[Ip-health] NIH Statement on Sharing and Distributing Mouse Resources

Jamie Love james.love at keionline.org
Thu Aug 23 14:26:36 PDT 2012


This FAQ describes NIH policy on the sharing of intellectual property
and materials from "mouse resources" created with NIH funds.  It is
good illustration of how NIH policy can be shaped to protect access to
knowledge, and a template for how the NIH could expand such policies
into both upstream and downstream areas of R&D, not only for research
involving mice as research inputs, but for all sorts of research
grants.   Jamie

http://www.nih.gov/science/models/mouse/sharing/5.html

	
V. Frequently Asked Questions (FAQs) and Answers

Definition and Policy

Q1: What is the definition of the term "mouse resources"?

A1: The term "mouse resources" includes genetically modified mice,
inbred mouse strains, mutagenesis protocols, as well as DNA vectors
and murine embryonic stem cells used in the production of knockout
mice. Genetically modified mice are mice in which mutations have been
induced by chemicals, irradiation, and transgenesis (e.g.., knockouts
and injection of DNA into blastocysts), in addition to mice that have
had spontaneously occurring mutations.


Q2: What is NIH policy regarding the distribution and sharing of
mutant mouse strains created with NIH funds?

A2: The NIH expects mouse resources generated with the aid of NIH
funding to be timely distributed and shared with the scientific
community. Investigators submitting an NIH application must include a
concise plan addressing the timely distribution of mouse resources,
unless the proposed research will not generate such resources.


Q3: To whom does this policy apply?

A3: This statement applies to extramural investigators funded by NIH
extramural grants, cooperative agreements, and contracts, including
SBIR and STTR grants. This statement also applies to NIH intramural
investigators supported by NIH intramural funds.


Q4: Is this a new policy?

A4: This statement is an extension of NIH Grants Policy, [NIH Grants
Policy Statement (http://grants.nih.gov/grants/policy/nihgps_2001/)
and Principles and Guidelines for Recipients of NIH Research Grants
and Contracts on Obtaining and Disseminating Biomedical Research
Resources: Final Notice, December 1999
(http://ott.od.nih.gov/NewPages/RTguide_final.html)].


Impact of Sharing of Mouse Resources on Research Practices

Q5: My colleagues and I spent considerable time, energy, and resources
on generating and characterizing the mouse resources we created. We
want to maximize the fruits of our labor. Can we delay sharing until
publication so other experiments can be performed and manuscripts
prepared?

A5: NIH recognizes that the investigators who generated the mouse
resources have a legitimate interest in benefiting from their
investment of time and effort. However, unnecessary delay of
publication and prolonged exclusive use of the mice are not in the
best interests of the research community or the public health.
Therefore, not sharing mice for a prolonged period will generally not
be considered an acceptable plan. Furthermore, it may not be in your
best interest as an investigator. If your publication is delayed,
other investigators may publish papers first and receive credit for
the same mutant mouse that you and your colleague have generated and
have been characterizing. You may wish to maximize your productivity
and the impact of your work by engaging in collaborations before and
after publication describing the mutant mouse. By publishing in a
timely manner, you and your colleagues will likely be able to publish
your work in a high-impact journal, which will benefit the research
community, as well as your career and the careers of your colleagues.


Q6: Can I require investigators using my mouse resources to add my
name to the papers they publish?

A6: No. You may only require them to do so if you are involved in
collaboration with them and contribute intellectually to the paper.
This type of stipulation hinders open scientific inquiry and generates
potential conflicts of interest. Investigators using the mutant mouse
may find results that directly contradict your results. However, it is
appropriate for you to be acknowledged as the source of research
resources upon which the manuscript is based.


Q7: Is there a requirement for citation or acknowledgement of the
investigators who generated the mouse resources in papers based on
research that used the mouse?

A7: It is appropriate to acknowledge the source of the mutant mouse
upon which the manuscript is based. This follows best practices for
scientific publication. Journals usually have an acknowledgement
section. Before submitting a paper, you should read and consult the
editorial policies of the journal.


Q8: If I made a knockout mouse or a transgenic mouse, can I distribute
only the DNA vectors?

