
current Good Clinical Practices, and current Good Manufacturing Practices and
all other legal requirements.
8.3 MARKETING EFFORTS; REQUIRED MARKETS. Alcon, its Affiliates and
sublicensees each, will use reasonable best efforts to obtain MA of, and to
commercialize, the Licensed Product and the related Device for sale in, at a
minimum, the United States, Europe and Japan, as well as in other countries in
the Territory according to the Development Plan. Such reasonable best efforts
shall require the dedication by Alcon, its Affiliates and Alcon sublicensees of
resources consistent with the resources which would have been used by Alcon at
the relevant time in relation to a product with similar clinical applications
generated from Alcon's own research endeavor which Alcon had decided to market.
8.4 REPORTS AND DATA. Alcon shall provide written quarterly development
progress reports to Pharmacyclics. Alcon will provide Pharmacyclics with access
to all data generated by Alcon for use by Pharmacyclics and its licensees in
support of Licensed Product development outside of the Field, at no cost to
Pharmacyclics; provided, however, Pharmacyclics may only provide such data to a
given third party licensee for use outside the Field if such third party
licensee has agreed that Pharmacyclics may provide Alcon with access to all data
generated by such third party licensee for use by Alcon in support of Licensed
Product development inside the Field, at no cost to Alcon. Accordingly, to the
extent not precluded by third-party contracts, Pharmacyclics will provide Alcon
with access to all data generated by Pharmacyclics and its licensees for use by
Alcon in support of Licensed Product development inside the Field, at no cost to
Alcon. In addition to the foregoing, Alcon shall use best efforts to give
Pharmacyclics the opportunity to review and comment upon all preclinical and
clinical protocols, prior to implementation, in order to advise Alcon of any
possible improvements to the proposed protocol Pharmacyclics believes to be
necessary or useful, provided, however, Pharmacyclics shall provide its comments
on a given protocol, if any, to Alcon within three (3) business days of
Pharmacyclics' receipt of such protocol. In all events the final decision as to
the content and timing of the filing of such protocols with a Health Authority
shall be made by Alcon.
8.5 MARKETING RESTRICTIONS. Alcon hereby covenants that it will not,
without the prior written authorization of Pharmacyclics, solicit the sale of
Licensed Products, or advertise, market or promote Licensed Products outside of
the Field.
8.6 TRADEMARK. Alcon, its Affiliates and permitted sublicensees shall sell
the Licensed Product in the Territory using a trademark selected by Alcon and
approved by Pharmacyclics, such approval not to be unreasonably withheld (the
"Trademark"). Alcon shall own the Trademark and the use thereof will inure
strictly to Alcon's benefit.
8.7 PACKAGING. Unless otherwise agreed, the Licensed Product shall be sold
under Alcon's name or trade name. All packaging for the Licensed Product shall
comply with applicable government rules and regulations. In addition, packaging
for the Licensed Product shall indicate, as appropriate: (i) that Pharmacyclics
is the holder of the patent(s) under which the Licensed Product is licensed; and
(ii) the name of the manufacturer(s) of the Licensed Product.
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8.8 COSTS. Alcon shall be responsible for all costs and expenses associated
with its development and commercialization of Licensed Products. Pharmacyclics
shall provide, upon reasonable request, reasonable assistance to Alcon in such
development efforts, at Alcon's expense, if approved in advance by Alcon.
9. REGULATORY MATTERS.
9.1 GOVERNMENT APPROVAL. Alcon will be responsible for the administrative
handling of all filings and other communications with Health
Authorities (including, but not limited to, INDs, NDAs and XXXx) in
all countries of the Territory for the Licensed Product and the Device
in the Field (collectively, the "Regulatory Filings"), unless
otherwise required by the Device manufacturer or required by the laws
or regulations of the applicable jurisdiction. Alcon shall use best
efforts to give Pharmacyclics the opportunity to comment upon, prior
to filing, all Regulatory Filings, in order to advise Alcon of any
possible improvements of the proposed filings Pharmacyclics believes
to be necessary or useful provided, however, Pharmacyclics shall
provide its comments on a given Regulatory Filing, if any, to Alcon
within three (3) business days of Pharmacyclics' receipt of such
filing. It is understood that Alcon may provide components of such
Regulatory Filings to Pharmacyclics in a piecemeal manner, as such
components are prepared by Alcon. Alcon shall in good faith consider
Pharmacyclics' opinion and advice when filing the Regulatory Filings.
Notwithstanding the foregoing, in all events the final decision as to
the content and timing of such filings shall be made by Alcon. Alcon
will pay all fees and expenses related thereto. Alcon shall keep
Pharmacyclics informed of the status of Regulatory Filings on an
ongoing and timely basis, including, providing copies of all
Regulatory Filings and any supplements or amendments thereto, to
Pharmacyclics. Alcon shall be the sole holder of the Regulatory
Filings, and will at its own expense, be responsible for all
administrative matters necessary to compile and submit the Regulatory
Filings for the Licensed Product in each country of the Territory.
Alcon shall also be responsible for maintaining the Regulatory Filings
and will bear the registration renewal fees for the Regulatory Filings
of the Licensed Product in each country of the Territory in which same
are filed.
9.2 RIGHT TO REFERENCE DATA. Each party shall grant the other party and the
other party's sublicensees, for no additional consideration, the right to
reference stability and other required chemistry, manufacturing and control data
for Drug Substance and finished Licensed Product formulation, including any Drug
Master Files owned by HCC, in support of all regulatory filings, to the extent
owned or controlled by the granting party.
9.3 ADVERSE REACTION REPORTING.
(a) Alcon shall advise Pharmacyclics, by telephone or facsimile,
within such time as is required by the FDA or foreign equivalent (with respect
to the severity and/or increased frequency of such adverse reaction) after it
becomes aware of any adverse reaction to the use of the Licensed Product
developed, marketed or sold by Alcon. Alcon shall provide Pharmacyclics with a
written report delivered by confirmed facsimile of any reported adverse
reaction, stating
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the full facts known to it, including but not limited to customer name, address,
telephone number and lot or serial number, as appropriate. For the avoidance of
doubt, notwithstanding anything in this Section 9.3(a), Alcon shall be
responsible for all adverse event reporting with the applicable Health
Authorities for Licensed Product developed, marketed or sold by Alcon.
