ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
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EXHIBIT 10.42
AMENDED AND RESTATED
AGREEMENT
ON G-CSF IN THE EU
BETWEEN
AMGEN INC.
AND
F. HOFFMANN-LA ROCHE LTD
TABLE OF CONTENTS
ARTICLE PAGE
1. DEFINITIONS 1
2. GRANTS AND OBLIGATIONS 6
3. COLLABORATION IN CLINICAL RESEARCH
DEVELOPMENT, REGISTRATION & MARKETING 14
4. OWNERSHIP, PREPARATION AND FILING
OF CPMP, NDA's and MA/V's 19
5. SUPPLY 22
6. MARKETING 28
7. COMPENSATION 34
8. REPORTS AND PAYMENTS 36
9. WARRANTIES AND INDEMNIFICATION 38
10. PATENT AND TRADEMARK INFRINGEMENT 39
11. TERM AND TERMINATION 40
12. MISCELLANEOUS 42
AMENDED AND RESTATED
AGREEMENT
ON G-CSF IN THE EU
This Agreement is made and effective as of the 10th day of
April 1997 ("Effective Date") by and between AMGEN INC., a
Delaware corporation located at Thousand Oaks, California, USA
(hereinafter "AMGEN") and F. HOFFMANN-LA ROCHE LTD, a corporation
organized and existing under the laws of Switzerland located at
Basel, Switzerland (hereinafter "ROCHE").
WHEREAS, AMGEN possesses rights in and to a pharmaceutical
product known as G-CSF;
WHEREAS, AMGEN and ROCHE have entered into a contractual
relationship regarding G-CSF in the European Union;
WHEREAS, AMGEN and ROCHE have agreed to modify their present
relationship as set forth herein.
NOW, THEREFORE, for and in consideration of the mutual
covenants contained herein, ROCHE and AMGEN hereby agree as
follows:
ARTICLE 1
DEFINITIONS
1.01 "Affiliate" shall mean:
(a) An organization which owns, directly or indirectly, a
controlling interest in AMGEN or ROCHE by stock ownership
or otherwise; or
(b) An organization in which AMGEN or ROCHE or its
stockholders own, directly or indirectly, a controlling
interest by stock ownership or otherwise; or
(c) An organization having its majority ownership directly or
indirectly common to the majority ownership of AMGEN or
ROCHE.
1.02 "KIRIN" shall mean, collectively, KIRIN BREWERY INC., a
Japanese company and KIRIN-AMGEN, INC., a California
corporation, fifty percent (50%) owned by AMGEN, as the case
may be in the context used in a particular section of this
Agreement.
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1.03 "Territory" shall mean all countries which are currently
members of the European Union ("EU") together with those
countries that join the EU during the Term of this Agreement.
As soon as any EU member country may withdraw or become
excluded from the EU, then as from the effective date of such
withdrawal or exclusion, such country shall automatically be
considered as a country of the territory of the Agreement on
G-CSF in Certain European Countries dated as of the first day
of January 1989.
1.04 "G-CSF" shall mean a polypeptide of 174 or 175 amino acids,
with an amino acid sequence according to positions +1 to 174
of Table VII of International Patent Application Publication
No. WO 87/01132 with possibly an additional N-terminal
methionine, obtained by recombinant DNA technology, having
the biological properties of naturally-occurring pluripotent
granulocyte colony-stimulating factor.
1.05 "Product" shall mean: (1) any product consisting of or
containing as an active ingredient G-CSF or (2) a Second
Generation Product, if any, that becomes a Product pursuant
to the provisions of Section 2.03 hereof. For illustration,
the term Product shall include, without limitation, bulk
forms of the Product ("Bulk Product") and/or finished and
packaged dosage units of the Product ("Finished Product").
1.06 "Patents" shall mean all patents (including inventor's
certificates) and applications therefor owned and/or
controlled by AMGEN in the countries of the Territory,
including without limitation any substitutions, extensions,
reissues, renewals, divisions, continuations or
continuations-in-part thereof or therefor covering G-CSF or a
Product or inventions, arising from or made during the course
of this Agreement.
Notwithstanding the foregoing, the term "Patents" shall have
the following meaning in reference to a Second Generation
Product that becomes a Product pursuant to Section 2.03:
"Patents" shall mean all patents (including inventor's
certificates) and applications therefor owned and/or
controlled by AMGEN or ROCHE or in which either party has any
interest (including but not limited to the ***********
Patents) in the countries of the Territory, including without
limitation any substitutions, extensions, reissues, renewals,
divisions, continuations or continuations-in-part thereof or
therefore covering a Product or inventions, arising from or
made during the course of this Agreement."
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1.07 "Term of this Agreement" shall mean the period commencing on
the Effective Date of this Agreement and ending, unless
terminated sooner or prolonged in accordance with this
Agreement, on December 31, 2010, or until the date of
*************************************************************
************* in which either party has any right or interest
claiming a Product approved for sale in the EU,
******************. If, however,
*************************************************************
*************************************************************
******, the term of this Agreement **************** until the
*************************************************************
************************************. The latest of any of
the dates in this Section 1.07 is hereinafter referred to as
the "Scheduled Termination Date".
1.08 "Confidential Information" shall mean information which
relates to G-CSF or a Product, including financial
statements, costs and expense data, marketing, distribution
and consumer data, production data, know-how, trade secrets,
secret processes and formulae, technical data and reports
including gene technology, biochemical, toxicological,
pharmacokinetic, manufacturing and formulation data, clinical
data, regulatory correspondence or any other information
which is not generally ascertainable from public or published
information, regardless or whether such information was
provided pursuant to the terms of this Agreement, by request
of the other party or in any other manner.
By way of illustration, Confidential Information shall
include without limitation, all information developed or to
be developed by a party to this Agreement, its Affiliates,
and/or clinicians, and all material and information submitted
to and/or filed with a governmental regulatory agency or any
other equivalent agency covering a Product. Confidential
Information shall also include without limitation all
information related to G-CSF or a Product contained in all
documents submitted in connection with INDs (Investigational
New Drug), NDAs (New Drug Application), CTCs (Clinical Trial
Certificate), AMM (Authorisation de Mise au Marche) and other
regulatory submissions throughout the world covering a
Product.
1.09 "Trademark" shall mean the trademark NEUPOGEN(R) owned by
AMGEN and all other trademarks, if any, adopted, used and/or
owned by AMGEN in connection with a Product.
3
1.10 "CPMP" shall mean either (i) the Committee for Proprietary
Medical Products, (ii) its procedures, including its
"bio/high tech" concertation procedures or (iii) the
marketing authorization applications as per such procedures
as the case may be in the context used in a particular
section of this Agreement.
1.11 "Net Sales" shall mean the gross invoice price billed for
Product to third parties by AMGEN or ROCHE and/or each of its
Affiliates (but not including invoices relating to
transactions between and/or among AMGEN, ROCHE, and/or each
of its Affiliates) with respect to a Product in the
Territory, less those deductions normally made under
generally accepted accounting principles and described in
detail in the Supplementary Agreement.
1.12 "Operating Profit or Loss" shall mean the combined profit or
loss of both companies resulting from the activities
described in this Agreement and described in detail in the
Supplementary Agreement.
1.13 "Operating Costs and Expenses" shall mean those costs and
expenses which are included in the calculation of Operating
Profit or Loss. They are described in detail in the
Supplementary Agreement.
1.14 "Supplementary Agreement" shall mean the supplementary
agreement attached hereto as Appendix 1.14, which is hereby
modified effective as of the Effective Date to (1) change all
references therein from Swiss francs to U.S. Dollars to
reflect the change in the functional currency of this
Agreement from Swiss francs to U.S. Dollars and (2) apply
mutatis mutandis except where the context requires otherwise.
It is the intent of the parties to revise the Supplementary
Agreement as soon as practicable following the execution of
this Agreement in order to memorialize previously agreed
alterations thereto.
1.15 "Scheduled Termination Date" shall have the meaning set forth
in Section 1.07.
1.16 "EMEA" shall mean either (i) the European Agency for the
Evaluation of Medicinal Products, (ii) its procedures and
approval systems, including its centralized approval
procedure or (iii) the marketing authorization applications
as per such procedures as the case may be in the context used
in a particular section of this Agreement.
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1.17 "Second Generation Product" shall mean any product consisting
of or containing as an active ingredient any of the following
************ (other than G-CSF) which
******************************************************:
(i)
*****************************************************
*******************************************;
(ii)*************************************************
*****************************************************
*****;
(iii)*******************************;
(iv)*************************************************
**********************************;
(v)
*****************************************************
**********************; and
(vi)
*****************************************************
*****************************************************
***************************************************.
1.18 "Current GMP Requirements" shall mean those current
practices, as amended from time to time, related to the
manufacture of biotechnology products and their precursors
laid down in guidelines and regulations such as the GMP rules
of the World Health Organization, the United States Code of
Federal Regulations, the Guide to Inspection of Bulk
Pharmaceutical Chemicals (U.S. Department of Health and Human
Services, Revised September 1991), the Pharmaceutical
Inspection Convention, and the European Community Guide to
Good Manufacturing Practice in the production of
pharmaceutical products.
1.19 In the terms defined herein, the singular shall include the
plural and vice versa.
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ARTICLE 2
GRANTS AND OBLIGATIONS
2.01 (a) AMGEN hereby grants to ROCHE and its Affiliates, under
the Patents and Trademarks and the conditions herein imposed,
the ****************** right to formulate and fill Finished
Product in any country of the Territory or in Switzerland,
*******************************.
By mutual agreement between parties hereto, ROCHE shall have
the right to have formulated and/or filled Finished Product
by a particular independent third party in any country of the
Territory or in Switzerland.
All rights of ROCHE and its Affiliates under this subsection
(a) shall terminate with regard to each country (including
with respect to all Products sold in each such country) on
the respective dates set forth in Appendix 2.01 (a) and AMGEN
shall formulate and fill each Finished Product itself.
(b) AMGEN hereby grants to ROCHE and its Affiliates, under
the Patents and the conditions herein imposed, the
*************************************************************
****** right to use and sell (including the right to promote
and detail) each Finished Product in the Territory,
*******************************; provided, however, that
AMGEN and ROCHE have agreed to certain other terms relating
to Spain and Italy which are set forth in Appendix 2.01,
which terms shall supplement (and if in conflict shall
supersede) all other terms of this Agreement. All rights and
obligations specified in Appendix 2.01 shall also apply to
any Second Generation Product that becomes a Product pursuant
to the terms of Section 2.03.
It is, however, understood that AMGEN shall retain the right
to ******************************* with ***** in the
Territory as further described hereinbelow.
All rights of ROCHE and its Affiliates under this subsection
(b) to use and sell (but not the right to ******************)
shall terminate for each Product with regard to the countries
and upon the respective dates set forth in Appendix 2.01 (b).
(c) AMGEN and ROCHE shall each have the right and obligation
to co-develop each Product to be promoted, detailed and sold
in all countries of the Territory, as set forth in more
detail hereinbelow.
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(d) During the Term of this Agreement, AMGEN shall not
either, directly or indirectly or expressly or by
implication,
*************************************************************
*******************************:
(i)
*****************************************************
**************************** in any country in the
Territory or in Switzerland, or
(ii)*********************************************************
****** in any country of the Territory, except where such
arrangements are made primarily for the provision of
logistic or related services or back-up supply.
e) AMGEN hereby grants to ROCHE and ROCHE to AMGEN a
************ right and license in each country in the
Territory to that portion of their respective Confidential
Information, **************, as is necessary to perform their
respective obligations as set forth in this Agreement, such
right and license to continue in each country of the
Territory until the Scheduled Termination Date.
(f) AMGEN hereby grants to ROCHE a ************ right and
license in each country of the Territory to AMGEN's Trademark
for use as set forth in this Agreement in connection with
each Product to which such Trademark is applicable, such
right and license to continue in each country of the
Territory until the Scheduled Termination Date.
Except as necessary to perform ROCHE's obligations set forth
in this Agreement, ROCHE's right and license under this
subsection (f) shall terminate for each Product with regard
to the countries and upon the respective dates set forth in
Appendix 2.01 (b).
2.02 It shall be a material obligation of each party hereunder to
act in accordance with accepted business practices and all
material legal requirements in carrying out its rights and
responsibilities hereunder.
2.03 Second Generation Product.
(a) General
It is the desire of the parties to develop and commercialize
a Second Generation Product for the Territory, subject to and
in accordance with the rights, obligations and conditions set
forth in this Agreement. Any future decision by AMGEN and
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ROCHE to develop a Second Generation Product for the
Territory shall be
*************************************************************
*************************************************************
*************************************************************
*************************************************************
***************, the Second Generation Product shall be
deemed to be a "Product" within the meaning of this Agreement
and development will be governed by the terms of Article 3
hereof. The specific Second Generation Product to be
developed shall be ********************, in accordance with
the Evaluation Plan attached hereto as Appendix 2.03. Prior
to completion of the Evaluation Plan, AMGEN and ROCHE shall
(unless the parties
*****************************************) meet ********* (as
part of the ******************************* meetings) to
discuss matters relating to the Evaluation Plan for a Second
Generation Product for the Territory. Any and all information
exchanged by the parties during the period of the Evaluation
Plan shall be considered Confidential Information of the
party disclosing such information and shall be governed by
the terms of Sections 1.08, 2.01 e), 12.02 and 12.03 of this
Agreement. In order to preserve its rights and satisfy its
obligations under the License Agreement dated January 1, 1996
between ROCHE, Hoffmann-La Roche Inc. and
*************************** ("***********") (the "***********
License"), ROCHE shall inform *********** on the evaluation
process of the Second Generation Product and the respective
results to the extent related to the ***** Product (as
hereinafter defined) or the *********** Patents (as
hereinafter defined); provided, however, that prior thereto
ROCHE shall obtain from *********** (and deliver to AMGEN) a
written agreement in favor of ROCHE and AMGEN whereby
*********** agrees to treat any and all such information as
Confidential Information governed by the terms of Sections
1.08, 12.02 and 12.03 of this Agreement.
Upon selection of a Product for development following
completion of the Evaluation Plan, AMGEN and ROCHE shall use
their best efforts to prepare a Clinical R&D Plan described
in Section 3.03 (c) hereof. Thereafter, AMGEN and ROCHE
shall exercise commercially reasonable efforts to develop and
commercialize the Product in accordance with the Clinical R&D
Plan in the Territory. AMGEN shall control development,
preclinical, clinical, regulatory and marketing of a Second
Generation Product (including preclinical, clinical and other
matters prior to the time it becomes a Product) and shall
distribute, and
*************************************************************
*************************. The Clinical R&D Plan including
launch date shall be mutually agreed upon.
