Document:

exv4w3

Exhibit 4.3

[Form of Face of Security]

     [Include if Global Security — THIS SECURITY IS A GLOBAL SECURITY WITHIN THE MEANING OF THE
INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE
THEREOF. THIS SECURITY MAY NOT BE EXCHANGED IN WHOLE OR IN PART FOR A SECURITY REGISTERED, AND NO
TRANSFER OF THIS SECURITY IN WHOLE OR IN PART MAY BE REGISTERED, IN THE NAME OF ANY PERSON OTHER
THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE
INDENTURE.]

     [Include if Global Security and the Depositary therefor is DTC — Unless this certificate is
presented by an authorized representative of The Depository Trust Company, a New York corporation
(“DTC”), to Issuer or its agent for registration of transfer, exchange, or payment, and any
certificate issued is registered in the name of Cede & Co. or in such other name as is requested by
an authorized representative of DTC (and any payment is made to Cede & Co. or to such other entity
as is requested by an authorized representative of DTC), ANY TRANSFER, PLEDGE, OR OTHER USE HEREOF
FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL inasmuch as the registered owner hereof,
Cede & Co., has an interest herein.]

BAKER HUGHES INCORPORATED

5.125% Senior Notes due 2040

			
	No. [___]
	 	$[                    ]

CUSIP No. 057224AZ0

ISIN No. US057224AZ09

     BAKER HUGHES INCORPORATED, a corporation duly organized and existing under the laws of the
State of Delaware (herein called the “Company”, which term includes any successor Person under the
Indenture hereinafter referred to), for value received, hereby promises to pay to
        , or registered assigns, the principal sum of           
           Dollars on September
15, 2040, and to pay interest thereon from August 24, 2010 or from the most recent
Interest Payment Date to which interest has been paid or duly provided for, semi-annually on March
15 and September 15 in each year, commencing March 15, 2011, and at the Maturity thereof, at the rate of 5.125% per annum, until the principal
hereof is paid or made available for payment. The interest so payable, and punctually paid or duly
provided for, on any Interest Payment Date will, as provided in such Indenture, be paid to the
Person in whose name this Security (or one or more Predecessor Securities) is registered at the
close of business on the Regular Record Date for such interest, which shall be the March 1 or
September 1 (whether or not a Business Day), as the case may be, next preceding such Interest
Payment Date. Any such interest so payable, but not punctually paid or duly provided for, will
forthwith cease to be payable to the Holder on such Regular Record Date and may either be paid to
the Person in whose name this Security (or one or more Predecessor Securities) is registered at

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the close of business on a Special Record Date for the payment of such Defaulted Interest to be
fixed by the Trustee, notice whereof shall be given to Holders of Securities of this series not
less than 10 days prior to such Special Record Date, or be paid in any other lawful manner not
inconsistent with the requirements of any securities exchange on which this Security may be listed,
and upon such notice as may be required by such exchange, all as more fully provided in said
Indenture.

     Payment of the principal of (and premium, if any) and any such interest on this Security will
be made (x) if this Security is a Global Security, through the Depositary or (y) if this Security
is not a Global Security, at the office or agency of the Company maintained for that purpose in New
York, New York, against surrender of this Security in the case of any payment due at the Maturity
of the principal thereof or any payment of interest that becomes payable on a day other than an
Interest Payment Date, and in the case of clause (x) or clause (y), in such coin or currency of the
United States of America as at the time of payment is legal tender for payment of public and
private debts; provided, however, that if this Security is not a Global Security, (i) payment of
interest on an Interest Payment Date will be made by check mailed to the address of the Person
entitled thereto as such address shall appear in the Security Register; and all other payments will
be made by check against surrender of this Security; (ii) all payments by check will be made in
next-day funds (i.e., funds that become available on the day after the check is cashed); and (iii)
notwithstanding clauses (i) and (ii) above, with respect to any payment of any amount due on this
Security, if this Security is in a denomination of at least $1,000,000 and the Holder hereof at the
time of surrender hereof or, in the case of any payment of interest on any Interest Payment Date,
the Holder thereof on the related Regular Record Date delivers a written request to the Paying
Agent to make such payment by wire transfer at least five Business Days before the date such
payment becomes due, together with appropriate wire transfer instructions specifying an account at
a bank in New York, New York, the Company shall make such payment by wire transfer of immediately
available funds to such account at such bank in New York City, any such wire instructions, once
properly given by a Holder as to this Security, remaining in effect as to such Holder and this
Security unless and until new instructions are given in the manner described above and provided
further, that notwithstanding anything in the foregoing to the contrary, if this Security is a
Global Security, payment shall be made pursuant to the Applicable Procedures of the Depositary as
permitted in said Indenture.

     Reference is hereby made to the further provisions of this Security set forth on the reverse
hereof, which further provisions shall for all purposes have the same effect as if set forth at
this place.

     Unless the certificate of authentication hereon has been executed by or on behalf of the
Trustee referred to on the reverse hereof by manual signature, this Security shall not be entitled
to any benefit under the Indenture or be valid or obligatory for any purpose.

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     IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed under its
corporate seal.

	 	 	 	 	 
	[SEAL]                                           	BAKER HUGHES INCORPORATED

 	 
	 	By:  	 	 
	 	 	Name:  	 	 
	 	 	Title:  	 	 
	 

	 	 	 	 	 
	 	 	 
	Attest:  	 	 	 
	 	 	 	 
	 	 	 	 

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CERTIFICATE OF AUTHENTICATION

     This is one of the Securities of the series
designated herein and referred to in the
within-mentioned Indenture.

