Exhibit
10.1
EXECUTION
COPY
DUPUYTREN’S DISEASE
LICENSE AGREEMENT
This
DUPUYTREN’S DISEASE LICENSE AGREEMENT (the “
Agreement ”), effective as of November 21, 2006 (the
“ Effective Date ”), is entered into by and
between BioSpecifics Technologies Corp., a corporation organized
and existing under the laws of Delaware (“ BTC
”), and the Research Foundation of the State University of
New York for and on behalf of Stony Brook University, a nonprofit,
educational corporation organized and existing under the laws of
New York (the “ Research Foundation ”). BTC and
the Research Foundation shall sometimes be referred to herein
individually as a “ Party ” and collectively as
“ Parties .”
RECITALS
WHEREAS,
<OMITTED AND FILED
SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION>
WHEREAS,
<OMITTED AND FILED
SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION>
WHEREAS,
<OMITTED AND FILED
SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION>
WHEREAS, <OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION>
WHEREAS, <OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION>
WHEREAS, <OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION>
WHEREAS, <OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION>
WHEREAS, <OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION>
WHEREAS, <OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION>
WHEREAS, <OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION>
WHEREAS, the Research Foundation now wishes to
license the Licensed Know-How to BTC, and BTC wishes to license the
Licensed Know-How from the Research
Foundation, on
the terms and conditions set forth in this Agreement.
NOW, THEREFORE,
in consideration of the mutual promises, covenants and agreements
set forth below, the Parties agree as follows:
ARTICLE
I.
DEFINITIONS
For the
purposes of this Agreement, the following capitalized words and
phrases, whether used in the singular or plural, shall have the
following meanings:
1.1 “
Affiliate ” means any corporation or other business
entity controlled by, controlling, or under common control with
another entity, with “control” meaning direct or
indirect beneficial ownership of more than 50% (or such lesser
percent provided that ownership is accompanied by the power to
direct the management or policies of the entity) of (a) the voting
stock in the case of a corporation, or (b) the profits interest or
decision-making authority in the case of an unincorporated business
entity.
1.2
“ Auxilium ”
means Auxilium Pharmaceuticals, Inc., a corporation organized and
existing under the laws of Delaware.
1.3
“ Auxilium License
Agreement ” means the agreement dated as of June 3, 2004
by and between BTC and Auxilium, as amended on May 6, 2005 and as
may be subsequently amended from time to time, by which BTC granted
to Auxilium certain licenses, as defined therein.
1.4
“ BTC Patents ”
has the meaning set forth above in the recitals.
1.5
“ Combination Product
” means any product containing both an agent or ingredient
which constitutes a Licensed Product and one or more other active
agents or ingredients which do not constitute Licensed
Products.
1.6
“ Development Program
” means the clinical studies previously performed by B&H
with injectable collagenase pertaining to Dupuytren’s
disease, as described more fully in Article II hereof.
1.7
“ EMEA ” means
the European Medicines Evaluation Agency, which coordinates the
scientific review of human pharmaceutical products under the
centralized licensing procedure of the European Community, and
includes any successor agency.
1.8
“ Enzyme ” means
an enzyme constituted of collagenase obtained by fermentation of
Clostridium histolyticum, purified by chromatography,
lyophilized and substantially free from other proteinases, and any
variants or derivatives thereof.
1.9
“ European Union
“ or “EU” means the countries of the European
Union (or its successor) as constituted on the Effective Date and
future members of the European Union upon their admission for full
membership with commercial rights and privileges.
1.10
“ FDA ” has the
meaning set forth above in the recitals.
1.11
“ Field ” means
the prevention or treatment of Dupuytren’s
disease.
1.12
“ First Commercial
Sale ” means (a) the date of first sale following FDA or
other regulatory approval of the NDA, MAA (as defined below) or
equivalent marketing license application filed for a Licensed
Product in any country, or (b) if regulatory approval is not
required the first commercial sale of a Licensed Product in either
case, to an independent party not an Affiliate, Sublicensee or
subagent of the seller.