(b) Pharmacyclics shall advise Alcon, by telephone or facsimile,
within such time as is required by the FDA or foreign equivalent (with respect
to the severity and/or increased frequency of such adverse reaction) after it
becomes aware of any adverse reaction to the use of the Licensed Product
developed, marketed or sold outside the Field by Pharmacyclics or a third party
licensee. Pharmacyclics shall provide Alcon with a written report delivered by
confirmed facsimile of any reported adverse reaction, stating the full facts
known to it.
9.4 COMPLIANCE. Alcon shall comply with all health registration laws,
regulations and orders of any government entity within the Territory and with
all other governmental requirements relating to the promotion, marketing and
sale of the Licensed Products.
10. LIABILITY AND INDEMNIFICATION.
10.1 INDEMNIFICATION BY ALCON. Except for Costs covered by Section 10.2,
Alcon shall indemnify, defend and hold harmless Pharmacyclics, its Affiliates
and sublicensees and all officers, directors, employees and agents thereof
(collectively, "Pharmacyclics Indemnitees") from all damages, losses, claims,
judgments, liabilities, cost and expenses, including without limitation,
reasonable attorneys fees and expenses (collectively, "Costs"), whether the
foregoing are based in contract, tort, negligence or product liability incurred
by or assessed against any Pharmacyclics Indemnitees that arise out of or
incident to injury or death of persons or damage to or destruction of property
caused or alleged to be caused by: (i) the negligence, recklessness or willful
misconduct of Alcon or its officers or employees; or (ii) any representation
made or warranty given by Alcon with respect to the Licensed Product (other than
the labeling for the Licensed Product as approved by the FDA, EMEA or Health
Authority). In the event of any such claim against or Costs incurred by any of
the Pharmacyclics Indemnitees, Pharmacyclics shall promptly notify Alcon of such
claim or Costs. Alcon shall manage and control, at its sole expense, the defense
and/or settlement of any such claim against a Pharmacyclics Indemnitee. The
Pharmacyclics Indemnitees shall cooperate with Alcon and may, at their option
and expense, be represented in (but not control) any such action or proceeding.
Alcon shall not be liable for any settlement entered into or cost or expense
incurred by the Pharmacyclics Indemnitees in relation to any such action or
proceeding without Alcon's written authorization (unless Alcon shall have failed
to assume management and control of the defense and settlement of the matter as
provided above in this Section 10.1).
10.2 INDEMNIFICATION BY PHARMACYCLICS. Except for Costs covered by Section
10.1, Pharmacyclics shall indemnify, defend and hold harmless Alcon, its
Affiliates and sublicensees and all officers, directors, employees and agents
thereof (collectively, "Alcon Indemnitees") from all Costs, whether the
foregoing are based in contract, tort, negligence or product liability, incurred
by or assessed against any Alcon Indemnitees that arise out of or incident to
injury or death of persons or damage to or destruction of any property caused or
alleged to be caused by the negligence, recklessness or willful misconduct of
Pharmacyclics or its officers or employees. In
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the event of any such claim against or Costs incurred by any of the Alcon
Indemnitees, Alcon shall promptly notify Pharmacyclics of such claim or Costs.
Pharmacyclics shall manage and control, at its sole expense, the defense and/or
settlement of any such claim against an Alcon Indemnitee. The Alcon Indemnitees
shall cooperate with Pharmacyclics and may, at their option and expense, be
represented in (but not control) any such action or proceeding. Pharmacyclics
shall not be liable for any settlement entered into or cost or expense incurred
by the Alcon Indemnitees in relation to any such action or proceeding without
Pharmacyclics' written authorization (unless Pharmacyclics shall have failed to
assume management and control of the defense and settlement of the matter as
provided above in this Section 10.2).
11. INTELLECTUAL PROPERTY DEVELOPED POST-EVALUATION PERIOD.
11.1 OWNERSHIP OF INTELLECTUAL PROPERTY.
(a) Except as provided in this Agreement, Pharmacyclics shall retain
all of its right, title and interest in and to all Pharmacyclics Technology,
copyrights, trade marks, trade name, and all other intellectual property owned
by it as of the Effective Date which is embodied in or appurtenant to Licensed
Products.
(b) Ownership of inventions (whether or not patentable) arising from
work performed after the Evaluation Period, if any, pursuant to this Agreement
shall be determined in accordance with the principles of United States laws of
inventorship.
11.2 LICENSES.
(a) LICENSE FOR USE OUTSIDE THE FIELD OF OPHTHALMOLOGY. Alcon hereby
grants to Pharmacyclics a worldwide, non-exclusive, royalty-free license, with
the right to sublicense, under the Alcon Post-Evaluation Period Intellectual
Property, to make, use, sell, offer for sale and import Licensed Product and any
Device outside the Field. For purposes of this Section 11.2, "Alcon
Post-Evaluation Period Intellectual Property" shall mean all patentable and
non-patentable inventions, know-how, technology, data, and analyses of results
relating to PCI-0123, other Licensed Products and Devices that are developed
after the Evaluation Period by employees, agents or others acting on behalf of
Alcon.
11.3 PATENT PROSECUTION AND MAINTENANCE.
(a) Pharmacyclics has the sole right to continue prosecution and
maintenance of the Pharmacyclics Patents, at its own expense. Pharmacyclics
shall provide Alcon with copies of all patent applications, prosecution
documents, correspondence with government entities, and other information that
Alcon may request with respect to the Pharmacyclics Patents.
(b) Pharmacyclics shall have the right, at its option, to prepare,
file and prosecute any patent applications with respect to any Pharmacyclics
Inventions owned solely by Pharmacyclics. In connection therewith, Alcon agrees
to cooperate with Pharmacyclics in the preparation and prosecution of all such
patent applications and in the maintenance of any patents issued.
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(c) The Parties shall mutually determine which Party shall file,
prosecute and maintain patent applications with respect to inventions jointly
owned by Pharmacyclics and Alcon. The Parties shall bear all out-of-pocket costs
of such patents equally, and shall cooperate with each other in connection with
all such filings. Each Party shall have the right to review and comment on any
joint patent application prior to its filing, and to consult with the filing
Party with respect to prosecution of such application.
