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Table of Contents
.
1.0 Introduction........................................................................ .........................................4
1.1 Purpose of the NIH Guidelines ........................................................................4
..
..
.. of Recombinant DNA Molecules .....................................................4
1.2 Definition
.
1.3 Compliance with the Guidelines ......................................................................4
1.4 The.. Policies on Compliance ............................................................................5
2.0 Responsibilities ........................................................................ ..................................5
2.1 Recombinant DNA Safety Committee .............................................................5
2.2 Principal Investigator ........................................................................ .............6
3.0 Approval Procedures ..................................................................................................7
3.1 Registration Document ....................................................................................7
3.2 Training ........................................................................ ...................................7
3.3 Changes in Approved Research ......................................................................8
3.4 Laboratory Inspections .....................................................................................8
4.0 Risk Groups and Biosafety Levels ...............................................................................8
4.1 Risk Groups and Risk Assessment ..................................................................8
4.2 Physical Containments .....................................................................................9
5.0 Recombinant DNA Experiments Covered by the NIH Guidelines ..............................10
5.1 Experiments that require RDSC approval, RAC review, and NIH director
2
Approval before Initiation .................................................................................10
5.2 Experiments that Require NIH/OBA and RDSC Approval Before Initiation .....10
5.3 Experiments that Require RDSC and Institutional Review Board
Approvals and RAC Review Before Research Participant Enrollment ............10
5.4 Experiments that Require RDSC Approval Before Initiation of Experiment .....11
5.5 Experiments that Require RDSC Notification at the Time of Initiation .............12
5.6 Experiments that are Exempt from NIH Review but are Recommended for
RDSC Registration or Approval .......................................................................12
6.0 Additional Guidelines of Protocols for the Transfer of Recombinant DNA
Molecules into Human Subjects ................................................................................13
Appendix
A. The Uniform Biological Material Transfer Agreement
B. TSU Recombinant DNA Registration Form
3
1.0 Introduction
This manual is to provide a practical reference on the safety of research involving recombinant DNA at Texas
Southern University (TSU). The manual has been adapted from the current version of the NIH Guidelines
for Research Involving Recombinant DNA Molecules (NIH Guidelines, January 2001).
The condensed guidelines presented in this manual are more specifically provided to assist the Recombinant
DNA Safety Committee (RDSC) and relevant researchers in determining the safety and containment as well
as review levels of research protocols involving the use of DNA at TSU. Because the RDSC at TSU is a
newly formed committee and the researchers at TSU are not familiar with the NIH Guidelines, it is
recommended that all researchers involved in the use of DNA submit the enclosed Registration Form to the
RDSC. The RDSC will help researchers to decide the levels for review and safety containment for all
relevant proposals. This abstracted manual is not inclusive, please see the complete Guidelines for
Research Involving Recombinant DNA Molecules (January 2001, downloadable from the NIH Homepage)
and updates for details.
1.1 Purpose of the NIH Guidelines
The purpose of the NIH Guidelines is to specify practices for construction and handling: (i) recombinant
deoxyribonucleic acid (DNA) molecules, and (ii) organisms and viruses containing recombinant DNA
molecules.
1.2 Definition of Recombinant DNA molecules
Recombinant DNA molecules are defined as either: (i) molecules that are constructed outside living cells by
joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell, or (ii)
molecules that result from the replication of those described in (i) above.
Synthetic DNA segments which are likely to yield a potentially harmful polynucleotide or polypeptide (e.g., a
toxin or a pharmacologically active agent) are considered as equivalent to their natural DNA counterpart. If
the synthetic DNA segment is not expressed in vivo as a biologically active polynucleotide or polypeptide
product, it is exempt from the NIH guidelines. Genomic DNA of plants and bacteria that have acquired a
transposable element, even if the latter was donated from a recombinant vector no longer present, are not
subject to the NIH guidelines unless the transposon itself contains recombinant DNA.
1.3 Compliance with the Guidelines
Research involving recombinant DNA shall comply with the National Institute of Health's "NIH Guidelines for
Research Involving Recombinant DNA Molecules" (NIH Guidelines). The recombinant DNA guidelines are
applicable to all recombinant DNA research within the United States or its territories, which is conducted at or
sponsored by an institution that receives any support for recombinant DNA research from NIH. Any individual
receiving support for research involving recombinant DNA must be associated with or sponsored by an
institution that can and does assume the responsibilities assigned in the guidelines.
