05-15346. Government-Owned Inventions; Availability for Licensing

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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Immunogenic Peptides From Human Papillomavirus Type 16 E2

Samir N. Khleif and Jiahua Qian (NCI).

U.S. Provisional Application No. 60/671,463 filed 15 Apr. 2005 (DHHS Reference No. E-155-2005/0-US-01).

U.S. Provisional Application No. 60/680,000 filed 12 May 2005 (DHHS Reference No. E-155-2005/1-US-01).

Licensing Contact: Michael Shmilovich; 301/435-5019; [e-mail].

Available for licensing, commercial development and biological materials licensing are CD8+ T cell epitopes from HPV16 E2 (Human Papillomavirus serotype 16 E2). These epitopes generated from amino acid positions 69-77 (ALQAIELQL) and 138-147 (YICEEASVTV) bind to HLA.A2 and elicit CD8+ cytotoxic T cell responses that lyse tumor cells of low-grade cervical neoplasia (wart).

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

HIV gp41-Membrane Proximal Region Arrayed on Hepatitis B Surface Antigen Particles for HIV Diagnostic and Vaccine Applications

Richard T. Wyatt (NIAID), Sanjay K. Phogat (NIAID), Ira Berkower (FDA).

U.S. Provisional Application No. 60/653,930 filed 18 Feb. 2005 (DHHS Reference No. E-123-2005/0-US-01).

Licensing Contact: Susan Ano; 301/435-5515; [e-mail].

This technology describes vectors encoding the membrane proximal region (MPR) and select variants from HIV-1 gp41 linked to the hepatitis B surface antigen (HBsAg) and the resulting expressed particles for use in HIV diagnostic and vaccine applications. HIV-1 gp41 membrane proximal region contains two epitopes recognized by broadly neutralizing human monoclonal antibodies 2F5 and 4E10. However, immunization with gp41 MPR or the 2F5 or 4E10 epitopes have failed to raise neutralizing antibodies. In the subject technology, the particles were shown to bind antibodies from broadly neutralizing human sera and to the two known broadly neutralizing antibodies 2F5 and 4E10 with high relative affinities, demonstrating that the relevant epitopes are accessible for antibody binding and the potential utility of the particles in diagnostic applications. Additionally, these particles could be used to screen phage-display libraries for novel broadly cross-reactive neutralizing antibodies, of which only five are currently known. These particles could also be used for selection of MPR specific B cells. Lastly, these particles have been shown to be immunogenic and raise antibodies that recognize HIV-1 Env gp160 expressed on the cell surface. These immunogens can elicit neutralizing antibodies specific for HIV gp41 MPR, the MPR of gp41 is highly conserved across various HIV clades and therefore is likely to generate broadly neutralizing antibodies when administered in a proper presentation in a lipid context as is the case in HBsAg particles. Multiple copies of the MPR of HIV-1 gp41 arrayed on the particles could significantly increase the immunogenic potential compared to monomeric molecules. An increase of this nature has been observed with HBsAg and HPV virus-like particles in hepatitis B and cervical cancer vaccines, respectively, suggesting that particulate array may improve the presentation of selected epitopes to the immune system.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

North-2′-Deoxy-Methanocarbathymidines as Antiviral Agents Against Poxviruses

Christopher K. Tseng (NIAID), Victor E. Marquez (NCI).

U.S. Provisional Application No. 60/684,811 filed 25 May 2005 (DHHS Reference No. E-047-2005/0-US-01).

Licensing Contact: Robert M. Joynes; 301/594-6565; [e-mail].

This invention relates to a method for the prevention or treatment of poxvirus infection by administering an effective amount of an antiviral agent comprising a carbocyclic 2′-deoxynucleoside analog (as described in U.S. Patent Nos. 5,629,454 and 5,869,666) to an individual in need thereof. North-methanocarbathymidine (N-MCT), a thymidine analog with a pseudosugar moiety locked in the northern conformation, which was previously shown to exert strong activity against herpes simplex virus types 1 and 2, has been identified as exhibiting potent activity against poxviruses. N-MCT effectively blocks poxvirus synthesis through its phosphorylated metabolite, which is more efficiently produced in poxvirus-infected cells. This compound is approximately seven times more potent than cidofovir against vaccinia and cowpox in cell culture. The higher potency and target specificity of N-MCT against poxvirus, as well as its high margin of safety, makes it a highly desirable agent against the poxviridae family. In addition, the mechanism of N-MCT may be different from that of cidofovir, making it even more desirable due to the scarcity of the potential available efficacious anti-pox agents currently under development. This method of treating poxvirus with the described analogs is now available for licensing.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

A Novel Interleukin-12 (IL-12) Inducing Protein Isolated from Toxoplasma gondii Inflammatory Profilin (TGIP)

Alan Sher and Felix Yarovinsky (NIAID).

