EXHIBIT 10.27
LICENSE AGREEMENT
between
NOVARTIS PHARMA AG
and
MOLECULAR INSIGHT PHARMACEUTICALS INC.
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TABLE OF CONTENTS
ARTICLE I ................................................................. 4
Definitions ............................................................ 4
ARTICLE II ................................................................ 10
License and Call Back Right ............................................ 10
ARTICLE III ............................................................... 12
Manufacture and Supply.................................................. 12
ARTICLE IV ................................................................ 12
Development and Commercialization ...................................... 12
ARTICLE V ................................................................. 13
Consideration........................................................... 13
ARTICLE VI ................................................................ 17
Call Back Option and Right of First Refusal ............................ 17
ARTICLE VII ............................................................... 19
Intellectual Property .................................................. 19
ARTICLE VIII .............................................................. 22
Representations and Warranties ......................................... 22
ARTICLE IX ................................................................ 24
Confidentiality ........................................................ 24
ARTICLE X ................................................................. 26
Announcement and Publicity ............................................. 26
ARTICLE XI ................................................................ 26
Term and Termination ................................................... 26
ARTICLE XII ............................................................... 29
Indemnification and Insurance .......................................... 29
ARTICLE XIII .............................................................. 31
Information on Clinical Safety and Epidemiology ........................ 31
ARTICLE XIV ............................................................... 31
Governing Law and Jurisdiction ......................................... 31
ARTICLE XV ................................................................ 31
Miscellaneous Provisions ............................................... 31
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LICENSE AGREEMENT
MOLECULAR INSIGHT PHARMACEUTICALS INC. / NOVARTIS PHARMA AG
This License Agreement dated the 3rd day of November, 2006 (the "Execution
Date") is entered into by and between Novartis Pharma AG (referred to as
"Novartis"), a corporation organized and existing under the laws of the
Switzerland and having its principal offices at ▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇, ▇▇-▇▇▇▇ ▇▇▇▇▇,
▇▇▇▇▇▇▇▇▇▇▇ and Molecular Insight Pharmaceuticals Inc., a corporation organized
and existing under the laws of Delaware, with an office at ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇,
▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ ▇▇▇ (hereinafter "MIP").
INTRODUCTION
WHEREAS, ▇▇. ▇▇▇▇▇▇▇▇, Professor Dr. S.W.J. Lamberts ("Lamberts") and Sandoz
Pharma Ltd ("Sandoz" now Novartis) have made joint inventions relating to
labelled somatostatin analogues covered in the Patent Case 100-7382 and the
Patent Case 118-7595 (hereinafter the "Generic Patent"), as set out on Exhibit
1a;
WHEREAS, Sandoz has entered into an agreement with Mallinckrodt Medical Inc., a
company with its office in St Louis, USA, dated December 1st 1992, relating to
the development, the manufacture and the marketing of molecules for
radiodiagnostic and radiotherapeutic purposes (hereinafter referred to as the
"Master Agreement");
WHEREAS, Sandoz has identified edotreotide (the "Compound"), as a potential
compound for development under the Master Agreement, and has labelled it with
90Yttrium, which is specifically covered in the patent EP-B1-714911 and
equivalents (hereinafter referred to as "Novartis Specific Patent") as set out
in Exhibit 1b (the "Product");
WHEREAS, Sandoz has entered into an agreement with Mallinckrodt Medical Inc
dated October 1996, in accordance with the terms of the Master Agreement, under
which the Parties have agreed to collaborate in the development, manufacture and
marketing of such Product, (hereinafter referred to as the "Definitive
Agreement");
WHEREAS, Mallinckrodt B.V and Mallinckrodt Medical Inc. have been acquired by
Tyco Inc. and are now referred to as MMI;
WHEREAS, Novartis owns and/or Controls certain rights to the Generic Patent, to
Novartis Specific Patent and to the Trademark;
WHEREAS, MIP has certain expertise in developing radiopharmaceutical products;
WHEREAS MIP wishes to obtain and Novartis agrees to convey certain licenses to
the Generic Patent and to Novartis Specific Patent, to the Trademark, and
Novartis Know-How (all as defined below) for the purpose of continuing to
develop and commercializing the Product, and
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WHEREAS, MIP will enter into a separate agreement with MMI for the transfer of
the Product manufacturing know-how;
WHEREAS, Novartis will enter into a separate agreement with MMI which will cover
the termination of the Master Agreement and of the Definitive Agreement and will
address the responsibilities of each Party with regard to transfer of data and
intellectual property rights to MIP ("the Termination Letter").
NOW, THEREFORE, in consideration of the mutual promises, covenants and
agreements hereinafter set forth, the sufficiency of which is hereby
acknowledged, the Parties to this Agreement mutually agree as follows:
ARTICLE I
DEFINITIONS
For purposes of this Agreement, the following initially capitalized terms in
this Agreement, whether used in the singular or plural, shall have the following
meanings:
1.1 "ACCOUNTING STANDARDS" shall mean, with respect to MIP, US GAAP (United
States Generally Accepted Accounting Principles) and, with respect to
Novartis, IFRS (International Financial Reporting Standards).
1.2 "AFFILIATE shall mean any entity that directly or indirectly controls or is
controlled by or is under common Control with a Party to this Agreement.
For purposes of this definition, "control" or "controlled" means ownership
directly or through one or more Affiliates, of fifty percent (50%) or more
of the shares of stock entitled to vote for the election of directors, in
the case of a corporation, or fifty percent (50%) or more of the equity
interest in the case of any other type of legal entity, status as a general
partner in any partnership, or any other arrangement whereby a Party
controls or has the right to control the board of directors or equivalent
governing body of a corporation or other entity, or the ability to cause
the direction of the management or policies of a corporation or other
entity.
1.3 "AGREEMENT" shall mean this Agreement together with all exhibits,
schedules, and appendices attached to this Agreement, all as respectively
amended, modified or supplemented by the Parties in accordance with the
terms of this Agreement.
1.4 "CALENDAR YEAR" shall mean the calendar year, starting on January 1 and
ending on December 31, in which the first commercial sale of the Product
occurs and each successive calendar year.
1.5 "CHANGE OF CONTROL" shall mean any of the following events: (a) any Third
Party (or group of Third Parties acting in concert) becomes the beneficial
owner,
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directly or indirectly, of fifty percent (50%) or more of the voting power
of the stock then outstanding of MIP; (b) MIP consolidates with or merges
into another corporation or entity, or any corporation or entity
consolidates with or merges into MIP, in either event pursuant to a
transaction in which fifty percent (50%) or more of the total voting power
of the stock outstanding of the surviving entity normally entitled to vote
is not held by the Parties holding more than fifty percent (50%) of the
outstanding shares of MIP prior to such consolidation or merger; (c) any
Third Party (or group of Third Parties acting in concert) obtains the power
to direct or cause the direction of the management and policies of MIP by
any lawful means whatsoever; or (d) MIP conveys, transfers or leases all or
substantially all of its assets.
1.6 "COMMERCIALIZATION" or "COMMERCIALIZE" shall mean activities conducted by a
Party either by itself or through a Third Party and directed to marketing,
promoting, distributing, importing, exporting, offering for sale or selling
a Product, which may include pre-launch market preparation, whether
undertaken by a Party alone or with a partner or a sub-licensee. When used
as a verb, "Commercialize" means to engage in Commercialization.
1.7 "COMMERCIALLY REASONABLE EFFORT" shall mean the efforts and resources
customarily used in the industry by a company of similar size for a product
with an equivalent sales and profit potential to the Product.
1.8 "COMPOUND" shall mean the DOTA-chelated somatostatin peptide analogue known
as edotreotide.
1.9 "CONFIDENTIAL INFORMATION" shall mean and include any and all Know-How,
data and information, not in the public domain. It shall also include, but
not be limited to, information relating to the Product and/or Compound, or
the business, research and development activities, results of clinical
trials, regulatory proceedings, finances, contractual relationships and
operations of the Parties.
1.10 "CONTROLLED" OR "CONTROLS", when used in reference to intellectual
property, shall mean the legal authority or right of a Party hereto (or any
of its Affiliates) to grant a license or sub-license of intellectual
property rights to another Party, or to otherwise disclose proprietary or
trade secret information to such other Party, without breaching the terms
of any agreement with a Third Party, infringing upon the intellectual
property rights of a Third Party, or misappropriating the proprietary or
trade secret information of a Third Party.
1.11 "DEVELOPMENT" shall mean all activities conducted by a Party either by
itself or through a Third Party, as are necessary for an application for a
Marketing Authorization.
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1.12 "DEVELOPMENT COSTS" shall mean, with respect to the Compound or Product,
expenses and other costs, including regulatory expenses, incurred by or on
behalf of a Party in connection with the Development of the Compound or
Product, including, the costs of clinical trials, the preparation,
collation and/or validation of data from such clinical trials and the
preparation of medical writing and publishing.
1.13 "DIRECT COMPETITOR" shall mean a Third Party which has either a product
which has been launched within the last five years or a product in its
development pipeline in Phase III or in a later stage, all of which have a
similar mode of action as the Product.
1.14 "DOLLARS" or "USD" shall mean the lawful currency of the United States of
America.
1.15 "EFFECTIVE DATE" shall mean the date upon which Novartis receives a written
notification from MIP that MIP has executed the agreement with MMI as
referenced in article 15.1 hereof.
1.15A "EXECUTION DATE" shall mean the date set out at the outset of this
Agreement.
1.16 "FDA" shall mean the U.S. Food and Drug Administration or its successor
agency.
1.17 "FIRST COMMERCIAL SALE" shall mean the first sale of a Product to a Third
Party by MIP or an Affiliate or sub-licensee of MIP in a country in the
Territory following applicable Marketing Authorisation in one indication of
such Product in such country.
1.18 "GOOD CLINICAL PRACTICE" or "GCP" shall mean the generally accepted
standard of Good Clinical Practice within the pharmaceutical industry for
the design, conduct, performance, monitoring, auditing, recording, analyses
and reporting of clinical trials that provides assurance that the data and
reported results are clinical and accurate and that the rights, integrity
and confidentiality of the trial subjects are protected.
1.19 "GOOD MANUFACTURING PRACTICES" or "GMP" shall mean the then current Good
Manufacturing Practices as such term is defined from time to time by the
FDA or other relevant Governmental Authority having jurisdiction over the
development, manufacture or sale of the Product in the Territory pursuant
to its regulations, guidelines or otherwise.
1.20 "▇▇▇▇▇▇▇▇" shall mean ▇▇ ▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇ at the Erasmus Hospital in
Rotterdam named as a co-inventor on the Generic Patent.
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1.21 "▇▇▇▇▇▇▇▇ LICENSE" shall mean the agreement to be entered into by and
between ▇▇▇▇▇▇▇▇ and Novartis as referred to in article 15.2 and Exhibit 3.
1.22 "MARKETING AUTHORIZATION" shall mean, with respect to a country in the
Territory, the approval by the appropriate authority necessary for the
Commercialization of a Product in that country. For the sake of clarity,
Marketing Authorization shall not include the reimbursement approval.
1.23 "MIP FIELD" shall mean human oncology therapeutic use.
1.24 "MIP KNOW-HOW" shall mean any proprietary or non-proprietary information
including, but not limited to the manufacture and production, inventions,
discoveries, formulation, processes, trade secrets, expertise, developments
and regulatory information of the Compound Controlled by MIP, whether or
not protected under patent, trademark, copyright or other legal principles,
to which MIP has rights during the Term of this Agreement.
1.25 "MIP NEW INTELLECTUAL PROPERTY" shall include, but not be limited to any
data, results, and the like, whether patentable or not, as well MIP
Know-How, invented or generated by it or by its sub-licensees and any
interests in any co-owned intellectual property right which arises from the
development and/or the manufacture of the Compound and the Product. For the
purpose of articles 6.3, 7.6 (c) and 11.5 (c) (v), MIP New Intellectual
Property shall include any and all trademarks, including domain name, that
MIP uses in relation to the Product.
1.26 "NDA" or "NEW DRUG APPLICATION" shall mean a new drug application and all
amendments and supplements thereto filed with the FDA (as more fully
defined in 21 C.F.R. 314.5 et seq.), or the equivalent application filed
with any equivalent Regulatory Authority outside the USA (including any
supra-national agency such as the European Medicines Agency, hereinafter
"EMEA") requiring such filing, including all documents, data and other
information concerning a pharmaceutical product which are necessary for
gaining Marketing Authorization to market and sell such pharmaceutical
product.
1.27 "NDA ACCEPTANCE" shall mean the date upon which the Product NDA submitted
by MIP is deemed filable by the U.S. FDA or the equivalent dossier is
accepted for review by any other country's respective Regulatory Authority.
1.28 "NET SALES" shall mean with respect to the Product the gross amount
invoiced by or on behalf of the relevant Party and its Affiliates and
sub-licensees for the Product sold to Third Parties other than licensees or
sub-licensees in bona fide, arms-length transactions, less the following
customary deductions, determined in accordance with the Party's Accounting
Standards as generally and consistently applied by that Party, to the
extent included in the gross invoiced sales price of any Product or
otherwise directly paid or incurred by such Party, its Affiliates or
sub-licensees with respect to the sale of such Product,:
(i) normal and customary trade and quantity discounts actually
allowed and properly taken directly with respect to sales of the
Product;
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(ii) amounts actually repaid or credited by reasons of defects,
rejection recalls, returns, rebates and allowances of goods;
(iii) chargebacks and other amounts paid on sale or dispensing of such
Product;
(iv) amounts payable resulting from governmental mandated rebate
programs;
(v) tariffs, duties, excise, sales, value- added and other taxes
(other than taxes based on income);
(vi) retroactive price reductions specifically identifiable to the
Product that are actually allowed or granted;
(vii) customary cash discounts for timely payment;
(viii) delayed ship order credits;
(ix) discounts pursuant to indigent patient programs and patient
discount programs and coupon discounts; and
(x) all freight, postage and insurance included in the invoice price.
Sales from a Party to its Affiliates shall be disregarded for purposes of
calculating Net Sales. Any of the items set forth above that would
otherwise be deducted from the invoice price in the calculation of Net
Sales but which are separately charged to Third Parties shall not be
deducted from the invoice price in the calculation of Net Sales.
a) In the case of any sale or other disposal of the Product between or
among a Party and its Affiliates or sub-licensees, for resale, Net
Sales shall be calculated as above only on the value charged or
invoiced on the first arm's-length sale thereafter to a Third Party;
b) In the case of any sale which is not invoiced or is delivered before
invoice, Net Sales shall be calculated at the time of shipment or when
the Product is paid for, if paid for before shipment or invoice;
c) In the case of any sale or other disposal for value, such as barter or
counter-trade, of any Compound or Product, or part thereof, other than
in an arm's length transaction exclusively for money, Net Sales shall
be calculated as above on the value of the non-cash consideration
received or the fair market price (if higher) of the Product in the
country of sale or disposal;
In the event the Product is sold in a finished dosage form containing the
Compound in combination with one or more other active ingredients (a
"Combination Product"), the Net Sales of the Product, for the purposes of
determining royalty payments, shall be determined by multiplying the Net
Sales
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(as defined above in this Article) of the Combination Product by the
fraction, A/(A+B) where A is the weighted (by sales volume) average sale
price in a particular country of the Product when sold separately in
finished form and B is the weighted average sale price in that country of
the other product(s) sold separately in finished form. In the event that
such average sale price cannot be determined for both the Product and the
other product(s) in combination, Net Sales for purposes of determining
royalty payments shall be agreed by the Parties based on the relative value
contributed by each component, such agreement shall not be unreasonably
delayed or withheld.
1.29 "NOVARTIS KNOW-HOW" shall mean proprietary or non proprietary information
relating to the Compound and/or the Product excluding the regulatory CMC
information for the chemical manufacturing process. The information shall
include the relevant specifications, technical data, inventions,
discoveries, formulation, processes, trade secrets, expertise developments
and regulatory information of Product Controlled by Novartis as well as,
chemical, stability, pharmacological, safety, clinical data, analytical and
quality control data, whether or not protected under patent, trademark,
copyright or other legal principles, to which Novartis has rights at the
Effective Date. For the sake of clarity, any information related to the
manufacture of the Tyr-3 octreotide will not be disclosed to MIP.
1.30 "NOVARTIS MILESTONES" shall mean the milestone payments as well as the
license fee due by MIP as set forth under article 5.1, 5.2 and 5.3.
1.31 "NOVARTIS PATENTS" shall mean those patents and patent applications owned
or Controlled by Novartis during the term of this Agreement with a claim
encompassing Compound, Product, or any other formulations of Compound,
processes, uses and intermediates for the foregoing and shall include any
patents or patent applications and any continuations,
continuations-in-part, divisions, provisionals, substitutions, patents of
addition, reissues, examination, renewals or extensions thereof (including
any supplemental patent certificates) and any confirmation patent or
registration patent and all foreign counterparts of any of the foregoing.
Without limiting the generality of the definition set forth in this article
1.31, Novartis Patents existing on the Effective Date are listed in Exhibit
1a and 1b and include the Generic Patent and Novartis Specific Patent.
1.32 "NOVARTIS ROYALTIES" shall mean the royalty payments due by MIP as set
forth under article 5.4.
1.33 "OCTREOTHER(R)" shall mean the trademark selected by Novartis for the
Product.