(d) Alcon shall have the right, at its option, to prepare, file,
prosecute and maintain any patent applications with respect to any Alcon
Inventions owned solely by Alcon. With respect to the Alcon Patents, and in
connection therewith, Pharmacyclics agrees to cooperate with Alcon in the
preparation and prosecution of all such patent applications and in the
maintenance of any patents issued. Alcon shall provide Pharmacyclics with copies
of all patent applications, prosecution documents, correspondence with
government entities, and other information that Pharmacyclics may request with
respect to the Alcon Patents.
11.4 INFRINGEMENT OF THIRD PARTY PATENTS.
(a) If a third party asserts that a patent or other proprietary right
owned by it is infringed by the manufacture, use, importation, offer for sale or
sale of a Licensed Product in the Field and in the Territory and such alleged
infringement arises in whole or in part from Alcon's use of the Pharmacyclics
Technology (a "Claim"), the Party against whom such a Claim was asserted shall
immediately provide the other Party notice of such Claim and the related facts
in reasonable detail. Unless it is mutually agreed that the Parties should
proceed jointly in defending such an action, the Party sued shall defend such
action. The other Party shall cooperate in connection therewith and shall have
the right to be represented separately by counsel of its own choice, at its own
expense. The entity (whether Pharmacyclics or Alcon) that controls the defense
of such a Claim with respect to the Licensed Product in the Field and in the
Territory shall also have the right to control settlement of such Claim;
provided, however, that no settlement shall be entered into without the consent
of the other Party. To the extent that any of the costs set forth in clauses
(i), (ii) or (iii) of this sentence are attributable to infringement arising
from Alcon's use of the Pharmacyclics Technology, Alcon shall have the right to
deduct from and offset against royalties otherwise payable to Pharmacyclics
under Section 4.4(a), the following: (i) all litigation costs related to such
Claim; (ii) any money damages paid by Alcon or its Affiliates pursuant to any
judgment or settlement resulting from such Claim; and (iii) any royalty that
Alcon and/or its Affiliates and sublicensees are required to pay to a third
party in settlement of such Claim in order to continue to exercise Alcon's
license rights as set forth in this Agreement. Notwithstanding the foregoing, in
no event shall royalties owed Pharmacyclics under Section 4.4(a) be reduced by
more than (*) in any given royalty period.
(b) In the event a third party asserts that a patent or other
proprietary right owned by it is infringed by Pharmacyclics or its Affiliates as
a consequence of Alcon's manufacture, use, importation, offer for sale or sale
of a Licensed Product in the Field and in the Territory and such alleged
infringement does not arise from Alcon's use of the Pharmacyclics Technology,
Alcon shall indemnify and hold harmless Pharmacyclics, its Affiliates and
sublicensees and all officers, directors, employees and agents thereof from all
damages, losses,
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
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claims, judgments, liabilities, cost and expenses, including without limitation,
reasonable attorneys fees and expenses arising from such third party claims.
11.5 THIRD PARTY INFRINGEMENT/MISAPPROPRIATION.
(a) If either Party becomes aware of any infringement of the
Pharmacyclics Patents or misappropriation of the Pharmacyclics Know-How by a
third party in the Territory in the Field, such Party shall promptly give notice
thereof to the other Party and shall provide the other Party with any evidence
or other information in its possession relating to such infringement or
misappropriation. The Parties shall thereupon consult together in good faith as
to the action to be taken.
(b)
(1) Pharmacyclics shall have the first right, but not the
obligation, to commence legal proceedings against any infringer of any
Pharmacyclics Patent or misappropriation of Pharmacyclics Know-How in the
Territory in the Field and in this case (subject to the provisions of the next
two sentences) any damages recovered shall belong to Pharmacyclics. In the event
Pharmacyclics commences such legal proceedings, Alcon may join in such
proceedings within sixty (60) days after its receipt of notice from
Pharmacyclics of the commencement of such proceedings if Alcon agrees to pay an
amount equal to fifty percent (50%) of the cost of such proceedings. In such
event, any damages, settlement fees or other consideration for past or future
infringement in the Field and in the Territory received as a result of such
proceedings shall be shared by Pharmacyclics and Alcon equally.
(2) In the event Pharmacyclics does not initiate such
proceedings, Alcon may commence legal proceedings against any infringer of any
Pharmacyclics Patent or misappropriation of Pharmacyclics Know-How in the
Territory in the Field, and Pharmacyclics may join in such proceedings within
sixty (60) days after its receipt of notice from Alcon of the commencement of
such proceedings if Pharmacyclics agrees to pay an amount equal to fifty percent
(50%) of the cost of such proceedings. In such event, any damages, settlement
fees or other consideration for past or future infringement in the Field and in
the Territory received as a result of such proceedings shall be shared by
Pharmacyclics and Alcon equally. If Pharmacyclics does not commence or join any
legal proceedings against the infringement or misappropriation in the Territory
in the Field, Alcon may at its own cost and expense, and in its own name,
commence such legal proceedings and in such case any damages recovered shall
belong to Alcon. Further, in such event, Pharmacyclics shall cooperate with
Alcon as reasonably requested by Alcon and at Alcon's expense, and with respect
to any legal proceedings brought by Alcon, Pharmacyclics shall agree to be named
as a party thereto, provided that Alcon agrees to indemnify, defend and hold
harmless Pharmacyclics from all costs incurred by or assessed against
Pharmacyclics in connection with any actions or counterclaims relating to such
legal proceedings except in the case that the applicable Pharmacyclics Patent(s)
are invalidated, and, except for costs incurred by or assessed against
Pharmacyclics as a result of Pharmacyclics' negligence or willful misconduct
directly related to such proceedings.
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11.6 LOSS OF EXCLUSIVITY. In the event any federal agency exercises
march-in-rights as to any Licensed Product contemplated hereunder, Alcon shall
be afforded most favored licensee status with respect to any licenses granted in
the exercise of such march-in-rights, and shall be entitled to adopt the terms
of any such license deemed by Alcon to be more favorable to Alcon, and/or any
lower royalty rates; provided, however, that such march-in by any federal agency
was not enabled by Alcon's failure to achieve practical application of a
Licensed Product as defined in 35 U.S.C. Section 203. Pharmacyclics shall give
immediate notice to Alcon of any exercised march-in-rights.
12. WARRANTIES AND REPRESENTATIONS.
12.1 AUTHORIZATION. Each Party hereto represents and warrants to the other
that its execution and delivery hereof has been duly authorized by all necessary
corporate action and that the terms and conditions of this Agreement, and its
obligations hereunder, do not conflict with or violate any terms or conditions
of any other agreement or commitment to which it is a signatory or by which it
is bound.
