Exhibit 10.27
AMENDMENT AGREEMENT
TO THE
GLOBAL (NOW INCLUDING JAPAN)
CO-DEVELOPMENT, KNOW-HOW AND SUPPLY
AGREEMENT FOR GALANTAMINE
BETWEEN
SHIRE INTERNATIONAL LICENSING BV
AND
XXXXXXX PHARMACEUTICA NV
THIS AGREEMENT is made this 22nd day of July One Thousand nine hundred
and ninety nine by and between Shire International Licensing BV of
Xxxxxxxxxxxxxx 00, X.X. Xxx 000, 0000 XX Xxxxxxxxx, Xxxxxxxxxxx ("Shire") and
Xxxxxxx Pharmaceutica NV of Xxxxxxxxxxxxxx 00, X0000 Xxxxxx, Xxxxxxx
("Xxxxxxx").
WHEREAS Shire and Xxxxxxx entered into a Co-Development, Know-How and
Supply Agreement for galantamine on 30 November 1995 ("the Global Agreement").
WHEREAS Xxxxxxx concluded an arrangement with A+, Science Invest AB, a
Swedish corporation ("A+") in relation to the development of galantamine for
Obstructive Sleep Apnoea on 29 January 1999 ("the A+ Agreement") and Xxxxxxx and
Shire now wish to extend the arrangements in the Global Agreement to the
development of galantamine for use in the treatment of Obstructive Sleep Apnoea.
WHEREAS Xxxxxxx and Shire now wish to extend arrangements in the
Global Agreement to the development and exploitation of galantamine in Japan for
Alzheimer's disease and Chronic Fatigue Syndrome.
NOW THEREFORE IT IS HEREBY AGREED AS FOLLOWS:
Clause 1 Amendments to the Global Agreement
It is hereby agreed that the Global Agreement be amended as follows:
1.1 In Clause 1 the following definitions shall be amended as follows:
(a) in Clause 1.24 there shall be inserted after the word "Thailand"
the word "Japan;
(b) Clause 1.25 shall be deleted in its entirety and there shall be
inserted in substitution therefor:
"1.25 "Licensed Product(s)" any product containing Galantamine
(whether Natural Galantamine and/or
Synthetic Galantamine) which is used
for, and/or intended to be used for:
(1) the treatment of Alzheimer's
disease and/or related dementia
(2) the treatment of OSA
-2-
(3) subject to Clause 17 hereof the
treatment of CFS
(4) subject to Clause 18 other
indications as referred to in
that Clause;"
(c) In clause 1.33 in line 6 after the full stop insert the words
"(and following the inclusion in the Global Agreement of CFS
pursuant to clause 17.5 such term shall be deemed to include all
parents licensed to Shire or its Affiliates in the Territory in
respect of the use of Galantamine for CFS)."
(d) In clause 1.39 there shall be deleted the words "Galantamine in
the treatment Alzheimer's disease and related dementias" and
there shall be inserted in substitution therefor the words
"Licensed Product";
(e) In Clause 1.40 there shall be deleted the word "Japan";
(f) In Clause 1 insert the following additional definitions:
1.53 "OSA" Obstructive Sleep Apnoea;
1.54 "OSA Patents" each and every one of the patents,
patent application, supplementary
protection certificate in respect
therefor or additions, extensions,
replacements, divisions or
substitutions therefor licensed to
or owned by Xxxxxxx in respect of
the use of Licensed Product for OSA;
1.55 "OSA Know-how" all information (other than Shire
Know-How, Synaptech Know-How,
Development Data and Manufacturing
Intellectual Property rights) from
time to time during this Agreement
in Xxxxxxx'x possession or under its
control or licensed to it under the
A Agreement which it is free to
disclose relating to the use of
Galantamine for OSA;
-3-
(g) Upon execution by Synaptech, A, the patentee of the CFS patents,
Shire and Xxxxxxx of an agreement or agreements setting forth a
revised mechanism for the allocation of sales of Licensed Product
between Alzheimer's disease, CFS, OSA and (if appropriate) other
indications as that term is understood in Clause 18 of the Global
Agreement agreed pursuant to Clause 2.2 hereof or similar
provisions in agreements between such parties, Clause 8.3.5 shall
be deleted in its entirety and there shall subject to any such
agreements be substituted therefor:
"8.3.5 With regard to an individual sale of Licensed Product in
the Territory by Xxxxxxx, or an Affiliate or Business
Partner of Xxxxxxx, Xxxxxxx shall pay a royalty hereunder
on such sale on the basis that either (i) the Galantamine
will be used for the treatment of Alzheimer's disease and
related dementias or (ii) that it will be used for the
treatment of CFS or (iii) that it will be used for the
treatment of OSA. In no circumstances shall Xxxxxxx be
required to pay royalties on an individual Sale of
Galantamine in respect of Alzheimer's disease, CFS or OSA
under the Patents or OSA Patents."