1.13 “
Information ” means (a) techniques, technology,
practices, methods, procedures, inventions, discoveries, knowledge,
know-how, trade secrets, skill, experience, gene or protein
sequences, technical data, test data, analytical and quality
control data, formulas or software programs, and (b) all compounds,
compositions of matter, cells, cell lines, assays, and all other
biological or chemical materials and samples.
1.14 “
Joint Inventions ” means any inventions in the Field,
whether patentable or not, which are jointly conceived, discovered,
developed or otherwise made, during the Development Program by at
least one BTC employee or person contractually required to assign
or license the intellectual property rights covering such
inventions to BTC and at least one Stony Brook employee or person
contractually required by virtue of New York state law to assign or
license the intellectual property rights covering such inventions
to the Research Foundation.
1.15
“ Licensed Know-How
” means (i) any proprietary Information or materials related
to the manufacture, preparation, formulation, use or development of
the Enzyme, the Licensed Products or injectable collagenase
pertaining to Dupuytren’s disease and shall include
formulations, processes, techniques, formulas, biological,
chemical, assay control and manufacturing, technical, pre-clinical,
clinical or other data, methods, know-how, and trade secrets; (ii)
all Information, not generally known, which is owned by the
Research Foundation or is rightfully held with right to sublicense
as of the Effective Date, or which was developed, discovered,
conceived, reduced to practice, or acquired by the Research
Foundation or by B&H and assigned by B&H to the Research
Foundation as a result of the Development Program and which (a)
relates to the Licensed Products or (b) relates to the methods,
processes or techniques for the manufacture or use of the Licensed
Products or (c) relates to injectable collagenase pertaining to
Dupuytren’s disease and (iii) any Joint
Inventions.
1.16
“ Licensed Products
” means pharmaceutical products containing Enzyme as an
active ingredient and any reformulation, improvement, enhancement,
combination, refinement, or modification thereof, which are made,
used and sold in the Field; provided however, the Licensed Products
shall specifically exclude dermal formulations labeled for topical
administration.
1.17
“ MAA ” means a
Marketing Authorization Application filed with the EMEA.
1.18
“ NDA ” means a
New Drug Application, Biologics License Application or a Product
License Application filed with the FDA.
(a) with respect to sales of Licensed Products by
BTC or its Affiliates, the gross sales price actually received less
the following items to the extent they are paid and included in the
invoice price:
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(i)
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customary trade
discounts actually allowed;
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(ii)
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packing,
freight, and insurance costs;
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(iii)
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sales, use,
value-added and excise taxes;
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(iv)
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import, export
and customs duties and taxes;
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(v)
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credit for
returns, allowances or trades actually allowed; and
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(vi)
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government
mandated rebates, if any; and
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(b) with respect to sales of Licensed Products by a
Sublicensee (as defined below), the net sales price as required to
be reported to BTC by the Sublicensee pursuant to the written
sublicense agreement between them.
Sales by BTC,
its Affiliates and Sublicensees to resellers or others for further
formulation, processing, repackaging or relabeling shall be
excluded, and only the subsequent resale to independent customers
shall be deemed Net Sales.
In the case of
Combination Products for which the agent or ingredient constituting
a Licensed Product and each of the other active agents or
ingredients not constituting a Licensed Product have established
market prices when sold separately, Net Sales shall be determined
by multiplying the Net Sales for each such Combination Product by a
fraction, the numerator of which shall be the established market
price for the Licensed Products contained in the Combination
Product and the denominator of which shall be the sum of the
established market prices for the Licensed Products plus the other
active agents or ingredients contained in the Combination Product.
When separate market prices are not established, then the Parties
shall negotiate in good faith to determine a fair and equitable
method of calculating Net Sales for the Combination Product in
question, taking into account factors such as relative cost and
relative therapeutic or diagnostic contribution.
