Exhibit 10.4
|
AERES Biomedical Ltd.
|
Lpath Therapeutics, Inc.
|
****CONFIDENTIAL PORTIONS OF THIS
AGREEMENT HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT****
RESEARCH COLLABORATION
AGREEMENT
This Research Collaboration
Agreement is (“Agreement”) entered into and
effective this day
of
August, 2005 (hereinafter the “Effective Date”), by and
between
(1)
AERES Biomedical
Limited , whose principal
place of business is situated at 1-3 Burtonhole Lane, Mill Hill,
London NW7 1AD, England (hereinafter also called
“AERES”);
and:
(2)
Lpath
Therapeutics, Inc. ,
whose principal place of business is located at 9191 Towne Center
Dr., Suite 310, San Diego, CA 92122 U.S.A. (hereinafter
also called “LPT”);
Recitals
WHEREAS, LPT has identified, developed and has know-how
and proprietary rights to certain monoclonal antibodies, including
a murine monoclonal antibody against Sphingosine-1-phosphate,
designated by LPT as Sphingomab™ ; and
WHEREAS, LPT has research expertise, know-how, and
proprietary rights relating to discovery research leading toward
new therapeutic products based on LPT monoclonal antibodies;
and
WHEREAS, AERES has genetic engineering expertise to
modify murine antibodies wherein certain regions of the
immunoglobulin are changed from mouse to human, which modification
is sometimes, in one aspect, referred to as
“humanizing” or “humanization”;
and
WHEREAS, AERES has developed processes and vectors to
humanize murine antibodies and has successfully humanized
antibodies for third parties and has the right to grant licenses to
third parties under the Licensed Patent Rights as hereinafter
defined; and
WHEREAS, AERES is an Affiliate of Medical Research
Council Technology whose principal office is situated at 20 Park
Crescent, London W1N 4AL (hereinafter also called
“MRCT”); and
WHEREAS, LPT is desirous of modifying its
Sphingomab™ antibody and of having AERES perform such
modification, and AERES is desirous of carrying out such
modification;
NOW, THEREFORE,
in consideration of the foregoing
promises and of the mutual covenants and obligations hereinafter
set forth, the parties agree as follows:
ARTICLE I - Definitions
As used in this Agreement, the
following terms when used with initial capital letters, shall have
the following meanings, the singular shall include the plural and
vice versa:
1.1
“AERES
Invention” shall mean any discovery or invention to the
extent (i) made or conceived or reduced to practice by or on
behalf of AERES in the performance of the humanization of
LPT’s Sphingomab™ antibody under this Agreement,
whether or not patentable, and (ii) covering only generally
applicable methods or techniques for humanizing antibody proteins
or for constructing a vector or reagent used to humanize or express
an antibody.
1.2
“AERES
IP” shall mean (i) any AERES Invention and (ii) all
patented and non-patented proprietary technology and information,
in any form whatsoever, that is: (a) necessary or useful for
making and using the Licensed Products, without regard to whether
or not the technology or information is patentable; (b) owned,
controlled, or developed by AERES, as of the Effective Date or
hereafter during the term of this Agreement; and (c) provided
by AERES to LPT hereunder, including, but not limited to
discoveries, formulae, materials, practices, methods, knowledge,
know-how, processes, trade secrets, ideas, concepts, manufacturing,
engineering, standard operating procedures, flow diagrams and
charts, quality assurance, quality control data, technical data,
manufacturing technology, research data and records, and all other
confidential or proprietary technical and business information
relating to the humanization of murine antibodies, generation of
chimeric antibodies, or any gene expression vectors used in such
methods and all improvements or modifications thereto. For
purposes of clarity, AERES IP includes AERES Inventions that
satisfy (a), (b) and (c), above, while AERES IP does not
include Licensed Patent Rights as defined hereunder.
1.3
“Affiliate” shall
mean any entity that directly or indirectly controls, is controlled
by, or is under common control with a party, and for the purposes
of this Paragraph 1.3, “control” shall mean ownership
of more than fifty percent (50%) of the voting interest, or such
lower maximum amount allowed by the law governing the ownership of
said organization.
