EXHIBIT 10.27
CONFIDENTIAL TREATMENT REQUESTED
(*) Denotes information for which confidential treatment has been requested.
Confidential portions omitted have been filed separately with the Commission.
AGREEMENT
This Agreement is entered into this 12 day of November 1996, by and between
NEUREX, a company organized and existing under the laws of the State of
California, U.S.A., having its registered office at 0000 Xxxxxx Xxxxxx
Xxxxxxxxxx, Xxxxxxxx (U.S.A.) and principal office at 0000 Xxxxx Xxxxxx, Xxxxx
Xxxx, Xxxxxxxxxx 00000-0000 (U.S.A.), represented by its Chairman and C.E.O.,
Mr. Xxxx Xxxxxxx, hereinafter referred to as NEUREX, and SOCIETE DE CONSEILS, DE
RECHERCHES ET D'APPLICATIONS SCIENTIFIQUE (S.C.R.A.S.), a company organized and
existing under the laws of France, having its registered office at 00/00 xxx xx
Xxxxxxx Xxxxxxx, 00000 Xxxxx (Xxxxxx), represented by Mr. Philippe Beaufour,
Director, hereinafter referred to as SCRAS.
Witnesseth that
Whereas SmithKline Xxxxxxx Co., a corporation of the Commonwealth of
Pennsylvania, having a place of business at Xxx Xxxxxxxx Xxxxx, X.X. Xxx 0000,
Xxxxxxxxxxxx, Xxxxxxxxxxxx 00000 (U.S.A.), and NEUREX, have entered into a
License and Supply Agreement on April 5th, 1994, whereby SmithKline Xxxxxxx Co.
(i) grants NEUREX an exclusive license for all the countries and territories in
the world, with the right to grant sublicenses, to make, have made, use, and
sell a chemical compound known as Fenoldopam under certain patents proprietary
to SmithKline Xxxxxxx Co., (ii) assigned to NEUREX all of SmithKline Xxxxxxx
Co.'s rights, title, and interest in the Trademark name for Fenoldopam
"Corlopam(R)", in all countries where registered, and (iii) supplies NEUREX with
substantial quantities of the chemical compound known as Fenoldopam.
Whereas NEUREX has developed a Product (as hereinafter defined) containing
Fenoldopam and indicated for blood pressure control in operating and
post-operating rooms, as well as hypertension crisis emergency treatment, and
intends to market such pharmaceutical Product under the trademark Corlopam(R).
Whereas NEUREX has (i) completed clinical, pharmaceutical, and toxicological
studies in order to file for the Product marketing authorizations, (ii)
consequently filed in the United States of America and in certain European
countries, for the Product registration, and (iii) wishes to grant SCRAS, whose
identity has been duly notified to and approved by SmithKline Xxxxxxx Co., the
rights to pack, label, promote, and market the Product under the trademark
Corlopam(R) in the Territory (as hereinafter defined), under the relevant
patents, trademarks, and marketing authorization files.
Whereas SCRAS is willing to be granted by NEUREX, a license with the right to
grant further sublicenses to the member companies of the Beaufour-Xxxxx Group,
under the relevant patents, marketing authorization files, and trademark, to
pursue the Corlopam(R) marketing authorization process in the Territory as
hereinafter defined, to purchase from NEUREX the Product, and to pack, label,
promote and market the Product in the Territory under the trademark Corlopam(R).
Whereas NEUREX warrants that on the date of execution of this Agreement, NEUREX
has not presently reached Phase I clinical trials in the development of any
additional formulation and/or indication of the Compound (as hereinafter
defined), prodrugs of the Compound, and more generally any compound belonging to
the Dopaminergic compound family for cardiovascular or renal disease. NEUREX
warrants that on the date of execution of this Agreement it is not in the
process of negotiating the licensing-in or the acquisition of third parties'
rights in the Territory on developments which have reached Phase I clinical
trials, in connection with the aforesaid additional formulations, indications,
prodrugs, and/or compound family.
Now, therefore, in consideration of the premises set forth above and made a part
hereof and the mutual promises hereinafter contained, and intending to be
legally bound, the parties hereto agree as follows
ARTICLE 1 - DEFINITION
As used in this Agreement, the following terms have the meanings indicated.
Affiliate means when referring to a party, any person, corporation or
entity which directly or indirectly controls, is controlled by or
under a common control with such party. For the purpose of this
definition, control shall be deemed to exist if there exists
ownership of more than 50 % of the share capital and/or the
voting rights of such a person, corporation or entity.
Compound means the chemical compound known as SK&F 82526 or Fenoldopam,
whose more specific chemical name is
6-chloro-2,3,4,5-tetrahydro-1-(p-hydroxyphenyl
-1H-3-benzazepine-7,8-diol methane sulfonate for intravenous
infusion, including the corresponding amine, other acid addition
salts, hydrates, solvates, polymorphs, but specifically excluding
Fenoldopam prodrugs, and shall include compositions comprising
such compound, the corresponding amine, other acid addition
salts, hydrates, solvates, polymorphs but specifically excluding
Fenoldopam prodrugs.
Effective Date means that date as of which this Agreement is effective and
shall be the date of execution of this Agreement first written
above.
Marketing Authorization Files means those clinical, pharmacological, and
toxicological study reports, and all other reports and documents
that are required to obtain the Marketing Authorization as
defined hereunder of the Product as defined hereinafter, in the
United States of America, Belgium, Germany, Italy, the
Netherlands, Portugal, Spain, and Switzerland.
Marketing Authorization(s) means the pharmacological, toxicological,
clinical, and Product price and reimbursement, approvals and
decisions from the relevant regulatory authorities in each
country of the Territory, that are required in such country for
importation, promotion, distribution and sale of the Product into
the Territory.
Net Turnover means the gross amount of sales achieved by SCRAS or any
of its Affiliates or sublicensees through the sale of the Product
in the Territory to third parties other than to Affiliates or
sublicensees in the Territory, less all sales, value added,
customs, taxes and duties, trade discounts, and shipping costs.
New Therapeutical Indications means the acute renal failure and
retrogenic nephrotoxicity treatment which NEUREX is considering
developing as Product new therapeutical indications, according to
the NEUREX Program as defined hereunder.
NEUREX Program means the feasibility study and development program that
NEUREX is considering undertaking, relating to the New
Therapeutical Indications, the summary of which are described in
Appendix D attached hereto.
Patents means all patents granted in the Territory as defined
hereinafter, and patent applications held in the Territory, which
are or become owned by SmithKline Xxxxxxx Co. or NEUREX, or to
which SmithKline Xxxxxxx Co. or NEUREX otherwise has, now or in
the future, the right to grant licenses or sublicenses, which
generically or specifically claim the Compound. Included within
the definition of Patents are all continuations,
continuations-in-part, divisions, patents of addition, reissues,
renewals, or extensions thereof, and all supplementary protection
certificates, valid or having legal effects in the Territory. The
current list of patent applications and granted patents
encompassed within Patents is set forth in Appendix A attached
hereto. The supplementary protection certificates referred to
hereabove are meant to include all such right based upon a patent
that excludes others from making, using or selling the Compound.
Product means the pharmaceutical specialty developed by NEUREX containing
the Compound, in intravenous form and indicated for blood
pressure control in operating and post-operating rooms, as well
as hypertension crisis emergency treatment.
Product Net Price means the Product selling price by SCRAS' (or by any of
SCRAS' Affiliate or sublicensees) to third parties, before
customs and value added taxes, and transportation costs to said
third parties, and after deduction of trade discounts.
Product Transfer Price means the Product selling price invoiced by NEUREX
or by any third party designated by NEUREX, to SCRAS (or to any
of SCRAS' Affiliates or sublicensees), before value added taxes.