The safe conduct of experiments involving recombinant DNA depends on the individual conducting such
activities. The guidelines cannot anticipate every possible situation. The NIH guidelines are intended to assist
the institution, institutional biosafety committee (IBC) on recombinant DNA (designated as the Recombinant
DNA Safety Committee---RDSC, at TSU), Chemical and Biological Safety Officer, and principal investigator in
4
determining safeguards that should be implemented. It is the responsibility of Texas Southern University and
those associated with it to adhere to the intent of the NIH guidelines as well as to its specifics.
Thus, as a condition for funding of recombinant DNA research, an institution shall ensure that such research
conducted at or sponsored by the institution, irrespective of the source of funding, shall comply with the NIH
Guidelines.
1.4 The policies on compliance
All NIH-funded and all non-NIH-funded projects involving recombinant DNA techniques must comply with the
NIH Guidelines. Non-compliance may result in: (i) suspension, limitation, or termination of financial
assistance for the noncompliant NIH-funded research project and of NIH funds for other recombinant DNA
research at the institution, or (ii) a requirement for prior NIH approval of any or all recombinant DNA projects
at the institution.
2.0 Responsibilities
Texas Southern University is responsible for ensuring that the research is conducted in full conformity with
the provisions of the NIH guidelines. This section describes and assigns those responsibilities.
2.1 Recombinant DNA Safety Committee
The Recombinant DNA Safety Committee (RDSC) is responsible for coordinating the recombinant DNA
safety program for the University.
The RDSC establishes and implements policies that provide for the safe conduct of recombinant DNA
research and that ensure compliance with the NIH guidelines. The RDSC comprises at least three members
who collectively have experience and expertise in recombinant DNA technology. They possess the capability
to assess the safety of recombinant DNA research and to identify any potential risk to public health or the
environment.
The RDSC is responsible for reviewing recombinant DNA research conducted at or sponsored by the
University for compliance with the NIH guidelines as specified in Section III of the NIH guidelines. The
committee approves those research projects that are found to conform to the NIH guidelines. The RDSC
review shall include
1. an independent assessment of the containment levels required by the NIH guidelines for the proposed
research;
2. assessment of the facilities, procedures, practices, training, and expertise of documented personnel
involved in recombinant DNA research;
3. notifying the principal investigator of the results of the committee's review;
4. reviewing recombinant DNA research conducted at TSU to ensure compliance with the NIH guidelines;
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5. adopting emergency plans covering accidental spills and personnel contamination resulting from
recombinant DNA research;
6. periodic inspections to ensure that laboratory standards are rigorously followed (Note: laboratories are
periodically inspected as part of the laboratory safety program);
7. providing advice on laboratory security;
8. providing technical advice to principal investigators on recombinant DNA laboratory safety procedures;
9. reporting any significant problems with or violations of the NIH guidelines and any significant researchrelated accidents to the appropriate institutional official and NIH/Office of Recombinant DNA Activities
within 30 days.
2.2 Principal Investigator
The principal investigator is responsible for full compliance with the NIH guidelines in the conduct of
recombinant DNA research. As part of this responsibility, the principal investigator shall
1)
2)
3)
make an initial determination of the biosafety levels and the required levels of physical
accordance with the NIH guidelines;
containment in
select appropriate microbiological practices and laboratory techniques to be used for the
research;
submit the initial research protocol and any subsequent changes (e.g., changes in the source of
host-vector system) to the RDSC for review and approval or disapproval;
4)
remain in communication with the RDSC throughout the duration of the project;
5)
make available to all laboratory staff the protocols that describe the potential biohazards and the
precautions to be taken;
DNA or
6)
instruct and train laboratory staff in the practices and techniques required to ensure safety
and the
procedures for dealing with accidents;
7) supervise the safety performance of the laboratory staff to ensure that the required safety practices and
techniques are employed;
8)
investigate and report any significant problems pertaining to the operation and implementation of
containment practices and procedures in writing to the RDSC;
9)
correct work errors and conditions that may result in the release of recombinant DNA
materials;
10) ensure the integrity of the physical containment (e.g., biological safety cabinets) and the biological
containment (e.g., purity and genotypic and phenotypic characteristics);
11) initiate or modify no recombinant DNA research prior to RDSC approval until that research or the
proposed modification thereof has been approved by the RDSC and has met all other
requirements of
the NIH guidelines;
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12) determine whether experiments are covered by Section III-E of the NIH guidelines and ensure that the
appropriate procedures are followed and immediately report any significant problems,
violations of the
NIH guidelines, or any significant research-related accidents to the RDSC and
other appropriate
authorities;
13) be adequately trained in good microbiological techniques;
14) comply with shipping requirements for recombinant DNA molecules.
