[Federal Register Volume 71, Number 94 (Tuesday, May 16, 2006)]
[Notices]
[Pages 28355-28358]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-7428]


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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.

[[Page 28356]]


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.

T-Cell Receptor Recognizing Renal Cell Carcinoma

    Description of Invention: Renal cell carcinoma (RCC) is the most 
common renal tumor with approximately 30,000 cases per year in the USA. 
The survival rate for this cancer is very low, where only 10% of 
patients survive because this carcinoma is resistant to most 
chemotherapies.
    This technology describes a T-cell receptor that was cloned from a 
human immune cell. This T-cell receptor recognizes a number of human 
kidney tumors and is not limited to use in patients with specific MHC 
types. This cell was able to kill other kidney cancer cells in other 
patients, and when this T-cell was introduced into other human immune 
cells, these cells also acquired the ability to kill kidney cancer 
cells. This invention also describes novel methods using dendritic 
cells to generate both CD4+ and CD8+ RCC-reactive T-cells for use in 
antigen identification and therapeutic protocols. This is the first and 
only cloned T-cell receptor that recognizes a majority of human kidney 
tumors.
    Applications: A therapeutic for patients suffering from renal cell 
carcinoma; a novel method using dendritic cells to prime T-cell 
responses; a novel method of constructing and inserting light chain 
genes of the T-cell receptor into other patient's T-cells.
    Market: There are approximately 30,000 new estimated cases of renal 
cell carcinoma per year in the USA. The total market size in the USA in 
the range of $2 billion dollars.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Qiong J. Wang, Ken-ichi Hanada and James C. Yang (NCI).
    Publication: QJ Wang et al., ``Generating renal cancer-reactive T-
cells using dendritic cells (DCs) to present autologous tumor,'' J 
Immunother. 2005 Nov-Dec 28(6):551-559.
    Patent Status: U.S. Provisional Application No. 60/776,194 filed 24 
Feb 2006 (HHS Reference No. E-106-2006/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Michelle A. Booden, Ph.D.; 301/451-7337; 
[email protected].
    Collaborative Research Opportunity: The NCI Surgery Branch is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
T-cell receptors and their clinical use as cancer treatments. Please 
contact Dr. Steven Rosenberg at (301) 496-4164 or [email protected] for 
more information.

Preparation of a Peptide Targeted Human RNase, RGD-Eosinophil Derived 
Neurotoxin (RGD-EDN) To Specifically Target Tumor Vasculature

    Description of Technology: Cancer is the second leading cause of 
death in the United States and it is estimated that there will be 
approximately 600,000 deaths caused by cancer in 2006. A major drawback 
of the existing chemotherapies is the cytotoxic side-effects that are 
associated with them. Thus, there is a need to develop new therapeutic 
approaches with reduced side-effects.
    Anti-angiogenic therapy is a recent approach in cancer therapeutics 
targeting the formation of blood vessels that are necessary for tumor 
growth. Anti-angiogenic therapeutic agents are generally devoid of 
toxic side-effects, recently gaining attention as cancer therapeutics 
with tremendous promise. Recently, the anti-angiogenic molecule 
bevacizumab (Avastin), a monoclonal antibody against the vascular 
endothelial growth factor (VEGF), has gained approval from the FDA for 
the first-line treatment of metastatic colon cancer in combination with 
standard chemotherapy.
    This technology describes a novel anti-angiogenic method for 
treating cancer. The [alpha]v[beta]3-integrin is upregulated on tumor 
endothelial cells and can bind RGD (Arg-Gly-Asp) peptides. By tagging 
the RGD peptide with the normally non-cytotoxic eosinophil-derived 
neurotoxin (EDN), this RNase molecule can be targeted to human vascular 
endothelial cells where it becomes cytotoxic. These RGD-EDN molecules 
inhibit the adhesion of HUVEC cells in response to endothelial growth 
factors. These molecules have also been shown to inhibit tumor growth 
in mice with Kaposi's sarcoma. This technology has therapeutic 
potential for a broad spectrum of cancer related diseases alone, or in 
combination with existing therapies.
    Applications: A novel therapeutic molecule, RGD tagged EDN (RGD-
EDN); an anti-angiogenic cancer therapy for targeting RGD-EDN to 
endothelial cells via binding to the RGD receptor [alpha]v[beta]3 
integrin.
    Market: 600,000 deaths from cancer related diseases estimated in 
2006; the technology platform involving novel anti-angiogenic cancer 
therapy technology has a potential market of more than 2 billion U.S. 
dollars.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Dianne L. Newton, Zhongyu Zhu, and Susanna M. Rybak 
(NCI).
    Publications:
    1. A Dricu et al., ``A synthetic peptide derived from the human 
eosinophil-derived neurotoxin induces apoptosis in Kaposi's sarcoma 
cells,'' Anticancer Res. 2004 May-Jun; 24(3a):1427-1432.
    2. M Fani et al, ``Comparative evaluation of linear and cyclic 
99mTc-RGD peptides for targeting of integrins in tumor angiogenesis,'' 
Anticancer Res. 2006 Jan-Feb; 26(1A):431-434.
    3. DL Newton et al., ``Construction and characterization of RNase-
based targeted therapeutics,'' Methods Mol Biol. 2003; 207:283-304.
    4. A Capello et al., ``Anticancer activity of targeted proapoptotic 
peptides,'' J Nucl Med. 2006 Jan; 47(1):122-129.
    Patent Status: U.S. Provisional Application No. 60/782,968 filed 15 
Mar 2006 (HHS Reference No. E-094-2006/0-US-01).
    Licensing Status: Available for non-exclusive and exclusive 
licensing.
    Licensing Contact: David Lambertson, Ph.D.; 301/435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Biological Testing Branch, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize Peptide Targeted Human RNases. 
Please contact Bjarne Gabrielsen at (301) 846-5465 or [email protected] for 
more information.