12.2 DISCLAIMER. EXCEPT AS EXPRESSLY SET FORTH IN THIS AGREEMENT, THE
PHARMACYCLICS TECHNOLOGY IS PROVIDED TO ALCON HEREUNDER WITH NO WARRANTIES OF
ANY KIND, EXPRESS OR IMPLIED, INCLUDING ANY WARRANTY OF DESIGN, MERCHANTABILITY
OR FITNESS FOR A PARTICULAR PURPOSE.
12.3 WARRANTY. Pharmacyclics expressly warrants that, to the best of its
knowledge and as of the Effective Date, Alcon is free to practice, including the
marketing and sale of, any of the Licensed Products contemplated hereunder, and
that Pharmacyclics has no knowledge of any patents which could so encumber
Alcon.
13. TERM. The Term of this Agreement ("Term") shall run from the Effective
Date and terminate upon the last to expire of all royalty or other payment
obligations hereunder, or as earlier terminated pursuant to Article 14.
14. TERMINATION.
14.1 DURING EVALUATION PERIOD.
(a) TERMINATION BY ALCON. During the Evaluation Period, Alcon may
terminate this Agreement for any reason upon thirty (30) days written notice to
Pharmacyclics.
(b) TERMINATION BY PHARMACYCLICS. If, during the Evaluation Period,
Alcon initiates evaluation of a Competitive Product, other than for competitive
comparison, or initiates the development of, or commences in-licensing
discussions for, a Competitive Product, then Pharmacyclics shall have the right
to immediately terminate this Agreement. Alcon shall promptly notify
Pharmacyclics if it undertakes any of the above activities.
14.2 EARLY TERMINATION BY ALCON. Following the Determination, Alcon may
terminate this Agreement for any reason or no reason, upon ninety (90) days
written notice to
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Pharmacyclics. In the event of any such termination, the provisions of Section
14.3(a) through (e) shall apply.
14.3 EARLY TERMINATION BY PHARMACYCLICS. Failure by Alcon to comply with
any of its material obligations and conditions in this Agreement shall be
considered a breach of this Agreement, and shall entitle Pharmacyclics to give
Alcon notice requiring Alcon to cure such breach. Alcon shall have sixty (60)
days to cure any such breach, except for breaches arising from failure to pay,
in which case Alcon shall have twenty (20) days to cure. In the event Alcon does
not cure any such breach in the time provided, Pharmacyclics may terminate this
Agreement by giving notice to take effect immediately. Upon any termination
under this Section 14.3, Pharmacyclics shall be entitled to such remedies as are
available at law and in equity and in addition:
(a) all licenses granted to Alcon under this Agreement shall
terminate, except for the license grant contained in Section 2.6;
(b) Pharmacyclics may, at its option, assume sponsorship of any
clinical trials for the Licensed Product in the Field then in effect. In
addition, Alcon will transfer to Pharmacyclics ownership of any Regulatory
Filings (as such term is defined in Section 9.1); provided, however, that
Pharmacyclics first reimburse Alcon for all of Alcon's out-of-pocket development
costs related to such trials and any XXXx and/or NDAs. Upon receipt of such
reimbursement, Alcon will use reasonable best efforts to cooperate with
Pharmacyclics and all government entities in causing such transfer to occur.
Alcon will bring all documentation relating to clinical trials up to date and
will transfer ownership of such documentation to Pharmacyclics;
(c) Alcon may sell off any existing inventory of Licensed Product,
provided it continues to comply with its payment obligations related thereto;
(d) To the extent not previously provided, Alcon shall transfer to
Pharmacyclics copies of all files, information, raw data, analyses and reports
relating to the Licensed Product and Devices and (i) with respect to Licensed
Product, Pharmacyclics and its licensees shall have the right to use such files,
information, raw data, analyses and reports both inside and outside of the Field
and (ii), with respect to Devices, to the extent not precluded by third-party
agreements, Pharmacyclics and its licensees shall have the right to use such
files, information, raw data, analyses and reports both inside and outside of
the Field;
(e) Pharmacyclics will grant to Alcon a worldwide, non-exclusive,
royalty-free license, without right to sublicense, under the Pharmacyclics
Post-Evaluation Period Intellectual Property, to make, use, sell, offer for sale
and import any Device inside the Field. For purposes of this Section 14.3(e),
"Pharmacyclics Post-Evaluation Period Intellectual Property" shall mean all
patentable and non-patentable inventions, know-how, technology, data, and
analyses of results relating to Devices, that are developed after the Evaluation
Period by employees, agents or others acting on behalf of Pharmacyclics.
Notwithstanding the foregoing, and without prejudice to Pharmacyclics' right to
terminate this Agreement under this Section 14.3, Pharmacyclics shall refer the
dispute (Alcon's material
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breach) to the CEOs of both parties for resolution for a ninety (90) day period
prior to taking any legal action against Alcon.
14.4 TERMINATION BY ALCON. Failure by Pharmacyclics to comply with any of
its material obligations and conditions in this Agreement shall be considered a
breach of this Agreement, and shall entitle Alcon to give Pharmacyclics notice
requiring Pharmacyclics to cure any such breach within sixty (60) days. Any
alleged breach or default under a Pharmacyclics Supply Agreement or any alleged
breach by Pharmacyclics' suppliers shall not be considered a breach or default
by Pharmacyclics of this Agreement. In the event Pharmacyclics fails to cure
such breach within the time provided, Alcon may terminate this Agreement. Upon
any termination under this Section 14.4, Alcon shall be entitled to such
remedies as are available at law and in equity and in addition:
(a) Alcon may sell off any existing inventory of Licensed Product,
provided it continues to comply with its payment obligations related thereto;
and
(b) Alcon shall retain ownership of all INDs, XXXx, NDAs or MAs which
relate to the Licensed Product and the Device(s).
(c) To the extent not previously provided, Pharmacyclics shall
transfer to Alcon copies of all files, information, raw data, analyses and
reports relating to the Devices and, to the extent not precluded by third-party
agreements, Alcon and its licensees shall have the right to use such files,
information, raw data, analyses and reports as they relate to Devices inside the
Field;
(d) Pharmacyclics will grant to Alcon a worldwide, non-exclusive,
royalty-free license, without right to sublicense, under the Pharmacyclics
Post-Evaluation Period Intellectual Property, to make, use, sell, offer for sale
and import any Device inside the Field. For purposes of this Section 14.4(d),
"Pharmacyclics Post-Evaluation Period Intellectual Property" shall mean all
patentable and non-patentable inventions, know-how, technology, data, and
analyses of results relating to Devices, that are developed after the Evaluation
Period by employees, agents or others acting on behalf of Pharmacyclics.