(h) In Clause 4.4 of the Global Agreement there shall be deleted the
words **** and third party suppliers of Galantamine
Raw Material (including without limitation" and delete the
remaining parenthesis.
(i) In Clause 6 of the Global Agreement there shall be inserted the
following:
"6.1.13 Xxxxxxx shall pay to Shire on the Net Sales Value of all
Licensed Product sold by Xxxxxxx its Affiliates or
Business Partners in Japan:
6.1.13.1 in respect of sales of
Licensed Product for
Alzheimer's disease a royalty
of ****% (**** per cent):
6.1.13.2 in respect of sales of
Licensed Product for CFS a
royalty of ****% (**** per
cent)
6.1.14 Xxxxxxx shall pay to Shire on the Net Sales Value of all
Licensed product sold by Xxxxxxx, its Affiliates or
Business Partners in the Territory for OSA a royalty of
---------
**** Portions of this Exhibit which have been omitted based upon a request for
confidential treatment. The omitted portions have been separately filed
with the Commission.
-4-
6.1.14.1 ****% (**** per cent) where
there is a Licensed Patent in
the country in which Licensed
product is sold; and
6.1.14.2 ****% (**** per cent) in any
other country.
6.1.15 The royalties payable pursuant to Clause 6.1.13.1,
6.1.13.2 and 6.1.14.1 in any country in the Territory
shall be paid for that country for so long as there is a
Licensed Patent (being a patent for CFS or an OSA Patent
as the case may be in respect of Clauses 6.1.13.2 and
6.1.14 respectively) where the Licensed Product is sold
for the indication referred to or where there is no such
Licensed Patent for a period of **** years from
Commercial Delivery for that indication.
6.1.16 None of the provisions set forth in this Agreement
under which royalties may be reduced shall apply to the
royalties payable pursuant to Clauses 6.1.13 or 6.1.14
except in the case of infringement of the OSA patents
where, provided Xxxxxxx uses its reasonable efforts to
prevent or terminate such infringement, the provisions
of Clauses 12.1.1, 12.1.2, 12.1.3, 12.1.4 and the
second sentence of Clause 12.1.5 shall apply and in
relation to which any references to "Secondary Royalty"
shall be read to mean a royalty of ****%";
6.1.17 In addition to the royalties payable under the Global
Agreement by Xxxxxxx to Shire, Xxxxxxx will in addition
pay to Shire royalties under the sub-license granted
under clause 17.5.4 equal to the royalties payable by
Shire under its Agreement with Snorasson dated March
1992 as amended in June 1996 ("the CFS Agreement")
(j) In Clause 3 of the Global Agreement there shall be inserted the
following:
"3.5 Milestone Payments CFS Japan
Xxxxxxx shall pay to Shire in full without any deductions
whatsoever the following non-fundable sums:
---------
**** Portions of this Exhibit which have been omitted based upon a request for
confidential treatment. The omitted portions have been separately filed
with the Commission.
-5-
3.5.1 upon completion of a phase II clinical study in Japan
the results of which permit the conduct of a phase
III clinical study for Licensed Product for use in
CFS the sum of $**** (**** United States Dollars).
3.5.2 within 30 days of the date of submission of the
application for a Product Approval for use of
Licensed Product for CFS in Japan the sum of (Pounds)
**** (**** Pounds sterling) and
3.5.3 within 30 days of the date of grant of the Product
Approval for use of Licensed Product for CFS in Japan
the sum of (Pounds) **** (**** Pounds sterling)."
(k) Clause 10.10 of the Global Agreement shall be deleted in its
entirety and there shall be substituted therefor:
"10.10 in this Clause 10 the term "Licensed Product" shall
include any product containing Galantamine which is used for or
intended for use for the treatment of any indication for which a
Product Approval granted to Shire or Xxxxxxx or their respective
Affiliates or Business Partners is for the time being in force."
(l) In Clause 12 there shall be inserted the following:
12.4 Infringement of third party's patent rights
12.4.1 In the event that the use or sale of Licensed
Product for use in OSA is alleged to infringe or
constitutes an infringement of intellectual
property rights of a third party in a country, each
party shall, as soon as it becomes aware of the
same, notify the other thereof in writing, giving
in the same notice full details known to it of the
rights of such third party and the extent of any
alleged infringement. To the extent a third party
patent contains claims in relation to the use of
galantamine in OSA, the parties shall after receipt
of such notice discuss the infringement claim and a
potential course of action in close collaboration
---------
**** Portions of this Exhibit which have been omitted based upon a request for
confidential treatment. The omitted portions have been separately filed
with the Commission.
-6-
with A and in accordance with the provisions of the A
Agreement. Such course of action may include: (a)
modifying the therapeutic and/or prophylactic claims
of the Licensed Product so as to be non-infringing;
(b) obtaining an appropriate license from such third
party; or (c) contesting the claim or suit. Xxxxxxx
(and/or A in accordance with the provisions of the A
Agreement) will decide upon the course of action in
the interest of the further commercialization of
galantamine for use in the treatment of OSA.
