EXHIBIT 10.4
STANDARD FORM 26 (REV. 4-85)
NSN 7540-01-152-8069
OMB No. 0990-0115
RFP 95-3
AWARD/CONTRACT
1. THIS CONTRACT IS A RATED ORDER UNDER DPAS (15 CFR 350)
RATING
PAGE 1 OF PAGES 21
2. CONTRACT (Proc. inst. ident.) No. NO1-AI-55277
3. EFFECTIVE DATE September 30, 1995
4. REQUISITION/PURCHASE REQUEST/PROJECT N0. 000948
5. ISSUED BY CODE 2668-55277
National Institutes of Health
Contract Management Branch, NIAID
Solar Building, Room 3007
6003 Executive Boulevard MSC 7610
Bethesda, Maryland 20892-7610
6. ADMINISTERED BY (If other than item 5) CODE
7. NAME AND ADDRESS OF CONTRACTOR (No., street, city, country, State and Zip
Code)
BTRL Contracts and Services, Inc., dba/
Biotech Research Laboratories
3 Taft Court
Rockville, Maryland 20850
8. DELIVERY
FOB ORIGIN
OTHER (See below) DESTINATION
9. DISCOUNT FOR PROMPT PAYMENT N/A
10. SUBMIT INVOICES
(4 copies unless otherwise specified) TO THE ADDRESS SHOWN IN
ITEM G.3
CODE
FACILITY CODE
11. SHIP TO/MARK FOR
See Article F.1.
12. PAYMENT WILL BE MADE BY
See Article G.3.
CODE
13. AUTHORITY FOR USING OTHER THAN FULL AND OPEN COMPETITION N/A
10 U.S.C. 2304 (c)( )41 U.S.C. 253(c)( )
14. ACCOUNTING AND APPROPRIATION DATA
CAN#58425674 (Amount Obligated - $387,353)
DOC#300N1A155277
EIN#1-043152484-A1
SOC#25.55
15A. ITEM NO.
15B. SUPPLIES/SERVICES
15C. QUANTITY
15D. UNIT
15E. UNIT PRICE
15F. AMOUNT
Research & Development Contract
Title: MAO/Assessment of Humoral Immune Responses (G)
Period: September 30, 1995 through September 29, 1997
Amount allotted: $387,353 Awarded under MA N01-AI-42602
Contract Type: Cost Reimbursement/Completion
FY 95 387,353
FY 96 226,739
15G. TOTAL AMOUNT OF CONTRACT $614,092
16. TABLE OF CONTENTS
( ) SEC. DESCRIPTION PAGE(S) ( ) SEC. DESCRIPTION PAGE(S)
PART I - THE SCHEDULE PART II - CONTRACT CLAUSES
X A SOLICITATION/CONTRACT FORM 1 X 1 CONTRACT CLAUSES 11
X B SUPPLIES OR SERVICES AND PRICES/COSTS 3 PART III - LIST OF DOCUMENTS,
EXHIBITS AND OTHER ATTACH.
X C DESCRIPTION/SPECS./WORK STATEMENT 7 X J LIST OF ATTACHMENTS 12
X D PACKAGING AND MARKING 7 PART IV- REPRESENTATIONS AND INSTRUCTIONS
X E INSPECTION AND ACCEPTANCE 7 X K REPRESENTATIONS, CERTIFICATIONS AND OTHER
STATEMENTS OF OFFERORS 13
X G CONTRACT ADMINISTRATION DATA 9
11 L INSTRS., CONDS., AND NOTICES TO OFFERORS
X H SPECIAL CONTRACT REQUIREMENTS 10 M EVALUATION FACTORS FOR AWARD
CONTRACTING OFFICER WILL COMPLETE ITEM 17 OR 18 AS APPLICABLE
17. X CONTRACTOR'S NEGOTIATED AGREEMENT (Contractor is required to sign this
document and return 3 copies to issuing office.) Contractor agrees to furnish
and deliver all items or perform all the services set forth or otherwise
identified above and on any continuation sheets for the consideration stated
herein. The rights and obligations of the parties to this contract shall be
subject to and governed by the following documents: (a) this award/contract, (b)
the solicitation, if any, and (c) such provisions, representations,
certifications, and specifications, as are attached or incorporated by reference
herein. (Attachments are listed herein.)
18. AWARD (Contractor is not required to sign this document.) Your offer on
Solicitation Number including the full additions or changes made by you which
additions or changes are set forth in full above, is hereby accepted as to the
items listed above and on any continuation sheets. This award consummates the
contract which consists of the following documents: (a) the Government's
solicitation and your offer, and (b) this award/contract. No further contractual
document is necessary.