Gross Margin means the Product Net Price minus (i) the Product Transfer
Price, (ii) SCRAS' (or any of SCRAS' Affiliates or sublicensees')
direct costs incurred in bringing the Product to an inventory and
saleable stage, and (iii) import customs taxes.
Specifications means the specifications with respect to the formulation, quality
control, packaging, container description, storage instructions,
or any other features relating to the Compound and the Product
that are described in Appendix B attached hereto.
Territory means the world excluding Japan and all countries in the
Americas. Trademark means the trademark Corlopam(R) as registered
in those countries listed in Appendix C attached hereto and as
further registered in the Territory pursuant to Article 4 of this
Agreement.
ARTICLE 2 - GRANT OF RIGHTS
2.1 Subject to the terms of this Agreement, NEUREX hereby grants to SCRAS an
exclusive sublicense under the Patents, the Marketing Authorization File,
as well as the existing and future Marketing Authorizations, and an
exclusive license under the Trademark, all of which to pack, label, sell,
distribute, and promote the Product in the Territory under the Trademark
or under any of SCRAS' or its Affiliates' name or trademarks.
SCRAS agrees that it shall never gain any title in the Patents, the
Trademark, the Marketing Authorization File and/or the Marketing
Authorizations, which are and shall all remain NEUREX and/or SmithKline
Xxxxxxx Co. sole property.
2.2 SCRAS shall be entitled to grant further sublicenses in whole or in part,
to any Affiliate of SCRAS, subject to prior written notice to NEUREX.
SCRAS shall not be entitled to grant further sublicenses in whole or in
part to any other third parties, without first obtaining the express
prior written approval from NEUREX which approval shall not be
unreasonably withheld.
ARTICLE 3 - MARKETING AUTHORIZATIONS TRANSFER AND FILING
3.1 Forthwith as of the Effective Date, NEUREX shall undertake at no cost for
SCRAS, all proceedings with the relevant national regulatory authorities,
in order to transfer into the name of SCRAS or of any of its Affiliates
or sublicensees indicated by SCRAS, all pending Marketing Authorizations
applications in the Territory such as those pending applications in
Belgium, the Netherlands, and Italy, in order to enable SCRAS or its
Affiliates or sublicensees, to pursue in its own name the relevant filing
proceedings.
SCRAS shall provide NEUREX with reports on a quarter basis concerning
SCRAS' activities to obtain Marketing Authorizations. SCRAS and NEUREX
will hold monthly telephone conferences with respect to said SCRAS'
activities.
3.2 SCRAS shall file in its own name or in the name of any of its Affiliates
or sublicensees, for the relevant Marketing Authorizations in countries
of the Territory to be freely determined by SCRAS, following the filing
pace that SCRAS shall deem appropriate, except for the Marketing
Authorization filing in France and Germany which SCRAS shall undertake as
a priority.
NEUREX shall forward to SCRAS forthwith as from the Effective Date, the
whole of the Marketing Authorization Files, as well as all relevant
information necessary to enable SCRAS to complete the Product Marketing
Authorization filings and the Product packing and labeling in finished
form in conformity with the Marketing Authorization Files.
NEUREX shall give technical and administrative assistance to SCRAS as
SCRAS may require to progress the registration, packing, and labeling of
the Product. Such assistance as SCRAS may reasonably require shall be
given free of charge to SCRAS for countries where advanced royalty
payments are to be made by SCRAS under this Agreement. All technical and
administrative assistance that SCRAS may require from NEUREX in
connection with countries in the Territory other than the aforesaid,
shall be charged by NEUREX to SCRAS up to an amount to be reasonably
agreed upon by the parties. All out-of-pocket expenses incurred by NEUREX
in the provision of the technical assistance referred to in this Article
3.2 such as traveling, transportation, and lodging expenses, shall be
reimbursed by SCRAS after SCRAS' receipt of an invoice therefore.
Should any further clinical, pharmacological, toxicological, or other
scientific, studies be required by regulatory authorities in the
Territory in connection with obtaining Marketing Authorizations, NEUREX
shall fund all such studies up to an amount not exceeding one million
U.S. Dollars (USD 1,000,000) provided that these studies are required for
submission and complete approval of a Marketing Authorization. Such
NEUREX' contribution shall be allocated to one or several studies with
respect to Marketing Authorization filing and proceedings in one or
several countries of the Territory, such country (or countries) and
corresponding studies to be elected by SCRAS. SCRAS shall conduct all
such required studies with NEUREX reasonable technical and administrative
assistance. NEUREX shall provide SCRAS with enough quantities of Product
free of charge in order for SCRAS conducting all such required studies.
The USD 1,000,000 NEUREX' contribution shall exclude the value of such
Product free units.
3.3 NEUREX may withdraw those member countries of the European Union from the
scope of this Agreement, where (i) no Marketing Authorization will have
been granted to SCRAS, at the expiration of a five-year period as from
the Effective Date, or (ii) SCRAS would not have launched the Product
within nine month after the relevant Marketing Authorization is granted.
NEUREX may withdraw those countries other than the member countries of
the European Union from the scope of this Agreement, where:
(i) no Marketing Authorization will have been granted to SCRAS, at
the expiration of a four-year period as from filing for the
relevant Marketing Authorization; or
(ii) SCRAS would not have launched the Product at the expiration
of a nine-month period after the relevant Marketing Authorization
is obtained; or
(iii) SCRAS will not have submitted requisite Marketing
Authorization applications within eighteen (18) months as from
obtaining the Product Marketing Authorization (a) in the United
Kingdom for those countries listed in Xxxxxxxx X0 attached hereto,
(b) in France for those countries listed in Xxxxxxxx X0 attached
hereto, (c) in the United States of America for those countries
listed in Xxxxxxxx X0 attached hereto, in which last case NEUREX
shall provide SCRAS with the relevant Marketing Authorization file
formatted as requested by SCRAS for application in each such
country, and, subject to SCRAS providing NEUREX within six (6)
months as from issue of the Product Marketing Authorization in the
United States with a list of planned filing dates for the
countries in Xxxxxxxx X0, the eighteen-month delay shall be
extended on a country by country basis by the period of time
necessary for NEUREX to provide SCRAS with the said formatted
Marketing Authorization files.
NEUREX may enforce the provisions identified as (i) in the first two
paragraphs of this Article 3.3, provided however that NEUREX brings
evidence of SCRAS not making reasonable efforts to obtain the relevant
Marketing Authorizations.
The status of member country of the European Union shall be determined
for each country of the Territory, at the date of expiration of the
relevant time limit in consideration of which NEUREX intends to exercise
its right of country withdrawal pursuant to this Article 3.3.
3.4 SCRAS shall be free to entrust with the packing, labeling, physical
distribution and/or promotion of the Product in a finished form, any
Affiliate or third party on behalf of SCRAS or any Affiliate, subject in
this last case to prior notice to NEUREX of the identity of said third
party.
3.5 NEUREX shall, forthwith as of the Effective Date, supply SCRAS with
copies of NEUREX', or NEUREX' other licensee's or distributor's,
promotional literature and existing sales training materials related to
the Product for use by SCRAS in developing promotional literature and
sales training materials for the Product in the Territory.
SCRAS shall develop, print and use, at its own costs, promotional
materials in connection with the sale of the Product in the Territory.
SCRAS agrees that all such promotional materials shall be in line with
NEUREX' promotional materials. Should SCRAS want to make a major
modification to the medical information to be contained in the
promotional materials, the parties would meet without delay to agree on
the terms to be communicated by such promotional materials. The parties
agree that the copyrights, design, and artwork related to such newly
defined communication shall be proprietary and confidential to SCRAS and
that NEUREX may only use the same with the prior written consent of
SCRAS.