3.0 Approval Procedures
3.1 Registration Document
Principal investigators intending to use recombinant DNA molecules shall notify the RDSC by contacting the
RDSC for information and the registration form. The principal investigator shall prepare the registration
document according to the nature of the research. A copy of the current NIH guidelines should be available
for reference.
3.2 Training
Principal investigators performing recombinant DNA experiments shall file a Statement of Training and/or
Experience with the RDSC for all active researchers.
3.3 Changes in Approved Research
Principal investigators wishing to modify approved research are responsible for notifying the RDSC. Principal
investigators must file a new or amended registration document when there are changes in their research
protocols that require reclassification.
3.4 Laboratory Inspections
Laboratory inspections are required for recombinant DNA experiments that are regulated by the NIH
guidelines. The RDSC will inspect newly registered laboratories working at biosafety level 2 (BL2) as part of its
normal laboratory inspection functions (see next section for the description of biosafety levels). Inspection and
certification of newly registered laboratories by the RDSC are required for recombinant DNA experiments
performed at biosafety level 3 (BL3). BL3 laboratories are to be inspected annually by the RDSC.
4.0 Biosafety Issues on Recombinant DNA
4.1 Risk Groups and Risk Assessment
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Agents are classified into four Risk Groups (RGs) according to their relative pathogenicity for healthy adult
humans by the following criteria: (1) Risk Group 1 (RG1) agents are not associated with disease in healthy
adult humans. (2) Risk Group 2 (RG2) agents are associated with human disease which is rarely serious and
for which preventive or therapeutic interventions are often available. (3) Risk Group 3 (RG3) agents are
associated with serious or lethal human disease for which preventive or therapeutic interventions may be
available. (4) Risk Group 4 (RG4) agents are likely to cause serious or lethal human disease for which
preventive or therapeutic interventions are not usually available.
An initial risk assessment should be made based on the RGs of an agent (see Appendix B of the NIH
Guidelines for the Classification of Human Etiologic Agents on the Basis of Hazard). The appropriate
containment for an experiment can be determined based upon the agent itself (such as virulence and
pathogenicity) and the nature of the experimental protocol.
Biosafety levels consist of combinations of laboratory practices and techniques, safety equipment, and
laboratory facilities appropriate for the operations performed and are based on the potential hazards imposed
by the agents used and for the laboratory function and activity. Biosafety Level 4 provides the most stringent
containment conditions, Biosafety Level 1 the least stringent.
The containment level required may be equivalent to the Risk Group classification of the agent. For example,
the RG2 dengue viruses may be cultured under the Biosafety Level (BL) 2 containment; however, when such
agents are used for animal inoculation or transmission studies, a higher containment level is recommended.
BL2 containment is recommended for activities involving all blood-contaminated clinical specimens, body
fluids, and tissues from all humans, or from HIN- or HBV-infected or inoculated laboratory animals.
For research involving plants, four biosafety levels (BL1-P through BL4-P) are described in Appendix P of the
NIH Guidelines. For research involving animals, four biosafety levels (BL1-N through BL-4N) are described in
Appendix Q of the NIH Guidelines.
4.2 Physical Containments:
The objective of physical containment is to confine organisms containing recombinant DNA molecules and
thus to reduce the potential for exposure of the lab worker, persons outside of the lab, and the environment to
organisms containing recombinant DNA molecules. Four biosafety levels (BL1~4) or four levels of physical
containment, are described.
BL1. BL1 is suitable for work involving agents with no known or minimal potential hazard to laboratory
personnel or the environment. The laboratory is not separated from the general traffic areas of the building,
and work is generally conducted on open bench tops. No special containment equipment is required. Specific
considerations including standard microbiological practices are enforced. All work surfaces and contaminated
wastes are decontaminated with disinfectants such as bleach or autoclave. Mouth pipette is prohibited.
Eating, drinking, smoking, and applying cosmetics are not permitted in the work area of the laboratory.
Persons wash their hands after they handle materials involving organisms containing recombinant DNA
molecules and before exiting the laboratory. All procedures are performed carefully to minimize the creation of
aerosols. An insect and rodent control program is in effect.
BL2. BL2 is suitable for work involving agents of moderate potential hazard to personnel or the environment.
