Exhibit 10.6
EXCLUSIVE LICENSE
AGREEMENT
between
THE REGENTS OF THE UNIVERSITY OF
CALIFORNIA
and
NEUROGESX, INC.
for
HIGH DOSE CAPSAICIN FOR NEUROPATHIC
PAIN
UCSF Case No. SF00-056
UC Case No. SF00-056
EXCLUSIVE LICENSE
AGREEMENT
For
HIGH DOSE CAPSAICIN FOR
NEUROPATHIC PAIN
This license agreement (the
“Agreement”) is made effective November 1, 2000
(the “Effective Date”) between THE REGENTS OF THE
UNIVERSITY OF CALIFORNIA, a California corporation having its
statewide administrative offices at 1111 Franklin Street, Oakland,
California 94607-5200, (“The Regents”), and acting
through its Office of Technology Management, University of
California San Francisco, 1294 Ninth Avenue - Suite 1, Box 1209,
San Francisco, CA 94143-1209 (“UCSF”), and NEUROGESX,
INC., a California corporation having a principal place of business
at 969C Industrial Boulevard, San Carlos, California, (the
“Licensee”).
BACKGROUND
A. Certain inventions, generally
characterized as “High Dose Capsaicin Relieves Neuropathic
Pain” (collectively the “Invention”), were made
in the course of research at the University of California San
Francisco by Wendye R. Robbins as described in UCSF Case Number
SF00-056, and are covered by Regents’ Patent Rights as
defined below;
B. The Licensee has evaluated the
Invention under a Secrecy Agreement with The Regents effective
August 20, 1999 (U.C. Control
No. 2000-20-0104);
E. The Licensee and The Regents have
executed a Letter of Intent dated June 1, 2000 (U.C. Control
No. 2000-30-0050) for the purpose of negotiating a license to
Regents’ Patent Rights;
F. The Licensee wishes to obtain
rights from The Regents for the commercial development, use, and
sale of products from the Invention, and The Regents is willing to
grant those rights so that the Invention may be developed to its
fullest and the benefits enjoyed by the general public;
and
G. The Licensee is a “small
business firm” as defined in 15 U.S.C. §632;
H. Licensee recognizes and agrees
that royalties due under this Agreement will be paid on both
pending patent applications and issued patents;
In view of the foregoing, the
parties agree:
1. DEFINITIONS
1.1 “Regents’ Patent
Rights” means the Regents’ interest in any subject
matter claimed in or covered by any of the following: Pending U.S.
Patent Application Serial No. 08/746,207 entitled
“Therapeutic Method with Capsaicin and Capsaicin
Analogs” filed November 6, 1996, the
continuation-in-part U.S. Patent Application Serial
No. 08/990,633 entitled “Transdermal Therapeutic Device
and Method with Capsaicin and Capsaicin Analogs” filed
December 15, 1997 and assigned to The Regents; pending PCT
Patent Application Serial No. PCT/US98/25794 of the same title,
filed December 8, 1998 and assigned to The Regents; and
continuing applications thereof including divisions, substitutions,
continuation-in-part applications (but only to the extent however,
that claims in the continuation-in-part applications are entitled
to the priority filing date of the foregoing applications); any
patents issuing on said applications including reissues,
reexaminations and extensions; and any corresponding foreign
applications or patents based on said applications.
1.2 “Licensed Product”
means any material for which the manufacture, use, sale, or import
would constitute an infringement of a Valid Claim within the
Regents’ Patent Rights if not for the license granted to the
Licensee under this Agreement.
1.3 “Licensed Method”
means any method for which the use or sale would constitute an
infringement of a Valid Claim within the Regents’ Patent
Rights if not for the license granted to the Licensee under this
Agreement.
1.4 “Net Sales” means
the total of the gross invoice prices of Licensed Products sold or
Licensed Methods performed by the Licensee, an Affiliate, or a
Sublicensee, less the sum of the following actual and customary
deductions where applicable: cash, trade, or quantity discounts;
sales, use, tariff, import/export duties or other excise taxes
imposed on particular sales; transportation charges and allowances
(including insurance); or credits to customers because of
rejections, returns, or expired goods. For purposes of calculating
Net Sales, transfers to an Affiliate or Sublicensee for end use by
the Affiliate or Sublicensee will be treated as sales to an
independent third party for purposes of calculating earned
royalties (as specified in Article 7)
1.5 “Affiliate” means
any corporation or other business entity in which the Licensee owns
or controls, directly or indirectly, at least fifty percent
(50%) of the outstanding stock or other voting rights entitled
to elect directors, or in which the Licensee is owned or controlled
directly or indirectly by at least fifty percent (50%) of the
outstanding stock or other voting rights entitled to elect
directors; but in any country where the local law does not permit
foreign equity participation of at least fifty percent (50%), then
an “Affiliate” includes any company in which the
Licensee owns or controls or is owned or controlled by, directly or
indirectly, the maximum percentage of outstanding stock or voting
rights permitted by local law.
