National Institutes of Health, Public Health Service, HHS.
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.
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.
Novel System for HIV-1 Vaccine Development
Description of Technology: The available technologies describe specific immunogenic peptides, peptide modifications and methods for identifying additional immunogens against HIV-1 surface proteins, gp120 and gp41. Additionally, detailed methods for use of the described immunogenic peptides in the development of vaccines and diagnostics for HIV-1 are disclosed. The current technologies further include a comprehensive system for immunogen design, comprising in silico design coupled to feedback from X-ray crystallography, antigenic analysis, and immunization.
The described methodology demonstrates how to transplant a given HIV-1 epitope recognized by broadly neutralizing antibodies into an appropriate scaffold, while preserving its structure and antigenicity. Conservation of the three dimensional structure may lead to the generation of antibodies with broadly neutralizing characteristics, similar to the template antibody. Such epitope-transplant scaffolds may serve as valuable diagnostics to identify specific serum reactivity against the target HIV-1 epitopes. The subject scaffolding technology may be applied to any virus for which a broadly neutralizing Start Printed Page 10229antibody and its respective epitope has been characterized at the atomic-level.
1. Immunogens that elicit immune responses to HIV-1.
2. Efficient development of vaccines against HIV-1.
3. Screening tool to isolate antibodies with activities similar to identified template antibody.
Inventors: Peter D. Kwong et al. (NIAID)
1. G Ofek, W Schief, J Guenaga, et al. Epitope-transplant scaffolds: Automated design, structural analysis, and antigenic characteristics. Manuscript in preparation (2007).
2. T Zhou, L Xu, B Dey, AJ Hessell, DV Ryk, SH Xiang, X Yang, MY Zhang, MB Zwick, J Arthos, DR Burton, DS Dimitrov, J Sodroski, R Wyatt, GJ Nabel, PD Kwong. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature. 2007 Feb 15;445(7129):732-737.
3. DC Douek, PD Kwong, GJ Nabel. The rational design of an AIDS vaccine. Cell. 2006 Feb 24;124(4):677-681.
4. G Ofek, M Tang, A Sambor, H Katinger, JR Mascola, R Wyatt, PD Kwong. Structure and mechanistic analysis of the anti-HIV-1 antibody 2F5 in complex with its gp41 epitope. J Virol. 2004 Oct;78(19):10724-10737.
1. PCT Application No. PCT/US2005/016633 filed 13 May 2005, which published as WO 2005/111079 on 24 Nov 2005 (HHS Reference No. E-218-2004/0-PCT-02), and National Stage filed in the U.S. on 26 Nov 2006 (HHS Reference No. E-218-2004/0-US-03), entitled “HIV Vaccine Immunogens and Immunization Strategies to Elicit Broadly-Neutralizing Anti-HIV-1 Antibodies Against the Membrane Proximal of HIV gp41”.
2. PCT Application No. PCT/US2006/034681 filed 06 Sep 2006 (HHS Reference No. E-324-2005/3-PCT-01), entitled “Conformationally Stabilized HIV Envelope Immunogens and Triggering HIV-1 Envelope to Reveal Cryptic V3-Loop Epitopes”
3. PCT Application No. PCT/US2006/034882 filed 06 Sep 2006 (HHS Reference No. E-280-2006/1-PCT-01), entitled “HIV gp120 Crystal Structure and Its Use to Identify Immunogens”
4. U.S. Provisional Application No. 60/840,119 filed 25 Aug 2006 (HHS Reference No. E-302-2006/0-US-01), entitled “Epitope-Transplant Scaffolds and Their Use”
Licensing Availability: Available for non-exclusive or exclusive licensing.
Licensing Contact: Susan Ano, Ph.D.; 301/435-5515; email@example.com
CCR5-Specific Human Monoclonal Antibodies
Description of Technology: The subject invention provides the composition claims related to anti-CCR5 monoclonal antibodies, their fusion protein, conjugates, derivatives, or fragments, DNA sequences encoding such antibodies, host cells containing such DNA sequences, as well as the methods to produce them recombinantly and their pharmacological composition.
It has been demonstrated that the HIV co-receptor CCR5 plays an important role in virus entry. The subject antibodies exhibited neutralization activity against HIV-1 infection by binding to cell associated CCR5 in vitro. Moreover, subject antibodies have potentially lower immunogenicity and toxicity, because they are fully human antibodies. Therefore, subject anti-CCR5 antibodies have a potential as a therapeutic and/or prophylactic in combination with other HIV-1 neutralizing antibodies and anti-retroviral drugs.
Applications: HIV treatment and prevention.
Development Status: In vitro data is available at this time.
Inventors: Dimiter S. Dimitrov and Mei-Yun Zhang (NCI).
1. C Pastori et al. Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: A possible protective effect against disease progression. Blood. 2006 Jun 15;107(12):4825-4833.
2. MY Zhang, B Vu, CC Huang, I Sidirov, V Choudhly, PD Kwong, DS Dimitrov. Identification of human monoclonal antibodies specific for CCR5 from an antibody library derived from HIV-infected long-term non-progressors. Retrovirology. 2006 Dec 21;3 Suppl 1:S61.
3. DS Dimitrov. Virus entry: molecular mechanisms and biomedical applications. Nat Rev Microbiol. 2004 Feb;2(2):109-122.
Patent Status: U.S. Provisional Application No. 60/859,401 filed 15 Nov 2006 (HHS Reference No. E-297-2006/0-US-01)
Licensing Availability: Available for exclusive and non-exclusive licensing.
Licensing Contact: Sally Hu, Ph.D.; 301/435-5606; HuS@mail.nih.gov.
Collaborative Research Opportunity: The NCI CCR Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize monoclonal antibodies. Please contact John D. Hewes, Ph.D. at 301-435-3121 or firstname.lastname@example.org for more information.Start Signature
Dated: February 28, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of Technology Transfer National Institutes of Health.
[FR Doc. E7-3959 Filed 3-6-07; 8:45 am]
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