Document:

exv10w30c

 

Exhibit 10.30C

Second Amendment to the License Agreement

     This Second Amendment to the License Agreement (the “Second Amendment”) is made and
entered into as of August 20, 2004, by and between The University of Kansas Center for
Research, Inc., a Kansas not-for-profit corporation (“Licensor”), and ProQuest
Pharmaceuticals, Inc., a Kansas corporation (“Licensee”). Licensor and Licensee may be
referred to herein as a “Party” or, collectively, as “Parties.”

Recitals

     Whereas, Licensor and Licensee entered into a License Agreement (the “Agreement”)
effective April 2, 1999, wherein Licensor granted Licensee an exclusive license under certain
proprietary cyclic peptide and prodrug technologies to develop, make, use and sell products; and

     Whereas, on April 26, 2002, the parties entered into a First Amendment to the License
Agreement (the “First Amendment”), effective February 6, 2002, wherein the parties amended the
terms and conditions of the Agreement (with the initial Agreement, as amended by the First
Amendment, being referred to herein as the “Amended Agreement”); and

     Whereas, the Parties now desire to make certain additional amendments to the terms of
the Amended Agreement to license an additional invention;

     Now, therefore, the Parties agree as follows:

	1.  	Amendment of the Amended Agreement

     The Parties hereby agree to amend the terms of the Amended Agreement as provided below,
effective as of August 20, 2004. To the extent that the Amended Agreement is explicitly amended by
this Second Amendment, the terms of the Second Amendment will control where the terms of the
Amended Agreement are contrary to or conflict with the following provisions. Where the Amended
Agreement is not explicitly amended, the terms of the Amended Agreement will remain in force.
Capitalized terms used in this Second Amendment that are not otherwise defined herein shall have
the same meanings as such terms are defined in the Amended Agreement.

     1.1 Amendment of Article 1 of the Amended Agreement

Paragraph 1.08 of the Amended Agreement is amended by adding the following second
sub-paragraph to such Paragraph:

 

 

On June 11, 2002, Dr. Roger A. Rajewski and Dr. Michelle P. McIntosh submitted to KU and
Licensor a certain invention disclosure questionnaire describing an invention referred to as
“Delivery of a Sedative/Anti-Emetic Compound Via Inhalation (the “Inhalation Technology”).
(The invention disclosure questionnaire and related draft patent application are attached
hereto as Exhibits 1 and 2.) The term “Patent Rights” shall also include – in addition to
any rights that would be otherwise treated as “Patent Rights” under Paragraph 1.08 – (i) the
draft patent application and any revisions thereof filed on the Inhalation Technology (which
patent application shall be treated as patents within the definition of “Existing
Application”), (ii) any patents issued thereon, (iii) all patents and patent applications
claiming (or which could claim) priority therefrom including all divisions, continuations,
continuations-in-part, patents of addition, and substitutions of any of the foregoing, (iv)
any corresponding foreign patent applications and patents, and (v) all registrations,
reissues, reexaminations or extensions of any kind with respect to any of the foregoing.

               1.2 Amendment of Paragraph 3.01 of the Amended Agreement

Paragraph 3.01 of the Amended Agreement is hereby deleted and replaced in its entirety as
follows:

3.01 As consideration for the license granted to Licensee by Licensor under this Agreement,
Licensee shall pay to Licensor as royalties the following percentages of License Revenue
derived by Licensee for each patent:

	 	 	 	 	 
	Patent or Application	 	Percentage of License Revenue	 
	U.S. Patent No. 5,672,584 – Cyclic Prodrugs
of Peptides and Peptide Nucleic Acids Having
Improved Metabolic Stability and Cell
Membrane Permeability
	 	 	2.0	%
	U.S. Patent No. 6,204,257 – Water Soluble
Prodrugs of Hindered Alcohols and Phenols
(the “Alcohol and Phenol Patent”)
	 	 	2.0	%
	U.S. Patent No. 6,451,776 – Water Soluble
Prodrugs of Hindered Alcohols and Phenols
(the “Alcohol and Phenol Patent II”)
	 	 	2.0	%