3.6 During the term of this Agreement, each party shall promptly inform the
other party of any information that it obtains or develops regarding the
utility and safety of the Product. Al1 information received on adverse
experiences associated with the use of the Product are to be reported by
one party to the other as follows:
(i) fatal or life threatening adverse experiences to be reported
within one business day of receipt;
(ii) all other serious adverse experiences to be reported within
two business days of receipt;
(iii) a summary of all adverse experiences to be reported on a
quarterly basis.
The above requirements apply to both commercialized Product as well as
the use of the Product in clinical trials, and to all adverse experiences
whether or not considered causally related to the Product.
ARTICLE 4 - TRADEMARK: WARRANTIES - PACKAGING
4.1 NEUREX warrants that SmithKline Xxxxxxx Co. has duly transferred to
NEUREX its full ownership of the Trademark and to be at present the full
and sole proprietor of the Trademark. NEUREX warrants that the Trademark
is registered, valid and duly opposable in those countries listed in
Appendix C attached hereto and that at the Effective Date, no
infringement claim, nor legal action or threat whatsoever, is pending
against the existence, validity, or ownership of the Trademark. NEUREX
warrants that to the best of its knowledge, the use of the Trademark will
not infringe any trademark or other similar rights or any rights of any
third party.
Upon request from SCRAS, NEUREX agrees to use its reasonable efforts to
obtain at its own costs and without delay, the registration of the
Trademark in those countries of the Territory where SCRAS requires the
Trademark be registered, but no later than upon the date on which SCRAS
intends to launch the Product in the corresponding countries.
NEUREX agrees to sign all documents necessary to register SCRAS as a
registered user of the Trademark when so reasonably required by SCRAS for
any country in the Territory.
4.2 NEUREX commits itself to maintain any Trademark under registration or
registered in the Territory as of the Effective Date or registered in the
Territory pursuant to article 4.1 hereabove, and to undertake all related
proceedings at its own costs, such as but without limitation, renewal
proceedings.
4.3 Except as provided hereunder, SCRAS shall have no obligation related to
the Trademark presentation as far as the Product packaging and labeling,
and the promotional materials are concerned. The parties agree that the
packaging of the Product shall mention SCRAS (or any of its Affiliates)
as the exploiting laboratory in each country of the Territory.
SCRAS has no obligation to market the Product under the Trademark, and
may freely decide to market the Product under any trademark which SCRAS
is entitled to use, under SCRAS' or any of its Affiliate's own name, or
under the Product generic name, provided however in such cases that SCRAS
shall bear all costs associated with maintaining the Trademark in those
countries where SCRAS elects not to sell the Product under the Trademark.
SCRAS shall be entitled to modify the Marketing Authorizations in the
Territory accordingly.
SCRAS agrees that it shall comply with the following:
(a) SCRAS shall not have the right to use any proprietary brand
name or trademark along with the Trademark other than as permitted
in writing by NEUREX.
(b) SCRAS shall not have the right to use a Trademark as part of
any corporate, partnership or other entity name or other product
name.
(c) SCRAS shall not actively offer for sale outside the Territory
any product, compound, item, or drug (including the Product) that
is identified by the Trademark during the terms of this Agreement.
ARTICLE 5 - PATENTS WARRANTIES
5.1 NEUREX warrants that the Patents are the sole ownership of SmithKline
Xxxxxxx Co., are valid, existing, and opposable to third parties in those
countries of the Territory where granted as appearing in Appendix A
hereto, and that at the Effective Date, no infringement claim, nor legal
action or threat whatsoever is pending against the existence, validity,
or ownership of the Patents. NEUREX warrants that to the best of its
knowledge, the use of any of the Patents will not infringe any patent or
other similar rights or any rights of any third party.
5.2 NEUREX commits itself to fully maintain the Patents in the Territory, and
shall be responsible for all Patents matters at NEUREX' expense.
5.3 NEUREX declares to be vested with the necessary powers of attorney and
shall have the obligation, to seek extensions of the terms of the Patents
and to seek to obtain Supplementary Protection Certificates throughout
the Territory.
ARTICLE 6 - DEFENSE OF RIGHTS
6.1 Each party shall immediately inform the other as soon as possible of any
infringement or alleged infringement of either of the Trademark or the
Patents by a third party having effect in the Territory, and of any claim
made by a third party that such third party's intellectual property
rights are infringed by either of the Trademark or the Patents.
6.2 Prosecution of infringing acts by third parties and defense of claims of
infringement by third parties relating to the Trademark or the Patents,
shall be the sole responsibility of NEUREX.
NEUREX declares and warrants to be vested with all the necessary powers
of attorney from SmithKline Xxxxxxx Co. as far as the Patents are
concerned.
NEUREX shall promptly take, at its own expense, all appropriate actions
against, and litigate, settle or compromise, any such infringing acts or
claims of infringement so that SCRAS may continue to freely benefit from
the rights granted hereunder. SCRAS agrees to provide NEUREX all
documents reasonably requested by NEUREX necessary to prosecute an
infringement of either of the Trademark or the Patents, to defend a claim
of infringement made by a third party against either of the Trademark or
the Patents.
NEUREX hereby agrees to indemnify and hold SCRAS harmless from and
against any claim, expenses and/or damages (including SCRAS reasonable
attorney's fees) incurred or suffered by SCRAS as a result of such
claims.
ARTICLE 7 - ROYALTIES
7.1 In consideration of the licenses granted herein and the release of the
Marketing Authorization Files, SCRAS agrees to pay to NEUREX a lump sum
of two million United States Dollars (USD 2,000,000) according to the
following timetable, and subject to receipt by SCRAS of the corresponding
invoices:
U.S. Dollars one million (USD 1,000,000) upon execution of this
Agreement,
U.S. Dollars two hundred and fifty thousand (USD 250,000) upon
obtaining the Product Marketing Authorization in each of France,
Germany, the United Kingdom, and Italy, provided the Product selling
and reimbursement price fixed in each such country by the relevant
authorities be based on a one-patient twenty-four (24) hour course of
therapy and enables SCRAS to invoice U.S. Dollars [*] per such course
of therapy.
The product selling and reimbursement price as hereabove fixed is
hereinafter referred to as the Product Minimum Price.
7.2 SCRAS shall pay to NEUREX in U.S. Dollars on a semester basis, a royalty of
[*] of the Net Turnover.
The royalty rate shall amount to [*] of the Net Turnover, for the portion
of the Net Turnover exceeding U.S. Dollars [*] during each one calendar
year, in the Territory.
When marketing the Product in the Territory, SCRAS shall forward to
NEUREX, within thirty (30) days after the end of each calendar semester,
a report showing the gross sales and Net Turnover of the Product in the
local currency, and the Net Turnover in U.S. Dollars, on a
country-by-country basis. For the purpose of the hereby Article 7.2, the
U.S. Dollar exchange rate used to reckon the Net Turnover country by
country, shall be the exchange rate in effect on the last business day of
the corresponding calendar semester, as published in the Wall Street
Journal (or other reputable daily business newspaper if the exchange
rates ever cease to be published in the Wall Street Journal).
7.3 SCRAS shall make advanced royalty payments to NEUREX according to the
following timetable:
U.S.D. five hundred thousand (USD 500,000) upon obtaining the Product
Marketing Authorization in each of France, Germany, the United Kingdom,
Italy, and Spain, and in either Belgium or the Netherlands (whichever is
earliest in the latter two), provided the Marketing Authorization be
issued in each such country with the Product Minimum Price.
It is agreed by the parties that such advanced royalty payments shall be
credited against thirty per cent (30%) of all royalties due by SCRAS to
NEUREX in each calendar year pursuant to Article 7.2 of this Agreement,
until all advanced royalty payments have been entirely credited.