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Adoptive Immunotherapy With Autologous Natural Killer Cells

    Description of Technology: Dr. Rosenberg and colleagues have 
clearly demonstrated that T-lymphocytes can mediate the regression of 
metastatic melanoma. However, not all patients with cancer are eligible 
for or respond to this type of immunotherapy. In some patients, the 
tumor infiltrating lymphocytes (TIL) do not expand sufficiently, or do 
not exhibit sufficient tumor specific reactivity.
    Studies in mice have shown that adoptive transfer of NK cells 
activated in vitro can significantly reduce the load of Acute 
Myelogenous Leukemia (AML), and intravenously-injected autologous NK 
cells have been shown to significantly decrease melanoma tumor 
outgrowths. To this end, Dr. Rosenberg and colleagues have developed an 
alternative type of immunotherapy, which involves the adoptive transfer 
of autologous natural killer (NK) cells. This method consists of three 
parts: (a) Isolation and expansion of NK cells ex-vivo; (b) 
Administration of nonmyeloablative lymphodepleting chemotherapy regimen 
to the patient; and (c) Reconstitution of the patient's immune system 
by infusion of NK cells and interleukin 2. This approach also offers 
the possibility of treating AIDS, immunodeficiency, and autoimmune 
diseases for which immune cells can impact the clinical outcome.
    Development Status: This work has not yet been published; however, 
Dr. Rosenberg and colleagues have developed a clinical protocol and are 
awaiting IRB approval to begin enrolling patients in a Phase I clinical 
trial.
    Inventors: Steven A. Rosenberg and Maria R. Parkhurst (NCI).
    Publications:
    1. IRB approved protocol in press.
    2. SA Rosenberg and ME Dudley, ``Cancer regression n patients with 
metastatic melanoma after the transfer of autologous antitumor 
lymphocytes,'' Proc. Natl. Acad. Sci USA 2004 Oct 5;101 Suppl 2:14639-
14645.
    3. ME Dudley et al., ``Adoptive cell transfer therapy following 
non-myeloablative but lymphodepleting chemotherapy for the treatment of 
patients with refractory metastatic melanoma,'' J. Clin. Oncol. 2005 
Apr 1;23(10):2346-2357.
    4. U Siegler et al., ``Activated natural killer cells from patients 
with acute myeloid leukemia are cytotoxic against autologous leukemic 
blasts in NOD/SCID mice,'' Leukemia 2005 Dec;19(12): 2215-2222.
    5. F Lozupone et al., ``Effect of human natural killer and 
gammadelta T cells on the growth of human autologous melanoma 
xenografts in SCID mice,'' Cancer Res. 2004 Jan 1;64:378-385.
    Patent Status: U.S. Provisional Application No. 60/779,863 filed 06 
Mar 2006 (HHS Reference No. E-090-2006/ 0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Michelle A. Booden, Ph.D.; 301/451-7337; 
[email protected]
    Collaborative Research Opportunity: The NCI Surgery Branch is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
Natural Killer (NK) cells for their clinical use as cancer treatments. 
Please contact Dr. Steven Rosenberg at (301) 496-4164 or 
[email protected] for more information.

Sensitive Antibody-Based Assay for the Measurement of c-Met 
Concentration Shed in Bodily Fluids Useful in the Diagnosis and 
Prognosis of Cancer