12.4.2 In the event Shire is being sued or is under threat
of suit in any country of the Excluded Territory,
Shire shall promptly inform Xxxxxxx thereof in
accordance with the provisions of Clause 12.4.1
above. In the event Shire and Xxxxxxx (in
consultation with A) can not agree within twenty-one
(21) days on an appropriate course of action in such
countries as set forth in Clause 12.4.1, Shire shall
be entitled to discontinue the commercialization of
the Licensed Product for the use in OSA pending a
resolution of the alleged infringement claim.
12.4.3 Xxxxxxx shall hold harmless Shire and its Affiliates
with respect to any such alleged infringements in the
Excluded Territory provided Shire (i) complies with
the provisions of Clause 12.4.1 and 12.4.2, (ii)
allows Xxxxxxx to conduct the defense of any such
alleged infringement (provided always Shire can
participate in the defense at its own cost), (iii)
Shire does not compromise or settle any alleged
infringement claim without Xxxxxxx'x prior written
approval not to be unreasonably withheld or delayed
and (iv) Shire complies with the reasonable
instructions of Xxxxxxx (and A) in connection with
any such alleged infringement. Xxxxxxx'x hold
harmless obligation shall not apply in respect of any
period after the sublicensing or assignment
-7-
of the OSA Agreement to Shire pursuant to Clause 14
hereof.
12.5 Enforcement of OSA Patents
12.5.1 In the event that in any country in the Territory
in which Xxxxxxx is marketing Licensed Product,
there if infringement of an OSA Patent by a third
party, the party first becoming aware of such
infringement shall notify the other in writing to
that effect, including with said written notice
evidence establishing a prima facie case of
infringement by such third party.
Xxxxxxx shall have the right but not the obligation
to take action to stop such infringement in its own
name, at its own expense and on its own behalf and
by counsel of its own choice. If Xxxxxxx elects to
take action against such infringement, it will keep
Shire regularly informed on the status of any such
action. Subject to the provisions of the A
Agreement, Xxxxxxx shall be entitled to all damages
awarded or received in settlement of such suit.
12.5.2 In any such suit involving the use of galantamine
in the treatment of OSA Shire shall reasonably
cooperate with Xxxxxxx (and A as the case may be)
and in the Excluded Territories Shire shall have
the right, subject to the provisions of the A
Agreement and more in particular the provisions of
Articles 12.2 and 12.3 thereof, to be represented
by its own counsel at its own expense."
(m) In Clause 13.1.2 after the word "Territory" in line 6 thereof
insert the words "or arising from or in connection with the
failure of any Finished Product supplied by Xxxxxxx to Shire for
resale and supply by Shire in the Excluded Territory to meet
specification therefor or such Finished Product being defective."
(n) In Clause 13.1.3 add at the end of the Clause "and except to the
extent that any such claims, demands, losses, damages and/or
expenses
-8-
result from Finished Product supplied by Xxxxxxx to Shire being
defective or failing to meet specification."
(o) In Clause 15.5 of the Global Agreement after the letters "CPS"
insert the word and letters "and OSA."
(p) In Clause 19 of the Agreement, Clause 19.1 shall be deleted and
there shall be inserted:
"19.1 Xxxxxxx hereby grants to Shire an option for a period of
**** after the **** of the **** in the country for a sum
equal to concerned to the aggregate of acquire the the
following: exclusive rights to market and sell the
Licensed Product in any one of **** for a sum equal to the
aggregate of the following:
19.1.1 in respect of the sales of Licensed Product
for Alzheimer's disease a sum equivalent to
**** times the average annual value of the
Net Sales Value of the Licensed Product sold
in the country selected by Shire calculated
over the **** Quarters following the date of
**** in such country; and
19.1.2 in respect of the sales of Licensed Products
for OSA and/or CPS a sum calculated using the
following formula
Y = M x MCY
where Y = sum payable
M = the appropriate multiplier for either CFS or OSA taken from
column (2) or (3) depending on the time which has elapsed
since the date of first Commercial Delivery until the date of
the exercise of the option
MCY = the annual sales calculated for the appropriate period as
shown in column (4) or (5)
---------
**** Portions of this Exhibit which have been omitted based upon a request for
confidential treatment. The omitted portions have been separately filed
with the Commission.