7.4
7.4.1 Should the Product Marketing Authorization be issued in either France,
Germany, the United Kingdom, Italy, Spain, Belgium, or the Netherlands,
with a Product selling and reimbursement price inferior to the Product
Minimum Price, no lump sum as referred to in Article 7.1, nor advanced
royalty payment as referred to in Article 7.3, shall be due by SCRAS for
the corresponding country(ies).
7.4.2 Should no Marketing Authorization or only one or two Marketing
Authorizations, be issued with the Product Minimum Price among France,
Germany, the United Kingdom, and Italy, within three years as from the
Effective Date, SCRAS shall have the option to terminate this Agreement
upon notice served to NEUREX within six months as from expiration of said
three year period, in which case NEUREX shall refund to SCRAS 100% of all
lump sums and advanced royalties paid by SCRAS as from the Effective Date
pursuant to Articles 7.1 and 7.3 of this Agreement, after deduction of
the advanced royalties which would have been credited against royalties
due by SCRAS during said three-year period.
Should SCRAS notify NEUREX of its intention to waive said option, or
should SCRAS fail to exercise said option within six months as from
expiration of the three-year period, this Agreement shall continue in
full force and effect, except that no further lump-sum nor advanced
royalties shall be due by SCRAS to NEUREX when obtaining Marketing
Authorizations in France, Germany, Italy, the United Kingdom, Spain,
Belgium, and the Netherlands, whether such Marketing Authorizations are
obtained with or without the Product Minimum Price.
7.4.3 Should three or four Marketing Authorizations be issued with the Product
Minimum Price among France, Germany, the United Kingdom, and Italy,
within three years as from the Effective Date, Article 7.4.2 shall not
apply.
7.5 The amounts to be paid by SCRAS to NEUREX under Articles 7.1, 7.2, and
7.3 of this Agreement, shall be due and payable within 120 days as from
receipt by SCRAS of the corresponding invoices issued in accordance with
the relevant contractual provisions. Such payments shall be made by wire
transfer (net of bank charges) to an account designated by NEUREX on
NEUREX' invoices.
All payments made by SCRAS to NEUREX under Article 7 of this Agreement
shall be received by NEUREX net of all taxes or deductions that may be
levied by the relevant authorities and consequently withheld by SCRAS
from all such payments. SCRAS shall provide NEUREX with the corresponding
receipts and tax payment justifications in order for NEUREX to apply for
the relevant tax credits.
SCRAS shall provide NEUREX and any representatives of NEUREX with access
during normal business hours with five working days advance notice, to
business records relating to Net Turnover and the calculation of
royalties due to NEUREX.
ARTICLE 8 - SUPPLY OF PRODUCT
8.1 During the whole duration of this Agreement, NEUREX shall supply SCRAS
with all SCRAS' promotional and commercial requirements for the Product.
Except as provided in this Article 8.1, in Article 11, and in Article 13
of this Agreement, and except for those countries of the Territory which
shall have been specifically withdrawn from the scope of this Agreement
pursuant to Article 3.3, SCRAS shall exclusively purchase the Product
from NEUREX, and NEUREX shall not directly or indirectly supply any third
party with the Product nor the Compound for final use or sale in the
Territory in whatever form, in the field of pharmaceutical specialties.
NEUREX shall supply the Product as bulk ampoules in the form,
presentation, and dosage as described in Appendix B. NEUREX shall supply
ampoules to SCRAS packed and labeled in accordance with regulatory
requirements for ampoules bulk export outside the U.S.A. and/or outside
other countries where NEUREX designated manufacturers are located, and
import in France.
NEUREX will identify a second source for the manufacture and sale to
SCRAS, of the Compound and the Product substance, in full compliance with
the conditions set forth in this Agreement. If NEUREX has not identified
a second source within [*] years as from the Effective Date, or before
there is less than [*] years of Compound and Product substance inventory,
whichever occurs first, then NEUREX will provide SCRAS with synthesis
information and know-how free of charge to enable SCRAS to manufacture
the Compound and the Product substance, and will grant SCRAS a
royalty-free exclusive license in the Territory under all patents
proprietary or licensed to NEUREX which are necessary to manufacture the
Compound and the Product substance, including but not limited to patents
claiming a process for manufacturing the Compound or the Product
substance, an intermediate used in such process, and/or any improvements
in connection thereof. The aforesaid royalty-free exclusive patent
license shall provide for patent warranties and defense provisions no
less favourable than as set out in Articles 5 and 6 of this Agreement, in
connection with the manufacturing and sale by SCRAS of the Compound
and/or the Product Substance. NEUREX hereby warrants that the aforesaid
proprietary or licensed patents to NEUREX, will provide SCRAS sufficient
and complete rights to manufacture the Compound and the Product
substance.
8.2 NEUREX warrants that the Compound and all lots of Product, will be
manufactured in accordance with applicable Good Manufacturing Practice
requirements, that adequate quality test control procedures are observed
and accurate records kept of any test and results undertaken pursuant to
any such quality control procedures.
NEUREX warrants that the Compound and all quantities of Product delivered
to SCRAS pursuant to this Agreement meet the Specifications. Any
amendments to the Specifications must be agreed in writing between the
parties.
NEUREX shall with each delivery of Product to SCRAS supply a certificate
of analysis related to each batch delivered, incorporating an active
ingredient test and a signed statement that each of such batch conforms
with the Specifications and accords with the relevant Marketing
Authorization, that the Compound and the Product meet all stability
requirements, that the manufacturing procedures have been checked in
conformity with GMP requirements.
NEUREX shall further deliver to SCRAS all information related to the
manufacture and control methods in respect of the Compound and the
Product so as to enable SCRAS to perform all necessary Compound and
Product testing as may be required by applicable laws, before packing,
labeling, and sale in the Territory. NEUREX agrees to provide SCRAS with
reasonable technical assistance free of charge, should supplementary
heavy Product or Compound controls be required by applicable laws for
sale by SCRAS in the Territory.
8.3 In the case of non conformity to the Specifications of any quantity of
Product delivered to SCRAS, NEUREX shall take back, at its expense, the
quantities concerned and shall replace them promptly, so that SCRAS' sale
agenda be not disturbed.
Any dispute between the parties regarding the conformity to the
Specifications of any quantity of the Product delivered hereunder shall
be referred to an expert, jointly appointed by the parties within thirty
days from the receipt by NEUREX of the notice of claim of SCRAS. The
opinion of such expert shall be definitive and binding upon the parties.
The cost of such independent advice shall be equally shared between the
parties, unless the expert otherwise decide. Should the parties not agree
on the appointment of such expert, the most diligent party shall require
the President of the commercial court of its residence to proceed to such
appointment, which shall be binding upon the parties.
8.4 Within six months of the first anticipated Product launch in the
Territory and every following calendar year, on December 15 at the
latest, SCRAS shall provide NEUREX with written forecasts of the
quantities of Product on a country by country basis, which it will
require during the following calendar year so that NEUREX may plan its
production. The forecasts shall set forth the dates at which deliveries
shall be made. Forecasts shall not be binding upon SCRAS.
SCRAS shall place contractually binding orders for Product to NEUREX
giving no less than ninety (90) days notice of delivery. Each order shall
state the date and location where delivery shall be made. NEUREX shall
supply SCRAS no later than fifteen (15) days after the delivery dates
required by SCRAS. Should orders exceed one hundred twenty percent (120%)
of the forecasts, NEUREX agrees to use its reasonable endeavours to meet
SCRAS' requested quantities of Product and delivery date.
8.5. The Product Transfer Price shall be CPT place of delivery mentioned in
SCRAS' orders (Incoterms 1990).