A8: Sharing the mice, sperm, and/or embryos may be the most efficient
and effective means of meeting the best interests of the scientific
community and of furthering research. Providing vectors used in the
generation of transgenic or knockout mice may be an efficient and
effective distribution alternative for furthering research in some
cases. This situation would be acceptable, if you can show that the
person requesting the mutant mouse can: 1) make the mouse from the
reagents given; 2) make the same allele as the mouse you made; 3) make
the mouse at a cost that is equal to or less than the cost to breed
and ship the mice or breed the mice from cryopreserved sperm or
embryos; and 4) generate the number of mice equal to or greater than
the number of mice that could be generated from cyropreserved sperm or
embryos in the same period of time. In any event, NIH expects you to
make the mice available to the scientific community as well as
reagents such as vectors and cell lines used to generate the mutant
mouse strains.


Q9: Can I patent my mouse resources to protect my intellectual
property rights and the property rights of my institution?

A9: Yes. You and your institution may choose to retain title to
subject inventions such as a mutant mouse developed under federal
funding under the provision of the Bayh-Dole Act and incur all the
costs and expenses of filing patents on this technology. However, such
a research resource must still be made reasonably available and
accessible to the research community in accordance with the NIH Grants
Policy Statement (http://grants.nih.gov/grants/policy/nihgps_2001/),
including the NIH Research Tools Policy
(http://ott.od.nih.gov/NewPages/RTguide_final.html). If a
Determination of Exceptional Circumstances (DEC) is announced before a
grant or contract is awarded, you may not patent a technology covered
under the approved DEC.


Q10: Could patenting of mice interfere with the distribution of mutant
mice to the scientific community?

A10: Patenting of mice could possibly interfere with the distribution
of mutant mice to the scientific community if such patents are
enforced inappropriately. However, the NIH Research Tools Policy
provides guidance on the appropriate implementation and use of
intellectual property. This policy also provides for reasonable
availability and accessibility of such resources to effectively
further the research enterprise
(http://ott.od.nih.gov/NewPages/RTguide_final.html).


Q11: What types of agreements are acceptable under NIH policy?

A11: Most transfers to not-for-profit entities should be implemented
under terms no more restrictive than the Uniform Biological Materials
Transfer Agreement (UBMTA) (http://ott.od.nih.gov/newpages/UBMTA.pdf).
In particular, recipients are expected to use the Simple Letter
Agreement provided at
http://ott.od.nih.gov/NewPages/RTguide_final.html, or another document
with no more restrictive terms, to readily transfer unpatented tools
developed with NIH funds to other recipients for use in NIH-funded
projects. If the materials are patented or licensed to an exclusive
provider, other arrangements may be used, but commercialization option
rights, royalty reach-through, or product reach-through rights back to
the provider are inappropriate. Similarly, when for-profit entities
are seeking access to NIH-funded tools for internal use, recipients
should ensure that the tools are transferred with the fewest
encumbrances possible. The Simple Letter Agreement may be expanded for
use in transferring tools to for-profit entities, or simple internal
use license agreements with execution or annual use fees may be
appropriate. [http://ott.od.nih.gov/NewPages/RTguide_final.html] There
may be additional issues regarding genetically modified mice.
Therefore, you should confer with your organization's technology
transfer office and sponsored research program office to transfer such
mice. Your transfer agreement may also need to address issues of
animal custody, care, and use under all applicable Federal laws,
including but not limited to the Animal Welfare Act.


Q12: If I receive funding from both the NIH and a biotechnology
company and the company's sharing policy conflicts with the NIH, which
policy should I follow?

A12: Organizations receiving funding from the NIH must have policies
and procedures in place to ensure that any agreements entered into
with third parties are consistent with the terms and conditions of
their NIH funding award, including the provision of intellectual
property rights to the NIH, and that third parties are informed of the
NIH requirements [see the NIH Grants Policy Statement for guidance
(http://grants.nih.gov/grants/policy/policy.htm)]. Therefore, to
remain in compliance with the NIH award, you will need to revise any
third-party agreements that are inconsistent with the terms and
conditions of an NIH award. For guidance, see "Developing Sponsored
Research Agreements: Considerations for Recipients of NIH Research
Grants and Contracts" (http://ott.od.nih.gov/newpages/text-com.htm)
and "Intellectual Property Reporting for NIH Grantees That Also Have
Involvement with the Veterans Administration"
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-033.html).