19A. NAME AND TITLE OF SIGNER (Type or print)
Mark Manak, Senior Vice President
20A. NAME OF CONTRACTING OFFICER
Jacqueline C. Holden, Contracting Officer
AIDS Preclinical Research Contract Section, CMB, NIAID, HIH
19B. NAME OF CONTRACTOR
BY Mark Manak
(Signature of person authorized to sign)
19C. DATE SIGNED
9/25/95
20B. UNITED STATES OF AMERICA
BY Jacqueline C. Holden
(Signature of Contracting Officer)
20C. DATE SIGNED
9/27/95
DETAILED TABLE OF MASTER AGREEMENT ORDER (MAO) CONTENTS
-------------------------------------------------------
PART I - THE SCHEDULE
SECTION A - SOLICITATION/CONTRACT FORM........................................................................... 1
--------------------------------------
SECTION B - SUPPLIES OR SERVICES AND PRICES/COSTS................................................................. 3
-------------------------------------------------
ARTICLE B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES..................................................... 3
ARTICLE B.2. ESTIMATED COST AND FIXED FEE.................................................................. 3
ARTICLE B.3. PROVISIONS APPLICABLE TO DIRECT COSTS......................................................... 3
ARTICLE B.4. ADVANCE UNDERSTANDINGS........................................................................ 5
SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT............................................................. 7
-----------------------------------------------------
ARTICLE C.1. STATEMENT OF WORK............................................................................. 7
ARTICLE C.2. REPORTING REQUIREMENTS........................................................................ 7
SECTION D - PACKAGING, MARKING AND SHIPPING....................................................................... 7
-------------------------------------------
SECTION E - INSPECTION AND ACCEPTANCE............................................................................. 7
-------------------------------------
SECTION F - DELIVERIES OR PERFORMANCE............................................................................. 8
-------------------------------------
ARTICLE F.1. DELIVERIES.................................................................................... 8
ARTICLE F.2. STOP WORK ORDER............................................................................... 8
SECTION G - CONTRACT ADMINISTRATION DATA.......................................................................... 9
----------------------------------------
ARTICLE G.1. PROJECT OFFICER............................................................................... 9
ARTICLE G.2. KEY PERSONNEL................................................................................. 9
ARTICLE G.3. INVOICE SUBMISSION............................................................................ 9
ARTICLE G.4. GOVERNMENT PROPERTY.......................................................................... 9
ARTICLE G.5. GOVERNMENT SUPPLY SOURCES.......................................................................9
SECTION H - SPECIAL MASTER AGREEMENT ORDER REQUIREMENTS.......................................................... 10
-------------------------------------------------------
ARTICLE H.1. HUMAN SUBJECTS............................................................................... 10
ARTICLE H.2. SALARY RATE LIMITATION LEGISLATION PROVISIONS................................................ 10
PART II................................................................................................................. 11
SECTION I - MASTER AGREEMENT ORDER CLAUSES........................................................................ 11
------------------------------------------
ARTICLE I.1. GENERAL CLAUSES FOR A COST-REIMBURSEMENT RESEARCH AND
DEVELOPMENT MASTER AGREEMENT ORDER.................................................................... 11
ARTICLE I.2. AUTHORIZED SUBSTITUTIONS OF CLAUSES........................................................... 11
ARTICLE I.3. ADDITIONAL MAO CLAUSES........................................................................ 11
ARTICLE I.4. ADDITIONAL FAR CLAUSES INCLUDED IN FULL TEXT.................................................. 11
PART III................................................................................................................ 12
SECTION J - LIST OF ATTACHMENTS................................................................................... 12
-------------------------------
Statement of Work................................................................................................. 12
PART IV................................................................................................................. 13
SECTION K - REPRESENTATIONS AND CERTIFICATIONS.................................................................... 13
----------------------------------------------
Representations and Certifications.......................................................................... 13
2
SECTION B - SUPPLIES OR SERVICES AND PRICES/COSTS
- -------------------------------------------------
[THIS MAO IS AWARDED UNDER MASTER AGREEMENT NO1-AI-42602 FOR HIV PRECLINICAL
VACCINE DEVELOPMENT]
ARTICLE B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES
- -------------------------------------------------------
The purpose of this master agreement order (MAO) is for the Assessment of
Humoral Immune Response.
ARTICLE B.2. ESTIMATED COST AND FIXED FEE
- ------------------------------------------
a. The estimated cost of this MAO is $573,918
b. The fixed fee for this MAO is $40,174. The fixed fee shall be paid in
installments based on the percentage of completion of work, as determined
by the Contracting Officer, and subject to withholding provisions of the
clauses ALLOWABLE COST AND PAYMENT AND FIXED FEE referenced in the General
Clause Listing in PART II, ARTICLE I.1. of this MAO.
Payment of fixed fee shall not be made in less than monthly installments.
c. The Government's obligation, represented by the sum of the estimated cost
plus fixed fee, is $614,092.
d. Total funds currently available for payment and allotted to this MAO are
$387,353 of which $362,012 represents the estimated costs, and of which
$25,341 represents the fixed fee. For further provisions on funding see
the LIMITATION OF FUNDS clause referenced in Part II, ARTICLE I.2.
Authorized Substitutions of Clauses of the Master Agreement (MA).
e. It is estimated that the amount currently allotted will cover performance
of the MAO through September 29, 1996.
f. Increments to be allotted to this contract are estimated as follows:
Estimated Fixed Total Estimated
FY Period Cost Fee Cost Plus Fee
----- --------------------- ---------- -------- --------------
95 09/30/95 - 09/29/96 $362,012 $25,341 $387,353
96 09/30/96 - 09/29/97 $211,906 $14,833 $226,739
Totals $573,918 $40,174 $614,092
g. The Contracting Officer may allot additional funds to the MAO without the
concurrence of the MAO Holder.
ARTICLE B.3. PROVISIONS APPLICABLE TO DIRECT COSTS
- ---------------------------------------------------
a. Items Unallowable Unless Otherwise Provided
Notwithstanding the clause(s), ALLOWABLE COST AND PAYMENT, [and FIXED
FEE,] incorporated in this MAO, unless authorized in writing by the
Contracting Officer, the costs of the following items or activities shall
be unallowable as direct costs:
(1) Acquisition, by purchase or lease, of any interest in real property;
(2) Special rearrangement or alteration of facilities;
(3) Purchase or lease of any item of general purpose office furniture or
office equipment regardless of dollar value. (General purpose
equipment is defined as any items of personal property which are
usable for purposes other than research, such as office equipment
and furnishings, pocket calculators, etc.);
3
(4) Travel to attend general scientific meetings (a general scientific
meeting is defined as an assemblage of scientific/technical
personnel held to exchange information and ideas through a scheduled
program of presentations; includes conferences, congresses,
seminars, symposia and workshops; usually sponsored by a national
organization);
(5) Foreign travel - See Paragraph b. below;
(6) Overtime premium;
(7) Consultant fees;
(8) Subcontracts;
(9) Accountable Government property (defined as both real and personal
property with an acquisition cost of $1,000 or more and a life
expectancy of more than two years) and "sensitive items" (defined
and listed in the Contractor's Guide for Control of Government
Property, 1990, regardless of acquisition value.
b. Travel Costs
(1) Domestic Travel
(a) Total expenditures for domestic travel (transportation, lodging,
subsistence, and incidental expenses) incurred in direct performance
of this MAO shall not exceed $-0- without the prior written approval
of the Contracting Officer.