All Product so delivered hereunder shall be invoiced by NEUREX at the CPT
Product Transfer Price per unit which shall be fixed by NEUREX so as to
procure SCRAS during the whole duration of this Agreement, a minimum of
[*] Gross Margin provided that at no time shall the Product Transfer
Price be less than NEUREX' cost of goods to manufacture the Product. In
order to procure SCRAS a minimum of [*] Gross Margin, NEUREX shall adjust
the Product Transfer Price (i) every two years, and (ii) at the beginning
of any calendar quarter following any given calendar quarter during which
the Gross Margin fell below [*], provided that at no time shall the
Product Transfer Price be less than NEUREX' cost of goods to manufacture
the Product.
If at any time during the first five years as from SCRAS first obtaining
the Product Marketing Authorization in the Territory, NEUREX is not able
to adapt the Product Transfer Price in order to provide SCRAS with the
aforesaid [*] minimum Gross Margin, due to the Product Transfer Price
being equal or inferior to NEUREX' costs of goods to manufacture the
Product, NEUREX shall procure SCRAS with the [*] minimum Gross Margin by
reducing the royalty rates fixed in article 7.2 of this Agreement by one
(1) point for every one (1) point inferior to the [*] Gross Margin, with
a maximum of ten-point royalty reduction (or should the case be pursuant
to Article 7.2, second paragraph of this Agreement, with a maximum of
twelve-point royalty reduction). After expiration of said five-year
period, NEUREX royalty rate reductions as set out hereabove shall be at
NEUREX' option. All such royalties adjustments and reimbursements shall
be made at the end of each calendar year.
Should SCRAS' Gross Margin be inferior to [*] at any time after
expiration of the five-year period referred to in the previous paragraph,
NEUREX shall provide SCRAS, if SCRAS so requests, with synthesis
information and know-how free of charge to enable SCRAS to manufacture
the Compound and the Product substance, and will grant SCRAS a
royalty-free exclusive license in the Territory under all patents
proprietary or licensed to NEUREX which are necessary to manufacture the
Compound and the Product substance, including but not limited to patents
claiming a process for manufacturing the Compound or the Product
substance, an intermediate used in such process, and/or any improvements
in connection thereof. The aforesaid royalty-free exclusive patent
license shall provide for patent warranties and defense provisions no
less favourable than as set out in Articles 5 and 6 of this Agreement, in
connection with the manufacturing and sale by SCRAS of the Compound
and/or the Product Substance. NEUREX hereby warrants that the aforesaid
proprietary or licensed patents to NEUREX, will provide SCRAS sufficient
and complete rights to manufacture the Compound and the Product
substance.
8.6 All payments to be made by SCRAS pursuant to this Article 8 shall be made
in U.S. Dollars by cheque or wire transfer (net of bank charges) to an
account designated by NEUREX on NEUREX invoice within 60 days of the date
of receipt of the corresponding invoice.
SCRAS shall be entitled to withhold payment by reason of a dispute as to
the conformity of any quantity of the Product or Compound to the
Specifications.
8.7 Without prejudice to the provisions of Article 8.5 hereabove, at the
beginning of each calendar year during the term of this Agreement, NEUREX
shall provide SCRAS with free quantities of Product, reckoned as set out
hereunder on a country by country basis exclusively for SCRAS conducting
promotional activities in the Territory:
For the calendar year following the year during which the Product is
launched in the corresponding country: ten per cent (10%) of the
forecasted Product sales in such country for said calendar year;
For the second calendar year following the year during which the
Product is launched in the corresponding country: five per cent (5%) of
the forecasted Product sales in such country for said calendar year.
For the third calendar year following the year during which the
Product is launched in the corresponding country: five per cent (5%) of
the forecasted Product sales in such country for said calendar year.
At the end of each calendar year, NEUREX shall make all necessary
invoicing or credit adjustments on a country by country basis for
quantities of free Products provided to SCRAS, depending on whether the
Product sales realized during the corresponding calendar year in the
corresponding country exceeded or where inferior to, the forecasted
Product sales. SCRAS shall provide documentation for Product sales within
each country in the Territory where free Product is provided.
ARTICLE 9 - PRODUCT LIABILITY - INDEMNIFICATION
9.1 NEUREX agrees to indemnify and hold harmless SCRAS from any and all
claims, damages and expenses (including reasonable attorneys' fees) which
may be sustained or suffered by SCRAS by virtue of death or injury
resulting from administration or use of any of the Compound or the
Product, arising from (i) the development, manufacturing, defaults, or
the handling and/or storage of the Compound and/or the Product by NEUREX
or SmithKline Xxxxxxx Co., or (ii) omissions or defaults in the
instructions for use of the Product prescribed by NEUREX, or (iii) a
default from NEUREX in making those notifications referred to in Article
3.5 of this Agreement.
SCRAS hereby agrees to indemnify and hold NEUREX harmless from any and
all claims, damages and expenses (including reasonable attorneys' fees)
which may be suffered or sustained by NEUREX by virtue of death or injury
resulting from administration or use of the Product, which arise solely
from the packing, labeling, handling, storage, distribution and/or
promotion of the Product by SCRAS, its Affiliates, or its sublicensees,
and which are not the result of NEUREX fault or negligence.
9.2 The Party requested to provide indemnification pursuant to this Article 9
(the Indemnifying Party) as to a particular claim of a third party shall
have the sole control of the defense, litigation or settlement of such
claim and shall have the right to elect the legal counsel who shall
assist the Parties with respect to such claim. The Indemnifying Party
shall be excused from its obligation to defend and hold harmless the
other Party with respect to any such claim, should the other Party:
(i) fail to give immediate notice to the Indemnifying Party of any such
claim; or
(ii) act to the detriment of such claim, or of the Indemnifying Party's
efforts to effect a compromise or settlement with respect to such claim,
or make any admission or take any action regarding such claim without the
Indemnifying Party's prior consent; or
(iii) obtain release or indemnification from another party from such claim, but
only to the extent of such other release or indemnification.
Notwithstanding any of the aforesaid, the non indemnifying party shall be
entitled to undertake all protective measures or actions that this party
may deem appropriate in order to secure its factual or legal position, or
to prevent the situation from aggravating.
9.3 The provisions of this Article 9 shall survive the earlier
termination or the expiration of this Agreement.
ARTICLE 10 - PRODUCT RECALL
10.1 In the event either party has reason to believe that one or more lots of
any Product supplied hereunder should be recalled or withdrawn from
distribution such party shall immediately inform the other in writing.
To the extent permitted by circumstances, the parties will confer before
initiating any recall but the decision as to whether or not to initiate a
recall in the Territory shall be solely SCRAS'. Except as otherwise
provided herein, the costs of any recall will be allocated between the
parties in accordance with the parties' respective indemnification
obligations set forth in Article 9.1 herein.
10.2 If such recall is required because of failure of the Compound or the
Product to conform to warranty as provided in Article 8 of this Agreement
or for any reason other than that mentioned in article 10.3 below, then
such recall may be conducted immediately by SCRAS in the Territory if
SCRAS so requests. The costs and expenses of such recall shall be
reimbursed by NEUREX to SCRAS.
10.3 If such recall is required because of a negligent act or omission by
SCRAS in the packing, labeling, handling, storage, distribution or
promotion of the Product, then such recall shall be conducted by SCRAS at
SCRAS' sole costs and expenses, and SCRAS shall not be entitled to any
credit, replacement or refund for the Product so recalled.
10.4 If such recall is required because of a joint act or omission of the
parties, SCRAS shall conduct the recall immediately and the parties shall
negotiate in good faith an appropriate allocation of the costs and
expenses of the recall.
10.6 The provisions of this Article 10 shall survive the earlier termination
or the expiration of this Agreement.
