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###### Department of Health and Human Services

###### National Institutes of Health

# AGENCY:

National Institutes of Health, Public Health Service, HHS.

# ACTION:

Notice.

# 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.

## Immunogenic Peptide from NGEP Protein for Developing Prostate Cancer Vaccines

*Description of Technology:*                     The NGEP protein is only present in the prostate and is typically overexpressed on prostate cancer cells. Hence, as a novel prostate tumor-associated antigen (TAA) it is a good target for developing active immunotherapies to kill prostate cancer cells. For example, NGEP could be used in a vaccine to activate an individual's immune system to recognize and kill NGEP-expressing prostate cancer cells. However, TAAs typically are not very effective in inciting an immune response. This can be overcome by identifying portions (epitopes) of the                           ( print page 32938)                        TAA that are more immunologically active.                

Investigators at the NIH have identified a small peptide fragment of the NGEP protein (NGEP CTL peptide epitope) that is very effective in activating cytotoxic lymphocytes, causing them to destroy prostate cancer cells and has great potential for development of a variety of active immunotherapy strategies, such as vector-based cancer vaccines, to treat and prevent prostate cancer. In addition, it could be used for developing sensitive immunoassays for measuring the immune response of a prostate cancer patient during immunotherapy.

*Applications:*
      - Peptide cancer vaccine.
      - Vector-based cancer vaccine.
      - Liposome-based cancer vaccine.
      - Cellular cancer vaccine.
      - In vitro diagnostic for monitoring the immune response of prostate cancer patients during cancer vaccine trials.

*Advantages:*
      - Small biologic therapeutic.
      - Can be chemically synthesized or produced recombinantly.
      - DNA encoded peptide allows molecular engineering.
      - Can be used as a tumor antigen with the clinically proven TRICOM-based vaccine technology.

*Development Status:*                     Early stage.                

*Market:*                     Prostate cancer is the second-leading cause of cancer death in men. It is estimated that in the United States there will be 192,280 new cases of prostate cancer and 27,360 deaths due to prostate cancer in 2009.                

*Inventors:*                     Jeffrey Schlom                     *et al.*                     (NCI).                

*Publications:*                     No publications directly related to this technology.                

*Patent Status:*                     U.S. Provisional Application No. 61/170,900 filed 20 Apr 2009 (HHS Reference No. E-042-2009/0-US-01).                

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     Sabarni Chatterjee, PhD; 301-435-5587;                     *chatterjeesa@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Cancer Institute, Center for Cancer Research, Laboratory of Tumor Immunology and Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Kevin Brand, J.D. at 301-451-4566 or                     *brandk@mail.nih.gov*                     for more information.                

## Gene Expression Signature Predictive of Response to Chemotherapy

*Description of Technology:*                     Combination cisplatin and fluorouracil (CF) is a reference chemotherapy regimen for metastatic gastric cancer. However, to date, no genome-wide studies have identified distinctions in gene expression that predict which subjects with metastatic disease will benefit from this therapy and which subjects will not exhibit a therapeutic response to chemotherapy. Given the toxicity of chemotherapy, however, defining parameters that identify those subjects who will likely benefit from chemotherapy is of paramount importance. Early identification of non-responders would provide opportunities to explore alternate or novel therapeutic approaches. Thus, a need exists to identify methods of predicting a subject's response to chemotherapy prior to receiving the treatment.                

Scientists at the National Institutes of Health have discovered a three-gene signature that can be used to determine the chemotherapy response in patients with cancer. By measuring the expression of three cancer-specific genes it can be determined if a patient with an epithelial cancer such as gastric, bladder, head and neck, esophageal or cervical cancers, will respond to CF treatment. The inventors have demonstrated that examining these expression levels has high fidelity in identifying CF treatment non-responders. Further, the invention describes a mechanism that can help patients identified as non-responders become responsive to treatment. Therefore these methods have the potential to reduce fatalities caused by metastatic gastric cancer by identifying patients early on who are non-responsive to standard CF treatment and customizing a new treatment plan which may be better suited to their individual needs.

*Applications:*
      - Prognostic testing of epithelial cancer patients.
      - Customized treatment for gastric cancer patients identified as CF treatment non-responders.

*Advantages:*
      - Expression levels of cancer-specific genes can be used to determine if metastatic gastric cancer patients are responsive to combination cisplatin and fluorouracil (CF) treatment.
      - Fatalities due to metastatic gastric cancer may be reduced by customizing the treatment of non-responders.