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	Patent or Application	 	Percentage of License Revenue	 
	U.S. Patent No. 5,985,856 – Water Soluble
Prodrugs of Secondary and Tertiary Amine
Containing Drugs and Methods of Making
Thereof (the “Secondary and Tertiary Amine
Patent”)
	 	 	2.0	%
	Any patent or patent application described
in the second sub-paragraph of Paragraph
1.08 (i.e., the sub-paragraph dealing with
the Inhalation Technology)
	 	 	2.0	%

     (i) No royalties shall be owed in connection with an individual patent listed above
until a United States patent application is issued from the United States Patent and
Trademark Office with respect to that patent. From the Effective Date until the issuance of
any patent described in the second sub-paragraph of Paragraph 1.08, Licensee shall record
and maintain complete and accurate records of License Revenue potentially allocable to the
Existing Applications (i.e., the application(s) described in the second sub-paragraph of
Paragraph 1.08). If any such Existing Application issues as a patent, then Licensee shall
pay to Licensor such percentage of License Revenue allocable as above to each such issued
patent as is or has been received by Licensee for the period beginning on the Effective Date
and ending as set forth in subsection (ii) below.

     (ii) Subject to Paragraph 7.05, royalties due under this Paragraph 3.01 shall be
payable on a country-by-country and Product-by-Product (as applicable) basis until the
expiration, nullification, final judgment of invalidity or abandonment after exhaustion of
all appeals of the last-to-expire, last-to-be nullified, last-to-be held invalid or last to
be abandoned claim of an issued patent under the Patent Rights or under the Existing
Applications in such country covering a Product or other applicable License Revenue.

     (iii) Notwithstanding the foregoing provisions of this Article 3, in no event shall the
royalty payable with respect to License Revenue from a particular Product exceed 2.0%,
regardless of the number of patents that cover such Product.

          
        1.3 Amendment of Article 7 of the Amended Agreement

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Article 7 of the Amended Agreement is hereby deleted and replaced in its entirety as
follows:

Article 7 – Patent Prosecution and Maintenance.

7.01
Beginning August 20, 2004, Licensee –
as between parties hereto – shall be responsible
for the preparation, filing and prosecution of the Existing Applications (defined in Section
1.1 above) in the United States. Except as set forth in Section 7.05 below, (i) beginning
August 20, 2004, Licensee shall diligently endeavor to prepare, file and prosecute the
Existing Applications, (ii) Licensee shall be responsible for and shall pay all fees and
expenses associated with such preparation, filing and prosecution of the Existing
Applications in the United States (to the extent such fees and expenses are incurred after
August 20, 2004), and (iii) Licensee shall be responsible for, and shall pay all fees and
expenses associated with, the maintenance of (a) the Cyclic Peptide Patent, the Second and
Tertiary Amine Patent, the Alcohol and Phenol Patent and the Alcohol and Phenol Patent II,
and (b) all other Patents issuing from such Existing Applications.

7.02 Licensee shall have the right to prepare, file, prosecute and maintain, at its own
expense, additional patent applications in the United States claming (or which could claim)
priority from the Existing Applications.

7.03 (i) Beginning August 20, 2004, Licensee shall be solely responsible for the preparation,
filing, prosecution and maintenance of patent applications under the Patent Rights in foreign
countries designated by Licensee; and except as set forth in Section 7.05 below, (a) Licensee shall
pay all fees and expenses associated with preparing, filing and prosecuting such applications (to
the extent incurred after August 20, 2004), and (b) Licensee shall be responsible for all fees and
expenses associated with the maintenance of Patents arising from such applications (to the extent
incurred after August 20, 2004).

     (ii) Subject to Paragraph 7.05 below, Licensee shall reimburse Licensor for all reasonable
costs and expenses incurred after the Amendment Effective Date and prior to August 20, 2004, and
associated with the filing, prosecution and maintenance of Patent Rights in non-United States
countries as were (a) agreed upon in writing by the parties, and (b) actually incurred by Licensor
and not reimbursed by Third Parties. Licensee shall reimburse such amount within thirty (30) days
of receipt from Licensor of an invoice itemization and documenting such costs and expenses.