Dated:                     

	 	 	 	 	 
	 	THE BANK OF NEW YORK MELLON TRUST

COMPANY, N.A., AS TRUSTEE

 	 
	 	By:  	 	 
	 	 	Authorized Signatory 	 
	 	 	 	 

4

 

	 	 	 	 	 

[Form of Reverse of Security]

     This Security is one of a duly authorized issue of senior securities of the Company (herein
called the “Securities”), issued and to be issued in one or more series under an Indenture, dated
as of October 28, 2008 (herein called the “Indenture”, which term shall have the meaning assigned
to it in such instrument), between the Company and The Bank of New York Mellon Trust Company, N.A.,
as Trustee (herein called the “Trustee”, which term includes any successor trustee under the
Indenture), and reference is hereby made to the Indenture for a statement of the respective rights,
limitations of rights, duties and immunities thereunder of the Company, the Trustee and the Holders
of the Securities and of the terms upon which the Securities are, and are to be, authenticated and
delivered. This Security is one of the series designated on the face hereof limited in aggregate
principal amount to $1,500,000,000 (plus such additional amounts of Securities of this series as
may be authorized for issuance from time to time by or pursuant to a Board Resolution and set forth
in an Officers’ Certificate prior to the issuance thereof) except for Securities of this series
authenticated and delivered upon registration of transfer of, or in exchange for, or in lieu of,
other Securities of this series pursuant to the Indenture.

     The Securities of this series are subject to redemption upon prior notice, as provided below,
at any time, as a whole or in part, at the election of the Company, at a Redemption Price equal to
the greater of (i) 100% of the principal amount of the Securities of this series to be redeemed or
(ii) the sum of the present values of the remaining scheduled payments of principal and interest on
the Securities of this series to be redeemed from the Redemption Date to the Stated Maturity of the
Securities of this series to be redeemed (exclusive of any interest accrued to the Redemption
Date), discounted to the date on which the Securities of this series are to be redeemed on a
semi-annual basis assuming a 360-day year consisting of twelve 30-day months, at the Treasury Rate
plus 25 basis points, plus any interest accrued but not paid on the Securities of this series to be
redeemed to the date on which the Securities of this series are to be redeemed (subject to the
right of Holders on the relevant Regular Record Date to receive interest due on the relevant
Interest Payment Date). Unless the Company defaults in payment of the Redemption Price, on and
after the Redemption Date interest will cease to accrue on the Securities of this series or
portions thereof called for redemption. If less than all of the Securities of this series are to
be redeemed at any time, the Trustee will select Securities of this series for redemption on a pro
rata basis. No Securities of this series of $2,000 or less can be redeemed in part. Notices of
redemption will be delivered at least 30 but not more than 60 days before the Redemption Date to
each Holder of Securities of this series to be redeemed at its registered address, except that
notices may be mailed more than 60 days prior to a Redemption Date if the notice is issued in
connection with a Covenant Defeasance or Defeasance with respect to the Securities of this series
or a satisfaction and discharge of the Indenture with respect to Securities of this series. Notice
of any redemption, may, at the Company’s discretion, be subject to one or more conditions
precedent. A notice of redemption need not set forth the exact Redemption Price but only the manner
of calculation thereof.

     “Treasury Rate” means, with respect to any Redemption Date for the Securities of this series,
(i) the yield, under the heading which represents the average for the

R-1

 

immediately preceding week, appearing in the most recently published statistical release designated
“H.15(519)” or any successor publication which is published weekly by the Board of Governors of the
Federal Reserve System and which establishes yields on actively traded United States Treasury
securities adjusted to constant maturity under the caption “Treasury Constant Maturities,” for the
maturity corresponding to the Comparable Treasury Issue with respect to Securities of this series
(if no maturity is within three months before or after the Stated Maturity Date for the Securities
of this series, yields for the two published maturities most closely corresponding to the
Comparable Treasury Issue shall be determined and the Treasury Rate shall be interpolated or
extrapolated from such yields on a straight line basis, rounding to the nearest month) or (ii) if
that release (or any successor release) is not published during the week preceding the calculation
date or does not contain such yields, the rate per annum equal to the semiannual equivalent yield
to maturity of the Comparable Treasury Issue, calculated using a price for the Comparable Treasury
Issue (expressed as a percentage of its principal amount) equal to the Comparable Treasury Price
for that Redemption Date. The Treasury Rate shall be calculated on the third Business Day
preceding the Redemption Date.

     “Comparable Treasury Issue” means, with respect to the Securities of this series, the United
States Treasury security selected by an Independent Investment Banker as having a maturity
comparable to the remaining term of the Securities of this series to be redeemed that would be
utilized, at the time of selection and in accordance with customary financial practice, in pricing
new issues of corporate debt securities of comparable maturity to the remaining term of the
Securities of this series to be redeemed. “Independent Investment Banker” means one of the
Reference Treasury Dealers appointed by the Trustee after consultation with the Company.

     “Comparable Treasury Price” means with respect to any Redemption Date for any Securities of
this series (i) the average of four Reference Treasury Dealer Quotations for that Redemption Date,
after excluding the highest and lowest such Reference Treasury Dealer Quotations, or (ii) if the
Trustee obtains fewer than four such Reference Treasury Dealer Quotations, the average of all such
quotations.

     “Reference Treasury Dealer” means each of J.P. Morgan Securities Inc., Barclays Capital Inc.,
RBS Securities Inc., UBS Securities LLC and two other primary U.S. Government securities dealers in
the United States (each, a “Primary Treasury Dealer”) appointed by the Trustee in consultation with
the Company; provided, however, that if any of the foregoing shall cease to be a Primary Treasury
Dealer, the Company shall substitute therefor another Primary Treasury Dealer.