1.34 "PARTY" OR "PARTIES" shall mean MIP or Novartis, or MIP and Novartis,
whichever the context admits.
1.35 "PERSON" shall mean any individual, corporation, partnership, association,
joint-stock company, trust, unincorporated organization or government or
political subdivision thereof.
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1.36 "PRODUCT" shall mean the yttrium radiolabeled Compound for therapeutic use
and indium 111 radiolabeled Compound for dosimetry purposes, both in a form
ready for use in human clinical trials and/or by the ultimate consumer with
the possible trademark of OctreoTher(R).
1.37 "REGULATORY AUTHORITY" shall mean the FDA or any foreign counterpart or
additional governmental or regulatory agencies in the Territory responsible
for applicable Marketing Authorization.
1.38 "ROYALTY TERM" shall have the meaning as set forth in article 5.4 (b).
1.39 "SUB-LICENSEE" shall mean a Third Party to whom MIP may grant a right or
license to use Novartis Patents or Novartis Know-How to make, use or sell
any Product under all or part of Novartis' Patents or Know-How in the
Territory.
1.40 "TERM" shall have the meaning as set forth in article 11.1 (a).
1.41 "TERMINATION LETTER" shall mean the agreement to be entered into by
Novartis and MMI as set forth in the introduction
1.42 "TERRITORY" shall mean all the countries and territories of the world.
1.43 "THIRD PARTY" shall mean any Person or other entity other than MIP,
Novartis or their respective Affiliates or Sub-licensees of rights conveyed
under this Agreement, except as provided under Article 8.
1.44 "TRADEMARK" shall mean the trademark as defined in article 1.33 and 8.7 as
well as any internet domain name using OctreoTher.
1.45 "USA" shall mean the United States of America.
1.46 "VALID CLAIM" shall mean an issued claim of a Novartis Patent which claim
has not been held invalid or unenforceable by final decision of a court or
other governmental agency of competent jurisdiction, unappealable or
unappealed within the time allowed for appeal, and which is not admitted to
be invalid or unenforceable through reissue, disclaimer or otherwise.
ARTICLE II
LICENSE
2.1 GRANT TO MIP
2.1.1 Subject to the terms and conditions of this Agreement, Novartis
hereby grants to MIP a world-wide, non-exclusive, royalty-bearing
license under its rights in the Generic Patent to use, make,
offer to sell, sell and import the Compound and the Product in
the MIP
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Field, as well as to use the Indium 111 labelled Compound for
dosimetry purposes in relation to the Product therapy
administration.
2.1.2 Subject to the terms and conditions of this Agreement, Novartis
hereby grants to MIP a world-wide, exclusive, royalty-bearing
license under Novartis Specific Patent and Novartis Know-How to
use, make, offer to sell, sell and import the Compound and the
Product in the MIP Field.
2.2 SUB-LICENSE. MIP shall have the right to grant, under the license granted
in article 2.1, sub-licenses to Third Parties with respect to the Product,
provided MIP has discussed its intention to sub-license such rights with
Novartis prior to making any commitment with a Third Party and provided
that the terms and conditions of sub-license agreements shall be consistent
with the terms of this agreement. MIP shall undertake to enforce the
provisions of such sub-license agreements and shall remain responsible for
the performance of sub-licensee's obligations. MIP shall cause each
sub-licensee to execute any and all additional documents reasonably
requested by Novartis to reflect the conditions set forth in this article.
2.3 LIMITATIONS OF RIGHTS. It is acknowledged and agreed that no license is
granted by Novartis to MIP other than the license expressly granted by the
provisions of article 2.1 and that Novartis retains all other rights under
Novartis Know-How and Novartis Patents.
2.4 TRANSFER OF NOVARTIS KNOW-HOW AND NOVARTIS FILES.
2.4.1. Novartis undertakes to physically transfer the content of its
investigational new drug application in the United States or
equivalent documents for other countries, and all related amendments,
correspondence, meeting minutes and any other documents (hereinafter
collectively referred to as "IND") upon the effective date of this
Agreement. For the avoidance of doubt, this does not include those
parts of the IND Controlled by MMI or any information related to the
manufacture of the Tyr-3 octreotide.
2.4.2 Except as provided above, Novartis shall use reasonable efforts to
disclose to MIP within ninety (90) days, or such longer period as
reasonably required by Novartis, of the Effective Date all the
Novartis Know-How needed pursuant to the terms of this Agreement as
listed in Exhibit 2 attached hereto as well as the data and
information related to the Compound and/or the Product available on
the Effective Date on an "as is" basis. For the sake of clarity
Novartis shall not be requested to perform additional clinical trials,
nor to perform any cleaning of trial data. Data and files shall be
transferred as is with no further obligations on Novartis. Thereafter,
during the term of this Agreement, Novartis shall upon written request
of MIP disclose any additional information among Novartis Know-How,
which is reasonably available and is related to the Compound
("Additional Support"). The Novartis Know-How provided hereunder
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shall remain the property of Novartis, but MIP shall be free to use it
within the licenses granted above. Should MIP request Additional
Support six months after execution of this Agreement or later, such
Additional Support shall be charged to MIP at **
2.4.3 Novartis will communicate to all Regulatory Authorities within whose
jurisdiction an application to conduct clinical trials using the
Product or Compound has been filed to request transfer of the
sponsorship of these applications to MIP. MIP agrees to accept said
transfer and to conduct all subsequent activities and maintenance of
the documents including periodic updates as required by the national
regulations. MIP shall provide to Novartis a copy of the acceptance
letter from the appropriate Regulatory Authorities relating to such
transfer(s).
2.5 LIAISON. Each of MIP and Novartis shall, upon execution of this Agreement
identify within thirty (30) days a primary contact person (the "Contact"),
to act as liaisons for the purpose of this Agreement, which role shall
include but not be limited to receiving the reports set forth in article
6.2. The Parties may change their respective Contact at any time by
providing written notice to the other Party.
ARTICLE III
MANUFACTURE AND SUPPLY
3.1 RESPONSIBILITY MANUFACTURING. MIP shall be responsible at its expense for
manufacturing of Compound and Product. Should MIP elect to have the
manufacture of the Compound and/or the Product performed by a Third-Party,
MIP shall ensure that such Third Party is bound by confidentiality
provisions as strict as the ones imposed on MIP.
3.2 PROVISION OF COMPOUND AND PRODUCT FROM NOVARTIS'S INVENTORY.
Within thirty (30) days of the Effective date of this Agreement, Novartis
shall provide to MIP or MIP designated subcontractor(s) ** of
Compound for the restricted use in technical tests. In no event shall such
material be used in humans.
It is the common understanding of the Parties that Novartis shall in no way
be required to produce or provide further Compound beyond the **
mentioned in the first sentence of this article 3.2 and made available at
the Effective Date.
Shipments of Compound shall be made EXW ("EX WORKS", as such term is
defined in INCOTERMS 2000), Novartis' shipping point at the Novartis
Facility. Novartis fulfills its obligations to deliver when the goods are
made available at its premises to MIP.
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** denotes confidential treatment requested
ARTICLE IV
DEVELOPMENT AND COMMERCIALIZATION
4.1 DEVELOPMENT COSTS. MIP shall bear all the costs and be responsible for any
Development that has to be conducted from the Effective Date.
4.2 REPORTS. With respect to each Product in the MIP Field, MIP shall provide
to Novartis every six months a summary report which shall set forth the
results of the development work and regulatory activities performed during
the preceding year and summarize the activities planned for the coming
year. Such reports shall be prepared by MIP and provided to Novartis within
sixty (60) days after the end of each six month period and shall include
Phase IV activities, when applicable.
4.3 DEVELOPMENT EFFORTS. MIP shall use Commercially Reasonable Efforts to
develop and register the Product and shall be solely responsible for
compiling the NDA for each Product in the MIP Field at its own expense.
4.4 CLINICAL TRIALS. MIP shall be solely responsible for and shall bear all the
costs related to the conduct of clinical trials required to file NDAs in
the Territory, including the on-going trials, for instance the study
R21CA91578-01 in pediatric neuroblastoma. MIP undertakes to run the
clinical trial program in accordance with GCP
4.5 MARKETING EFFORTS - MARKET LAUNCH. MIP shall use Commercially Reasonable
Efforts to launch and sell the Product for as long as this Agreement is
in place.
4.6 BOOKING SALES. MIP shall, at its own expense, book sales of Product as
distributed by or on behalf of MIP.
4.7 PRICING. MIP shall be free to set prices of Product.
ARTICLE V
CONSIDERATION
5.1 LICENSE FEE. In consideration of the rights granted to MIP under this
Agreement, MIP shall pay to Novartis or to such other Affiliates as
Novartis may direct a license fee of ** within thirty (30) days of the
Effective Date. Except as provided in article 15.1, such amount shall not
be credited against any royalty or other payments to be made pursuant to
this Agreement and shall not be refundable
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* confidential treatment requested *
5.2 MILESTONE PAYMENTS. In consideration of the rights granted to MIP by
Novartis hereunder, MIP shall make the following milestone payments to
Novartis or to such other Affiliate as Novartis may direct:
(A) ** upon an NDA Acceptance by either the FDA or the EMEA whichever NDA
Acceptance comes first.
(B) ** upon granting of the Marketing Authorization by either the FDA or
the EMEA whichever approval comes first, ** of which shall be
creditable against future royalty payments
MIP shall, spontaneously notify Novartis of such events upon occurrence
thereof, whereupon Novartis shall submit an invoice to MIP requesting such
milestone payment. The payments made by MIP hereunder shall in no event be
refundable and shall each be payable only once.
The payments made by MIP under article 5.2 shall be made in US dollars by
MIP to a bank account designated by Novartis.
5.3 ADDITIONAL MILESTONE PAYMENTS. Should Novartis decide not to exercise its
Call-Back Option as set forth in Article 6, the following additional
milestone payments shall be due to Novartis:
a) An additional ** once MIP annual Net Sales amount of ** is achieved,
payable in two equal installments, the first payment due by January
31st of the Calendar Year following the year in which the milestone is
achieved and the second payment 12 months later.
b) An additional ** once MIP annual Net Sales of ** is achieved, payable
in two equal installments, the first payment due by January 31st of
the Calendar Year following the year in which the milestone is
achieved and the second payment 12 months later.
c) An additional ** once MIP annual Net Sales amount to ** is achieved,
payable in two equal installments, the first payment by January 31st
of the Calendar Year following the year in which the milestone is
achieved and the second payment 12 months later.
5.4 ROYALTIES. In addition to the license fees set forth in article 5.1 and the
milestone payments set forth in article 5.2 and 5.3 and as further
consideration for the license granted to MIP hereunder, MIP agrees to pay
to Novartis royalties on MIP's and/or its Sub-licensee's aggregate Net
Sales in the Territory, during the Royalty Term at a rate calculated
according to the following:
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(A) ROYALTY CALCULATION:
- ** of the annual Net Sales of the Product for Net Sales amounting
to less than ** annually.
- ** of the Net Sales of the Product on the incremental sales
between ** and ** annually.
- ** of the Net sales of the Product on the incremental sales over
**.
(B) ROYALTY TERM: Royalties shall be payable quarterly on a country-by-country
basis from the First Commercial Sale of the Product in the country until
the occurrence of the later of: (i) the expiration of the latest to expire
Novartis Patents including any extensions in each such country or (ii) 10
years from First Commercial Sale.
(C) THE COMBINATION ROYALTY: In the event that Compound and / or Product ("MIP
Component") is formulated with another active ingredient or a second
product to comprise a fixed Combination Product, the "net sales" of the MIP
Component, for purposes of determining royalty payments to Novartis, shall
be determined by multiplying the Net Sales of the Combination Product by
the fraction, A/(A+B), whereas A is the weighted average sales price of the
Product (by sales volume) when sold independently and B is the weighted
average sales price (by sales volume) of the other product-component when
sold independently. In the event the weighted average sales price cannot be
determined for either "A" or "B", the Parties hereto shall agree on an
alternative method for calculating "net sales" of the MIP Component of the
Combination Product for purposes of calculating royalties to Novartis. In
such event, the Parties shall agree on the methodology prior to submitting
the registration dossier for the Combination Product, taking into account
relevant factors such as, but not limited to, the relative cost and value
contributed by each component weighted proportionally.
(D) ROYALTY OFFSET. ** of the milestone payment due by MIP to Novartis upon
approval as set forth in 5.2 (b) shall be offset against future royalties.
5.5 SALES REPORTS.
(A) SUBSTANCE OF REPORTS. After the First Commercial Sale of Product and
during the Term of this Agreement, MIP shall furnish or cause to be
furnished to Novartis on a quarterly basis a written report showing
the Net Sales of Product in each country in the
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Territory.
(B) TIMING. Each quarterly report shall be due within sixty (60) days
following the close of each quarter.
(C) RECORDS. MIP shall keep accurate records in sufficient detail to
enable the amounts due hereunder to be determined and to be verified
by an independent certified public accountant mutually agreed upon by
the Parties pursuant to article 5.5 (e).
(D) CURRENCY EXCHANGE. All royalty payments shall be made in US dollars
("USD") With respect to sales or other dispositions of Product
invoiced in a currency other than USD, the Net Sales and amounts due
to Novartis hereunder will be expressed in USD equivalent calculated
on a monthly basis in the currency of the country of sale and
converted to their dollar equivalent using the Daily Spot Rate on the
last day of the period, published in the Reuters System - Reuters
Daily Rates between 09:00 a.m. and 10 a.m. CET.
(E) ROYALTY PAYMENT DUE DATE; ACCRUAL. Royalty payments shall be made to
the address designated by Novartis. Royalties which have accrued
during any calendar year and are required to be shown on a sales
report provided under this Article 5 of the Agreement shall be due and
payable on the date such sales report is due.
(I) MIP and Sub-licensees shall keep for three (3) years from the
date of each payment of royalties complete and accurate records
of sales by MIP and Sub-licensees of Product in sufficient detail
to allow the accruing royalties to be determined accurately.
(II) Novartis shall have the right for a period of three (3) years
after receiving any report or statement with respect to royalties
due and payable to appoint an independent certified public
accountant reasonably acceptable to MIP to inspect the relevant
records of MIP and its Affiliates and Sub-licensees to verify
such report or statement. Novartis may exercise this right once
with respect to each year's Net Sales. If the right is not
exercised during the three (3) year period described, the report
shall be deemed accepted. Novartis may exercise this right only
once in any year.
(III) MIP and Sub-licensees shall each make its records available for
inspection by such independent certified public accountant during
regular business hours at such place or places where such records
are customarily kept,
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upon reasonable notice from Novartis, solely to verify the
accuracy of the reports and payments. Such inspection right shall
not be exercised more than once in any Calendar Year.
(IV) Novartis agrees to hold in strict confidence and use only for the
purpose described in this Article 5 all information concerning
royalty payments and reports, and all information learned in the
course of any audit or inspection (and not to make copies of such
reports and information), except to the extent necessary for
Novartis to reveal such information in order to enforce its
rights under this Agreement or if disclosure is required by law,
regulation or judicial order or to MMI as may be necessary to
share Royalty payments pursuant to the Termination Letter. The
results of each inspection, if any, shall be binding on both
Parties.
(V) Novartis shall pay for such inspections, except that in the event
there is any upward adjustment in aggregate royalties payable for
any year shown by such inspection of more than five percent (5%)
of the amount paid, MIP shall pay for such inspection. Any
overpayments shall be fully creditable against amounts payable in
subsequent payment periods.
(VI) Any upward adjustment in aggregate royalties payable for any year
shown by such inspection of not more than ten percent (10%) of
the amount paid shall not be deemed a Material Breach according
to article 11.3, but shall be repayable by MIP in full with
interest as set forth in article 5.7 and promptly be paid upon
Novartis' request.
(VII) MIP shall include in each sub-license or commercialisation
agreement entered into by it pursuant to this Agreement a
provision requiring the Sub-licensee or commercialization partner
to keep and maintain adequate records of sales made pursuant to
such sub-license or commercialisation agreement and to grant
access to such records by the aforementioned independent public
accountant for the reasons specified in this article.
5.6 TAX WITHHOLDING. All payments pursuant to this Agreement are exclusive of
any applicable Value Added Tax. Withholding tax applied by a government of
any country of the Territory on payments made by MIP to Novartis hereunder
shall be borne by Novartis. MIP, its Affiliates and Sub-licensees, shall
cooperate with Novartis to enable Novartis to claim exemption therefore
under any double
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taxation or similar agreement in force and shall provide to Novartis proper
evidence of payments of withholding tax and assist Novartis by obtaining or
providing in as far as reasonably possible the required documentation for
the purpose of Novartis' returns. MIP undertakes to make all payments due
under this Agreement that are subject to a withholding tax treatment,
including double taxation or similar agreement, from the USA.
5.7 INTEREST DUE In case of any delay in payment (including underpayment) by
MIP to Novartis not occasioned by Force Majeure, interest on the overdue
payment shall accrue at an annual interest rate, compounded monthly, equal
to the London Interbank Offer Rate (LIBOR) + three percent (3%), as
determined for each month on the last day of that month, assessed from the
day payment was initially due. The foregoing interest shall be due from MIP
without any special notice.
ARTICLE VI
CALL BACK OPTION AND RIGHT OF FIRST DISCUSSIONS.