     (iii) Upon completion of Licensee’s Phase I Financing, Licensee shall promptly reimburse
Licensor for reasonable costs and expenses
associated with the filing and prosecution of Patent Rights in non-United States countries as were:

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(a) agreed upon in writing by the Parties or agreed upon in writing by ProQuest (as may be
evidenced by Licensor’s receipt of invoice from patent counsel for expenses directed by ProQuest)
and (b) actually incurred by Licensor and not reimbursed by Third Parties for the period beginning
on the Effective Date and ending on the Amendment Effective Date. Attached is a true and correct
statement that sets forth the amount of such costs and expenses (Exhibit 3). Licensee shall have
the right to audit and verify the invoices and relevant documents that support such costs and
expenses. Licensee shall reimburse Licensor for such filing and patent costs as set forth in this
subsection (iii) in four (4) equal payments. The first such payment shall be due within sixty (60)
days of the completion of Licensee’s Phase I Financing, and the subsequent three (3) payments shall
be made, respectively, at four (4) month intervals thereafter.

7.04 Licensor and Licensee shall cooperate fully in (i) the preparation, filing, prosecution and
maintenance of Patent Rights and of all Patents and Patent applications licensed to Licensee
hereunder, and (ii) the execution of all papers and instruments required to apply for, prosecute
and maintain Patent Rights in any country. Each party shall provide to the other prompt notice as
to all matters which come to its attention and which may affect the preparation, filing,
prosecution or maintenance of any Patent Rights. Licensee shall provide Licensor with copies of
all relevant documents and shall solicit comments from Licensor regarding the prosecution of the
patent applications under Patent Rights. Licensee shall provide Licensor sufficient time before
the due date and filing thereof to review and comment on patent applications and all material
correspondence to and from the U.S. Patent and Trademark Office and patent offices in foreign
countries related to all Patent Rights governed by this Agreement. Licensee shall use all
reasonable efforts to amend any such Patent applications to include claims reasonably requested by
Licensor.

7.05 Pursuant to Paragraph 9.03, Licensee may terminate its obligations under Paragraph 7.01, 7.02
and 7.03 as to all Patent Rights or as to any jurisdiction or any part of the Patent Rights upon
sixty (60) days prior written notification to Licensor of such termination. If Licensee so elects,
then both the scope of the license grant in Article 2 and the payment obligations under Paragraphs
3.01, 7.01, 7.02 and 7.03 shall be narrowed accordingly. Nothing in this section shall relieve
Licensee of (i) its obligations to reimburse Licensor for all expenses of any Patent Rights
incurred by Licensor prior to the surrender by Licensee of such Patent Rights or (ii) any
obligation hereunder to pay for expenses incurred by Licensee.

7.06 In the event Licensee elects not to pursue the Patent prosecution within its control of any
Patent Rights, Licensee shall give Licensor sufficient notice to afford Licensor the opportunity to
do so at Licensor’s cost, in which event
Licensor will own such Patent Rights free and clear of any license to Licensee under this
Agreement.

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     1.4. Clarification of Effective Date.

Section 1.3 above adopts a new Article 7 that amends the Amended Agreement. New Sections 7.01 and
7.03 contain certain provisions that, by their terms, do not apply to periods prior to August 20,
2004. The parties acknowledge and agree that with respect to such provisions in new Section 7.01
and 7.03, periods prior to August 20, 2004 shall be governed by the provisions of the Amended
Agreement, as it existed prior to the Second Amendment.

     1.5. Amendment of Paragraph 9.03 of the Amended Agreement.

Paragraph 9.03 of the Amended Agreement is hereby deleted and replaced in its entirety as follows:

9.03 In addition, Licensee will have the right to terminate this Agreement in its entirety, or as
to either the Cyclic Peptide Patent, the Secondary and Tertiary Amine Patent, the Alcohol and
Phenol Patent, the Alcohol and Phenol Patent II, or any patent described in the second
sub-paragraph of Paragraph 1.08 above (relating to the Inhalation Technology), upon sixty (60) days
prior written notice to Licensor. Upon a termination of this Agreement with respect to the Cyclic
Peptide Patent, the Secondary and Tertiary Amine Patent, the Alcohol and Phenol Patent, the Alcohol
and Phenol Patent II, or any patent described in the second sub-paragraph of 1.08 above (relating
to the Inhalation Technology), the same shall thereafter cease to be within the definition of
License for all purposes of this Agreement. Upon the termination of this Agreement with respect to
any particular patent or application, the same, and all divisions, continuations,
continuations-in-part, foreign counterparts, patents of addition, and substitutions of, and all
patents issuing on, such patent or application, together with all registrations, reissues,
reexaminations or extensions of any kind with respect to any of such patents, shall cease to be
within the definition of Patent Rights for all purposes of this Agreement.

	2.  	Miscellaneous
	 
	2.1  	Full Force and Effect. This Second Amendment amends the terms of the Amended Agreement and
is deemed incorporated into, and governed by all other terms of, the Amended Agreement. The
provisions of the Amended Agreement, as amended by this Second Amendment, remain in full
force and effect.
	 
	2.2  	Counterparts. This Second Amendment may be executed in two or more counterparts, each of
which shall be deemed an original, but all of which together shall constitute one and the same
instrument.

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     In Witness
Whereof, the Parties have executed this Second Amendment in duplicate
originals by their authorized officers and such Second Amendment is effective as of August 20,
2004.

	 	 	 	 	 
	 	The University of Kansas Center for Research, Inc.

 	 
	 	By:  	/s/ George S. Wilson
 	 
	 	 	Name:  	George S. Wilson 	 
	 	 	Title:  	Assoc. Vice Provost for Research 	 
	 
	 	ProQuest Pharmaceuticals, Inc.

 	 
	 	By:  	/s/ Osborne S. Wong
 	 
	 	 	Name:  	Osborne S. Wong 	 
	 	 	Title:  	President 	 
	 

7exv10w30d

 

EXHIBIT 10.30 D

THIRD AMENDMENT TO LICENSE AGREEMENT

     This Third Amendment to the License Agreement (the “Third Amendment”) is made and
entered into as of November 23, 2004 (“Third Amendment Execution Date”), by and between The
University of Kansas Center for Research, Inc., a Kansas not-for-profit corporation
(“Licensor”), and ProQuest Pharmaceuticals, Inc., a Delaware corporation and successor by
merger to ProQuest Pharmaceuticals, Inc., a Kansas corporation, (“Licensee”). Licensor
and Licensee may be referred to herein as “Party” or, collectively, as “Parties.” All capitalized
terms used but not defined in this Third Amendment have the meaning given them in the Agreement.

     Whereas, Licensor and Licensee are parties to the License Agreement dated April 2,
1999, as amended April 26, 2002 (effective February 6, 2002) and August 20, 2004 (the “Agreement”),
pursuant to which Licensor granted to Licensee an exclusive license under certain proprietary
cyclic peptide, prodrug and inhalation technologies to develop, make, use and sell products;

     Whereas, Licensor and Licensee are also parties to the License Agreement dated July
6, 2001 (the “2001 License”) pursuant to which Licensor granted to Licensee an exclusive license
under certain pending US and foreign patent applications claiming novel N-H bond containing
prodrugs;

     Whereas, Licensee desires to return to Licensor all Patent Rights under the Agreement
(except those specifically described in the amended Section 1.08 below) including without
limitation those rights relating to US Patent 5,672,584 (the Cyclic Peptide Patent) and any
corresponding foreign patent applications and patents, US Patent 6,451,776 (the “Alcohol Prodrug
Patent”), US Patent 5,985,856 (the Secondary and Tertiary Amine Patent) and any corresponding
foreign patent applications and patents (collectively, the “Returned Patent Rights”), and Licensee
desires to terminate and return all rights under the 2001 License; and

     Whereas, the Parties now desire to document the termination of the 2001 License and
to amend the Agreement to narrow the licensed rights to certain prodrug technologies and to reflect
the Parties’ agreement regarding the elimination of certain payment terms under the Agreement.