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(b) *********** License
If the agreed upon Second Generation Product includes any
technology claimed in or covered by the *********** PATENTS
(as defined in the *********** License and hereinafter
referred to as the "*********** Patents") in the "***********
License", ROCHE will grant AMGEN an **********************
sublicense for the Territory under any rights ROCHE may have
with respect to the *********** Patents under the ***********
License. ROCHE shall not
****************************************** any of its rights
under the *********** License. ROCHE and its Affiliates will
commercialize a Second Generation Product in the Territory
only under rights granted by AMGEN.
(c) AMGEN Products
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*********************************** This paragraph shall not
apply to G-CSF (Neupogen(R)) or a Second Generation Product
which AMGEN or its licensee/partner brings to the Territory
in a cell therapy, ex-vivo expansion application.
(d) ROCHE Products
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
**********************************
(e) Development Costs
As from the Effective Date, AMGEN and ROCHE shall share, in
accordance with the then current profit split in Article 7,
************************************ in the Territory for a
Second Generation Product or a Product, including:
-
*******************************************************
******************; and
9
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-
*******************************************************
*************************** License. Such costs shall
include ********* payable to *********** as follows:
i) ***************** of the NET SALES (as defined in
the *********** License) of the
******************************** product described and
claimed by *********** in the *********** Patents as
********** (the "***** Product"), provided, however,
that in the event that
(1)certain ********* have to be paid to a third party
due to a patent issue, in such case the *******
payable to *********** shall be
****************************************************
**********; or
(2)the ***** Product shall face significant competition
from a third party
****************************************************
************************ the ******* payable to
*********** in any such country shall be
****************************************************
*****************;
provided further that the total deduction in the
aggregate from (1) and (2) shall not cause the
************ payable to *********** to be less than
*****************.
If both (1) and (2) are applicable, the calculation in
(1) shall be made first and then (2) shall be
calculated.
ii)For a Second Generation Product other than the *****
Product the making, using, selling, offering for sale,
or importing of which would, but for ***********
License, infringe one or more valid issued claims
included in the *********** Patents, all *************
as per i) will be ****************************.
iii)For a Second Generation Product the making, using,
selling, offering for sale or importing of which does
not infringe one or more valid issued claims included
in the *********** Patents, all ************* as per i)
will be **************.
iv)The ********* under iii) above shall be payable so
long as the *********** License is in full force and
effect.
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Such costs shall also include the ********** payable to
*********** as follows:
(1)************
************************************
********************** shall be payable no later
than **************
(2)********************
*************************************************
shall be payable *********************** after the
first entry of a patient in a ************** with a
Second Generation Product in any EU country or the
****************** as agreed to in the time and
events schedule in the Clinical R&D Plan (to be
established after the completion of the Evaluation
Plan), whichever is earlier.
(3)******************
*************************************************
shall be payable *********************** after 50%
of patients have been enrolled in a ***************
with a Second Generation Product in any EU country,
or to ********************************* as agreed to
in the time and events schedule of Clinical R&D
Plan, whichever occurs earlier.
(4)****************
************************************
*********************************** shall be payable
*********************** after the submission of the
first Second Generation Product license
*********************************** to the Authority
in ********************************** or the
*********************** as agreed to in the time and
events schedule in the Clinical R&D Plan, whichever
is earlier.
(5)With respect to
****************************************************
***** of (3) above and
****************************************************
******************* of (4) above, shall be
creditable against the payment of ******* payable to
***********.
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(f) ********* of Second Generation Products
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
*************************************************************
**************************
i)
*****************************************************
*****************************************************
****
ii)
*****************************************************
*****************************************************
****
iii)***********************************************************
*****************************************************
iv)
*****************************************************
*****************************************************
********************
v)
*****************************************************
*****************************************************
*
(g) Manufacturing
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If the agreed upon Second Generation Product is the *****
Product, ***** shall have the rights to manufacture the bulk
form of the Product for the Territory and supply and deliver
it DDP (Incoterms 1990) at a price equal to
********************************** (as defined in the
*********** License) of the Product in the Territory. Until
such *************** is available, the Product shall be
delivered at the expected average *************** in the
Territory to be agreed by the parties and ***********. All
Second Generation Products other than the *********** Product
will be manufactured, formulated and filled by AMGEN for the
Territory.
(h) Miscellaneous
There is nothing in the Kirin-AMGEN Agreements that restricts
AMGEN from fulfilling its obligations under this Agreement
regarding any Second Generation Product in the Territory.
There is nothing in this Agreement that restricts any party
from commercializing in the ROE *************** and ROW
(throughout the world,
*************************************************************
***************************** a Second Generation Product
that is not being commercialized in the EU.
(i) Applicability of Other Provisions of this Agreement
If and when a Second Generation Product becomes a "Product"
pursuant to this Section 2.03, then in addition to the
provisions of this Section 2.03 the other provisions of this
Agreement shall also apply with respect to such Product.
2.04 AMGEN shall have sole ownership of the G-CSF Product and all
related rights during the Term and following expiration or
termination thereof.
With respect to any Second Generation Product that becomes a
Product pursuant to Section 2.03:
(1) if the Product is the ***** Product or is otherwise
covered by the *********** Patents, then AMGEN shall have
the rights described in Section 2.03(b) for the Term and
the parties shall
********************************************* under the
*********** License (taking into account ROCHE's
obligations to ***********) following expiration or
termination of this Agreement;
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(2) if the Product is covered by any ROCHE Patents, then
ROCHE shall have sole ownership of the Product and all
related rights during the Term and following expiration
or termination thereof but AMGEN shall have an
*********************************************************
***************************************** license to the
Product for the Term and the parties shall
********************************************* following
expiration or termination of this Agreement; and
(3) if the Product is covered by any AMGEN Patents, then
AMGEN shall have sole ownership of the Product and all
related rights during the Term and following expiration
or termination thereof but the parties shall
********************************************* following
expiration or termination of this Agreement.
ARTICLE 3
COLLABORATION IN CLINICAL RESEARCH, DEVELOPMENT,
REGISTRATION AND MARKETING
3.01 AMGEN and ROCHE shall cooperate in reasonable ways to develop
and exchange data and information about each Product so as to
obtain the authorization and to develop the ability to
formulate, ship and sell the Product in the Territory.
Pursuant to the terms of this Agreement, the parties shall
use reasonably diligent efforts consistent with prudent
business practice to
(i) optimally develop each Product,
(ii)obtain rapidly the necessary governmental authorization
and approval to sell each Product in commercial
quantities, and
(iii)sell each Product in all countries in the Territory.
3.02 (a) The parties shall each appoint two (2) authorized
representatives ("Coordinators") between whom communications
will be directed with regard to each Product. Each party will
notify the other as to the name of the individuals so
appointed. Each party may replace its Coordinators at any
time, upon written notice to the other party.
The four (4) Coordinators shall form a joint committee
("Product Management Committee") and shall confer regularly
to discuss and to coordinate the effective performance of the
terms of this Agreement.
14
The Product Management Committee is expected to meet
regularly to
(i) review pertinent information and data
(ii)approve the budgets proposed by the sub-teams and the
countries.
(iii)resolve differences of opinion within the sub-teams, if
any.
(iv)harmonize and coordinate all efforts in view of obtaining
authorization and ability to market each Product in each
country in the Territory and to further develop, promote
and detail each Product in each country of the Territory
pursuant to Article 6.
(b) The Product Management Committee shall establish one or
more operating dedicated sub-teams for the whole Territory
directed by the Product Management Committee and consisting
of representatives of each party which will meet regularly at
mutually agreeable times and locations.
3.03 (a) One of the sub-teams of subsection 3.02(b), the joint
international clinical development team ("Product Clinical
Team") shall consist of two (2) permanent representatives of
each AMGEN and ROCHE. Each party may replace its
representatives at any time, upon written notice to the other
party.
(b) The Product Clinical Team will be responsible to discuss
and coordinate the generation and exchange of information and
data necessary to obtain and maintain approval of each
Product in each country of the Territory, and formulate the
strategies, the plans and the programs that should be
implemented to most effectively and efficiently obtain such
approvals. Illustratively, the Product Clinical Team shall:
(i) formulate and coordinate plans for the development of
data and information necessary to obtain governmental
approvals of each Product in each country of the
Territory, taking into consideration, if applicable,
AMGEN's development plans for the USA and AMGEN's results
elaborated in the USA, and
(ii)coordinate the preparation and the filing of all
governmental applications for approvals necessary to
distribute and market each Product in each country of the
Territory, taking into consideration, if applicable, and
using to the extent reasonably possible, AMGEN's clinical
development plans as well as any data and submissions to
the FDA on each Product.
(c) The Product Clinical Team shall create and execute a
Joint Clinical Research and Development Plan for the
Territory ("Clinical R&D Plan") which shall describe the
clinical program necessary for the preparation and filing of
15
the first as well as subsequent NDA's in the Territory and
any additional studies and/or programs required to support
NDA claims and/or to generate scientific publications with
due regard for the overall international plan created by
AMGEN with input from ROCHE and KIRIN and consideration of
pre-clinical and clinical data.
The Clinical R&D Plan will include the description of:
(i) clinical strategies, rationale, objectives, general
program and study designs, location of studies, principal
investigator name, time schedules, number of patients
planned, status of studies and program, responsibility
for monitoring and data handling and any critical issues
and recommendations relative to the clinical development
of each Product, and
(ii)strategies, plans and status of IND, NDA and MAA (or
equivalent documents, including EMEA) preparation and
submission to governmental authorities to obtain
authorization to carry out clinical studies and to obtain
from all necessary governmental authorities marketing
approval of each Product in each country of the
Territory.
(iii)estimates of costs of implementing the approval Clinical
R&D Plan and the AMGEN and ROCHE personnel and external
personnel and resources required to execute the approved
Clinical R&D Plan.
(d) The Product Clinical Team shall, inter alia, be
responsible for the following issues:
(i) assuring that the clinical program is carried out to
mutually acceptable levels of Good Clinical Practice
procedures,
(ii)preparing and approving individual study protocols, case
record forms, final study reports and any other official
clinical research documents,
(iii)establishing and maintaining a compatible international
computerized database on an AMGEN-based computer to
which ROCHE and AMGEN shall have terminal access.
(iv)the appropriate collection and transfer of reportable
adverse event data to satisfy governmental agencies and
post-marketing surveillance throughout the world, and
(v) creating and proposing to the Product Management
Committee a detailed clinical budget, monitoring actual
expenditures versus budget and proposing appropriate
revisions to this budget.
16
(vi)reviewing and approving the promotional materials of each
country in the Territory to ensure compliance with
approved labeling.
(vii)creating an environment in which the clinical
development of each Product can be harmoniously and
efficiently carried out.
(e) The provisions of the Clinical R&D Plan and any other R&D
matters shall be agreed to by the Product Clinical Team and
approved by the Product Management Committee, and if the
Product Clinical Team cannot reach a consensus agreement,
then the matter(s) in dispute shall be referred to the
Product Management Committee.
(f) In the event that the Product Management Committee is
unable to reach a consensus decision on any R&D matter, the
President of AMGEN shall be entitled to make the final
determination.
3.04 (a) The other of the sub-teams of subsection 3.02(b), the
joint marketing team ("Product Marketing Team") shall also
consist of two (2) permanent members of each AMGEN and ROCHE.
Each party may replace its representatives at any time, upon
written notice to the other party.
(b) The Product Marketing Team shall have the responsibility
for the marketing functions as set forth in Article 6 of this
Agreement.
(c) All items regarding the marketing functions shall be
agreed to by the Marketing Team and approved by the Product
Management Committee, and if the Product Marketing Team
cannot reach a consensus agreement, then the matter(s) in
dispute shall be referred to the Product Management
Committee.
(d) In the event that the Product Management Committee is
unable to reach a consensus decision on marketing matters,
the President of AMGEN shall be entitled to make the final
determination.
3.05 AMGEN and ROCHE shall promptly furnish each other with all
Confidential Information in its possession and control with
respect to each Product in the Territory, which has not been
previously furnished to the other and which may aid the other
in performing its responsibilities under this Agreement.
Moreover, the parties will provide each other, through the
Product Clinical Team, with the results of all of its pre-
clinical and clinical studies on G-CSF throughout the world,
and with
17
(i) quarterly status reports and data on its clinical
development efforts with respect to G-CSF outside the
Territory to which the other party may not have access
otherwise;
(ii)data and information on animal and human studies relative
to G-CSF known to it; and
(iii)information and data regarding G-CSF which was submitted
or will be submitted by ROCHE or its Affiliates, AMGEN or
its Affiliates, or KIRIN (to the extent possible
according to contractual relations) to governmental
authorities throughout all countries of the world outside
the Territory to obtain authorization to initiate
investigational use in humans and/or to obtain approval
to market G-CSF in commercial quantities in such
countries, including but not limited to control, pre-
clinical and clinical information and data.
3.06 The results of all clinical studies and experiments with
respect to each Product conducted in connection with this
Agreement, and related technical information, shall be
delivered promptly to AMGEN by ROCHE and to ROCHE by AMGEN,
and may be used by each and its Affiliates, as well as KIRIN,
in connection with further development and marketing of each
Product and applications to governmental authorities
throughout the world.
3.07 In accordance with the Clinical R&D Plan, AMGEN (or in the
case of a Second Generation Product that becomes a Product,
either AMGEN or ROCHE, as mutually agreed by the parties)
shall supply quantities of each Product in a form suitable
for clinical trials which would enable the parties to
continue to analyze each Product and to initiate and to
continue tests including, but not limited to,
pharmacological, toxicological, microbiological, and clinical
tests on each Product as well as material for formulation
tests on the Product which in both the Product Clinical
Team's as well as in the Product Marketing Team's reasonable
judgment may be necessary to obtain the authorization and the
ability to formulate the Finished Product in any country of
the Territory as well as to ship and sell each Product in the
Territory.
3.08 AMGEN and ROCHE will promptly seek and use its best efforts
to obtain all necessary FDA, EMEA and other applicable
governmental authorizations throughout the world required for
the party supplying each Product pursuant to Section 3.07 to
manufacture, ship and export each Product from the USA (or
other country of export) to all countries in the Territory
and in Switzerland for the parties to be able to conduct pre-
clinical and clinical trials.
18
3.09 During the Term of this Agreement, each party shall promptly
furnish the other party with information concerning
unexpected side effects, injury, toxicity or sensitivity
reactions or unexpected incidence and severity thereof
associated with animal or clinical uses, studies,
investigations or tests with each Product, whether or not
determined to be attributable to each Product.
