[Federal Register Volume 75, Number 213 (Thursday, November 4, 2010)]
[Notices]
[Pages 67985-67987]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-27912]


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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, HHS.

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.

System for Magnetic Resonance Spectroscopy of Brain Tissue for Pattern-
Based Diagnostics

    Description of Invention: Available for licensing and commercial 
development is a system for preprocessing magnetic resonance 
spectroscopy (MRS) data of brain tissue for pattern-based diagnostics. 
The MRS preprocessing system includes an MRS preprocessing module that 
executes an operation that normalizes MRS spectrum data, recalibrates 
and scales the normalized MRS spectrum data, and then renormalizes the 
scaled MRS spectrum data. The resulting preprocessed MRS data is used 
to assist in identifying abnormalities in tissues shown in MRS scans. 
Raw MRS spectrum data and scaling the raw MRS spectrum data is achieved 
by a plurality of weighting constants to generate a preprocessed MRS 
spectrum data. The method may also include providing raw MRS spectrum 
data, recalibrating the raw MRS spectrum data, and scaling the 
recalibrated MRS spectrum data by using a plurality of weighting 
constants to generate a preprocessed MRS spectrum data.

Applications

     MRI Imaging.
     Brain Imaging.
     Neurology.
    Inventors: Jon G. Wilkes (FDA/NCTR), Dan A. Buzatu (FDA/NCTR), 
Pierre Alusta (FDA/NCTR), Bruce A. Pearce (FDA/NCTR), Richard Beger 
(FDA/NCTR), Inessa Im (FDA/NCTR).
    Patent Status: U.S. Provisional Application No. 61/261,170 filed 13 
Nov 2009 (HHS Reference No. E-298-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The FDA National Center for 
Toxicological Research is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize FDA's magnetic resonance spectroscopy 
technology in various imaging and diagnostic applications. Please 
contact Alice Y. Welch, PhD at 301-796-8449 or [email protected] 
for more information.

Cancer-Linked Sequences Encoding the A2BP1/FOX1 Gene

    Description of Invention: Mesothelioma is a rare type of cancer in 
which malignant cells are found in the lining of the chest or abdomen. 
Symptoms are frequently misdiagnosed and an accurate diagnosis 
generally does not occur until advanced stages, and patients live on 
average nine to thirteen months after an accurate diagnosis. To date, 
there are no effective systemic treatments.
    Researchers at the National Cancer Institute, NIH, have identified 
a recurrent alteration in the DNA sequence for ataxin-2 binding protein 
(A2BP1/FOX1) in human mesothelioma and colorectal cancers that is 
present in at least twenty percent (20%) of cancer cell lines and 
primary tumor samples. The sequence is not present in normal tissue, 
proving that it has arisen as an acquired somatic mutation in cancer. 
Furthermore, additional data suggests a possible role for the 
alteration in neurological diseases such as autism,

[[Page 67986]]

inherited mental retardation, and seizures.
    This discovery offers a new approach for the diagnosis and early 
detection of cancer.
    Applications: Development of assays for detection, diagnosis, or 
prognosis of diseases associated with chromosomal disruptions of the 
ataxin-2 binding protein 1 (A2BP1 or FOX1) gene, such as cancer and 
neurological disorders.
    Development Status: Pre-clinical.
    Inventors: Frederic J. Kaye (NCI).
    Relevant Publication: Beroukhim R et al. The landscape of somatic 
copy-number alteration across human cancers. Nature 2010 Feb 18; 
463(7283):899-905. [PubMed: 20164920]

Patent Status

     U.S. Provisional Application No. 61/121,997 filed 12 Dec 
2008 (HHS Reference No. E-180-2008/0-US-01).
     International Patent Application No. PCT/US09/67502 filed 
10 Dec 2009, which published as WO 2010/068757 on 17 Jun 2010 (HHS 
Reference No. E-180-2008/0-PCT-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Patrick P. McCue, PhD; 301-435-5560; 
[email protected].

Insertion of Foreign Genes in Rubella Virus and Their Stable Expression 
in a Live, Attenuated Viral Vaccine