ARTICLE 11 - RESERVED RIGHTS
11.1 Exclusive option rights on NEUREX Program:
When NEUREX reaches to the preparation of Clinical studies Phase III in
connection with the NEUREX Program, SCRAS shall have the option to
participate on an exclusive basis in the NEUREX Program and consequently
be granted the corresponding exclusive distribution and promotional
rights in the Territory. SCRAS shall exercise said option by paying to
NEUREX U.S. Dollars five hundred thousand (USD 500,000) upon acceptance
by SCRAS of the Phase III Protocol (which shall have been submitted to
SCRAS and mutually discussed and agreed upon in good faith between SCRAS
and NEUREX). NEUREX undertakes to make all modifications to the protocol
reasonably required by SCRAS.
When the relevant Marketing Authorization is obtained in at least two
countries among France, Germany, the United Kingdom, and Italy, SCRAS
shall pay to NEUREX U.S. Dollars two million (USD 2,000,000).
11.2 NEUREX shall provide SCRAS with all information and marketing
authorization files related to research and developments made directly by
NEUREX, or through its Affiliates or licensees (in which last case
provided NEUREX has rights to said information and files), in connection
with (i) all additional indications of the Compound, (ii) all intravenous
formulations of the Compound, and/or (iii) all chemical improvements or
derivatives of the Compound excluding prodrugs of the Compound developed
for cardiovascular or renal indications, all of which for the purpose of
SCRAS filing for the relevant marketing authorization or extensions in
the Territory. Should the relevant authorities in the Territory issue the
relevant Marketing Authorizations or extensions without requiring any
complementary development and/or costs, NEUREX shall grant to SCRAS the
corresponding exclusive distribution and promotional rights free of
charge in the Territory.
Should the relevant authorities in the Territory require that
complementary development or costs be undertaken for the purpose of
issuing the relevant Marketing Authorizations or extensions, NEUREX and
SCRAS shall discuss in good faith the conditions under which SCRAS and
NEUREX would undertake and finance such developments and/or costs in
order for NEUREX to grant to SCRAS the relevant exclusive distribution
and promotional rights in the Territory.
NEUREX shall negotiate in good faith to grant SCRAS an exclusive option
to participate in all developments of prodrugs of the Compound for
cardiovascular or renal indications. NEUREX shall offer said options to
SCRAS upon completion of the relevant Phase II clinical trials. NEUREX
and SCRAS shall discuss in good faith the conditions under which NEUREX
and SCRAS shall undertake and finance such developments, and the
financial conditions under which NEUREX shall grant to SCRAS the
corresponding rights in the Territory.
NEUREX shall present to and discuss in good faith with SCRAS development
arrangements and opportunities, as well as marketing arrangements and
opportunities in the Territory for Prodrugs of the Compound for chronic
indications and any indication not covered by the previous paragraph,
which NEUREX is considering developing and/or marketing.
11.3 Should SCRAS reject the options referred to in Articles 11.1 and 11.2 -
first paragraph, after NEUREX presented them to SCRAS, the obligations of
the parties under said Articles 11.1 and 11.2 - first paragraph shall
cease.
After NEUREX has presented to SCRAS the options referred to in Article
11.2 - second, third and fourth paragraphs, and discussions have been
held, and if no agreement is reached between the parties, the obligations
under Article 11.2 - second, third and fourth paragraphs shall cease.
ARTICLE 12 - CONFIDENTIALITY
12.1 Except as provided in this Agreement for Product promotional activities
by SCRAS and Marketing Authorizations filings in the Territory, each
party shall keep secret and confidential for the term of this Agreement
all documents and information communicated to it by the other party on a
confidential basis relating to the Compound, the Product, or any trade or
technical secret related to the disclosing party. Each party further
agrees that for the same period it will not, without the consent of the
other party, use confidential information for any purpose other than
carrying out this Agreement, provided however if either party is
requested or required by any law, regulation, or similar authority to
disclose any confidential document or information, such party may do so
provided that such party (i) undertakes all appropriate measures in order
to protect the secrecy of all such confidential document or information,
prior to their disclosure to any authority, and (ii) inform the other
party of all such measures and disclosures.
12.2 Each party shall have no obligation to maintain the confidentiality of
any specific item of information that is (i) in the public domain or
otherwise available to the public without restriction on its use, (ii)
publicly known through no fault of the receiving party or its employees,
(iii) available to the receiving party or already received at the time of
disclosure, without any obligation of confidentiality from a person not
having a confidential relationship with the disclosing party or its
Affiliates.
12.3 Nothing herein shall be construed as preventing each party from
disclosing any information received from the other party, to an
Affiliate, or to any of SCRAS' future sublicensee or distributor related
to the purpose of this Agreement, provided such Affiliate, sublicensee or
distributor has undertaken a similar obligation of confidentiality with
respect to the confidential information.
ARTICLE 13 - TERM AND TERMINATION
13.1 Royalty obligations under Article 7.2 shall expire on a country per
country basis, upon the earlier of:
(i) ten (10) years from the date the first Marketing Authorization is
granted in the corresponding country;
(ii) the introduction in the corresponding country of a competing
product containing the Compound, as from the date the competing
product's marketing authorization is granted, or such competing
product is launched, whichever is earlier;
(iii) the introduction in the corresponding country of any
pharmaceutical product constituting or resulting from breach of
any of the warranties appearing in the fifth paragraph of the
preamble of this Agreement.
Upon expiry of royalty obligations pursuant to this Article 13. 1, SCRAS
shall give preference to NEUREX as the Product supplier, unless third
parties offer the Compound or the Product for sale to SCRAS providing
SCRAS with over ten percent (10%) increase of SCRAS' gross margin (after
deduction of all costs of goods) on the sale of the Product in the
Territory, in which case SCRAS shall be free to purchase the Product from
such third parties.
13.2 Unless otherwise terminated, this Agreement shall expire upon the
latest of:
expiration, lapse, or invalidation of the last remaining Patent
in the Territory; or (ii) twenty (20) years as from the Effective Date.
13.3 Should one of the following event affect either party, the other party
may terminate this Agreement:
(i) Either party becomes insolvent, is declared bankrupt, put into
liquidation, whether voluntarily or by court decision, is obliged
to make an assignment of its assets to the benefit of any third
party or requests the appointment of a receiver or is subject to a
similar procedure;
(ii) Either party is in breach hereunder and has not cured such default
within thirty days following the receipt of a notice sent to it to
that effect by the non defaulting party;
(iii) Force majeure events, as hereinafter defined, preventing either
party from fulfilling its obligations hereunder during a period of
more than three consecutive months, if no mutually acceptable
solution is agreed upon by the parties forthwith after the
expiration of the three month period.
13.4 Earlier termination of this Agreement under Article 13.3 shall not
require resort to any court or compliance with any other formality, and
in case of earlier termination under Article 13.3 (ii), shall not
prejudice the right of the non defaulting party to recover any damages
for breach of this Agreement.
Any and all amounts outstanding at the date of earlier termination under
Article 13.3 shall remain due and be paid on due date as provided herein.
13.5 In case of earlier termination of this Agreement under Article 13.3,
NEUREX shall refund SCRAS all creditable advanced royalty payments made
by SCRAS pursuant to Article 7.3 of this Agreement, that have not been
fully compensated with royalties due by SCRAS pursuant to Article 7.2 of
this Agreement, without prejudice to the provisions of Article 13.4.
13.6 Upon earlier termination of this Agreement, NEUREX may upon notice to
SCRAS within two months following such termination, (i) elect to purchase
all quantities of Product then in the possession of SCRAS, at the actual
Product Transfer Price, or (ii) authorize SCRAS to pack and label the
Product with the remaining inventory of Product and to sell all such
remaining Product during a period not to exceed nine (9) months following
the date of such termination, period after which any Product inventory
held by SCRAS shall be destroyed.