3.10 Each party, free of charge, shall also permit a reasonable
number of representatives of the other party to this
Agreement or its Affiliates at reasonable time and upon
reasonable notice, to observe, review, make copies of, and/or
discuss the results of studies and/or submissions (except
studies or submissions relating to manufacturing the Bulk
Product to the extent not necessary for seeking marketing
approval) to the governmental authorities concerning each
Product with scientists or clinicians employed by it (or its
Affiliates) or doing research under its auspices, at any
location mutually agreeable to the parties hereto.
ARTICLE 4
OWNERSHIP, PREPARATION AND FILING OF
EMEA, CPMP, NDA's and MA/V's
4.01 In connection with its tasks contained in Section 3.03
hereinabove, the Product Clinical Team shall prepare and
complete a marketing application and variations for new
indications and new galenical forms pursuant to the CPMP/EMEA
"bio/high tech" concertation procedure ("MA/V Filing") with
respect to each Product for use in each country of the
Territory.
Such MA/V shall contain all data and information deemed
necessary to obtain and maintain approval of the respective
marketing authorizations (including variations) in each
country of the Territory ("Country MA/V") with respect to the
indications of each Product agreed upon by the Product
Clinical Team.
Notwithstanding the foregoing, if applicable, the MA/V Filing
shall instead be made pursuant to the centralized approval
procedure of the EMEA (or other then applicable and
appropriate procedure) in order to obtain and maintain
approval of the centrally approval marketing authorization
(including variations) for the EU (the "EU MA/V").
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4.02 All data, information, results, etc., including Confidential
Information, contained in the
*************************************************************
*******************************, provided, however, that
*************************************************************
************* and all data, information, results, etc.,
including Confidential Information, as is necessary for ROCHE
to perform its duties as set forth in this Agreement and the
*********** License.
4.03 (a) ***** shall have the ********* in the preparation and
filing of the
*************************************************************
*************************************************************
********, respectively, with the respective authorities of
the rapporteur country of the Territory and lodged with the
CPMP/EMEA secretariat.
*************************************************************
********************************************************,
respectively, with the respective authorities in each country
of the Territory, ************************************.
(b) ************************, respectively, subject to
consultation with and approval by the Product Clinical Team,
shall be responsible for filing responses to questions and
comments received from governmental authorities with respect
to Country MA/V's and for filing reports necessary to
maintain Country MA/V's.
In carrying out such responsibilities, AMGEN and its
Affiliates, and ROCHE and its Affiliates shall advise the
Product Clinical Team of all communications by them with
governmental authorities that may be considered significant
and shall, if requested by the Product Clinical Team, submit
for prior review all proposed filings.
4.04 (a) AMGEN and ROCHE shall, in principle, attend all meetings,
if any, with CPMP, EMEA and other drug regulatory personnel
of the EU. AMGEN shall have the lead role in making
presentations in such meetings.
(b) AMGEN and its Affiliates, respectively, subject to
consultation with and approval by the Product Clinical Team,
shall be responsible for responding to questions and comments
received from governmental authorities.
(c) In the event that the Product Clinical Team or the
parties are unable to reach a consensus decision on any
regulatory matter, AMGEN shall be entitled to make the final
determination.
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4.05 (a) With regard to the countries and upon the respective
dates set forth in Appendix 2.01 (b):
(i) the rights and obligations of
************************ in Sections 4.03 (a) and (b)
shall terminate and thereafter the following shall apply
in lieu thereof with respect to each Product: *****
shall have the lead role in preparation and filing of the
*********** and shall file the *********** in its ****
with the EMEA (or other than applicable regulatory
agency). The parties shall mutually agree on the method
of the filing(s), if any, necessary to enable ***** and
***** to sell each Product in the Territory pursuant to
the terms of this Agreement. ***** shall be the holder of
each **** and *********************************,
respectively, subject to consultation with and the
approval by the Product Clinical Team, shall be
responsible for filing responses to questions and
comments received from any and all regulatory authorities
with respect to the ***********. Following receipt of the
**** or ********************************* will file
reports necessary to maintain the MA/V or EU MA/V and
respond to inquiries and comments from any and all
regulatory authorities. In carrying out such
responsibilities, ************************ shall advise
the Product Clinical Team of all communications by them
with governmental authorities that may be considered
significant and shall, if requested by the Product
Clinical Team, submit for prior review all proposed
filings.
(ii)all data and documents with respect to a
***************************** shall be handed over by
***** to *****, which shall be entitled to use such data
and documents for its own purposes and for the purposes
of this Agreement.
(iii)****** shall cooperate with ***** on a timely basis
and in every proper way to
*********************************************************
************ to ***** and ***** shall seek, and use its
best efforts to obtain, the necessary authorization from
the pertinent governmental authorities
****************************
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(iv) to the extent necessary, applicable governmental
authorizations and approvals in the country shall be
*********** to the extent permitted by laws and
regulations, from ***** to
******************************************** for such
transfer shall be charged to the
************************* provided for hereunder.
Notwithstanding the foregoing, ROCHE shall retain its rights
and obligations under this Article 4 with respect to Italy
(ROCHE-Trademark) (Granulokine(R)) until the Scheduled
Termination Date.
ARTICLE 5
SUPPLY
5.01 With respect to the Territory, AMGEN shall supply ROCHE,
******* and under the terms of this Agreement, with
requirements of Finished Product for clinical purposes and
Bulk Product for all developmental and commercial purposes
for all countries of the Territory and shall obtain
authorization form the FDA to manufacture, ship and export
from the USA Bulk Product and Finished Product for clinical
purposes in and to any appropriate countries of the Territory
or Switzerland.
5.02 (a) For the whole Territory, the Product Marketing Team shall
provide AMGEN (i) within **************** of signing this
Agreement a preliminary ************ forecast of the total
requirements for Bulk Product, and (ii) at least
**************** before the beginning of each calendar year
with a ********* forecast of the total requirements for the
Bulk Product in the respective calendar year.
(b) Thereafter, a revised estimate of the requirements will
be given prior to each calendar quarter for the subsequent
four calendar quarters.
(c) Within *************** before the date ROCHE requires to
receive the amount of Bulk Product as per subsections (a) and
(b) of this Section 5.02, ROCHE shall place firm orders
setting forth the quantities of Bulk Product to be supplied
by AMGEN.
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(d) ROCHE's firm orders shall specify reasonable delivery
dates and instructions for shipping and packaging as
aforesaid. If there is any inconsistency between any of the
terms and conditions of a ROCHE order and the terms and
conditions of this Agreement, the terms and conditions of
this Agreement shall prevail.
5.03 AMGEN will manufacture Bulk Product and ROCHE will formulate
and fill Finished Product strictly
(i) in accordance with established written manufacturing
procedures and Finished Product specifications according
to Current GMP Requirements,
(ii)which will meet the requirements set forth in accordance
with applicable laws and regulations for shipment of the
Bulk Product into any of the countries of the Territory
or into Switzerland, and
(iii)which will meet the requirements set forth in all
governmental submissions filed by ROCHE or AMGEN with
regulatory agencies for the manufacture of the Bulk
Product into Finished Product.
Each party shall promptly advise the other party of any new
instructions or specifications required by the foreign
regulatory agencies and the parties shall confer with respect
to the best mode of compliance with such requirements.
5.04 (a) AMGEN will provide ROCHE with a certificate of analysis
for each lot of Product produced. In order to comply with
Current GMP Requirements, ROCHE requests and AMGEN agrees to
supply ROCHE with all procedures, including SOP's, allowing
ROCHE to perform:
(i) The analyses of the Product upon arrival at ROCHE's
designated facility(ies), and
(ii)The analyses of the finished pharmaceutical form before
ROCHE supplies to the trade or the Clinical Research
Centers.
(b) On receipt of a delivery of the Bulk Product ordered,
ROCHE shall check whether it complies with the
specifications. Any discernible non-compliance has to be
reported in writing to AMGEN immediately, together with all
test data, at the latest within ************* after receipt
of the delivery. At the same time ROCHE sends the written
notification, ROCHE shall also send to AMGEN a sample of the
Bulk Product delivered. Otherwise, it will be assumed that
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the Bulk Product delivered has been approved. In the event of
a duly claimed and justified notice of non-compliance, AMGEN
shall make good the order by delivering new material.
5.05 AMGEN will use its best efforts to comply with the sales
forecasts, estimates and orders provided for under this
Article and to ship Bulk Product in accordance with ROCHE's
firm orders, and ROCHE will use its best efforts to formulate
and fill Product promptly and efficiently so as to ensure
that a sufficient supply of Product is available to commence
and continue distribution of the Product in each country of
the Territory as soon as reasonably practicable with
reasonably adequate inventory. The Bulk Product shall be
shipped "DDP (Incoterms 1990)" to ROCHE's facility. In
addition, AMGEN shall use its best efforts to have
********************************** to it which can produce an
amount of Bulk Product which is at least ********************
over the Product Marketing Team sales estimates for the
forthcoming year.
5.06 Should, at any future time, ROCHE's requirements of Bulk
Product exceed the anticipated requirements for a calendar
year, ROCHE shall provide AMGEN, as soon as practicable,
with reasonable written notice to this effect with an
indication of the total amount of such excess requirements.
AMGEN shall use its best efforts to supply such excess
requirements and shall, within **************** from the
receipt of such notice, advise ROCHE in writing as to AMGEN's
ability to provide such supply.
5.07 (a) AMGEN shall furnish ROCHE full descriptions and
instructions concerning the methods, formulae and standards
to be employed by ROCHE to formulate and fill Finished
Product, including such written procedures, flow sheets,
specifications for raw materials, packaging materials and
finished dosage units as well as in-process control
procedures and other process and control data necessary for
the formulation and filling of the Finished Products. AMGEN
shall provide ROCHE from time to time during the Term of this
Agreement with any modifications or supplements to the
information previously furnished to ROCHE.
(b) As far as possible AMGEN is ready, at the request of
ROCHE, to temporarily delegate AMGEN manufacturing experts to
give advice to ROCHE concerning the analytical methods,
formulation and filling of the Finished Product and to
instruct its personnel.
24
5.08 In the event that the Bulk Product cannot be exported out of
the USA and into any of the countries of the Territory or
Switzerland to a facility of ROCHE's designation, AMGEN shall
be responsible, at its cost, for arranging non-U.S.
manufacture and shipping of Bulk Product to ROCHE for
commercial purposes.
(a) In the event that AMGEN is unable or unwilling to supply
an adequate quantity of Bulk Product from its own facilities
or third party facilities, ROCHE will make its manufacturing
facilities available to AMGEN for manufacture of Bulk Product
with priority equal to its other products.
(b) Subsection (a) of this Section 5.08 shall apply mutatis
mutandis if ROCHE is unable or unwilling to formulate and/or
fill or have formulated or filled Finished Product.
5.09 AMGEN will use its best efforts to arrange for shipment of
Bulk Product to ROCHE. If other sources or Product for
clinical trials are unavailable, ROCHE will make its
manufacturing facilities to AMGEN for manufacture of Product
for clinical trials.
5.10 (a) All of ROCHE's rights and obligations under this Section
5 shall terminate with regard to the countries and upon the
respective dates given in Appendix 2.01 (a) and, as from such
dates, AMGEN shall manufacture, fill, formulate, ship and
otherwise supply and invoice all Finished Product in such
countries. Notwithstanding the foregoing, ROCHE shall
continue to invoice the Finished Product in Italy (ROCHE-
Trademark (Granulokine(R)) only) until the Scheduled
Termination Date and in Greece until the time, if any, that
AMGEN assumes primary responsibility for marketing the
Product in Greece.
As from the respective dates and countries in Appendix 2.01
(a) the following provisions shall apply:
(i) ROCHE's overall bulk supply forecasts and delivery
schedules shall be adjusted to exclude Product amounts
targeted for the country;
(ii)ROCHE shall terminate formulating and filling of
Finished Product intended to be sold in the country and
ROCHE's inventory of Finished Product targeted for such
country shall be handled as agreed by the parties;
(iii)Sales revenues and/or out of pocket expenses as well
as direct and indirect internal costs for the country,
accrued until such date but not yet received or paid by
ROCHE, shall be considered to be outstanding.
25
(b) The parties have agreed that AMGEN will supply
requirements for Italy and Greece with formulated, filled and
Finished Product on the respective dates set forth in
Appendix 2.01 (a), provided that: (1) AMGEN's production and
distribution facility in The Netherlands must have been
approved as a distribution and production site to the extent
required by regulatory requirements in Italy or Greece, as
the case may be; (2) Finished Product for Greece and Finished
Product (ROCHE - Trademark) (Granulokine(R)) for Italy with
ROCHE make-up in accordance with regulatory requirements in
Italy or Greece, as the case may be, shall be delivered by
AMGEN to ROCHE (CIP) (Incoterms 1990) (ROCHE's warehouse
Basel, Switzerland) for shipping and invoicing by ROCHE to
customers in Italy or Greece, as the case may be; (3)
Finished Product (Neupogen(R)) for Italy with make-up in
accordance with regulatory requirements in Italy shall be
supplied, delivered, shipped and invoiced by AMGEN as
required by arrangements, if any, between AMGEN and any
distributor in Italy; and (4) any changes to the then current
pack, its size and dimensions, its text on the product, pack
and enclosures (i.e.: SmPC and PIL) or other like changes
must have been approved in compliance with regulatory
requirements in Italy or Greece. In addition, as from AMGEN
assuming such supply requirements in Italy (ROCHE-Trademark)
(Granulokine(R)) or Greece, the following terms shall apply:
(i) The Finished Product will be manufactured, formulated
and filled according to Current GMP Requirements and
will conform to the lot release specifications
accepted by the appropriate regulatory authorities
and contained in the Country MA/V or EU MA/V (the
"Specifications"). ROCHE shall notify AMGEN of any
changes to the Specifications required by the rules,
regulations or requirements of the appropriate
regulatory authorities.
(ii)AMGEN will provide ROCHE with a certificate of
analysis for each lot of Finished Product produced.
In order to comply with Current GMP Requirements,
ROCHE requests and AMGEN agrees to supply ROCHE with
all procedures, including SOP's, allowing ROCHE to
perform the analysis of the Finished Product upon
arrival at ROCHE's designated warehouse.
(iii)On receipt of a delivery of the Finished Product
ordered, ROCHE shall check whether it complies with
the Specifications. Any discernible noncompliance has
to be reported in writing to AMGEN immediately,
together with all test data, at the latest within six
(6) weeks after receipt of the delivery. At the same
time ROCHE sends the written notification, ROCHE
shall also send to AMGEN a sample of the Finished
Product delivered. Otherwise, it will be assumed that
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the Finished Product delivered has been approved. In
the event of a duly claimed and justified notice of
non-compliance, AMGEN shall make good the order by
delivering new material.
(iv)AMGEN will use its best efforts to supply Finished
Product promptly and efficiently so as to ensure that
a sufficient supply of Finished Product is available
for distribution as soon as reasonably practicable
with reasonably adequate inventory.