6.1 CALL BACK OPTION. Subject to the provisions of this article 6, Novartis
shall have a one time call back option to re-acquire the rights to the
Compound and Product in the event that MIP Net Sales of the Product first
reaches ** in a calendar year ("Call Back Option"). Within twenty (20) days
of receipt of such information from MIP, Novartis shall notify MIP in
writing of its intention to perform a due diligence (the "Novartis
Notification"). The Call Back Option shall be exercisable by Novartis
during the ninety (90) days after Novartis has completed its due diligence
("Call Back Period").
6.2 INFORMATION. In order to enable Novartis to determine whether it wishes to
exercise the Call Back Option, Novartis shall be entitled to perform a full
due diligence of all the information reasonably available to MIP, at
Novartis' expense, Such information shall include, but not be limited to
all relevant clinical data, manufacturing data, marketing data, and other
data reasonably needed by Novartis for reviewing its interest in exercising
the Call Back Option. Such data shall be limited to data not previously
furnished to Novartis pursuant to articles 5.5(a) and 4.2. Within thirty
(30) days of the Novartis Notification, MIP shall give access to Novartis
to all information necessary to complete the due diligence..
6.3 EXERCISE OF CALL-BACK OPTION. If Novartis exercises the Call-Back Option
("Call Back Exercise"), the following rights and obligations shall apply as
between the Parties:
(A) This Agreement, including the licenses and rights granted by Novartis
to MIP shall terminate and MIP shall grant to Novartis an exclusive,
worldwide license in the MIP Field under all MIP Know-How, MIP New
Intellectual Property and MIP' interest in any Third Party
intellectual property if such interest may be conveyed, as necessary
for Novartis to
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develop, make, use, sell, offer for sale and import the Compound
and/or Products and Novartis shall conduct (or have conducted) under
its control the Commercialization of the Product. MIP undertakes to
use Commercially Reasonable Efforts to secure sub-license rights under
any Third Party intellectual property.
(B) In return for the termination of this Agreement and for the grant of
the license in article 6.3 (a), Novartis shall pay to MIP an amount
equal to ** the annual Net Sales achieved during the year described in
article 6.1.
(C) In the event that Novartis at its sole discretion, decides to involve
MIP in the further Development of the Compound after Novartis has
exercised the Call Back Option, the Parties may discuss the nature and
scope of such MIP involvement and agree in writing the nature of any
further MIP involvement, but there shall be no obligation on Novartis
to do so.
(D) All obligations on MIP to pay Novartis Milestones as set forth in
article 5 which at the time of the Call back Exercise, are not already
due and payable pursuant to article 5 shall lapse.
(E) For the sake of clarity Novartis will not pay MIP any royalties.
(F) Any sub-licenses will be transferred to Novartis
6.4 NON-EXERCISE OF CALL BACK OPTION. If Novartis does not exercise the Call
Back Option, the Additional Milestones shall be due as set forth in article
5.3
6.5 RIGHTS OF FIRST DISCUSSIONS. In the event MIP intends to grant
Co-Commercialisation Rights to Compound and/or Product to a Third Party
("Co-Commercialisation Partner") under the license granted in article 2.1,
MIP undertakes to inform Novartis immediately of such intention and
Novartis shall have forty-five (45) days to inform MIP of its interest to
enter into such Co-Commercialisation agreement with MIP.
ARTICLE VII
INTELLECTUAL PROPERTY
7.1 NOVARTIS PATENTABLE INVENTIONS AND KNOW-HOW
(A) NOVARTIS PATENTS PROSECUTION. During the term of the Agreement,
Novartis shall at its discretion be responsible for the prosecution
and maintenance of Novartis Patents which are listed in Exhibit 1.
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(B) COOPERATION. Novartis agrees that it will, no less frequently than
once a year during the Term of this Agreement, inform MIP in writing
of any changes to the Novartis Patents by providing an updated Exhibit
1, and further agrees that it shall not abandon the Novartis Specific
Patent in any country of the Territory, without first offering to
assign it to MIP at MIP's costs.
7.2 INFRINGEMENT CLAIMS BY THIRD PARTIES.
(A) NOTICE. If the manufacture, use or sale of Product results in a claim
or a threatened claim by a Third Party against a Party hereto for
patent infringement or for inducing or contributing to patent
infringement ("Infringement Claim"), the Party first having notice of
an Infringement Claim shall promptly notify the other in writing. The
notice shall set forth the facts of the Infringement Claim in
reasonable detail.
(B) For the purpose of this article 7.2, Third Party shall exclude
▇▇▇▇▇▇▇▇ and MMI.
(C) THIRD PARTY LICENSES. In the event the Parties agree that practicing
under the Novartis Patents in connection with manufacture, use or sale
of Product in a country would infringe a Third Party Patent and a
license to such Third Party Patent is available and MIP in its sole
discretion seeks such a license, the Parties agree that:
(I) MIP will use commercially reasonable efforts to obtain any
such required licenses under the Third Party's Patents; and
(II) In the event that MIP obtain any such required licenses from
Third Party under which MIP shall pay the Third Party
certain royalties, MIP may deduct such Third Party payment
from its royalty payments to Novartis under article 5 but in
no event will such deductions reduce the Royalty payments in
any quarter to Novartis by greater than **.
(D) LITIGATION. If a Third Party asserts that a patent, trademark or other
intellectual properties owned by it is infringed by the importation,
manufacture, offer for sale, use or sale of Compound or Product, or if
either Party learns of a claim or assertion that the manufacture, use,
marketing, promotion, importation, offer for sale, distribution or
sale of Compound or Product infringes or otherwise violates the
intellectual property rights of any Third Party, then such Party will
promptly notify the other Party in writing. Novartis will have the
first right, but not the obligation, to control such defense at its
own expense. If Novartis does not assume control of such defense
within 120 days of the notice described above, then MIP shall have the
right to control such defense at its own
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expense. In any event, the Party not controlling such defense will
have the right to be represented in any such action by counsel of its
choosing at its own expense. The Party controlling such defense shall
keep the other Party advised of the status of such action and shall
consider recommendations made by the other Party in respect thereto.
The Party not controlling such defense will assist and cooperate in
any such infringement litigation at the defending Party's reasonable
request and expense
The costs and expenses (including attorneys' fees) of any suit brought
in accordance with this Article shall be borne by the Party
controlling the prosecution of such suit. Any costs borne by MIP in
accordance with this article shall however be entirely off-set against
any payments due to Novartis under Article 5.
7.3 INFRINGEMENT CLAIMS AGAINST THIRD PARTIES
(A) NOTICE. If any Novartis Patents are infringed by a Third Party, the
Party to this Agreement first having knowledge of such infringement,
or knowledge of a reasonable probability of such infringement, shall
promptly notify the other in writing. The notice shall set forth the
facts of such infringement in reasonable detail.
(B) INSTITUTION OF PROCEEDINGS. Novartis shall have the primary right, but
not the obligation, to institute, prosecute, and control with its own
counsel at its own expense any action or proceeding with respect to
infringement of the claims of such Novartis Patents. In the event,
Novartis does not take any action with respect to any such
infringement within 120 days after receiving notice of such
infringement thereof, MIP may at its own discretion and at its own
expense undertake such defense thereof. The Party undertaking the
defense shall have the sole charge and direction of the defense of any
such suit or action and the other Party shall have the right, but not
the obligation at its own expense, to be represented in such action by
its own counsel action. Each Party agrees to cooperate fully in the
prosecution of any such suit or action undertaken hereunder by the
other Party and to provide all evidence in its reasonable control.
(C) DIVISION OF DAMAGES AWARD. Each Party shall recover their respective
actual out-of-pocket expenses, or equitable proportions thereof,
associated with any litigation or settlement thereof from any recovery
made by any Party. Any excess amount allocated as a damage award shall
be shared between the Parties as follows: Novartis shall be allocated
an amount equal to its royalty loss and MIP shall be allocated the
remainder of damages; any amount allocated as a penalty shall be
shared equally between the Parties.
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(D) SETTLEMENT. The Parties shall keep each other informed of the status
of and of their respective activities regarding any litigation or
settlement thereof concerning Product; provided, however, that no
settlement or consent judgment or other voluntary final disposition of
a suit under this article 7 may be undertaken without the consent of
the other Party if such settlement would require the other Party to be
subject to an injunction or to make a monetary payment or would
otherwise adversely affect the other Party's rights under this
Agreement
7.4 NOTICE OF CERTIFICATION. Novartis and MIP each shall immediately give
notice to the other of any certification filed under the "U.S. Drug Price
Competition and Patent Term Restoration Act of 1984" (or its foreign
equivalent) claiming that a Novartis Patent is invalid or that infringement
will not arise from the manufacture, use or sale of any Product by a Third
Party.
(A) If Novartis decides not to bring infringement proceedings against the
entity making such a certification, Novartis shall give notice to MIP
of its decision not to bring suit within twenty-one (21) days after
receipt of notice of such certification.
(B) MIP may then, but is not required to, bring suit against the Party
that filed the certification at its own expense.
(C) Any suit by MIP or Novartis shall either be in the name of MIP or in
the name of Novartis, or jointly in the name of MIP and Novartis, as
may be required by law.
(D) For this purpose, the Party not bringing suit shall execute such legal
papers necessary for the prosecution of such suit as may be reasonably
requested by the Party bringing suit.
7.5 PATENT TERM EXTENSIONS. The Parties shall cooperate in good faith with each
other in gaining patent term extension wherever applicable to the Novartis
Specific Patent covering Compound or Product. All filings for such
extension shall be made by the Party responsible for prosecution and
maintenance of the Novartis Specific Patent, provided, however, that in the
event that the Party who is responsible for prosecution and maintenance of
the Novartis Specific Patent elects not to file for an extension, such
Party shall (i) inform the other Party of its intention not to file and
(ii) the other Party shall have the right to file for such extension.
7.6 MIP NEW INTELLECTUAL PROPERTY
(A) Ownership of New Intellectual Property. During the Term of the
Agreement, MIP New Intellectual Property shall be owned by MIP. MIP
shall inform Novartis of new patent applications and action on them in
the report provided by MIP to Novartis pursuant to article 4.2
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(B) MIP shall have the sole right to file, prosecute, and maintain all of
the patents within the MIP New Intellectual Property included herein,
and shall have the right to determine whether or not, and where, to
file a patent application, to abandon the prosecution of any patent or
patent application, or to discontinue the maintenance of any patent
application. (c) Should Novartis terminate this Agreement due to a
breach by MIP of its obligation hereunder, MIP shall grant to Novartis
a perpetual, world-wide, royalty-bearing, exclusive license to such
MIP New Intellectual Property, with the right to grant sub-licenses,
to use any MIP New Intellectual Property invented or generated by
persons obliged to assign their rights to MIP in the MIP Field. The
royalty rate on the Novartis' Net Sales of the Product shall be
determined by the Parties upon termination of the Agreement, shall be
based on reasonable commercial terms and in no event shall exceed
** of the royalty rates payable by MIP under article 5.4 of this
Agreement.
7.7 TRADEMARK
(A) Generalities. Novartis shall grant an exclusive, world-wide,
royalty-free license to use the trademark OctreoTher without any warranty
that this will be approved by the Regulatory Authorities anywhere in the
world. MIP may decide to use a different trademark in which case MIP should
inform Novartis of such decision.
(B) Use of the Trademarks. MIP and/or its Sub-licensee may promote, market,
sell and distribute the Product in the Territory exclusively under the
Trademark during the Term; provided, however, that MIP may rebrand any or
all Products and sell such Products under its own trademark. For the sake
of clarity, MIP and/or its Sub-licensee may, at its discretion, elect to
continue using the Trademarks after the Term.
ARTICLE VIII
REPRESENTATIONS AND WARRANTIES
8.1 NOVARTIS REPRESENTS AND WARRANTS
(A) This Agreement has been duly executed and delivered by Novartis and
constitutes the valid and binding obligation of Novartis, enforceable
against Novartis in accordance with its terms except as enforceability
may be limited by bankruptcy, fraudulent conveyance, insolvency,
reorganization, moratorium and other laws relating to or affecting
creditors' rights generally and by general equitable principles. The
execution, delivery and performance of this Agreement have been duly
authorized by all necessary action on the part of Novartis, its
officers and directors.
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(B) As of the Effective Date and except as it relates to the rights owned
or Controlled by MMI which shall be licensed by MMI to MIP under a
separate agreement, Novartis owns or possesses adequate licenses or
other rights necessary to make, use and sell the Compound and the
Product covered by the Novartis Patents and Novartis Know-How to grant
the licenses herein and the granting of the licenses to MIP hereunder
does not violate any right known to Novartis of a Third Party.
(C) Except as it relates to information owned or Controlled by MMI and
except as it relates to disputed co-ownership rights with ▇▇▇▇▇▇▇▇
applicable to the performance of clinical trials in certain countries,
Novartis represents that as of the Effective Date it is not aware of
any information that the development, manufacture, use or sale of
Compound or Product pursuant to this Agreement may infringe or
conflict with any Third Party right or patent, and Novartis is not
aware of any pending patent application that, if issued, would be
infringed by the development, manufacture, use or sale of Compound or
Product pursuant to this Agreement.
(D) Provided Novartis and MMI execute the Termination Letter which shall
address the termination of the Definitive Agreement and of the Master
Agreement, and provided MIP and MMI enter into a license agreement to
cover the use of the rights owned and Controlled by MMI, the
execution, delivery and performance of this Agreement by Novartis does
not conflict with any agreement, instrument or understanding, oral or
written, to which it is a Party or by which it may be bound, and, to
the best of its knowledge, does not violate any material law or
regulation of any court, governmental body or administrative or other
agency having authority over it.
(E) Subject to the limitations in article 1.29, Novartis has disclosed to
MIP any and all material information in its Control pertaining to the
suitability of Compound as a pharmaceutical candidate.
(F) Novartis is not currently a Party to, and during the term of this
Agreement will not enter into, any agreements, oral or written, that
are inconsistent with its obligations under this Agreement.
(G) Novartis is duly organized and validly existing under the laws of the
country of its incorporation and has full legal power and authority to
enter into this Agreement.
(H) Novartis is not subject to any order, decree or injunction by a court
of competent jurisdiction which prevents or materially delays the
consummation of the transactions contemplated by this Agreement.
8.2 MIP REPRESENTS AND WARRANTS
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(A) This Agreement has been duly executed and delivered by MIP and
constitutes the valid and binding obligation of MIP, enforceable
against MIP in accordance with its terms except as enforceability may
be limited by bankruptcy, fraudulent conveyance, insolvency,
reorganization, moratorium and other laws relating to or affecting
creditors' rights generally and by general equitable principles. The
execution, delivery and performance of this Agreement have been duly
authorized by all necessary action on the part of MIP, its officers
and directors;
(B) MIP is not currently a Party to, and during the term of this Agreement
will not enter into, any agreements, oral or written, that are
inconsistent with its obligations under this Agreement;
(C) MIP is duly organized and validly existing under the laws of the State
of Delaware, USA and has full legal power and authority to enter into
this Agreement; and
(D) MIP is not subject to any order, decree or injunction by a court of
competent jurisdiction which prevents or materially delays the
consummation of the transactions contemplated by this Agreement.
8.3 THE LIMITED WARRANTIES CONTAINED IN THIS ARTICLE ARE THE SOLE WARRANTIES
GIVEN BY THE PARTIES AND ARE MADE EXPRESSLY IN LIEU OF AND EXCLUDE ANY
IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE,
TITLE, INFRINGEMENT OR OTHERWISE, AND ALL OTHER EXPRESS OR IMPLIED
REPRESENTATIONS AND WARRANTIES PROVIDED BY COMMON LAW, STATUTE OR OTHERWISE
ARE HEREBY DISCLAIMED BY BOTH PARTIES.
ARTICLE IX
CONFIDENTIALITY
9.1 CONFIDENTIALITY. Subject to the exercise of the licenses granted in Article
2, during the Term of this Agreement, and for a period of five (5) years
thereafter, each Party hereto will maintain in confidence all information
generated under this Agreement as well as any information disclosed by the
other Party hereto ("Confidential Information"). Neither Party shall use,
disclose or grant use of such Confidential Information except as required
under this Agreement. Each Party shall use the same standard of care as it
uses to protect its own Confidential Information to ensure that its and its
Affiliates' employees, agents, consultants, Sub-licensee(s) and clinical
investigators only make use of Confidential Information for the purpose of
this Agreement and do not disclose or make any unauthorized use of such
Confidential Information. Each Party shall promptly notify the other upon
discovery of any unauthorized use or disclosure of
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Confidential Information. Confidential Information shall not include any
information which and to the extent:
(A) was already known to the receiving Party, other than under an
obligation of confidentiality, at the time of disclosure by the other
Party;
(B) was generally available to the public or otherwise part of the public
domain at the time of its disclosure to the other Party;
(C) becomes generally available to the public or otherwise part of the
public domain after its disclosure and other than through any act or
omission of the receiving Party in breach of this Agreement;
(D) was disclosed to the receiving Party, by a Third Party who had no
obligation to the other Party not to disclose such information; or
(E) was independently developed by the receiving Party without reference
to the disclosure by the other Party.
9.2 The Parties agree that the material financial terms of the Agreement and
the reports described in article 4.2 shall be considered the Confidential
Information of both Parties. As specified in article 9.3, Novartis hereby
consents to disclosure by MIP, of both the existence of and terms of this
Agreement, to the Securities Exchange Commission. MIP shall request the SEC
to provide confidential treatment of the material financial terms of this
Agreement.