-9-
---------------------------------------------------------------------------------------------------------------------
(1) (2) (3) (4) (5)
---------------------------------------------------------------------------------------------------------------------
Time elapsed since date Multiplier M Method of Calculating Yearly Sales
of First Commercial
Delivery ("FCD") at
date of exercise of
option by Shire
--------------------------------------------------------------------------------------------
CFS OSA CFS OSA
---------------------------------------------------------------------------------------------------------------------
Prior to date of FCD **** **** average of sales made in an agreed estimate of
--------------------------------------------------- Quarter **** and **** sales in the Quarters ****
Less than **** months Quarters
after FCD **** ****
---------------------------------------------------------------------------------------
More than **** months annual sales assessed using an
after FCD but up to agreed estimate of actual
**** months after FCD **** **** sales for Quarters ****
---------------------------------------------------------------------------------------------------------------------
More than **** months annual sales calculated using actual sales for the last
after FCD but up to average of actual sales for **** Quarters immediately
**** months after FCD Quarters **** and the preceding the date of
last **** Quarters immediately exercise of the option
**** **** preceding the date of exercise
---------------------------------------------------------------------------------------------------------------------
More than **** months annual sales calculated using actual sales for the last
after FCD but up to the average of actual sales **** Quarters immediately
**** months after FCD for Quarters **** and preceding the date of
the last **** Quarters exercise of the option
immediately preceding the date
**** **** of exercise
---------------------------------------------------------------------------------------------------------------------
More than **** months annual sales calculated using actual sales for the last
after FCD the average of actual sales **** Quarters immediately
for Quarters **** and the preceding the date of
last **** Quarters immediately exercise of the option
**** **** preceding the date of exercise
---------------------------------------------------------------------------------------------------------------------
Provided that:
(1) Where reference is made to an estimate in this Clause the
relevant sales shall be recalculated using the actual figures for
the period in question as soon as reasonably practicable
following that period and balancing payment will be made by Shire
or a refund [(subject to the commitment of equivalent sales and
marketing effort by Shire in the aggregate and appropriate to the
efforts to be made judged by reference to the pharmaceutical
industry taken as a whole)] will be made by Xxxxxxx of the
difference between such estimate and the calculation made using
actuals.
---------
**** Portions of this Exhibit which have been omitted based upon a request for
confidential treatment. The omitted portions have been separately filed
with the Commission.
-10-
(2) Where a reference is made to sales this shall be construed as a
reference to Net Sales Value.
(3) Sales of Licensed Product for CFS, OSA and Alzheimer's disease
shall be calculated with reference to the mechanism agreed
pursuant to Clause 2.2 of the Amendment by which this Clause was
inserted.
(4) Where a calculation of sales is to be made by reference to the
actual sales of the 4 Quarters immediately preceding the date
upon which the option is exercised the annual sales shall be
established by reference to the average sales in each such
Quarter and there shall be deducted from such sales any sales not
derived in the ordinary course of business and in the event of a
dispute the matter shall be referred to the expert pursuant to
Clause 12.2.
(5) For the avoidance of doubt where at the time of exercise of the
options by Shire the development of Licensed Product for OSA or
CFS has ceased or will cease no payment shall be due under this
Clause in respect of the indication in question.
(6) If the option is exercised during a Quarter, reference will be
made in making any calculation to the last complete Quarter.
(q) In Clause 19.2 at the end of the sentence insert the words
"except in respect of Licensed Product for use in the treatment
of OSA in respect of which the payment shall be a sum equivalent
to 3 times average annual sales calculated as aforesaid. Sales
for each indication shall be calculated with reference to the
mechanism as agreed pursuant to Clause 2.2 of the Amendment by
which this clause was inserted.
(r) In Clause 23, Clause 23.2.2 shall be deleted in its entirety.
(s) In Clause 23.2.4 after the words "Synaptech-Xxxxxxx License
Agreement" add the words "(including any extension thereof to
Japan)."
(t) In Clause 26 in line 1 the reference to "Major Countries" shall
be deemed to exclude the USA.
Clause 2 Supplementary Provisions
The following provisions are supplementary to the Global Agreement and
shall form part thereof.
-11-
2.1 Development
2.1.1 The development of Licensed Product for OSA shall be conducted
by and at the expense of Xxxxxxx. The provisions of Clause 4 of
the Global Agreement other than Clauses 4.7, 4.8, 4.9 and 4.10
shall not apply to the developments of Licensed Product for
OSA. Notwithstanding the foregoing Xxxxxxx shall keep Shire
informed on the progress of the development of Licensed Product
for OSA on a regular basis and in particular but without
prejudice to the generality of the foregoing Xxxxxxx shall
provide Shire at intervals of six months until completion or
cessation of development a report summarizing the work
undertaken or to be undertaken and the results thereof.
2.1.2 With regard to any matter arising from the development of
Licensed Product for OSA which might reasonably be expected to
affect the manufacture, sale, supply, development or licensing
of Licensed Product for Alzheimer's disease or CFS, Xxxxxxx
shall inform Shire forthwith on becoming aware thereof in
sufficient detail to enable Shire to obtain a full
understanding thereof.