(v) In order to facilitate AMGEN's supply planning, ROCHE
shall provide AMGEN during the first month of every
calendar quarter with the estimate of ROCHE's
requirement of the Finished Product for the next
twenty-four (24) months. ROCHE shall furnish AMGEN
firm purchase orders for its planned requirements not
later than sixty (60) days prior to the requested
shipdate. AMGEN may supply but shall not be obligated
to supply in any one month more than fifty percent
(50%) of ROCHE's quarterly estimate.
(vi)Pricing for the Finished Product delivered by AMGEN
to ROCHE will be established annually by the parties,
but shall include
************************************ and ***********
for the ****************. Freight and insurance will
be paid for by AMGEN but included in AMGEN's variable
costs. ROCHE's payment for Finished Product shall be
made not later than **************** following
ROCHE's receipt of delivery.
5.11 Notwithstanding anything in this Article 5 and in lieu of the
foregoing provisions, the following shall apply to the supply
of any Second Generation Product that becomes a Product
pursuant to the terms of Section 2.03 hereof:
(a) Clinical Supply. The clinical supply of the Product
shall be manufactured and supplied at cost by AMGEN or
ROCHE as mutually agreed and shall be subject to
provisions of Section 3.07 and 3.08.
(b) Commercial Supply. If the Product is the *****
Product, the parties shall negotiate an agreement with
*********** pursuant to which *********** will enter into
a definitive agreement with either AMGEN or ROCHE to
manufacture the Bulk Product for the Territory and supply
it to AMGEN for formulation, filling, labeling and
packaging by AMGEN into Finished Product. If the Product
is not the ***** Product, AMGEN shall manufacture,
formulate, fill, label and package into Finished Product.
In either case, AMGEN shall invoice (except as specified
in Section 2.03(f)) and distribute the Finished Product.
27
(c) Standards of Supply. Bulk Product will be manufactured
and Finished Product formulated and filled strictly:
(i)in accordance with established written
manufacturing procedures and Finished Product
specifications according to Current GMP
Requirements,
(ii)which will meet the requirements set forth in
accordance with applicable laws and regulations
for shipment of the Bulk Product or Finished
Product into any countries of the Territory or
into Switzerland, and
(iii)which will meet the requirements set forth in
all governmental submissions by AMGEN with
regulatory agencies for the manufacture of the
Bulk Product into Finished Product.
ARTICLE 6
MARKETING
6.01 (a) ROCHE and AMGEN shall use best efforts consistent with
accepted pharmaceutical business practices and legal
requirements to deploy their sales forces to promote and
detail each Product in the Territory on a country-by-country
basis in such manner and with such expedition as they would
have adopted in launching, promoting, detailing, selling and
marketing a pharmaceutical product of their own innovation
and consistent with the approved country Marketing Plan.
(b) AMGEN shall use its best efforts consistent with accepted
pharmaceutical business practices and legal requirements:
(i) to build a new organization in particular countries
of the Territory which can perform AMGEN's
responsibilities hereunder;
(ii)to promote, detail, sell and market each Product in
each country in the Territory in which it has a sales
force.
6.02 (a) In developing a marketing strategy, the Product Marketing
Team will review and approve the promotion, detailing and
marketing plans of the Product in the Territory and the
strategies and programs to maximize sales of each Product in
each country of the Territory.
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Illustratively, the Product Marketing Team shall
(i) using any AMGEN core program as a guide, review and
approve the prelaunch activities and the launch plans of
each Product in each country in the Territory; and
(ii)make suggestions for continuing promotion and detailing
efforts with respect to each Product in the Territory,
taking into account AMGEN's experience inside and outside
the Territory;
(iii)ensure the exchange of promotional material and
experiences, both within and outside the Territory.
(b) In each country of the Territory, on a country-by-country
basis, ROCHE will have the final responsibility, with the
cooperation and assistance of AMGEN, over marketing matters
provided however, after *************** and upon
****************************** notice to ROCHE prior to the
beginning of a ************************, AMGEN may assume
such final responsibility and control for such
************************ and ****************** thereafter in
Greece or any new EU country.
ROCHE's rights and obligations to assume final responsibility
and control over marketing matters for each Product has or
will terminate with regard to the countries and upon the
respective dates set forth Appendix 6.02 (b) and AMGEN has or
shall therefore assume such final responsibility and control
in such countries and as of such dates, however ROCHE shall
continue to participate in the Product Marketing Team as it
has done before except that ROCHE will not have final
responsibility and control thereover.
(c) The Product Marketing Team shall meet annually in the
Territory or in Switzerland in order to review marketing
plans for specified periods for the Territory ("Marketing
Plan").
A Marketing Plan generally consists of the following
elements:
(i) Prerequisites
- Product Profile
- Patent Status
- Trade Mark
- Price and Reimbursement
- Packaging
- Manufacturing and Logistics
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(ii) Targets
- Unit Sales
- Market Share
(iii) Strategy/Objectives
- Positioning (in therapy)
- Target Audience
- Media Selection
- Marketing Investment
(iv) Implementation
- Priority in Relation to Other Products
- Time Table
- Field Staff (training, sales-time, incentives)
- Medical Marketing and Publications
- Congresses, Symposia, Round-Tables
- Sampling
- Journal Advertising
- Direct Mail
- Public Relations
(v) Budget
(d) The provisions of the Marketing Plan shall be reviewed by
the Product Marketing Team and approved by the Product
Management Committee, and if the Product Marketing Team
cannot reach a consensus agreement, then the matters in
dispute shall be referred to the Product Management
Committee.
(e) ROCHE shall have the final responsibility for the
Marketing Plan; provided, however, that after ***************
and upon ****************************** notice to ROCHE prior
to the beginning of a ************************, AMGEN may
assume such final responsibility and control over the
Marketing Plan for each Product for such
************************ and ****************** thereafter in
Greece or any new EU country.
All of ROCHE's rights and obligations to assume final
responsibility for the Marketing Plan for each Product has or
will terminate with regard to the countries and upon the
respective dates given in Appendix 6.02 (b) and AMGEN has or
shall therefore assume such final responsibility and control
in such countries and on such dates, however ROCHE shall
continue to participate in developing and formulating the
Marketing Plan in that country as it has done before except
that ROCHE will not have final responsibility and control
thereover.
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(f) Notwithstanding who has final responsibility or control,
a party shall have the right to comment upon and make
marketing recommendations to the other party regarding the
other party's activities under this Agreement, which
recommendations the other party shall thoroughly evaluate and
consider, taking into account the other party's expertise and
experience.
6.03 In each country in the Territory and subject to any other
provision of this Agreement, each party will provide the
other with all information helpful for the detailing and
promotion of each Product within a reasonable time after such
information becomes known to the party, provided such
information is not received under a secrecy obligation to a
third party or is otherwise restricted.
6.04 ************************* in which
*********************************************************,
ROCHE and AMGEN shall create and develop through the Product
Marketing Team and under the guidance and supervision of the
Product Management Committee, respectively, core sales and
promotional materials relating to each Product for
distribution to independent third parties of the medical and
health community in the Territory. In so doing, any AMGEN
core program shall be considered.
AMGEN and ROCHE may each develop promotional or sales
training materials intended to be used outside the Territory
and, if such materials are used (or adapted for use) in the
Territory with the prior approval of the Product Marketing
Team, charge an appropriate portion of the related costs to
the Operating Profit and Operating Loss account hereunder. To
the extent that materials developed for the Territory are
modified and used outside the Territory, the party using such
materials outside the Territory shall pay or reimburse to the
AMGEN/ROCHE Operating Profit or Loss ten percent (10%) of the
costs incurred in developing such materials for the
Territory.
ROCHE's Affiliates are requested to use such core materials
as much as possible but are free to adapt them as they see
fit. With just cause, ROCHE's Affiliates can develop their
own materials which will be submitted for review to the
Product Marketing Team.
ROCHE shall provide AMGEN through the Product Marketing Team
and the Product Management Committee, respectively, with such
materials, in amounts which are reasonable under the terms of
the Marketing Plan for the promotion and detailing by AMGEN
in cooperation with ROCHE in a given country to members of
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the medical and health community. It is understood that AMGEN
shall supply, **************, to ROCHE samples of sales and
promotional material which AMGEN intends to use outside the
Territory so that ROCHE, with the assistance and cooperation
of AMGEN through the Product Marketing Team and the Product
Management Committee, respectively, may at its discretion
modify or have modified the material and distribute it to
members of the medical and health community in the Territory;
the same applies to samples of promotional material being
created by ROCHE outside the Territory.
This Subsection 6.04 shall apply mutatis mutandis should
AMGEN assume final responsibility in a country.
6.05 Neither party shall have any responsibility for the hiring,
firing or compensation of the other party's employees or for
any employee benefits. No employee or representative of a
party shall have any authority to bind or obligate the other
party to this Agreement for any sum or in any manner
whatsoever, or to create or impose any contractual or other
liability on the other party without said party's authorized
written approval.
6.06 All of the transition dates referenced in Appendices 2.01 (a)
and (b) shall apply as from such dates regardless of any
delay or inability to transfer any government authorizations
or approvals on or prior to any such dates; provided,
however, that in the event that any required MA/V's cannot be
transferred as of any such dates through no fault of ROCHE,
then AMGEN shall defend ROCHE, its agents, directors,
officers and employees ("Representatives") at its cost and
expense, and will indemnify and hold harmless ROCHE and its
Representatives from and against any and all claims for
losses, costs, damages, fees or expenses incurred by ROCHE as
the MA/V holder to the extent they arise out of or in
connection with any action or failure to act by AMGEN. Any
such claim shall be controlled by the provisions of Section
9.02 (c) hereof.
As from the Effective Date, ROCHE's sales force shall
continue active participation at a reduced level. The parties
shall, as part of the annual budget process, determine the
specific participation and role of the ROCHE sales force on
a country-by-country basis. If the parties are unable to
reach a consensus determination, the President of AMGEN shall
be entitled to make the final determination. The parties have
agreed to the level of ROCHE's sales force participation for
1997 and 1998, with a copy of the 1998 participation set
forth in Appendix 6.06. Beginning in 1998 and thereafter, the
level of ROCHE's sales force participation in the Territory
32
as a whole (aggregating the ROCHE sales forces for all
Products in all countries in the Territory) shall roughly
approximate ROCHE's then current profit participation in
Article 7; provided however, that the ROCHE sales force
participation for all Products shall not exceed the level
already established for 1997 on a country-by-country basis.
Notwithstanding the foregoing, following a proposal by ROCHE
to AMGEN of reasonable proposed plans acceptable to AMGEN
(with acceptance by AMGEN not to be withheld arbitrarily) to
include a sales force non-billable to the Operating Profit or
Loss for any Product in any country of the Territory, ROCHE
shall be entitled to have a sales force for any such Product
in any country in the Territory if and for so long as: (1)
it bears all of the costs (direct and indirect) associated
therewith (i.e. - such costs are not included in the
Operating Profit or Loss), (2) the activities of such sales
force are consistent with the approved applicable country
Marketing Plans and (3) any and all sales of each such
Product by such sales force are included in the Operating
Profit or Loss.
Notwithstanding anything in this Agreement, with regard to
the participation rights conferred upon ROCHE in Articles 2
through 6 of this Agreement neither AMGEN nor the Operating
Profit or Loss shall bear any direct or indirect costs (i.e.
- such costs are not included in the Operating Profit or
Loss) relating to or in connection with any of such rights,
except those costs reasonably necessary to support the agreed
ROCHE sales force charged to the Operating Profit or Loss.
6.07 The following provisions of Sections 6.07 (a) and (b) shall
apply on a country-by-country basis only with respect to and
during the period in which ROCHE maintains a sales force in
that country billable to the Operating Profit or Loss (or
non-billable if AMGEN agrees that such provisions shall not
apply) and in all other countries each Product shall be
presented solely as an AMGEN product:
(a) With respect to each Product, AMGEN and ROCHE will be
presented and described, by each party hereto, to the medical
and paramedical communities, investors, the press and the
trade as joining in the development, detailing and promotion
of each Product in the Territory, and all written information
(including, but not limited to, educational materials,
journal advertisements, direct mail, sales pieces and other
promotional material) and, to the extent practicable, all
oral information, disseminated or presented, respectively, to
such communities and trade regarding the detailing and
promoting of each Product in the Territory will state this
33
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
collaboration. Neither party shall distribute or have
distributed any such information which bears the name of the
other without the prior written approval of the other, which
approval shall not be unreasonably withheld. Major public
announcements, especially those of regulatory filing and
approvals, will include the names of both AMGEN and ROCHE and
will recognize the innovative role of AMGEN, the important
contributions of ROCHE and the joint AMGEN/ROCHE efforts to
complete registration and launch. Each Product shall be
represented solely as an AMGEN/ROCHE product.
(b) When packaged, and to the extent permitted under the law
of each country of the Territory, each Product will bear the
Trademark and the label of AMGEN/ROCHE.
(c) Each party at its option may issue press releases or
other public announcements relating to each Product or the
Agreement contemplated by this Agreement, provided, however,
that without the prior approval of the other party, neither
party shall issue a press release or public announcement
which has, as a major focus, either the joint development,
detailing and promotion of any Product in the Territory or
such agreement, which approval shall not be unreasonably
withheld. Moreover, neither party may issue a press release
or other public announcement which mentions the other party
by name, without the prior written approval of the other
party, which approval shall not be unreasonably withheld.
Notwithstanding the foregoing, either party may issue such
press releases or make such public disclosures as may be
required by law or regulation.
ARTICLE 7
COMPENSATION
7.01 (a) In each calendar year during the Term of this Agreement,
AMGEN and ROCHE shall share on the
*************************************************************
****************, the **************** or ************** for
each Product for such calendar year for each country in the
Territory.
**** ***** *****
**** ** **
**** ** **
**** ** **
****** ** **
*********
****************
34
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
(b) "****************" or "**************" for each Product
in a country is determined and further defined in the
Supplementary Agreement and shall be calculated and converted
into Swiss francs prior to the Effective Date and shall be
calculated and converted into U.S. Dollars thereafter.
(c) In determining **************** or
************************************* be considered an
*************************************** with respect to G-CSF
shall mean *************************************** on account
of ********* in a country in the Territory in a calendar
year, which ******* is payable by ***** for the calendar year
to *************** in respect of the making, use or sale of
G-CSF in or for any country in the Territory.
*********************** with respect to a Second Generation
Product that becomes a Product pursuant to Section 2.03 shall
mean *************************************** on account of
*********************** in the case the Product is the *****
Product) in a country in the Territory in a calendar year,
which ******* is payable by ***** or ***** (including the
********* payable to *********** set forth in Section 2.03
(e) necessary to ******************** under the ***********
License) to any *********** in respect of the making, use or
sale of the Product for any country in the Territory.