Notwithstanding the foregoing, and without prejudice to Alcon's right to
terminate this Agreement under this Section 14.4, Alcon shall refer the dispute
(Pharmacyclics' material breach) to the CEOs of both parties for resolution for
a ninety (90) day period prior to taking any legal action against Pharmacyclics.
14.5 TERMINATION FOR A COMPETITIVE PRODUCT. Pharmacyclics shall have the
right to terminate this agreement under the conditions set forth in Section 3.8.
In the event of any such termination, the provisions of Section 14.3(a) through
(e) shall apply.
14.6 DAMAGES. IN NO EVENT SHALL EITHER PARTY, ITS DIRECTORS, OFFICERS,
EMPLOYEES, AGENTS OR AFFILIATES BE LIABLE TO THE OTHER PARTY FOR ANY INDIRECT,
INCIDENTAL, SPECIAL, EXEMPLARY OR CONSEQUENTIAL DAMAGES, WHETHER BASED UPON A
CLAIM OR ACTION OF
30.
00
XXXXXXXX, XXXXXXXX, XXXXXXXXXX, XXXXXX LIABILITY OR OTHER TORT, OR OTHERWISE,
ARISING OUT OF THIS AGREEMENT.
14.7 WAIVER. The right of either Party to terminate this Agreement, as
hereinabove provided, shall not be affected in any way by its waiver of, or
failure to take action with respect to, any previous default. 14.8 SURVIVAL.
Notwithstanding anything else in this Agreement to the contrary, the Parties
agree that Section 2.6 and Articles 10, 11, 12 and 15 shall survive the
termination or expiration of this Agreement, as the case may be, to the extent
required thereby for the full observation and performance by either or both of
the Parties hereto.
14.8 SURVIVAL. Notwithstanding anything else in this Agreement to the
contrary, the Parties agree that Section 2.6 and Articles 10, 11, 12 and 15
shall survive the termination or expiration of this Agreement, as the case may
be, to the extent required thereby for the full observation and performance by
either or both of the Parties hereto.
15. CONFIDENTIALITY.
15.1 CONFIDENTIAL INFORMATION. All information considered confidential by
the disclosing party shall be marked "Confidential" or, if disclosed in a manner
other than a document shall be followed within thirty (30) days by a written
statement describing the information and identifying it as confidential.
15.2 TREATMENT OF CONFIDENTIAL INFORMATION. Each party shall treat all
information obtained from the other party in the manner described above or
developed pursuant to this Agreement ("Confidential Information") as secret and
shall not disclose any of such Confidential Information to any third party.
Furthermore, the parties shall not use Confidential Information, except for the
purpose of exercising the rights granted and performing their obligations
hereunder. The foregoing obligations of confidential treatment and non-use shall
expire five (5) years from the date of termination of this Agreement.
15.3 EXCEPTIONS. The above obligations do not apply to Confidential
Information, which:
(a) at the time of disclosure is in the public domain; or
(b) thereafter lawfully becomes a part of the public domain other than
through disclosure by or through the receiving party; or
(c) was known to the receiving party prior to the disclosure thereof
by the disclosing party, as evidenced in the receiving party's written records;
or
(d) is disclosed to the receiving party by a third party not under
obligation of confidentiality to the disclosing party with respect to said
disclosure; or
(e) is subsequently developed by an employee of the receiving party
without actual knowledge of its disclosure by the disclosing party; or
(f) the receiving party is required by law (including the rules and
regulations of the SEC or a national exchange on which its stock is traded, or
the FDA or foreign counterpart
31.
32
thereto) to disclose, provided that it gives the disclosing party reasonable
notice of its intent to disclose such information
15.4 TERMS OF THIS AGREEMENT. Subject to Article 16 the Parties agree that
the existence and terms of this Agreement shall be considered Confidential
Information subject to Section 15.2, except that relevant portions of the
Agreement may be confidentially disclosed to any Pharmacyclics licensees or
potential licensees, wherein such licensees are licensing a Licensed Product for
use outside the Field, and wherein such relevant portions are for the purpose of
informing the Pharmacyclics licensees of their rights and obligations under any
agreement made with Pharmacyclics. Likewise, Pharmacyclics shall confidentially
disclose to Alcon, relevant portions of any agreement made with a third party
licensee, wherein such licensees are licensing a Licensed Product for use
outside the Field, and wherein such relevant portions are for the purpose of
informing Alcon of its rights and obligations under this Agreement.
15.5 PRIOR CONFIDENTIALITY AGREEMENTS. Information disclosed under the
terms of the confidentiality agreements by and between the parties dated April
3, 1996 and August 7, 1997 shall be covered by the terms of this Article 15.
16. PUBLICITY.
16.1 The Parties agree that, subject to the terms of this Article 16, with
respect to any press releases regarding this Agreement, each shall review the
other Party's proposed press releases prior to their distribution to the media
and public. The initial press releases have been approved by the parties as of
the Effective Date. Subject to Article 15, if, within forty-eight (48) hours of
receipt of any subsequent press release, the receiving Party does not object to
its contents, the receiving Party's acceptance shall be deemed to have been
given, and the disclosing Party shall be free to distribute the press release.
If the receiving Party does object to the contents of the press release within
forty-eight (48) hours of its receipt, the Parties agree to discuss within the
following forty-eight (48) hours a mutually acceptable solution.
16.2 Notwithstanding Section 16.1, if a Party's proposed press release uses
language which is substantially similar with respect to this Agreement as
language in a previous press release which was approved by the other party, no
review by the other party is required.
17. FORCE MAJEURE. Neither Party shall be considered in default or be liable to
the other Party for any delay in performance or non-performance caused by
circumstances beyond the reasonable control of such Party, including but not
limited to acts of God, explosion, fire, flood, war, whether declared or not,
accident, labor strike, sabotage order or decrees or any court or action of
governmental authority.
