[Federal Register: June 7, 2005 (Volume 70, Number 108)]
[Notices]
[Page 33183-33185]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr07jn05-62]
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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;
sayyidf@mail.nih.gov.
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;
shmilovm@mail.nih.gov.
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;
pontzern@mail.nih.gov.
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;
joynesr@mail.nih.gov.
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;
boodenm@mail.nih.gov.
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; anos@mail.nih.gov.
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