     “Reference Treasury Dealer Quotations” means, with respect to each Reference Treasury Dealer
and any Redemption Date, the average, as determined by the Trustee, of the bid and asked prices for
the Comparable Treasury Issue (expressed in each case as a percentage of its principal amount)
quoted in writing to the Trustee by that Reference Treasury Dealer at 5:00 p.m. (New York City
time) on the third Business Day preceding that Redemption Date.

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     In the event of redemption of this Security in part only, a new Security or Securities of this
series and of like tenor for the unredeemed portion hereof will be issued in the name of the Holder
hereof upon the cancellation hereof.

     The Indenture contains provisions for defeasance at any time of the entire indebtedness of
this Security or certain restrictive covenants and Events of Default with respect to this Security,
in each case upon compliance with certain conditions set forth in the Indenture.

     If an Event of Default with respect to Securities of this series shall occur and be
continuing, the principal of the Securities of this series may be declared due and payable in the
manner and with the effect provided in the Indenture.

     The Indenture permits, with certain exceptions as therein provided, the amendment thereof and
the modification of the rights and obligations of the Company and the rights of the Holders of the
Securities of each series to be affected under the Indenture at any time by the Company and the
Trustee with the consent of the Holders of a majority in principal amount of the Securities at the
time Outstanding of all series to be affected (considered together as one class for this purpose).
The Indenture also contains provisions (i) permitting the Holders of a majority in principal amount
of the Securities at the time Outstanding of all series to be affected under the Indenture
(considered together as one class for this purpose), on behalf of the Holders of all Securities of
such series, to waive compliance by the Company with certain provisions of the Indenture and (ii)
permitting the Holders of a majority in principal amount of the Securities at the time Outstanding
of any series to be affected under the Indenture (with each such series considered separately for
this purpose), on behalf of the Holders of all Securities of such series, to waive certain past
defaults under the Indenture and their consequences. Any such consent or waiver by the Holder of
this Security shall be conclusive and binding upon such Holder and upon all future Holders of this
Security and of any Security issued upon the registration of transfer hereof or in exchange herefor
or in lieu hereof, whether or not notation of such consent or waiver is made upon this Security.

     As provided in and subject to the provisions of the Indenture, the Holder of this Security
shall not have the right to institute any proceeding with respect to the Indenture, or for the
appointment of a receiver or trustee, or for any other remedy thereunder, unless such Holder shall
have previously given the Trustee written notice of a continuing Event of Default with respect to
the Securities of this series, the Holders of not less than 25% in principal amount of the
Securities of this series at the time Outstanding shall have made written request to the Trustee to
institute proceedings in respect of such Event of Default as Trustee and offered the Trustee
indemnity reasonably satisfactory to it, and the Trustee shall not have received from the Holders
of a majority in principal amount of Securities of this series at the time Outstanding a direction
inconsistent with such request, and shall have failed to institute any such proceeding, for 60 days
after receipt of such notice, request and offer of indemnity. The foregoing shall not apply to any
suit instituted by the Holder of this Security for the enforcement of any payment of principal
hereof or any premium or interest hereon on or after the respective due dates expressed herein.

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     No reference herein to the Indenture and no provision of this Security or of the Indenture
shall alter or impair the obligation of the Company, which is absolute and unconditional, to pay
the principal of and any premium and interest on this Security at the times, place and rate, and in
the coin or currency, herein prescribed.

     As provided in the Indenture and subject to certain limitations therein set forth, the
transfer of this Security is registrable in the Security Register, upon surrender of this Security
for registration of transfer at the office or agency of the Company in any place where the
principal of and any premium and interest on this Security are payable, duly endorsed by, or
accompanied by a written instrument of transfer in form satisfactory to the Company and the
Security Registrar duly executed by, the Holder hereof or his attorney duly authorized in writing,
and thereupon one or more new Securities of this series and of like tenor, of authorized
denominations and for the same aggregate principal amount, will be issued to the designated
transferee or transferees.

     The Securities of this series are issuable only in registered form without coupons in minimum
denominations of $2,000 and multiples of $1,000 in excess thereof. As provided in the Indenture and
subject to certain limitations therein set forth, Securities of this series are exchangeable for a
like aggregate principal amount of Securities of this series and of like tenor of a different
authorized denomination, as requested by the Holder surrendering the same.

     No service charge shall be made for any such registration of transfer or exchange, but the
Company may require payment of a sum sufficient to cover any tax or other governmental charge
payable in connection therewith.

     Prior to due presentment of this Security for registration of transfer, the Company, the
Trustee and any agent of the Company or the Trustee may treat the Person in whose name this
Security is registered as the owner hereof for all purposes, whether or not this Security be
overdue, and neither the Company, the Trustee nor any such agent shall be affected by notice to the
contrary.

     This Security and the Indenture shall be governed by and construed in accordance with the law
of the State of New York.

     All terms used in this Security which are defined in the Indenture shall have the meanings
assigned to them in the Indenture.

R-4Exhibit 10.1

Exhibit 10.1

SPONSORED RESEARCH AGREEMENT

THIS AGREEMENT, effective this 18th day of August 2010 by and between Omni Bio
Operating, Inc. (hereinafter referred to as “Sponsor”), having a principal place of business
at 5350 South Roslyn, Suite 430 Greenwood Village, CO 80111 and THE REGENTS OF THE UNIVERSITY OF
COLORADO, a body corporate, contracting for and on behalf of the University of Colorado Denver, a
public educational institution of the State of Colorado (hereinafter referred to as “University”).