18. SUCCESSION AND ASSIGNMENT. This Agreement may not be assigned or otherwise
transferred by either Party without the prior written consent of the other
Party, which shall not be unreasonably withheld or delayed; provided that either
Party may assign this Agreement or any of its rights hereunder to any of its
Affiliates (although, in such event, Alcon shall assure that its Affiliates
perform all of Alcon's obligations set forth in this Agreement); and provided
further, that either Party may assign this Agreement in connection with the
merger, consolidation, transfer
32.
33
or sale of substantially all of the assets the business unit to which this
Agreement relates. Any purported assignment in violation of the preceding
sentence shall be void. Any permitted assignee shall assume all obligations of
its assignor under this Agreement. No assignment shall relieve either Party of
responsibility for the performance of any accrued obligation which such Party
then has hereunder.
19. NOTICES. Any notice or report required or permitted to be given or made
under this Agreement by one of the Parties to the other shall be in writing and
shall be deemed to have been delivered upon personal delivery or (a) in the case
of notices provided between Parties in the continental United States,
forty-eight (48) hours after deposit in the mail or noon on the business day
next following deposit with a reputable overnight courier, (b) in the case of
notices provided between Parties, at least one of which is outside the United
States, ten (10) days after deposit in the mail or noon on the second business
day next following deposit with a reputable overnight express courier service,
and (c) in the case of notices provided by telecopy (which notice shall be
followed immediately by an additional notice pursuant to clause (a) or (b) above
if the notice is of a default hereunder)' upon completion of transmissions to
the addressee's telecopier, as follows (or at such other addresses or facsimile
numbers as may have been furnished in writing by one of the Parties to the other
as provided in this Section 19):
If to Pharmacyclics: Pharmacyclics, Inc.
000 X. Xxxxxx Xxxxxx
Xxxxxxxxx, XX
00000-0000
U.S.A.
Attention: Xxxx Xxxxxx, Vice President,
Business Development
If to Alcon: Alcon Pharmaceuticals Ltd.
Xxxxxxxxxxxxx 00
XX-0000 Xxxx
Xxxxxxxxxxx
Attention: Xxxxx Xxxxxx, General Manager
With a copy to: Alcon Laboratories, Inc.
0000 Xxxxx Xxxxxxx
Xxxx Xxxxx, Xxxxx 00000
U.S.A
Attention: Xxxxx Xxxx, Ph.D.
Vice President, Intellectual Property Law
and R&D Counsel
20. AFFILIATES. To the extent that any obligations or agreements are imposed
upon Affiliates of a Party under this Agreement, such Party shall cause
such Affiliates to fulfill such obligations and agreements.
21. WAIVER. Failure of either Party to require, in one or more instances,
performance by the other Party in strict accordance with the terms and
conditions of this Agreement shall not be deemed a waiver or relinquishment
of the future performance of any such terms and conditions or of any other
term and condition of this Agreement.
33.
34
22. ENTIRE AGREEMENT AND AMENDMENT; TITLES.
22.1 ENTIRE AGREEMENT. This Agreement, together with its Appendices,
constitutes the entire agreement between the Parties with respect to the subject
matter hereof. In the event of an inconsistency between the text of this
Agreement and one or more Appendices, the text of this Agreement shall prevail.
It cancels and supersedes all prior written and oral agreements, understandings
and declarations between the Parties in respect of the subject matter of this
Agreement.
22.2 TITLES. The titles of the Sections of this Agreement are for general
reference and convenience only and this Agreement shall not be construed and
interpreted by reference to such titles.
23. SEVERABILITY. In case one or several provisions of this Agreement should be
declared ineffective or void by any court of competent jurisdiction or a
government agency having jurisdiction, such declaration shall not affect the
remainder of this Agreement which will remain in full force and effect. The
provisions which were declared ineffective or void shall be replaced by new
effective ones which shall be in their sense and regarding the intentions of the
Parties in respect of this Agreement as similar as possible to the provisions
ineffective or void.
24. NO AGENCY. Nothing herein shall be deemed to constitute either Party as the
agent or representative of the other Party, or both Parties as joint venturers
or partners for any purpose. Except as set forth herein, neither Party shall be
responsible for the acts or omissions of the other Party, and neither Party will
have authority to act on behalf of, represent or obligate the other Party in any
way without prior written authority from the other Party.
25. GOVERNING LAW. This Agreement is governed by, and construed in accordance
with, the laws of the State of California without reference to choice of law
principles. Any claim or controversy arising out of or related to this Agreement
or any breach hereof shall be submitted to a court of applicable jurisdiction in
the State of California, and each party hereby consents to the jurisdiction and
venue of such court.
26. MODIFICATIONS. Any modification or addition to this Agreement shall be
valid only if it is confirmed in writing by the duly authorized officers of both
Parties.
34.
35
27. LITIGATION. If any party to this agreement institutes legal proceedings
against the other party with respect to this Agreement, the losing or defaulting
party shall pay the prevailing party reasonable attorneys' fees, costs and
expenses incurred in connection with the prosecution or defense of the action.
IN WITNESS WHEREOF, the Parties hereto have caused this Agreement to be
executed in duplicate by their duly authorized representatives as of the date
first above written.
Pharmacyclics, Inc. Alcon Pharmaceuticals Ltd.
By: /s/ Xxxx Xxxxxx By: /s/ [ILLEGIBLE]
---------------------------------- ------------------------------
Title: VP/CFO Title: Gen. Mgr.
------------------------------- ---------------------------
Date: 16-DEC '97 Date: Dec. 16, 1997
-------------------------------- ----------------------------
Appendices attached hereto:
Appendix A: PCI-0123
Appendix B: Pharmacyclics Patents
Appendix C: Structure of Texaphyrin
Appendix D: Evaluation Plan
Appendix E: PCI-0123 Substance Specifications
Appendix F: PCI-0123 Formulation Specification
Appendix G: Initial Timeline and Development Plan for United States,
Europe and Japan
35.
36
APPENDIX A
PCI-0123 STRUCTURE
[GRAPHIC OMITTED]
36.
00
XXXXXXXX X
PHARMACYCLICS PATENTS AND PATENT APPLICATIONS:
-----------------------------------------------------------------------------------------------------------
Title Country Xxx./Appln. No.