     Now, Therefore, in consideration of the foregoing premises and the covenants
contained herein, and for other good and valuable consideration, the receipt and sufficiency of
which are hereby acknowledged, Licensor and Licensee hereby agree as follows:

1. Third Amendment Effective Date. This Third Amendment is subject to, and shall become effective
upon, the Effective Time of the merger of Licensee with and into a wholly-owned subsidiary of
Guilford Pharmaceuticals Inc. pursuant to the terms of the Agreement and Plan of Merger by and
among Licensee, Guilford Pharmaceuticals Inc. and PQ Acquisition Sub., Inc. (the date on which the
Effective Time occurs, the “Third Amendment Effective Date”). If the Effective Time of such merger
has not occurred by March 31, 2005, this Third Amendment shall be of no further force and effect.

2. Patent Rights Definition. Section 1.08 of the Agreement, is deleted in its entirety and
replaced with the following:

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1.08 “Patent Rights” shall mean (i) U.S. Patent 6,204,257 (the “Phenol Prodrug Patent”),
(ii) any corresponding foreign patent applications and patents, (iii) U.S. patent
application 10/208647 (a pending continuation application claiming the priority date of the
Phenol Prodrug Patent), and (iv) all divisions, continuations, continuations-in-part,
patents of addition, and substitutions of, and all patents issuing on, any of the foregoing,
together with all registrations, reissues, reexaminations or extensions of any kind with
respect to any such patents, in each case to the extent the same claim and disclose subject
matter in the Phenol Prodrug Patent and any patents issued thereon.

On June 11, 2002, Dr. Roger A. Rajewski and Dr. Michelle P. McIntosh submitted to KU and
Licensor a certain invention disclosure questionnaire describing an invention referred to as
“Delivery of a Sedative/Anti-Emetic Compound Via Inhalation (the “Inhalation Technology”).
The term “Patent Rights” shall also include – in addition to any rights that would otherwise
be treated as “Patent Rights” under this Section 1.08 – (i) the draft patent application
related to the Inhalation Technology, and any revisions thereof, in existence on the Third
Amendment Effective Date (“Existing Application”), (ii) any patents issued thereon, (iii)
all patents and patent applications claiming (or which could claim) priority therefrom
including all divisions, continuations, continuations-in-part, patents of addition, and
substitutions of any of the foregoing, (iv) any corresponding foreign patent applications
and patents, and (v) all registrations, reissues, reexaminations or extensions of any kind
with respect to any of the foregoing.

3.   Exhibit A. Exhibit A is hereby deleted in its entirety. Exhibits 1 and 2, to the extent
incorporated under the Agreement by the amendment dated August 20, 2004 are hereby deleted in their
entirety.

4.   License Definition. Section 1.07 of the Agreement is deleted in its entirety and replaced with
the following:

1.07 “License Revenue” shall mean the gross amount of revenues, including royalties,
lump-sum payments, annual fees and other payments, received by Licensee from the sale, or
use of Product, or received by Licensee or its Affiliates solely in connection with Product
under a License. For clarity, License Revenue does not include any amounts received by
Licensee from the sale or use of Propofol Product or received by Licensee or its Affiliates
in connection with Propofol Product under a License.

5.   Phase 1 Financing Definition. Section 1.09 is hereby deleted in its entirety.

6.   Product Definition. Section 1.10 of the Agreement is deleted in its entirety and replaced with
the following:

1.10 “Product” shall mean any pharmaceutical or veterinary products covered by one or more
of the claims of an issued patent under the Patent Rights, but excluding Propofol Product.
For clarity, “Product” shall include compositions of matter, processes of making, and
methods of using.

7.   Propofol Product Definition. Article 1 of the Agreement is amended to add the following new
definition in Section 1.14:

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1.14 “Propofol Product” shall mean prodrugs of propofol, their compositions, methods of use,
and processes for making as claimed by the Patent Rights.

8.   Propofol Product Buyout. As consideration for the purchase of Licensor’s rights to receive
royalty payments earned under the License Agreement based on the development, manufacture, use,
distribution or sale of the Propofol Product by or on behalf of Licensee, Licensee shall pay
Licensor on the Third Amendment Effective Date a total payment equal to One Hundred Eighty Thousand
Dollars ($180,000.00).