1.4
“Business
Day” means any day, except Saturday and Sunday, on which
commercial banking institutions are open for business (i) in
New York, U.S.A., in the case of LPT and (ii) in London, U.K.,
in the case of AERES. Any other reference in this Agreement
to “day” whether or not capitalized shall refer to a
calendar day, not a Business Day.
1.5
“Commercial
Introduction” shall mean the date upon which LPT or one or
more Affiliates or Licensees (as defined hereunder) first achieves
Net Sales following the final issuance of all required licenses and
approvals by the United States Food and Drug Administration
(“FDA”) (or equivalent licenses and approvals in a
country other than the United States) allowing for the manufacture
and sale of a Licensed Product for human use.
1.6
“Commercial
Sale” means, with respect to a Licensed Product in a
particular country, the sale to a third party purchaser by LPT, its
Affiliates, and/or its Licensees of Licensed Products in such
country after all Regulatory Approvals have been obtained in
such
2
country and, if
Regulatory Approval is not required in such country, any commercial
sale of Licensed Products in such country.
1.7
“Confidential
Information” means all secret, confidential, or proprietary
information or data, whether provided in written, oral, video,
computer, or other form or format, provided by one party
(“the Disclosing Party”) to the other party (the
“Receiving Party”) pursuant to this Agreement or
generated pursuant to this Agreement, including, but not limited
to, information relating to the Disclosing Party’s existing
or proposed research and development efforts, patent applications,
business or products, the terms of this Agreement, and any other
materials that have not been made available by the Disclosing Party
to the general public. Notwithstanding the foregoing
sentence, Confidential Information shall not include any
information or materials that:
(i)
were already
known to the Receiving Party (other than under obligation of
confidentiality) at the time of disclosure by the Disclosing Party,
to the extent the Receiving Party has documentary evidence to that
effect;
(ii)
were generally
available to the public or otherwise part of the public domain at
the time of its disclosure to the Receiving Party;
(iii)
became generally
available to the public or otherwise part of the public domain
after its disclosure or development, as the case may be, and other
than through any act or omission of a party in breach of such
party’s confidentiality obligations under this
Agreement;
(iv)
were subsequently
lawfully disclosed to the Receiving Party by a third party who had
no obligation to the Disclosing Party not to disclose such
information to others;
(v)
were
independently discovered or developed by or on behalf of the
Receiving Party without the use of the Disclosing Party’s
Confidential Information, to the extent the Receiving Party has
documentary evidence to that effect;
(vi)
is approved for
release by the Disclosing Party in writing; or
(vii)
were required by
law to be disclosed.
1.8
“Designated
Antibody” shall mean a Humanized Antibody for which LPT seeks
regulatory approval through the conduct of human clinical trials,
or a US BLA, or an equivalent regulatory approval in any
country.
1.9
“Humanized
Antibody” shall mean an antibody that binds to
Sphingosine-1-phosphate and is made by AERES under this Agreement,
the antibody comprising murine complementarity determining regions
(‘CDRs’ as identified in Exhibit A 1. Winter
Patent”) derived from Sphingomab™ together with human
framework regions, and any modifications thereof.
1.10
“Licensed
Patent Rights” shall mean the patents and patent applications
licensed to AERES and with respect to which AERES has the right to
authorize and grant sublicenses, as
3
detailed in
Exhibit A hereto, including any divisions, renewals,
continuations, extensions, reexaminations, reissues, or
continuations-in-part (to the extent that any such
continuation-in-part claims subject matter as disclosed in the
patents and applications listed in Exhibit A) thereof, as well
as any patent that issues from any of the foregoing.
1.11
“Licensed
Product” shall mean a product comprising a Humanized
Antibody, the manufacture, use, offer for sale, sale, or
importation of which by an unlicensed third party would infringe
one or more Valid Claims of the Licensed Patent Rights, or which
incorporates AERES IP or AERES Inventions. The term
“Licensed Product” does not include chimeric antibodies
or murine antibodies.
1.12
“Licensee” shall
mean any organization licensed by LPT to manufacture or sell
Licensed Products. For clarity, the term
“Licensee” shall include any Sublicensee of LPT under
the Licensed Patent Rights as herein defined.