Specific considerations are as for BL1 and in addition: The PI limits access to the laboratory. When the
8
organisms containing recombinant DNA require special provisions (e.g., vaccination), a hazard sign using the
universal biohazard symbol is posted on the access door. Lab coats are worn. When appropriate, considering
the agent handled baseline serum samples for lab personnel are collected and stored. A biosafety manual is
prepared or adopted by the PI. Class I or II biological safety cabinets are used whenever: (i) procedures with
a high potential for creating aerosols are conducted or (ii) high concentrations or large volumes of organisms
containing recombinant DNA are used.
BL3. BL3 is applicable to clinical, diagnostic, teaching, research, or production facilities in which work is
conducted with indigenous or exotic agents which may cause serious or potentially lethal disease as a result of
exposure by the inhalation route. Specific considerations are as for BL2 and in addition: Persons under 16
years of age shall not enter the lab. Lab doors are kept closed when experiments are in progress. All
activities involving organisms containing recombinant DNA are conducted in biological safety cabinets or other
physical containment devices. Molded surgical masks or respirators are worn in rooms containing
experimental animals. Vacuum lines are protected with HEPA filters and liquid disinfectant traps. Passage
through two sets of doors is the basic requirement for entry into the lab from access corridors. Access doors
to the lab are self-closing. Windows in the lab are sealed. An autoclave is preferably available within the lab.
A ducted air ventilation system that directs airflow into the lab through the entry area is provided. The exhaust
air is not recirculated to any other area of the building.
BL4. Specific considerations are as for BL3 and in addition: Only persons whose presence is required for
program purposes are allowed entry. A logbook signed by all personnel indicates the date and time of entry
and exit. Personnel enter and leave the facility only through clothing change and shower rooms. Personnel
shower each time they leave the facility. A system is set up for reporting lab accidents or illnesses. Biological
materials to be removed from class III cabinets in a viable or intact state are transferred to a nonbreakable,
sealed primary container and then enclosed in a nonbreakable, sealed secondary container that is removed
from the facility through a disinfectant tank, fumigation chamber, or an airlock designed for this purpose. No
non-viable materials are to be removed unless they first have been autoclaved or decontaminated. Supplies
and materials are brought in by way of double-door autoclave, fumigation chamber, or airlock. Walls, floors,
and ceilings of the facility are sealed. An individual supply and exhaust air ventilation system is provided.
5.0 Recombinant DNA Experiments Covered by the NIH Guidelines
According to the NIH Guidelines, there are six categories of experiments involving recombinant DNA, which are
described in the following (5.1~5.6):
5.1 Experiments that require Institutional Biosafety Committee (RDSC at TSU) approval, RAC (national
recombinant DNA advisory committee) review, and NIH director approval before initiation.
1.
Deliberate release into the environment of any organisms containing recombinant DNA,
except certain plants.
2.
Deliberate transfer of a drug resistance trait to microorganisms that are not known to acquire it
naturally.
3.
Deliberate transfer of certain recombinant DNA molecules into a human subject that are deemed
Major Actions by the NIH (see Appendix D of the NIH Guidelines for examples).
9
5.2 Experiments that require NIH/OBA (Office of biotechnology Activities) and RDSC approval before
initiation.
Experiments involving the cloning of toxin molecules with LD50 of less than 100 anograms per kilogram
body weight. Examples: botulinum, tetanus, and diphtheria toxins; S. dysenteriae neurotoxin.
5.3 Experiments that require RDSC and Institutional Review Board Approvals and RAC Review
before
Research Participant Enrollment.
For experiments involving the deliberate transfer of recombinant DNA, or DNA or RNA derived from
recombinant DNA, into one or more human research participants (human gene transfer), no research
participants shall be enrolled until the RAC review process has been completed.
5.4 Experiments that require RDSC approval before initiation of the experiment (generally BL2 or higher
containment required).
Prior to the initiation of an experiment in this category, the PI must submit a registration document to the
RDSC which contains the following information: (i) the source(s) of DNA; (ii) the nature of the insert DNA
sequences; (iii) the host(s) and vector(s) to be used; (iv) if an attempt will be made to obtain expression of a
foreign gene, and if so, indicate the protein that will be produced; and (v) the containment conditions that
will be implemented
according to the NIH Guidelines. The registration form shall be dated, signed by the PI, and filed with the
RDSC (see Appendix A).
1.