*Market:*                     In 2008, it is estimated that there will be 21,500 new cases and 10,880 deaths from gastric cancer in the United States.                

*Development Status:*                     Patient tissue sample data available.                

*Inventors:*                     Jeffrey E. Green and Hark Kyun Kim (NCI).                

*Patent Status:*                     U.S. Provisional Application No. 61/195,123 filed 03 Oct 2008 (HHS Reference No. E-282-2008/0-US-01).                

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     Surekha Vathyam, PhD; 301-435-4076;                     *vathyams@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Cancer Institute, Center for Cancer Research, Laboratory of Cancer Biology and Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Gene Expression Signature Predictive of Response to Chemotherapy. Please contact John D. Hewes, PhD at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                

## Therapeutic Applications of a p53 Isoform in Regenerative Medicine, Aging, and Cancer

*Description of Technology:*                     p53 plays a critical role in carcinogenesis and aging as a key regulator of cell cycle progression, senescence and apoptosis. The inventors have discovered that a natural variant of p53 (Δ133p53) inhibits p53-dependent cell senescence. Utilizing Δ133p53 siRNAs, the inventors have data demonstrating that siRNA-treated human fibroblast undergo cell senescence, thereby indicating that Δ133p53 inhibition could be a novel approach for cell senescence-mediated anti-proliferative therapy, including anti-cancer treatments. Alternatively, enhanced expression with Δ133p53 can extend the replicative lifespan of normal human cells. This technology may provide a new method in the field of regenerative medicine for aging-related degenerative disease.                

Also available for licensing are Δ133p53 siRNAs and shRNA vectors, as well as a Δ133p53 overexpression vector, which can be used for cancer and age-related degenerative therapeutics. The shRNA can be stably integrated into the cellular genome for long-term Δ133p53 inhibition.

The inventors have also discovered that another p53 variant (p53β) accelerates p53-dependent cell senescence, and developed a vector for overexpressing p53β, which could be used for cell senescence-mediated anti-proliferative therapy.

*Applications:*
      - Method to treat cancer.
      - Method to treat aging related disorders.
      - Method to promote tissue regeneration.       ( print page 32939)      
      - Pharmaceutical compositions to inhibit cancer or promote cell regeneration.

*Advantages:*
      - Ability to treat a wide variety of cancers and age-related diseases as p53 is present in normal cells.
      - shRNA therapeutics are stably integrated into genome for long-term treatment.

*Development Status:*                     The technology is currently in the pre-clinical stage of development.                

*Market:*
      - An estimated 1,479,350 new cancer diagnoses in the U.S. in 2009.
      - Cancer is the second leading cause of death in United States.
      - It is estimated that the cancer therapeutic market would double to $50 billion a year in 2010 from $25 billion in 2006.

*Inventors:*                     Curtis C. Harris (NCI)                     *et al.*

*Relevant Publications:*

                    1. K Fujita                     *et al.*                     p53 isoforms, Δ133p53 and p53β, are endogenous regulators of replicative cellular senescence. Nat Cell Biol., in press.                

2. International Agency Research on Cancer Conference, Lyon, France, November 13, 2007.

*Patent Status:*
      - U.S. Provisional Application No. 60/987,340 filed 12 Nov 2007 (HHS Reference No. E-033-2008/0-US-01).
      - PCT Application No. PCT/US2008/080648 filed 21 Oct 2008 (HHS Reference No. E-033-2008/0-PCT-02).

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     Jennifer Wong; 301-435-4633;                     *wongje@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Cancer Institute, Laboratory of Human Carcinogenesis, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact                     *Curtis_Harris@nih.gov*                     for more information.                

## Novel Compounds that Specifically Kill Multi-Drug Resistant Cancer Cells

*Description of Invention:*                     One of the major hindrances to successful cancer chemotherapy is the development of multi-drug resistance (MDR) in cancer cells. MDR is frequently caused by the increased expression or activity of ABC transporter proteins in response to the toxic agents used in chemotherapy. Research has generally been directed to overcoming MDR by inhibiting the activity of ABC transporters. However, compounds that inhibit ABC transporter activity often elicit strong and undesirable side-effects, restricting their usefulness as therapeutics.                