Q13: Can I charge money to investigators requesting mouse resources?

A13: Yes, you can charge for shipping and distributing the mouse
resource so long as the mouse resource remains reasonably available
and accessible to the research community. For additional information,
see section II of this document, under "General considerations for
submission of mutant mice to a repository." You should also confer
with your technology transfer office and/or office of sponsored
programs for guidance.


Q14: I don't want to share my mutant mice and reagents used to make
the mice. Can I be forced to do so?

A14: Sharing of research resources is a very important NIH policy. NIH
requires that you include a plan for sharing mice in your application
and the quality of that plan can affect the institute's decision to
make an award.

The Scientific Review Group (SRG) may comment on your sharing plan
during the peer review of your application. If your application is
selected for an award, NIH program staff will review and ask you to
address and resolve any concerns about the sharing plan (as well as
any other issues raised in the review). These issues must be resolved
before making any award. If your application is funded, you will be
expected to share mice according to the sharing plan consistent with
NIH policy. Failure to comply with your sharing plan may be carefully
considered in future funding decisions for you and your institution.


Q15: What can I do if I believe an investigator is refusing my request
for mutant mice?

A15: If you believe an investigator will refuse your request, you
should still make the initial request. In certain cases, you should
make your request for mice in writing. The request must contain a
brief outline of your research objectives and IACUC approval
information. If the provider refuses your request, you could ask why.

If the response letter details how the investigator is making good
faith efforts to abide by his/her approved sharing plans and provides
a reasonable explanation as to why the mice are not yet currently
available, you should try to find another source of these mice. For
example, the investigator may have deposited his mice with a
repository but the repository does not have sufficient stock to
distribute the mice yet. On the other hand, if no letter is received
or if you still do not believe the inventor of the mutant mouse strain
is acting in good faith, you should speak with your NIH program
officer. Also, you should confer with your own organization's
technology transfer office and/or office of sponsored programs for
guidance.


Q16. I am an investigator without NIH funding. What should I do if I
encounter an investigator who refuses to share NIH generated mouse
resources? I do not have a program officer to contact.

A16. Send a written request to the investigator specifying the
objectives of your research and your IACUC approval information. If
you do not receive a response or you believe the response to be
inadequate, you may wish to confer with your own technology transfer
office and/or office of sponsored programs for additional guidance.
You may also consider conferring with a member of the Extramural
Technology Transfer Policy Staff at the NIH Office of Technology
Transfer. The NIH Office of Technology Transfer is the primary NIH
office handling both extramural and intramural technology transfer
policy matters for all of NIH.

Extramural Technology Transfer Policy Staff
NIH Office of Technology Transfer (NIH-OTT)
6011 Executive Boulevard, Suite 325
Rockville, Maryland 20852
Telephone: (301) 496-7057
Fax: (301) 402-0220
Email: NIHOTT at nih.gov

Rationale for Sharing of Mouse Resources

Q17: Why should I make my mouse resources available to the scientific community?

A17: The timely distribution of mouse resources furthers research and
scientific progress without needless duplication of effort. It also
enables other investigators to extend the scope of research to
investigation beyond that envisioned by the creator of the mutant
mouse strain. These resources afford rich opportunities for new areas
of inquiry. There are more experiments to be done than can be carried
out by the laboratory of a single investigator. By making mouse
resources more widely available, students, post-docs, and
investigators learn new methods of analysis, thus improving training.
The expansion of the pool of trained investigators and the
availability of mouse resources to the scientific community may lead
to more rapid breakthroughs for diagnosis, prevention, and treatment
of disease and improvements in public health. These goals are central
to the mission of the NIH.


Q18: Is sharing and distribution of unique resources such as mouse
resources with the scientific community widely accepted as good
practice?