Experiments using human or animal pathogens (risk groups 2, 3, 4 or restricted agents)
vector systems.
as host-
a. introduction of recombinant DNA into risk group 2 agents can be carried out at BL2.
b. introduction of recombinant DNA into risk group 3 agents can be carried out at BL3.
c. introduction of recombinant DNA into risk group 4 agents can be carried out at BL4.
d. introduction of recombinant DNA into restricted agents is a case-by-case situation to be
decided after NIH review.
e. in all cases, whole animal experiments will require containment levels equivalent to the risk group.
2. Experiments in which DNA from risk group 2, 3, 4, or restricted human or animal pathogens is cloned in
nonpathogenic prokaryotic or lower eukaryotic host-vector systems.
a. cloning of DNA from risk group 2 or 3 agents can be carried out at BL2.
b. cloning of DNA from risk group 4 agents can be carried out at BL4 unless a totally and irreversibly
defective fraction of the genome was cloned (BL2).
c. cloning of DNA from restricted agents is a case-by-case situation.
d. specific lowering of containment to BL1 for particular experiments can be approved by the RDSC.
10
3. Experiments involving the use of infectious viruses or defective viruses in the presence of helper virus in
tissue culture systems.
a. risk group 2 agent work can be carried out at BL2.
b. risk group 3 agent work can be carried out at BL3.
c. risk group 4 agent work can be carried out at BL4.
d. restricted agent work is a case-by-case situation.
4. Experiments involving the generation of transgenic animals and experiments involving viable recombinant
DNA-modified microorganisms tested on whole animals (not lower than BL2 containment). Introduction of
recombinant DNA (i.e., naked DNA injections) into a non-human vertebrate or invertebrate organism (BL1),
unless the DNA represents greater than two-thirds of a eukaryotic viral genome.
5. Experiments involving whole plants.
6. Work involving more than 10 liters of culture.
5.5 Experiments that require RDSC notification prior to or at the time of initiation (BL1 containment
required).
Such experiments may be conducted at BL1 containment. A registration document shall be dated and signed by
the investigator and filed with the RDSC at the time the experiments are initiated. The
RDSC reviews and
approves all such proposals.
1. Experiments involving no more than two-thirds of any eukaryotic viral genome (except risk group 3, 4, or
restricted agents; see III-D of the NIH Guidelines) when performed in tissue culture in the absence of helper
virus.
2. Experiments involving whole plants
3. Experiments involving the generation of transgenic rodents judged to require only BL1
containment.
5.6 Experiments that are exempt from NIH review but are recommended for RDSC registration or approval
(BL1 containment suggested).
1. Those experiments involving recombinant DNA molecules that:
a. are not in organisms or viruses.
b. consist entirely of DNA segments from a single nonchromosomal or viral DNA source, though one or
more of the segments may be a synthetic equivalent.
c. consist entirely of DNA from a prokaryotic host including its indigenous plasmids or viruses when
propagated only in that host (or a closely related strain), or when transferred to another host by well
established physiological means.
11
d. consist entirely of DNA from a eukaryotic host including its mitochondria or plasmids (but excluding
viruses) when propagated only in that host (or a closely related strain of the same species).
e. consist entirely of DNA segments from different species that exchange DNA by known physiological
processes, though one or more of the segments may be a synthetic equivalent.
f.
contains less than one-half of any eukaryotic viral genome from risk groups 1 or 2, and are propagated
and maintained in cells in tissue culture. However, experiments that involve the deliberate introduction
of genes coding for the biosynthesis of molecules toxic to vertebrates or whose other aspects warrant a
section III-A or III-B (NIH Guidelines) designation are not exempt.
2. Experiments which use E. coli K-12 host-vector systems provided that the E. coli host contains no
conjugation-proficient plasmids or generalized transducing phages, and that lambdoid or Ff phages or nonconjugative plasmids are used as vectors.
3. Experiments involving S. cerevisiae or S. uvarum host-vector systems.
4. Experiments involving any asporogenic B. subtilis or asporogenic B. licheniformis host-vector system.
5. Experiments involving recombinant DNA molecules derived entirely from extrachromosomal elements and
maintained in the natural host from a number of Bacillus, Listeria, Pediococcus,
Staphylococcus, and
Streptococcus species (see NIH Guidelines for a specific listing).
6. The purchase or transfer of transgenic rodents for experiments that require BL1 containment.
6.0 Additional Guidelines for Protocols of the Transfer of Recombinant
DNA Molecules into Human Participants
In addition to submitting a review/approval form to the RDSC, researchers proposing experiments involving the
transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA, into human research
participants, must submit information addressing an additional set of points. Please contact the RSDC to
request specific guidelines in this category.