(Domestic travel is defined as MA Holder travel directly applicable
to performance under this MAO; includes travel to discuss progress
under this MAO with the Project Officer or Contracting Officer or to
attend meetings, called by the NIAID, of collaborating program
investigators to discuss program progress and plans. The domestic
travel amount above does not include scientific meeting travel which
is defined in Article B.3.a. above and which shall be specifically
approved in writing by the Contracting Officer.)
(b) The cost of travel by privately-owned automobile shall be reimbursed
at the mileage rate prescribed by the MA Holder's established,
generally applicable travel policy in lieu of actual costs,
provided, however, that such reimbursement shall not exceed the
otherwise allowable comparative cost of travel by common carrier.
(c) Reasonable actual costs of lodging and subsistence, or per diem in
lieu of actual costs, shall be allowable to the extent that such
actual costs or per diem amounts do not exceed the amounts or per
diem rates prescribed by the MA Holder's established, generally
applicable travel policy.
(d) Any revision to the MA Holder's established, generally applicable
travel policy submitted to the cognizant audit agency during the
period of performance of this MAO shall be effective, without formal
modification to this MAO, upon delivery to the Contracting Officer
of notice describing such revised policy together with evidence of
submission thereof to the cognizant audit agency.
(2) Foreign Travel
Requests for foreign travel must be submitted at least six weeks in
advance and shall contain the following: (a) meeting(s) and place(s) to be
visited, with costs and dates; (b) name(s) and title(s) of Master
Agreement Holder's personnel to travel and their functions in the specific
Master Agreement Order project; (c) the Master Agreement Order purposes to
be served by the travel; (d) how travel of Master Agreement Order
personnel will benefit and contribute to accomplishing the specific Master
Agreement Order project, or will otherwise justify the expenditure of NIH
Master Agreement Order funds; (e) how such advantages justify the costs
for travel and absence from the project of more than one person if such
are suggested; and (f) what additional functions may be performed by the
travelers to accomplish other purposes of the specific Master Agreement
Order and thus further benefit the project.
4
ARTICLE B.4. ADVANCE UNDERSTANDINGS
- ------------------------------------
a. The estimated level of effort set forth below is for guidance to serve not
as a measure of the MAO Holder's obligation but as a further description
of the required tasks. It will represent the basis of direct labor agreed
to in the MAO negotiations for the period from September 30, 1995 through
September 29, 1997, and will be used by both the Government and the MAO
Holder to monitor progress toward achievement of the MAO objectives.
Total Estimated Total Estimated Total Estimated
Labor Category Year 1 Hours Year 2 Hours Number of Hours
-------------- ------------ ------------ ---------------
Principal Investigator 375 375 750
Co-Investigator 1,404 749 2,153
Technician 1,872 1,872 3,744
Technician 1,872 936 2,808
Technician 1,872 0 1,872
TOTAL 7,395 3,932 11,327
b. The total costs negotiated for this MAO only cover Vaccine Studies in
support of Section B of the Statement of Work. Section A of the Statement
of Work is also attached to this contract should it be necessary to
perform assays in support of Vaccine Studies for Section A. If it is
necessary to perform Section A assays, the costs for those assays shall be
offset against the cost negotiated for performance of Section B assays.
c. The MAO Holder agrees to abide by the terms of FAR 52.247-63, Preference
for U.S.-Flag Air Carriers. This provision states in part that, in
performing work under this MAO, the MAO Holder shall utilize U.S. flag air
carriers unless service by those carriers is not available. If U.S. flag
air carriers are not available the MAO Holder shall so certify in writing
and include that certification/justification in the request for advance
approval of foreign travel. (Cost/lower fares are not acceptable reasons
for proposing to utilize foreign air carriers.)
d. The MAO Holder agrees to submit an annual and a final inventory of
Government property as required by the DHHS "Contractor's Guide for
Control of Government Property." Inventories shall be submitted to the
Contract Property Administrator identified in Article G.4. of this
contract, with a copy to the Contracting Officer. Annual inventories shall
be submitted by October 31 each year.
e. The MAO Holder agrees to immediately notify the Contracting Officer in
writing if there is a projected overrun (in any amount) or unexpended
balance (greater than 10%) in the overall budget at the end of any funding
period, and the reasons for the variance (see also the requirements of the
Limitation of Funds clause in the MAO).
f. If the MAO contains any specific limitations/ceilings on particular costs,
these shall always prevail until modified in the MAO.
g. The MAO Holder agrees that samples/products received from/through the
Government for utilization under this contract shall be used only for
purposes required by this MAO.
h. Publication of Manuscripts or Abstracts
Because there is a possibility that the MAO Holder will be evaluating
proprietary compounds provided to the Government by a third party, it is
essential to include provisions that will protect the rights of the third
party suppliers as follows:
The MAO Holder agrees that manuscripts/abstracts based on
data/information generated under this MAO will not be submitted for
publication until written Project Officer clearance has been
received. MAO support shall be acknowledged in all such
publications. A "publication" is defined as an issue of printed
material offered for distribution or any communication or oral
presentation of information.
5
The Project Officer will review all manuscripts/documents in a
period of time not to exceed 30 calendar days from receipt, and will
either grant clearance for publication/disclosure, recommend changes
or, as applicable, refer the document to the Supplier of the
compound for their review. NIAID will use its best efforts to assist
and expedite the review process by the Supplier wherever possible.
i. Correspondence Procedures
To promote timely and effective administration, correspondence (except for
invoices/financial reports, technical progress reports/other deliverables)
submitted under this MAO shall be subject to the following procedures:
1. Technical correspondence shall be addressed to the Project Officer
with an information copy of the basic correspondence to the
Contracting Officer. (As used herein, technical correspondence
excludes correspondence which proposes deviations from or
modifications of MAO requirements, terms or conditions.)