1.13
“LPT
Invention” shall mean any discovery or invention to the
extent (i) made or conceived or reduced to practice by or on
behalf of AERES, whether alone or jointly with LPT, in the
performance of the humanization of LPT’s Sphingomab™
antibody, whether or not patentable, and (ii) not an AERES
Invention. For the purpose of clarity, LPT Inventions shall
include without limitation all of the DNA sequences encoding
Humanised Antibody genes included in the AERES Deliverables as
defined in Paragraph 2.2 but otherwise excluding DNA sequences
encoding for AERES’ proprietary expression vectors.
.
1.14
“LPT
IP” shall mean any and all patented and non-patented
proprietary technology and information, in any form whatsoever,
that is necessary or useful for making and using Humanized
Antibodies, without regard to whether or not the technology or
information is patentable, which is (i) owned with the right
to disclose or otherwise controlled by LPT as of the Effective Date
or hereafter during the term of this Agreement and is first
disclosed by LPT to AERES, or (ii) is assigned, or is obliged
hereunder to be assigned, to LPT by AERES, including, without
limitation, processes, techniques, methods, products, transformed
cells, other biological materials and compositions which are
necessary or useful for making or using the Humanized
Antibodies. LPT IP shall not include AERES IP or AERES
Inventions.
1.15
“Net
Sales” shall mean the amount received in respect of gross
sales by LPT, its Affiliates and/or its Licensees from the sale of
Licensed Products to independent third parties, less the following
amounts: (i) discounts or rebates actually allowed or granted;
(ii) credits or allowances actually granted on rejections or
returns (not exceeding the original billing), including for recalls
or damaged goods; (iii) outbound freight, postage, shipping,
and insurance charges prepaid or allowed; (iv) sales, tariff
duties, surcharges, and/or use or excise taxes, levies, or other
similar governmental charges included in the invoiced amount; and
(v) any similar and customary deductions taken in accordance
with U.S. generally accepted accounting principles (GAAP)
consistently applied. Provision of Licensed Products for
promotional, sampling, or educational purposes and for use in
clinical trials contemplated under this Agreement shall not be
considered in determining Net Sales, so long as no consideration
(monetary or non-monetary other than incidental) is received in
exchange therefor. No allowance or deduction shall be made for
commissions or collections or overhead, by whatever name
known.
4
1.16
“Regulatory
Approval” in a country means any and all approvals (including
price and reimbursement approvals), licenses, registrations, or
authorization of any governmental agency, necessary for the
manufacture, use, storage, import, transport, and/or sale of a
Licensed Product in such country.
1.17
“Research
Collaboration” means the research activities undertaken by
the parties in accordance with the Research Plan as set forth in
Annex A hereto.
1.18
“Sublicense”,
“Sublicense Agreement” and “Sublicensee”
shall mean, and include, without limitation, any relationship in
which LPT grants a third party a license, option, right of first
refusal, or other such right under any of the licenses granted by
AERES to LPT under this Agreement for the purpose of allowing such
third party to develop and commercialize one or more Licensed
Products.
1.19
“Valid
Claim” shall mean a claim in any unexpired issued patent
within the Licensed Patent Rights or AERES IP which has not been
held invalid by a non-appealed or unappealable decision by a court
or other appropriate body of competent jurisdiction.
ARTICLE II - Research
Collaboration
2.1
Upon the
execution of this Agreement and the receipt from LPT of the
necessary materials and information as specified in Paragraph 2.2,
below, AERES will undertake the humanization of LPT’s
Sphingomab™ antibody in accordance with the Research set
forth in Annex A hereto. The Research Plan may be amended as
mutually agreed to by the parties. The parties agree to use
commercially reasonable efforts to perform their respective
responsibilities under the Research Collaboration.