    Description of Technology: This invention described and claimed in 
these patent applications provide for methods and assays which may be 
used to diagnose and follow the progression of cancers associated with 
c-Met expression. The data supporting this application suggests that c-
Met expression may be an appropriate biomarker in certain types of 
cancer. In particular, the applications describe a sensitive assay 
useful for monitoring levels of c-Met shed in the urine or blood. The 
assay was developed using commercially available reagents. The 
applications contain data, derived from patient samples, supporting the 
clinical utility of the assay. In particular, the data shows the use of 
the assay to detect levels of shed c-Met in patients with bladder 
cancer, renal cancers and prostate cancer. Data showing the 
applicability of the assay for glioblastoma was derived using murine 
models of cancer for glioblastoma. Data showing the applicability of 
the assay for breast cancer, melanoma and prostate cancer was derived 
using various human cell line model systems.
    HGF/met signaling has been most widely studied in settings related 
to cancer. It has been demonstrated to have a role in metastasis and 
angiogenesis. In addition to cancer, HGF activity has also been linked, 
through its role in apoptosis, to Alzheimer's disease and 
cardiovascular disease.
    These applications have not been published. The investigators 
presented their work in a poster session at the AACR Meeting April 16-
20, 2005 (Abstract 2788) (http://www.abstractonline.com/ viewer/
viewAbstract.asp?CKey= %7bAD0F2047-14FA-4BEE-AE98- 
0DAF2F26EF1A%7d&MKey= %7b218FF7E7-9F17-4030-9BB4- 8C029B0C9B4E%7d&AKey= 
%7b728BCE9C-121B-46B9-A8EE- DC51FDFC6C15%7d&SKey= %7bA5AFD1D5-1D83-
4F0E-9FD5-AC7119D62D8E). At this time there are no other publications 
related to this work. Dr. Bottaro's Web site is http://ccr.cancer.gov/Staff/Staff.asp?profileid=8410 profileid=8410.
    Inventors: Donald Bottaro and Pathirage G. Dharmawardana (both of 
NCI).
    Patent Status: U.S. Provisional Application No. 60/734,993 filed 08 
Nov 2005 (HHS Reference No. E-261- 2005/0-US-01) and U.S. Provisional 
Application No. 60/780,626 filed 09 Mar 2006 (HHS Reference No. E-261-
2005/ 1-US-01), entitled ``Methods for Diagnosing and Monitoring the 
Progression of Cancer.'' At this time only U.S. Patent protection has 
been sought for this technology. There are no foreign counterpart 
patent applications.
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Susan S. Rucker, Esq.; 301/435-4478; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Urologic Oncology Branch, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize HGF/c-Met signaling as it relates 
to tissue repair and regeneration, cancer, and other diseases. Please 
contact Brian W. Bailey, Ph.D. at (301) 451-2158 or [email protected] for more information.

Use of Cripto-1 as a Biomarker for Neurodegenerative Disease and Method 
of Inhibiting Progression Thereof

    Description of Technology: Cripto-1 is a gene that is currently 
thought to play an important role in several cancers, and is being 
developed in clinical trials as a cancer therapeutic. Presented in this 
invention is another use of Cripto-1 as a biomarker and possible 
therapeutic target for a variety of neurodegenerative diseases, 
including NeuroAIDS, Alzheimer's disease (AD), multiple sclerosis (MS), 
amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and 
encephalitis. Cripto-1 and concomitant protein expression appears to be 
overexpressed by 20-fold or more in the brains of macaque monkeys and 
humans afflicted with NeuroAIDS. This expression is confined to neurons 
related to neurodegeneration.

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Inhibition of Cripto-1 may be associated with inhibiting the 
progression of these diseases via a disclosed method for inhibiting the 
expression or downstream signaling pathways mediated by Cripto-1. This 
inhibition can be achieved through the expression of various inhibitory 
oligonucleotides. Additionally, the development of antibodies against 
Cripto-1 has already been achieved for the detection of Cripto-1 in 
human pathological specimens.
    It is estimated that by 2050, 14 million Americans will suffer from 
AD, representing national annual costs for caring and due to 
productivity lost of approximately $160 billion. Despite active 
research in this area, there remains urgent need to identify 
differentially expressed genes in and to develop methods for detecting 
neurodegenerative disease through assaying expression levels of 
specific genes. Currently, there are no drugs directed at inhibiting 
Cripto-1 as a therapeutic agent for AD or other neurodegenerative 
diseases. This invention holds the promise of market opportunities 
through pursuing development of Cripto-1 as a biomarker for diagnosis 
of and possible target for therapeutic intervention of these diseases.
    Inventors: David S. Salomon (NCI) et al.
    Publications:
    1. CL Parish et al., ``Cripto as a target for improving embryonic 
stem cell-based therapy in Parkinson's disease,'' Stem Cells 2005 Apr; 
23(4):471-476.
    2. HB Adkins et al., ``Antibody blockade of the Cripto CFC domain 
suppresses tumor cell growth in vivo,'' J Clin Invest. 2003 Aug 15; 
112(4): 575-587.
    Patent Status: U.S. Provisional Application No. 60/508,750 filed 03 
Oct 2003 (HHS Reference No. E-075-2003/0-US-01); PCT Application No. 
PCT/US04/32649 filed 01 Oct 2004 (HHS Reference No. E-075-2003/0-PCT-
02), which published as WO 2005/033341 on 02 Jun 2005.
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Michelle A. Booden, Ph.D.; 301/451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Mammary Biology and Tumorigenesis Laboratory, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize this 
technology. Please contact Jeffrey Hildesheim, Ph.D. at (301) 435-1569 
or [email protected] for more information.

    Dated: May 5, 2006.
David R. Sadowski,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
[FR Doc. E6-7428 Filed 5-15-06; 8:45 am]
BILLING CODE 4140-01-P