9.    License Grant.

       (a) Sections 2.01 and 2.02 of the Agreement are deleted in their entirety and
replaced with the following:

2.01 Subject to the limitations in Sections 2.03, Licensor hereby grants to Licensee and
Licensee accepts, an exclusive, worldwide license under the Patent Rights and Know-How to
develop, have developed, make, have made, use, distribute for sale, have distributed for
sale, sell and have sold Product, upon the terms and subject to the conditions of this
Article and this Agreement.

2.02 Subject to the limitations in Sections 2.03, Licensor hereby grants to Licensee and
Licensee accepts, an irrevocable, royalty-free, fully-paid, exclusive, worldwide license
under the Patent Rights and Know-How to develop, have developed, make, have made, use,
distribute for sale, have distributed for sale, sell and have sold Propofol Product, upon
the terms and subject to the conditions of this Article and this Agreement.

(b) Section 2.04 is hereby deleted in its entirety.

  10. Amendment of Article 3.

        (a) Section 3.01 of the Agreement is deleted in its entirety and replaced with the
following:

3.01 As consideration for the license granted to Licensee by Licensor under Section 2.01 of
this Agreement, Licensee shall pay to Licensor as royalties two percent (2%) of License
Revenue derived by Licensee under the Patent Rights from the sale or use of Product.

               (i) Royalties due under this Section 3.01 shall be payable on a country-by-country and
Product-by-Product (as applicable) basis until the expiration, nullification, final judgment
of invalidity or abandonment after exhaustion of all appeals of the last-to-expire,
last-to-be nullified, last-to-be held invalid or last-to-be abandoned claim of an issued
patent under the Patent Rights in such country covering a Product or other applicable
License Revenue.

               (ii) Notwithstanding the foregoing provisions of this Article 3, in no event shall the
royalty payable with respect to License Revenue from a particular Product exceed 2.0%,
regardless of the number of patents that cover such Product.

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(b) Sections 3.02, 3.03 and 3.04 are deleted in their entirety.

11. Amendment of Article 5. Section 5.01 of the Agreement is deleted in its entirety and replaced
with the following:

     5.01 Licensor shall deliver to Licensee, and Licensee shall have the right to use during the
term of this Agreement, all available Know-How, documents, information and data which is owned by
Licensor which may be reasonably expected to assist Licensee in the development and
commercialization of Product and/or Propofol Product.

12. Payment of Past Patent Expenses. In full satisfaction of Licensee’s obligation under Section
7.03(iii) of the Agreement, Licensee shall pay to Licensor on the Third Amendment Effective Date a
total payment equal to Two Hundred Forty Three Thousand Six Dollars and Fifty Six Cents
($243,006.56). Licensee shall be responsible for all patent expenses for Returned Patent Rights
incurred on or before the Third Amendment Effective Date. As of the Third Amendment Effective
Date, Licensor shall be solely responsible for any further prosecution and maintenance of the
Returned Patent Rights that Licensor elects to undertake, at its sole discretion, and Licensor
shall be responsible for any fees and expenses related thereto incurred after the Third Amendment
Effective Date.

13. Amendment of Article 7. Article 7 is deleted in its entirety and replaced with the following:

ARTICLE 7 – PATENT PROSECUTION AND MAINTENANCE

7.01 Beginning on the Third Amendment Effective Date, Licensee – as between the parties
hereto – shall be responsible for the preparation, filing and prosecution of the Existing
Application in the United States. Except as set forth in Section 7.05 below, (i) beginning
on the Third Amendment Effective Date, Licensee shall diligently endeavor to prepare, file
and prosecute the Existing Application, and (ii) Licensee shall be responsible for and shall
pay all fees and expenses associated with such preparation, filing and prosecution of the
Existing Application in the United States (to the extent such fees and expenses are incurred
after the Third Amendment Effective Date). Beginning on the Third Amendment Effective Date,
Licensee shall be responsible for, and shall pay all fees and expenses associated with, the
maintenance of (a) the Phenol Prodrug Patent and any foreign counterparts of the foregoing,
and (b) all other patents issuing from the Existing Application.