2.2
Under the
Research Plan, AERES shall provide the following biological
materials, data, information, and reports to LPT (collectively, the
“AERES Deliverables”):
(i)
[Gene
expression vector inserts
incorporating Sphingomab™
heavy chain and light cha
in CDRs, one or
more (if more than one is made by AERES) of each of (a) and
(b) below:]
(a)
[Sphingomab™ human
heavy chain framework region gene insert (but not the heavy chain
expression vector) made by replacing the original human CDRs in the
human heavy chain framework region with the Sphingomab mouse CDRs;]
and
(b)
[Sphingomab™ human
light chain framework region gene insert (but not the light chain
expression vector) made by replacing the original human CDRs in the
human light chain framework region with the Sphingomab mouse
CDRs;]
(ii)
All data and
reports relevant to the humanization of Sphingomab™
including, but not limited to data on antigen binding and
expression levels.
5
(iii)
Final written
reports setting forth in reasonable detail the results of
AERES’s humanisation of LPT antibody Sphingomab™
including, without limitation, the structural and synthesis
information (including, but not limited to, the DNA and amino acid
sequence information) for all Humanised Antibodies.
2.3
After the
Effective Date, LPT shall, at its expense and without charge to
AERES, deliver to AERES at least one cell line that produces
LPT’s Sphingomab™ antibody and such LPT know-how
including related technical information as sufficient (in the
reasonable judgment of both parties) to enable AERES to carry out
its humanization obligations under this Agreement (the “LPT
Deliverables”). The LPT Deliverables shall be
deemed to be Confidential Information of LPT; provided, however,
that the obligations hereunder of non-use and non-disclosure
related to any LPT Deliverable shall continue for so long as such
LPT Deliverable remains Confidential Information. The
transfer from LPT to AERES of the cell line(s) producing
LPT’s Sphingomab™ antibody is solely for the purpose of
AERES conducting its humanization obligations under this Agreement,
and for no other purpose, and AERES shall hold the LPT Deliverables
in strict confidence. AERES shall maintain within its sole
possession and control the cell lines producing LPT’s
Sphingomab™ antibody, Sphingomab™ antibody expressed
from such cell line(s), and any vectors containing LPT’s
Sphingomab™ antibody. Notwithstanding anything to the
contrary herein, except for the purpose of carrying out the
activities specified in the Research Plan, AERES will not for its
own account or for the benefit of a third party propagate, culture,
express, produce, distribute, transfer, or sell any LPT Deliverable
or any product or material derived therefrom for any purpose
whatsoever without the prior written consent of LPT.
2.4
AERES shall
maintain an appropriate, secure work site for conducting its
activities under the Research Plan. AERES shall cause its
research teams performing the activities under the Research Plan to
keep detailed contemporaneous records and data in connection with
the Research Plan, and to prepare reports detailing work to date,
which shall be furnished to LPT in a timely manner upon completion
of each research milestone specified in the Research Plan or as
otherwise agreed between the parties. AERES shall permit duly
authorized employees of LPT to have access to AERES’s
laboratories from time to time at mutually agreeable times and upon
reasonable notice. Any AERES personnel performing work
pursuant to the Research Plan shall be obligated under his/her
terms and conditions of employment to (i) assign his/her
entire worldwide right, title, and interest in and to any
discovery, invention, improvement, or technological advance,
including any AERES Invention, and any associated intellectual
property, including any AERES IP, to AERES and (ii) comply at
all times with the confidentiality obligations imposed on AERES
under this Agreement.
2.5
Upon completion
of its research activities hereunder or the earlier termination
thereof in accordance with the terms hereof, AERES shall provide to
LPT samples of all Humanised Antibodies and cell lines expressing
the same, as agreed to by the parties, and AERES shall issue a
final written report to LPT. The final written report shall
set forth in reasonable detail the results of AERES’
humanisation of LPT antibody [XYZ] including, without limitation,
the structural and synthesis information (including, but not
limited to, the DNA and amino acid sequence information) for all
Humanised Antibodies.