1.20 “
Orphan Drug Designation ” means the special
designation of Licensed Product(s) by FDA’s Orphan Product
Division which provides the Licensed Product(s) with the
opportunity to obtain additional market exclusivity from the date
the drug receives FDA approval and also possible tax and regulatory
approval benefits. The term “Orphan Drug Designation”
shall include any foreign counterparts of the foregoing.
1.21 “
Sublicensee ” means Auxilium or any person or entity
who receives in the future a sublicense from BTC pursuant to
Article III hereof.
1.22
“ Territory ”
means all countries of the world.
ARTICLE
II.
DEVELOPMENT
PROGRAM
2.1
Development Program . Pursuant to the Royalty Agreement and
certain other prior agreements, which are being terminated
contemporaneously herewith, B & H, individually or collectively
together with other Stony Brook employees, performed certain
pre-clinical, clinical, regulatory, process development and
manufacturing work related to injectable collagenase pertaining to
Dupuytren’s disease.
2.2
FDA Letters. The Research Foundation consents to, and
otherwise ratifies, the action previously taken by B&H pursuant
to the Royalty Agreement in executing and delivering the FDA
Letters.
ARTICLE
III.
LICENSE
GRANT
3.1
License Grant. The Research Foundation hereby grants to BTC
and its Affiliates a worldwide exclusive license for the Licensed
Know-How in the Field. The Research Foundation further grants to
BTC and its Affiliates a worldwide exclusive license to use the
Licensed Know-How to make, use and sell in any manner Licensed
Products in the Field, except to the extent that BTC, its
Affiliates or Sublicensees enters into a material transfer
agreement, clinical trial agreement or any similar agreement that
allows the Research Foundation to do research or clinical
development.
(a) BTC shall be entitled to grant sublicenses of
its rights hereunder, provided that any Net Sales of Licensed
Products by a BTC Sublicensee shall be deemed to be Net Sales of
BTC for purposes of royalty payments due hereunder, and BTC shall
remain obligated to pay all royalties due with respect to Licensed
Products sold by any Sublicensee. If BTC shall grant any
sublicenses in addition to the Auxilium License Agreement under
this Agreement, then it shall obtain the written commitment of such
additional Sublicensees to abide by all applicable terms and
conditions of this Agreement and BTC shall remain fully responsible
to the Research Foundation for the performance of all such terms by
such additional Sublicensees. Upon the termination of this
Agreement, each additional Sublicensee shall have the option to
convert its sublicense to a direct license with the Research
Foundation on the same terms as in the sublicense
agreement.
(b) The Research Foundation hereby acknowledges and
consents to the sublicense that BTC has previously granted to
Auxilium pursuant to the Auxilium License Agreement in respect of
the Licensed Products.
3.3
Subagents. It is agreed that BTC has the right to take the
following actions, none of which shall constitute a sublicense
hereunder and none of which shall be subject to Section 3.2
herein:
(a) appointing an agent or distributor to market,
sell or otherwise dispose of Licensed Products; and
(b) subcontracting the development, manufacture or
packaging of Licensed Products.
3.4
Term. The term of said license will continue in effect for
as long as the Licensed Products are sold.
3.5
<OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION>
ARTICLE
IV.
ROYALTIES
4.1
Royalties. Commencing with the First Commercial Sale, BTC
will pay running royalties on Net Sales of Licensed Products by BTC
and its Affiliates and Sublicensees on a country-by-country basis.
<OMITTED AND FILED
SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION>
4.2
Royalty
Period. The royalty obligations of BTC shall commence upon the
date of the First Commercial Sale and continue for the longer of
(i) the last to expire valid claim of a patent covering the
Licensed Product, (ii) the expiration of the regulatory exclusivity
period conveyed by Orphan Drug Designation with respect to the
Licensed Product or (iii) June 3, 2016.
4.3
Currency; Conversion; Taxes.