7.02 Licensee shall have the right to prepare, file, prosecute and maintain, at its own
expense, additional patent applications in the United States and foreign countries claiming
(or which could claim) priority from the Existing Application or the Phenol Prodrug Patent
(including the pending U.S. continuation application 10/208647, which claims the benefit of
the filing date of the Phenol Prodrug Patent).

7.03 Beginning on the Third Amendment Effective Date, Licensee shall be solely responsible
for the preparation, filing, prosecution and maintenance of pending patent applications
under the Patent Rights in foreign countries designated by Licensee; and except as set forth
in Section 7.05 below, (i) Licensee shall pay all fees and expenses

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associated with preparing, filing and prosecuting such applications (to the extent incurred
after the Third Amendment Effective Date), and (ii) Licensee shall be responsible for all
fees and expenses associated with the maintenance of patents arising from such applications
(to the extent incurred after on the Third Amendment Effective Date).

7.04 Licensor and Licensee shall cooperate fully in (i) the preparation, filing, prosecution
and maintenance of Patent Rights and of all patents and patent applications licensed to
Licensee hereunder, and (ii) the execution of all papers and instruments required to apply
for, prosecute and maintain Patent Rights in any country. Each party shall provide to the
other prompt notice as to all matters which come to its attention and which may affect the
preparation, filing, prosecution or maintenance of any Patent Rights. Licensee shall
provide Licensor with copies of all relevant documents and shall solicit comments from
Licensor regarding the prosecution of the patent applications under Patent Rights. Licensee
shall provide Licensor sufficient time before the due date and filing thereof to review and
comment on patent applications and all material correspondence to and from the U. S. Patent
and Trademark Office and patent offices in foreign countries related to all Patent Rights
governed by this Agreement. Licensee shall use all reasonable efforts to amend any such
patent applications to include claims reasonably requested by Licensor.

7.05 If Licensee elects not to pursue the patent prosecution of any pending application
within the Patent Rights, Licensee shall give Licensor sufficient notice to afford Licensor
the opportunity to do so at Licensor’s cost, in which event Licensor’s interest in any
patents issuing therefrom shall be free and clear of any license to Licensee under Section
2.01 of this Agreement.

14. Publication Rights for Inhalation Technology. If the Existing Application claiming the
Inhalation Technology is not filed pursuant to Section 7.01 of the Agreement within ninety (90)
days after the Third Amendment Effective Date and unless the Licensor and Licensee otherwise agree,
Licensor shall have the right to permit the inventors and their collaborators to pursue scientific
publications and presentations relating to the Inhalation Technology.

15. Termination Rights. Article 9 is deleted in its entirety and replaced with the following:

ARTICLE 9 – TERM AND TERMINATION

9.01 The term of this Agreement and the royalty payment obligations under Section 3.01
hereof (unless earlier terminated under this Article 9) expire upon the expiration,
nullification, final judgment of invalidity or abandonment after exhaustion of all appeals
of the last of the Patent Rights to expire, or the abandonment of the last pending patent
application within the Patent Rights, after which the licenses pursuant to this Agreement
with respect to the Know-How for such licenses shall be fully paid-up.

9.02 If either party materially defaults in its performance of this Agreement, including
failure to make any payment due under this Agreement, and if such default is not cured
within sixty (60) days after receiving written notice from the other party with respect to
such default, then such other party shall have the right to terminate this Agreement.

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16.  Rights and Duties Upon Termination. Article 10 is deleted in its entirety and replaced with
the following:

ARTICLE 10 – RIGHTS AND DUTIES UPON TERMINATION

10.01 Termination of this Agreement shall terminate all outstanding obligations and
liabilities between the parties arising from this Agreement except those described in
Sections 2.02 (and 2.03 to the extent limiting Section 2.02), 6.01, 8.08, 11.01 and
12.01-12.03, which sections shall survive termination. In addition, any other provision
required to interpret and enforce the parties’ rights and obligations under this Agreement
shall also survive, but only to the extent required for the full observation and performance
of this Agreement.