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THE UNIFORM BIOLOGICAL MATERIAL TRANSFER AGREEMENT
I.
DEFINITIONS:
A.
PROVIDER: Organization providing the ORIGINAL MATERIAL. The name and address of this
party will be specified in an implementing letter.
B.
PROVIDER SCIENTIST:
implementing letter.
C.
RECIPIENT: Organization receiving the ORIGINAL MATERIAL. The name and address of this
party will be specified in an implementing letter.
D.
RECIPIENT SCIENTIST:
implementing letter.
E.
ORIGINAL MATERIAL: The description of the material being transferred will be specified in an
implementing letter.
F.
MATERIAL: ORIGINAL MATERIAL, PROGENY, and UNMODIFIED DERIVATIVES. The
MATERIAL shall not include: (a) MODIFICATIONS or (b) other substances created by the
RECIPIENT through the use of the MATERIAL which are not MODIFICATIONS, PROGENY, or
UNMODIFIED DERIVATIVES.
G.
PROGENY: Unmodified descendant from the MATERIAL, such as virus from virus, cell from
cell, or organism from organism.
H.
UNMODIFIED DERIVATIVES: Substances created by the RECIPIENT which constitute an
unmodified functional sub-unit or product expressed by the ORIGINAL MATERIAL. Some
examples include: subclones of unmodified cell lines, purified or fractionated subsets of the
ORIGINAL MATERIAL, proteins expressed by DNA/RNA supplied by the PROVIDER, or
monoclonal antibodies secreted by a hybridoma cell line.
I.
MODIFICATIONS:
MATERIAL.
J.
COMMERCIAL PURPOSES: The sale, lease, license, or other transfer of the MATERIAL or
MODIFICATIONS to a for-profit organization. COMMERCIAL PURPOSES shall also include
uses of the MATERIAL or MODIFICATIONS by any organization, including RECIPIENT, to
perform contract research, to screen compound libraries, to produce or manufacture products
for general sale, or to conduct research activities that result in any sale, lease, license, or
transfer of the MATERIAL or MODIFICATIONS to a for-profit organization. However,
industrially sponsored academic research shall not be considered a use of the MATERIAL or
MODIFICATIONS for COMMERCIAL PURPOSES per se, unless any of the above conditions of
this definition are met.
K.
NONPROFIT ORGANIZATION(S): A university or other institution of higher education or an
organization of the type described in section 501(c) (3) of the Internal Revenue Code of 1954
(26 U.S.C. 501(c)) and exempt from taxation under section 501(a) of the Internal Revenue Code
The name and address of this party will be specified in an
The name and address of this party will be specified in an
Substances created by the RECIPIENT which contain/incorporate the
13
(26 U.S.C. 501(a)) or any nonprofit scientific or educational organization qualified under a state
nonprofit organization statute. As used herein, the term also includes government agencies.
II.
TERMS AND CONDITIONS OF THIS AGREEMENT
A.
The PROVIDER retains ownership of the MATERIAL, including any MATERIAL contained or
incorporated in MODIFICATIONS.
B.
The RECIPIENT retains ownership of:
1.
MODIFICATIONS (except that, the PROVIDER retains ownership rights to the
MATERIAL included therein), and
2.
those substances created through the use of the MATERIAL or MODIFICATIONS, but
which are not PROGENY, UNMODIFIED DERIVATIVES or MODIFICATIONS (i.e., do
not contain the ORIGINAL MATERIAL, PROGENY, and UNMODIFIED
DERIVATIVES).
If either 1or 2 results from the collaborative efforts of the PROVIDER and the RECIPIENT, joint
ownership may be negotiated.
C.
D.
The RECIPIENT and the RECIPIENT SCIENTIST agree that the MATERIAL:
1.
is to be used solely for teaching and academic research purposes;
2.
will not be used in human subjects, in clinical trials, or for diagnostic purposes involving
human subjects without the written consent of the PROVIDER;
3.
is to be used only at the RECIPIENT organization and only in the RECIPIENT
SCIENTIST's laboratory under the direction of the RECIPIENT SCIENTIST or others
working under his/her direct supervision; and
4.
will not be transferred to anyone else within the RECIPIENT organization without the
prior written consent of the PROVIDER.