WITNESSETH:

Whereas, the Sponsor has executed an Exclusive License Agreement with the Regents of the
University of Colorado for certain Patent Rights to be exploited in the field of use relative to
the scope of work described in the attached Appendix A of this agreement; and

WHEREAS, the Sponsor desires research services in accordance with the scope of work described
in the attached Appendix A of this Agreement; and

WHEREAS, the performance of such research services is consistent and compatible with and
beneficial to the academic role and mission of the University as an institution of higher
education;

NOW THEREFORE, in consideration of the mutual premises and convenants contained herein, and
other good and valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the parties hereto expressly agree as follows:

Article 1 — Definitions

For purposes of this Agreement, the following terms shall have the following meanings:

	1.1	 	“Project” shall mean the research services to be performed under this Agreement
as described in Appendix A hereof, under the direction and supervision of University’s
Principal Investigator (hereinafter called the “PI”).
	 
	1.2	 	“Equipment” is defined as any tangible item of property with a unit cost of $5,000
or more and an expected useful life of one year or more.
	 
	1.3	 	“University Intellectual Property” shall mean individually and collectively all inventions,
improvements, and discoveries, which are conceived and/or made in the performance of Project
solely by one or more University personnel.
	 
	1.4	 	The term “Know-how” shall mean all unpatented and unpatentable technical information, trade
secrets, devices, models, things, know-how, methods,
documents, materials, and all other confidential information related to the Project which
was developed by the Pl.

 

 

 

Article 2 — Research work

	2.1	 	University will use its reasonable best efforts to conduct the Project in accordance with the
terms and conditions of this Agreement, and will furnish the facilities necessary to carry out
the Project.
	 
	2.2	 	The Project will be carried out under the direction and supervision of Dr. Leland Shapiro,
the University designated Pl.
	 
	2.3	 	University does not guarantee specific results, and the Project will be conducted
only on reasonable best efforts basis.
	 
	2.4	 	University will keep accurate financial and scientific records relating to the
Project and will make records available to Sponsor or its authorized representative
throughout the Term of the Agreement during normal business hours upon reasonable notice.

Article 3 — Agreement Duration

	3.1	 	This agreement shall become effective on August, 18, 2010 and shall terminate on August 17,
2012, unless a subsequent time extension, supplement, addition, continuation or renewal is
mutually agreed upon in writing between the parties.

Article 4 — Compensation

	4.1	 	As consideration for the performance by University of its obligations under this
Agreement, and subject to Paragraphs 4.2, 4.3 and 16.1, Sponsor agrees to pay University a
fixed-price total of Four Hundred Thirty-nine Thousand, One Hundred Ten) Dollars,
($439,110), in accordance with the budget described in the attached Appendix B of this
Agreement. Sponsor shall remit not less than twelve and one-half percent (12.5%) of the
total contract price upon execution by both parties of this Agreement ($54,888.75). The
remaining amount of the contract price due under this Agreement shall be paid in equal
increments upon receipt of invoices from University issued quarterly commencing November 18,
2010. Invoices are due and payable within thirty (30) days.
	 
	4.2	 	If this Agreement is terminated for any reason by Sponsor under Paragraph 16.1, Sponsor
shall, up to a maximum of the amount stated in Paragraph 4.1 hereof, reimburse University for
the total actual and reasonable costs incurred by University for the Project through the date
of termination, including those costs necessary to implement the early termination of this
Agreement and costs incurred by University as a result of non-cancelable obligations which may
extend beyond the date of such termination.

 

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	4.3	 	If this Agreement is terminated for any reason by University under Paragraph 16.1,
Sponsor shall, subject to the provision hereafter and Paragraph 8, reimburse University for
those actual and reasonable costs in Appendix B incurred by University for the Project
through the date of termination; provided that in no event shall such costs exceed the
amount stated in Paragraph 4.1 hereof and such costs shall not include any charges or
expenses incurred to implement the early termination or as a result of non-cancelable
obligations of the University which may extend beyond the date of such termination.
	 
	4.4	 	All payment checks shall be made payable to University of Colorado Denver. The Tax F.D.
Number is 84-6000555. All payment checks shall be forwarded to the following address:

Grants and Contracts, #091991LS

F428, P.O. Box 238

Denver, Colorado 80291-0238

Article 5 — Reporting Requirements

	5.1	 	 University will provide reports on the progress of Project in accordance with the
following schedule:

			
	Progress reports	 	For the periods ending every three months from the effective date of this
Agreement (with the report to be delivered within 45 days of the ending of the period).
	 
	Final report	 	Within 90 days of the termination of this Agreement

	 	 	The progress reports will indicate the work completed (e.g. work performed and data in
summary form and raw data), and the work (experiments) to be performed during the next
reporting period, any problems encountered and the proposed solution for each problem.
Additionally, the report will note any of the specific aims of the work that were not
initiated, and if so the reason. The PI shall meet or participate in a phone conference
with the Sponsor on a quarterly basis during the course of the Project to review progress
and future activities.

Article 6 — Publications and Academic Rights

	6.1	 	Sponsor recognizes that because University is a public institution of higher education and
engages only in research that is compatible with its academic role and mission, the results of
University research must be publishable. Sponsor agrees that University personnel engaged in
Project shall be permitted to present at symposia, national or regional professional meetings,
and to publish in journals, theses or dissertations, or otherwise of their own choosing,
methods and results of Project, provided, however, that Sponsor shall have been furnished
copies of any proposed publication to a journal, editor, or other third party.
	 