The ********************* paid prior to the Effective Date
(specified as a percentage of *********) included the
following:
Party *******
***************** ****
*********************** **
******************* ***
The ********************* payable on and after the Effective
Date shall include, but not be limited to, the following
********* (specified as a percentage of *********):
Party *******
***************** ***********************
***************************************************
************
******* **********************
******** ****
*********************** **
35
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
Notwithstanding the foregoing, no other ********* payable to
******************* shall be considered *********************
included in *************** (i.e. ***************** not to
exceed ***), unless otherwise negotiated between the parties
pursuant to Sections 2.03 (c) or 2.03 (d).
Each party will provide documentation satisfactory to the
other to confirm to such other party's reasonable
satisfaction that the ******* payments to such *************
for a calendar year are required pursuant to agreements in
respect of the making, use or sale of each Product in or for
any country in the Territory in the given calendar year.
*************************************************************
*************************************************************
***************************************************.
(d) As from the Effective Date, in determining
************************, included in *************** shall
be ***************************** incurred by ***** in the
Territory (and outside the Territory to the extent benefiting
potential sales reasonably expected by both parties of the
Product in the Territory) for all indications of each
Product. Included in such ***** shall be the following *****
incurred after the Effective Date, some of which were
previously considered ************:
*************************************************************
************************** shall consult with ***** prior to
incurring any ********************************** in
connection with formulation and fill and supply activities.
ARTICLE 8
REPORTS AND PAYMENTS
8.01 During the Term of this Agreement, each party shall provide
to the other party the necessary information so that
************************ may be calculated. Each local ROCHE
Affiliate or AMGEN Affiliate, respectively, will send to
ROCHE and AMGEN, respectively, the
*******************************. ROCHE and AMGEN,
respectively, will each calculate the
***************************. The respective
**************************** by Affiliate and total
************* will be exchanged within one hundred and twenty
(120) days after the end of each calendar year between AMGEN
and ROCHE. AMGEN/ROCHE ************************* will be
*************************************************************
************************** and approved by the party not
responsible for ************* within **************** upon
receipt thereof.
36
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
Resulting estimated *************************************
calculated in accordance with Section 7.01 will be settled
and paid according to the following schedule:
(a) ********* settlements will be made based on
******************************************* based on the pro
rata budget for said quarter, as determined by party
responsible for reporting. A respective country will be
settled on a ********* basis if the country's
********************** do not exceed significantly the
****************************** of all countries in the
Territory. Cash transfer in connection with the *********
settlements will take place **************** after the end of
each *******.
(b) ********************************** will be made based on
the ************************ as outlined in the Supplementary
Agreement and will consider the prevailing *********
settlements. Cash transfer in connection with the
********************************** will take place within
******** after ******* and *********** of the respective
calendar year.
8.02 As from the Effective Date, all sums due to a party under
this Agreement will be payable by the other party in U.S.
Dollars to the following address:
For AMGEN:
AMGEN INC.
1840 DeHavilland Drive
Thousand Oaks, California 91320 U.S.A.
For ROCHE:
F. HOFFMANN-LA ROCHE LTD
Grenzacherstrasse 124
CH-4070 Basel, Switzerland
or any other place or bank account as AMGEN or ROCHE may
designate in writing. Since sales may be made in another
currency, conversion of sales and Operating Costs and
Expenses to Swiss francs prior to the Effective Date and U.S.
Dollars thereafter shall be at rates determined in
accordance with the Supplementary Agreement calculated by
ROCHE through the 1997 calendar year and AMGEN thereafter,
provided that such rates and methodology shall be subject to
both parties reasonable approval.
37
8.03 Further, if a law or governmental regulation should require
withholding of taxes, said taxes will be deducted from such
remitted amount and will be paid to the proper taxing
authority, and proof of payment will be secured and sent to
the party receiving the amount as evidence of such payment in
such form as required by the tax authorities have in
jurisdiction thereover.
8.04 Auditing of ROCHE's books and records will be accomplished by
ROCHE's internal auditors and will be documented by means of
certification from the internal audit staff. In addition, the
workpapers of the AMGEN/ROCHE consolidation will be available
to AMGEN's auditors.
Auditing of AMGEN's books and records will be accomplished by
AMGEN's internal auditors and will be documented by means of
certification from the internal audit staff. In addition, the
workpapers of the AMGEN/ROCHE consolidation will be available
to ROCHE's auditors.
ARTICLE 9
WARRANTIES AND INDEMNIFICATION
9.01 Each party warrants and represents to the other that it has
the full right and authority to enter into this Agreement,
and that it is not aware of any impediment that would inhibit
its ability to perform its obligations under this Agreement.
9.02 (a) During the Term of this Agreement, each party will
provide through self insurance or a combination of self
insurance and commercially placed insurance coverage in
respect of product liability. The terms of any insurance
coverage shall include insurance against the obligations
assumed by the parties hereunder. Evidence of the existence
and continuation of such insurance shall be provided, upon
written request, to the other party annually and at such
other times as the other party may reasonably request. A
party shall notify the other of any cancellation of or
material change in any such insurance arrangements prior, if
possible, to such cancellation or material change, but in any
event, as soon as possible.
(b) ROCHE shall defend AMGEN, its agents, directors, officers
and employees at its cost and expense, and will indemnify and
hold harmless AMGEN, its agents, directors, officers and
employees from and against any and all claims for losses,
costs, damages, fees or expenses to the extent they arise out
of or in connection with ROCHE's manufacture or distribution
of each Product and/or delivery of the Product to AMGEN,
provided that the foregoing indemnity shall not apply to the
extent that any actual or alleged losses, costs, damages,
fees or expenses are specifically and proximately due to
AMGEN's failure to properly manufacture and/or delivery the
38
Bulk Product. In the event of any such claim against AMGEN or
any agent, director, officer or employee, AMGEN shall
promptly notify ROCHE in writing of the claim and ROCHE shall
manage and control, at its sole expense, the defense of the
claim and its settlement. AMGEN shall cooperate with ROCHE
and may, at its option an expense, be represented in any such
action or proceeding. ROCHE shall not be liable for any
litigation costs or expenses incurred be AMGEN without
ROCHE's written authorization.
(c) AMGEN shall defend ROCHE, its agents, directors, officers
and employees at its cost and expense, and will indemnify and
hold harmless ROCHE, its agents, directors, officers and
employees from and against any and all claims for losses,
costs, damages, fees or expenses to the extent they arise out
of or in connection with AMGEN's manufacture or distribution
of each Product and/or delivery of the Product to ROCHE. In
the event of any such claim against ROCHE or any agent,
director, officer or employee, ROCHE shall promptly notify
AMGEN in writing of the claim and AMGEN shall manage and
control, at its sole expense, the defense of the claim and
its settlement. ROCHE shall cooperate with AMGEN and may, at
its option and expense, be represented in any such action or
proceeding. AMGEN shall not be liable for any litigation
costs or expenses incurred be ROCHE without AMGEN's written
authorization.
ARTICLE 10
PATENT AND TRADEMARK INFRINGEMENT
10.01 (a) In the event that AMGEN or ROCHE become aware of any
infringement by a third party of any Trademark or Patents,
each party shall inform the other in writing of all available
evidence and details available concerning said infringement.
AMGEN and ROCHE shall then consult with each other as to the
best manner in which to proceed. AMGEN shall have the sole
right but not the obligation to bring, defend, maintain any
appropriate suit or action or to control the conduct thereof
against the infringer. If ROCHE agrees to equally share all
expenses, ROCHE shall also share the recoveries due to any
such action. If ROCHE does not agree to share all expenses,
AMGEN will receive all recoveries due to any such action. If
AMGEN requests ROCHE to join AMGEN in such suit or action,
ROCHE shall execute all papers and perform such other acts as
may be reasonably required. Should AMGEN lack standing to
bring any such action, then AMGEN may ask ROCHE to do so. If
ROCHE elects to bring suit, AMGEN shall cooperate with ROCHE
in conducting the suit and the parties shall share expenses
and recoveries equally.
39
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
(b) If AMGEN fails to bring legal action or terminate an
infringing activity within nine (9) months of notification of
infringing activity, ROCHE shall have the right but not the
obligation to bring suit against the infringer in the country
of the Territory. If ROCHE elects to bring suit, AMGEN shall
cooperate with ROCHE in conducting the suit and the parties
shall share expenses and recoveries equally.
10.02 In the event that AMGEN and/or ROCHE are sued or
threatened with suit by a third party who claims that the
manufacture, use or sale of any Product is an infringement of
one or more claims of a patent owned by the third party, the
parties shall consult with each other as to the best manner
to proceed. ROCHE and AMGEN agree to equally share the costs
of such suit or threatened suit. If the settlement of a
lawsuit or threatened lawsuit or other action requires any
payments or license in order to manufacture, use or sell any
Product, AMGEN and ROCHE agree to equally share any such
payments and/or license fees including royalties.
ARTICLE 11
TERM AND TERMINATION
11.01 Either party may terminate this Agreement for "Good
Cause" (as defined in Section 11.03 below), on a country-by-
country basis, effective at any time after providing
**************** written notice; provided that the other
party shall have an opportunity to cure any defect or
omission during such ************** period. Should such cure
be effected, such notice with respect to such Good Cause
shall be null and void.
Should the Agreement be terminated in a country by ***** for
Good Cause,
(i) ***** shall receive its share of **************** or pay
its share of ************** for that country under
Section **** for the calendar year in which termination
occurs,
(ii)For subsequent years, ***** shall receive or pay the
************************************************* it
would have received for that country in accordance with
Section ******* if ****************************.
Should the Agreement be terminated in a country by ***** for
Good Cause,
40
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
(i) ***** shall receive the amount in U.S. Dollars in that
country up to and including the
********************************************,
(ii)*** shall receive
**************************************************** for
that country.
11.02(a) "Good Cause" shall include
(i) the failure of the other party to comply with any of its
material obligations contained in this Agreement in a
country of the Territory;
(ii)any action or proceeding before any court or governmental
agency or other regulatory or administrative agency or
commission, by any governmental or other regulatory or
administrative agency or commission or by any other
person, successfully challenging this Agreement or the
relationship or actions of the parties contemplated
hereby or otherwise materially and adversely affecting
the business or property (including the goodwill and
business reputation and character) of a party hereto;
(iii)termination (a) by ROCHE or Hoffmann-La Roche Inc. for
any reason, or (b) by AMGEN due to the failure of ROCHE
or any Affiliate of ROCHE (including but not limited to
Hoffmann-La Roche Inc.) to comply with any of its or
their material obligations contained therein, of either
of the License Agreements of even date herewith with
respect to the **************************; or
(iv)(a) ROCHE's failure to obtain ************* consent to
the sublicense referred to in Section 2.03 (b) ; or
(b) ROCHE's subsequent termination of such sublicense; or
(c) termination of the *********** License by ROCHE; or
(d) termination of the *********** License by
*********** due to the failure of ROCHE or any Affiliate
of ROCHE to comply with any of its or their material
obligations thereunder through no fault of AMGEN;
provided, however, that in such event termination of this
Agreement shall not effective until fault is established
or mutually agreed, but if it is established or agreed
that AMGEN is not at fault then termination shall be
effective retroactive to the date AMGEN provided ROCHE
with notice of termination and ROCHE shall receive only
its share of Operating Profit or Loss up to and including
the calendar month of the date of notice of termination.
41
11.03 Any other provision of this Agreement notwithstanding,
termination of this Agreement for Good Cause shall be without
prejudice to
(i) any remedies which either party may then or thereafter
have hereunder or at law; and
(ii)either party's right to obtain performance of any
obligations provided for in this Agreement which survive
termination by their terms or by a fair interpretation of
this Agreement.
ARTICLE 12
MISCELLANEOUS
12.01(a) This Agreement shall be governed by and interpreted under
the laws of England and the regulations of the EU.
(b) In the event of any controversy or claim arising out of
or relating to any provision of this Agreement or the breach
thereof, the parties shall try to settle those conflicts
amicably between themselves.
(c) Should they fail to agree, any controversy, dispute or
claim which may arise out of or in connection with this
Agreement, or the breach, termination or validity thereof,
shall be settled by final and binding arbitration pursuant to
the Rules of Conciliation and Arbitration of the
International Chamber of Commerce (Paris) as hereinafter
provided:
(i) The Arbitration Tribunal shall consist of three
arbitrators. Each party shall nominate in the request for
arbitration and the answer thereto one arbitrator and the
two arbitrators so named will then jointly appoint the
third arbitrator as chairman of the Arbitration Tribunal.
If one party fails to nominate its arbitrator or, if the
parties' arbitrators cannot agree on the person to be
named as chairman within sixty (60) days, the Court of
Arbitration of the International Chamber of Commerce
shall make the necessary appointments for arbitrator or
chairman.
(ii)The place of arbitration shall be in London, England, and
the arbitration procedure shall be held in English. The
procedural law of the place of arbitration shall apply
where the said Rules are silent.
(iii)The award of the Arbitration Tribunal shall be final
and judgment upon such an award may be entered in any
competent court or application may be made to any
competent court for judicial acceptance of such an award
and order of enforcement.
42
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
12.02 For a period commencing September 26, 1988 and ending
************** from the termination or expiration of this
Agreement:
(a) each party agrees not to use Confidential Information
furnished by the other party for any purpose inconsistent
with this Agreement; and
(b) each party will treat Confidential Information furnished
by the other party as if it were its own proprietary
information and will not disclose it to any third party other
than its Affiliates or consultants without the prior written
consent of the other party who furnished such information;
provided, however, that such Confidential Information may be
disclosed if in the reasonable opinion of recipient's counsel
such disclosure is necessary to comply with the requirements
of any law, governmental order (including a court order) or
regulation. Recipient shall notify and consult with the
disclosing party prior to such disclosure of information.
Prior to the oral or written presentation or submission for
publication of any data or information with respect to a
Product or Second Generation Product being evaluated,
developed or commercialized for the Territory, each party
will provide a copy of the proposed presentation or
publication to the other party for review. If the data or
information relates to the ***** Product or is covered by the
*********** Patents then it shall also be submitted to
*********** for review. The proposed manuscript, presentation
outline or other information shall be submitted to the
reviewing party as soon as practicable but in no event less
then fifteen (15) days prior to the proposed presentation or
publication. The parties will cooperate and, if necessary,
delay the publication or presentation to permit patent filing
and any other protections to be instituted to protect any
such proposed disclosure before the disclosure occurs. Upon
request, the presenting or publishing party will remove any
Confidential Information belonging to the other party from
any presentation or publication.