9.3 Each Party may disclose the Confidential Information to the extent such
disclosure is reasonably necessary in filing or prosecuting patent
applications, prosecuting or defending litigation, or complying with any
applicable statute or governmental regulation provided such Party has given
the disclosing Party prompt written notice allowing it to limit such
disclosure but except as specified in article 9.2 above. In addition,
either Party may disclose Confidential Information to its Affiliates and to
its Sub-licensees; provided, however, in connection with any such
disclosure the disclosing Party shall secure confidential treatment of such
Confidential Information.
9.4 The Parties shall undertake to ensure that all their employees who have
access to Confidential Information of the other Party are under obligations
of confidentiality fully consistent with those provided in this article.
9.5 MIP agrees that the terms, including but not limited to the financial
terms, may be disclosed by Novartis to MMI without further notice, provided
MMI shall be subject to the same confidential obligations as set forth
herein.
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ARTICLE X
ANNOUNCEMENT AND PUBLICITY
10.1 Except with the prior written consent of the other Party not to be
unreasonably withheld, neither Party hereto shall make any disclosure to
any third Party except Affiliates concerning the terms of this Agreement.
Each Party will inform the other prior to the disclosure of this Agreement
or any of its terms to any government authorities or agencies and will
observe all reasonable requirements of the other in regard to any such
disclosure. The restrictions on disclosure specified herein shall not apply
to announcements required by law or regulations or stock exchange rules,
including announcements required by law, regulations or stock exchange
rules to be made by either Party to their respective shareholders.. It is,
however, the Parties' intent that they will co-ordinate to such extent as
may be reasonably possible with respect to the wording of any such
announcements and that the financial terms of this Agreement shall not be
made public. Novartis acknowledges that it is in MIP's interest to announce
the completion of this Agreement.
10.2 MIP will, and will cause its Sub-licensees to obtain Novartis' prior
written permission to use Novartis' name, symbols and any other marks in
any form of publicity
ARTICLE XI
TERM AND TERMINATION
11.1
(A) TERM. Unless earlier terminated as provided under article 6, (Novartis
Call-Back Option) 11.2 or 11.3 the term of this Agreement shall
commence as of the Effective Date and shall remain in full force and
effect on a country-by-country basis until the end of the last to
expire payment obligations of MIP under article 5.4(b) ("Term").
(B) ACCRUED OBLIGATIONS. Except where explicitly provided elsewhere herein
or in any applicable Swiss Laws, termination of this Agreement for any
reason, or expiration of this Agreement, will not affect: (i)
obligations, including the payment of any royalties or other sums
which have accrued as of the date of termination or expiration, and
(ii) rights and obligations which, from the context thereof, are
intended to survive termination or expiration of this Agreement.
11.2 TERMINATION FOR INSOLVENCY. Either Party may terminate this Agreement
immediately upon delivery of written notice to the other Party (a) upon the
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institution by or against the other Party of insolvency, receivership or
bankruptcy proceedings or any other proceedings for the settlement of the
other Party's debts; provided, however with respect to involuntary
proceedings, that such proceedings are not dismissed within one hundred and
twenty (120) days; (b) upon the other Party's making an assignment for the
benefit of creditors; (c) upon the other Party's dissolution or ceasing to
do business.
11.3 MATERIAL BREACH. If either Party is in breach of any material obligation
hereunder and, in the case of a breach capable of remedy, it shall not have
been remedied by the defaulting Party within sixty (60) days of written
notice specifying the breach and requiring its remedy, the Party not in
breach of the material obligation may forthwith terminate this Agreement by
notice without prejudice to the accrued rights of either Party.
11.4 CHANGE OF CONTROL. Novartis may terminate this Agreement forthwith at any
time in the event that there is a Change of Control provided such Change in
Control results in MIP being owned by a Direct Competitor.
11.5 EFFECT OF TERMINATION.
(A) EFFECT ON LICENSE. Upon the expiration or earlier termination of this
Agreement, the rights licensed under this Agreement shall be treated
as follows:
(I) Upon expiration of the Term, MIP shall have a fully paid-up,
perpetual, irrevocable, royalty-free, transferable, worldwide,
non-exclusive right and license under the Novartis Patents and
Novartis Know-How existing as of the date of such expiration to
make, use, offer to sell, import and sell Product in the
Territory.
(II) Upon early termination pursuant to article 6, 11.2, 11.3 or 11.4
if Novartis is the terminating Party, all Novartis' rights to the
Compound and Product shall revert to Novartis, including but not
limited to the license granted under article 2.1.
(III) Upon early termination by MIP pursuant to article 11.3 due to a
material breach by Novartis of its obligations under this
Agreement, MIP shall be granted a perpetual, worldwide,
royalty-bearing, non-exclusive license, with the right to
sub-license, under the Novartis Patents and Novartis Know-How
existing as of the date of such expiration to make, use, offer to
sell, import and sell Product in the Territory in the MIP Field
("Early Termination License"). The royalty rate for the Early
Termination License shall equal the percentage agreed in article
5.4 reduced by ** ("Reduced Royalty Rate").
(B) EFFECT ON TRADEMARK:
28
* confidential treatment requested *
(I) Upon expiration of the Term, MIP and/or its Sub-licensee may
continue to use the Trademark in connection with the sale of the
Product.
(II) Upon early termination of this Agreement by Novartis pursuant to
article 11.2,11.3 or 11.4 if Novartis is the terminating Party,
all the rights to use the Trademark(s) shall revert to Novartis.
(C) ONGOING OBLIGATIONS.
(I) Upon expiration or termination of this Agreement for any reason,
each Party shall immediately return to the other Party or destroy
any Confidential Information disclosed by the other Party, except
for one copy which may be retained to determine its continuing
obligations pursuant to this Agreement.
(II) Upon early termination by Novartis pursuant to article 11.2, 11.3
or 11.4 above, MIP shall have no further right to use or refer to
the Novartis Know-How owned by Novartis and MIP shall transfer to
Novartis all documentation embodying or referring to Novartis
Know-How.
(III) Upon early termination by Novartis pursuant to articles 11.2,
11.3 or 11.4 above and at Novartis' election, MIP will
immediately transfer ownership of all Marketing Authorizations at
Novartis costs and shall give an access right to all clinical
development, regulatory and manufacturing data, as well as to all
other relevant information to Novartis or its Third Party
licensee which shall be free to use it.
(IV) Upon early termination by Novartis pursuant to article 11.2, 11.3
or 11.4 above, MIP shall transfer to Novartis upon Novartis'
request all its stock of Compound and Product at cost.
(V) Upon early termination of this Agreement by Novartis pursuant to
article 11.2, 11.3 or 11.4 above and at Novartis's election, MIP
shall grant to Novartis, a non-exclusive, world-wide,
royalty-bearing license to any MIP New Intellectual Property,
including but not limited to pre-clinical and clinical trial
results and regulatory files and filings related to Product and
Compound as set forth in article 7.6(c).. In addition, MIP shall
provide at Novartis' request, the reasonable assistance of
appropriate MIP personnel in connection with the transfer
therewith.
(VI) INVENTORY. Notwithstanding the foregoing, upon early termination
of this Agreement pursuant to articles 11.2 or 11.3 and unless
MIP exercises its right under article 11.5(a) (iii) in which case
this article does not apply, MIP shall have the right to sell all
remaining
29
Product in its inventory within six (6) months after the date of
termination, subject to the payment to Novartis of the amounts
specified in article 5. Thereafter, MIP agrees to destroy any
remaining supply of Product at Novartis' request.
ARTICLE XII
INDEMNIFICATION AND INSURANCE
12.1 MIP will indemnify, defend and hold Novartis harmless from and against any
and all costs, losses, claims, liabilities, fines, penalties, damages,
expenses, court costs, interest, and reasonable fees and disbursements of
counsel, consultants, and expert witnesses ("Damages") incurred or suffered
by Novartis arising out of or resulting from: (i) MIP's breach of a
material term if this Agreement; (ii) MIP's breach of any of its
representations or warranties hereunder; or (ii) the development,
manufacture, handling, use, marketing, sale or other disposition, of
Compound and/or Product by any of MIP, its Affiliates, Sub-licensees, and
their contractors in the MIP Field except to the extent that such Damages
are due to Novartis' or Novartis' directors', officers', employees', or
Affiliates' negligence or wilful misconduct.
12.2 Novartis will indemnify, defend and hold MIP harmless from and against any
and all Damages incurred or suffered by MIP arising out of or resulting
from: (i) Novartis' breach of a material term if this Agreement; (ii)
Novartis' breach of any of its representations or warranties hereunder or
failure to perform duly and punctually any of its covenants, agreements, or
undertakings contained in this Agreement; except to the extent that such
Damages are due to MIP's or MIP's directors', officers', employees', or
Affiliates' negligence or wilful misconduct.
12.3 The Parties agree as follows:
(A) Each Party shall give the other Party prompt written notice of any
claim or threat of claim it receives with respect to any matter for
which it may be entitled to indemnification, and the indemnifier shall
thereafter defend or settle (subject to article 12.3.(d)) any such
claim at the indemnifier's sole expense, with counsel selected by the
indemnifier. In the defence or settlement of any such claim, the
indemnified Party shall co-operate with and assist the indemnifier to
the extent reasonably possible, but the indemnifier shall bear and pay
any and all expenses incurred by the indemnified Party in providing
such co-operation and assistance, either directly or upon request of
the indemnified Party who has incurred such expense. Failure to give
notice shall not constitute a defence, in whole or in part, to any
claim by any indemnified person hereunder except to the extent the
rights of the indemnifier are materially prejudiced by such failure to
give notice.
30
(B) Notwithstanding the foregoing, upon any claim being made by a person
not a Party to this Agreement (and not an Affiliate of a Party) with
respect to any matter to which the foregoing indemnities relate, the
indemnified Party may make settlement of such claim on not less than
30 days prior written notice of the proposed terms thereof to the
indemnifier; provided, however, that if within said 30-day period the
indemnifier shall have requested the indemnified Party not to settle
such claim and to deny such claim, the indemnified Party will promptly
comply and the indemnifier shall have the right to defend the claim at
the indemnifier's sole expense and with counsel reasonably acceptable
to the indemnified Party. In the event that the indemnifier has not
responded to such notice within such 30-day period, such absence of
response shall be deemed a written consent to the proposed settlement.
(C) Notwithstanding that the indemnifier has assumed the defence of any
claim with counsel selected by the indemnifier, the indemnified Party
shall have the right to employ its own counsel, at its sole expense.
If, in good faith, an indemnified Party concludes that there are
specific defences available to the indemnified Party which are
different from or in addition to those available to the indemnifier
with respect to the scope of the foregoing indemnities, then such
indemnified Party shall have the right to direct the defence of any
such defence of any such claim and each Party shall pay all its own
costs, fees and damages.
(D) Neither Party will conduct itself in a way that could prejudice the
defense of any such claims or threats.
12.4 References in this Article 12 to a Party that may be entitled to
indemnification shall also include its Affiliates and its and their
officers, directors, employees and agents.
12.5
(A) The Parties agree to maintain insurance, including but not limited to
product liability insurance and Clinical Trial insurance in the case
of MIP, with respect to their activities hereunder. Such insurance
shall be in such amounts and subject to such deductibles based upon
standards prevailing in the industry at the time.
(B) The Parties may satisfy its obligations under this article through
self-insurance to the same extent.
12.6 LIMITATION OF DAMAGES. Neither Party or its affiliates shall have any
liability for any special, incidental, or consequential damages, including,
but not limited to the loss of opportunity, revenue or profit, in
connection with or arising
31
out of this Agreement, even if it shall have been advised of the
possibility of such damages.
ARTICLE XIII
INFORMATION ON CLINICAL SAFETY AND EPIDEMIOLOGY
13.1 MIP shall be fully responsible for ensuring compliance with all
pharmacovigilance obligations, including the holding and maintaining of the
global safety database for the Product. Within thirty days (30) of the
Effective date, Novartis will provide a paper copy of the global safety
database relating to the Product to MIP.
ARTICLE XIV
GOVERNING LAW AND JURISDICTION
14.1 The construction, validity and performance of this Agreement will be
governed in all respects by Swiss Law. All disputes arising out of or
affecting this Agreement which cannot be resolved amicably shall be
submitted to the exclusive jurisdiction of the courts of Basel-Stadt,
Switzerland, should Novartis be the defendant, and of the courts of
Massachusetts, should MIP be the defendant.
ARTICLE XV
MISCELLANEOUS PROVISIONS
15.1 CONDITIONAL AGREEMENT. The execution of the Termination Letter and the
agreement between MIP and MMI which shall cover the transfer of all data,
information and any Intellectual Property Rights Controlled by MMI to MIP
are conditions precedent to the effectiveness and force of this Agreement.
Should any of these documents not be completed, this Agreement shall be
deemed null and void and neither Party will have any obligation to the
other.
15.2 EXHIBIT 3. In the event that Novartis and ▇▇▇▇▇▇▇▇ enter into the ▇▇▇▇▇▇▇▇
License, Novartis will notify MIP thereof in writing and the Exhibit 3
shall from receipt of such notification automatically and immediately
become a part of this Agreement including the grant by ▇▇▇▇▇▇▇▇ and
Novartis to MIP of an exclusive world-wide royalty bearing licence under
the Generic Patent, with the right to grant sub-licenses, to develop, have
developed, offer for sale, offer for
32
distribution, to use, sell, import, export, manufacture, distribute and
commercialise the Compound and the Product, and all of the terms set out in
Exhibit 3. This Agreement shall then be deemed amended accordingly.
15.3 WAIVER. The failure on the part of MIP or Novartis to exercise or enforce
any rights conferred upon it hereunder shall not be deemed to be a waiver
of any such rights nor operate to bar the exercise or enforcement thereof
at any time or times thereafter. The observance of any term of this
Agreement may be waived (either generally or in a particular instance and
either retroactively or prospectively) by the Party entitled to enforce
such term, but any such waiver shall be effective only if in writing signed
by the non-waiving Party.
15.4 FORCE MAJEURE. Neither Party shall be held liable or responsible to the
other Party nor be deemed to have defaulted under or breached this
Agreement for failure or delay in fulfilling or performing any term of this
Agreement, other than an obligation to make a payment, when such failure or
delay is caused by or results from fire, floods, embargoes, government
regulations, prohibitions or interventions, war, acts of war (whether war
be declared or not), insurrections, riots, civil commotions, strikes,
lockouts, or any other cause beyond the reasonable control of the affected
Party. If a force majeure circumstance persists for more than 12 months,
the Parties shall discuss in good faith about termination of this
Agreement.
15.5 SEVERABILITY. It is the intention of the Parties to comply with all
applicable laws domestic or foreign in connection with the performance of
its obligations hereunder. In the event that any provision of this
Agreement, or any part hereof, is found invalid or unenforceable, the
remainder of this Agreement will be binding on the Parties hereto, and will
be construed as if the invalid or unenforceable provision or part thereof
had been deleted, and the Agreement shall be deemed modified to the extent
necessary to render the surviving provisions enforceable to the fullest
extent permitted by law.
15.6 GOVERNMENT ACTS. In the event that any act, regulation, directive, or law
of a government, including its departments, agencies or courts, should make
impossible or prohibit, restrain, modify or limit any material act or
obligation of MIP or Novartis under this Agreement, the Party, if any, not
so affected shall have the right, at its option, to suspend or terminate
this Agreement as to such country, if good faith negotiations between the
Parties to make such modifications to this Agreement as may be necessary to
fairly address the impact thereof, after a reasonable period of time are
not successful in producing mutually acceptable modifications to this
Agreement.
15.7 ASSIGNMENT. This Agreement may not be assigned or otherwise transferred by
either Party without the prior written consent of the other Party;
provided, however, that either Party may assign this Agreement, without the
consent of the other Party, (i) to any of its Affiliates, if the assigning
Party guarantees the full performance of its Affiliates' obligations
hereunder or (ii) in connection with the
33
transfer or sale of all or substantially all of its assets or business or
in the event of its merger or consolidation with another company. In all
cases the assigning Party shall provide the other Party with prompt notice
of any such assignment. Any purported assignment in contravention of this
article shall, at the option of the non assigning Party, be null and void
and of no effect. No assignment shall release either Party from
responsibility for the performance of any accrued obligation of such Party
hereunder.
15.8 COUNTERPARTS. This Agreement may be executed in two copies, both of which
shall be deemed to be originals, and all of which shall constitute one and
the same Agreement.
15.9 NO AGENCY. Nothing herein contained shall be deemed to create an agency,
joint venture, amalgamation, partnership or similar relationship between
Novartis and MIP. Notwithstanding any of the provisions of this Agreement,
neither Party shall at any time enter into, incur, or hold itself out to
third Parties as having authority to enter into or incur, on behalf of the
other Party, any commitment, expense, or liability whatsoever, and all
contracts, expenses and liabilities undertaken or incurred by one Party in
connection with or relating to the development, manufacture or sale
Compound or Product shall be undertaken, incurred or paid exclusively by
that Party, and not as an agent or representative of the other Party.
