[Federal Register Volume 74, Number 68 (Friday, April 10, 2009)]
[Notices]
[Pages 16402-16405]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-8208]


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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

[[Page 16403]]

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.

Treating Cancer Through Immunotherapy With Herceptin-Based Receptors 
Specific for ErbB2 (Her2/Neu)

    Description of Technology: There is an urgent need to develop new 
therapeutic strategies for patients with cancer that combine fewer 
side-effects and more specific anti-tumor activity. Adoptive 
immunotherapy is a promising new approach to cancer treatment that 
engineers an individual's innate and adaptive immune system to fight 
against specific diseases, including cancer.
    Chimeric antigen receptors (CARs) are hybrid proteins consisting of 
the portion of an antibody that recognizes a tumor-associated antigen 
(TAA) fused to protein domains that signal to activate the CAR-
expressing cell. Human cells that express CARs, most notably T cells, 
can recognize specific tumor antigens with high reactivity to mediate 
an immune response that promotes tumor killing in targeted cancer 
cells.
    Scientists at the National Institutes of Health (NIH) have 
developed CARs with high affinity for the ErbB2 (also known as Her2/
Neu) antigen, which is overexpressed on a variety of cancer cells, 
including lung, breast, colorectal, ovary, prostate, and head and neck 
squamous cell cancer. These ErbB2-specific CARs are herceptin-based 
receptors composed of the part of a humanized herceptin antibody that 
recognizes ErbB2 and a portion of the T cell receptor (TCR)-related 
protein, CD3. The herceptin-CAR framework was selected since the 
herceptin monoclonal antibody has been proven to be an effective 
treatment for breast cancer. These ErbB2-specific CARs expressed in the 
context of T cells could prove to be powerful new immunotherapeutic 
tools for attacking ErbB2+ tumors after their infusion into patients.
    Applications:
     Immunotherapeutics to treat and/or prevent the 
reoccurrence of a variety of human cancers that overexpress human ErbB2 
by inserting herceptin-based CAR sequences into patient T cells.
     A drug component of a combination immunotherapy regimen 
aimed at targeting the specific tumor-associated antigens expressed by 
cancer cells within individual patients.
    Advantages:
     This discovery is widely applicable to many different 
cancers: ErbB2 is overexpressed in many cancers, including lung, 
breast, colorectal, ovary, prostate, and head and neck squamous cell 
cancer. Anti-ErbB2 CAR immunotherapy could treat a variety of cancer 
types while reducing the side-effects of treatment.
     The technology is based on an already approved antibody: 
The herceptin monoclonal antibody is a U.S. Food and Drug 
Administration (FDA) approved treatment for ErbB2+ breast cancer 
patients. This current herceptin-based CAR immunotherapy treatment is 
predicted to draw favorable consideration from the FDA as it proceeds 
through clinical trials.
    Development Status: This technology will soon enter the clinical 
stage of development since the inventors plan to initiate clinical 
trials using CAR engineered lymphocytes for adoptive immunotherapy of 
cancer. A clinical protocol is under review.
    Market: Cancer continues to be a medical and financial burden on 
U.S. public health. Statistically, in the U.S. cancer is the second 
leading cause of death with over 565,000 deaths reported in 2008 and 
almost 1.5 million new cases were reported (excluding some skin 
cancers) in 2008. In 2007, the NIH estimated that the overall cost of 
cancer was $219.2 billion dollars and $89 billion went to direct 
medical costs. The fight against cancer will continue to benefit from 
the development of new therapeutics aimed at treating individual 
patients.
    Inventors: Steven A. Rosenberg et al. (NCI).
    Patent Status: U.S. Provisional Application No. 61/154,080 filed 20 
Feb 2009 (HHS Reference No. E-045-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Samuel E. Bish, PhD; 301-435-5282; 
[email protected]
    Collaborative Research Opportunity: Dr. Steven A. Rosenberg of the 
NCI Surgery Branch is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize therapeutic T cell receptor technologies. 
Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