2.1.3 The development of Licensed Product for use in Alzheimer's
disease in Japan and CFS in the Territory shall be conducted by
and at the expense of Xxxxxxx. Xxxxxxx shall:
2.1.3.1 as soon as reasonably practicable following the
execution hereof propose to Shire a development plan
for Licensed Product for use in Alzheimer's disease in
Japan for agreement by the DMC;
2.1.3.2 as soon as reasonably practicable after the extension
of the Global Agreement to CFS pursuant to Clause 17
thereof propose to Shire a development plan for
development of Licensed Product for use in CFS in the
Territory for agreement by the DMC.
2.1.4 The provisions of Clause 9 of the Global Agreement to the
extent that they impose on Xxxxxxx an obligation to use
reasonable efforts in the development of Licensed Product shall
not apply to the development of Licensed Product for OSA.
-12-
2.1.5 The provisions of Clause 5 of the Global Agreement shall not
apply in relation to development costs for Licensed Product for
OSA or for Alzheimer's disease or CFS in so far as they relate
to Japan.
2.2 Xxxxxxx and Shire each recognises and agrees that a mechanism is
required to ensure that sales of Licensed Product for different
indications for which Licensed Product may be supplied in accordance
with a marketing authorisation are attributed to the indication in
question. It is further recognised and agreed that Xxxxxxx has
incorporated within the A+ Agreement a provision by which sales are
allocated in the form attached in the Schedule hereto. Xxxxxxx and
Shire each hereby agrees to use its reasonable efforts to obtain the
agreement of the respective patentees and licensors for Alzheimer's
disease and CFS to the variation and amendment of the licenses between
Xxxxxxx or Shire and such licensor to reflect the provisions set forth
in the Schedule hereto. Upon such agreements Xxxxxxx and Shire
further agree to amend the terms of any sublicence between Xxxxxxx and
Shire and the terms of the Global Agreement to reflect the provisions
of such Schedule. Xxxxxxx further undertakes to use its reasonable
efforts to ensure that its licence with A+ is varied and amended to
the extent necessary to be identical to the provisions agreed with the
licensors in respect of Alzheimer's disease and CFS.
2.3 Where Shire holds a licence under the patent of a third party relating
to the use of Licensed Product for OSA and (1) Xxxxxxx or a court or
other authority having jurisdiction determines that Xxxxxxx requires a
licence under any such patent in order to manufacture, use, supply or
sell Licensed Product for OSA and (2) Shire has not licensed such
patent under the terms of the Global Agreement for its principal
indication and (3) Shire is entitled to receive royalties from Xxxxxxx
under the Global Agreement for the use of Licensed Product for OSA
then to the extent that Xxxxxxx requires an enabling licence under
such patent determined as aforesaid for the use of Licensed Product
for use in the treatment of OSA Shire will use its reasonable
endeavours following full consultation with Xxxxxxx to obtain the
consent of the third party licenser of such patent to the grant of an
enabling licence at royalty rates appropriate thereto. For the
avoidance of doubt, nothing in this Clause 2.4 shall in any way
derogate from the obligations of Xxxxxxx under the Global Agreement in
respect of any indication other than OSA for which Licensed Product
may be manufactured, used, sold or supplied.
-13-
2.4 Reasonable Endeavours
Where in Clauses 2.2 and 2.3 above reference is made to the use of
reasonable endeavours by Shire or Xxxxxxx it is hereby agreed that such
endeavours shall not include the making of any payment whether of a lump sum
nature or royalties.
2.5 Challenge to Validity
The payment of royalties by Xxxxxxx to Shire in respect of the sale or
supply of Licensed Product for use in OSA is conditional upon Shire not
initiating proceedings to invalidate the OSA patent and in the event that it
does so (1) the obligation of Xxxxxxx to pay royalties in respect of sales of
Licensed Product and (2) any licenses granted by Xxxxxxx to Shire or its
Affiliates in the Excluded Territory under the OSA Patent shall cease and be
suspended until such time as the challenge to the validity is withdrawn or
terminated.
2.6 Ownership and Maintenance of Product Approvals
2.6.1 Notwithstanding the provisions of Clauses 4.4 of the Global
Agreement Shire and Xxxxxxx shall appoint one or more
representative(s) from those of their employees employed to
manage applications for and the maintenance of and variation of
Product Approvals for Licensed Product to liaise with regard to
the prosecution for and maintenance of Product Approvals for
each indication to avoid, remove or minimize any potential
conflict between the Product Approvals for each different
indication or for each country in the Territory or Excluded
Territory in accordance with a Standard Operating Procedure to
be agreed. Subject to the above-mentioned Standard Operating
Procedure Shire and Xxxxxxx agree that they will not make any
variation or alteration to any Product Approval without first
notifying the other of its intention to make any applications
for any material variation or alteration as aforesaid and
taking account of observations of the other to the extent
reasonably practicable following good faith consultation unless
such alteration or variation has been required by law or
regulation or by a regulatory authority having jurisdiction or
for reasons of health or safety in which event such alteration
or variation shall be made and the party making such alteration
and variation shall consult with the other to the extent
practicable.