2. Other correspondence shall be addressed to the Contracting Officer,
with an information copy of the basic correspondence to the Project
Officer.
3. Subject Line(s). All correspondence shall contain a subject line
commencing with the contract number as illustrated below:
SUBJECT: Contract No. NO1-AI-55277
Request for Approval of
6
SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT
- -----------------------------------------------------
ARTICLE C.1. STATEMENT OF WORK
- -------------------------------
a. Independently and not as an agent of the Government, the MAO Holder shall
furnish all the necessary services, qualified personnel, material,
equipment, and facilities, not otherwise provided by the Government as
needed to perform the Statement of Work, SECTION J, ATTACHMENT 1, dated
September 30, 1995, attached hereto and incorporated herein.
b. If there is any inconsistency between the MAO Holder's technical proposal
and the work described in this Article C.1., Paragraph a., the terms and
conditions of this Article C.1., Paragraph a, shall control.
ARTICLE C.2. REPORTING REQUIREMENTS
- ------------------------------------
a. Technical Reports
In addition to those reports required by the other terms of this MAO, the
MAO Holder shall prepare and submit the following reports in the manner
stated below and in accordance with ARTICLE F.1. DELIVERIES of this MAO:
(1) Quarterly Progress Report
By the fifteenth calendar day of the month following the end of each
quarter, the MAO Holder shall submit (5) copies of a quarterly
technical report. Four (4) copies shall be submitted to the Project
Officer and one (1) copy shall be submitted to the Contracting
Officer. This report shall include a description of the activities
during the reporting period, and the activities planned for the
ensuing reporting period. The first reporting period consists of the
first full three months of performance including any fractional part
of the initial month. Thereafter, the reporting period shall consist
of three full calendar months. A quarterly report shall not be
submitted when a final report is due.
(2) Final Report
The MAO Holder shall submit five (5) copies of the final report
documents. Four (4) copies shall be submitted to the Project Officer
and (1) copy shall be submitted to the Contracting Officer. This
report is to include a summation of the work performed and results
obtained for the entire MAO period of performance. This report shall
be in sufficient detail to describe comprehensively the results
achieved. The Final Report shall be submitted no later than the
completion date of this MAO.
SECTION D - PACKAGING, MARKING AND SHIPPING
- -------------------------------------------
All deliverables required under this MAO shall be packaged, marked and shipped
in accordance with Government specifications. The MAO Holder shall guarantee
that all required materials shall be delivered in immediate usable and
acceptable condition.
SECTION E - INSPECTION AND ACCEPTANCE
- -------------------------------------
a. For the purpose of this ARTICLE, the designated Project Officer is the
authorized representative of the Contracting Officer, who shall perform
inspection and acceptance of materials and services to be provided.
b. Inspection and acceptance will be performed at the Project Officer's
address listed in the clause entitled "Deliveries" in Section F.
Acceptance may be presumed unless otherwise indicated in writing by the
Contracting Officer or the duly authorized representative within 30 days
of receipt.
c. This MAO incorporates the following clause by reference, with the same
force and effect as if it were given in full text. Upon request, the
Contracting Officer will make its full text available.
FAR Clause 52.246-9, INSPECTION OF RESEARCH AND DEVELOPMENT - (SHORT
FORM)(APRIL 1984).
7
SECTION F - DELIVERIES OR PERFORMANCE
- -------------------------------------
ARTICLE F.1. DELIVERIES
- ------------------------
a. Satisfactory performance of this MAO shall be deemed to occur upon
delivery and acceptance by the Contracting Officer, or the duly authorized
representative, of the following items in accordance with the stated
delivery schedule:
The items specified below as described in (SECTION C, ARTICLE C.2. shall
be delivered f.o.b. destination as set forth in FAR 52.247-35, F.O.B.
DESTINATION, WITHIN CONSIGNEES PREMISES (APRIL 1984), and in accordance
with and by the date(s) specified below [and any specifications stated in
SECTION D, PACKAGING, MARKING AND SHIPPING, of this MAO]:
Item Description Quantity Delivery Schedule
---- ----------- -------- -----------------
1. Quarterly 5 01/15/96, 97,
04/15/96, 97,
07/15/96, 97,
10/15/96
2. Final 5 By completion date of this
contract
The above items shall be addressed and delivered to:
Addressee Deliverable Item No. Quantity
--------- -------------------- --------
Project Officer a.1. 4
PRB, DAIDS a.2. 4
Solar Bldg., Rm. 2A38
6003 Executive Blvd.
Bethesda, MD. 20892
Contracting Officer a.1. 1
CMB, DEA, NIAID, NIH a.2. 1
Solar Bldg., Rm. 3C07
6003 Executive Blvd.
Bethesda, MD. 20892
ARTICLE F.2. STOP WORK ORDER
- -----------------------------
This MAO incorporates the following clause by reference, with the same force and
effect as if it were given in full text. Upon request, the Contracting Officer
will make its full text available.
FEDERAL ACQUISITION REGULATION (48 CFR CHAPTER 1) CLAUSE:
52.212-13, STOP WORK ORDER (AUGUST 1989) with ALTERNATE I (APRIL 1984).
8
SECTION G - CONTRACT ADMINISTRATION DATA
- ----------------------------------------
ARTICLE G.1. PROJECT OFFICER
- -----------------------------
Pursuant to the Project Officer Article incorporated in the MA, the following
Project Officers will represent the Government for the purpose of this MAO:
MAO Project Officer: Nancy Miller, Ph.D.