Investigators at the NIH previously identified that the compound NSC73306 had the ability to specifically kill cancer cells that overexpressed an ABC transporter responsible for MDR. Importantly, this “MDR-selective compound” is not an inhibitor of ABC transporters, reducing the likelihood of undesirable side-effects if used as a therapeutic.

Using NSC 73306 as a model, new MDR-selective compounds have been created with improved solubility and selectivity. These new MDR-selective compounds can also selectively kill MDR cancer cells, with their efficacy correlating directly with the level of ABC transporter expression. Recent evidence also shows that these new MDR-selective compounds have the ability to decrease the expression of ABC transporters, potentially re-sensitizing the cancer cells to chemotherapeutic agents. Thus, MDR-selective compounds represent a powerful strategy for treating multi-drug resistant cancers as a direct chemotherapeutic and as agents that can re-sensitize MDR cancer cells for treatment with additional chemotherapeutic agents.

*Applications:*
      - Treatment of cancers associated with multi-drug resistance, either alone or in combination with other therapeutics.
      - Development of a pharmacophore for improved effectiveness in treating cancers associated with multi-drug resistance.
      - Re-sensitization of multi-drug resistant cancer cells to chemotherapeutic agents.

*Advantages:*
      - MDR-selective compounds capitalize on one of the most common drawbacks to cancer therapies (MDR) by using it as an advantage for treating cancer.
      - The compositions do not inhibit the activity of ABC transporters, thereby reducing the chance of undesired side-effects during treatment.
      - The effects of MDR-selective compounds correlate with the level of ABC transporter expression, allowing healthy cells which do not express high levels of ABC transporters to better survive treatments.
      - Increased specificity allows the new MDR-selective compounds to be tailored to treating cancers associated with the overexpression and hyperactivity of particular ABC transporters.
      - Increased solubility of the new MDR-selective compounds allows greater access to cancer cells, thereby increasing therapeutic effectiveness.

*Development Status:*                     Preclinical stage of development.                

*Patent Status:*                     PCT Application No. PCT/US2009/000861 (HHS Reference No. E-017-2008/0-PCT-02).                

*Inventors:*                     Matthew D. Hall                     *et al.*                     (NCI).                

For more information, see:
      - MD Hall et al.                      Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells. J Med Chem. 2009 May 28;52(10):3191-3204.                
      - US Patent Application Publication 20080214606 A1 (US Patent Application 11/629,233).

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     David A. Lambertson, PhD; 301-435-4632;                     *lambertsond@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Cancer Institute, Laboratory of Cell Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the agents described here. Please contact John D. Hewes, PhD  at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                

## Methods for Treating Cancer in Humans Using IL-21

*Description of Invention:*                     The present invention discloses the use of IL-21 for cancer therapy, cancer prevention, and method to induce apoptosis. When compared to similar cytokines, IL-21 has shown substantial anticancer activity and reduced toxicity in murine models.                

IL-21 belongs to the class I family of cytokines and is closely related to IL-2 and IL-15. Some cancer patients have shown significant response to administration of IL-2. However, IL-2 has also been associated with severe toxicity leading to a variety of undesirable side effects. This invention attempts to resolve the toxicity concerns and presents a new therapy for cancer prevention and treatment.

*Applications:*                     Method to treat and prevent cancer.                

*Advantages:*                     Targeted therapy to minimize negative side effects of IL-2 cancer therapeutics.                

*Development Status:*                     Pre-clinical.                

*Inventors:*                     Patrick Hwu (formerly NCI), Gang Wang (formerly NCI), Warren J. Leonard (NHLBI), Rosanne Spolski (NHLBI),                     *et al.*

*Related Publications:*

                    1. R Spolsi and WJ Leonard. Interleukin-21: Basic biology and implications for cancer and                           ( print page 32940)                        autoimmunity. Annu Rev Immunol. 2008;26:57-79.                

2. WJ Leonard and R Spolski. Interleukin-21: A modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol. 2005 Sep;5(9):688-698.

3. G Wang et al. In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Cancer Res. 2003 Dec15;63(24):9016-9022.

*Patent Status:*                     U.S. Patent Application No. 10/508,978 filed 19 Nov 2004 (HHS Reference No. E-137-2002/0-US-03).                

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     Jennifer Wong; 301-435-4633;                     *wongje@mail.nih.gov.*

Dated: July 1, 2009.

Richard U. Rodriguez,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.

[FR Doc. E9-16300 Filed 7-8-09; 8:45 am]

BILLING CODE 4140-01-P