Document Headings

                    Document headings vary by document type but may contain                    the following:                  
                -                       the agency or agencies that issued and signed a document                    
                -                       the number of the CFR title and the number of each part                      the document amends, proposes to amend, or is directly                      related to                    
                -                       the agency docket number / agency internal file number                    
                -                       the RIN which identifies each regulatory action listed in                      the Unified Agenda of Federal Regulatory and Deregulatory                      Actions                    

                    See the                                          Document Drafting Handbook                                        for more details.                  

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

###### National Institutes of Health 

# AGENCY:

National Institutes of Health, Public Health Service, DHHS. 

# 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. 

##                     The Use of Rabbits With Defined Immunoglobulin Light Chain Genes (Ckappa                     b Allotypes) To Optimize Production of Chimeric and Humanized Monoclonal Antibodies for Therapeutic, Imaging and Diagnostic Applications                 

Rose G. Mage, Cornelius Alexander (NIAID). 

DHHS Reference No. E-332-2004/0—Research Tool. 

                    Licensing Contact: Pradeep Ghosh; (301) 435-5282;                     *ghoshpr@mail.nih.gov.*

Biological materials are important research tools that can be used for diagnostic as well as therapeutic purposes. Antibodies have become viable drugs in the market today and there is a general market need for systems that may facilitate production of efficient and effective antibodies. In recent years, monoclonal antibodies have gained significant importance in their use, both as diagnostics and therapeutics, to intervene and combat diseases such as cancer, cardiovascular diseases, and infections. The present invention relates to the discovery of rabbits, genetically defined as b9, as the biological vehicle for the isolation of chimeric phage displaying Fab with human constant regions and rabbit immunoglobulin heavy and light chain variable regions for the development of diagnostic antibodies and humanized monoclonal therapeutic antibodies of high affinity and specificity (Popkov et al., J. Molec. Biol. 325: 325-335, 2003; Popkov et al. J. Immunol. Methods 288: 149-164, 2004). Recently, many effective antibodies have been developed as a result of the integration of antibody libraries with phage display technology. The rabbit model described in this invention may be used for production of antibodies that may cross react with both human and mouse antigens. Rabbit monoclonal antibodies that react with both human and mouse antigens are of particular relevance for the preclinical evaluation of therapeutic antibodies in mouse models of human diseases. Therefore, this invention has a broad commercial potential in its use as a source for producing monoclonal antibodies for therapeutic interventions in infectious, autoimmune and neurological diseases, nerve damage and cancer. 

## Methods for Diagnosis of Atherosclerosis 

Paul Hwang et al. (NHLBI). 

U.S. Provisional Application No. 60/607,031 filed 03 Sep 2004 (DHHS Reference No. E-276-2004/0-US-01). 

                    Licensing Contact: Fatima Sayyid; 301/435-4521;                     *sayyidf@mail.nih.gov.*

In industrialized countries coronary heart disease and stroke due to atherosclerosis are the leading causes of morbidity and mortality. Coronary heart disease is the single largest cause of death in the U.S.A. and will cost approximately $133.2 billion according to the 2004 American Heart Association statistics update. 

The identification of more sensitive and specific markers of atherosclerosis that are non-invasive and cost-effective may have profound impacts on public health. One such strategy involves the detection of marker genes or their products in blood or serum. Such markers may help identify high-risk patients with subclinical atherosclerosis who may benefit from intensive primary prevention or they may help determine the activity of established disease for monitoring response to treatment, resulting in more targeted secondary prevention.

The present invention relates to methods for detecting atherosclerosis using highly reactive biomarkers (FOS and/or DUSP1) expressed in blood cells or released into serum. Because these markers are also involved in pathogenesis, they may serve as potential targets for drug discovery and for intervention to modify disease progression. 

## An Improved Method To Separate and Expand Antigen-Specific T Cells 

Jonming Li and John Barrett (NHLBI). 

U.S. Provisional Application No. 60/606,197 filed 31 Aug 2004 (DHHS Reference No. E-246-2004/0-US-01). 

                    Licensing Contact: Fatima Sayyid; (301) 435-4521;                     *sayyidf@mail.nih.gov.*

                    Stem cell transplants can be used to treat patients with leukemia or other disorders. Transplanted donor T cells (lymphocytes) exert strong alloimmune                           ( print page 75994)                        graft versus leukemia and other anti-tumor effects however they can also cause potentially lethal graft versus host disease (GVHD), requiring post-transplant immunosuppression. Such immunosuppression may place patients at a greater risk of contracting potentially fatal cytomegalovirus infection further reducing their capacity to be cured of their malignant disease.                 

The transfer of T lymphocytes specific for leukemia cells or micro-organism antigens can be useful since therapeutic immune effects would be enhanced while GVHD reactions would not be induced. Currently available methods for isolating and expanding antigen-specific T cells including selection using HLA tetramers, magnetic beads binding to activation markers or laborious limiting dilution techniques are unreliable, poorly reproducible, expensive and impede clinical progress. 

The present invention relates to methods for selecting and expanding antigen specific T-cells that recognize a pre selected target antigen, to purified populations of antigen-specific T cells that recognize a pre selected target antigen and to therapeutic uses of antigen-specific T cells that recognize a pre selected target antigen. Potential applications include treatment of cytomegalovirus, Epstein-Barr virus and adenovirus reactivation following stem cell transplantation or organ transplantation, prevention and treatment of leukemic relapse after transplantation or chemotherapy using autologous expanded T cells, and selective depletion of alloreactive T cells from transplants which may produce GVHD. 

## Novel Compounds for Selectively Inactivating Pain Pathways 

Peter Blumberg, Jeewoo Lee (NCI). 

U.S. Provisional Application No. 60/558,003 filed 26 Mar 2004 (DHHS Reference No. E-141-2004/0-US-01). 

                    Licensing Contact: Norbert Pontzer; 301/435-5502;                     *pontzern@mail.nih.gov.*

Available for licensing are compositions and methods for the long-term control of pain and other pathological conditions caused by the over-activity of pain pathways. Neurons in the dorsal root, trigeminal and nodose ganglia project unmyelinated C-fibers and Aδ-fibers that transmit pain and temperature sensation between the periphery and spinal cord. Along with acute and chronic pain, over activation of those pathways leads to neurogenic and neuropathic inflammation leading to such conditions as post-herpetic neuralgia, diabetic neuropathy, cystitis, and reflex sympathetic dystrophy among many others. 

These neurons are activated both centrally and peripherally by a relatively non-selective cation channel initially identified as site of action of capsaicin, the pungent ingredient in chili peppers. That channel is now called VR1 or TRPV1 and is found in high concentration only on C and Aδ neurons. These inventors previously discovered and patented resiniferatoxin (RTX), an ultrapotent agonist of the VR1 receptor. RTX desensitizes C and Aδ-fibers when applied peripherally and may selectively ablate those neurons when applied centrally without causing substantial pain from activation of the neurons. RTX type compounds thus provide a method of controlling pain other conditions caused by C and Aδ-fiber activity. The present invention provides new RTX analogues that may have an improved therapeutic index and metabolic profile. 

Dated: December 9, 2004. 

Steven M. Ferguson, 

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

[FR Doc. 04-27783 Filed 12-17-04; 8:45 am] 

BILLING CODE 4140-01-P