Peptides for Treating Mesothelin- and/or CA125-Expressing Cancers

    Description of Technology: Mesothelin is a cell surface 
glycoprotein that is highly expressed in many cancers, including 
malignant mesothelioma and ovarian cancer. Mesothelin interacts with 
another cell surface protein that is also highly expressed on some 
cancer cells: CA125 (MUC16). Evidence indicates that this interaction 
mediates cell adhesion during tumor implantation and metastasis. This 
suggested that the disruption of the mesothelin-CA125 interaction may 
prevent the growth and spreading of tumors.
    NIH inventors have generated specific peptides, based on the CA125 
binding domain of mesothelin, that block the interaction between 
mesothelin and CA125. Significantly, blocking the interaction disrupted 
cell adhesion in cancer cells expressing both mesothelin and CA125. 
Antibodies that recognize the specific mesothelin peptides were also 
capable of disrupting the mesothelin-CA125 interaction. The peptides 
bound CA125 on cancer cells. As a result, these peptides are excellent 
candidates for a new cancer therapeutic.
    Applications:
     Treatment of cancers that express mesothelin and CA125 by 
disrupting the mesothelin-CA125 interaction
     Treatment of CA125-expressing cancers by binding cell 
surface CA125
     Direct inhibition of the mesothelin-CA125 interaction with 
specific peptides
     Inhibition of the mesothelin-CA125 interaction by using 
specific peptides as a vaccine
    Advantages:
     The specific peptides are from a human protein and may not 
elicit a strong immunogenic response that would inhibit its 
effectiveness as a blocking agent
     Any immunogenic response to the specific peptides would 
have a potential beneficial effect by generating antibodies that also 
inhibit mesothelin-CA125 interaction and inhibit CA125-expressing tumor 
growth
    Inventors: Mitchell Ho (NCI) et al.
    Patent Status:
     PCT Application PCT/US2008/85743 (HHS Reference E-336-
2008/0-PCT-01)

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    For more information, see:
     US Patent 6,083,502 entitled ``Mesothelium Antigen and 
Methods and Kits For Targeting It''
     PCT Application PCT/US97/0224 entitled ``Mesothelium 
Antigen and Methods and Kits For Targeting It''
     US Patent 6,809,184 entitled ``Antibodies, Including Fv 
Molecules, and Immunoconjugates Having High Binding Affinity for 
Mesothelin and Methods for Their Use''
     PCT Application PCT/US98/25270 entitled ``Antibodies, 
Including Fv Molecules, and Immunoconjugates Having High Binding 
Affinity for Mesothelin and Methods for Their Use''
     US Patent 7,081,518 entitled ``Anti-mesothelin antibodies 
having high binding affinity''
     PCT Application PCT/US00/14829 entitled ``Immunoconjugates 
Having High Binding Affinity Improvement of scFVsr Ab's with Higher 
Affinity for Mesothelin''
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Molecular Biology, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize peptides for treating mesothelin- 
and/or CA125-expressing cancers. Please contact Mitchell Ho at 301-451-
8727 and/or [email protected] for more information.

An Imaging Radiotracer for the Noninvasive Detection of HER2-Positive 
Tumors

    Description of Technology: Investigators at the NIH have developed 
a novel imaging radiotracer composed of an Affibody[supreg] molecule 
uniquely labeled with 18F for noninvasively locating and measuring the 
expression of HER2 breast cancer biomarker in tumors anywhere in the 
body. The over expression of HER2 in cells is a diagnostic marker for a 
particularly aggressive form of breast cancer. Currently, localized 
biopsies are needed to diagnose HER2-positive breast cancer. 
Noninvasive detection of HER2-positive cells in whole body will help to 
identify patients that can benefit from HER2-targeted therapies such as 
the monoclonal antibody trastuzumab. This imaging compound will also be 
useful for monitoring the tumor response to HER2-targeted therapies. 
The use of Affibody[supreg] molecule is advantageous because it is 
recombinant protein of relatively small size (more than 20 times 
smaller than antibodies), readily producible and having a high binding 
affinity to HER2. This allows the imaging compound to permeate the body 
easily and bind to the HER2-positive cells selectively. Conjugating 
Affibody[supreg] molecule to the positron-emitting radionuclide 18F 
enables noninvasive imaging using positron emission tomography (PET). 
The utility of this targeted radiotracer for detecting HER2-positive 
tumors has already been validated in animals.
    Applications:
     Diagnostic and prognostic for HER2-positive tumors in 
breast cancer patients.
     Monitoring effectiveness of HER2-targeted therapy.
     Research tool for the in vivo study of HER2-positive 
carcinomas.
    Advantages:
     Noninvasive.
     Detection of metastasis of HER2-positive tumors.
     Timely monitoring of tumor response to therapy.
     Improved accuracy in prognosis of patient survival.
    Development Status: Pre-clinical in vitro and in vivo data 
available
    Market:
     Breast cancer is the second leading cause of cancer death 
in women.
     In 2008, an estimated 182,460 new cases of invasive breast 
cancer were expected among women in the United States.
    Inventors: Jacek Capala (NCI) et al.
    Publications:
    1. D Kiesewetter et al. Radiolabeling of HER2-specific 
Affibody[reg] molecule with F-18. J Fluor Chem. 2008 Sep;129(9):799-
806, doi:10.1016/j.jfluchem.2008.06.021.
    2. Kramer-Marek et al. [18F]FBEM-ZHER2:342-Affibody molecule--a new 
molecular tracer for in vivo monitoring of HER2 expression by positron 
emission tomography. Eur J Nucl Med Mol Imaging. 2008 May;35(5):100818. 
doi:10.1016/j.jphotobiol.2006.08.011.
    Patent Status:
    U.S. Provisional Application No. 60/891,875 filed 27 Feb 2007 (HHS 
Reference No. E-086-2007/0-US-01)
    PCT Application No. PCT/US2008/055144 filed 27 Feb 2008, which 
published as WO 2008/118601 on 02 Oct 2008 (HHS Reference No. E-086-
2007/0-PCT-02)
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Radiation Oncology Branch, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
Affibody[reg] molecules for diagnosis and molecular therapy of HER1- or 
HER2-positive tumors. Please contact John D. Hewes, PhD at 301-435-3121 
or [email protected] for more information.