15.10 NOTICE. All communications between the Parties with respect to any of the
provisions of this Agreement will be sent to the addresses set out below,
or to other addresses as designated by one Party to the other by notice
pursuant hereto, by internationally recognized courier or by prepaid
certified, air mail (which shall be deemed received by the other Party on
the seventh Day following deposit in the mails), or by facsimile
transmission or other electronic means of communication (which shall be
deemed received when transmitted), with confirmation by letter given by the
close of business on or before the next following day:
If to Novartis, at:
Novartis Pharma AG
▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇
▇▇-▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇
Attn: Head of BD&L
With a copy to:
Novartis Pharma AG
▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇
▇▇-▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇
Attn: General Counsel
If to MIP at:
Molecular Insight
34
Pharmaceuticals, Inc.
▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ ▇▇▇
Attn: VP Commercial and Business Development
With a copy to:
▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇, Esq.
▇▇▇▇▇▇▇▇ & ▇▇▇▇ LLP
▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇
▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ ▇▇▇
15.11 SURVIVAL. Except where explicitly provided elsewhere herein, termination
of this Agreement for any reason, or expiration of this Agreement, will not
affect: (i) obligations, including the payment of any sums which have
accrued as of the date of termination or expiration, and (ii) rights and
obligations which, from the context thereof, are intended to survive
termination or expiration of this Agreement.
15.12 HEADINGS. The paragraph headings are for convenience only and will not be
deemed to affect in any way the language of the provisions to which they
refer.
15.13 ENTIRE AGREEMENT. This Agreement together with its Exhibits shall
supersede any prior agreement between the Parties and constitutes the
entire understanding of the Parties relating to the matters referred to
herein, and may only be amended by a written document, duly executed on
behalf of the respective Parties. However the terms of this Agreement shall
prevail over any conflicting terms contained in any of the Exhibits.
35
IN WITNESS WHEREOF, the Parties hereto have caused this Agreement to be executed
by their duly authorized representatives as of the day and year first above
written.
Novartis Pharma AG
By: /s/ ▇.▇. Sequier
--------------------------------------
Name: ▇.▇. Sequier
------------------------------------
Title: Business Developing & Licensing
-----------------------------------
By: /s/ ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇
--------------------------------------
Name: ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇
------------------------------------
Title: General Counsel, Novartis Pharma AG
-----------------------------------
Molecular Insight Pharmaceuticals Inc.
By: /s/ ▇▇▇▇▇ ▇. ▇▇▇▇▇▇
--------------------------------------
Name: ▇▇▇▇▇ ▇. ▇▇▇▇▇▇
------------------------------------
Title: Chairman & CEO
-----------------------------------
36
Exhibit 1
Patent
EXHIBIT 1A
1. Generic Patent (100-7382)
COUNTRY GRANT. DATE PATENT NO. EXP. DATE
------- ----------- ----------- ---------
Australia 04.06.93 633859 04.12.09
Austria 09.12.97 403476 30.11.09
Belgium 20.11.90 1002296 05.12.09
Canada 22.02.00 2004532 04.12.09
Cyprus 01.12.95 1893 01.12.09
Denmark 30.08.04 175338 05.12.09
Finland 30.09.98 101967 11.07.14
Finland 31.12.98 102540 04.12.09
France 21.04.95 8915993 04.12.09
Germany 20.04.06 3991505 30.11.09
Great Britain 20.01.93 2225579 01.12.09
Greece 26.11.96 1002475 05.12.09
Hong Kong 21.12.95 1899/95 01.12.09
Hungary 20.09.95 211468 01.12.09
Ireland 05.12.94 62091 04.12.09
Israel 25.09.94 92534 04.12.09
Italy 19.10.93 1239285 05.12.09
Japan 10.06.05 3686503 04.12.09
Japan 05.12.97 2726320 04.12.09
Korea-South 22.07.98 156541 22.07.13
Luxemburg 18.09.91 87633 05.12.09
Malaysia 31.03.95 106120 31.03.10
Netherlands 03.04.03 194828 04.12.09
New Zealand 20.01.94 231623 04.12.09
Nigeria 13.04.93 10732 05.12.09
Pakistan 21.03.92 132014 05.12.00
Philippines 07.05.96 29649 07.05.13
Poland 28.09.93 163432 04.12.09
Portugal 20.10.95 92487 20.10.10
Saudi Arabia* 01.01.09
Singapore 15.04.97 38709 01.12.09
South Africa 28.08.91 89/9285 05.12.09
Spain 22.11.91 2023533 05.12.09
Sweden 09.11.98 8904087-7 04.12.09
Switzerland 30.08.91 678329-6 30.11.09
37
COUNTRY GRANT. DATE PATENT NO. EXP. DATE
------- ----------- ----------- ---------
Tanganyika 30.09.97 2533 01.12.09
Trinidad+Tobago 14.11.95 78/95 01.12.09
USA 19.05.98 5753627 06.06.15
USA 07.07.98 5776894 07.07.15
* Saudi Arabia: patent application still pending, filing number 95160495
38
EXHIBIT 1A (CONTINUATION)
2. Additional Use Patent (118-7595)
COUNTRY GRANT. DATE PATENT NO. EXP. DATE
------- ----------- ---------- ---------
Belgium 05.01.93 1004645 19.02.11
France 20.01.95 9101993 18.02.11
Germany* 13.02.11
Great Britain 20.04.94 2241167 18.02.11
Hong Kong 10.04.97 434/97 18.02.11
Italy 15.07.94 1244496 19.02.11
Japan 15.03.02 3288055 21.02.11
Switzerland 28.02.94 683318-4 19.02.11
USA 26.09.00 6123916 26.09.17
* Germany: patent application still pending. Filing number: P4104308.1
39
EXHIBIT 1B
Novartis Specific Patent
COUNTRY APPL. DATE ▇▇▇▇.▇▇. GRANT. DATE PATENT NO. EXP. DATE
------- ---------- ----------- ----------- ------------ ---------
Argentina 05.09.95 333413 22.03.04 AR256010M 05.09.15
Australia 04.09.95 30414/▇▇ ▇▇.▇▇.▇▇ 703057 04.09.15
Austria 04.09.95 95810545.4 07.03.01 714911 04.09.15
Belgium 04.09.95 95810545.4 07.03.01 714911 04.09.15
Brazil 05.09.95 PI9503936-8 22.06.04 PI9503936-8 05.09.15
Canada 05.09.95 2157530 05.09.15
Chile 05.09.95 1351/95 10.10.00 40732 10.10.15
China 05.09.95 115610/▇▇ ▇▇.▇▇.▇▇ ZL95115610.1 05.09.15
Colombia 05.09.95 95040393 30.07.01 27134 05.09.15
Czech Republic 04.09.95 PV1995-2263 14.06.00 287012 04.09.15
Denmark 04.09.95 95810545.4 07.03.01 714911 04.09.15
Ecuador 05.09.95 SP 95-1528 20.06.97 PI 97-1158 05.09.15
Europe 04.09.95 95810545.4 07.03.01 714911 04.09.15
Finland 04.09.95 4147/95 13.10.06 117424 04.09.15
France 04.09.95 95810545.4 07.03.01 714911 04.09.15
Germany 04.09.95 69520256.1 07.03.01 714911 04.09.15
Great Britain 04.09.95 95810545.4 07.03.01 714911 04.09.15
Greece 04.09.95 95810545.4 07.03.01 714911 04.09.15
Hungary 04.09.95 2577/95 10.05.00 218284 04.09.15
India 24.08.95 1092/MAS/95 24.08.15
Ireland 04.09.95 95810545.4 07.03.01 714911 04.09.15
Israel 04.09.95 115154 14.11.00 115154 04.09.15
Italy 04.09.95 95810545.4 07.03.01 714911 04.09.15
Japan 05.09.95 227906/▇▇ ▇▇.▇▇.▇▇ 3054346 05.09.15
Korea-South 05.09.95 28905/▇▇ ▇▇.▇▇.▇▇ 364111 05.09.15
Luxemburg 04.09.95 95810545.4 07.03.01 714911 04.09.15
Malaysia 05.09.95 PI95002626 05.09.15
Mexico 04.09.95 9503785 29.03.00 195731 04.09.15
Netherlands 04.09.95 95810545.4 07.03.01 714911 04.09.15
New Zealand 04.09.95 272919 17.04.97 272919 04.09.15
Norway 04.09.95 19953457 23.02.04 316569 04.09.15
Pakistan 03.09.95 467/95 03.09.97 134791 06.09.10
Peru 04.09.95 277844 28.02.01 001736 04.09.15
Philippines 04.09.95 51237 29.10.04 ▇-▇▇▇▇-▇▇▇▇▇ 29.10.21
Poland 04.09.95 P310274 10.05.01 182434 04.09.15
Portugal 04.09.95 95810545.4 07.03.01 714911 04.09.15
Russia 04.09.95 95114740 13.04.00 2156774 04.09.15
Singapore 04.09.95 9501282-9 16.11.01 50356 04.09.15
Slovak Republic 04.09.95 1088/95 04.11.03 283774 04.09.15
Slovenia 04.09.95 P9530491 07.03.01 714911 04.09.15
South Africa 06.09.95 95/7475 28.05.97 7475/95 06.09.15
Spain 04.09.95 95810545.4 07.03.01 714911 04.09.15
Sweden 04.09.95 95810545.4 07.03.01 714911 04.09.15
40
COUNTRY APPL. DATE ▇▇▇▇.▇▇. GRANT. DATE PATENT NO. EXP. DATE
------- ---------- ----------- ----------- ------------ ---------
Switzerland 04.09.95 95810545.4 07.03.01 714911 04.09.15
Taiwan 08.09.95 84-109395 16.08.00 114095 08.09.15
Thailand 04.09.95 27824/▇▇ ▇▇.▇▇.▇▇ 11623 04.09.15
Turkey 06.09.95 1094/95 22.04.02 TR199501094B 06.09.15
USA 23.04.97 09/609844 21.08.01 6277356 01.09.15
USA 23.04.97 08/842125 06.02.01 6183721 01.09.15
Venezuela 06.09.95 1572-95 08.01.99 06.09.15
41
Exhibit 2
Novartis Know - How
42
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 08/10/2006 This Annual Report covers the period June 11, 2005 through June 142
10, 2006 (PS)
53,442 90 Y-SMT 487 04/07/2006 Request for a Type C meeting to discuss the future development of 141
OctreoTher on April 11, 2006.
53,442 90 Y-SMT 487 03/15/2006 FDA LETTER stating that NVS request for meeting, dated March 1, 2006,
is premature due to FDA unanswered questions, which were discussed in
the May 20, 2005 teleconference related to the drug development for
OctreoTher.
53,442 90 Y-SMT 487 03/01/2006 Request for a Type A meeting to discuss the future development of 140
OctreoTher.
53,442 90 Y-SMT 487 07/29/2005 E-MAIL outlining interactions (TELECONS) between NVS and the Agency.
July 29 telecon updated FDA on NVS senior management decision to seek
a development partner for SMT487 and confirmed that serial no 138
should be archived for future reference.
53,442 90 Y-SMT 487 07/26/2005 This Annual Report covers the period June 11, 2004 to June 10, 2005. 139
No information.
53,442 90 Y-SMT 487 07/11/2005 TELECON with FDA to followup on discussion regarding NVS submission
dated 5/16/2005 (SN 138), which responds to a request for additional
information prior to making a decision on the Subpart H applicability.
(86 vols, 1 CD). FDA commented that the meeting minutes as documented
in email of May 24, 2005 were satisfactory and reflected the
Division's thinking that the project was in Phase 1/2 development.
53,442 90 Y-SMT 487 06/16/2005 TELECON with FDA (v-mail message left) to followup on discussion
regarding NVS submission dated 5/16/2005 (SN 138), which responds to a
request for additional information prior to making a decision on the
Subpart H applicability. (86 vols, 1 CD). Updated FDA that Senior
Management has not met for the team to present proposals.
53,442 90 Y-SMT 487 06/16/2005 TELECON (June 15-16, 2005) with FDA concerning receipt of amendment to
the orphan drug application submitted June 6, 2005. FDA left a
voice-mail on June 16, 2005 confirming receipt of the amendment.
53,442 90 Y-SMT 487 05/27/2005 TELECON with FDA (v-mail message left) to followup on discussion
regarding NVS submission dated 5/16/2005 (SN 138), which responds to a
request for additional information prior to making a decision on the
Subpart H applicability. (86 vols, 1 CD). (Serial No. 138).
53,442 90 Y-SMT 487 05/24/2005 TELECON w/FDA to discuss the NVS submission dated 5/16/2005 (SN 138),
which responds to a request for additional information prior to making
a decision on the Subpart H applicability. (86 vols, 1 CD). During
this discussion, FDA stated they are willing to work with the company,
but several issues needed to be resolved prior to moving ahead.
53,442 90 Y-SMT 487 05/24/2005 E-MAIL to FDA regarding information discussed in telecon on May
20, 2005 and to notify FDA that NVS will require additional time to
discuss comments internally and will contact FDA when NVS is ready to
have a telecon.
53,442 90 Y-SMT 487 05/20/2005 TELECON with FDA to discuss NVS submission dated May 16, 2005. in
response to FDA questions dated August 27, 2003
53,442 90 Y-SMT 487 05/16/2005 Response for FDA request for information. Submission consist of 86 138
volumes.
53,442 90 Y-SMT 487 03/03/2005 TELECON with FDA to discuss format for sending responses to FDA
request dated August 27, 2003.
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 02/16/2005 TELECON with FDA to discuss FDA FAX dated August 27, 2003 regarding
submission dated July 22, 2003. Confirmed number of paper copies, as
well as e-copies required by FDA.
53,442 90 Y-SMT 487 10/20/2004 New Investigator to Study No. 2201:▇▇. ▇. ▇▇▇▇▇▇▇ replaces ▇. ▇▇▇▇▇▇; 137 2201 2202
Study No. 2202: ▇▇. ▇. ▇▇▇▇▇▇▇ replaces ▇. ▇▇▇▇▇▇.
53,442 90 Y-SMT 487 07/29/2004 [FRANCE] ▇▇. ▇▇▇▇▇▇▇: Hypotension, diarrhoea, vomiting, 136 2202
hyperglycaemia, hypokalaemia, blood bicarbone decreased; Follow-up#2
53,442 90 Y-SMT 487 07/07/2004 This Annual Report covers the period June 11, 2003 through June 10, 135
2004. Includes clinical study information and preclinical study
information.
53,442 90 Y-SMT 487 07/06/2004 [AUSTRALIA] ▇▇. ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇: Pancytopenia; Follow-up#1 134 0103
53,442 90 Y-SMT 487 12/01/2003 ▇▇. ▇▇▇▇▇ ▇▇▇▇▇; Malignant neoplasm progression, malabsorption, 133 B151
cauda equina syndrome, spondylitis NOS, ammonia increased, prothrombin
time prolonged, blood sodium decreased, thrombocytopenia, malnutrition
NOS, rigors, pyrexia, asthenia, anaemia NOS, weight decreased, oedema
peripheral, spinal compression fracture, mastoiditis NOS, neurological
NOS, balance impaired NOS, agitation, confusional state; Follow-up#1
53,442 90 Y-SMT 487 10/28/2003 ▇▇. ▇▇▇▇▇ ▇▇▇▇▇; Weight decreased, malabsorption, thrombocytopenia, 132 B151
malignant neoplasm progression, cauda equina syndrome, spondylitis
NOS, ammonia increased, prothrombin time prolonged, blood sodium
decreased, malnutrition NOS, rigors, pyrexia, asthenia, anaemia NOS,
oedema peripheral, spinal compression fracture, mastoiditis NOS,
neurological disorder NOS, balance impaired NOS, agitation,
confusional state.
53,442 90 Y-SMT 487 10/21/2003 Fax to FDA. 7-Day Safety Report.
53,442 90 Y-SMT 487 09/05/2003 This Annual Report covers the period June 11, 2002 through June 131
10, 2003. Includes clinical study information, preclinical study
information, general investigational plan for the coming year,
investigator's brochure and a foreign marketing developments.
53,442 90 Y-SMT 487 08/27/2003 FAX from FDA containing clinical comments concerning the submission
dated July 22, 2003.
53,442 90 Y-SMT 487 08/20/2003 Submission of pharmacology report entitled, "Inhibition of specific 130
P450 enzyme activities by SMT487 in human liver microsomes".
53,442 90 Y-SMT 487 08/04/2003 [BELGIUM] Prof. ▇▇. ▇. ▇▇▇▇▇▇▇; Trombotic microangiopathy NOS, renal 129 B151
failure NOS, glomerulosclerosis NOS, hypertension NOS, proteinuria,
creatinine renal clearance decreased; Follow-up#1
53,442 90 Y-SMT 487 07/22/2003 Correspondence asking for the Division's feedback on the Subpart 128
H filing strategy proposal provided.
53,442 90 Y-SMT 487 07/18/2003 [BELGIUM] Prof. Van Cutsem: Metabolic encephalopathy NOS, hepatic 127 2202
necrosis, urinary tract infection NOS, somnolence, blood bilirubin
increased, memory impairment, hepatic encephalopathy, confusional
state, pyrexia, coma, brain oedema, ammonia increased; Follow-up#3
53,442 90 Y-SMT 487 03/31/2003 FDA LETTER concerning the issues involving the drug development for
carcinoid and islet cell patients who are refractory to somatostatin
analogue treatment.
53,442 90 Y-SMT 487 03/20/2003 FDA minutes of a meeting held on March 20, 2003, to discuss issues
with the drug development program.