Royalty payments shall be paid in
U.S. Dollars at the address of the Research Foundation set forth in
Section 10.6 below, or such other place as the Research Foundation
may reasonably designate in writing, consistent with applicable
laws and regulations. Any taxes which BTC or its Affiliates or
Sublicensees shall be required by law to withhold or pay upon
remittance of the royalty payments shall be deducted from the
royalty payable to the Research Foundation and paid on its behalf
as required. BTC shall furnish the original of any official
receipts for such taxes. If any currency conversion shall be
required in connection with the payment of royalties hereunder,
such conversion shall be made by using the average of the daily
exchange rates for such currency quoted by the Wall Street
Journal’s (New York edition) foreign exchange desk for each
of the last three (3) banking days of each calendar quarter, or, in
the case of sales by Sublicensees, using the exchange rates
provided for in the written agreements between BTC and such
Sublicensees.
4.4
Currency Transfer Restrictions. If in any country in the
Territory the payment or transfer of royalties on Net Sales in such
country is prohibited by law or regulation, BTC shall notify the
Research Foundation of the conditions preventing such
transfer, and
shall deposit the blocked payments in local currency in a
recognized banking institution in the relevant country for the
credit of the Research Foundation.
4.5
Payments by Others. With respect to any sales of Licensed
Products by BTC, its Affiliates or Sublicensees, BTC shall have the
right to cause any Affiliate, Sublicensee or other designee to make
direct payment to the Research Foundation of the royalties
otherwise due for such sales. The Research Foundation shall accept
such payments and the amount of royalties to be paid by BTC shall
be reduced by the amount of such payments actually received by the
Research Foundation.
ARTICLE
V.
REPORTS, PAYMENTS AND
ACCOUNTING
5.1
Royalty Reports and Payments. BTC agrees to make written
reports and royalty payments to the Research Foundation within 90
days after the close of each calendar quarter during the term of
this Agreement, beginning with the quarter in which the First
Commercial Sale occurs. These reports shall show for the calendar
quarter in question all Net Sales of Licensed Products and the
royalty due thereon, together with the same information for
Licensed Products sold by Affiliates and Sublicensees (if
applicable). With respect to sales of Licensed Products by
Sublicensees, reports need only include information reflected in
the reports required by Section 5.4 below which are actually
received during the calendar quarter in question. Concurrently with
the making of each report, BTC shall remit any royalty payment due
for the period covered by the report. BTC will make a good faith
attempt, using commercially reasonable biotech industry practices,
to differentiate between Net Sales of Licensed Products and sales
of similar products outside of the Field in calculating the amount
of the royalty due hereunder to the Research Foundation. Absent
manifest error, BTC’s good faith differentiation shall be
binding and conclusive on the Parties.
5.2
Termination Report. Within ninety (90) days after the date
on which BTC and its Affiliates and Sublicensees last sell any
Licensed Products, BTC shall make a final termination report
containing the same quarterly information required
above.
5.3
Accounting. BTC agrees to keep written or digitally stored
records for a period of three (3) years from the end of each
reporting period in sufficient detail to enable the royalties
payable to be determined, and further agrees to permit its books
and records to be examined during normal business hours by an
independent accounting firm, selected by the Research Foundation
and reasonably satisfactory to BTC, from time-to-time on reasonable
notice, but not more often than once per year. Such examination
must be made confidentially and the auditing firm shall be required
to enter into reasonable confidentiality agreements. The expense of
such examination shall be borne by the Research Foundation except
that in the event the results of the audit reveal a discrepancy in
the Research Foundation’s favor of 10% or more, then
reasonable out-of-pocket audit fees shall be paid by BTC. Any
discrepancy will be promptly corrected by a payment or refund, as
appropriate.
5.4
Third
Party Reports. BTC agrees to require, as a term of any
sublicense agreement, that the Sublicensee shall render written
reports to BTC of Net Sales of Licensed Products no less frequently
than twice per year and in sufficient detail to enable the
royalties payable by BTC hereunder to be determined (“
Third Party Reports ”). BTC shall also require
Sublicensees to keep records concerning Net Sales for a period of
at least three (3) years, and to permit reasonable examination of
such records by an independent accounting firm selected by BTC.
Not