The RECIPIENT and the RECIPIENT SCIENTIST agree to refer to the PROVIDER any request
for the MATERIAL from anyone other than those persons working under the RECIPIENT
SCIENTIST's direct supervision. To the extent supplies are available, the PROVIDER or the
PROVIDER SCIENTIST agrees to make the MATERIAL available, under a separate
implementing letter to this Agreement or other agreement having terms consistent with the terms
of this Agreement, to other scientists (at least those at NONPROFIT ORGANIZATION(S)) who
wish to replicate the RECIPIENT SCIENTIST's research; provided that such other scientists
reimburse the PROVIDER for any costs relating to the preparation and distribution of the
MATERIAL.
1.
The RECIPIENT and/or the RECIPIENT SCIENTIST shall have the right, without
restriction, to distribute substances created by the RECIPIENT through the use of the
ORIGINAL MATERIAL only if those substances are not PROGENY, UNMODIFIED
DERIVATIVES, or MODIFICATIONS.
14
2.
Under a separate implementing letter to this Agreement (or an agreement at least as
protective of the PROVIDER's rights), the RECIPIENT may distribute MODIFICATIONS
to NONPROFIT ORGANIZATION(S) for research and teaching purposes only.
3.
Without written consent from the PROVIDER, the RECIPIENT and/or the RECIPIENT
SCIENTIST may NOT provide MODIFICATIONS for COMMERCIAL PURPOSES. It is
recognized by the RECIPIENT that such COMMERCIAL PURPOSES may require a
commercial license from the PROVIDER and the PROVIDER has no obligation to grant
a commercial license to its ownership interest in the MATERIAL incorporated in the
MODIFICATIONS. Nothing in this paragraph, however, shall prevent the RECIPIENT
from granting commercial licenses under the RECIPIENT's intellectual property rights
claiming such MODIFICATIONS, or methods of their manufacture or their use.
E.
The RECIPIENT acknowledges that the MATERIAL is or may be the subject of a patent
application. Except as provided in this Agreement, no express or implied licenses or other rights
are provided to the RECIPIENT under any patents, patent applications, trade secrets or other
proprietary rights of the PROVIDER, including any altered forms of the MATERIAL made by the
PROVIDER. In particular, no express or implied licenses or other rights are provided to use the
MATERIAL, MODIFICATIONS, or any related patents of the PROVIDER for COMMERCIAL
PURPOSES.
F.
If the RECIPIENT desires to use or license the MATERIAL or MODIFICATIONS for
COMMERCIAL PURPOSES, the RECIPIENT agrees, in advance of such use, to negotiate in
good faith with the PROVIDER to establish the terms of a commercial license. It is understood
by the RECIPIENT that the PROVIDER shall have no obligation to grant such a license to the
RECIPIENT, and may grant exclusive or non-exclusive commercial licenses to others, or sell or
assign all or part of the rights in the MATERIAL to any third party(ies), subject to any preexisting rights held by others and obligations to the Federal Government.
G.
The RECIPIENT is free to file patent application(s) claiming inventions made by the RECIPIENT
through the use of the MATERIAL but agrees to notify the PROVIDER upon filing a patent
application claiming MODIFICATIONS or method(s) of manufacture or use(s) of the MATERIAL.
H.
Any MATERIAL delivered pursuant to the Agreement is understood to be experimental in nature
and may have hazardous properties. The PROVIDER MAKES NO REPRESENTATIONS AND
EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESSED OR IMPLIED. THERE
ARE NO EXPRESS OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR
A PARTICULAR PURPOSE, OR THAT THE USE OF THE MATERIAL WILL NOT INFRINGE
ANY PATENT, COPYRIGHT, TRADEMARK, OR OTHER PROPRIETARY RIGHTS.
I.
Except to the extent prohibited by law, the RECIPIENT assumes all liability for damages which
may arise from its use, storage or disposal of the MATERIAL. The PROVIDER will not be liable
to the RECIPIENT for any loss, claim or demand made by the RECIPIENT, or made against the
RECIPIENT by any other party, due to or arising from the use of the MATERIAL by the
RECIPIENT, except to the extent permitted by law when caused by the gross negligence or
willful misconduct of the PROVIDER.
J.
This agreement shall not be interpreted to prevent or delay publication of research findings
resulting from the use of the MATERIAL or the MODIFICATIONS. The RECIPIENT SCIENTIST
15
agrees to provide appropriate acknowledgement of the source of the MATERIAL in all
publication.
K.
The RECIPIENT agrees to use the MATERIAL in compliance with all applicable statutes and
regulations, including Public Health Service and National Institutes of Health regulations and
guidelines such as, for example, those relating to research involving the use of animals or
recombinant DNA.