	6.2	 	University shall own all right, title and interest in and to any and all copyrights or
copyrightable material, including software programs, first produced, composed, or fixed in
any tangible medium of expression in the performance of work under this Agreement, and
University shall have the sole right to determine the disposition of all or any thereof.

 

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Article 7 — Confidential Information

	7.1.	 	The parties may wish, from time to time, in connection with work contemplated under this
Agreement, to disclose confidential information to each other (“Confidential Information”).
Each party will use reasonable efforts to prevent the
disclosure of the other party’s Confidential Information to third parties for a period
of five (5) years from receipt thereof, provided that the recipient party’s obligation
hereunder shall not apply to information that:

	 	a.	 	is not disclosed in writing or reduced to writing and so marked with an
appropriate confidentiality legend within thirty (30) days of disclosure; is already
in recipient party’s possession at the time of disclosure thereof;
	 
	 	c.	 	is or later becomes part of the public domain through no fault of
recipient party;
	 
	 	d.	 	is received from a third party having no obligations of confidentiality
to disclosing party;
	 
	 	e.	 	is independently developed by the recipient party; or
	 
	 	f.	 	is required by law or regulation to be disclosed.

	7.2	 	In the event that information is required to be disclosed pursuant to subsection (f), the
party required to make disclosure shall notify the other to allow that party to assert
whatever exclusions or exemptions may be available to it under such law or regulation.

	7.3	 	Sponsor acknowledges that University is subject to the Colorado Public Records Act (C.R.S. §§
24-72-201 et seq.). All Confidential Information of Sponsor shall be treated by University as
confidential, as set forth in this Article 7, to the extent permitted under §§ 24-72-204. If
University is required by Colorado Public Records Act (C.R.S. §§ 24-72-201 et seq.) to
disclose any Sponsor Confidential Information, (i) the University will use reasonable best
efforts to notify Sponsor in advance of such disclosure, and Sponsor shall have been given the
opportunity to oppose such disclosure by University by seeking a protective order or other
appropriate remedy; (ii) University shall disclose only that portion of Confidential
Information legally required to be disclosed; and (iii) University shall exercise all
reasonable efforts to maintain the confidential treatment of Confidential
Information.

 

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	7.4	 	Confidential Information shall be clearly marked by the disclosing party with the
legend, “CONFIDENTIAL INFORMATION” or another appropriate proprietary
legend. If disclosed orally, the employee(s) making the disclosure shall be
responsible for clearly informing the recipient’s employee(s), in writing within
thirty (30) days, of the confidentiality of the information disclosed.

Article 8 — Patents and Inventions

	8.1	 	All rights and title to University Intellectual Property and Know-How under Project
shall belong to University which shall, unless otherwise agreed to between the parties, have
the right, if it so chooses, to proceed at its expense to obtain patent protection to all
inventions and discoveries arising therefrom.
	 
	8.2	 	Subject to University obligations, if any, to the Federal Government arising from
use of Federally supplied funds or equipment in the Project, University hereby grants to
Sponsor, without option fee other than the consideration of the research sponsored herein
and the reimbursement of University for all patent expenses incurred for the subject
Invention prior to and during the option period and appertaining license negotiation period,
an option to acquire an exclusive, worldwide, royalty-bearing license of University’s rights
to any Invention arising out of the research performed under this Agreement, which option
shall extend for ninety (90) days after Sponsor’s receipt of the Invention disclosure. If
Sponsor notifies University in writing of its exercise of the option within the option
period, then the parties shall proceed in good faith to negotiate a license agreement within
sixty (60) days after notification of exercise. If Sponsor does not exercise this option, or
notifies University that it will not exercise this option, or the parties fail to sign a
license agreement within said sixty (60) day negotiation period, then Sponsor’s option to
University’s rights in the subject Invention shall terminate.

 

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	8.3	 	The parties mutually acknowledge that the United States government, as a matter of
statutory right under Code of Federal Regulations, 37 CFR, Part 401, “Rights to Inventions
Made by Non-Profit Organizations and Small Business Firms Under Government Grants, Contracts
and Cooperative Agreements”, holds or may hold a non-exclusive license and certain other
rights under patents on inventions made as a consequence of research whose funding includes
funds supplied by the United States government. In the event that the United States
government has such rights or in the future is found to have such rights with respect to all
or any new inventions or discoveries, any license contemplated or granted under this
Agreement, even if termed “exclusive” license, shall be understood to be subject to the
rights of the United States government, without any effect on the parties’ remaining
obligations, as set forth in the license or in this Agreement.
	 
	8.4	 	Nothing in Article 8 shall be construed as granting Sponsor expressly, by implication, or
estoppel any rights or licenses to use inventions, improvements or discoveries not conceived
and/or made in the performance of the Project, or under any patents not falling under the
definition of University Intellectual property including patents, inventions and discoveries
which may dominate University Intellectual Property and which may be owned or controlled by
the Regents of the University of Colorado, the University Technology Corporation or any entity
related thereto.

Article 9 — Liability, Indemnification, and Insurance

	9.1	 	University hereto agrees to be responsible and assume liability for its own
wrongful or negligent acts or omissions, or those of its officers, agents or employees to
the full extent allowed by law.
	 
	9.2	 	Notwithstanding any other provision of this Agreement to the contrary, no term or
condition of this Agreement shall be construed or interpreted as a waiver, either express or
implied, of any of the immunities, rights, benefits or protection provided to the Regents
under governmental immunity laws from time to time applicable to the Regents, including,
without limitation, the Colorado Governmental Immunity Act (CRS Section 24-10-101 through
24-10-120).
	 