10.02 Upon termination of this Agreement for any reason, Licensee’s rights in the Patent
Rights, Know-How and in the Product shall terminate, and for so long as the Patent Rights
are in effect, Licensee and its Affiliates shall cease manufacture, development, marketing
and sale of Product, and all originals and copies of know-how, data, results and other
information collected and/or generated by Licensee and its Affiliates relating to Product
prior to termination shall be delivered to Licensor within thirty (30) days thereafter,
except for one copy thereof which may be retained in Licensee’s legal files solely for the
purpose of establishing the extent of its obligations thereunder. Notwithstanding anything
to the contrary contained in this Agreement (including the preceding sentence), Licensee’s
rights in the Patent Rights, Know How and Product to the extent related to the Propofol
Product and in the Propofol Product shall survive the termination of this Agreement and
remain in full force and effect.

17. Amendment of Section 11.01. Section 11.01 is deleted in its entirety and replaced with the
following:

     Licensee shall indemnify, defend and hold harmless Licensor, the University of Kansas, their
Affiliates, and their current and former directors, trustees, officers, faculty, employees,
students and agents, and their respective successors, heirs and assigns (collectively the
“Indemnitees”), harmless from and against any and all liabilities, losses, claims, demands,
damages, costs and expenses, fines, penalties or money judgments including without limitation court
costs and reasonable attorneys’ fees (hereinafter “Liabilities”) incurred by or against Indemnitees
or any of them arising out of the use, manufacture, sale, storage or advertising of any Product or
Propofol Product.

18. Rights and Duties Upon Return. As of the Third Amendment Effective Date, Licensee shall have
no further rights with respect to the Returned Patent Rights. Within thirty (30) days of the Third
Amendment Effective Date, Licensee shall return to Licensor all originals and copies of know-how,
data, results and information collected and/or generated by Licensee relating to the Returned
Patent Rights. Notwithstanding the return of the Returned Patent Rights, Licensee acknowledges
that it remains responsible for its activities with respect to the Returned Patent Rights occurring
prior to the Third Amendment Effective Date, and any liability related thereto. For avoidance of
doubt, Licensee’s indemnification obligation under Section 11.01 of the

6

 

Agreement shall survive the return of the Returned Patent Rights with respect to events occurring
prior to the Third Amendment Effective Date.

19. 2001 License Agreement Termination. The 2001 License is hereby terminated in its entirety
effective upon the Third Amendment Effective Date. As of the Third Amendment Effective Date,
Licensee shall have no further rights with respect to the Patent Rights under the 2001 License and
shall have those obligations under the Agreement specified to survive pursuant to Article 10.
Within thirty (30) days of the Third Amendment Effective Date, Licensee shall return to Licensor
all originals and copies of know-how, data, results and information collected and/or generated by
Licensee relating to Product (as defined in the 2001 License). As of the Third Amendment Effective
Date, Licensor shall be solely responsible for any further prosecution and maintenance of such
Patent Rights that Licensor elects to undertake, at its sole discretion, and Licensor shall be
responsible for any fees and expenses related thereto incurred after the Third Amendment Effective
Date.

20. No Other Modifications. Except as specifically amended by this Third Amendment, the terms and
conditions of the Agreement shall remain in full force and effect. This Third Amendment may be
executed in two or more counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.

<< Signature Page Follows >>

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In Witness Whereof, the Parties hereto have caused this Third Amendment to be executed by
their duly authorized officers as of the Third Amendment Execution Date.

	 	 	 	 	 	 	 	 	 	 	 	 	 
	The University of Kansas	 	 	 	ProQuest Pharmaceuticals, Inc.	 	 	 	 
	Center for Research, Inc.	 	 	 	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 
	By:
	 	/s/ James A. Roberts	 	 	 	By:	 	/s/ Osborne S. Wong	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 
	Name:
	 	James A. Roberts	 	 	 	Name:	 	Osborne S. Wong	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 	 	 
	Title:
	 	President	 	 	 	Title:	 	President	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 

THIRD AMENDMENT TO LICENSE AGREEMENT

SIGNATURE PAGE

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