53,442 90 Y-SMT 487 03/18/2003 FAX to FDA containing information for the March 20, 2003, meeting.
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 03/18/2003 FAX to FDA containing responses to clinical questions 1 & 3 faxed
March 14, 2003.
53,442 90 Y-SMT 487 03/14/2003 Response to FDA requests for information on an initial and follow-up 126
Safety Report for case PHHO2002GB09656 (Serial No. 123 & 125).
53,442 90 Y-SMT 487 03/14/2003 FAX from FDA containing clinical requests in preparation to the March
20, 2003, meeting.
53,442 90 Y-SMT 487 03/12/2003 [GREAT BRITAIN] ▇▇. ▇. ▇▇▇▇▇▇; Fluid overload, phlebothrombosis, 125 2201
malignant neoplasm progression, cardiac failure congestive, anuria,
renal failure NOS, pulmonary congestion, cardio-respiratory arrest,
dyspnoea NOS, pulmonary embolism; Follow-up#1
53,442 90 Y-SMT 487 03/04/2003 Replacement questions for the Type C meeting scheduled March 20, 2003. 124
53,442 90 Y-SMT 487 02/26/2003 [GREAT BRITAIN] ▇▇. ▇. ▇▇▇▇▇▇; Fluid overload, phlebothrombosis, 123 2201
malignant neoplasm progression, cardiac failure congestive, anuria,
renal failure NOS, pulmonary congestion, cardio-respiratory arrest,
dyspnoea NOS, pulmonary embolism.
53,442 90 Y-SMT 487 02/26/2003 FAX from FDA containing clinical comments on safety report dated
February 19, 2003.
53,442 90 Y-SMT 487 02/19/2003 This Briefing Book is being submitted in preparation for the scheduled 122
Type C meeting on March 20, 2003, to discuss the interim results of
our Phase I/II development program and the potential for these data to
support a filing.
53,442 90 Y-SMT 487 02/19/2003 FAX to FDA. (7-Day Safety Report).
53,442 90 Y-SMT 487 02/06/2003 In reference to the Type B meeting request (Serial No. 120), this 121
correspondence asks the Division to reconsider Novartis' request to
include a representative from the Division of Oncology Drug Products.
53,442 90 Y-SMT 487 01/31/2003 FDA LETTER containing meeting specifics in response to request
dated January 16, 2003.
53,442 90 Y-SMT 487 01/16/2003 Request for a Type B meeting with the Division to discuss the interim 120
results of Phase I/II development program.
53,442 90 Y-SMT 487 11/06/2002 This correspondence informs FDA that the regulatory responsibility 119
for this product has been transferred from ▇. ▇▇▇▇▇▇▇ to ▇.
▇▇▇▇▇▇▇▇.
53,442 90 Y-SMT 487 10/21/2002 This Annual Report covers the period June 11, 2001 through June 10, 118
2002. Includes preclinical and clinical study/safety information and a
revised Investigator's Brochure dated May 31, 2002.
53,442 90 Y-SMT 487 10/01/2002 This submission responds to the FDA request for additional information 117
on the safety report for case PHEH2002US04426.
53,442 90 Y-SMT 487 09/30/2002 ▇▇. ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇; Tumour necrosis, skin fissures, wound drainage; 116 103
Follow-up#2
53,442 90 Y-SMT 487 09/24/2002 [France] ▇▇. ▇▇▇▇ ▇▇▇▇▇▇; Hypothermia, hypoxia, Follow up #1 115 2202
53,442 90 Y-SMT 487 09/13/2002 [France] ▇▇. ▇▇▇▇▇▇▇; Hypotension NOS, diarrhoea NOS, vomiting 114 2202
NOS, hyperglycaemia NOS, hypokalaemia, follow up #1
53,442 90 Y-SMT 487 09/12/2002 [France] ▇▇. ▇▇▇▇ ▇▇▇▇▇▇; Hypothermia, hypoxia 113 2202
53,442 90 Y-SMT 487 09/04/2002 [France] ▇▇. ▇▇▇▇ ▇▇▇▇▇▇; hypothermia, hypoxia. (7 day report) 2202
53,442 90 Y-SMT 487 09/04/2002 [France] ▇▇. ▇▇▇▇▇▇-Chazot; Carcinoid syndrome,oedema NOS 112 2202
anaemia NOS, condition aggravated, hypotension NOS,
oliguria,diarrhoea NOSoedema NOS diarrhoea NOS,
hyponatraemia; follow-up 2
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 09/03/2002 [France] ▇▇. ▇▇▇▇ ▇▇▇▇▇▇; Carcinoid syndrome, metastatic pain 110 2202
flushing, hypotension NOS, bone pain aggravated, abdominal pain NOS.
FOLLOW UP #2
53,442 90 Y-SMT 487 09/03/2002 ▇▇ ▇▇▇▇▇▇ ▇'▇▇▇▇▇▇▇ MD; Dehydration, hiccups, pneumonia NOS, pyrexia, 111 2202
white blood cell count increased. FOLLOW UP #2
53,442 90 Y-SMT 487 08/29/2002 ▇▇ ▇▇▇▇▇▇ ▇'▇▇▇▇▇▇▇ MD; Dehydration, hiccups, pneumonia NOS, pyrexia, 109 2202
white blood cell count increased. FOLLOW UP #1
53,442 90 Y-SMT 487 06/20/2002 Amendment No. 5 to Study No. 103; Amendment No. 2 to Study No. 2201; 108 103 2201
Amendment No. 2 to Study No. 2202; Investigator's Brochure Edition 5,
dated May 31, 2001.
53,442 90 Y-SMT 487 06/20/2002 [United Kingdom] ▇▇. ▇▇▇▇▇▇▇; Protocol No. SMT487A 2202; carcinoid 107 2202
syndrome, collase, sweating increased, hypotension NOS, cardiac output
decreased, pallor; follow-up
53,442 90 Y-SMT 487 06/12/2002 [France] ▇▇. ▇▇▇▇▇▇▇; Carcinoid sydrome, chest pain, diarrhoea NOS, 106 2202
vomiting NOS, asthenia, hyperglycaemia NOS, sweating increased,
flushing, back pain, follow up #1
53,442 90 Y-SMT 487 06/11/2002 New investigators to Study No. 2201: Drs. ▇. ▇. ▇▇▇▇▇▇ and T. 103 2201
▇'▇▇▇▇▇▇▇
53,442 90 Y-SMT 487 05/30/2002 ▇▇. ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇; Protocol No. SMT487A 103; tumour necrosis, skin 104 103
fissures, wound drainage; follow-up
53,442 90 Y-SMT 487 05/28/2002 [France] ▇▇. ▇▇▇▇▇▇▇; Protocol No. SMT487A 2202; chest pain, diarrhoea 103 2202
NOS, vomiting NOS, asthenia, hyperglycaemia NOS, sweating increased,
flushing, back pain
53,442 90 Y-SMT 487 05/22/2002 ▇▇. ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇; Protocol No. SMT487A 103; skin fissures, 102 A103
wound drainage
53,442 90 Y-SMT 487 04/29/2002 [GREAT BRITAIN] ▇▇. ▇▇▇▇▇▇▇; Carcinoid syndrome, collapse, sweating 101 2202
increased, hypotension NOS, cardiac output decreased, pallor.
53,442 90 Y-SMT 487 04/15/2002 TELECON with FDA to discuss a suspected serious adverse event report;
MCN PHHO2002GB01805
53,442 90 Y-SMT 487 04/12/2002 ▇▇ ▇▇▇▇▇▇ ▇'▇▇▇▇▇▇▇; Dehydration, hiccups, pneumonia NOS, pyrexia, 100
white blood cell count increased.
53,442 90 Y-SMT 487 04/10/2002 New investigator to Study No. 2201: ▇. ▇▇▇▇▇, MD 099 2201
53,442 90 Y-SMT 487 03/29/2002 [Great Britain] ▇▇. ▇▇▇▇▇▇▇; Protocol No. SMT487A 2202; 098 2202
Carcinoid syndrome, collapse, sweating increased, htpotension NOS,
cardiac output decreased, pallor; follow-up
53,442 90 Y-SMT 487 03/27/2002 FAX from FDA containing responses to the Novartis' discussion
questions and additional Division comments.
53,442 90 Y-SMT 487 03/25/2002 FAX from FDA containing a literature reference for the teleconference
scheduled for March 25, 2002.
53,442 90 Y-SMT 487 03/25/2002 FAX from FDA containing FDA attendees at the March 25, 2002,
teleconference.
53,442 90 Y-SMT 487 03/21/2002 This Briefing Book is being submitted in preparation for the 097
teleconference scheduled for March 25, 2002, to discuss the
development program for this product.
53,442 90 Y-SMT 487 03/21/2002 [Great Britain] ▇▇. ▇▇▇▇▇▇▇; Carcinoid syndrome, collapse, sweating 096 2202
increased, htpotension NOS, cardiac output decreased, pallor
53,442 90 Y-SMT 487 03/13/2002 FAX to FDA of a 7-Day Safety Report; Protocol No. SMT487A 2202; 2202
carcinoid syndrome, collapse, sweating increased, hypotension NOS,
cardiac output decreased, pallor
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 03/01/2002 New investigator to Study No. 2202: ▇. ▇'▇▇▇▇▇▇▇ 095 2202
53,442 90 Y-SMT 487 02/21/2002 In preparation for the March 25, 2002, teleconference, this 094
submission contains briefing materials to support the discussion of
the development program for this product.
53,442 90 Y-SMT 487 02/14/2002 New investigator to Study No. 2202: ▇. ▇▇▇▇▇▇, MD. Changes in FDA form 093 2201 2202
1572 to Studies No. 2201 and 2202
53,442 90 Y-SMT 487 01/31/2002 Amendment No. 2 to Study No. B101. 092 B101
53,442 90 Y-SMT 487 01/31/2002 FDA LETTER scheduling a type C meeting in response to the January 25,
2002, request for a type B meeting.
53,442 90 Y-SMT 487 01/25/2002 Type B meeting request (end of Phase I/II) in order to assess if the 091
current development program will be acceptable for registration.
53,442 90 Y-SMT 487 01/15/2002 [France] ▇▇. ▇▇▇▇ ▇▇▇▇▇▇; Protocol No. SMT487A 2202; carcinoid 090 2202
syndrome, metastatic pain, flushing, hypotension NOS; follow-up
53,442 90 Y-SMT 487 01/04/2002 FAX from FDA containing chemistry comments on the July 19, 2001,
submission.
53,442 90 Y-SMT 487 01/03/2002 New investigator to Study No. 2202: ▇▇ ▇. ▇▇▇▇▇▇, MD 089 2202
53,442 90 Y-SMT 487 12/21/2001 Response to FDA comments regarding Amendment No. 4 to 088
Protocol No. 0103.
53,442 90 Y-SMT 487 12/11/2001 FAX from FDA containing clinical comments on the submission
dated November 28, 2001.
53,442 90 Y-SMT 487 12/11/2001 [Australia] Dr. ▇▇▇▇▇▇ ▇▇▇▇▇; Protocol No. CSMT487 0103; cystitis 087 0103
NOS, dysuria, micturition urgency, urine low decreased; follow-up
53,442 90 Y-SMT 487 12/11/2001 [France] Protocol No. SMT487A 2202; carcinoid syndrome, 086 2202
metastatic pain
53,442 90 Y-SMT 487 12/10/2001 Amendment No. 1 to Protocol 2201. 085 2201
53,442 90 Y-SMT 487 12/10/2001 Amendment No. 1 to Protocol 2202 084 2202
53,442 90 Y-SMT 487 12/04/2001 [France] ▇▇. ▇▇▇▇▇▇-Chazot; Protocol No. SMT487A 2201; carcinoid 083 2201
syndrome, anaemia NOS, condition aggravated, hypotension NOS,
oliguria, oedema NOS diarrhoea NOS, hyponatraemia; follow-up
53,442 90 Y-SMT 487 11/29/2001 New investigator to Study No. 0103: ▇. ▇▇▇▇▇▇, MD 082 0103
53,442 90 Y-SMT 487 11/28/2001 Amendment No. 4 to Study No. 0103 081 0103
53,442 90 Y-SMT 487 11/27/2001 [France] ▇▇. ▇▇▇▇▇▇-Chazot; Protocol No. SMT487A 2201; carcinoid 080 2201
syndrome, condition aggravated, hypotension NOS, oliguria,
anaemia NOS, oedema NOS, hyponatraemia
53,442 90 Y-SMT 487 11/13/2001 This amendment provides for two new, additional dosage strengths 079
(3330 and 4440 MBq/vial).
53,442 90 Y-SMT 487 11/01/2001 Correspondence informing the Division that ▇▇▇▇▇ Koecne, DRA, 078
will assume responsibility as the Novartis liaison for this project.
53,442 90 Y-SMT 487 10/31/2001 [Belgium] Prof van Cutsem; Protocol No. SMT487A 2202; metabolic 077 2202
encephalopathy NOS, hepatic necrosis, urinary tract infection NOS,
hepatic encephalopathy, confusion, pyrexia, somnolence, coma,
ammonia increased, memory impairment, blood bilirubin increased,
cerebral oedema; follow-up
53,442 90 Y-SMT 487 10/31/2001 [Belgium] Prof van Cutsem; Protocol No. SMT487A 2202; metabolic 076 2202
encephalopathy NOS, hepatic necrosis, urinary tract infection NOS,
hepatic encephalopathy, confusion, pyrexia, somnolence, coma
NEC, ammonia increased, memory impairment, blood bilirubin
increased; follow-up
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 10/17/2001 [France] ▇▇. ▇▇▇▇▇▇▇; Protocol No. SMT487A 2202; hypotension 075 2202
NOS, diarrhoea NOS, vomiting NOS, hyperglycaemia NOS,
hypokalaemia
53,442 90 Y-SMT 487 10/12/2001 New investigators to Study No. 0103: Drs. ▇. ▇. ▇▇▇▇▇▇, E. Van Cutsem, 074 0103 2201 2
J. Le Cloirec, ▇-▇ ▇▇▇▇▇▇▇, ▇. ▇▇▇▇▇, ▇. ▇▇ ▇▇▇▇▇▇▇, B. Chazot, ▇.
▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇-▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇▇; Study No.
2201: Drs. ▇. ▇▇▇▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇, E. Van Cutsem, ▇. ▇▇▇▇▇▇▇, J. Le
Cloirec, ▇-▇ ▇▇▇▇▇▇▇, ▇. ▇▇▇▇▇, ▇. ▇▇ ▇▇▇▇▇▇▇, B. Chazot, ▇. ▇▇▇▇▇▇,
▇. ▇▇▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇-▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇▇; Study No. 2202:
Drs. ▇. ▇▇▇▇▇▇, J. Le Cloirec, ▇-▇ ▇▇▇▇▇▇▇, ▇. ▇▇▇▇▇, ▇. ▇▇ ▇▇▇▇▇▇▇,
B. Chazot, ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇-▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇▇
53,442 90 Y-SMT 487 10/11/2001 [Australia] Dr. ▇▇▇▇▇▇ ▇▇▇▇▇; Protocol No. CSMT487 0103; cystitis 073 0103
NOS, dysuria; follow-up
53,442 90 Y-SMT 487 10/10/2001 FAX from FDA containing changes in document serial numbers for
three submissions.
53,442 90 Y-SMT 487 10/03/2001 FAX to FDA of a follow-up 7-Day Safety Report: [Australia] ▇▇. ▇▇▇▇▇▇ 0103
▇▇▇▇▇; Protocol No. CSMT487 0103; pancreatic carcinoma NOS, metastases
to liver, metastases to spine, condition aggravated, bone pain,
performance status decreased, pancytopenia, liver function tests NOS
abnormal; follow-up
53,442 90 Y-SMT 487 10/03/2001 [Australia] Dr. ▇▇▇▇▇▇ ▇▇▇▇▇; Protocol No. CSMT487 0103; 072 0103
pancreatic carcinoma NOS, metastases to liver, metastases to spine,
condition aggravated, bone pain, performance status decreased,
pancytopenia, liver function tests NOS abnormal; follow-up
53,442 90 Y-SMT 487 10/02/2001 [Australia] Dr. ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇; Protocol No. CSMT487 0103; 071 0103
tumour flare, blindness transient, diarrhoea aggravated, weakness;
follow-up
53,442 90 Y-SMT 487 10/02/2001 [Belgium] Prof van Cutsem; Protocol No. SMT487A 2202; metabolic 070 2202
encephalopathy NOS, hepatic necrosis, urinary tract infection NOS,
hepatic encephalopathy, confusion, pyrexia, somnolence, coma NEC,
ammonia increased, memory impairment
53,442 90 Y-SMT 487 09/13/2001 New investigators to Study No. 0103: Drs. ▇. ▇▇▇▇▇▇▇▇▇▇▇, K. 067 0103 2202
▇▇▇▇▇▇; new investigator to Study No. 2202: ▇▇. ▇. ▇▇▇▇▇▇▇
53,442 90 Y-SMT 487 09/07/2001 ▇▇. ▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇; Protocol No. CSMT487 0103; haemorrhagic 0103
stroke, thrombocytopenia
53,442 90 Y-SMT 487 09/05/2001 FAX to FDA of a 7-Day Safety Report: [Australia] Dr. ▇▇▇▇▇ 0103
Milleshkin; Protocol No. CSMT487 0103; pulmonary oedema NOS,
hepatic failure, pneumonitis NOS, anaemia NOS, thrombocytopenia,
cardiac failure congestive, myocardial infarction, drug ineffective,
condition aggravated, dyspnoea NOS, cough
53,442 90 Y-SMT 487 08/31/2001 [Australia] Dr. M. Michael; Protocol No. CSMT487 0103; 063 0103
▇▇▇▇▇▇▇-▇▇▇▇▇ syndrome, somatostatinoma, haematemesis,
vomiting NOS; follow-up
53,442 90 Y-SMT 487 08/31/2001 [Australia] Dr. ▇▇▇▇▇ Milleshkin; Protocol No. CSMT487 0103; 064 0103
pulmonary oedema NOS
53,442 90 Y-SMT 487 08/31/2001 FAX to FDA of a 7-Day Safety Report: ▇▇. ▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇; 0103
Protocol No. CSMT487 0103; haemorrhagic stroke,
thrombocytopenia
53,442 90 Y-SMT 487 08/31/2001 [Australia] Dr. ▇▇▇▇▇▇ ▇▇▇▇▇; Protocol No. CSMT487 0103; tumour 065 0103
flare, bone pain
53,442 90 Y-SMT 487 08/28/2001 FAX to FDA of a 7-Day Safety Report; ▇▇. ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇; 0103
Protocol No. CSMT487 0103; pancytopenia
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 08/21/2001 New investigators to Study No. 0103: Drs. ▇. ▇. ▇▇▇▇▇▇▇▇▇, ▇. ▇. 062 0103
▇▇▇▇▇▇, M.Kitchener, ▇. ▇▇▇▇▇▇▇
53,442 90 Y-SMT 487 08/20/2001 This Annual Report covers the period June 11, 2000, through June 061
10, 2001. Includes preclinical and clinical study information.