	9.3	 	Sponsor shall indemnify, save and hold harmless University, its employees and
agents, against any and all claims, damages, liability and court awards including costs,
expenses, and attorney fees incurred as a result of any act or omission by the Sponsor, or
its employees, agents, Subcontractors, or assignees pursuant to the terms of this Agreement.
Additionally, Colo. Rev. Stat. Section 23-20-100 states that the Colorado Attorney General
must represent the University in all actions. Provided that any such representation arises
out of Sponsor’s indemnification obligations under this Section 9.3, Sponsor agrees to
indemnify University for the reasonable cost of the representation by the Colorado Attorney
General.

 

Page 6

 

	9.4	 	Each party warrants and represents that it has adequate liability insurance for the
protection of itself and its officers, employees, and agents, while acting within the scope
of their employment by the party.

	9.5	 	No liability hereunder shall result to a party by reason of delay in performance
caused by force majeure, that is, circumstances beyond the reasonable control of the party,
including, without limitation, acts of God, fire, flood, war, civil unrest, or shortage of
or inability to obtain material or equipment.

Article 10 — Equipment

	10.1	 	All equipment purchased by University under the terms of this Agreement shall become the
property of University upon acquisition.

Article 11 — Independent Contractor

	11.1	 	In the performance of all services hereunder, neither party is authorized or empowered to act
as agent for the other for any purpose and shall not on behalf of the other enter into any
contract, warranty, or representation as to any matter. Neither party shall be bound by the
acts or conduct of the other.

Article 12 — Compliance with Laws

	12.1	 	Each party agrees that it will comply with all applicable federal, state and local laws,
codes, regulations, rules and orders in the performance and direction of the work contemplated
under this Agreement.

Article 13 — Governing Law

	13.1	 	This Agreement shall be governed and construed in accordance with the laws of
the State of Colorado and any and all disputes arising hereunder shall be
resolved in the courts of the State of Colorado; provided, however, that any patent
question or controversy shall be resolved in the courts having jurisdiction over the patent
or patents in question and in accordance with the laws applicable to such patent or
patents.

Article 14 Assignment

	14.1	 	Neither party shall assign or transfer any interest in this Agreement, nor assign any
claims for money due or to become due during this Agreement without the prior written
approval of the other party, which approval shall not be unreasonably withheld.
Notwithstanding the foregoing, Sponsor will not breach this agreement if it assigns this
agreement to a successor in interest or assignee of all the business or assets of the
Sponsor to which this agreement pertains.

 

Page 7

 

Article 15 — Use of Name

	15.1	 	Each party agrees not to include the name or any logotypes or symbols of the other party or
the names of any researchers at such institutions in any advertising, sales promotion or
other publicity matter without the prior written approval of the other party. However,
nothing in this Article or elsewhere in this Agreement is intended to restrict either party
from disclosing the existence, nature, Project title, name of Sponsor and any additional
matters required by law to be disclosed, or from including those items of information in the
routine reporting of its activities.

Article 16 — Term and Termination

	16.1	 	This Agreement may be terminated by either party upon written notice delivered to the other
party at least forty-five (45) days prior to the intended date of termination. Termination
of this Agreement, however effectuated, shall not release the parties from their rights and
obligations under Articles 4, 6, 8, 9, 15, and 20. Either party shall have the right, at its
option, to cancel and terminate this Agreement in the event that the other party shall
become involved in insolvency, dissolution, bankruptcy or receivership proceedings affecting
the operation of its business or in the event that the other party shall discontinue its
business for any reason.

	16.2	 	The failure of Sponsor to make the required payments to the University as outlined in
Article 4, within thirty (30) calendar days after such payments are due shall constitute a
default of this Agreement by Sponsor. A default by Sponsor shall relieve the University, at
its choice, of any and all of its obligations or duties under this Agreement and shall also
divest Sponsor of all of its rights under this Agreement. However, Sponsor default of this
Agreement shall not relieve Sponsor of its obligations under this Agreement, including but
not limited to its obligations to pay the University plus eight percent (8%) interest. By
exercising its rights under this default provision, the University does not waive any rights
it may have to pursue and collect unpaid monies owed to the University by Sponsor under this
Agreement. Furthermore, should the University prevail in its pursuit of unpaid monies from
Sponsor, the parties agree that Sponsor will be responsible for all of the University’s
attorney fees, collection costs, and court fees associated with pursuing such action.

Article 17 — Changes, Modifications, and Amendments

	17.1	 	This Agreement constitutes the entire agreement between the parties. Neither party shall be
bound by any agreement, convenants or warranties made by its agents or employees, or any
other persons, either oral or written, unless such agreements, convenants and warranties
shall be reduced to writing and signed by the authorized officer of such party and shall
expressly refer to this Research
Agreement. The failure of either of the parties at any time or times to require performance
by the other of any provisions hereof shall in no manner affect the right of the
first-mentioned party thereafter to enforce the same. The waiver by either of the parties
of any breach of any provision hereof shall never be construed to be a waiver of any
succeeding breach of such provision or a waiver of the provisions itself.

 

Page 8

 

	17.2	 	If any provision of this Agreement is judicially determined to be void or unenforceable,
such provision shall be deemed to be severable from the other provisions of this Agreement
which shall remain in full force and effect. Either party may request that a provision
otherwise void or unenforceable be reformed so as to be valid and enforceable to the
maximum extent permitted by law.

Article 18 — Notices

	18.1	 	All notices required by this Agreement shall be by written instrument executed by the
parties hereto and shall be directed to the following individuals:

	 	 	 	 	 	 	 
	 

	 	For the University:
	 	Original to:
	 	Leland Shapiro, M.D., F.A.C.P. 