12.03 A party shall be relieved of any and all of the
obligations of Section 12.02 with respect to a specific item
of Confidential Information if:
(a) such Confidential Information was known to the party
receiving the Confidential Information prior to receipt from
the disclosing party; or
(b) such Confidential Information was at the time of
disclosure to the party receiving the Confidential
Information generally available to the public or which became
43
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
generally available to the public through no fault
attributable to the party receiving the Confidential
Information; or
(c) such Confidential Information was made available to the
party receiving the Confidential Information for its use or
disclosure from any third person who was at the time of
transmitting such Confidential Information not under a non-
disclosure obligation to the other party.
12.04 During the Term of this Agreement and for *********
thereafter, for a period of ****************** immediately
after voluntary or involuntary termination of an employee who
was involved in promoting or detailing each Product for a
party to this Agreement, the other party to the Agreement
shall not engage such former employee in any work or other
activity (whether as consultant, employee or otherwise),
involving promoting, detailing or marketing each Product for
such other party, without the prior written approval of the
party who was the employer of the former employee.
12.05 This Agreement shall be binding upon, and shall inure to
the benefit of successors to a party hereto, provided
however, that neither this Agreement nor any of the rights or
obligations hereunder shall be assignable without the prior
written consent of both parties.
12.06 Any notice required to be given hereunder shall be
considered properly given if sent by certified mail, return
receipt requested, to the respective address of each party as
follows:
F. Hoffmann-La ROCHE Ltd
Grenzacherstrasse 124
CH-4070 Basel, Switzerland
Attention: Corporate Law Department
and
AMGEN Inc.
1840 DeHavilland Drive
Thousand Oaks, California 91320 U.S.A.
Attention: Corporate Secretary
with a copy to:
AMGEN (Europe) AG
Alpenquai 30
6002 Luzern, Switzerland
Attention: Vice President, Europe
44
or such other address as the addressee shall have last
furnished in writing in accordance with this provision to the
addresser.
12.07 If any provision of this Agreement is held to be invalid,
such invalidity shall not affect the validity of the
remaining provisions.
12.08 In the event that either party is prevented from
performing or is unable to perform any of its obligations
under this Agreement due to any act of God, fire, casualty,
flood, war, strike, lockout, failure of public utilities,
injunction or any act, exercise, assertion or requirement of
governmental authority, including any governmental law,
order, regulation permanently or temporarily prohibiting or
reducing the level of research, development or production
work hereunder or the manufacture, use or sale of Product,
epidemic, destruction of production facilities, riots,
insurrection, inability to procure or use materials, labor,
equipment, transportation or energy sufficient to meet
experimentation or manufacturing needs; or any other cause
beyond the reasonable control of the party invoking this
Section 12.08 provided such party shall have used its best
efforts to avoid such occurrence; such party shall give
notice to the other party in writing promptly, and thereupon
the affected party's performance shall be excused and the
time for performance shall be extended for the period of
delay or inability to perform due to such occurrence.
12.09 The waiver by either party of a breach or a default of
any provision of this Agreement by the other party shall not
be construed as a waiver of any succeeding breach of the same
or any other provision, nor shall any delay or omission on
the part of either party to exercise or avail itself of any
right, power or privilege that it has or may have hereunder
operate as a waiver of any right, power or privilege by such
party.
12.10 In the event that any provision of this Agreement is held
by a court of competent jurisdiction to be unenforceable
because it is invalid or in conflict with any law of any
relevant jurisdiction, the validity of the remaining
provisions shall not be affected, and the rights and
obligations of the parties shall be construed and enforced as
if the Agreement did not contain the particular provisions
held to be unenforceable.
12.11 All captions hereunder are for convenience only and shall
not be interpreted as having any substantive meaning.
12.12 All covenants, agreements, representations and warranties
made hereunder shall be deemed to have been relied upon
notwithstanding any investigation heretofore or hereafter
made and shall survive the execution of this Agreement.
45
12.13 This Agreement (including all Appendices attached hereto
which shall be considered part of this Agreement) constitutes
the complete and final agreement between the parties hereto
with respect to the within subject matter for the Territory
and cancels and supersedes all prior negotiations,
correspondence, understanding and agreements, whether written
or oral, respecting the subject matter thereof. This
Agreement may be changed only in writing signed by properly
authorized representatives of AMGEN and ROCHE. Any
inconsistency between this Agreement and the Supplementary
Agreement shall be construed in favor of this Agreement.
12.14 This Agreement may be executed in any number of
counterparts, each of which need not contain the signature of
more than one party but all such counterparts taken together
shall constitute one and the same agreement.
12.15 This Agreement is not intended to create a partnership
and except as expressly set forth herein neither party shall
have the power or authority to bind or obligate the other
party.
IN WITNESS WHEREOF, AMGEN INC. AND F. HOFFMANN-LA ROCHE LTD, have
caused this Agreement to be duly executed by their authorized
representatives, in duplicate on the dates written herein below.
Thousand Oaks, California, AMGEN INC.
January 26 , 1998 By: /s/Kevin Sharer
Its: President
Basel, Switzerland, F. HOFFMANN-LA ROCHE LTD
January 26 , 1998 By: /s/Erich Platzer
Its: Business Manager, Oncology
46
Appendix 1.14
SUPPLEMENTARY AGREEMENT TO
AGREEMENT ON G-CSF IN THE EC
BETWEEN
AMGEN INC.
AND
F. HOFFMAN-LA ROCHE & CO. LIMITED COMPANY
This document is the Supplementary Agreement regarding the
definition of Operating Profit or Operating Loss referred to in
Articles 1.18, 1.19 and 7.01(a) of the Agreement on G-CSF in the
EC (European Community) between F. Hoffmann-LaRoche & Co. Limited
Company (Roche) and Amgen Inc. (Amgen), dated September 26, 1988.
In addition, this supplementary agreement covers the financial
planning, accounting policies and procedures to be followed in
determining the Operating Profit and or Loss and related sharing
of profit and expenses. For purposes of this agreement the
consolidated accounting of operations will be referred to as AMRO.
1. Principles of Reporting
The presentation of results of operations will follow the
Roche format of presentation used for distribution to
management, which is as follows:
Sales
Sales Deductions
Cost of Goods Sold
Fixed Production Costs
Commercial Services
Research and Development
Other Operating Inc./Exp.
Technical Services
Administration
Operating Profit (Loss)
Amgen will make the appropriate adjustments to its financial
statements to conform to the Roche format of reporting
results of operations.
2. Frequency of Reporting
Reporting of AMRO will be done twice a year, at the end of 6
months and the end of 12 months. The fiscal year of the
venture will be a calendar year.
47
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
On an interim basis Roche will supply Amgen with certain
information:
Sales in units, local currency and Swiss francs will be
reported monthly by country.
Key events such as -
Start of clinical trials;
Seminars/Congresses attended or held;
Filings of regulatory documents;
Approvals by regulatory agencies;
will be reported as they occur.
Amgen's European Chief Financial Officer or designee
will meet regularly with Roche's designated financial
controller to review:
Performance Information
Actual Results
Latest Estimates
Consolidated results of operations will be prepared in
accordance with the calendar of financial reporting used by
Roche.
3. Budgeting
The financial responsibility for the budget will rest with
the G-CSF Clinical team and G-CSF Marketing team with final
approval by the G-CSF Management Committee. The timing of
planning will conform to Roche's planning cycle. In broad
terms a preliminary budget will be due at *******
headquarters in ***** on **********. Consolidation will be
completed in November and budget approved in December.
Budgets will be prepared on an annual basis. Sales will be
the only element of the financial plan which will be planned
on a monthly basis.
Budgets will be supplemented with detailed business plans for
clinical trials, registrations applications, and detailed
plans for product introduction.
Budget variances and performance analysis will be done in the
local currency of the country in question. Budgets, as
stated in local currency, cannot be exceeded without formal
approval by the G-CSF Management Committee.
The Management Committee may adjust the budget during the
course of the year.
48
4. Definitions
Sales -
Amounts invoiced to third parties
Less: Returns and credits
Rebates
Volume discounts
Sales taxes/other taxes related to sales
Sales deductions -
Consists of direct and variable expenses incurred
in the distribution of goods and services sold.
Which includes:
Outward freight (all outward expenses for
freight in connection with the distribution of
goods sold)
Transportation insurance
Packing materials (for dispatch of goods sold
such as boxes, drums, etc.)
Other direct distribution expenses
Cost of Goods Sold -
Cost of goods sold consists of the direct
production costs which include the following:
Raw materials
Packaging materials
Auxiliary materials
Outside contractors
Personnel costs (Salary and Wages)
Energy (Variable cost)
Workshop (Repairs and maintenance)
(Variable cost primarily preventative
maintenance)
Quality control (Variable cost-related to
product testing)
Waste disposal (Variable cost)
Fixed Production Costs -
Fixed production costs will include those
manufacturing costs which are period costs and do
not vary based on production volume. These costs
include the following:
Production management and planning
Equipment depreciation & rental
Building depreciation & rental
Energy (Boiler rooms, general consumption of
utilities, fixed costs)
49
Workshop (repairs and maintenance) (major
replacement not dependent on volume, fixed
costs)
Quality control (fixed costs - process
testing)
Waste disposal (fixed costs)
Commercial Services -
Commercial Services consists of two major areas:
Marketing
Commercial Services Infrastructure
(In Amgen books and records this area is
referred to as Marketing)
Marketing consists of all activities which are
focused on the introduction, promotion and selling
of pharmaceutical products. Within the scope of
this area will be:
Field staff -
Field staff comprises all the costs of the
entire field staff including its management
and support (training, record files, etc.)
Internal Marketing Services -
Internal marketing services comprises the
entire marketing organization with the
exception of the field staff and
infrastructure.
Activities included in this area are as
follows:
Market Research
Pricing
Regional Coordination and Documentation
Product Management
Technical Promotion
Medical Information Services
Marketing Clinicals Studies
C-CSF product specific costs will be chargeable to the
operations of the Product.
The types of costs or expenses to be included in this area
shall be:
50
Sales and promotional materials
Seminars, exhibits, and conventions
Advertising in journals, mailings and other media
Post-marketing surveillance
Costs related to institutional promotion, or promotion of the
company which is not product specific, will not be chargeable
to the operations of the Product.
Commercial Services Infrastructure -
Costs in this area include:
Commercial Service Manager (G-CSF Team Manager) and
Secretary
Registration
Strategic and Operational Planning
Marketing Administration
Health Economics
Other staff reporting to the Commercial Services
Manager
Attached to this agreement are the current charts of accounts for
Roche and Amgen concerning Commercial Services (Exhibit I), and
Marketing (Exhibit V), respectively.
Account definitions, where available, are included in Exhibit III.
Research and Development -
Those expenses, direct and indirect, required to obtain the
authorization and/or ability to manufacture, formulate, fill,
ship and/or sell the Product in commercial quantities to
third Parties in the Territory.
Such expense shall include but not limited to:
Costs of research, proposals or studies on the
toxicological, pharmaceutical, formulation or clinical
aspects of the Product conducted internally or by
individual investigators, hospitals or medical centers,
or clinical research organizations, or consultants
necessary for the purpose of obtaining and/or
maintaining approval of the Product by a government
organization in a country in the Territory. In
addition, costs for preparing, submitting, reviewing or
developing data or information for the purpose of
submission to a governmental authority to obtain and/or
maintain approval of the Product in a country.
These costs shall include expenses for data management,
statistical designs and studies, document preparation,
and other similar expenses associated with the clinical
testing program.
51
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
It is understood that obtaining FDA authorization to ship
product from the USA into the territory or Switzerland shall
be at ******* sole expense.
Attached to this agreement as Exhibit II and Exhibit IV are
the current charts of accounts for Roche and Amgen,
respectively. In addition, account definitions, where
available, are included in Exhibit III.
Other Income/Expense -
Other Income/Expense will include the following items:
Bad debt expenses
Inventory write-offs
Cash discounts
Royalty expense
Technical Services -
Technical services includes the following functions:
Technical Services Admin.
Engineering
Technical Safety & Environment Protection
Materials Management
Costs relating to the Product in this area will be
limited to allocations to support manufacturing.
Administration -
Administration shall consist of the following:
Personnel
Data Processing
General Services - (This cost area covers the
internal postal system, the telephone
exchange, the microfilm office, the in-house
printing shop and central reprography service,
etc.)
Costs relating to the Product in this area will be
limited to expenses that are directly related to the
functional areas of Manufacturing, Commercial Services
and Research and Development.
5. Manufacturing Costs and Cost of Goods Sold -
The elements and characterization of manufacturing costs will
conform to Roche's accounting policies and practices. To the
extent that Amgen has cost elements included in manufacturing
52
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
costs that do not conform to Roche's accounting practices
such costs will be accounted for as per the category of costs
normally used by Roche.
In order to achieve a proper and acceptable accounting for
manufacturing costs for the Product, standard costs per unit
for direct manufacturing costs and fixed production costs
will be established. Such standards will be established
annually; variances from standard will not be charged or
credited to Cost and Goods Sold.
In addition, annually, a standard cost for samples and
clinical requirements will be developed.
6. Bulk Transfer of Product
Pricing for bulk G-CSF shipped by Amgen to Roche will be at a
cost based on a standard set ********. The bulk transfer
price will be the
*****************************************************.
Payments for bulk shipments will be made on a
*************************************************************
************************************************.
Freight and insurance will be paid for by Amgen and included
in the standard cost of the bulk Product.
Samples required by local Amgen companies will be provided by
local Roche companies and will be billed at cost.
Roche will maintain one inventory to service all bulk
inventory requirements on a worldwide basis.
7. Foreign Exchange -
The functional currency for accounting for operating profit
will be Swiss francs.
Amgen will bill shipments of bulk Product in Swiss
francs.
Roche will maintain the bulk inventory of Product in
Swiss francs.
Roche affiliates will account for inventory in local
currency.
Each statement of operations will be translated into Swiss
francs on an average rate for the reporting period, except
for sales which is translated on a monthly weighted average.
53
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
8. Auditing of Accounts -
Auditing of Roche's books and records will be accomplished by
Roche's internal auditors and will be documented by means of
certification from the internal audit staff. In addition,
the workpapers of the AMRO consolidation will be available to
Amgen's auditors.
Amgen will request that its public accounting firm, Arthur
Young and Co., review its financial records and accountings
of AMRO activities and provide a "comfort letter" to Roche
concerning the accuracy, consistency, and adherence to the
accounting agreement.
9. Interim Compensation Payments of Partners -
Compensation payments for operating income and expense will
be made ********* between the partners based on budget. Such
payments will be made ******* after each fiscal quarter. At
the end of each ********* period a settlement will be made to
adjust budgeted income and expense to actual. Such a
settlement will take into consideration quarterly operating
income and expense compensation, and payments made for
transfer of bulk Product. Settlement payments will be made
as soon as the actual operating expense and income are
consolidated and approved by the partners, but in no event
later than ******** after ******* and ***********.