53,442 90 Y-SMT 487 08/14/2001 FAX to FDA concerning a correction to a Serial Number (Serial No.
58 was corrected to Serial No. 57).
53,442 90 Y-SMT 487 07/31/2001 [Australia] Dr. ▇▇▇▇▇▇ ▇▇▇▇▇; Protocol No. CSMT487 0103; cystitis 060 0103
NOS, dysuria
53,442 90 Y-SMT 487 07/24/2001 [Australia] Dr. ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇; Protocol No. CSMT487 0103; 059 0103
blindness transient, tumour flare, diarrhoea aggravated, weakness
53,442 90 Y-SMT 487 07/19/2001 This proposal for registration stability is in follow-up to the FDA 058
meeting held on June 21, 2001, in reference to the CMC issue
discussed in the briefing book.
53,442 90 Y-SMT 487 07/12/2001 [Australia] Dr. M. Michael; Protocol No. CSMT487 0103; 057 0103
▇▇▇▇▇▇▇-▇▇▇▇▇ syndrome, somatostatinoma, haematemesis,
vomiting NOS; follow-up
53,442 90 Y-SMT 487 07/11/2001 FAX from FDA containing overheads from the June 21, 2001
meeting.
53,442 90 Y-SMT 487 07/02/2001 [Australia] Dr. M. Michael; Protocol No. CSMT487 0103; 056 0103
▇▇▇▇▇▇▇-▇▇▇▇▇ syndrome, haematemesis, vomiting NOS
53,442 90 Y-SMT 487 06/18/2001 FAX to FDA containing a revised list of planned attendees for the
June 21, 2001, meeting.
53,442 90 Y-SMT 487 06/11/2001 FAX from FDA containing comments from the clinical and
pharmacology/toxicology reviewers on submission dated February 12,
2001.
53,442 90 Y-SMT 487 06/01/2001 New protocols: Study No. CSMT487A 2201 entitled, "A phase II 054 2201& 2202
open-label multi-center study to evaluate the efficacy and safety of
90Y-SMT 487 in subjects with metastatic insulinoma"; Study No.
CSMT487A 2202 entitled, "A phase II open-label multi-center study to
evaluate the efficacy and safety of 90Y-SMT 487 in subjects with
symptomatic malignant carcinoid tumors".
53,442 90 Y-SMT 487 05/18/2001 This Briefing Book is being submitted in preparation for the June 053
21, 2001 meeting with the Division. The documentation consists of the
registration program, preliminary results from the ongoing Phase I/II
studies, protocol outline and specific proposals for consideration.
53,442 90 Y-SMT 487 05/07/2001 In reference to the April 9, 2001, FDA request and the Novartis' 052
response of April 25, 2001, this submission contains the remaining
requested information.
53,442 90 Y-SMT 487 05/02/2001 [Neatherlands] ▇▇. ▇.▇. ▇▇▇▇▇▇▇▇; Protocol No. SMTB-151; 051 B151
myelodysplastic snydrome NOS, phlebitis NOS, urinary tract infection
NOS, peptic ulcer, epilepsy NOS, hypokalaemia, hypomagnesaemia,
metaboic acidosis NOS, anaemia NOS, leukopenia NOS, thrombocytopenia,
pyrexia, shivering, oesophageal stenosis, upper gastrointestinal
haemorrhage, hypovolaemic shock, gastritis haemorrhagic melaena;
follow-up #2
53,442 90 Y-SMT 487 04/26/2001 FDA LETTER which schedules a Type B meeting as requested in Novartis'
correspondence of March 30, 2001. Background information is requested.
53,442 90 Y-SMT 487 04/25/2001 In response to an FDA facsimile dated April 9, 2001, this submission 050
contains the requested clinical and pharmacology/toxicology
information. (4 vols)
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 04/24/2001 [Neatherlands] ▇▇. ▇.▇. ▇▇▇▇▇▇▇▇; Protocol No. SMTB-151; 049 B151
myelodysplastic syndrome NOS, anaemia Nos, leukopenia NOS,
thrombocytopenia; follow-up #1
53,442 90 Y-SMT 487 04/18/2001 Response to clinical comments provided in an FDA facsimile dated 048
April 11, 2001.
53,442 90 Y-SMT 487 04/11/2001 FAX from FDA requesting information on patient No. 1301.
53,442 90 Y-SMT 487 04/10/2001 FAX to FDA containing a list of planned particpants for the
teleconference being held today.
53,442 90 Y-SMT 487 04/10/2001 TELECON with FDA to discuss dosimetry issues related to the
treatment of pediatric patients.
53,442 90 Y-SMT 487 04/06/2001 New investigators to Study No. 0103: Drs. ▇. ▇. ▇'▇▇▇▇▇▇▇, S. P. 047 0103
▇▇▇▇▇▇
53,442 90 Y-SMT 487 03/30/2001 This correspondence requests a meeting with the Division to 046
discuss the overall development and registration program for patients
with metastatic insulinoma and symptomatic malignant carcinoid tumors.
Availability of supporting documentation is also provided.
53,442 90 Y-SMT 487 03/26/2001 Amendment No. 3 to Study No. 0103. 045 0103
53,442 90 Y-SMT 487 02/16/2001 This letter authorizes the FDA to refer to this IND to support the 044
conduct of a clinical trial being submitted by ▇. ▇'▇▇▇▇▇▇▇, MD.
53,442 90 Y-SMT 487 02/12/2001 [Netherlands] ▇▇. ▇. ▇. ▇▇▇▇▇▇▇▇; Protocol No. SMTB 151; 043 B151
myelodysplastic syndrome NOS, anaemia NOS, leukopenia NOS,
thrombocytopenia
53,442 90 Y-SMT 487 02/12/2001 [Belgium] Dr. Yamar; Protocol No. SMTB 151; myelodysplastic 042 B151
syndrome NOS, anaemia NOS
53,442 90 Y-SMT 487 02/08/2001 FAX to FDA concerning a life-threatening adverse event: B151
[Netherland] ▇▇. ▇. ▇. ▇▇▇▇▇▇▇▇; Protocol No. SMTB 151;
myelodysplastic syndrome NOS, anaemia NOS, leukopenia NOS,
thrombocytopenia
53,442 90 Y-SMT 487 02/01/2001 Amendment No. 2 to Study No. 0103. 041 0103
53,442 90 Y-SMT 487 12/20/2000 Changes in FDA Form 1572 and new investigators to Study No. 040 0103
CSMT487 0103: Drs. ▇. ▇▇▇▇▇▇▇▇▇▇, D. R. J. ▇▇▇▇▇
53,442 90 Y-SMT 487 11/22/2000 This submission is in response to FDA clinical reviewer's 039 B151
comments dated November 13, 2000 regarding protocol SMT B151.
53,442 90 Y-SMT 487 11/13/2000 FAX from FDA containing additional comments from the Clinical
Reviewer concerning Novartis' correspondence dated November 9, 2000.
53,442 90 Y-SMT 487 11/09/2000 This correspondence responds to the clinical comments provided 038
in the October 27, 2000, facsimile.
53,442 90 Y-SMT 487 11/01/2000 New investigator to Study No. CSMT487A 0103: ▇. ▇▇▇▇▇▇▇, MD 037 0103
53,442 90 Y-SMT 487 10/20/2000 Amendment No. 1 to Study No. 0103. 036 0103
53,442 90 Y-SMT 487 08/22/2000 This Annual Report covers the period June 11, 1999 through June 035
10, 2000. Includes preclinical and clinical study information,
manufacturing changes and an Investigator's Brochure dated May 2,
2000.
53,442 90 Y-SMT 487 08/14/2000 New Investigator; ▇▇. ▇▇▇▇▇ ▇. ▇▇▇▇▇ to Study CSMT487A 0103. 034 0103
53,442 90 Y-SMT 487 07/26/2000 This submission contains the minutes of the June 16, 2000, 032
teleconference to discuss the fixed dose regimen planned for Protocol
103 and about the potential renal radiation effects.
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 05/19/2000 This amendment contains updated information on the Final 031
Intermediate and Drug Substance/Drug Products for this IND. Included
is a change in the specification limit of incorporated 90Y from 99.5%
to 99.3%; background information and rationale are provided.
53,442 90 Y-SMT 487 04/13/2000 Responses to FDA clinical comments of March 29, 2000, on Study 030 B103
SMT B103, Serial No. 029, submitted March 1, 2000.
53,442 90 Y-SMT 487 03/29/2000 FDA Fax: Requesting responses to the FDA clinical comments for
submission Serial No. 029, dated March 1, 2000;
53,442 90 Y-SMT 487 03/01/2000 New protocol for Study No. CSMT487A 0103 entitled: A phase II, 029 0103
open-label, multi-center study to determine the efficacy of 90Y-SMT
487 administered intravenously to patients with refractory small cell
lung or advanced metastatic breast cancer expressing somatostatin
receptors as determined by OctreoScan scintigraphy.
53,442 90 Y-SMT 487 08/25/1999 This Annual Reports covers the period June 11, 1998 through June 028
10, 1999. Included are clinical and preclinical information, CMC
changes and an Investigator's Brochure.
53,442 90 Y-SMT 487 08/02/1999 Fax to FDA providing additional information on safety report
requested in a fax July 30, 1999.
53,442 90 Y-SMT 487 07/30/1999 FAX from FDA requesting additional information on safety report
submitted June 1, 1999.
53,442 90 Y-SMT 487 06/01/1999 (Belgium) Pauwels, S.; thrombotic microangiopathy nos, 027
glomerulonephritis.
53,442 90 Y-SMT 487 03/25/1999 Annual Report covering the period from June 11, 1997 through 026
June 10, 1998. Also includes Pre-clinical, and General Investigational
Plan for the Coming Year information.
53,442 90 Y-SMT 487 03/04/1999 Submitted a copy of the minutes from the FDA Teleconference on B151
March 4, 1999 to resolve dosing issues and reach agreement on a
clinical development plan to allow continuation of dose escalation in
study B151 and inclusion of patients with antibodies to octreotide.
53,442 90 Y-SMT 487 02/16/1999 Submitted Amendment No. 6 to Protocol SMT B151. Also submitted 025 B151
a copy of the Novartis meeting minutes.
53,442 90 Y-SMT 487 01/14/1999 Submitted proposed revisions to Study SMT B151 discussed at the 024 B151
January 7, 1999 meeting regarding dose escalation and inclusion of
patients with antibodies to Study SMT B151.
53,442 90 Y-SMT 487 01/05/1999 Submitted a copy of the update on Kantonsspital-Basel clinical
study and updated tracking and dosing information for Study SMT B151
in preparation for the 1/7/99 meeting which provides an update to
information provided in Novartis' 12/9/98 briefing document.
53,442 90 Y-SMT 487 12/09/1998 Submitted copies of the briefing documentation for the January 7, 023
1999 meeting with the Division.
53,442 90 Y-SMT 487 11/11/1998 Submitted by fax a protocol summary describing how 111In-SMT
487 and L-lysine are to be administered and a proposed list of CMC
documentation used to support the use these products in an additional
Phase I biodistribution study discussed in the 10/26/98
correspondence.
53,442 90 Y-SMT 487 10/26/1998 Submitted a request for a meeting with the Division to discuss 022
Novartis' proposal for continuation of dosing beyond the imposed
limit.
53,442 90 Y-SMT 487 09/17/1998 Submitted by Fax to the FDA information requested in their August
18, 1998 letter regarding pre- and post-dose hematology for patient
1501 and the definition for INR.
REF PRODUCT DATE DESCRIPTION SERIAL NO. PROTOCOL
--- ------------ ---------- ---------------------------------------------------------------------- ---------- ---------
53,442 90 Y-SMT 487 08/13/1998 TELECON with FDA regarding a request for protocol exception submitted
8/11/98 - protocol B151. The FDA had no objection and Novartis could
enroll the patient described in the request. The FDA recommended that
Novartis consider conducting a side arm study in patients with
antibodies to 90Y-SMT 487 or octreotides to develop appropriate
labeling information in this patient population.
53,442 90 Y-SMT 487 08/11/1998 Submitted a justification to permit an exception to protocol SMT 021 B151
B151 restriction to exclude patients with antibodies to 90Y-SMT 487
or octreotide.
53,442 90 Y-SMT 487 08/04/1998 Kvols, L.; bleeding time increased, melaena, prothrombin 020 SMTB/151
decreased.
53,442 90 Y-SMT 487 07/20/1998 TELECON with ▇▇▇▇ ▇▇▇ stating that Drs. Yaes and ▇▇▇▇▇ have B101
given permission to treat both patients for whom protocol
exceptions were requested on 7/14/98.
53,442 90 Y-SMT 487 07/16/1998 Submitted responses to comments from the medical review of IND 019
amendments 014 (3/12/98), 015 (05/7/98), and 016 (5/14/98).
53,442 90 Y-SMT 487 07/14/1998 Submitted a request for protocol exceptions to permit inclusion in 018 B151
Study SMT B151 of two patients with antibodies cross reactive with
the study drug.
53,442 90 Y-SMT 487 06/29/1998 FDA Fax: draft medical comments for amendments 014, 015, 016 dated
March 12, May 7, and May 14, 1998, respectively.
53,442 90 Y-SMT 487 06/23/1998 Kvols, L.; haemolysis, jaundice. 017 SMTB/151
53,442 90 Y-SMT 487 05/15/1998 TELECON with FDA approving Novartis' request to treat pt. 1206 as
a protocol exception.
53,442 90 Y-SMT 487 05/14/1998 TELEFAX to FDA submitting a brief history of patient 1206 for
consideration of the protocol exception.
53,442 90 Y-SMT 487 05/14/1998 Submitted Amendment No. 5 to Protocol SMT B151. 016 B151
53,442 90 Y-SMT 487 05/07/1998 Submitted by Fax a request for a protocol exception to study SMT 015 B151
B151, to exclude patients with antibodies to 90Y-SM 487 or
octreotide.
53,442 90 Y-SMT 487 03/12/1998 Submitted Amendment No. 4 to Protocol SMT B151. 014 SMT B151
53,442 90 Y-SMT 487 02/03/1998 Submitted Amendment No. 3 to Protocol SMT B151. 013 B151
53,442 90 Y-SMT 487 01/26/1998 Submitted the following new investigator to Protocol SMT B151: Dr. ▇▇▇ ▇▇▇ ▇▇▇▇
▇▇▇▇▇.
53,442 90 Y-SMT 487 01/23/1998 Submitted Amendment No. 2 to Protocol SMT B151. 011 SMT B151
53,442 90 Y-SMT 487 01/23/1998 TELECON from FDA: Informed that DMIRDP accepted response to
all outstanding stafety issues pertaining to study B151 and this
study may proceed with FP/FV on 1/26/98. Also, the 1/22/98 fax
responding to DMIRDP concerns and an initial assessment of CMC
amendment dated 1/9/98 is acceptable.
53,442 90 Y-SMT 487 01/09/1998 Information Amendment: Submitted documentation to fulfull 010
agreements reached in the October 3, 1997 teleconference
regarding chemistry issues.
Note: In addition to what is listed above, applicable materials include
correspondence and submissions from April 30, 1996 - December 3, 1997, as well
as, submissions and correspondence related to orphan drug application 02-1609
(dated July 19, 2002 - July 28, 2005).
EXHIBIT 3
ADDENDUM AGREEMENT
43
EXHIBIT 3
AMENDMENT TO THE LICENSE AGREEMENT BETWEEN NOVARTIS PHARMA
AG AND MOLECULAR INSIGHT PHARMACEUTICALS INC.