1.6 “Field of Use” means
all fields and uses.
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1.7 “Commercial Sale”
means with respect to each Licensed Product in each country, a bona
fide commercial sale of such Licensed Product following marketing
approval by the regulatory authority in such country; provided that
where such a first commercial sale has occurred in a country for
which government pricing or government reimbursement approval is
needed for widespread commercial sale (for clarification, the
parties acknowledge that no such approval is required in the United
States) then a sale shall not be deemed a Commercial Sale until
such pricing or reimbursement approval has been
obtained.
1.8 “IND” means an
Investigational New Drug Application, as defined in the U.S.
Federal Food, Drug and Cosmetic Act and the regulations promulgated
thereunder, or comparable filing in a foreign jurisdiction, in each
case with respect to a Licensed Product.
1.9 “NDA” means a New
Drug Application, as defined in the U.S. Food, Drug and Cosmetic
Act and the regulations promulgated thereunder, and all subsequent
supplements to that NDA, as well as any equivalent foreign
application, registration or certification in the relevant country,
such as a Marketing Approval Application (“MAA”) in
Europe, in each case with respect to a Licensed Product.
1.10 “Phase I” means a
clinical trial involving the initial introduction of a Licensed
Product into humans and which is designed to determine the
metabolism and pharmacologic actions of the Licensed Product in
humans, the side effects associated with increasing doses, and, if
possible, to gain early evidence on effectiveness.
1.11 “Phase III” means
human clinical trials of a Licensed Product performed after
obtaining preliminary evidence suggesting effectiveness of the
drug, and are intended to gather the additional information about
effectiveness and safety that is needed to evaluate the overall
benefit-risk relationship of the drug, to provide an adequate basis
for physician labeling, and to form the basis for approval to
market such Licensed Product.
1.12 “Valid Claim” means
a claim of an issued and unexpired patent or a claim of a pending
patent application within the Regents’ Patent Rights which
has not been held invalid or unenforceable by a court or other
government agency of competent jurisdiction from which no appeal
can be or has been taken, and has not been admitted to be invalid
or unenforceable through re-examination, disclaimer or otherwise;
provided that if a claim of a pending application has not issued as
a claim of an issued patent within the Regents’ Patent Rights
within ten (10) years after the filing date from which such
claim takes priority, such pending claim shall not be a Valid Claim
for purposes of this Agreement until such time as such claim
issues.
1.13 “Sublicensee”
means, with respect to a particular Licensed Product, a third party
to whom Licensee has granted a right or license to make, use, sell
or import such Licensed Product or practice the Licensed Method. As
used in this Agreement, “Sublicensee” shall also
include a non-Affiliate third party to whom Licensee has granted
directly or indirectly a right to distribute such Licensed Product,
provided that such third party is responsible for some or all of
the marketing and promotion of such Licensed Product within the
territorial region in which it has such sublicensed
rights.
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2. LIFE OF PATENT EXCLUSIVE GRANT
2.1 Subject to the limitations set
forth in this Agreement, The Regents grants to the Licensee a
world-wide license under Regents’ Patent Rights to make, have
made, use, sell, offer to sell, import, have imported, and
otherwise exploit Licensed Products and to practice Licensed
Methods.
2.2 Except as otherwise provided in
this Agreement, the license granted in Paragraph 2.1 is exclusive
for the life of this Agreement.
2.3 The license granted in
Paragraphs 2.1 and 2.2 is limited to methods and products that are
within the Field of Use. For other methods and products, the
Licensee has no license under this Agreement.
2.4 To the extent it is legally
able, The Regents also grants Licensee a non-exclusive license to
any proprietary know-how relating to Regents’ Patent Rights
that The Regents has an interest in and is reasonably needed by
Licensee to practice and/or commercially develop Licensed Products
and/or Licensed Methods.
2.5 The Regents reserves the
nontransferable right to use the Invention and associated
technology for its own bona fide non-commercial research and
education purposes.