10. Responsibility for Reporting -
The responsibility for accounting shall be placed with the
company responsible for distribution and invoicing of
customers.
11. Amgen Accounting for Internal R&D and Marketing -
To the extent that Amgen establishes departments that are
wholly dedicated to G-CSF in Europe, such operating costs
will be charged to the operating results of the Product based
on actual, limited by the prevailing budget.
If resources are provided by departments which are not wholly
dedicated to G-CSF Europe, then an hourly rate for that
department will be developed, and applied to time reported by
staff working in that department, to account for internal
operating costs of that department for the purposes of this
agreement. The hourly rate will be based on the current
Amgen budget, adjusted for inflation.
54
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
12. Allocation of Technical Services and Administration -
Roche will conduct an annual study to determine the total
percentage relationship of Technical Services to COGS. The
percentage of Administrative Expense to the total of
Commercial Services and Research and Development will be
calculated similarly.
Amgen will determine a similar percentage of Administration
to the total of Marketing and Research and Development.
Amgen may review the percentage after the initial year to
determine its appropriateness. Amgen will not charge
operations of the Product with "start-up" costs for its
European operations. In addition, administration expenses
associated with operations in the United States will not be
charged to the expenses of the Product.
These percentages will be applied to actual and budgeted
Commercial Services (Marketing) and Research and Development
expenses to determine Technical Services (Roche only) and
Administration expense for the consolidated statement of
operations and budget.
Third party legal expenses or product liability insurance
will not be permitted in the calculation of an administrative
percentage.
13. Definition of Net Sales for Royalty Calculations -
Net Sales for purposes of calculating royalties shall be
Sales, as defined in part 4 of this agreement, less any cash
discounts charged to other income and expenses.
14. Start of Operations -
Operation of AMRO will commence ***************. Costs
incurred, and approved by the Management Committee will be
charged to AMRO operations after ***************. Costs
incurred prior to *************** are not chargeable to AMRO.
Costs for **************** that are in progress at
*************** and directed towards supporting filing in
Europe can be charged to the AMRO operation after approval by
the G-CSF Clinical Team.
15. Guidelines for Charging Costs to AMRO -
55
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
I. If an element of cost is
************************************** to the
development or commercialization of G-CSF as a product
*************, then **** of that element will be
chargeable ******* on the basis agreed to by the
partners.
II. If an expense to a *********** is
****************************************** to the
development or commercialization of G-CSF as a product
within ****** then:
a) If the amount of that element of cost utilized in
the development or commercialization of G-CSF
***************************************************
***************************************************
****** then the amount used may be charged *******.
b) Upon approval by the Management Committee of an
activity or expense which benefits G-CSF in cases
where there is
**************************************** available,
then:
i) If ***************** expense is determined by
the partners to be utilized in the development
or commercialization of G-CSF, then **** of
the element may be charged *******.
ii) If ******************** of the expense is
determined by the partners to be utilized in
the development or commercialization of G-CSF,
then *** of the element may be charged
*******.
iii) If there is
************************************ in the
development or commercialization G-CSF, but it
is also
****************************************, then
** of that expense may be charged *******.
56
Attest: AMGEN INC.
By /s/ Robert D. Weist By /s/ Lowell E. Sears
Date 1/19/89 Date 1/19/89
F. HOFFMAN-LA ROCHE & CO.,
LIMITED COMPANY
By /s/ Stephan C.J. Walsh
Date 24 January 1989
By /s/[illegible]
Date 24 January 1989
57
Exhibit I
AMRO
Roche
Commercial Services
Chart of Accounts
COST TYPE TITLE
4219.01 TEMPORARY HELP (from temporary agencies)
4223.02 TRAINING
4311.01 TRAVEL COSTS
4311.51 VISITORS' COSTS
4312.01 RENT - REAL ESTATE, OFFICES
4312.04 LEASING - EDP EQUIPMENT
4314.01 DEPRECIATION
4350.01 ADVERTISING - PRINTING
4350.04 SLIDES, PHOTOS
4350.05 CONGRESSES, CONVENTIONS
4350.15 MARKET RESEARCH
4350.16 AGENCY, CONSULTING EXPENSES
4350.18 OTHER ADVERTISING EXPENSES
4350.19 OTHER MARKETING EXPENSES
4361.03 OUTSIDE PRINTING, PHOTOS
4361.21 ASSOCIATION DUES
4361.54 REGISTRATION FEES - AUTHORITIES
4371.21 BOOKS, PERIODICALS
4371.22 OUTSIDE PROGRAMMING - EDP
4371.31 OP/APPL SOFTWARE
4371.41 SPECIAL SHIPPING COSTS
4371.91 OTHER OUTSIDE WORK
6001.96 SAMPLES
6112.95 ENERGY
6011.02 SALARIES & BENEFITS
6011.03 SALARIES & BENEFITS (Temporaries employed by Roche
on Roche P/R)
58
Exhibit II
AMRO
Roche
Clinical Research and Development
Chart of Accounts
COST TYPE TITLE
4111.32 CHEMICALS
4219.01 TEMPORARY HELP (from Temporary Agencies)
4223.02 TRAINING
4311.01 TRAVEL COSTS
4311.51 VISITORS' COSTS
4312.07 RENT - REAL ESTATE, OFFICES
4312.04 LEASING-EDP EQUIPMENT
4314.01 DEPRECIATION
4331.02 FEES & GRANTS
4331.03 EXPENSES FOR BIOMETRY (Statistical evaluation of
clinical trials by Third Party)
4361.03 OUTSIDE PRINTING, PHOTOS
4371.21 BOOKS, PERIODICALS
4371.31 OP/APPL SOFTWARE
4371.41 SPECIAL SHIPPING COSTS
4371.91 OTHER OUTSIDE WORK
6001.16 TECHNICAL ARTICLES
6001.95 AUXILIARY MATERIALS
6001.96 SAMPLES
6001.96 SALARIES (Full-time employees)
6011.03 SALARIES (TEMPS) - (Temporaries employed by Roche
on Roche P/R)
6111.95 REPAIR MATERIALS
6112.95 ENERGY
6113.95 QUALITY CONTROL
59
Exhibit III
Account No.
Description: Personnel Expenses
6011.02 Definition:
6011.03
4219.01 Personnel expenses include all payments made
to employees in the form of wages and
salaries. Also included, are expenses related
to pensions, welfare and other employee
benefits.
Description: Wages and Salaries
6011.02 Definition:
6011.03
4219.01 This position includes all remuneration paid
to employees in the form of:
- Salaries
- Wages
- Overtime pay
- Shift, holiday and other premiums
- Disability payments to employees
- Vacations and other paid absences
- Employee awards and bonuses
- Salesmen's commissions and other employee
commissions.
The above payments made to temporary personnel,
summer employees, etc., are included under this
position. Also included are wages and salaries
paid to outside agencies providing temporary
workers and employees.
Payments made to former employees (pensioners)
are not included under this position.
Description: Pension, Welfare and Other Employee
Benefits
6011.02 Definition:
6011.03
This position includes all costs incurred for
employee benefits, other than direct remuneration
to the employee. Expenses reported under this
position include:
- Company paid insurance premiums (life
insurance, hospital insurance, medical
insurance, etc.)
60
- Workmen's compensation insurance
- Payments to pension fund, trust or other social
institutions
- Payments to retirement plans and matching
contributions to savings plans
Account No.
Description: Energies
6112.95 Definition:
This position represents the consumption of
purchased energies such as electricity, natural
gas, gasolines, diesel fuel, oil, coal,
pressurized gases, etc., as well as any other
related charges.
Description: Repairs and Maintenance
6111.95 Definition:
Minor repairs and maintenance expenditures
required throughout the economic life of an asset
in order to keep it in efficient operating
condition. The distinguishing characteristics of
such expenditures are that they do not add to the
value or extend the useful life of property.
Repairs and maintenance have to be considered as
current period expenses and should not be
deferred over subsequent periods. This account
contains only invoiced costs for repairs and
maintenance from third parties (incl. material).
Also to be included here are expenses for
material for which no inventory-accounts are
kept.
In addition, any expenditure of a fixed asset
nature, which by local tax regulations may be
regarded as a deductible expense, could be
included here.
Description: Rent and Leasehold
6116.95 Definition:
4312.04
Expenses included in this category are rental and
non-capitalized leasing costs incurred by the
company for:
- Property, buildings and plants
61
- Machinery and equipment
- Office equipment, furniture and fixtures
- EDP equipment and software licensing
- Parking lots rented for personnel
- Other rental or leasing expenses
Account No.
Description: Travel and Entertainment Expenses
4311.01 Definition:
4311.51
This position includes all costs incurred by
employees (including field staff) while traveling
on company business and/or entertaining business
associates.
Exceptional entertainment expenses (such as
company anniversary celebrations) should be
reported as non-operating expenses.
Description: Advertising and Promotion
4350.01
4350.04
4350.05
4350.15 Definition:
4350.18
4350.19 Items classified in this category include all
costs paid to third parties for advertising and
promotion of company products and/or services.
Types of advertising and promotion include:
- Radio and television advertising
- Samples distributed to outsiders
- Journal advertising
- Promotional material
- Material and space for conventions and
exhibitions
Self-produced and distributed samples are not to
be included here.
If however, inventory accounts for all or certain
promotion materials are maintained, the
corresponding expense should appear under
"Material and Merchandise Expense."
62
Account No.
Description: Outside Services for Research and
Development
4111.32
4331.02
4331.03 Definition:
4361.02
4371.91 This account includes Third Party expenses
directly related to research and development,
such as:
- Fees and grants
- Research chemicals
- Clinical trials
- Test animals (including inward freight,
transportation, insurance, etc.)
- Animal feed
- Printing, photocopying, photography, etc.
- All other expenses directly related to the
research activity.
Note:
Under outside expenses, we understand expenses
paid to third party only.
Description: Depreciation of Property, Plant and
Equipment
4314.01 Definition:
Depreciation is a systematic charge against
income which distributes the cost or other basic
values of fixed assets over the estimated useful
life of the asset. Depreciation expense for the
year is that portion of the decrease in book
value of the asset charged during the current
period (cost value and revaluation value).
63
Account No.
Description: Other Outside Services
4371.21
4223.02
4371.31
4371.41
4361.21
4361.03
4361.54 Definition:
4371.91
4350.16 This account includes all other operational
expenses that cannot be assigned to one of the
above mentioned positions. Expenses in this
category include:
Office Supplies
Office supplies are charged directly to operating
expenses. If however, inventory accounts for all
of certain office supplies are maintained, the
corresponding expense should appear under
"Material and Merchandise Expense."
Books and Periodicals
All expenses for books, professional literature,
magazines and newspapers.
Printing, Photocopying, etc.
All outside expenses for printing, photocopying
and other reprographic services except those
pertaining directly and exclusively to either
research and development or sales and promotion
activities.
Translations
Fees and expenses for translations performed by
outsiders except those pertaining directly and
exclusively to sales and promotion activities.
Telephone, Cable and Telex Expense
All regular and incidental (including
installation) expenses for telephone, cable and
telex services.
Postage
All outside postage costs, except those relating
to sales and promotion activities (sending out
samples, sales literature, etc.). These are to
be recorded under "Advertising and Promotion."
64
Account No.
Description: Other Outside Services (cont.)
Definition: (cont.)
Association and Membership Dues
Items such as dues paid to trade, industry and
employers' associations, and membership fees paid
to private clubs on behalf of certain employees.
Management Consultancy Expenses
Apart from the usual items, this account should
also include software development services in
connection with electronic data processing.
Not to be included are payments made to or
received from the other parties as a result of
the outcome of such proceedings. These payments
are to be shown under non-operating income and/or
expenses.
Notarial and Registration Fees
All notarial and registration fees and expenses
incurred in connection with verifications,
attestations, etc. Examples of such costs are
the legitimization of contracts.
Public Permits and Dues
Building, driving, road, radio and other such
permits or dues which are issued or levied by
public authorities.
Outside Contractors' Fees
All fees and expenses by outside manufacturers
for work performed on saleable goods.
Other Personnel Expenses
Outside expenses in connection with: hiring of
staff, recruitment and relocation of personnel,
personnel training, welfare activities and staff
relations, contract transport for daily
conveyance of employees to and from work and
payments or provisions for dismissal indemnities.
Miscellaneous
Such general outside service expenses that cannot
be charged to one of the above accounts.
65
Account No.
Description: Royalty Expense - Third Parties
Definition:
This position represents expenses charged against
the current operating period for amounts paid or
payable to third parties in the form of license
fees or royalties for the use of patents,
trademarks, copyrights, and other similar
intangible rights.
Description: Cash Discounts
Definition:
This position represents cash discounts granted
to third parties customers upon payment of their
account(s) within a stipulated period.
Description: Bad Debt Expense
Definition:
This position represents the total amount of
write-offs or amounts reserved against future
write-offs of trade accounts or notes receivable
or other short-term receivables, which the
company records as expense during the current
operating period. Bad debt expense is charged
with specific accounts that have been written off
during the year, as well as after establishing
the new balances for the allowance for doubtful
accounts with third parties.
Description: Inventory Write-Offs
Definition:
This position represents the total current period
inventory write-offs that should not be charged
to production cost. The various types of
inventory adjustments are obsolescence (e.g.
inventory which exceeds quality control
expiration date and represents not further
value), book-to-physical adjustments, damages
occurred in warehouses and other similar reasons.
When inventory adjustments occur as a direct
result of production activity, these adjustments
would normally be charged to production cost.
The position here would usually include only
those inventory adjustments which cannot be
related to manufacturing or other direct
activities of the current operating period.
