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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.

##                     Radiotracers for Imaging Cannabinoid Sub-Type1 (CB                    1                    ) Receptor                

*Description of Technology:*                     The present invention relates to novel radiolabeled compounds for imaging cannabinoid sub-type 1 (CB1) receptors in brains of mammals, particularly humans, using positron emission tomography (PET) or single photon emission computed tomography                           ( print page 50831)                        (SPECT). These radioligands can be used in clinical research, diagnostics, or drug discovery and development, in that, they permit understanding of the role of CB1                     receptors in neuropsychiatric disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, multiple sclerosis, depression, mood disorder, anxiety, schizophrenia, drug addiction, alcohol disorder, obesity and anorexia.                

*Applications:*
      -  In vivo                      imaging of CB 1                      receptor in mammals, particularly humans                
      - Diagnostic imaging of CB 1                      receptors in subjects having a neurological, neuropsychiatric, neurodegenerative or other condition and treatment                
      - Pharmaceutical composition
      - Diagnostic kits

*Advantages:*                     The principal radioligand under the claim is effective for imaging CB1                     receptors                     *in vivo*                     with PET.                

*Development Status:*                     Primary radioligand has been evaluated in non-human primates with PET.                

*Market:*                     Radioligands may be useful for performing drug occupancy studies of CB1                     receptors, and for neuropsychiatric studies and investigations with imaging techniques (                    *e.g.*, PET or SPECT).                

*Patent Status:*                     U.S. Provisional Application No. 61/052,581 filed 12 May 2008 (HHS Reference No. E-155-2008/0-US-01).                

*Inventors:*                     Victor W. Pike (NIMH), Sean R. Donohue (NIMH),                     *et al.*

*Relevant Publications:*

                    1. SR Donohue, C Halldin, VW Pike. Synthesis and structure-activity relationships (SARs) of 1,5-diarylpyrazole cannabinoid type-1 (CB1) receptor ligands for potential use in molecular imaging. Bioorg Med Chem. 2006 Jun 1;14(11):3712-3720.                

                    2. SR Donohue, VW Pike, SJ Finnema, P Truong, J Andersson, B Gulya                                        s, C Halldin. Discovery and labeling of high affinity 3,4-diarylpyrazolines as candidate radioligands for                     *in vivo*                     imaging of cannabinoid subtype-1 (CB1) receptors. J Med Chem., in press.                

*Licensing Status:*                     Available for exclusive or non-exclusive licensing.                

*Licensing Contact:*                     RC Tang, JD, LLM; 301-435-5031;                     *tangrc@mail.nih.gov.*

## HIV Immunogen and Method of Making and Using Same

*Description of Technology:*                     The invention describes composition and methods of preventing HIV infection using a truncated version of the HIV gp41 subunit of                     *Env*                     fused to human Fc through a flexible linker as a vaccine immunogen. This immunogen binds several broadly cross-reactive HIV-1 neutralizing human monoclonal antibodies recently identified and developed by the inventor's laboratory, including m44. m44 does not react with self-antigen suggesting that this immunogen may elicit antibodies which are not regulated by tolerance mechanisms, a problem suggested as the cause of failure for some of the gp41-based immunogens previously tested. Rabbits immunized with this fusion construct developed broad-neutralizing antibodies against several HIV-isolates from different clades in a cell line/pseudovirus assay with high titer. Preclinical testing of these novel immunogens in primate models is currently being planned.                

*Applications:*                     Treatment and prevention of HIV infection.                

*Advantages:*
      - Has potential to elicit broad neutralizing antibodies against several HIV isolates from different clades.
      - Immunogen is based on the gp41 subunit of the HIV Env , a region more conserved than the gp120 subunit of                      Env                      and fusion to Fc increases the stability and half-life of the immunogen.                
      - Potentially elicits antibodies that are not regulated by tolerance mechanisms.

*Development Status:*                     Data can be provided upon request.                

*Market:*                     Preventative or treatment for HIV infection.                

*Inventors:*                     Dimiter S. Dimitrov and Mei-yun Zhang (NCI).                

*Publications:*

1. M-Y Zhang, V Choudhry, IA Sidorov, V Tenev, BK Vu, A Choudhary, H Lu, GM Stiegler, HWD Katinger, S Jiang, CC Broder, DS Dimitrov. Selection of a novel gp41-specific HIV-1 neutralizing human antibody by competitive antigen panning. J Immunol Methods 2006 Dec 20;317(1-2):21-30.

2. M-Y Zhang, DS Dimitrov. Novel approaches for identification of broadly cross-reactive HIV-1 neutralizing human monoclonal antibodies and improvement of their potency. Curr Pharm Des. 2007;13(2):203-212.

3. V Choudhry, M-Y Zhang, IA Sidorov, JM Louis, I Harris, AS Dimitrov, P Bouma, F Cham, A Choudhary, SM Rybak, T Fouts, DC Montefiori, CC Broder, GV Quinnan, DS Dimitrov. Cross-reactive HIV-1 neutralizing monoclonal antibodies selected by screening of an immune human phage library against an envelope glycoprotein (gp140) isolated from a patient (R2) with broadly HIV-1 neutralizing antibodies. Virology 2007 Jun 20;363(1):79-90.

4. M-Y Zhang, BK Vu, A Choudhary, H Lu, M Humbert, H Ong, M Alam, RM Ruprecht, G Quinnan, S Jiang, DC Montefiori, JR Mascola, CC Broder, BF Haynes, DS Dimitrov. Cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody that recognizes a novel conformational epitope on gp41 and lacks reactivity against self-antigens. J Virol. 2008 Jul;82(14):6869-6879.