    Description of Invention: Rubella virus (RUB) is the only member of 
the Rubivirus genus of the family Togaviridae. The RUB genomic RNA is a 
single-stranded, 9762-nt, positive-sense RNA that contains two long 
open reading frames (ORFs): A 5'-proximal ORF which encodes 
nonstructural proteins (NSP) that function primarily in viral RNA 
replication, including the RdRp, and a 3'-proximal ORF which encodes 
the virion structural proteins (SP), the capsid protein (C), and two 
envelope glycoproteins, E1 and E2. The genomic RNA serves as a template 
for synthesis of a complementary minus-strand RNA which is the template 
for synthesis of both the genomic RNA and the subgenomic (SG) RNA, from 
which the structural proteins are translated.
    All earlier efforts at expressing foreign genes in rubella virus 
failed due to stability of the insert. The inventors have found a way 
to insert foreign genes into rubella virus such that the foreign genes 
can be expressed stably over many passages of the virus. More 
specifically, based on an earlier observation that rubella virus can 
tolerate a small deletion in the nonstructural genes and still 
replicate normally, the inventors' have used this deletion to make room 
for insertion of a foreign gene. Thus, the inventors have 
conceptualized and reduced to practice a new way to use the already-
approved rubella vaccine as a viral vector to express the additional 
protein antigens of a second (or multiple other) viruses. This is 
highly advantageous because it allows for production of a live virus 
vaccine when attenuation is not possible for highly virulent viruses 
such as HIV.
    Furthermore, another advantage of this vaccine is that virus titers 
in cell culture reach one thousand (1000) human doses per milliliter 
(ml) of culture supernatant. This is highly desirable for production of 
multiple millions of doses for the developing world. In the developed 
world, this vaccine could be substituted for the current vaccine at 
almost no cost and used to immunize against rubella plus the inserted 
antigen(s). Without vaccination, the average age of becoming 
seropositive for rubella is approximately nine (9) years old. This new 
vaccine could be given to one to two year olds with a booster at nine 
years old. Additionally, this vaccine is already approved, so the safe 
and immunogenic doses are already known.

Applications

     Vaccines for the prevention of rubella and other 
indications.
     Use of rubella vector for expression of foreign genes.

Advantages

     Novel vaccine candidate
     Rapid production time
    Development Status: Preclinical studies have been conducted by the 
inventors.
    Inventors: Ira Berkower and Angelo Spadaccini (FDA).

Patent Status

     U.S. Provisional Application No. 61/252,568 filed 16 Oct 
2009 (HHS Reference No. E-156-2008/0-US-01).
     International Patent Application No. PCT/US2010/052948 
filed 15 Oct 2010 (HHS Reference No. E-156-2008/0-PCT-02).
    Relevant Publication: Spadaccini A, Vimik K, Ni Y, Prutzman K, 
Berkower I. Stable expression of a foreign protein by a replication-
competent rubella viral vector. Vaccine. 2010 Feb 3;28(5):1181-1187. 
[PubMed: 19945412].
    Licensing Status: Available for licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].

Inhibition of Cell Motility, Angiogenesis and Metastasis

    Description of Invention: The present invention relates to potent, 
highly selective antagonists of Grb2 Src homology-2 (SH2) domain 
binding. Grb2, through its SH2 domain, mediates growth factor driven 
cell motility in vitro and angiogenesis in vivo. These synthetic, small 
molecule antagonists have been shown to block cell motility stimulated 
by hepatocyte growth factor (HGF), fibroblast growth factor (FGF), 
epidermal growth factor (EGF), and vascular endothelial cell growth 
factor (VEGF). They also potently inhibit HGF- and VEGF-stimulated 
morphogenesis and angiogenesis, respectively, in several model systems. 
HGF stimulates mitogenesis, motogenesis and morphogenesis in a wide 
range of cellular targets during development and adulthood, and its 
signaling pathway is frequently over-activated in human cancers, 
including colon, gastric, breast, lung, thyroid and renal carcinomas, 
melanoma, several sarcomas as well as glioblastoma. The ability of HGF 
to initiate a program of cell dissociation and increased cell motility 
coupled with increased protease production promotes aggressive cellular 
invasion and is frequently linked to tumor metastasis.
    Metastasis, the primary cause of death in most forms of cancer, is 
a multistep process whereby cells from the primary tumor spread 
systemically and colonize distant new sites. Blocking critical steps in 
this process could potentially inhibit tumor metastasis and 
dramatically improve cancer survival rates. The small, synthetic Grb2 
SH2 domain antagonists described in this invention have been shown to 
inhibit the induced and spontaneous metastasis of melanoma- and 
prostate cancer-derived tumor cells in mice. These results establish a 
critical role for Grb2 SH2 domain-mediated interactions in the 
metastatic process and support the potential efficacy of this class of 
compound in reducing the metastatic spread of primary solid tumors in 
humans.
    Applications and Modality: Inhibition of cell motility-dependent 
processes, including angiogenesis and metastasis, in several types of 
cancer such as prostate, colon, gastric, breast, lung, thyroid and 
renal carcinomas, melanoma and various sarcomas.
    Development Status: In vivo and in vitro studies have been 
conducted on this technology.

Market

     Cancer is the second leading cause of death in the U.S.