2.7 Co-promotion OSA
The marketing, commercialisation and licensing of OSA in the United
Kingdom and Ireland will be organised in accordance with the provisions of
Clause 10 of the Global
-14-
Agreement as well as with the provisions of the co-promotion agreements to be
entered into between Shire's and Xxxxxxx'x respective Affiliates.
Shire acknowledges that under the A+ Agreement, the United Kingdom is
classified as a major market for which Xxxxxxx has agreed to undertake certain
reasonable efforts as set forth in Article 7.1. of the A+ Agreement. It is
hereby agreed that such commitment shall be reflected in the respective rights
and obligations of the Affiliates of Shire and Xxxxxxx to be set forth in the
co-promotion agreement between such Affiliates to be implemented in a timely
manner in order to facilitate regulatory filing and Commercial Supply of
Licensed Product of OSA and provided Xxxxxxx continues with the development of
Licensed Product for OSA.
2.8 Trade Xxxx
Pursuant to Clause 11 of the Global Agreement Shire and Xxxxxxx have
agreed that Licensed Product for use in Alzheimer's disease will be marketed
under the name Reminyl and accordingly Xxxxxxx undertakes forthwith following
signature of this Agreement to execute an assignment of the trade xxxx Reminyl
in the UK and Ireland in a form approved by Shire and Xxxxxxx for the purpose.
2.9 Japan
Xxxxxxx and Shire agree that the provisions relating to Japan in the
Global Agreement and in particular but without prejudice to the generality of
the foregoing clauses 14.1.3 and 14.1.4 thereof shall be deemed to have been
satisfied by the payment of royalties pursuant to Clause 6.1.13.1 of the Global
Agreement as incorporated by this Agreement. Such provisions shall be of no
force and effect to the extent and for so long as agreements between Synaptech
as the patentee of Licensed Patents in respect of the use of galantamine in
Alzheimer's disease and Xxxxxxx remain in full force and effect and in the event
of the termination of such agreements by Synaptech Shire acknowledges that
Xxxxxxx has permitted Synaptech to refer to the Product Approval for licensed
Product in Japan for Alzheimer's Disease and related dementias as set forth in
and subject to Clause 6 of the Addendum to the Synaptech-Xxxxxxx License
Agreement dated June 29, 1999.
2.10 Development Data
Xxxxxxx shall make available to Shire or its Affiliates exclusively
for use in the Excluded Territory:
2.10.1 OSA Know-how reasonably required by Shire for the purpose of
making application for and maintaining Product Approvals for
Licensed Product for use in OSA in Excluded Territories;
-15-
2.10.2 OSA Know-how reasonably required by Shire for marketing and
pharmacovigilance.
2.11 Improvements
The provisions of Clause 14.3 of the Global Agreement shall be subject
to the following provisions:
2.11.1 when Improvements are disclosed pursuant to Clause 14.3.1 the
party making the disclosures shall provide such details as are
reasonably necessary for the other party to undertake scientific
and commercial assessment thereof and disclosure shall be made
as soon as is practicable but in any event in sufficient time to
enable a proper evaluation thereof by the receiving party prior
to commercial exploitation;
2.11.2 the licenses granted or to be granted pursuant to Clause
14.3.2, 14.3.3, 14.3.5 and 14.3.6 shall be subject to any pre-
existing agreements with third parties at the time of disclosure
and where the consent of a third party is required for the grant
of any such license then the disclosing party shall use its
reasonable endeavours to obtain such license;
2.11.3 any sub-licenses granted pursuant to clause 14.3 shall be
subject to any royalties payable to the patentee which shall be
paid in accordance with the terms of the license held by the
disclosing party.
2.12 Sub-Licenses
Any sub-license granted by Shire pursuant to Clause 17.5.4, or by
Xxxxxxx to Shire in respect of the OSA Patents and OSA Know-how relating to the
use of Licensed Product for CFS and OSA respectively shall unless otherwise
agreed by the licensor and Shire and Xxxxxxx be identical to the terms of any
head license between Shire or Xxxxxxx and the relevant third party licensor and
subject to the payment by the sub-licensee of any royalties reserved therein.
2.13 Other Cholinesterase Inhibitors
It is hereby agreed that Clause 20 shall not for the avoidance of
doubt apply to the development by Xxxxxxx of galantamine for the treatment of
OSA.
