[Federal Register Volume 70, Number 108 (Tuesday, June 7, 2005)]
[Notices]
[Pages 33183-33185]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-11221]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

Farnesyltransferase Inhibitors for Treatment of Laminopathies, Cellular 
Aging and Atherosclerosis

    Francis Collins (NHGRI) et al.
    U.S. Provisional Application No. 60/648,307 filed 28 Jan 2005 (DHHS 
Reference No. E-055-2005/0-US-01).
    Licensing Contact: Fatima Sayyid; 301/435-4521; 
[email protected].
    Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare 
progressive childhood disorder characterized by premature aging 
(progeria). Recently, the gene responsible for HGPS was identified 
(Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, et al. 
Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford 
progeria syndrome. Nature 2003; 423(6937): 293-8), and HGPS joined a 
group of syndromes--the laminopathies--all of which are caused by 
various mutations in the lamin A/C gene (LMNA). Lamin A is one of the 
family of proteins that is modified post-translationally by the 
addition of a farnesyl group. In progeria, the abnormal protein 
(progerin) can still be farnesylated, however, a subsequent cleavage is 
blocked.
    The present invention describes a possible treatment of 
laminopathies, cellular aging and aging-related conditions such as HGPS 
through the use of farnesyltransferase inhibitors (FTIs) and other 
related compounds. This treatment should lead to a decrease in the 
accumulation of abnormal proteins such as progerin in case of HGPS 
patients and therefore reduce or eliminate many of the devastating 
clinical symptoms of the underlying biological defect of nuclear 
membrane instability (Goldman R, Shumaker DK, Erdos MR, Eriksson M, 
Goldman AE, Gordon LB, Gruenbaum Y, Khuon S, Mendez M, Varga R, Collins 
FS. Accumulation of mutant lamin A causes progressive changes in 
nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl 
Acad Sci U S A 2004; 8963-8968.).
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Cell Culture System for Efficient Expression of Self-Replicating 
Norwalk Virus

    Kyeong-Ok Chang, Stanislav Sosnovtsev, Gael M. Belliot, Kim Y. 
Green (NIAID).
    U.S. Provisional Application filed 08 Apr 2005 (DHHS Reference No. 
E-043-2005/0-US-01).
    Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].
    Available for licensing and commercial development is a cell 
culture system for the efficient expression of self-replicating Norwalk 
virus (NV) RNA (NV replicons). This invention provides compositions and 
methods for preparing a cell-based system for molecular studies of NV 
replication and the development of antiviral drugs. A method related to 
effectively clearing NV replicons, by subjecting cells infected with NV 
replicon to IFN-alpha is included that demonstrates the applicability 
of this invention to drug development. A method of effectively clearing 
NV replicons, by subjecting cells expressing the NV replicon to 
nucleotide analogues is also provided. These methods provide molecular 
tools for the identification and development of treatments for NV and 
may also extend to other members

[[Page 33184]]

of the Calicivirus(es) (e.g., Norovirus, Sapovirus, Lagovirus and 
Vesivirus).

Therapeutic Delivery of Nitric Oxide From Novel Diazeniumdiolated 
Derivatives of Acrylonitrile-based Polymers

    Joseph Hrabie, Michael Citro, Frank DeRosa, and Larry Keefer (NCI).
    U.S. Provisional Application No. 60/613,257 filed 27 Sep 2004 (DHHS 
Reference No. E-188-2004/0-US-01).
    Licensing Contact: Norbert Pontzer; 301/435-5502; 
[email protected].
    Nucleophile/nitric oxide adduct ions (materials containing the X-
N2O2-functional group; known as diazeniumdiolates 
or NONOates) spontaneously dissociate at physiological pH to release 
nitric oxide (NO) with reproducible half-lives ranging from 2 seconds 
to 20 hours. The bulk of the known and patented NIH compositions and 
methods using diazeniumdiolates are derived from amine nucleophiles 
(i.e., where X-is R1R2N-). These inventors more 
recently developed simple and efficient chemical methods to produce 
diazeniumdiolates by bonding the N2O2-functional 
group directly to carbon atoms. Using these methods, the NIH inventors 
have now produced and tested polymers in which the NO releasing group 
is attached directly to the carbon backbone of polyacrylonitrile 
containing polymers.
    Available for licensing are compounds, compositions, medical 
devices, and methods of treatment using acrylonitrile-based polymers 
that release NO for a week or longer. Polyacrylonitrile itself, co-
polymers, admixtures, and products such as cloth and hollow fiber 
hemofilters have been treated and shown to release NO over time. These 
polyacrylonitrile-based products could be useful in conjunction with 
medical devices where the many therapeutic actions of NO would be 
beneficial. Treatments using stents,
extracorporeal blood tubing, shunts, wound dressings and many other 
devices could be greatly improved by NO actions including but not 
limited to prevention of clotting, promotion of tissue vascularization, 
and reduction of excessive tissue proliferation.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

A New Antiviral Pathway that is Responsible for Viral Clearance: 
Modulation of ADAR1 Activities Enhance Antiviral Therapies and Virus 
Infection of Tissue Culture Systems