ARTICLE G.2. KEY PERSONNEL
- ---------------------------
Pursuant to the Key Personnel clause incorporated in the MA, the following
individuals are considered to be essential to the work being performed
hereunder:
NAME TITLE
---- -----
Mark Cosentino, Ph.D. Principal Investigator
Hanna Weissberger, Ph.D. Co-Investigator
ARTICLE G.3. INVOICE SUBMISSION
- --------------------------------
a. INVOICE SUBMISSION - COST-REIMBURSEMENT MAOs
The Invoice/Financing Request Instructions for NIH Cost-Reimbursement Type
Contracts, NIH(RC)-1, set forth in your Master Agreement are incorporated
herein.
The invoice instructions and directions for the submission of
invoice/financing requests contained in the MA must be followed to meet
the requirements of a "proper" invoice, pursuant to FAR 32.9.
ARTICLE G.4. GOVERNMENT PROPERTY
- ---------------------------------
a. In addition to the requirements of the clause, GOVERNMENT PROPERTY,
incorporated in this Section I of this MAO, the MAO Holder shall comply
with the provisions of DHHS Publication, Contractor's Guide for Control of
Government Property, (1990), which is incorporated into this MAO by
reference. Among other issues, this publication provides a summary of the
MAO Holder's responsibilities regarding purchasing authorizations and
inventory and reporting requirements under the MAO. A copy of this
publication is available upon request to the Contract Property
Administrator at the following address:
Contracts Property Administrator
Research Contracts Property Administration, NIH
Building 13, Room 2E-65
9000 Rockville Pike
Bethesda, Maryland 20892
(301) 496-6466
ARTICLE G.5. GOVERNMENT SUPPLY SOURCES, is hereby incorporated into this MAO by
reference pursuant to the Master Agreement.
9
SECTION H - SPECIAL MASTER AGREEMENT ORDER REQUIREMENTS
- -------------------------------------------------------
The following Articles are incorporated into this MAO by reference pursuant to
the Master Agreement. [(Any MAO Articles which are not contained in the MA are
set forth below in full text)]:
a. ARTICLE H.1. HUMAN SUBJECTS
----------------------------
b. ARTICLE H.2. SALARY RATE LIMITATION LEGISLATION PROVISIONS
-----------------------------------------------------------
Paragraph b. of this ARTICLE is revised as follows:
b. Public Law No. Fiscal Year Salary Limitation
-------------- ----------- -----------------
103-333 1995 $125,000
10
PART II
- -------
SECTION I - MASTER AGREEMENT ORDER CLAUSES
- ------------------------------------------
The following Articles are incorporated into this MAO by reference pursuant to
the Master Agreement. [(Any MAO Articles which are not contained in the MA are
set forth below in full text)]:
a. ARTICLE I.1. GENERAL CLAUSES FOR A NEGOTIATED COST-REIMBURSEMENT MASTER
AGREEMENT ORDER
b. ARTICLE I.2. AUTHORIZED SUBSTITUTIONS OF CLAUSES]
For this Master Agreement Order (N01-AI-55277), FAR Clause 52.232-22,
LIMITATION OF FUNDS, (APRIL 1984) as contained in MA N01-AI-42602 is
deleted in its entirety and is replaced with FAR Clause 52.232-20,
LIMITATION OF COSTS.
c. ARTICLE I.3. ADDITIONAL MASTER AGREEMENT CLAUSES
d. ARTICLE I.4. ADDITIONAL FAR CLAUSES INCLUDED IN FULL TEXT
11
PART III
- --------
SECTION J - LIST OF ATTACHMENTS
- -------------------------------
Unless otherwise indicated below, the following documents are attached and
incorporated in this MAO:
1. Statement of Work, September 30, 1995; 8 pages.
2. Invoice/Financing Request Instructions for NIH Cost-Reimbursement Type
Contracts, NIH(RC)-1 (6/18/92), 4 pages. [This attachment is part of the
Master Agreement document and is incorporated into this MAO by reference.]
3. Safety and Health, PHSAR Clause 352.223-70, (4/84), 2 pages. [This
attachment is part of the Master Agreement document and is incorporated
into this MAO by reference.]
4. Procurement of Certain Equipment, NIH(RC)-7, (4/1/84), 1 page. [This
attachment is part of the Master Agreement document and is incorporated
into this MAO by reference.]
12
PART IV
- -------
SECTION K - REPRESENTATIONS AND CERTIFICATIONS
- ----------------------------------------------
The following documents are incorporated by reference in this MAO:
1. Representations and Certifications, dated September 15, 1995.
END of the SCHEDULE
(MASTER AGREEMENT ORDER)
13
MASTER AGREEMENT ORDER FOR CATEGORY G
STATEMENT OF WORK
ASSESSMENT OF HUMORAL IMMUNE RESPONSES
SECTION A: HUMORAL IMMUNE RESPONSES TO HIV VACCINES
Independently, and not as an agent of the Government, the Master Agreement Order
holder shall provide the necessary services, qualified personnel, material,
equipment, and facilities, not otherwise provided by the Government, as needed
to perform the tasks of the Statement of Work below:
The MAO Contractor shall perform assays to assess and characterize the humoral
immune responses of macaques that have been immunized with HIVenv or with a
combination of HIVenv and SIV non-env vaccines. Specifically the MAO Contractor
shall:
1. Conduct assays to determine the ability of sera or mucosal secretions from
monkeys immunized with HIV vaccines (or of sera from infected monkeys
after SHIV challenge) to neutralize infection of cell lines and/or primary
cells (PBMC) by the HIV strain used for the vaccine. Further characterize
the antibodies, including determining the neutralization titer against the
vaccine (homologous) HIV strain. If the appropriate SHIV virus stock is
available, determine the ability of the sera to neutralize the SHIV made
with the envelope gene of the homologous (vaccine) HIV.
2. For sera (or mucosal secretions) that were determined (above) to
neutralize the homologous strain of HIV, determine the neutralization
titer against infection of T cell lines and/or PBMC by heterologous
laboratory strains of HIV.