-16-
2.14 Termination of licenses
2.14.1 Where (1) each of Xxxxxxx'x licenses for Alzheimer's disease,
CFS and other indications are terminated by the relevant third
party licensors or (2) or the provisions of Clause 25 of the
Global Agreement apply, then Xxxxxxx shall either grant a
sublicense under the A+ Agreement or procure the assignment of
such agreement to Shire subject to Clause 2.12 above and the
payment by Shire of a royalty of ****% to Xxxxxxx on the Net
Sales Value of Licensed Product sold by Shire, its Affiliates
or its sublicensees in respect of sales of Licensed Product
for OSA in those countries where Xxxxxxx'x rights were
terminated as aforesaid. Such royalty shall be due and payable
for a period of 10 years following the first commercial sale
by Shire, its Affiliates or sub-licensees in such country or
countries or until expiration of the OSA Patent in such
country or countries, whichever occurs first.
2.14.2 Where the Global Agreement is terminated by Xxxxxxx pursuant
to Clause 23.1.1 then the provisions of Clause 24.3 shall
apply to the royalties to be paid pursuant to Clause 6.1.14.
Clause 3 Lump Sum Payments and Royalties
3.1 In consideration of Shire agreeing to amend the Global Agreement to
extend the rights thereunder in respect of the sale of Licensed
Product for use in CFS in Japan in accordance with and subject to the
terms of the Global Agreement and in particular but without limitation
Clause 17 thereof Xxxxxxx hereby agrees to pay to Shire within 30 days
of the date of confirmation that the success criteria referred to in
Clause 17.3 of the Global Agreement have been met, the non-refundable
sum of $**** (**** United States Dollars). Shire shall render an
invoice to Xxxxxxx for such payment.
3.2 In consideration of Xxxxxxx procuring access to certain intellectual
property of **** (and its Affiliates) and **** are procuring certain
sublicenses to Shire as set forth herein. Shire agrees to reimburse
Xxxxxxx with one half of each of the following payments:
(i) the sum of US $150,000 (one hundred and fifty thousand United
States Dollars) paid by Xxxxxxx to **** pursuant to Article 3.1
of the agreement referred to in Clause 3.4(ii) below and
accordingly Shire shall pay to Xxxxxxx the sum of US $75,000
(seventy five thousand United States Dollars), 30 days after the
date of this Agreement
---------
**** Portions of this Exhibit which have been omitted based upon a request for
confidential treatment. The omitted portions have been separately filed
with the Commission.
-17-
(ii) the sum of (Pounds) 200,000 (two hundred thousand pounds) paid
by Xxxxxxx to **** pursuant to Clause 3.1.1 of the agreement
referred to in Clause 5.1(a) below and accordingly Shire shall
pay to Xxxxxxx the sum of (Pounds) 100,000 (one hundred thousand
pounds), 30 days after the date of this Agreement.
3.3 Xxxxxxx shall notify of the payments made by it together with an
invoice therefor. Each of the sums referred to in (i) and (ii) above
are expressed to be inclusive of VAT or similar sales or other taxes.
3.4 With regard to the royalty payments payable by Xxxxxxx to **** or ****
as appropriate Xxxxxxx shall be entitled to deduct one half of such
royalties in accordance with the following provisions:
(i) **** (****%) of the royalty actually paid by Xxxxxxx to ****
under Clause 3.1.2 of the agreement between Shire, Xxxxxxx and
**** dated 6 August 1998 (the ****) may be deducted from the
payments to be made by Xxxxxxx to Shire pursuant to Clause 6.1
of the Global Agreement;
(ii) **** (****%) of the royalty actually paid by Xxxxxxx to ****
under Article 3.2 of the Agreement between Xxxxxxx and ****
dated 26 March 1998 and relating to the licensing of certain
patents in the United States, its territories and possessions
for the manufacture of Synthetic Galantamine (the ****) may be
deducted from royalties payable by Xxxxxxx to Shire in respect
of Net Sales Value of Licensed Product in the United States, its
territories and possessions pursuant to the Global Agreement.
3.5 The provisions of Clauses 6.2, 6.3, 6.4 and 6.5 and of Clauses 7.8.1
and 8.2 of the Global Agreement shall apply to the royalties and other
payments referred to in this Agreement.
3.6 For the purposes of calculating Standard Cost under the Global
Agreement (subject to any contrary arrangements in relation to the
supply of Licensed Product agreed in the co-promotion agreements
envisaged in Clause 10 of the Global Agreement) there shall be
disregarded for the purposes of such calculation the sums payable by
Xxxxxxx to **** and **** respectively under the agreements
referred to in Clause 5.1 above and any royalty payable thereunder by
Xxxxxxx to **** and **** respectively to the extent that
the same are deducted from royalties payable by Xxxxxxx to Shire
pursuant to the terms of the Global Agreement as supplemental by this
Agreement.
---------
**** Portions of this Exhibit which have been omitted based upon a request for
confidential treatment. The omitted portions have been separately filed
with the Commission.
-18-
Clause 4 ****
4.1 Xxxxxxx and Shire each hereby acknowledge that the obligations of
Shire and Xxxxxxx under Clause 16.4 of the Global Agreement have been
fully discharged and that save as provided in this Agreement the
Global Agreement shall not apply to the **** Intellectual Property and
for the avoidance of doubt from the date of this Agreement
Manufacturing Intellectual Property as defined in the Global Agreement
shall not be deemed to include any such intellectual property.