6
2.6
All worldwide
right, title, and interest in Humanised Antibodies, LPT Inventions
and LPT IP shall belong solely to LPT. At the request of LPT, AERES
shall execute such documents as LPT may reasonably request in order
to reflect LPT’s ownership of Humanized Antibodies, LPT
Inventions and LPT IP , and to cooperate with and assist LPT in all
material respects with regard to LPT’s efforts to register
LPT’s rights in and to the Humanised Antibodies, LPT
Inventions and LPT IP. AERES shall maintain, within its sole
possession and control, samples of Humanized Antibodies, samples of
any vectors containing Humanized Antibodies, and samples of cell
lines producing Humanized Antibodies, and AERES shall not
distribute, transfer, or sell any such Humanized Antibodies,
vectors, or cell lines (or any AERES Deliverable) to any third
party for any purpose whatsoever without the prior written consent
of LPT.
2.7
Notwithstanding
anything to the contrary herein, AERES retains all worldwide right,
title, and interest in the Licensed Patent Rights and AERES IP used
or developed in the performance of AERES’s obligations under
this Agreement. LPT is granted (under Paragraph 4.1, below) a
limited license to use any vectors and sequences included in the
AERES IP only insofar as such vectors and sequences are used in
conjunction with the expression of LPT’s Sphingomab™
antibody and Humanized Antibodies derived therefrom by AERES
subject to the terms of this Agreement. AERES shall not,
except in the event of termination of this Agreement by AERES
pursuant to Paragraphs 8.4, 8.5 or 8.6 hereof, exercise any of its
proprietary rights arising hereunder or otherwise restrict LPT from
commercializing any Humanized Antibody produced hereunder in any
manner. All AERES Inventions shall be owned by AERES and
shall be deemed to be included in the AERES IP and the Licensed
Patent Rights, as applicable.
ARTICLE III - Payments for the Research
Collaboration
3.1
LPT shall pay to
AERES for undertaking to perform the humanization work pursuant to
the Research Collaboration the sum of
[*** ]
United Kingdom Pounds
[*** ]
(the “Initial Payment”). The Initial Payment is
non-refundable and shall be made within thirty (30) days after the
Effective Date.
3.2
LPT will pay
AERES in United Kingdom Pounds for its research efforts carried out
in accordance with the Research Plan the research milestone
payments (the “Research Milestone Payments”) as set
forth in the cost schedule attached as Annex B within thirty
(30) days following the documented completion of, and delivery by
AERES of the AERES Deliverables and LPT’s receipt of an
invoice from AERES for, each research milestone specified in Annex
A (whether the applicable milestone is achieved by AERES or any of
its Affiliates or consultants). The Initial Payment and the
Research Milestone Payments shall be paid by wire transfer in
United Kingdom Pounds (UK£) within thirty (30) days of the
date of invoice by wire transfer to the account of AERES Biomedical
Ltd. at [***
],
or such other bank and/or account as may be notified to LPT by
AERES from time to time, and the transaction identified as
“Agreement dated [Effective Date] between AERES Biomedical
Ltd. and LPT”.
***CONFIDENTIAL PORTIONS OF THIS
AGREEMENT HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT.
7
3.3
In the event that
LPT does not agree that any one of the Research Milestones has been
met, LPT shall notify AERES within ten (10) Business Days from
the date of delivery of the materials or written report required by
said Milestone. LPT shall be deemed to have accepted a
particular AERES Deliverable unless it notifies AERES of any defect
or non-conformity within ten (10) Business Days after it
receives the particular AERES Deliverable. On receipt
of any such notification, LPT and AERES will each use best efforts
to reach agreement on the clarification and redefinition of the
Milestone(s) and (if applicable) corresponding cost schedule.
In the event of a dispute arising under this Paragraph 3.3, LPT
shall pay the disputed amount to AERES and payment so made will be
without prejudice to either party’s right to seek resolution
of the dispute under Paragraph 11.13, below.