Associate Professor of Medicine
 Denver Veterans
Affairs Medical Center
 1055 Clermont Street, Box 111 L 

Denver, CO 80220
	 

	 	 	 	 	 	(303) 399-8020 (X2837)

(303) 393-4692
	 
	 	 	 	 	 	 
	 

	 	 	 	Copy to:
	 	Harlan L. Ray

Contracts Manager 

Grants and Contracts, MS F-428 
Anschutz Medical Campus, Building
500 
P.O. Box 6508

Aurora, CO 80045-0508

303-724-0090

303-724-0814 (fax)
	 
	 	 	 	 	 	 
	 

	 	For Sponsor:
	 	Original to:
	 	Edward C. Larkin

Chief Operating Officer 

Omni Bio Operating, Inc.
 5350 South Roslyn, Suite 430

Greenwood Village, CO 80111

720-488-4708

 

Page 9

 

Article 19 — Order of Precedence

	 	19.1	 	In the event of any inconsistency between this Agreement and any other attachments
or documents, this Agreement shall control.

INTENTIONALLY LEFT BLANK

 

Page 10

 

IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be executed as of the
date set forth herein by their duly authorized representatives.

	 	 	 	 	 	 	 	 	 	 	 
	Omni Bio Operating, Inc.	 	 	 	THE REGENTS OF THE UNIVERSITY	 	 
	5350 South Roslyn, Suite 430	 	 	 	OF COLORADO, a body corporate,	 	 
	Greenwood Village, CO 80111	 	 	 	contracting for and on behalf of the
University of Colorado Denver	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	By:

	 	 	 	 	 	By:	 	 	 	 
	 

	 	 

	 	 
	 	 	 	 

	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	Name:

	 	 	 	 	 	Name:	 	 	 	 
	 

	 	 

	 	 
	 	 	 	 

	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	Title:

	 	 	 	 	 	Title:	 	 	 	 
	 

	 	 

	 	 
	 	 	 	 

	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	Date:

	 	 	 	 	 	Date:	 	 	 	 
	 

	 	 

	 	 
	 	 	 	 

	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	Principal Investigator	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	 

	 	 	 	 	 	By:	 	 	 	 
	 

	 	 	 	 	 	 	 	 

	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	Leland Shapiro	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	Title: Associate Professor of Medicines	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	 

	 	 	 	 	 	Date:	 	 	 	 
	 

	 	 
	 	 	 	 	 	 

	 	 

 

Page 11

 

Appendix A

INFLUENZA RESEARCH PROPOSAL FOR OMNI BIO OPERATING, INC

1. General goal- we will perform studies in vitro and in vivo to determine the biological
activity of alpha-I -antitrypsin (AAT) as an inhibitor of influenza (FLU).

2. Proposed studies:

a) Epidemiology- with collaborators in the department of biostatistics and division of
pulmonary medicine, we have determined that deficiency in AAT comprises a risk factor for FLU
infection. In these investigations, we will complete the biostatistical analysis required to show
that AAT deficiency in humans constitutes a risk factor for FLU infection. For this project we
will recruit the assistance of Dr. Samantha MaWhinney, a qualified biostatistician to conduct the
mathematical analyses. Dr. Martin Zamora will also participate, as the director of the CU Denver
lung transplant program.

b) In vitro- in these studies, we will determine the effect of AAT in reducing FLU virus
production in cells that are infected with FLU in the laboratory.

•Quantify the effect of AAT as a FLU inhibitor in primary Rhesus monkey kidney cells
infected with FLU. A primary cell system (as opposed to immortalized cell lines repeat)/
passaged in the laboratory) is ideal for our work with AAT because other commonly used (in
FLU research) cell lines such as MDCK (Madin Darby canine kidney) cells require the
addition of trypsin (an AAT substrate) to enable multiple rounds of influenza infection.
The Rhesus monkey kidney cell assay is used in clinical hospital microbiology laboratories
to diagnose FLU infection in patients. Therefore, this assay is validated and accepted for
use in FLU infection studies in vitro. Supernatants will be collected from infected cells
and analyzed
for influenza A nuclear protein (read as HA units) in an ELISA assay. Higher readings
are indicative of greater numbers of influenza virions being released from infected
cells.

•Semi-quantify the AAT effect in FLU infection in cells in the laboratory using
immunohistochemistry analysis. The same monkey kidney cells, plated in a larger format
(6-well plates), are stained at various times post-infection, with anti-influenza A
fluorescent antibody to compare plaque sizes and degree of intracellular dissemination.

•Test various AAT preparations for biological anti-FLU activity. We will also assess AAT
serine protease inhibitor activity for relevance in FLU suppression;
this will be accomplished by testing heat inactivated AAT, which is devoid of serine
protease inhibitor function. We will also repeat FLU infection studies using a standard
serine protease inhibitor mimic (Ala-Ala-Pro-Val-CMK). These reagents will be used as tools
to dissect AAT serine protease activity from additional (non-serine protease inhibitor) AAT
functions.

•Again using primary MK cells in the larger, 6-well format, quantify AAT on FLU effects
on cellular apoptosis, cytokine production, and caspase activation.

 

Page 12

 

These assays can be performed by analyzing cell supernatants or lysates (cytokines
by ELISA, caspase by Western blot analysis) or staining cells themselves for flow
analyses (apoptosis, cytokines, caspase).