Upon execution of the ▇▇▇▇▇▇▇▇ License, this Amendment by and between Novartis
Pharma AG (referred to as "Novartis"), a corporation organized and existing
under the laws of the Switzerland and having its principal offices at
▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇, ▇▇-▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇, and Molecular Insight
Pharmaceuticals Inc., a corporation organized and existing under the laws of
Delaware, with an office at ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ ▇▇▇
(hereinafter "MIP") shall become immediately and automatically effective
("Effective Date").
WHEREAS, ▇▇. ▇▇▇▇▇▇▇▇, Professor Dr. S.W.J. Lamberts ("Lamberts") and Sandoz
Pharma Ltd ("Sandoz" now Novartis) have made joint inventions relating to
labelled somatostatin analogues covered in the Patent Case 100-7382 and 118-7595
(hereinafter the "Generic Patent"), as set out on Exhibit 1a of the License
Agreement;
WHEREAS, ▇▇▇▇▇▇▇▇, Lamberts and Sandoz Pharma Ltd entered into a contractual
relationship dated 10 October 1989 (the "Letter Agreement") under which ▇▇▇▇▇▇▇▇
granted Novartis exclusivity to the Generic Patent in return of a royalty to be
determined within a subsequent agreement ("▇▇▇▇▇▇▇▇ License");
WHEREAS, Novartis and ▇▇▇▇▇▇▇▇ have now executed the ▇▇▇▇▇▇▇▇ License;
WHEREAS, Novartis and MIP have entered into a license agreement (hereinafter the
"License Agreement") under which MIP as granted a non-exclusive license to the
Generic Patent to develop, sale and promote the Product;
WHEREAS, MIP wishes now to be granted an exclusive license under the Generic
Patent;
WHEREAS, Novartis agrees to grant MIP an exclusive license provided MIP pays a
royalty to ▇▇▇▇▇▇▇▇ in addition to the royalties due to Novartis under the
License Agreement;
WHEREAS, the License Agreement shall be amended accordingly;
NOW, THEREFORE, in consideration of the promises, covenants and agreements
hereinafter set forth, the sufficiency of which is hereby acknowledged, the
parties to this Agreement all agree as follows:
1. DEFINITIONS:
"COMMERCIALIZATION" or "COMMERCIALIZE" shall mean activities conducted by a
Party either by itself or through a Third Party and directed to marketing,
promoting, distributing, importing, exporting, offering for sale or selling a
Product, which may include pre-launch market preparation, whether undertaken by
a Party alone or with a partner or a sub-licensee. When used as a verb,
"Commercialize" means to engage in Commercialization.
"COMPOUND" shall mean the DOTA-chelated somatostatin peptide analogue known as
edotreotide.
"FIRST COMMERCIAL SALES" shall mean the first shipment of the Product to an
independent Third Party by MIP, its Affiliates, its sub-licensee, in a country
following applicable Marketing Authorization of Product in such country.
"GENERIC PATENT" shall mean the patent application GB 8828364.3, referred to as
case 100-7382, referred to as Case 118-7595 and any corresponding patent
applications or patents including any and all substitutions, extensions,
re-examination, or supplementary protection certificates, reissues, renewals,
divisions, continuations or continuations-in-part thereof, provisional patents,
patents of addition, or registrations of any kind.
"▇▇▇▇▇▇▇▇" shall mean ▇▇ ▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇ at the Erasmus Hospital in Rotterdam.
"▇▇▇▇▇▇▇▇ LICENSE" shall mean the agreement executed by and between ▇▇▇▇▇▇▇▇ and
Novartis, completing the Letter Agreement, in which ▇▇▇▇▇▇▇▇ and Novartis have
agreed on the ownership of the Generic Patent, on the share of the rights under
such Generic Patent and on payments of some considerations to one another.
"▇▇▇▇▇▇▇▇ MILESTONES" shall mean the milestone payments due by MIP to ▇▇▇▇▇▇▇▇
as set forth in clause 2 below.
"▇▇▇▇▇▇▇▇ ROYALTIES" shall mean the royalty payments due by MIP to ▇▇▇▇▇▇▇▇, as
set forth in clause 2 below.
"MAJOR EUROPEAN COUNTRY" shall mean either one of France, Germany, UK, Spain or
Italy.
"MARKETING AUTHORIZATION" shall mean the approval necessary for the
Commercialization of a Product in a specific country.
"MIP FIELD" shall mean human oncology therapeutic use.
"NET SALES" shall mean with respect to the Product the gross amount invoiced by
or on behalf of the relevant Party and its Affiliates and sublicensees for the
Product sold to Third Parties other than licensees or sublicensees in bona fide,
arms-length transactions, less customary deductions, determined in accordance
with the Party's Accounting Standards as generally and consistently applied by
that Party, to the extent included in the gross invoiced sales price of any
Product or otherwise directly paid or incurred by such Party, its Affiliates or
sublicensees with respect to the sale of such Product, such as:
(i) normal and customary trade and quantity discounts actually allowed and
properly taken directly with respect to sales of the Product;
(ii) amounts actually repaid or credited by reasons of defects, rejection
recalls, returns, rebates and allowances of goods;
(iii) chargebacks and other amounts paid on sale or dispensing of such
Product;
(iv) amounts payable resulting from governmental mandated rebate programs;
(v) tariffs, duties, excise, sales, value- added and other taxes (other
than taxes based on income);
(vi) retroactive price reductions specifically identifiable to the Product
that are actually allowed or granted;
(vii) customary cash discounts for timely payment;
(vii) delayed ship order credits;
(viii) discounts pursuant to indigent patient programs and patient discount
programs, including coupon discounts; and
(x) all freight, postage and insurance included in the invoice price.
Sales from a Party to its Affiliates shall be disregarded for purposes of
calculating Net Sales. Any of the items set forth above that would
otherwise be deducted from the invoice price in the calculation of Net
Sales but which are separately charged to Third Parties shall not be
deducted from the invoice price in the calculation of Net Sales.
(a) In the case of any sale or other disposal of the Product between or
among a Party and its Affiliates or sublicensees, for resale, Net
Sales shall be calculated as above only on the value charged or
invoiced on the first arm's-length sale thereafter to a Third Party;
(b) In the case of any sale which is not invoiced or is delivered before
invoice, Net Sales shall be calculated at the time of shipment or when
the Product is paid for, if paid for before shipment or invoice;
"PARTY" OR "PARTIES" shall mean MIP or Novartis, or MIP and Novartis, whichever
the context admits.
"PERSON" shall mean any individual, corporation, partnership, association,
joint-stock company, trust, unincorporated organization or government or
political subdivision thereof.
"PRODUCT" shall mean the yttrium 90 radiolabeled Compound for therapeutic use
and indium 111 radiolabeled Compound for dosimetry purposes, both in a form
ready for use in human clinical trials and/or by the ultimate consumer with the
possible trademark of OctreoTher(R).
"THIRD PARTY" shall mean any Person or other entity other than MIP, Novartis or
their respective Affiliates or Sublicensees of rights conveyed under this
Agreement
2. GRANT OF AN EXCLUSIVE LICENSE
2.1 Subject to the terms and conditions of this Addendum Agreement, Novartis
hereby grants to MIP a world-wide, exclusive, royalty-bearing license under the
Generic Patent to use, make, offer to sell, sell and import the Compound and the
Product in the MIP Field, as well as to use the Indium 111 labelled Compound for
dosimetry purposes in relation to the Product therapy administration.
2.2 Clause 2.1 of the License Agreement is amended accordingly.
3. CONSIDERATIONS
(A) ▇▇▇▇▇▇▇▇ LICENSE FEE. Upon the Effective Date, MIP shall pay to ▇▇▇▇▇▇▇▇,
the amount of **. Such payment will be non-refundable and will not be subject to
any claims by Novartis, an Affiliate, a Third Party or any third party for any
reason, except that such payment shall be credited against royalty payments as
set forth in clause 3c) below
(B) ▇▇▇▇▇▇▇▇ MILESTONE PAYMENT. In addition, following execution of the ▇▇▇▇▇▇▇▇
License, MIP shall pay to ▇▇▇▇▇▇▇▇ a milestone payment of ** upon the grant of a
Marketing Authorization either by the FDA, by a Major European Country Health
Authority or by the Japanese Health Authority. Such payment will be
non-refundable and will not be subject to any claims by Novartis, an Affiliate,
or any Third Party for any reason.
(C) ▇▇▇▇▇▇▇▇ ROYALTIES. Following the execution of the ▇▇▇▇▇▇▇▇ License and
further to the lump sum payments above, MIP shall pay to ▇▇▇▇▇▇▇▇ the following
percentages in return for an exclusive license on the annual world-wide Net
Sales of such exclusively licensed Product:
- ** of the annual Net Sales of the Product for Net Sales amounting
less than ** annually.
- ** of the annual Net Sales of the Product on the incremental
sales between ** and **
- ** of the annual Net sales of the Product on the incremental sales
over USD **.
Payments to ▇▇▇▇▇▇▇▇ by MIP shall be made in Euros for all Net Sales invoiced in
Euros by MIP, without currency conversion, and in US Dollars for all other Net
Sales. Such payments will be non-refundable and will not be subject to any
claims by MIP or any Third Party, for any reason, except for the first **
which are offset against the first half payment of the License Fee as set
forth in 3a).
(D) ROYALTY TERM:
The duration of the royalty obligation shall be determined on a country by
country basis. Royalties shall be payable quarterly from the First Commercial
Sales of the Product in such country (i) for the period such Product's use or
sale is Covered by a Valid Patent Claim in such country, or (ii) for a period of
ten (10) years from First Commercial Sales; and if both (i) and (ii) are
applicable, for the longer of either..
(E) REPORTS.
MIP shall generate a report to submit to ▇▇▇▇▇▇▇▇ within sixty (60) days of the
end of each calendar quarter and, after receipt of invoice from ▇▇▇▇▇▇▇▇, MIP
shall make
* confidential treatment requested *
payment in full to ▇▇▇▇▇▇▇▇ within sixty (60) days. The report shall
set forth by country, (i) the Net Sales of Product, (ii) the number of units of
Product sold and the royalties payable hereunder, (iii) the withholding taxes,
if any, required by law to be deducted in respect of such sales; (iv) the date
of the First Commercial Sales of the Product in each country during the
reporting period; and (v) the exchange rates used in determining the amount of
US Dollars, for such payments that are to be made in US Dollars. With respect to
sales of the Product invoiced in Euros, the Net Sales, and royalties payable
shall be expressed in Euros. With respect to sales of the Product invoiced in a
currency other than U.S. Dollars ("USD"), the Net Sales and amounts due to
▇▇▇▇▇▇▇▇ hereunder will be expressed in the US Dollars equivalent calculated on
a monthly basis in the currency of the country of sale and converted to their US
Dollar equivalent using the following method: the Net Sales in each country in
the Territory at each quarterly period in US Dollars shall be calculated by
translating the cumulative Net Sales in local currency in each country in the
Territory into those in US Dollars using the exchange rate mechanism in
accordance with General Accounting Practice (GAP) as generally and consistently
applied by U.S. Commercial Pharmaceutical Companies, normally used and approved
by MIP accountants for such currency calculations.
(F) AUDITS.
Upon the written request of ▇▇▇▇▇▇▇▇, and not more than once in each calendar
year, MIP shall permit an independent certified public accounting firm of
nationally recognized standing, selected by ▇▇▇▇▇▇▇▇ and reasonably acceptable
to MIP, at ▇▇▇▇▇▇▇▇'▇ expense, to have access during normal business hours to
such records of MIP as may be reasonably necessary to verify the accuracy of the
royalty reports hereunder for any years ending not more than twenty-four (24)
months prior to the date of such request. The accounting firm shall disclose to
▇▇▇▇▇▇▇▇ only whether the records are correct or not and the specific details
concerning any discrepancies. All other confidential information of the
accounting firm, including working papers, shall be shared exclusively with the
legal counsel representing the requesting party, and its subcontractors, for the
purpose of analysis and verification, on a confidential basis, such that
information provided by the accounting firm shall not be disclosed to the
requesting party.
If such accounting firm concludes that additional royalties were owed
during such period, MIP shall pay the additional royalties within thirty (30)
days of the date of ▇▇▇▇▇▇▇▇ delivery to MIP such accounting firm's written
report so concluding. The fees charged by such accounting firm shall be paid by
▇▇▇▇▇▇▇▇, provided however, that if the audit discloses that the royalties
payable by MIP for the audited period are more than one hundred and five ten
percent (105%) of the royalties actually paid for such period, then MIP shall
pay the reasonable and direct fees and expenses charged by such accounting firm.
Any overpayment determined pursuant to this provision shall be credited to the
next payment due hereunder from MIP. If no further payments by MIP will be due
hereunder then a refund of any such overpayment will be made within thirty (30)
days of the delivery of a detailed written accountants' report to the Parties
hereto.
(G) UNDERPAYMENTS.
If at any time during the term of the Agreement and thereafter, it is determined
that MIP underreported sales to ▇▇▇▇▇▇▇▇, then any royalty payments related to
such under reporting of sales shall be reported and paid to ▇▇▇▇▇▇▇▇ within
sixty (60) days of MIP's first knowledge of such underpayment with Interest.
(G) INTEREST.
Payments due by MIP under the Agreement, when overdue, shall bear interest at a
rate per annum equal to LIBOR (London Interbank Offered Rate) plus one percent
(1%) at the time such payment is due, and for the time period until payment is
received by ▇▇▇▇▇▇▇▇.
(H) CONFIDENTIAL FINANCIAL INFORMATION.
▇▇▇▇▇▇▇▇ shall treat all financial information subject to review under this
Article 3 as confidential and shall cause its accounting firm to retain all such
financial information in confidence.
(I) PAYMENT METHOD.
Royalty and Interest payments by MIP under the Agreement shall be paid in US
Dollars and/or in Euros, by bank wire transfer or bank check in immediately
available funds to such account as ▇▇▇▇▇▇▇▇ shall designate before such payment
is due.
J) EXCHANGE CONTROL. If at any time legal restrictions prevent the prompt
remittance of part or all royalties with respect to any country where each
Product is sold, payment shall be made through such lawful means or methods as
MIP shall reasonably shall determine after consultation with ▇▇▇▇▇▇▇▇.
K) ROYALTY ACCRUAL. There shall be no obligation to pay ▇▇▇▇▇▇▇▇ royalties on a
reasonable amount of samples lawfully used in the Territory and on Product used
(and not sold) during pre-clinical or clinical testing, or for physician
preference testing, teaching or experimental purposes, or for any other similar
pre-commercial uses of Product.
4. SUPPLY OF THE PRODUCT AND OF THE COMPOUND
a) Commercial Supply to Erasmus Hospital. In the event that the Product is
commercialised in Europe, including in the Netherlands, MIP shall discuss in
good faith with ▇▇▇▇▇▇▇▇ and the Erasmus Hospital the supply procedure of the
Product to the Hospital under which the Hospital shall be granted a reasonable
quantity of the Product for its commercialisation requirements for a price which
shall in no event be greater than the price agreed with other hospitals in
Europe with similar size and stature.
5. PATENT MAINTENANCE AND DEFENSE
In the event that Novartis has lost interests in the Generic Patent and has
offered it to MIP, MIP undertakes the following:
a) MIP will keep ▇▇▇▇▇▇▇▇ informed before taking any major decision
relating to the maintenance of the Generic Patent, and shall provide
written notification of such change no less than ninety (90) days prior to
any change relating to the maintenance of the Patents in a country.
b) in the event that MIP decides to abandon the Generic Patent in one or
several countries, it shall provide written notice to ▇▇▇▇▇▇▇▇ thereof no
less than ninety (90) days prior to the final date for filing a response or
submitting a payment to the relevant governmental office regarding such
Generic Patent after which the Generic Patent would become abandoned. After
receiving such notice, ▇▇▇▇▇▇▇▇ may, but is not obligated to, elect to
continue preparation, filing and prosecution or maintenance of the
discontinued Generic Patent at his sole expense. Ownership of any such
discontinued Generic Patent shall at the request of ▇▇▇▇▇▇▇▇ be fully
assigned by MIP to ▇▇▇▇▇▇▇▇ and MIP shall promptly prepare and execute such
documents and perform such acts as may be reasonably necessary for
assigning such sole ownership to ▇▇▇▇▇▇▇▇ at MIP's sole expense and at no
cost to ▇▇▇▇▇▇▇▇. ▇▇▇▇▇▇▇▇ shall be responsible for the filing of any such
documents, and the expenses related to such filings.
c) MIP shall have the first right, but not the obligation to take,
institute and prosecute legal proceedings in case of Generic Patent rights
infringement or to control the defense of any declaratory judgment action
relating to the Generic Patent.
6. CONFIDENTIALITY
Except for the right to disclose the terms of this Addendum Agreement to
▇▇▇▇▇▇▇▇, the terms and conditions of this Addendum Agreement shall be
confidential and subject to the conditions as set forth in Article 9 of the
License Agreement.
7. ENTIRE AGREEMENT
Except as set forth in Section 2,3 and 5, this Addendum Agreement shall not
replace, amend, supersede or be in lieu of any provisions set forth in the
License Agreement.
8. ADDITIONAL AGREEMENT
Novartis agrees that MIP shall be entitled to enter into a separate agreement
with ▇▇▇▇▇▇▇▇ setting forth further terms and conditions of their collaboration.