*Patent Status:*                     U.S. Provisional Application No. 61/126,662 filed 06 May 2008 (HHS Reference No. E-072-2008/0-US-01).                

*Licensing Status:*                     Available for exclusive or non-exclusive licensing.                

*Licensing Contact:*                     Sally Hu, Ph.D.; 301-435-5606,                     *HuS@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Cancer Institute CCR Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                

## Cross-Reactive Neutralizing Human Domain Antibody Against HIV-1

*Description of Technology:*                     The invention describes the first identified anti-HIV human domain antibody (m36), which can potentially be used alone or synergistically with other anti-HIV antibodies and antiretroviral drugs as a therapeutic and/or preventative for HIV infection. It targets an epitope whose exposure is enhanced by binding of the HIV receptor CD4 to the HIV envelope glycoprotein (Env). M36 was identified by sequential panning of a newly developed large human VH library against Envs from different HIV-1 isolates. The antibody can neutralize HIV-1 primary isolates from different clades at low (nM) concentrations and due to its small size (14 kDa) is potentially able to efficiently penetrate lymphoid tissues where the virus replicates. The antibody is fairly well characterized and the inventors are generating derivatives of this antibody to improve the half-life and increase its potency and cross-reactivity.                

*Applications:*                     Treatment and prevention of HIV infections.                

*Advantages:*
      - Human monoclonal antibody, thus eliminating some of the issues associated with humanized or murine monoclonal antibodies.
      - Potential neutralization of HIV-1 primary isolates from different clades at nM concentrations.
      - Relatively small size allows for potential efficient penetration into lymphoid tissues.

*Development Status: In vitro*                     data is available.                          ( print page 50832)    

*Market:*                     HIV therapeutics and preventatives.                

*Inventors:*                     Dimiter Dimitrov and Weizao Chen (NCI).                

*Publications:*

                    1. MY Zhang                     *et al.*                     Identification of a Novel CD4i human monoclonal antibody Fab that neutralizes HIV-1 primary isolates from different clades. Antiviral Res. 2004 Mar;61(3):161-164.                

                    2. MY Zhang                     *et al.*                     Improved breath and potency of an HIV-1 neutralizing human single-chain antibody by random mutagenesis and sequential antigen panning. J Mol Biol. 2004 Jan 2;335(1):209-219.                

                    3. CC Huang                     *et al.*                     Structure of a V3-containing HIV-1 gp120 core. Science 2005 Nov 11; 310(5750):1025-1028.                

                    4. W Chen                     *et al.*                     Construction of a large phage-displayed human antibody domain library with a scaffold based on a newly identified highly soluble, stable heavy chain variable domain. J. Mol Biol. 2008, in press.                

                    5. W Chen                     *et al.*                     Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizers. Proc Natl Acad Sci USA., under review.                

*Patent Status:*                     U.S. Patent Application No. 61/019,426 filed 07 Jan 2008 (HHS Reference No. E-043-2008/0-US-01).                

*Licensing Status:*                     This invention is available for exclusive or non-exclusive licensing.                

*Licensing Contact:*                     Sally Hu, Ph.D.; 301-435-5606,                     *HuS@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Cancer Institute CCR Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize domain antibodies and nanoantibodies against HIV. Please contact John D. Hewes, Ph.D. at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                

##                     Monodisperse and Modified                     *Yersinia pestis*                     Capsular F1-V Antigen Fusion Proteins for Vaccination Against Bubonic and Pneumonic Plague                

*Description of Technology:*                     An effective plague vaccine against                     *Yersinia pestis*                     is currently unavailable in the U.S. The F1-V (fusion of two                     *Y. pestis*                     proteins, the Fraction 1 capsular antigen and a second immunogen called the V-antigen) vaccine of this invention is a monodispersed, mutated form of F1-V fusion protein. This is a promising candidate for commercialization.                

Features and benefits include:
      - The vaccine is substantially monomeric but does not tend to self-associate and form aggregates.
      - The antigen fusion proteins retain immunogenicity.
      - The associated, new manufacturing process provides an inexpensive means of making an effective vaccine.
      - The method eliminates the need for mixing components that is the case with competitive technology.

*Applications:*
      - An effective vaccine is needed where plague is endemic.
      - An important biodefense countermeasure against dissemination of weaponized plague is sought.

*Inventors:*                     David F. Nellis and Steven L. Giardina (NIAID).                

*Relevant Publication:*                     JL Goodin et al. Purification and protective efficacy of monomeric and modified                     *Yersinia pestis*                     capsular F1-V antigen fusion proteins for vaccination against plague. Protein Expr Purif. 2007 May;53(1):63-79.                

*Patent Status:*                     U.S. Patent Application No. 11/944,230 filed 21 Nov 2008 (HHS Reference No. E-189-2007/0-US-01).                

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

*Licensing Status:*                     Available for non-exclusive or exclusive licensing.                

*Licensing Contact:*                     Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301-435-4507;                     *thalhamc@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The NIAID is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this plague vaccine. Please contact Marguerite J. Miller at 301-435-8619 /or                     *millermarg@niaid.nih.gov*                     for more information.                

Dated: August 18, 2008.

Richard U. Rodriguez,

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

[FR Doc. E8-19917 Filed 8-27-08; 8:45 am]

BILLING CODE 4140-01-P