3. For sera (or mucosal secretions) that show the ability to neutralize
heterologous HIV isolates (above), determine the ability to neutralize
infection of T cell lines and/or primary PBMC and/or primary macrophages
by primary, "field" isolates of HIV grown only in primary cells.
4. Prior to conducting neutralization assays with the monkey sera from the
vaccine studies, grow appropriate HIV and SHIV virus stocks and
demonstrate that the viruses are able to be neutralized by sera from
HIV-infected people or SHIV-infected monkeys.
5. Receive, catalog, track, and maintain an inventory of the specimens that
arrive for evaluation:
a) Advise sample suppliers (Category B contractors) of the most
suitable manner for shipment of sera, whole blood, cells or other
specimens for evaluation and arrange for the transfer of these
specimens from primate laboratories to the Contractor. All shipments
must be coordinated so that activity/viability of specimens will not
be adversely affected.
b) When necessary, pick up or arrange for pick up of incoming specimen
shipments from a specified airport or other contact site in a timely
manner and assure maintenance of activity and/or viability of the
specimens by providing the appropriate temperature in transit from
the airport or other contact site to the Contractor's laboratory.
c) Receive and catalog specimens arriving for evaluation from the
primate laboratories. Maintain documentation on file for all
incoming specimens, including but not limited to:primate subject
identification number, trial site, protocol identification number,
specimen collection date and condition of sample upon arrival.
d) Store cataloged, aliquotted specimens under appropriate conditions
to retain maximum immunological activity.
e) Maintain specimen tracking and inventory system such that specimens
can be traced and located from receipt through processing and assay
analysis.
MAO Statement of Work ATTACHMENT 1
9/30/95
14
6. Maintain test result database and transfer data electronically:
a) Compile and maintain a computerized database of all neutralization
assays results, using a format compatible with the FOX-PRO data base
that NIAID plans to use to compile records and data from the vaccine
studies. Assay results are to be recorded with designations of study
protocol number, animal number, specimen collection date, and other
information requested by the Project Officer.
b) Transfer specified data electronically to the AIDS Vaccine
Evaluation Group (AVEG) Statistical and Coordinating Center (SCC)
and to the Project Officer at regular intervals as instructed by the
Project Officer (format to be agreed upon between NIAID and the
Contractor).
c) Ensure protection against the loss of data by the duplication of
data base files and programs for storage; provide for the security,
safety, and accuracy of data on the specimen inventory and the test
results database.
7. Provide facilities and resources
a) Provide facilities and equipment for the work to be conducted,
including a biosafety level 2 or 3 laboratory for conducting work
with live HIV and SHIV as well as samples from infected monkeys.
b) Provide, maintain, and operate facilities for controlled storage of
sera, virus stocks, cell stocks, and other samples and reagents,
including storage at -10 to -20 degrees C, at -70 to -90 degrees C,
and in liquid nitrogen conditions, with appropriate monitoring of
storage conditions to guarantee continuous proper storage. The
reliability of supply systems, electrical power, and backup support
systems shall be ensured by the contractor.
c) Provide protective garments, equipment and sufficient monitoring to
assure safe handling of potentially hazardous materials, including
radioactive materials. Specifically, the contractor shall comply
with all applicable health and safety regulations while conducting
the work set forth herein.
d) Conduct work under this contract in accordance with all applicable
Federal, state, and local laws, codes, ordinances and regulations,
and with the following basic references and other related
modifications by the Public Health Service:
(1) Biosafety in Microbiological and Biomedical Laboratories, U.S.
Department of Health and Human Services, Centers for Disease
Control and National Institutes of Health, HHS Pub. No. (NIH)
93-8395 published by the U.S. Government Printing Office,
third edition, May 1993, stock number 17-040-00523-7.
(2) Recommendations for Prevention of HIV Transmission in Health
Care Settings, Morbidity and Mortality Weekly Report, Vol. 36,
No. 2-S.
(3) Agent Summary Statement for Human Immunodeficiency Virus and
Report on Laboratory-Acquired Infection with Human
Immunodeficiency Virus, Morbidity and Mortality Weekly Report,
Vol. 37, No.S-4, pp.1-22.
(4) "Guidelines to Prevent Simian Immunodeficiency Virus Infection
in Laboratory Workers and Animal Handlers", Morbidity and
Mortality Weekly Report, Vol. 37, No. 45, pp. 693-704.
8. Designate a project coordinator to manage the day-to-day conduct of the
study, to interact with the Category B MAO laboratory or laboratories
providing non-human primate samples from the vaccine study or studies, and
to provide information on the status of the assay results to the Project
Officer.
9. Report data and results to NIAID or to a designated NIAID contractor.
Printouts of data and verbal reports of the status of the study are to be
provided on an ongoing basis during the course of the study at the request
of the Project Officer, in addition to the required periodic (quarterly
and final) written reports describing the progress of the study, and in
addition to the periodic electronic transfer of data described in item (6)
above.
MAO Statement of Work ATTACHMENT 1
9/30/95
15
SUMMARY OF VACCINE STUDIES FOR WHICH ASSAYS MAY BE REQUIRED
-----------------------------------------------------------
(SECTION A: HUMORAL IMMUNE RESPONSES TO HIV VACCINES)
VACCINE STUDY 7
- ---------------
Title: Evaluation of HIV DNA Vaccines in Monkeys Using the SHIV Model
Description: To compare routes of administration, rhesus monkeys will be
immunized by either intramuscular injection or by "gene gun" inoculation with
DNA constructs which express HIV-1 env proteins, together with DNA constructs
expressing SIV proteins. The animals will be challenged with SHIV to determine
if a protective response is induced and, if so, how soon it is induced and how
long it persists.
Number of monkeys: 24 (6 groups of 3; 3 groups of 2)
Length of study: 30 months
Number of inoculations per animal: 4 immunizations plus 1 virus challenge
VACCINE STUDY 8
- ---------------
Title: Evaluation of the Contribution of SIV Regulatory Genes to the Efficacy of
an HIV/SIV DNA Vaccine.