3. SUBLICENSES
3.1 The Regents also grants to the
Licensee the worldwide right to issue sublicenses to third parties
to make, have made, use, sell, offer to sell, import, have
imported, and otherwise exploit Licensed Products and to practice
Licensed Methods, as long as the Licensee has current exclusive
rights thereto under this Agreement. To the extent applicable,
sublicenses must include, at a minimum, all of the rights of and
obligations due to The Regents and contained in this
Agreement.
3.2 In addition, Licensee shall pay
The Regents a percentage of all compensation received by Licensee
from Sublicensees, other than royalties on sales of products and
Licensed Products, as direct consideration for the grant of a
sublicense for Licensed Products or Licensed Methods under the
Regents’ Patent Rights, as set forth below (“sublicense
fees”).
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3.2.1 Sublicense fees shall consist
of amounts received in the form of up-front fees and milestone
payments, but shall not include any amounts received as support for
research and development activities, as a loan, as income derived
from debt financing, for the purchase of an equity interest in the
Licensee, as reimbursement for patent and patent related expenses,
as earned royalties on net sales, or as consideration for the grant
of intellectual property rights and materials other than those
claimed under Regents’ Patent Rights. Licensee shall pay The
Regents the following percentages of sublicense fees:
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Aggregate Sublicense
Fees
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25%
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< $250,000
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10%
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$250,000 -- $2,000,000
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5%
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> $2,000,000
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3.2.2 For purposes of calculating
the applicable percentage for the foregoing, “Aggregate
Sublicense Fees” shall be the cumulative amount of sublicense
fees stated in each sublicense of Regents’ Patent Rights
entered into by Licensee and assuming that all milestone payments
therein are made to Licensee. However, the actual sublicensee fee
payments due The Regents from Licensee shall be determined based on
the actual amounts of sublicensee fees received by Licensee in each
calendar year during the term of this Agreement.
3.3 The Licensee shall promptly
provide The Regents with a copy of each sublicense issued; collect
all payments due The Regents from Sublicensees; and summarize and
deliver all reports due The Regents from Sublicensees, provided
that the Licensee may redact from such copy any terms which are not
necessary to determine whether Licensee has complied with its
obligations under this Agreement.
3.4 Upon termination of this
Agreement for any reason, the Licensee shall assign to The Regents
all sublicenses which are consistent with the rights and
obligations due The Regents hereunder. The Regents, at its sole
discretion, shall determine whether the Licensee shall cancel or
assign to The Regents any sublicenses that are inconsistent with
the rights and obligations due The Regents hereunder, provided
however, that prior to terminating any such sublicense, The Regents
shall discuss with the Sublicensee the terms under which such
Sublicensee may retain such sublicense.
4. PAYMENT TERMS
4.1 Licensee shall pay to The
Regents earned royalties (as specified in Section 7) on Net
Sales of Licensed Products on a Licensed Product-by-Licensed
Product and country-by-country basis. The earned royalty due
pursuant to this Section will continue on such basis until the sale
of a Licensed Product in such country does not infringe a Valid
Claim within the Regents’ Patent Rights.
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4.2 Licensee shall pay earned
royalties quarterly on or before February 28, May 31,
August 31 and November 30 of each calendar year. Each
payment will be for earned royalties accrued within the
Licensee’s most recently completed calendar
quarter.
4.3 Licensee shall pay the
applicable percentage of sublicense fees to The Regents on or
before February 28 of each calendar year. Each payment will be
for sublicensee fees received by Licensee during the most recently
completed calendar year.
4.4 Beginning in 2001, the Licensee
shall pay the annual maintenance fee (as defined in
Section 6.1) to The Regents on or before each anniversary of
the Effective Date.
4.5 All monies due The Regents are
payable in United States dollars. When Licensed Products are sold
for monies other than United States dollars, the Licensee shall
first determine the applicable earned royalty in the currency of
the country in which Licensed Products were sold and then convert
the amount into equivalent United States funds, using the exchange
rate quoted in the Wall Street Journal on the last business day of
the reporting period. In no event shall the Licensee be required to
pay The Regents more than twenty-five (25%) of its total
annual revenue derived from Licensed Products.
4.6 Earned royalties earned on sales
occurring in any country outside the United States may not be
reduced by any taxes, fees, or other charges imposed by the
government of such country on the payment of royalty income. The
Licensee is also responsible for all bank transfer charges.
Notwithstanding this, all payments made by the Licensee in
fulfillment of The Regents’ tax liability in any particular
country will be credited against earned royalties or fees due The
Regents for sales of Licensed Products in that country.