3.4
Except as
otherwise expressly provided herein or agreed to by the parties in
writing, all payments hereunder shall be made free and clear of and
without deduction or deferment in respect of any demand, set-off,
counterclaim, or other dispute, and so far as is legally possible,
such payment shall be made free and clear of any taxes payable on
said payments imposed by or under the authority of government or
any public authority, and, in particular, but without limitation
where any sums due to be paid to AERES hereunder are subject to any
withholding or similar tax, LPT shall pay such additional amount as
shall be required to ensure that the net amount received by AERES
hereunder will equal the full amount which would have been due to
AERES hereunder had no such tax been imposed or required by law to
be withheld, unless said tax is withheld for the benefit of
AERES. LPT and, without prejudice to the foregoing, AERES
shall use their best endeavours to do all such lawful acts and to
sign all such lawful documents as will enable LPT to take advantage
of any applicable legal provision or any double taxation treaty
with the object of paying the sums due AERES without imposing or
withholding any tax. However, as of the Effective Date, sales made
outside the EU do not attract any UK sales tax (i.e., they are
classified as “VAT Exempt” in respect of UK Value Added
Tax) while, aside from UK Corporation Tax payable by AERES which,
for the sake of clarity, is not rechargeable to LPT under this
Paragraph 3.4, AERES is not aware of any prospective change to the
VAT Exempt status or any withholding or other tax presently payable
on sales to the USA.
ARTICLE IV - License Grant and
Payments
4.1
AERES hereby
grants to LPT (i) a non-exclusive worldwide sublicense, with
the right to grant further Sublicenses, under the Licensed Patent
Rights to make, have made, use, import, offer for sale, and/or sell
Licensed Products; and (ii) an exclusive worldwide license,
with the right to grant Sublicenses, under the AERES IP to make,
have made, use, import, offer for sale, and/or sell Licensed
Products.
4.2
Granting of
Sublicenses
(i)
LPT, without
being required to obtain the consent of AERES, shall be entitled to
grant further non-exclusive Sublicenses to its Licensees to make,
have made, use, import, offer for sale, and/or sell Licensed
Products.
8
(ii)
LPT undertakes
upon the execution of any Sublicense Agreement under sub-clause 4.1
(i) above promptly to advise AERES of the identity of the
Sublicensee and nature of the rights so licensed.
4.3
The following
arrangements shall not require the prior consent of
AERES:
(i)
The appointment
of any person as agent or distributor to market, sell, use, or
otherwise dispose of the Products in any part of the
world.
(ii)
The
subcontracting of manufacture of Products by Licensee.
4.4
The following
arrangement shall require the prior written consent of
AERES:
(i)
LPT may authorize
a Licensee to grant further sublicenses under the Licensed Patent
Rights in respect of Licensed Products only with the prior written
consent of AERES such consent shall not unreasonably be withheld
but shall be subject to said Licensee also obtaining the consent of
MRC.
4.5
Regulatory
Milestone Payments . In consideration of
the rights, privileges, and licenses granted herein, LPT shall pay
to AERES in United States Dollars (US Dollars) each of the
following regulatory milestone payments in respect of each
Designated Antibody (“Regulatory Milestone
Payments”):
(i)
AERES will
receive either:
(a) [*** ]
of LPT’s negotiated Regulatory Milestone Payment (if any)
receivable from a development partner or Licensee, on first filing
of a US IND or equivalent in any country; or
[*** ]
US Dollars
[*** ];
or:
(b) [*** ]
US Dollars
[*** ],
whichever is the greater of (a) or (b);
(ii)
AERES will
receive either:
(a) [*** ]
of LPT’s negotiated Regulatory Milestone Payment(s) (if any)
receivable from a development partner or Licensee, subsequent to
filing of a US IND or equivalent in any country and up to or on
initiation of the first Phase II clinical trial in any country; or
[*** ]
US Dollars
[*** ];
or:
(b) [*** ]
US Dollars
[*** ],
whichever is the greater of (a) or (b);
(iii)
AERES will
receive either:
(a) [*** ]
of LPT’s negotiated Regulatory Milestone Payment(s) (if any)
receivable from a development partner or Licensee, subsequent to
the filing of a US BLA or equivalent in any country and up to or on
initiation of the first Phase III clinical trial in any country; or
[*** ]
US Dollars
[*** ]
or:
(b) [*** ]
US Dollars
[*** ],
whichever is the greater of (a) or (b);
***CONFIDENTIAL PORTIONS OF THIS
AGREEMENT HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT.