Description: Rhesus monkeys will be immunized intramuscularly with DNA
constructs encoding HIV envelope, DNA constructs expressing SIV proteins, and
DNA constructs expressing SIV regulatory gene products to determine if
theregulatory proteins elicit immune responses (particularly CTL responses) that
enhance the ability of the monkeys to resist infection with SHIV.
Number of monkeys: 20 (5 groups of 4)
Length of study: 24 months
Number of inoculations per animal: 4 immunizations plus 1 virus challenge
VACCINE STUDY 13
- ----------------
Title: Immunogenicity of a Soluble Oligomeric Form of the HIV-1 Envelope Protein
Description: Rhesus monkeys will be immunized with a purified oligomeric form of
the HIV-1 envelope protein to determine if monkeys will generate antibodies
(presumably to conformational epitopes of the oligomeric envelope) that are able
to neutralize genetically divergent strains of HIV-1. Vaccines based on
monomeric forms of the HIV-1 envelope generate predominantly type- specific
antibodies that neutralize a limited range of HIV-1 isolates, but preliminary
studies with the oligomeric form of the envelope indicate that antibodies to it
may be more broadly reactive. Animals will be challenged with SHIV after
immunization to determine the ability of the immune response to the oligomeric
envelope to protect monkeys from infection.
Number of monkeys: 18 (6 groups of 3)
Length of study: 24 months
Number of inoculations per animal: 5 immunizations plus 1 virus challenge
MAO Statement of Work ATTACHMENT 1
9/30/95
16
VACCINE STUDY 16
- ----------------
Title: Evaluation of a Recombinant Semliki Forest Virus/HIV Vaccine
Description: Rhesus monkeys will be immunized with an avirulent recombinant
Semliki Forest virus expressing HIV-1 envelope and SIV gag proteins. The monkeys
will be infected with the virus, which has a broad tissue tropism, by either
intramuscular, intravenous, subcutaneous, or mucosal site administration.
Animals will be challenged with SHIV to determine the efficacy of this vaccine
in protecting from virus infection.
Number of monkeys: 10 (5 groups of 2)
Length of study: 18 months
Number of inoculations per animal: 8 immunizations plus 1 virus challenge
MAO Statement of Work ATTACHMENT 1
9/30/95
17
SECTION B: HUMORAL IMMUNE RESPONSES TO SIV VACCINES
- ----------------------------------------------------
Independently, and not as an agent of the Government, the Master Agreement Order
holder shall provide the necessary services, qualified personnel, material,
equipment, and facilities, not otherwise provided by the Government, as needed
to perform the tasks of the Statement of Work below.
The MAO Contractor shall perform assays to assess the humoral immune responses
of macaques that have been immunized with an SIV vaccine. Specifically the MAO
Contractor shall:
1. Determine the capability of sera or mucosal secretions from monkeys
immunized with SIV vaccines to neutralize infection of cell lines and/or
primary cells (PBMC) by the SIV strain used for the vaccine. Further
characterize these antibodies, including determining the neutralization
titer against the vaccine (homologous) SIV strain.
2. For sera (or mucosal secretions) that were determined (above) to
neutralize the homologous strain of SIV, determine the neutralization
titer against infection of T cell lines and/or PBMC by a heterologous
strain or strains of SIV.
3. Prior to conducting neutralization assays with the monkey sera (or mucosla
secretions) from the vaccine studies, grow appropriate SIV virus stocks
and demonstrate that the viruses are able to be neutralized by sera from
SIV-infected monkeys.
4. Receive, catalog, track, and maintain an inventory of the specimens that
arrive for evaluation:
a) Advise sample suppliers (Category B contractors) of the most
suitable manner for shipment of sera, whole blood, cells or other
specimens for evaluation and arrange for the transfer of these
specimens from primate laboratories to the Contractor. All shipments
must be coordinated so that activity/viability of specimens will not
be adversely affected.
b) When necessary, pick up or arrange for pick up of incoming specimen
shipments from a specified airport or other contact site in a timely
manner and assure maintenance of activity and/or viability of the
specimens by providing the appropriate temperature in transit from
the airport or other contact site to the Contractor's laboratory.
c) Receive and catalog specimens arriving for evaluation from the
primate laboratories. Maintain documentation on file for all
incoming specimens, including but not limited to: primate subject
identification number, trial site, protocol identification number,
specimen collection date and condition of sample upon arrival.
d) Store cataloged, aliquotted specimens under appropriate conditions
to retain maximum immunological activity.
e) Maintain specimen tracking and inventory system such that specimens
can be traced and located from receipt through processing and assay
analysis.
5. Maintain test result database and transfer data electronically:
a) Compile and maintain a computerized database of all neutralization
assays results, using a format compatible with the FOX-PRO data base
that NIAID plans to use to compile records and data from the vaccine
studies. Assay results are to be recorded with designations of study
protocol number, animal number, specimen collection date, and other
information requested by the Project Officer.
b) Transfer specified data electronically to the AIDS Vaccine
Evaluation Group (AVEG) Statistical and Coordinating Center (SCC)
and to the Project Officer at regular intervals as instructed by the
Project Officer (format to be agreed upon between NIAID and the
Contractor).
MAO Statement of Work ATTACHMENT 1
9/30/95
18
c) Ensure protection against the loss of data by the duplication of
data base files and programs for storage; provide for the security
and safety of data on the specimen inventory and the test results
database.