Small-Molecule TSH Receptor Modulators for Diagnosis and Treatment of 
Thyroid Disease and Cancer

    Description of Technology: NIH investigators have discovered a 
series of low molecular weight thyroid-stimulating hormone (TSH) 
receptor modulators for use in evaluation and treatment of thyroid 
diseases, including thyroid cancer, hypothyroidism, and 
hyperthyroidism. Certain compounds encompassed by this technology are 
more potent and/or more specific TSH receptor activators than 
currently-available compounds; also, as small molecules, these 
compounds are orally available and are expected to be less costly and 
more straightforward to produce than recombinant protein counterparts 
currently on the market.
    According to the National Cancer Institute, over 37,000 new cases 
of thyroid cancer were diagnosed in the United States in 2008, and over 
1,500 people died of this disease. These numbers reflect a progressive 
increase in the incidence of thyroid cancer over the last several 
years. Because most cases of thyroid cancer are diagnosed in patients 
between the ages of 20 and 54, these patients will undergo decades of 
follow-up monitoring after cancer treatment. For the last decade, 
recombinant TSH protein has been used in this follow-up to increase 
detection sensitivity for recurrent or metastatic thyroid cancer, and 
to eliminate side effects associated with withdrawal of hormone 
replacement therapy. A small-molecule TSH receptor agonist encompassed 
by this technology would have utility similar to recombinant TSH, but 
would have several distinct advantages. For example, as a small 
molecule, rather than a recombinant protein, such a compound would be 
orally available, and would be less difficult and expensive to produce. 
These compounds are also more potent and/or specific for the TSH 
receptor than other known small-molecule TSH receptor agonists. In 
addition to use in thyroid cancer screening, these compounds may also 
be useful for adjunctive treatment (with radioactive iodide) of thyroid 
cancer, and certain forms of hypothyroidism.

[[Page 16405]]

    Hyperthyroidism, or an overactive thyroid gland, affects about 1% 
of people in the United States and is often caused by autoimmune over-
stimulation of the thyroid gland (Graves' disease), or by thyroid 
tumors. Drugs currently used for treatment of hyperthyroidism inhibit 
synthesis of thyroid hormones; the TSH receptor antagonist compounds 
encompassed by this technology have the advantage of directly 
inhibiting activity of the TSH receptor, rather than inhibiting thyroid 
hormone synthesis.
    Applications:
     Diagnostic tools for evaluation and treatment of thyroid 
cancer.
     Therapeutics for thyroid cancer, hyperthyroidism, and 
hypothyroidism.
    Market: Approximately 1 in 13 Americans suffers from a thyroid 
disorder, and 10 million have a thyroid-related condition that requires 
ongoing immunodiagnostic monitoring.
    Development Status: Early stage.
    Inventors: Marvin C. Gershengorn et al. (NIDDK)
    Publications:
    1. S Moore, H Jaeschke, G Kleinau, S Neumann, S Costanzi, JK Jiang, 
J Childress, BM Raaka, A Colson, R Paschke, G Krause, CJ Thomas, MC 
Gershengorn. Evaluation of small-molecule modulators of the luteinizing 
hormone/choriogonadotropin and thyroid stimulating hormone receptors: 
structure-activity relationships and selective binding patterns. J Med 
Chem. 2006 Jun 29;49(13):3888-3896.
    2. S Neumann, G Kleinau, S Costanzi, S Moore, BM Raaka, CJ Thomas, 
G Krause, MC Gershengorn. A low molecular weight antagonist for the 
human thyrotropin receptor with therapeutic potential for 
hyperthyroidism. Endocrinology 2008 Dec;149(12):5945-5950.
    3. Unpublished data are also available for review under a CDA.
    Patent Status:
    HHS Reference Nos. E-223-2006/0 and E-223-2006/1 --
     International Patent Application No. PCT/US2007/011951 
filed 17 May 2007, which published as WO 2007/136776 on 29 Nov 2007.
     National Phase entered in Australia, Canada, Europe, 
Japan, and the United States.
    HHS Reference No. E-284-2008/0 --
     International Patent Application No. PCT/US2008/011958 
filed 20 Oct 2008.
    Licensing Status: Available for licensing.
    Licensing Contact: Tara L. Kirby, PhD; 301-435-4426; 
[email protected].
    Collaborative Research Opportunity: The NIDDK, Clinical 
Endocrinology Branch is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize small molecule TSH receptor modulators. 
Please contact Patricia Mello Lake; 301-451-3636; [email protected] 
for more information.

    April 3, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E9-8208 Filed 4-9-09; 8:45 am]
BILLING CODE 4140-01-P