66
Exhibit IV
AMRO
Amgen
Chart of Accounts
Research and Development
Type of Expense
Salaries and Wages (included Temporaries)
Overtime
Employee Benefits
Employer taxes, Workers Comp. Ins.
and Annual Leave
Health insurance, other benefits
Recruiting and Relocation
R&D Operating Expense
Chemicals and reagents
Supplies
Animal Studies
Maintenance and repair
Equipment rental
Contract filling
Chemical analysis
Contract services
Internal lectures
Professional meetings
Society memberships
R&D consulting
Misc. supplies and expenses
Cost of sales absorption
Technology rights
Library
Grants
SAB expenses
Clinical and pre-clinical expenses
Data processing
Occupancy
Travel and entertainment
Telephone
Depreciation
Other expenses (Business Insurance)
67
Functions included in R&D:
Research
Pilot plant operations
Quality assurance
Process development
Regulatory affairs
Clinical affairs
68
Exhibit V
AMRO
Amgen
Major Cost Elements
Marketing
Type of Expense
Salaries and Wages (included Temporaries)
Overtime
Employee Benefits
Employer taxes, Workers Comp. Ins.
and Annual Leave
Health insurance, other benefits
Recruiting and Relocation
Occupancy
Travel and entertainment
Telephone
Depreciation
Marketing -
Advertising
Direct mail
Literature preparation
Medical education
Symposium/Lectures
Trade shows/exhibits
Sales training
Market research
Marketing consultants
Functions included in Marketing -
Marketing staff
Sales management
Detailing staff
Customer service
Order entry
Training
69
Appendix 2.01
Certain Other Rights in Spain and Italy
I. Spain
1. General Understanding
In addition to what is set forth in the Agreement AMGEN grants
to ROCHE the right to have marketed the Product in Spain under a
trademark owned by ROCHE (for the time being, ROCHE intends to use
the trademark GRANULOKINE(R)) (hereinafter referred to as the
"ROCHE-Trademark") and the right to sublicense such right to
market the Product in Spain to Laboratorios Pensa, Av. Mare de Deu
de Montserrat, Barcelona, Spain (hereinafter referred to as
"PENSA") under the ROCHE-Trademark, in accordance with the terms
herein.
2. Marketing by ROCHE Under the Trademark
ROCHE shall have the right to market the Product under the
Trademark in Spain until the Scheduled Termination Date (as
defined in the Agreement).
3. Sublicense to PENSA
a) AMGEN hereby grants ROCHE the limited right as set forth
herein to enter into a co-marketing agreement with PENSA for the
Product in Spain. Such co-marketing agreement will consist of a
license agreement between Productos ROCHE, S.A., Carretera de
Carabanchel a la de Andalucia s/n, E-28025 Madrid, Spain
(hereinafter referred to as "ROCHE-Spain") and PENSA ("License
Agreement") and a supply agreement between ROCHE and PENSA
("Supply Agreement") as well as a trademark license agreement
("ROCHE-Trademark Agreement") (the License Agreement, the Supply
Agreement and the ROCHE-Trademark Agreement are collectively
referred to as the "ROCHE-PENSA Agreements") copies of which have
been provided to AMGEN.
b) ROCHE and ROCHE-Spain will obtain AMGEN's written consent with
respect to the ROCHE-PENSA Agreements prior to entering into such
ROCHE-PENSA Agreements and, with respect to any future amendments
or waivers under ROCHE-PENSA Agreements, prior to any such
amendment or waiver. ROCHE and AMGEN agree that AMGEN is a third
party beneficiary of the ROCHE-PENSA Agreements. ROCHE agrees to
indemnify and hold AMGEN harmless from any damages suffered by
AMGEN by reason of any action taken by ROCHE or ROCHE-Spain or any
failure of ROCHE or ROCHE-Spain to act other than in accordance
with the terms hereof or the ROCHE-PENSA Agreements, respectively.
c) PENSA will market the Product under the ROCHE-Trademark for
the term of the ROCHE-PENSA Agreements. The term of the ROCHE-
PENSA Agreements shall last from January 1, 1992 until December
31, 1997. During such term the following shall apply:
70
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
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(i) While PENSA markets the Product under the ROCHE-Trademark
in Spain, the proceeds from the sale of the Product under
the ROCHE-Trademark will be included in the calculation of
Operating Profit or Loss.
(ii) ROCHE will send all reports as further described in Art.
6.1 of the ROCHE-PENSA License Agreement to AMGEN promptly
upon receipt by ROCHE or ROCHE-Spain.
(iii) ROCHE herewith declares that in the event ROCHE notifies
PENSA as per Art. 5.2 of the ROCHE-PENSA Supply Agreement
to interrupt the supply of the Product, ROCHE will appoint
AMGEN as the third party supplier as described in said
Art. 5.2 of the ROCHE-PENSA Supply Agreement, should AMGEN
so request.
(iv) With regard to Art. 3.2.9 Sections c) and d) of the
ROCHE-PENSA License Agreement, AMGEN will be accorded all
the rights and titles resulting from clinical trials as
per said Art. 3.2.9 Section c) and d) of the ROCHE-PENSA
License Agreement as anticipated in the EC-Agreement.
(v) ROCHE agrees that prior to the release of confidential
information by PENSA to third party collaborators under
Art. 7.1 of the ROCHE-PENSA License Agreement, PENSA will
receive written consent from ROCHE and ROCHE will receive
prior written consent from AMGEN, which will not be
unreasonably withheld.
(vi) ROCHE hereby warrants and represents that ROCHE-Spain
and PENSA will not modify the ROCHE-PENSA Agreements
without AMGEN's prior written consent, and that ROCHE will
cause ROCHE-Spain to perform its obligations contemplated
herein and as set forth in the ROCHE-PENSA Agreements.
(vii)
********************************************************
**********************************************************
**.
d) Upon the termination of the ROCHE-PENSA Agreements on December
31, 1997, the following shall apply:
(i) PENSA's right to use the ROCHE-Trademark will immediately
cease and PENSA will immediately transfer to ROCHE all
rights in the ROCHE-Trademark, including all goodwill
associated therewith;
(ii)ROCHE's right to use the ROCHE-Trademark in the Territory
will immediately cease;
(iii)ROCHE will grant to AMGEN all of ROCHE's rights in the
ROCHE-Trademark including all goodwill associated
therewith;
(iv)ROCHE will have no rights whatsoever to use the ROCHE-
Trademark in the Territory.
(v) AMGEN shall have the sole right to market the Product in
Spain under the Trademark.
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(vi)Notwithstanding Section 2.01(d) of the Agreement, AMGEN
shall grant to PENSA the rights set forth in Section I.3
(a) of this Appendix 2.01 for a term of **************.
The net proceeds received by AMGEN from the sale of the
Product by PENSA (or any subsequently appointed
distributor or AMGEN) will be included in the calculation
of Operating Profit and Operating Loss for the Term of the
Agreement.
**********************************************************
**********************************************************
********************************************.
Notwithstanding anything to the contrary contained in the
foregoing, ROCHE will continue to supply PENSA with the
Product until April 13, 1998 by extending its Supply
Agreement with PENSA until such date. The supply price
between January 1, 1998 and April 13, 1998 shall be agreed
by ROCHE, PENSA and AMGEN. Subject to the exception
contained in this provision (v), Section 2.01 (d) of the
Agreement shall remain in full force and effect.
II. Italy
1. General Understanding
In addition to what is set forth in the Agreement AMGEN grants
to ROCHE the right to market the Product in Italy (as used herein
Italy shall include the Vatican City and the Republic of San
Marino) under a trademark owned by ROCHE and the right to
sublicense such right to market the Product in Italy to Dompe
Biotech, S.p.A. Via S. Lucia, 4-20122 Milano, Italy, (hereinafter
referred to as "DOMPE") under the Trademark, in accordance with
the terms hereof.
2. Marketing by ROCHE Under ROCHE-Trademark
a) ROCHE will market the product under a trademark (for the time
being, ROCHE intends to use the trademark GRANULOKINE(R) owned by
ROCHE (hereinafter referred to as "ROCHE-Trademark").
b) ROCHE shall market the Product under the ROCHE-Trademark in
Italy until the Scheduled Termination Date (as defined in the
Agreement).
c) The Operating Profit or Loss from the sales of the Product
under the ROCHE-Trademark in Italy will be apportioned as set
forth in Art. 7.01(a) of the Agreement.
72
d) The parties agree to discuss revisions of the terms of the
Agreement in the event of any new indications or dosage forms
which significantly expand clinical and marketing resources needed
to adequately market and sell the Product under the ROCHE-
Trademark in Italy.
e) Following the termination of the marketing of the Product by
ROCHE under the ROCHE-Trademark in Italy, ROCHE will transfer the
ROCHE-Trademark to AMGEN or an Affiliate of AMGEN.
f) With respect to the marketing or promotion of the Product in
Italy by ROCHE (1) ROCHE shall provide AMGEN with all information
reasonably requested by it; (2) the Marketing Plan for the Product
shall be generally consistent with the Marketing Plans in the
other countries of the Territory; and (3) ROCHE may (but shall not
be obligated to) provide at least the comparable level of
marketing and promotion effort then being provided by other
companies distributing similar products in Italy, provided that
such right shall not change the level of ROCHE's billable sales
force participation in the Territory as a whole.
3. Sublicense to DOMPE
a) AMGEN hereby grants ROCHE the limited right as set forth
herein to enter into a co-marketing agreement with DOMPE for the
Product in Italy. Such co-marketing agreement will consist of a
license agreement between Prodotti ROCHE S.p.A., Piazza Durante
11. I-20131 Milano (hereinafter referred to as "ROCHE-Italy") and
DOMPE ("License Agreement") and a supply agreement between ROCHE
and DOMPE ("Supply Agreement") (both the License Agreement and the
Supply Agreement are collectively referred to as the "ROCHE-DOMPE
Agreements"), copies of which have been provided to AMGEN.
b) ROCHE and ROCHE-Italy will obtain AMGEN's written consent with
respect to the ROCHE-DOMPE Agreements prior to entering into such
ROCHE-DOMPE Agreements and, with respect to any future amendments
or waivers under the ROCHE-DOMPE Agreements, prior to any such
amendment or waiver. ROCHE and AMGEN agree that AMGEN is a third
party beneficiary of the ROCHE-DOMPE Agreements. ROCHE agrees to
indemnify and hold AMGEN harmless from any damages suffered by
AMGEN by reason of any action taken by ROCHE or ROCHE-Italy or any
failure of ROCHE or ROCHE-Italy to act other than in accordance
with the terms hereof or the ROCHE-DOMPE Agreements, respectively.
c) DOMPE will market the Product under the Trademark for the term
of the ROCHE-DOMPE Agreements. The ROCHE-DOMPE Agreements shall
terminate effective as from December 31, 1997.
Upon the termination of the ROCHE-DOMPE Agreements, AMGEN will
have the sole right to market the Product in Italy under the
Trademark.
d) Upon the termination of the ROCHE-DOMPE Agreements, the
following shall apply:
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(i) DOMPE's rights to use the Trademark will immediately cease
and DOMPE will immediately transfer to ROCHE all rights in
the Trademark, including all goodwill associated
therewith;
(ii)ROCHE's right to use the Trademark in the Territory will
immediately cease;
(iii)ROCHE will grant to AMGEN all of ROCHE's rights in the
Trademark including all goodwill associated therewith; and
(iv)ROCHE will have no rights whatsoever to use the Trademark
in the Territory.
e) While DOMPE markets the Product under the Trademark in Italy,
the proceeds from the sale of the Product under the Trademark will
be included in the calculation of Operating Profit or Operating
Loss.
f) Notwithstanding Section 2.01(d) of the Agreement, following
termination of the ROCHE-DOMPE Agreements on December 31, 1997,
AMGEN shall grant to DOMPE rights to distribute the Product in
Italy under the Trademark. Similar to the prior arrangements under
the ROCHE-DOMPE agreements,
******************************************************************
******************************************************* shall be
included in the calculation of Operating Profit and Operating Loss
for the Term of the Agreement.
g) The ************************ paid by DOMPE to ROCHE-Italy
under the ROCHE-DOMPE License Agreement will be included in the
calculation of Operating Profit or Operating Loss. Such *******
paid by DOMPE (or any other third party licensee or distributor)
to AMGEN after December 31, 1997 shall also be included in the
calculation of Operating Profit or Operating Loss. If no such
******* is paid, AMGEN shall contribute the financial equivalent
of such royalty to the Operating Profit.
h) ROCHE will send all reports as further described in Art. 7.2
and 6.1 of the ROCHE-DOMPE License Agreement to AMGEN promptly
upon receipt by ROCHE or ROCHE-Italy.
i) ROCHE agrees that prior to the release of confidential
information by DOMPE to third party collaborators under Art. 8.1
of the ROCHE-DOMPE License Agreement, DOMPE will receive written
consent from ROCHE and ROCHE will receive prior written consent
from AMGEN, which will not be unreasonably withheld.
j) The parties agree that at the end of the ROCHE-DOMPE
Agreements, ROCHE-Italy will promptly appoint AMGEN or its
designee as the transferee of the official registration for the
74
ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
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Product in Italy and under the Trademark and all relevant
documentation as further described in Art. 10.4 of the ROCHE-DOMPE
License Agreement.
k) If the ROCHE-DOMPE License Agreement terminates as set forth
in Art. 10.5 of the ROCHE-DOMPE License Agreement, the parties
agree that ROCHE-Italy will promptly appoint AMGEN or a third
party mutually agreed upon by ROCHE and AMGEN as the transferee of
the official registration for the specialty and all relevant
documentation as further described in Art. 10.5 of the ROCHE-DOMPE
License Agreement.
l) ROCHE hereby warrants and represents that ROCHE-Italy and
DOMPE will not modify the ROCHE-DOMPE Agreements without AMGEN's
prior written consent, and that ROCHE will cause ROCHE-Italy to
perform its obligations contemplated herein and as set forth in
the ROCHE-DOMPE Agreements.
m) The compensation due by ROCHE-Italy to DOMPE as per Art. 10.3
of the ROCHE-DOMPE License Agreement shall be paid by ROCHE-Italy
or ROCHE respectively and will be included in the calculation of
Operating Profit or Operating Loss.
Appendix 2.01 (a)
Dates of Formulation, Fill and Supply Transition
Country Date
*************** *********
******* *********
******* *********
****** *********
************** *********
******* *********
******* ********
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***** *********
***** ********
****** **********
******* **********
****** **********
****************** *****************************
************
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ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
Appendix 2.01 (b)
Transition Dates
Country Date
**************************************** ********
******************************* ********
*************** *********
******* *********
******* *********
****** *********
************** *********
******* **********
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****** ********
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*****************************
**************************
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*******************************
**************************
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ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
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Appendix 2.03
Evaluation Plan
******* - **********************************
-
*******************************
***********************************
***********************************
***********************************
****************
-
*******************************
***********************************
***********************************
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************************** -
***********************************
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***********************************
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-
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-
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ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
****************************- ******************************
***************
*******************************
***********************************
***********************************
***********************************
************
-
************************************
************************************
************************************
*******************
********************
************************************
******************************
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************************************
*********************************
**********************
************************************
**************************************
**************************************
**************************************
**************************************
**************************************
**********************************
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ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
Appendix 6.02 (b)
Assumption of Marketing Responsibility by AMGEN
- ********************************
*******
******
*****
*******
**************
***************
********
*******
**********
*******
*******
******
- ********************************
*******
*******************************
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ASTERISKS (*) INDICATE CONFIDENTIAL INFORMATION OMITTED AND FILED
SEPARATELY WITH THE SEC
Exhibit 6.06
***********************************
***************
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80