•Studies in collaboration with National Jewish Medical and Research Center
provide an opportunity to study the effects of AAT on influenza infection of primary human
respiratory epithelium. Type It pneumocytes, known to be primary targets/reservoirs for
FLU, are plated in a transwell system, which essentially “suspends” the polarized cell
monolayer on a thin, permeable membrane. This system allows us to assess differences in
degree of infection (by immuno-fluorescence staining), supernatant cytokine production (by
ELISA), and effects on signaling pathways (from cell lysates). The polarized orientation
(and separate media chambers) permits us to look at other questions, such as whether
supplying AAT from the top (usual) vs. (only) the underside of the cells is required for
effectiveness. We also wish to determine whether FLU infection
(from the top) influences/disrupts monolayer integrity and permits either a measurable
marker protein (also administered from the top) or influenza virions themselves to make
their way into the lower chamber. If the presence of AAT modifies/inhibits such movement
it would have great implications for bird flu, as this strain of influenza is reported to
be so severe because of its ability to move from lung to other organs.

c) In vivo- We will assess the effect of human AAT as a protective molecule for reducing the
effects of FLU infection in mice. These experiments will also be carried out in a collaboration at
NJ. To accomplish this, we will use a mouse strain transgenic for human AAT. The human AAT gene is
expressed primarily in the lung (via the surfactant D promoter), making it an invaluable animal
system to study AAT effects on respiratory viral challenge. The transgenic mice and control mice
will be intra-nasally infected with FLU and then monitored over a 1-2 week period for weight loss
and temperature change. This is essentially a mortality model, as mice that exhibit excessive
weight loss or temperature drop need to be euthanized, as per Animal Committee regulations. Animals
may be randomly selected at certain time points for serum collection and/or lung harvest/inflation.
The serum and/or homogenized lung tissue will be assayed for AAT, cytokine, or caspase levels.
Fixed (inflated) lungs are prepared (sectioned) for gross histology and other sections can be
stained for specific cell markers to help determine the makeup of the cellular infiltrate.

 

Page 13

 

Appendix B

YEAR 1

	 	 	 	 	 
	SALARIES
	 	 	 	 
	Technician (1)
	 	 	47,500	 
	+benefits (30%)
	 	 	14,250	 
	 
	 	 	 	 
	Dr. Shapiro (20% time)
	 	 	30,000	 
	+benefits (33%)
	 	 	10,000	 
	 
	 	 	 	 
	Dr. Oberley salary (with benefits, NJMRC)
	 	 	10,000	 
	 
	 	 	 	 
	REAGENTS
	 	 	 	 
	Alpha-1-antitrypsin (AAT)
	 	 	5,000	 
	Cell lines: monkey kidney cells
and lung epithelial cells
	 	 	5,000	 
	Influenza virus stock
	 	 	1,000	 
	Influenza ELISA kits (10 kits at
$500/kit)
	 	 	10,000	 
	Flow cytometry/fluorescence
microscopy for apoptosis
	 	 	5,000	 
	Cytakine assays
	 	 	5,000	 
	Chemical reagents
	 	 	5,000	 
	 
	 	 	 	 
	EQUIPMENT
	 	 	 	 
	-70°C Freezer
	 	 	12,000	 
	Refrigerated Microfuge
	 	 	6,500	 
	Platform Mixer (Rocking)
	 	 	1,500	 
	Pipetters + vacuum pipetter
	 	 	3,500	 
	Scale + Balance
	 	 	2,000	 
	Inverted Microscope
	 	 	7,500	 
	Refrigerator (2-door delicase)
	 	 	8,000	 
	Water bath + outboard
	 	 	2,000	 
	Plasticware + Glassware
	 	 	5,000	 
	 
	 	 	 	 
	TOTAL DIRECT COSTS
	 	 	195,750	 
	Indirect costs (26%)
	 	 	50,895	 
	 
	 	 	 	 
	TOTAL YEAR 1 BUDGET
	 	 	246,645	 

 

Page 14

 

YEAR 2

	 	 	 	 	 
	SALARIES
	 	 	 	 
	Technician (1)
	 	 	47,500	 
	+benefits (30%)
	 	 	14,250	 
	 
	 	 	 	 
	Dr. Shapiro (20% time)
	 	 	30,000	 
	+benefits (33%)
	 	 	10,000	 
	 
	 	 	 	 
	REAGENTS
	 	 	 	 
	Alpha-l-antitrypsin (PAT)
	 	 	5,000	 
	Cell lines: monkey kidney cells
and lung epithelial cells
	 	 	5,000	 
	Influenza virus stock
	 	 	1,000	 
	Influenza ELISA kits (10 kits at
$500/kit)
	 	 	10,000	 
	Flow cytometry/fluorescence
microscopy
	 	 	5,000	 
	Cytokine assays
	 	 	5,000	 
	Chemical reagents
	 	 	5,000	 
	AAT transgenic / WT mice
	 	 	10,000	 
	 
	 	 	 	 
	EQUIPMENT
	 	 	 	 
	Plasticware + Glassware
	 	 	5,000	 
	 
	 	 	 	 
	TOTAL DIRECT COSTS
	 	 	152,750	 
	Indirect costs (26%)
	 	 	39,715	 
	 
	 	 	 	 
	TOTAL YEAR 2 BUDGET
	 	 	192,465	 

TOTAL 2 YEAR BUDGET

	 	 	 	 	 
	2 YEAR TOTAL BUDGET
	 	 	348,500	 
	DIRECT COSTS
	 	 	 	 
	2 YEAR TOTAL BUDGET
	 	 	90.610	 
	INDIRECT COSTS
	 	 	 	 
	 
	 	 	 	 
	2 YEAR TOTAL BUDGET
	 	 	439,110	 

 

Page 15

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