[[Page 67987]]

     The worldwide incidence of new cancer patients is forecast 
to increase from 4.2 million cases in the major cancer markets in 2005 
to 4.6 million in 2010.
     It is estimated that the worldwide cancer marker will be 
worth 85.3 billion in 2010.
    Inventors: Donald P. Bottaro et al. (NCI).

Relevant Publications

1. Atabey N, Gao Y, Yao Z-J, Breckenridge D, Soon L, Soriano JV, Burke 
TR Jr, Bottaro DP. Potent blockade of Hepatocyte Growth Factor-
stimulated cell motility, matrix invasion and branching morphogenesis 
by antagonists of Grb2 Src homology 2 domain interactions. J Biol Chem. 
2001 Apr 27;276(17):14308-14314. [PubMed: 11278639].
2. Shi Z-D, Wei C-Q, Wang X, Lee K, Liu H, Zhang M, Vasselli J, Bottaro 
DP, Linehan WM, Yang D, Burke TR Jr. Macrocyclization in the design of 
tetra-tetrapeptide mimetics that display potent inhibition of Grb2 SH2 
domain binding in whole cell systems. In: Peptide Revolution: Genomics, 
Proteomics Therapeutics. Chorev, M and Sawyer, TK, Eds. American 
Peptide Society, pp 515-517, 2003.
3. Soriano JV, Lui N, Gao Y, Yao Z-J, Ishibashi T, Underhill C, Burke 
TR Jr, Bottaro DP. Inhibition of angiogenesis by growth factor receptor 
bound protein 2-Src homology 2 domain bound antagonists. Mol Cancer 
Ther. 2004 Oct;3(10):1289-1299. [PubMed: 15486196].
4. Shi Z-D, Karki RG, Worthy KM, Bindu LK, Dharmawardana PG, Nicklaus 
MC, Bottaro DP, Fisher RJ, Burke TR Jr. Utilization of a 
nitrobenzoxadiazole (NBD) fluorophore in the design of a Grb2 SH2 
domain-binding peptide mimetic. Bioorg Med Chem Lett. 2005 Mar 
1;15(5):1385-1388. [PubMed: 15713392].
5. Kang S-U, Shi, Z-D, Worthy KM, Bindu LK, Dharmawardana PG, Choyke 
SJ, Bottaro DP, Fisher RJ, Burke TR Jr. Examination of phosphoryl-
mimicking functionalities within a macrocyclic Grb2 SH2 domain-binding 
platform. J Med Chem. 2005 Jun 16;48(12):3945-3948. [PubMed: 15943469].
6. Shi Z-D, Peruzzi B, Dharmawardana PG, Leech T, Appella E, Worthy KM, 
Bindu LK, Fisher RJ, Bottaro DP, Burke TR Jr. Synthesis and use of C-
terminally biotinylated peptidomimetics with high Grb2 SH2 domain-
binding affinity. In: Understanding Biology Using Peptides, Blondelle 
SE (Ed), American Peptide Society, pp 208-209, 2005.
7. Dharmawardana PG, Peruzzi B, Giubellino A, Burke TR Jr, Bottaro DP. 
Molecular targeting of growth factor receptor-bound 2 (Grb-2) as an 
anti-cancer strategy. Anti-Cancer Drugs 2006 Jan;17(1):13-20. [PubMed: 
16317285].
8. Liu F, Worthy KM, Bindu L, Giubellino A, Bottaro DP, Fisher RJ, 
Burke TR Jr. Utilization of achiral alkenyl amines for the preparation 
of high affinity Grb2 SH2 domain-binding macrocycles by ring-closing 
metathesis. Org Biomol Chem. 2007 Jan 21;5(2):367-372. [PubMed: 
17205182].
9. Giubellino A, Gao Y, Lee S, Lee M-J, Vasselli JR, Medepalli S, 
Trepel JB, Burke TR Jr, Bottaro DP. Inhibition of tumor metastasis by a 
growth factor receptor bound protein Src domain-binding antagonist. 
Cancer Res. (Priority Report) 2007 Jul 1;67(13):6012-6016. [PubMed: 
17616655].

    Patent Status: U.S. Patent Application No. 11/525,672 filed 22 Sep 
2006 (HHS Reference No. E-265-1999/2-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].
    Collaborative Research Opportunity: The Urologic Oncology Branch of 
the National Cancer Institute is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize Grb2 SH2 domain antagonists as 
anti-cancer drugs. Please contact John D. Hewes, Ph.D. at 301-435-3121 
or [email protected] for more information.

    Dated: October 29, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-27912 Filed 11-3-10; 8:45 am]
BILLING CODE 4140-01-P