6. Provide facilities and resources:
a) Provide facilities and equipment for the work to be conducted,
including a biosafety level 2 or 3 laboratory for conducting work
with live HIV and SHIV as well as samples from infected monkeys.
b) Provide, maintain, and operate facilities for controlled storage of
sera, virus stocks, cell stocks, and other samples and reagents,
including storage at -10 to -20 degrees C, at -70 to -90 degrees C,
and in liquid nitrogen conditions, with appropriate monitoring of
storage conditions to guarantee continuous proper storage. The
reliability of supply systems, electrical power, and backup support
systems shall be ensured by the contractor.
c) Provide protective garments, equipment and sufficient monitoring to
assure safe handling of potentially hazardous materials, including
radioactive materials. Specifically, the contractor shall comply
with all applicable health and safety regulations while conducting
the work set forth herein.
d) The Contractor shall conduct work under this contract in accordance
with all applicable Federal, state, and local laws, codes,
ordinances and regulations, and with the following basic references
and other related modifications by the Public Health Service:
(1) Biosafety in Microbiological and Biomedical Laboratories, U.S.
Department of Health and Human Services, Centers for Disease
Control and National Institutes of Health, HHS Pub. No. (NIH)
93-8395 published by the U.S. Government Printing Office,
third edition, May 1993, stock number 17-040-00523-7.
(2) Recommendations for Prevention of HIV Transmission in Health
Care Settings, Morbidity and Mortality Weekly Report, Vol. 36,
No. 2-S.
(3) Agent Summary Statement for Human Immunodeficiency Virus and
Report on Laboratory-Acquired Infection with Human
Immunodeficiency Virus, Morbidity and Mortality Weekly Report,
Vol. 37, No.S-4, pp.1-22.
(4) "Guidelines to Prevent Simian Immunodeficiency Virus Infection
in Laboratory Workers and Animal Handlers," Morbidity and
Mortality Weekly Report, Vol. 37, No. 45, pp. 693-704.
7. Designate a project coordinator to manage the day-to-day conduct of the
study, to interact with the Category B MAO laboratory or laboratories
providing non-human primate samples from the vaccine study or studies, and
to provide information on the status of the assay results to the Project
Officer.
8. Report data and results to NIAID or to a designated NIAID contractor.
Printouts of data and verbal reports of the status of the study are to be
provided on an ongoing basis during the course of the study at the request
of the Project Officer, in addition to the required periodic (quarterly
and final) written reports describing the progress of the study, and in
addition to the periodic electronic transfer of data described in item (6)
above.
MAO Statement of Work ATTACHMENT 1
9/30/95
19
SUMMARY OF VACCINE STUDIES FOR WHICH ASSAYS MAY BE REQUIRED:
- ------------------------------------------------------------
(SECTION B: HUMORAL IMMUNE RESPONSES TO SIV VACCINES)
VACCINE STUDY 1
- ---------------
Title: Comparison of Different Routes of Immunization with ALVAC/SIV
Description: Rhesus monkeys will be immunized by three different routes with
recombinant avipox (ALVAC) expressing SIV genes. Intramuscular and two mucosal
routes are planned. Animals will be challenged with SIV administered
intravenously or at a mucosal surface to determine if there is a difference in
efficacy of the vaccine when administered by different routes and to determine
if mucosal routes of immunization are more effective at blocking infection at
mucosal surfaces than intramuscular immunizations. Monkeys will be followed
after challenge to determine whether infection has occurred and whether
immunization affects disease progression in any infected animals.
Number of monkeys: 48 (8 groups of 6)
Length of study: 32 months
Number of inoculations per animal: 5 immunizations plus 1 virus challenge
VACCINE STUDY 2
- ---------------
Title: Comparison of Different Routes of Immunization with NYVAC/SIV
Description: Rhesus monkeys will be immunized by three different routes with
recombinant attenuated vaccinia virus (NYVAC) expressing SIV proteins.
Intramuscular and two different mucosal routes are planned. Animals will be
challenged with SIV administered intravenously or at a mucosal surface to
determine if there is a difference in efficacy of the vaccine when administered
by different routes and to determine if mucosal routes of immunization are more
effective at blocking infection at mucosal surfaces than intramuscular
immunizations. Monkeys will be followed after challenge to determine whether
infection has occurred and whether immunization affects disease progression in
infected animals.
Number of monkeys: 48 (8 groups of 6)
Length of study: 32 months
Number of inoculations per animal: 5 immunizations plus 1 virus challenge
VACCINE STUDY 5
- ---------------
Title: Evaluation of Immunization with Recombinant Vaccinia/SIV Vaccine Followed
by Immunization with SIV Proteins
Description: Rhesus monkeys will be immunized with recombinant vaccinia
expressing SIV genes by intradermal, subcutaneous, intramuscular or oral routes,
followed by immunizations with SIV proteins. Animals will be challenged WITH SIV
to determine whether the efficacy of the vaccine is affected by the route of
administration.
Number of monkeys: 24 (4 groups of 6)
Length of study: 24 months
Number of inoculations per animal: 6 immunizations plus 1 virus challenge
MAO Statement of Work ATTACHMENT 1
9/30/95
20
VACCINE STUDY 14
- ----------------
Title: Evaluation of recombinant BCG/SIV vaccines
Description: Rhesus monkeys will be immunized orally with a live recombinant BCG
expressing SIV proteins, followed by immunization with a mixture of SIV
peptides. The monkeys will be challenged with SIV administered intravenously or
at a mucosal site different from the site of immunization to determine if the
live recombinant BCG vaccine administered by a mucosal route confers protection
from infection.
Number of monkeys: 16 (4 groups of 4)
Length of study: 30 months
Number of inoculations per animal: 4 immunizations plus 1 virus challenge
VACCINE STUDY 15
- ----------------
Title: Evaluation of a Recombinant Polio/SIV Vaccine
Description: Pig-tailed macaques will be immunized at two mucosal sites with
live recombinant poliovirus replicons expressing SIV proteins. This will be
followed by immunization with purified SIV proteins. The animals will be
challenged with SIV either intravenously or at a mucosal site used for
immunization or at a mucosal site different from the one used for immunization.
Number of monkeys: 30 (for immunizations: 6 groups of 4; for titration of
challenge virus stock: 6)
Length of study: 24 months
Number of inoculations per animal: 3 immunizations plus 1 virus challenge
MAO Statement of Work ATTACHMENT 1
9/30/95
21