If NEUREX exercises such purchase option, NEUREX shall bear the expenses
of any further transportation of such quantities, and shall pay for such
quantities upon satisfactory quality control completion to be made
forthwith as from the Compound or Product delivery to NEUREX.
13.7 Except as provided in Article 13.6 hereabove, after earlier termination
of this Agreement SCRAS shall have no further rights in the Patents, the
Trademark, the Marketing Authorization Files and Marketing
Authorizations, and shall not, either directly or indirectly, use or
permit the use of the same or of the promotional procedures, methods or
documentation relating to the Product.
Upon earlier termination of this Agreement for any reason whatsoever,
SCRAS shall undertake all proceedings in order to transfer all Marketing
Authorizations and the Trademark registrations should such registrations
be in the name of SCRAS or any Affiliate, to NEUREX or to any other third
party as may be indicated by NEUREX.
ARTICLE 14 - FORCE MAJEURE
14.1 Failure of a party to fulfill its obligations hereunder because of a case
of force majeure effecting the performance of such obligation shall not
constitute a default by such party and consequently shall not give rise
to liability to the other party. A case of force majeure shall include
any cause beyond the reasonable control of such party, including without
limitation, an event due to or action taken by any government or
administrative authority, fire, flood, act of God, embargo, war,
insurrection, general strike.
14.2 The party affected by such an event shall inform the other party as soon
as possible after the occurrence of such event, and send to the other
party ail appropriate justification evidencing the occurrence of such
event. If such an event shall continue for more than three months, the
parties act in good faith to find and implement a mutually acceptable
solution to the event, paying particular attention to the continuity of
the exploitation of the Product in the Territory.
ARTICLE 15 - MISCELLANEOUS
15.1 This Agreement may not be assigned by a party to any third party,
except to an Affiliate, without the prior written consent of the other
party.
15.2 Either party warrants that the execution, delivery and performance of
this Agreement does not violate the provisions of, or constitute a breach
or default under any agreement to which either party is a party.
15.3 This Agreement sets forth the entire agreement between the parties with
respect to its subject matter and merges all prior discussions,
negotiations, and agreement between them. The Confidentiality Agreement
executed between the parties shall be cancelled as from the Effective
Date. This Agreement may not be amended or modified in any manner except
by an instrument of subsequent date in writing signed by duly authorized
representatives of SCRAS and NEUREX.
15.4 Correspondence, notices and payments pursuant to this Agreement shall be
sent by registered mail with acknowledgment of receipt, first class
overnight mail return receipt requested, and/or by telefax, addressed to
the following attention:
For SCRAS: SCRAS - 00/00 xxx xx Xxxxxxx Xxxxxxx, 00000 Xxxxx (Xxxxxx)
Attention General Counsel - Copy to President of Business Development
For NEUREX: NEUREX - 0000 Xxxxx Xxxxxx, Xxxxx
Xxxx, Xxxxxxxxxx 00000-0000 (U.S.A.)
Attention Xxxx Xxxxxxx
Or such address as a party shall from time to time advise at the above
address.
Such correspondence and notice shall be deemed to have been received on the date
of receipt appearing on the acknowledgment of receipt for notice made by mail,
or on the date of the fax transmission receipt for notice made by fax.
15.5 SCRAS shall fulfill all formalities required in connection with this
Agreement under laws and regulations applying to each country in the
Territory. NEUREX shall fulfill all formalities required in connection
with this Agreement under laws and regulations of the State of California
and/or the United States of America.
15.6 The waiver by any party of any default under this Agreement or of any
covenant, agreement or condition contained herein shall not be construed
to constitute a definitive waiver of such or any other default or breach
whether similar or not.
15.7 If any provision of this Agreement shall for any reason be held to be
void, invalid, illegal or unenforceable in any respect, no other portion
of this Agreement shall be affected thereby; provided however, that the
parties shall in such case promptly negotiate in good faith such
adjustments in this Agreement as shall be necessary to make it fair and
equitable to the parties.
15.8 This Agreement shall be governed by and construed in accordance with the
laws of France.
All disputes arising in connection with the validity, interpretation,
execution or termination of this Agreement shall be finally settled under
the Rules of Conciliation and Arbitration of the International Chamber of
Commerce, by one or more arbitrators, appointed and ruling in accordance
with the said rules. The place of arbitration shall be Paris (France).
The language to be used in the arbitral proceedings shall be the English
language.
In witness whereof the parties hereto have executed this Agreement in
two copies
SCRAS NEUREX
/s/Philippe Beaufour /s/ Xxxx Xxxxxxx
------------------------------- -------------------------------
Philippe BEAUFOUR Xxxx XXXXXXX
Director Chairman & CEO
Appendix A - Patents - Patents registrations in the Territory Appendix B -
Compound and Product Specifications Appendix C - Trademark - Corlopam(R))
registrations in the Territory Appendix D - NEUREX Program Appendix E - (E1 - E2
- E3)
APPENDIX A
PATENT REGISTRATION IN THE TERRITORY
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Country Patent No. Expiry Date Note Claims
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
U.K. 1595502 07 Nov 1997 5 compound, phenethyl-amines, process
for preparingphenethyl-amines
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
U.K. 1595503 07 Nov 1997 5 intermediate for making fenoldopam
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Australia 534783 19 May 1996 - -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Austria 362379 15 Oct 1998 5 process, ring cyclization
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Belgium 860774 14 Nov 2002 1 compound
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Brunei 60/84 07 Nov 1997 8 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Cyprus 1246 07 Nov 1997 8 compound
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Denmark 156057 11 Nov 1997 5 ether inter.
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Denmark 154833 19 May 2000 5 Process
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- -----------------------------------
Denmark 156058 (Div) 11 Nov 1997 5 amine int.
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
France 7734311 15 Nov 1997 5 compound
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Germany P2751258 16 Nov 1995 - process for cycling the phenethyl
------------------------ ---------------------- ---------------------- ----------------------- amine-------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Greece 68523 23 May 1995 - -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Guernsey Conf. of U.K. 07 Nov 1997 8 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Hong Kong 930 07 Nov 1997 8 corresponds to U.K. 1595503
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Ireland 49815 21 May 1996 - -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Israel 53377 14 Nov 1997 8 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Italy 1126216 Oct 2014 2 process - ring formation from
------------------------ ---------------------- ---------------------- ----------------------- phenethyl amine---------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Jersey RP385 07 Nov 1997 8 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Kenya P3407B 07 Nov 1997 8 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Xxxxx Xxxxx 00000 24 May 1995 - -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Luxembourg 78513 15 Nov 1997 5 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- -----------------------------------a-
Country Patent No. Expiry Date Note Claims
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Malaya 382 07 Nov 1997 8 Conf. of U.K. patent
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Netherlands 185563 14 Nov 2002 3 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Xxx Xxxxxxx 000000 19 May 1996 - compound, process and composition
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Portugal 67260 18 April 1994 - process - cyclizing phenethyl amine
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Portugal 71262 27 March 1996 - -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Sabah 370 07 Nov 1997 8 Conf. of U.K. patent
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
South Africa 80/2325 18 April 2000 8 compound
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Sarawak C2252 07 Nov 1997 8 Conf. of U.K. patent
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Singapore 317/84 07 Nov 1997 8 Conf. of U.K. patent
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Spain 464044 05 Jul 1998 5,7 method for making ether int.