A18. Yes. Journals such as PNAS, Cell, Neuron, Immunity, The Journal
of Immunology, The Journal of Neuroscience, and Science require
investigators to make unique resources available so that the results
can be verified and additional research promoted. Both the Society for
Neuroscience, with a membership of 29,000 scientists, and FASEB,
consisting of 19 societies and a membership of 66,000 scientists, have
taken positions that are consonant with the NIH policy. The policy of
the Society of Neuroscience is that "unique and propagatable research
materials used in studies being reported must be made available to
qualified scientists for bona fide research purposes" (see
http://apu.sfn.org/content/AboutSfN1/Guidlines/guidelines.htm and
http://apu.sfn.org/content/AboutSfN1/Guidlines/guidelines.pdf) under
section 1.8 of "Guidelines: Responsible Conduct Regarding Scientific
Communication," Society for Neuroscience, 1998). In 1999, a letter
from David G. Kaufman, MD, PhD, FASEB President, to Barbara McGarey of
the NIH Office of Technology Transfer stated that the FASEB endorsed
the policy about sharing unique resources described in the document
"Sharing Biomedical Research Resources: Principles and Guidelines for
Recipients of NIH Research Grants and Contracts" (see
http://www.faseb.org/opar/letters/1999/McGarvey.html).


Q19: Who benefits from the sharing and distribution of mouse resources?

A19: Everyone benefits, including investigators, the scientific
community, and the public, from broader access and use of these
important scientific resources. Restricted availability of unique
research resources can impede the advancement of research and
improvement of medical care. The sharing of biomaterials, data, and
software in a timely manner has been an essential element in the rapid
progress made in the genetic analysis of mammalian genomes. Sharing
and distribution of unique resources such as mutant mice makes more
effective use of resources by avoiding duplication of effort, thereby
preserving resources and permitting investigators to focus on
scientific questions instead of resource generation. Some of these
questions and avenues of research may not have even been envisioned by
the inventor of the mutant mouse. As the creator of the mutant mouse,
your reputation will grow as the mutant mice are used in studies and
subsequently cited in publications. Finally, should there ever be a
disaster in your laboratory resulting in the destruction of your
mutant mouse strain, other laboratories could have stocks that could
be used to replenish your stock. In recent history, disasters such as
floods at Baylor University, fires at The Jackson Laboratory, and
power outages at Columbia University have occurred that have resulted
in loss of valuable research resources.


How Investigators Can Share Mouse Resources

Q20: What are the different means of sharing mouse resources?

A20: You can share under your own auspices or you can deposit and
distribute through a mouse repository.


Q21: The expectation that I provide thousands of mice to the
scientific community upon publication seems unrealistic and puts an
unnecessary burden upon my laboratory. Breeding mice isn't like
growing up a plasmid. To breed mice, I will need to hire a technician
and request more space in the mouse colony. Also, I need these mutant
mice for my own research program and just have enough to do the
experiments I proposed in my NIH research grant. How do I deal with
this problem?

A21: A solution to this problem is to provide a breeding pair to a
commercial vendor or to a national repository such as the NIH-funded
Mutant Mouse Regional Resource Centers (MMRRC) (http://www.mmrrc.org/)
that distributes mice consistent with NIH policy. (For some possible
repositories, a listing is in section IV of this document). These
repositories can breed mice and cryopreserve sperm and embryos. This
eliminates needless hassle and helps you to meet your obligations to
distribute mutant mice strains. Your breeding efforts can be focused
on your needs and those of your collaborators. Moreover, by providing
your mice to a repository, you provide insurance against any mishap.
Many investigators at Baylor were fortunate to have distributed their
mice to other investigators and repositories before the flood in 2001.
The flood destroyed their strains, but they were able to replenish
their stocks. Furthermore, fires have occurred at the Jackson
Laboratory and power failures have occurred at other institutions
resulting in loss of mouse strains.


Q22: Suppose all of the repositories refuse to accept my mutant mouse
strain. What should I do then?

A22: Repositories and vendors refuse to carry mutant mouse strains for
a variety of reasons. They may believe that there will not be
sufficient demand, that their capacity is currently being overtaxed,
or that the stock is too difficult to maintain. It is also possible
that a repository is at capacity or that they are having a problem
with disease. You may (1) request money in your budget to pay for the
cost of distributing mice, (2) request an administrative supplement,
or (3) apply for a competitive supplement to your grant. Before
submitting such a request, you should speak directly with your program
officer to determine if funds are available and/or whether an
institute supports supplement programs.


Q23: Because I anticipate relatively few requests for my mice, I'm
planning to share under my own auspices. Nevertheless, this will cost
technician time and will require special shipping equipment. How am I
supposed to cover these expenses?