9
(iv)
AERES will
receive either:
(a) [*** ]
of LPTs’ negotiated Regulatory Milestone Payment (if any)
from a development partner or Licensee on the first approval of a
US BLA or equivalent in any country; or
[***
] US Dollars
[*** ],
or:
(b) [*** ]
US Dollars
[*** ],
whichever is the greater of (a) or (b).
Each of the above Regulatory
Milestone Payments shall become due and payable forthwith upon the
corresponding payment becoming due and payable to LPT by a
development partner or Licensee or, where no such payment is
payable to LPT, on LPT first receiving notification from the
relevant regulatory authority of the granting of the Regulatory
Approval upon which it is contingent, as specified above in this
Clause 4.2. It is understood and agreed that each of the
above Regulatory Milestone Payments shall be due only one time with
respect to any Designated Antibody.
4.6
Royalties
. In
consideration of the rights, privileges and license granted herein,
LPT shall pay to AERES on a country-by-country, Licensed
Product-by-Licensed Product basis an earned royalty of [***
]
of the Net Sales
of Licensed Products, provided that there is at least one Valid
Claim within the Licensed Patent Rights in such country that covers
the Licensed Product; if not, the earned royalty shall be to
[*** ]
of Net Sales in such country. All royalties payable by LPT to AERES
shall be paid on a country-by-country basis from the date of the
first Commercial Sale by LPT, its Affiliates, and/or Licensees of
each Licensed Product in each country until the date which is the
later of: (i) the expiration of the last to expire Valid Claim
within the Licensed Patent Rights, a which claim covers the
manufacture, use, or sale of the applicable Licensed Product in
said country; or
(ii) [*** ]
years after the first Commercial Sale of the applicable Licensed
Product in said country if only covered by AERES IP (the
“Royalty Period”); provided , however ,
during any portion of the Royalty Period that there is no Valid
Claim in such country, the royalty rate shall be reduced to
[*** ].
On a country-by-country basis and on a Licensed Product-by-Licensed
Product basis, upon the scheduled expiration of the obligation to
pay royalties with respect to the sale of such Licensed Product in
such country, LPT shall have a fully paid-up, royalty free,
perpetual and irrevocable license, with the right to grant
Sublicenses, under the AERES IP to make, have made, use, import,
offer for sale and/or sell Licensed Products in said
country.
4.7
Limitations
. The
following limitations shall apply with respect to royalties payable
by LPT to AERES pursuant Paragraph 4.3, above:
(i)
Sales between LPT
and its Affliliates and/or Licensees shall not be subject to a
royalty, but in such cases the royalty specified in Paragraph 4.3,
above, shall be calculated upon LPT’s, its Affiliates and/or
Licensees’ Net Sales to independent third parties in
arm’s-length transactions. An agreement between LPT and an
Affiliate shall not be a sublicSublicense under the Licensed Patent
Rights. The obligation to pay a royalty to AERES under this
Article is imposed only
***CONFIDENTIAL PORTIONS OF THIS
AGREEMENT HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT.
10
once with respect to the
same unit of Licensed Product regardless of the number of Valid
Claims concerning the same.
(i) [***].
In the event that [***] pays [***] as consideration for [***] or
[***] where, [***], under Paragraph [***] will be (i) [***] or (ii)
where the [***] is [***] shall apply country by country only where
and to the extent that such [***].
(ii) Notwithstanding
anything to the contrary herein, it is understood and agreed that
the [***] that is equal to [***] as specified in the following
formula:
[***]
[Where [***] is the [***] or, if [***] generally
shall apply.]
4.8
LPT agrees that
any Sublicenses under the Licensed Patent Rights granted by it
shall provide that the obligations owed by LPT to AERES under
Articles IV, V, VII, VIII and X of this Agreement (save for
Paragraphs 8.9 and 8.10, which apply only to LPT) shall be
reflected in the wording of the Sublicense with obligations no less
onerous for the Sublicensee than those set forth in this Agreement
with respect to LPT which LPT shall use its best endeavours to
enforce to the benefit of AERES in the event of any breach thereof.
In particular LPT shall ensure that AERES can monitor and enforce
payment of all royalties due to it in consequence of this
Agreement.
4.9
If, during the
Term (defined in Paragra
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