    Deborah R. Taylor et al. (FDA).
    U.S. Provisional Application No. 60/605,238 filed 27 Aug 2004 (DHHS 
Reference No. E-121-2004/0-US-01).
    Licensing Contact: Robert M. Joynes; 301/594-6565; 
[email protected].
    This technology relates to the finding that the antiviral activity 
of interferon (IFN) is mediated by the activation of an enzyme RNA 
adenosine deaminase (ADAR1). This enzyme acts by deaminating adenosine 
residues in dsRNA molecules of the virus into inosine residues. This, 
in turn, may lead to mutations, genomic instability and ultimately to 
complete degradation and elimination of the virus. The subject patent 
application focuses on Hepatitis C virus (HCV), but may be broadly 
applied to the other viruses.
    Based on the above-described finding, the technology offers two 
important utilities in the medical field:
    1. Antiviral therapeutics: Because ADAR is so potent as an 
inhibitor of the growth of HCV, an agonist of this pathway or 
specifically of ADAR should enhance the clearance of the virus from the 
cells. Methods to identify such ADAR agonists are described in the 
subject patent applications.
    2. HCV cell line for drug and vaccine research: The finding 
described in the subject patent application may lead to an efficient 
cell line for growing HCV. Currently, there is not a good system to 
grow this virus. The addition of ADAR inhibitors (such as RNAi or 
chemicals that target the catalytic domain of ADAR) to the system will 
result in a system that can efficiently grow the virus. Such a cell 
line is important for vaccine development against HCV as well as the 
development of anti-viral therapeutics.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Compositions Comprising T Cell Receptors and Methods of Use Thereof

    Richard Morgan (NCI) and Steven Rosenberg (NCI).
    PCT Application No. PCT/US2004/029608 filed 13 Sep 2004 (DHHS 
Reference No. E-106-2004/0-PCT-01).
    Licensing Contact: Michelle A. Booden; 301/451-7337; 
[email protected].
    Historically, adoptive immunotherapy has shown promise in treating 
cancer. Traditionally, these adoptive techniques developed to date have 
relied on isolating and expanding T-cells reactive to a specific tumor 
associated antigen. However, the approach has been limited by number of 
isolatable T cells specific to a tumor-associated antigen in a cancer 
patient's immune system and a very time consuming procedure to isolate 
and expand the appropriate T-cells.
    This invention describes the composition and use of nucleic acid 
sequences that encode polypeptides capable of forming a T cell receptor 
(TCR) in a genetically engineered cell. Specifically, these nucleic 
acid sequences will encode TCR's specific to tumor associated antigens 
(TAA), gp100, NY-ESO-1, and MART-1. T Cells engineered with these tumor 
associated antigen specific TCRs show specific immune responses against 
TAA expressing cancer cells. This observation has a profound effect on 
the potential efficiency of new adoptive therapies targeted towards 
cancer.
    An adoptive therapy method has been developed using the TAA 
specific TCR nucleic acids to engineer isolated, non-specific T-cells. 
This method could eliminate the need to isolate and expand T-cells that 
may or may not be present in a cancer patient. Clinical trials are 
currently underway to prove the efficacy of this new adoptive therapy 
in malignant melanoma.
    Details of this invention are published in:
    1. Morgan RA, Dudley ME, Yu YY, Zheng Z, Robbins PF, Theoret MR, 
Wunderlich JR, Hughes MS, Restifo NP, Rosenberg SA. High efficiency TCR 
gene transfer into primary human lymphocytes affords avid recognition 
of melanoma tumor antigen glycoprotein 100 and does not alter the 
recognition of autologous melanoma antigens. J Immunol. 2003 Sep 
15;171(6):3287-95.
    2. Zhao Y, Zheng Z, Robbins PF, Khong HT, Rosenberg SA, Morgan RA. 
Primary human lymphocytes transduced with NY-ESO-1 antigen-specific TCR 
genes recognize and kill diverse human tumor cell lines. J Immunol. 
2005 Apr 1;174(7):4415-23.
    3. Hughes MS, Yu YY, Dudley ME, Zheng Z, Robbins PF, Li Y, 
Wunderlich J, Hawley RG, Moayeri M, Rosenberg SA, Morgan RA. Transfer 
of a TCR Gene Derived from a Patient with a Marked Antitumor Response 
Conveys Highly Active T-Cell Effector Functions. Hum Gene Ther. 2005 
Apr;16(4):457-72.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Retrovirus-Like Particles and Retroviral Vaccines

    David E. Ott (NCI).
    PCT Application filed 27 Oct 2003 (DHHS Reference No. E-236-2003/0-
PCT-01).

[[Page 33185]]

    Licensing Contact: Susan Ano; 301/435-5515; [email protected].
    This technology describes retrovirus-like particles and their 
production from retroviral constructs in which the gene encoding all 
but seven amino acids of the nucleocapsid (NC) protein was deleted. 
This deletion functionally eliminates packaging of the genomic RNA, 
thus resulting in non-infectious retrovirus-like particles. These 
particles can be used in vaccines or immunogenic compositions. Specific 
examples using HIV-1 constructs are given. Furthermore, efficient 
formation of these particles requires inhibition of the protease 
enzymatic activity, either by mutation to the protease gene in the 
construct or by protease inhibitor thereby ensuring the production of 
non-infectious retrovirus-like particles. This technology is further 
described in Ott et al., Journal of Virology, 2003, 77(5), 5547.

    Dated: May 26, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer,National Institutes of Health.
[FR Doc. 05-11221 Filed 6-6-05; 8:45 am]
BILLING CODE 4140-01-P