A23: NIH supports the sharing of research resources, and funding for
distribution and sharing should be addressed in your initial
application. You can request resources to share in your application,
and you should include information in your plan to share in the
relevant sections, such as budget, research plan, and animal subject
section. If you have already received your award, you should talk with
your NIH program official about the availability of supplemental
funding.


Q24: I don't anticipate a very big demand for my mutant mice. I don't
have the time or resources to respond to requests. What should I do?

A24: Some repositories, such as the MMRRC (http://www.mmrrc.org/),
offer to accept strains for cryopreservation only. This maintenance
level for mouse strains that are not in a significant demand by the
scientific research community conserves research dollars for the
repositories and allows preservation of a larger number of mouse
strains.


Q25: When I share mice, am I also supposed to share associated records
about mice and tools?

A25: Yes. You are expected to share any PCR assay protocols/primers,
tissue, DNA, or related research tools necessary for PCR assay and
genotyping of the mutant mouse strain. Distribution of other research
tools related to the mutant mouse strain should also be addressed in
the sharing plan. The breeding history of the mouse strains should
also be disclosed. However, some of this information may already be
disclosed in your publication. For additional details, please see
section II under "General considerations for submission of mutant mice
to a repository."


Q26: How well does the mouse need to be characterized before distribution?

A26: The amount of information needed from the provider may vary from
investigator to investigator. Criteria for acceptance of mouse strains
and resources vary among repositories. Steering or Coordinating
Committees oversee the acceptance of mouse strains into the
repositories. Information on web sites or phone conversations with
representatives from the repositories may provide guidance. However, a
few general rules apply: 1) The mutant strain should be of sufficient
interest to the general scientific community that the strain is
requested for research applications and 2) the mutant strain should
have been described in a peer-reviewed scientific publication or at a
scientific meeting.


Q27: How do I announce availability of mice?

A27: The best way to "advertise" the availability of a mutant mouse
model is through peer-reviewed publications and national and
international meetings. Additionally, submission of a mouse strain to
one of the repositories will "advertise" the strain on that website,
which can be searched by other researchers.


Q28: How do I find out what mice are available?

A28: You can find this information from publications and electronic
databases. Also, websites of mouse repositories generally list the
available mice. Please see section IV for a partial list of such
repositories and databases.


Q29: If an investigator without a biosafety level 3 (BSL-3 or P3)
containment facility requests a mutant strain of mice to be used in an
experiment studying an infectious agent that requires a BSL-3
facility, can the creator of the mutant mouse strain refuse to provide
the mutant mouse?

A29: The creator or source of mutant mice should not release animals
into a situation where they cannot be assured that the mice are
properly contained and maintained. Your transfer agreement document(s)
should address issues of animal custody, care, and use under all
applicable Federal laws, including but not limited to, the Animal
Welfare Act. One useful reference is the NIH/ARAC Animal Transfer
Agreement, which is available at
http://oacu.od.nih.gov/ARAC/transfer.htm. Your technology transfer
office, office of sponsored research programs, and/or office of animal
care should be conferred with, as appropriate, for such transfers.


Q30: If an investigator without IACUC approval requests mutant mice
from the creator of the mutant mouse strain, can the creator deny the
request?

A30: The requestor's institution is responsible for ensuring that all
requirements for animal care and housing are satisfied. However, some
simple questions regarding animal care and the availability of a
veterinarian responsible for the mice at the requestor's institution
will clarify most issues. For guidance in formulating your information
acquisition, please visit the Jackson Laboratory's Mice Orders website
at [http://jaxmice.jax.org/orders/newcustomer.html] and click on New
Customer Application Form
(http://jaxmice.jax.org/orders/newcustomerform.pdf). Another useful
reference is the NIH/ARAC Guidelines, which is available at
http://oacu.od.nih.gov/ARAC.


Q31: What is my responsibility if the mutant strain of mice that I
made became infected with a pathogen sometime during its generation
and breeding?

A31: It is advisable that mice be bred in a specific pathogen facility
(SPF). Sick mice can alter the results of experiments. It is likely
that the enthusiasm of a study section, as well as the enthusiasm of
NIH program staff, will be greatly dampened if a proposal is submitted
that does not describe the use of a barrier facility in the derivation
and breeding of mice. Should the investigator become aware that the
mice became infected during their creation and generation, the
investigator should take steps to re-derive the animals. It is not
necessary to start from scratch. Because national repositories
routinely re-derive newly accepted mutant mouse strains, any strain
deposited in a repository will be undergoing the process of
re-derivation. Therefore, each strain's submission to a repository is
handled on a case-by-case basis.