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Spain 491620/4 16 April 2001 5,7 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Sweden 436646 16 Nov 1997 5 Conversion of phenethyl amine to
------------------------ ---------------------- ---------------------- ----------------------- benzazepine-------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Switzerland 637383 01 Jan 1998 5 ether intermed., method for making
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Switzerland 635079 16 Nov 1997 5 process for making an ether an int
------------------------ ---------------------- ---------------------- ----------------------- by cyclizing an amine---------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Switzerland 638487 (Div) 01 Jan 1998 5 hydroxyl intermed used to make the
------------------------ ---------------------- ---------------------- ----------------------- amine process-----------------------
------------------------ ---------------------- ---------------------- ----------------------- -----------------------------------
Taiwan NI-15027 01 June 1996 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Tanganyika 2227 07 Nov 1997 8 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
Uganda 23 07 Nov 1997 8 -
------------------------ ---------------------- ---------------------- ----------------------- ------------------------------------
1 Marketing approval was granted in Belgium in March 1993. The patent expiration
date reflects a 5-year patent term extension granted through 14 November 2002.
2 Marketing approval was granted in October 1994 (decrees No. A251/94 and
A252/94). The patent expiration date reflects a 17-year extension period based
upon the granting of an SPC application filed in 1992 under Italian National Law
(Extension Certificate granted under National Law No. 349/91 on October 17,
1995).
3. Marketing approval was received in the Netherlands in June 1992. The patent
expiry date reflects a 5-year patent term extension granted through 14 November
2002.
4 For the Netherlands, Italy and Belgium, since extended patent coverage has
already been obtained for the product covered by the indicated aa basic patent
oo, additional SPCs covering the same product may not be obtained.
5 Patent term extension of a period not to exceed 5 years is available pending
marketing authorization for the product. An SPC (Supplementary Protection
Certificate) application for patent term extension must be filed in the
Industrial Property Office (i) before expiration of the lawful term of the
patent, AND (ii) within 6 months from the date of receiving marketing
authorization. For countries in which more than one patent covering the product
is in force, one patent must be selected as the aa basic patent oo, since a
patentee cannot obtain more than one SPC for the same product.
6 Amendments to the Swiss national patent legislation came into force on 1
September 1995 to make SPCs available in Switzerland.
7 The EEC Regulation providing for patent term extension will come into force in
Spain, Greece and Portugal on January 2, 1988.
8 Under those entries where such has not been indicated, it may also be possible
to obtain an extension of patent term coverage according to individual national
laws in these countries subject to verification.
9 To the extent that claims in the above patents cover a process for
manufacturing the Compound, an intermediate used in such process or use of the
Compound, and/or any improvements in connection thereof, they are excluded from
the Agreement except as provided in Paragraph 8.1(3) and Paragraph 8.5(4)
thereof.
APPENDIX B
Compound and Product Specifications
[*] Confidential treatment has been requested for the entire contents of this
Appendix B which has been filed separately with the Commission.
Appendix C
Schedule of Corlopam Trademarks
Owned by Neurex Corporation
------------------------- -------------------------- ---------------------------- -----------------------------------
Country Status Application/Registration #
------------------------- -------------------------- ---------------------------- -----------------------------------
------------------------- -------------------------- ---------------------------- -----------------------------------
------------------------- -------------------------- ---------------------------- -----------------------------------
Africa
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Egypt Registered 65866
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Nigeria Filed 47158/1985
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South Africa Registered 85/4249
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Asia/Pacific
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Australia Registered A428556
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Indonesia Registered 153067
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New Zealand Registered 186973
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Pakistan Registered 86702
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Philippines Registered 47972
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Singapore Registered 3784/88
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South Korea Registered 185642 (Korean characters)
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South Korea Registered 186023
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Taiwan Registered 428454
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Taiwan Registered 430069 (Taiwanese characters)
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Thailand Registered 126795
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Europe
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Denmark Registered 04082/1990
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Finland Registered 108554
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France Registered 1314252
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Greece Abandoned 80155 (Restoration required)
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* International Registered 4976252
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Ireland Registered 115608
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Italy Registered 603470
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Norway Registered 139349
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Sweden Registered 200236
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* International Registration No. 497625 is extended to the following
jurisdictions: France (home registration), Algeria, Armenia, Austria, Bulgaria,
Czechoslovakia, Germany, Hungary, Italy, Liechtenstein, Monaco, Morocco,
Romania, San Marino, Soviet Union (Russia), Switzerland, and Yugoslavia (not
Spain). Because U.S. corporations, such as Neurex, cannot avail themselves of
the International Registration process, Neurex has formed Neurex International,
a Liechtenstein corporation, which will obtain the assignment of the
international registration for Corlopam and, in turn, license the trademark to
Neurex.
APPENDIX D
NEUREX PROGRAM
FENOLDOPAM
TENTATIVE PHASE IV PROGRAM
The existing pharmacology, preclinical, and clinical database for Corlopam
suggests a range of opportunities to pursue additional indications for this
product. The initial Phase IV development program will focus primarily on
exploiting the positive renal benefits of Corlopam:
1. Pilot Renal Function Studies
These studies will determine the safety and efficacy of Corlopam in
normal volunteers and patients with acute renal insufficiency. An initial study
is designed as a randomized, placebo-controlled, cross-over investigation to
evaluate the pharmacology and dose-response of intravenous infusion of
fenoldopam on glomerular filtration rate (GFR), effective renal plasma flow
(ERPF), vasoactive hormone levels (i.e., PRA, PA, etc.), and the natriuretic and
kaliuretic response in sodium-balanced as well as sodium depleted, normal
volunteers (n = 8-12). The study will likely be performed at the Drug Evaluation
Unit at Hennepin County Medical Center in Minneapolis, MN and is scheduled to be
completed by year end.
The second pilot study is currently designed to be open-label, dose
ranging examination of a select group of septic patients (n = 5-25) who show
signs of early renal compromise that are suggestive of impending kidney injury
and are associated with a relatively poor outcome. The patients will be
normalized for volume status and various doses of fenoldopam will be assessed
for possible improvement in glomerular filtration rate. This study will likely
be performed at the University of Miami School of Medicine.
The final study is designed to establish proof-of-concept for the use
of fenoldopam in the prevention and/or reversal of renal vasoconstriction. This
open-label, dose ranging pilot study will examine Cyclosporine A-treated
transplant patients (n = 5-10), with stable allograft function, for an
investigation of the acute effects of intravenous fenoldopam on
cyclosporine-induced renal vasoconstriction. This study will likely be performed
at the University of Miami School of Medicine.
2. Post-Marketing Studies/Pivotal Trials
At least two major, multicenter (perhaps multinational) post-marketing
studies are planned during calendar years 1997 and 1998 to be designed based
upon the result of pilot trials. These studies are designed to investigate the
effects of intravenous fenoldopam on renal function in the subset of
hypertensive patients that have or are at risk of developing acute renal
insufficiency. These studies will be performed at 10-30 centers and will involve
approximately 200-400 patients each.
3. Alternative Delivery of CORLOPAM
Opportunities in the transdermal or buccal delivery forms of CORLOPAM
are currently being investigated with a number of supply companies. Such a
dosage form will provide a means of delivering Corlopam for both acute and
chronic renal insufficiency indications.
NOTE: The Phase IV program is contingent upon a program that is mutually
acceptable to Neurex and SCRAS.
APPENDIX E
- APPENDIX E1
All countries of the Territory other than those listed in Xxxxxxxx X0 and
Xxxxxxxx X0.
- XXXXXXXX X0:
BENIN
BURKINA FASO
BURUNDI
CAMEROON
CONGO
IVORY COAST
GABON
GUINEA
MALI
MAURITANIA
NIGER
CENTRAL AFRICA REPUBLIC
RWANDA
SENEGAL
CHAD
TOGO
ZAIRE
- APPENDIX E3:
AUSTRALIA
ISRAEL
KUWAIT
NEW ZEALAND
SAUDI ARABIA