-----------------------------------------------------------------------------------------------------------
Metal Complexes of Water-Soluble Texaphyrins Australia Xxx. 664877
-----------------------------------------------------------------------------------------------------------
(*) (*)
-----------------------------------------------------------------------------------------------------------
(*) (*)
-----------------------------------------------------------------------------------------------------------
(*) (*)
-----------------------------------------------------------------------------------------------------------
(*) (*)
-----------------------------------------------------------------------------------------------------------
Xxx Xxxxxxx Xxx. 000000
-----------------------------------------------------------------------------------------------------------
(*) (*)
-----------------------------------------------------------------------------------------------------------
(*) (*)
-----------------------------------------------------------------------------------------------------------
United States Xxx. 5,252,720
-----------------------------------------------------------------------------------------------------------
Hydroxylated Texaphyrins United States Xxx. 5,457,183
-----------------------------------------------------------------------------------------------------------
Metal Complexes of Texaphyrins United States (*)
-----------------------------------------------------------------------------------------------------------
Use of Texaphyrins in Ocular Diagnosis and Therapy United States (*)
-----------------------------------------------------------------------------------------------------------
PCT* (*)
-----------------------------------------------------------------------------------------------------------
Water-Soluble Texaphyrin Metal Complexes United States Xxx. 5,439,570
for Singlet Oxygen Production
-----------------------------------------------------------------------------------------------------------
Photodynamic Therapy of Pigment-Related Lesions PCT* (*)
-----------------------------------------------------------------------------------------------------------
United States (*)
-----------------------------------------------------------------------------------------------------------
37.
38
APPENDIX C
TEXAPHYRIN STRUCTURE
BASIC TEXAPHYRIN CORE STRUCTURE:
[GRAPHIC OMITTED]
BASIC TEXAPHYRIN CORE STRUCTURE, SHOWING THE TYPICAL SITES OF MODIFICATION:
[GRAPHIC OMITTED] [GRAPHIC OMITTED]
Structure (i), showing Structure (ii), showing
non-nitrogen substitutions: nitrogen substitutions:
38.
39
APPENDIX D
EVALUATION PLAN
(*)
(*)
(*)
(*)
(*)
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
39.
40
If the results indicate an ophthalmic safety and efficacy profile acceptable to
Alcon, then LuTex will be developed as described on the following pages.
--------------------------------------------------------------------------------
PCI-0123 SUPPLIES ESTIMATE FOR THE PROGRAM
PCI-0123 SUBSTANCE:
(*)
PCI-0123 FORMULATION: (assumption 0.23% PCI-0123/ml; 20 ml vials - SERES lots
unless Celanese lots are qualified)
(*)
* These amounts of PCI-0123 Substance and PCI-0123 Formulation will be provided
pursuant to a purchase order delivered by Alcon to Pharmacyclics promptly after
the Effective Date.
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
40.
41
APPENDIX E
DRUG SUBSTANCE SPECIFICATIONS:
I. EVALUATION PERIOD. It is understood that the Drug Substance
specifications for the Evaluation Plan will meet the current Drug Substance
profile produced by SERES, and as specified in Table 1, unless Drug Substance
becomes available from HCC
TABLE 1
Testing Requirements Method Specifications
(*) (*) (*)
================================================================================
(*) (*) (*)
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
41.
42
II. POST EVALUATION PERIOD. It is understood that the Drug
Substance will be produced by HCC with a demonstrated validated process
consistent with regulatory agencies/committees (i.e., FDA, EMEA, CPMP, MOH, ICH)
guidelines. In the event HCC is unable to meet the specifications in Table 2,
Pharmacyclics will be responsible for chemical and toxicological studies
necessary to establish the suitability of the Drug Substance in meeting the
above regulatory guidelines. Notwithstanding the foregoing, Alcon shall be
responsible for funding and conducting any studies specifically related to
ocular toxicity.
TABLE 2
Test Specifications
(*) (*)
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
42.
00
XXXXXXXX X
XXX-0000 XXXXXXXXXXX SPECIFICATIONS
-------------------------------------------------------------------------------
ITEM: LUTETIUM TEXAPHYRIN (PCI-0123) INJECTION 2 MG/ML
TESTING REQUIREMENTS METHOD SPECIFICATIONS
(*) (*) (*)
(*) (*) (*)
(*) (*) (*)
(*) (*) (*)
(*) (*) (*)
(*) (*) (*)
(*) (*) (*)
(*) (*) (*)
(*) (*) (*)
(*) (*)
-------------------------------------------------------------------------------
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
43.
44
-------------------------------------------------------------------------------
ITEM: LUTETIUM TEXAPHYRIN (PCI-0123) INJECTION 2 MG/ML
COMPOSITION PERCENT DEFINED AS [W/V]
(*) (*)
(*) (*)
(*) (*)
(*) (*)
Store under refrigeration (2(Degree)-8(Degree) C). Do not freeze.
-------------------------------------------------------------------------------
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
44.
45
APPENDIX G
INITIAL TIMELINE AND DEVELOPMENT PLAN FOR UNITED STATES, EUROPE AND JAPAN
DEVELOPMENT PLAN:
o OBJECTIVE:
(*)
o PERFORMANCE PROFILE:
(*)
o APPROACH:
(*)
ESTIMATED DEVELOPMENT EVENTS:
(*)
* Indicates that material has been omitted and confidential treatment has been
requested therefor. All such omitted material has been filed separately with
the Commission pursuant to Rule 406.
45.
46
TABLE OF CONTENTS
PAGE
1. DEFINITIONS.................................................................................1
1.1 Affiliate............................................................................1
1.2 Alcon Inventions.....................................................................1
1.3 Alcon Patents........................................................................1
1.4 Competitive Product..................................................................2
1.5 Confidential Information.............................................................2
1.6 Determination........................................................................2
1.7 Device...............................................................................2
1.8 Drug Substance.......................................................................2
1.9 EMEA.................................................................................2
1.10 Extended Lutetium Texaphyrin.........................................................2
1.11 Evaluation Period....................................................................2
1.12 Evaluation Plan......................................................................2
1.13 FDA..................................................................................2
1.14 FD&C Act.............................................................................2
1.15 Field................................................................................2
1.16 Fill and Finish......................................................................2
1.17 First Commercial Sale................................................................2
1.18 Good Clinical Practices..............................................................2
1.19 Good Laboratory Practices............................................................2
1.20 Good Manufacturing Practices.........................................................3
1.21 Health Authority.....................................................................3
1.22 HC Agreement.........................................................................3
1.23 HCC..................................................................................3
1.24 IND..................................................................................3
1.25 Licensed Product.....................................................................3
1.26 Lutetium Texaphyrin..................................................................3
1.27 MA...................................................................................3
1.28 MAA..................................................................................3
1.29 NDA..................................................................................3
i.