Clause 5 **** Sub-Licenses
5.1 Xxxxxxx hereby grants to Shire a license to use the parents and other
know-how and intellectual property assigned, transferred or licensed
to it pursuant to each of the following agreements.
(a) the **** Agreement referred to in Clause 3.4.(i) above and
any assignments made subsequent thereto assigning and licensing
certain intellectual property to Xxxxxxx and providing for the
payment by Xxxxxxx of certain sums in consideration thereof.
(b) the **** Agreement referred to in clause 3.4(ii) above
relating to the licensing of certain patents for the manufacture
of synthetic galantamine.
and a license to use all associated intellectual property of
Xxxxxxx which may be required or necessary for the exploitation
of the license for the manufacture and sale of synthetic
galantamine by or on behalf of Shire in accordance with the
following provisions of this Clause 5.
5.2 Each of the license granted by Xxxxxxx to Shire pursuant to Clause
5.1 above shall be subject to the term of the respective licenses and
agreements between Xxxxxxx and **** and **** respectively and shall be
exclusive, except with respect to **** and shall, subject to the terms
of any such headlicense, extend to the territory referred to therein
and be royalty free (save as to any payments to be made to **** or
****.
5.3 Unless otherwise stated each of the licenses granted by Xxxxxxx to
Shire may be exercised upon the happening of one or more of the
following events:
(a) in relation to the Xxxxxxx Territory, Shire Territory and
Excluded Territory upon the termination of the Sub-License and
Global Agreement
---------
**** Portions of this Exhibit which have been omitted based upon a request for
confidential treatment. The omitted portions have been separately filed
with the Commission.
-19-
otherwise than for breach of the terms thereof by Shire, the
insolvency of Shire or the discontinuation of sale of the
Licensed Product as a result of supply or technical issues agreed
by Shire and Xxxxxxx;
(b) in relation to the Excluded Territory (including pursuant to
Clause 19 of the Global Agreement any buy back country to the
extent it becomes an Excluded Territory) and pursuant to the
terms of the Global Agreement where Shire or its Affiliate
notifies Xxxxxxx that it is able to obtain supplies of Synthetic
Galantamine at a cost lower than the price at which Xxxxxxx has
offered to supply Shire or its Affiliates;
(c) subject to and in accordance with the terms of the Global
Agreement in relation to Japan in the event that the rights under
the Global Agreement granted to Xxxxxxx in respect of Japan
terminate;
(d) in relation to the manufacture of a product containing an
analogue of galantamine or equivalent to Licensed Product for
sale or supply in relation to any indications where Shire markets
the same with or without a third party in which event such rights
shall be non-exclusive.
5.4 In lieu of exercising the rights granted by Xxxxxxx to Shire pursuant
to Clause 5.1 above Shire may elect following consultation with
Xxxxxxx and with its agreement to have Synthetic Galantamine supplied
by Xxxxxxx to satisfy its reasonable requirements and at a price
determined in accordance with the Global Agreement.
Clause 6 Entire Agreement
6.1 The terms of this Agreement are supplemental to the Global Agreement
and the Xxxxx-Xxxxxxx Sub-License Agreement and any and all
supplemental and ancillary letters thereto and form part of the entire
agreement referred to in Clause 28 thereof and terms used in this
Agreement shall have the meaning ascribed thereto unless the context
otherwise requires.
__________________________________
For and on behalf of
Shire International Licensing BV
__________________________________
For and on behalf of
Xxxxxxx Pharmaceutica NV
SCHEDULE
--------
Provisional terms for the apportionment of galantamine in accordance
with IMS statistics on sales by indication
A. Countries with prescription audits
The following 24 countries represent 85% of the world pharmaceutical
market. In all of these countries IMS prescription audits exist and are
generally reliable:
USA Canada Switzerland
Japan Argentina Portugal
Germany Mexico Austria
France Australia Greece
Italy Belgium Finland
UK Netherlands South Africa
Brazil Sweden Denmark
Spain Taiwan Norway
-- The prescription audit will mention the number of prescription by
indication. The relevant indications are AD, CFS and OSA.
-- Prescriptions that are closely related to the 3 indications AD, CFS
and OSA will be included in the category to which they are closely
related.
-- The remaining prescriptions that are unrelated to one of the 3
indications will be divided proportionally over these 3
indications.
-- The relative proportion of the prescriptions will also be
considered to be the relative proportion of actual sales in the
market.
-- Until an indication is registered no prescriptions will be counted
for such indication.
B. In the remaining countries without (reliable) prescription market the
following mechanism will apply:
-- The split of the sales over the 3 indications will be based on a
weighted average of the countries.
-2-
-- The weighted average calculated for countries with prescription
will take into account the number of years after launch of an
indication.