Terms and conditions of strains submitted to a repository need to be
discussed on a case-by-case basis. For additional information, see
section II of this document under "General considerations for
submission of mutant mice to a repository."


Q32: How do I ship mice either to a repository or to a requesting investigator?

A32: In either case, you should talk to a representative of your
Laboratory Animal Care Unit at your institution and seek guidance.
These units ship and receive animals on a regular basis and will
provide you with the necessary help and information. For example, the
University of Florida maintains websites that provides useful
information about animal shipping and policies concerning animal care
(http://iacuc.ufl.edu/Guides.htm). Additionally, if you plan to submit
your mutant mouse strain to a repository, you will need to contact the
repository and work out shipping arrangements.


Q33: I am a foreign investigator who receives NIH funding. What are
the rules regarding shipping mice to the United States?

A33: Regulations may vary from state to state within the United
States. For information on importing animals into the United States,
please contact the Veterinary Services office in the destination
state. For information on exporting animals from the United States,
please contact the Veterinary Services office in the origination
state. A list of Veterinary Service offices can be found at the USDA
animal regulations library website
http://www.aphis.usda.gov/vs/area_offices.htm).

Permits can be found at
http://www.aphis.usda.gov/vs/import_export.htm. USDA permit should be
obtained if transgenic mice carrying receptors that enable them to
develop productive infections with human pathogens are imported into
the United States or transported within the United States.

You should also check with the Centers for Disease Control (CDC) for
their current guidelines regarding importation of animals to the
United States (http://www.cdc.gov/od/ohs/biosfty/imprtper.htm).

Your institution may be able to provide guidance regarding the
shipment of live animals and related research resources. You should
confer with applicable offices at your institution for appropriate
guidance.


Q34: What are the rules for exporting mice?

A34: Exports fall under the jurisdictions of the U.S. Department of
Commerce. For additional information, call (202) 501-7900 or visit
their website to obtain additional contact information
(http://www.commerce.gov).


Questions About the Mouse Sharing Plan

Q35: Do I need to address the sharing of unique resources such as the
distribution of my mouse resources in my application?

A35: Yes. You must address the sharing of mouse resources in the
sharing plan in your application. You can accomplish this in a brief
description of the plan in the vertebrate animal section, which
follows the research plan section. In addition to information required
in that section, your plan should also discuss how you will make your
mice available to the scientific community, how you will address
intellectual property issues, and how you will maintain your mice
under SPF conditions. An example of a sharing plan is included in
section III. If you are requesting funds to distribute animals or
resources, you should include this information in your budget
justification.


Q36: Should I discuss my sharing plan with my institutional technology
transfer office and business office?

A36: Yes. Issues surrounding the sharing plan and intellectual
property are complex. Plans should be developed with individuals from
your institution who have expertise in this area. These experts could
be from your sponsored research office, your technology transfer
office, your office of general counsel, and/or any other appropriate
office of your particular institution. Such consultation should help
clarify the policy of your institution regarding sharing and
distribution of research resources such as mutant mice, as well as
your institution's policy regarding intellectual property and any
inconsistent obligations with third parties.


Q37: In my sharing plan, should I describe how I plan to maintain my
mice free of pathogens and other microorganisms?

A37: It is extremely difficult to distribute mice infected with
pathogens and other microorganisms. In the methods section of your
proposal, you should describe how mice are maintained free of
pathogens and other microorganisms.


Q38: How will the adequacy of my sharing and distribution plan be evaluated?

A38: The Scientific Review Group (SRG) or study section may comment on
the adequacy of the sharing plan. These comments will not affect the
overall priority score assigned to the application. NIH program staff
will review the plan when making funding recommendations.


Q39: Will I have to document sharing of resources in the yearly
progress report for my continuing renewal?

A39. You should report the number of requests and number of requests
fulfilled when submitting your non-competing renewal progress report.
NIH Program Staff will examine this issue as one of the criteria for
continuation of funding.


Q40: What should be addressed in my research resources sharing plan?

A40: Sharing plans may vary. An example of a sharing plan which has
been found acceptable for a past RFA is in section III.




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