47
TABLE OF CONTENTS
(CONTINUED)
PAGE
1.30 Net Sales............................................................................3
1.31 Non-Lutetium Texaphyrin..............................................................4
1.32 Party................................................................................4
1.33 PCI-0123.............................................................................4
1.34 PCI-0123 Formulation.................................................................4
1.35 PCI-0123 Substance...................................................................4
1.36 Pharmacyclics Inventions.............................................................4
1.37 Pharmacyclics Know-How...............................................................4
1.38 Pharmacyclics Patents................................................................5
1.39 Pharmacyclics Technology.............................................................5
1.40 Phase II.............................................................................5
1.41 Phase III............................................................................5
1.42 PDT or Photodynamic Therapy..........................................................5
1.43 Program..............................................................................5
1.44 Program Intellectual Property........................................................5
1.45 Term.................................................................................5
1.46 Territory............................................................................5
1.47 Texaphyrin...........................................................................5
1.48 UT License...........................................................................5
2. EVALUATION PROGRAM..........................................................................5
2.1 Preparation and Conduct of Evaluation Plan...........................................5
2.2 Cost of the Program..................................................................6
2.3 Compliance with Law..................................................................6
2.4 Supply of PCI-0123 Substance and PCI-0123 Formulation................................6
2.5 Acquisition of Device................................................................6
2.6 Intellectual Property Developed during the Evaluation Period.........................6
2.7 Exchange of Information; Reports during the Evaluation Period........................7
2.8 Development and Commercialization Determination......................................8
3. LICENSE GRANTS; EXCLUSIVITY.................................................................9
3.1 Development and Evaluation Licenses..................................................9
ii.
48
TABLE OF CONTENTS
(CONTINUED)
PAGE
3.2 Commercialization License.............................................................9
3.3 UT License............................................................................9
3.4 Sublicense Rights.....................................................................9
3.5 Rights Upon Expiration................................................................9
3.6 Exclusivity; Right of First Negotiation...............................................9
3.7 Covenants of Alcon...................................................................12
3.8 Competitive Products.................................................................12
3.9 Development of Licensed Products Outside The Field...................................14
3.10 Modifications to Licensed Product....................................................15
3.11 Additional Licensed Products.........................................................16
4. LICENSE FEE, MILESTONE PAYMENTS AND ROYALTIES...............................................16
4.1 Technology Access Fee................................................................16
4.2 License Fee..........................................................................16
4.3 Milestone Payments...................................................................16
4.4 Royalties............................................................................17
4.5 Duration of Royalty Payments.........................................................18
5. PAYMENTS, REPORTS AND RECORDS...............................................................19
5.1 Payments.............................................................................19
5.2 Late Payments........................................................................19
5.3 Exchange Rates; Blocked Currency.....................................................19
6. MANUFACTURE AND SUPPLY OF LICENSED PRODUCT..................................................20
6.1 Supply of Drug Substance..............................................................20
6.2 Fill and Finish of Licensed Products..................................................20
6.3 Formulation Work......................................................................21
6.4 Standby License.......................................................................21
7. MANUFACTURE AND SUPPLY OF DEVICES...........................................................21
8. DILIGENCE IN DEVELOPMENT AND COMMERCIALIZATION..............................................22
8.1 Development Strategy..................................................................22
8.2 Development of Licensed Product.......................................................22
8.3 Marketing Efforts; Required Markets...................................................22
iii.
49
TABLE OF CONTENTS
(CONTINUED)
PAGE
8.4 Reports and Data......................................................................23
8.5 Marketing Restrictions................................................................23
8.6 Trademark.............................................................................23
8.7 Packaging.............................................................................23
8.8 Costs.................................................................................23
9. REGULATORY MATTERS..........................................................................23
9.1 Government Approval...................................................................23
9.2 Right to Reference Data...............................................................24
9.3 Adverse Reaction Reporting............................................................24
9.4 Compliance............................................................................25
10. LIABILITY AND INDEMNIFICATION..............................................................25
10.1 Indemnification by Alcon..............................................................25
10.2 Indemnification by Pharmacyclics......................................................25
11.INTELLECTUAL PROPERTY DEVELOPED POST-EVALUATION PERIOD......................................26
11.1 Ownership of Intellectual Property....................................................26
11.2 Licenses..............................................................................26
11.3 Patent Prosecution and Maintenance....................................................26
11.4 Infringement of Third Party Patents...................................................27
11.5 Third Party Infringement/Misappropriation.............................................27
11.6 Loss of Exclusivity...................................................................28
12. WARRANTIES AND REPRESENTATIONS.............................................................29
12.1 Authorization.........................................................................29
12.2 Disclaimer............................................................................29
12.3 Warranty..............................................................................29
13. TERM.......................................................................................29
14. TERMINATION................................................................................29
14.1 During Evaluation Period..............................................................29
14.2 Early Termination by Alcon............................................................29
14.3 Early Termination by Pharmacyclics....................................................29
14.4 Termination by Alcon..................................................................30
iv.
50
TABLE OF CONTENTS
(CONTINUED)
PAGE
14.5 Termination for a Competitive Product.................................................31
14.6 Damages...............................................................................31
14.7 Waiver................................................................................31
14.8 Survival..............................................................................32
15. CONFIDENTIALITY............................................................................32
15.1 Confidential Information.............................................................32
15.2 Treatment of Confidential Information................................................32
15.3 Exceptions...........................................................................32
15.4 Terms of this Agreement..............................................................32
15.5 Prior Confidentiality Agreements.....................................................33
16. PUBLICITY..................................................................................33
17. FORCE MAJEURE..............................................................................33
18. SUCCESSION AND ASSIGNMENT..................................................................33
19. NOTICES....................................................................................34
20. AFFILIATES.................................................................................34
21. WAIVER.....................................................................................34
22. ENTIRE AGREEMENT AND AMENDMENT; TITLES.....................................................35
22.1 Entire Agreement.....................................................................35
22.2 Titles...............................................................................35
23. SEVERABILITY...............................................................................35
24. NO AGENCY..................................................................................35
25. GOVERNING LAW..............................................................................35
26. MODIFICATIONS..............................................................................35
27. LITIGATION.................................................................................36
v.