4.7 If at any time legal
restrictions prevent the prompt remittance of earned royalties by
the Licensee from any country where a Licensed Product is sold, the
Licensee shall deposit the amount owed in an interest-bearing
account within that country until such time as the restrictions are
lifted, at which time the Licensee shall promptly convert the
current balance of said account into United States funds and pay
such amount to The Regents.
4.8 If any patent or Valid Claim
within Regents’ Patent Rights is held invalid in a final
decision by a court of competent jurisdiction and last resort and
from which no appeal has or can be taken, all obligation to pay
earned royalties based on that patent or Valid Claim or any Valid
Claim patentably indistinct therefrom will cease as of the date of
final decision. The Licensee will not, however, be relieved from
paying any earned royalties that accrued before the final decision
or that are based on another patent within Regents’ Patent
Right or Valid Claim not involved in the final decision.
4.9 If payments, rebillings or fees
are not received by The Regents when due, the Licensee shall pay to
The Regents interest charges on the unpaid amount at a rate of ten
percent (10%) per annum or the maximum permitted by law,
whichever is less. Interest is calculated from the date due until
actually received by The Regents.
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5. LICENSE-ISSUE FEE
5.1 Within sixty (60) days
after the Effective Date, the Licensee shall pay to The Regents a
license-issue fee equal to the total amount of out-of-pocket
costs and expenses of patent prosecution of the Regents’
Patent Rights incurred by The Regents through the Effective Date.
This fee is non-refundable, non-cancelable, and is not an advance
against earned royalties.
6. LICENSE MAINTENANCE
FEE
6.1 The Licensee shall also pay to
The Regents a royalty in the form of a license maintenance
fee of five thousand dollars ($5,000) beginning on the second
anniversary of the Effective Date and continuing annually on each
anniversary of the Effective Date thereafter. This license
maintenance fee is not due on any anniversary of the Effective Date
if, as of that Date, the Licensee, its Affiliates, or its
Sublicensees are engaged in Commercial Sales of a Licensed Product
and paying earned royalties to The Regents on the sales of such
Licensed Product. License maintenance fees are non-refundable and
not an advance against earned royalties, except that, if Licensee
completes the first Commercial Sale of a Licensed Product after
making such License Maintenance Fee payment but before the next
anniversary of the Effective Date, then Licensee may deduct such
amount from the earned royalties that would otherwise be due The
Regents.
7. EARNED ROYALTIES, MINIMUM ANNUAL
ROYALTIES AND MILESTONE PAYMENTS
7.1 The Licensee shall also pay to
The Regents an earned royalty of one percent (1%) of
the Net Sales of Licensed Products worldwide, up to a maximum of
one million dollars ($1,000,000) per year.
7.2 If it becomes necessary for
Licensee to license intellectual property rights from an
unaffiliated third party, and Licensee is required to pay a royalty
to that unaffiliated third party in order to practice Licensed
Methods and make, use or sell Licensed Products, and the combined
earned royalty due The Regents and unaffiliated third parties
exceeds eleven percent (11%), then the earned royalties to be
paid to The Regents by Licensee shall be reduced by an amount equal
to one-half (1/2) the excess over eleven percent (11%) of
the royalty rate(s) due to the unaffiliated third party(ies).
However, in no event shall the amount paid to The Regents be
reduced below fifty percent (50%) of the original earned
royalty amounts due The Regents.
7.3 No cumulation of earned
royalties shall be made in the event a Licensed Product is covered
by Valid Claims of more than one patent within Regents’
Patent Rights.
7.4 No earned royalty shall be
payable under this Article 7 with respect to transfers of
Licensed Product to customers or prospective customers for use in
research and/or development, in clinical trials or other regulatory
purposes, as samples, or in any other transfer that is not a
Commercial Sale.
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7.5 In the event that a Licensed
Product is sold in combination with other products, components or
services (other than another Licensed Product) for which no amounts
would be payable to The Regents if such other products, components
or services were sold or performed separately, amounts invoiced for
such combination sales for purposes of calculating Net Sales of the
Licensed Product in such combination shall be the Net Sales of the
Licensed Product calculated by multiplying the Net Sales of the
combination product by the fraction A/B where A is the average
price on a unit basis of Licensed Product containing a certain
amount (by weight) of active ingredient, and B is the average unit
price of the combination product containing the same amount of that
active ingredient. In the event that such average sale price cannot
be determined for both the Licensed Product and the other
product(s) in combination, Net Sales for purposes of determining
royalty payment shall be mutually agreed by the parties based on
relative value contributed by each component, and such agreement
shall not be unreasonably withheld.
7.6 Following the first Commercial
Sale of the first Licens