L.
This Agreement will terminate on the earliest of the following dates:
1.
when the MATERIAL becomes generally available from third parties, for example,
through reagent catalogs or public depositories, or
2.
on completion of the RECIPIENT's current research with the MATERIAL, or
3.
on thirty (30) days written notice by either party to the other, or
4.
on the date specified in an implementing letter, provided that:
a.
if termination should occur under L.1 the RECIPIENT shall be bound to the
PROVIDER by the least restrictive terms applicable to the MATERIAL obtained
from the then-available sources; and
b.
if termination should occur under L.2. or 4above, the RECIPIENT will
discontinue its use of the MATERIAL and will, upon direction of the
PROVIDER, return or destroy any remaining MATERIAL. The RECIPIENT, at
its discretion, will also either destroy the MODIFICATIONS or remain bound by
the terms of this agreement as they apply to MODIFICATIONS; and
c.
in the event the PROVIDER terminates this Agreement under L.3. other than for
breach of this Agreement or for cause such as an imminent health risk or patent
infringement, the PROVIDER will defer the effective date of termination for a
period of up to one year, upon request from the RECIPIENT, to permit
completion of research in progress. Upon the effective date of termination, or if
requested, the deferred effective date of termination, RECIPIENT will
discontinue its use of the MATERIAL and will, upon direction of the
PROVIDER, return or destroy any remaining MATERIAL. The RECIPIENT, at
its discretion, will also either destroy the MODIFICATIONS or remain bound by
the terms of this agreement as they apply to MODIFICATIONS.
M.
Paragraphs E, H and I shall survive termination.
N.
The MATERIAL is provided at no cost, or with an optional transmittal fee solely to reimburse the
PROVIDER for its preparation and distribution costs. If a fee is requested by the PROVIDER,
the amount will be indicated in an implementing letter.
16
UBMTA IMPLEMENTING LETTER
The purpose of this letter is to provide a record of the biological material transfer, to memorialize the agreement between the PROVIDER
SCIENTIST (identified below) and the RECIPIENT SCIENTIST (identified below) to abide by all terms and conditions of the Uniform
Biological Material Transfer Agreement ("UBMTA") published in the Federal Register on March 8, 1995, and to certify that the RECIPIENT
(identified below) organization has accepted and signed an unmodified copy of the UBMTA. The RECIPIENT organization's Authorized
Official also will sign this letter if the RECIPIENT SCIENTIST is not authorized to certify on behalf of the RECIPIENT organization. The
RECIPIENT SCIENTIST (and the Authorized Official of RECIPIENT, if necessary) should sign both copies of this letter and return one signed
copy to the PROVIDER. The PROVIDER SCIENTIST will forward the material to the RECIPIENT SCIENTIST upon receipt of the signed
copy from the RECIPIENT organization. The Implementing Letter is effective when signed by all parties. The parties executing this
Implementing Letter certify that their respective organizations have accepted and signed an unmodified copy of the UBMTA, and further
agree to be bound by its terms, for the transfer specified above. Please fill in all of the blank lines below:
1. ORIGINAL MATERIAL (Enter description):
Wild-type and mutant p-21 in pGEX-4T-3
2. Optional Termination Date: ________________________________________________
________________
_______
3. Optional Transmittal Fee (to reimburse the PROVIDER for preparation and distribution costs) Amount: $ _________________________
4. PROVIDER (Organization providing the ORIGINAL MATERIAL)
NAME OF ORGANIZATION:
STREET ADDRESS :
NAME
SIGNATURE:
CITY
TITLE:
STATE
ZIP CODE
DATE:
5. PROVIDER SCIENTIST
NAME
STREET ADDRESS
SIGNATURE:
TITLE:
CITY
STATE
DATE:
ZIP CODE
STATE
DATE:
ZIP CODE
6. RECIPIENT SCIENTIST
NAME
STREET ADDRESS
SIGNATURE:
TITLE:
CITY
7. RECIPIENT ORGANIZATION CERTIFICATION (Organization receiving the ORIGINAL MATERIAL) I hereby certify that the RECIPIENT organization has accepted
and signed an unmodified copy of the UBMTA (may be the RECIPIENT SCIENTIST if authorized by the RECIPIENT organization).
NAME OF ORGANIZATION:
STREET ADDRESS
NAME
SIGNATURE:
CITY
TITLE:
STATE
DATE:
ZIP CODE