U.S. Provisional Application 60/641,429 filed 06 Jan 2005 (DHHS Reference No. E-046-2005/0-US-01).

Licensing Contact: Michael Shmilovich; 301/435-5019; [e-mail].

Available for licensing and commercial development is a patent pending technology for identifying and isolating a novel interleukin-12 (IL-12) inducing protein isolated from Toxoplasma gondii (T. gondii), and to methods of using this protein for modulating immune responses. Interferon-γ (IFN-γ) is critical in host resistance to many pathogens and also has potent anti-tumor effects on certain IFN-γ sensitive tumors. IL-12 triggers the synthesis of IFN-γ, thus compounds that stimulate IL-12 production are likely to contribute to stimulation of host resistance to pathogens and IFN-γ sensitive tumors.

The isolated protein, Toxoplasma gondii Inflammatory Profilin (TGIP), also known as PFTG (Profilin Toxoplasma gondii) binds to Toll-like receptor 11 (TLR 11) and induces dendritic cell IL-12 production. The patent as filed discloses isolated TGIP polypeptide sequences, fusion proteins comprising a TGIP and antigen polypeptide portions, isolated nucleic acids encoding a fusion protein, and a promoter-linked polynucleotide encoding TGIP. Also described are methods for inducing a IL-12 response, a method for administering isolated TGIP for the treatment of pathogenic infection, a method for treating an IFN-γ sensitive cancer in a subject and methods for enhancing immune response against an antigen in a subject. Also with the scope of the invention are anti-TGIP antibodies. Since IL-12 also has other immunostimulatory effects, further identification of IL-12 inducing compounds will be useful for the design of immunostimulatory and adjuvant agents.

This research is described in Yarovinsky et al., “LR11 activation of dendritic cells by a protozoan profilin-like protein,” Science 2005 Jun 10; 308(5728):1626-9. Epub 2005 Apr 28.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Ultrahigh-Resolution Fiber-Optic Confocal Microscope And Method

Ilko Ilev (FDA/CDRH), Ronald Waynant (FDA/CDER), Israel Gannot (NICHD), Amir Gandjbakhche (NICHD).

U.S. Provisional Application No. 60/671,104 filed 14 Apr. 2005 (DHHS Reference No. E-038-2005/0-US-01).

Licensing Contact: Michael Shmilovich; 301/435-5019; [e-mail].

Public Health Service investigators have invented a single-mode fiber-optic confocal microscope for which a licensee and commercial developer is sought. The ultrahigh-resolution fiber-optic confocal microscope has an illumination system; three single-mode optical fibers, each optically coupled to a fiber coupler; a sample support stage arranged to receive illumination radiation from an end of one of the single-mode optical fibers; a detector arranged to receive output radiation from one of the single-mode optical fibers; and a lock-in amplifier electrically connected to the detector and the illumination system. The illumination system is adapted to provide illumination radiation that has a time-varying strength correlated with the detector by the lock-in amplifier. The invention provides improved methods and designs for confocal microscopy.

Integrin Alpha-V Beta-3 Antagonists for Use in Imaging and Therapy

S. Narasimhan Danthi et al. (CC).

U.S. Patent Application No. 10/911,988 filed 04 Aug 2004 (DHHS Reference No. E-170-2004/0-US-01).

Licensing Contact: Michael Shmilovich; 301/435-5019; [e-mail].

Available for licensing are compounds as shown below for imaging and therapy. These compounds are integrin α_vβ₃ receptor antagonists and are described and claimed in a patent application available for review. The patent application also includes claim coverage for the administration of these compounds containing a detectable moiety or pharmaceutical compositions of such imaging agents as part of the imaging of cells that express integrin α_vβ₃.

in which: X is either NH, O, or S; n is zero or a positive integer; R₁ is either CH₂, NH, O, or S; R₂ is either CHR₇, NR₇, O, or S, in which R₇ is H or alkyl; R₃ and R₄, which are either the same or different from each other, are either H, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, alkyl-substituted aryl, (alkylsubstitutedaryl)alkyl, hydroxy-substituted alkyl, hydroxy-substituted aryl, or (hydroxy-substituted aryl)alkyl; R₅ is either CH₂, NH, O, or S; and R₆ is either H or C(=Y)-R₈-R₉, in which: Y is either NH, O, or S; R₈ is either CHR₁₀, NR₁₀, O, or S, in which R₁₀ is H or alkyl; and R₉ is either H, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, alkylsubstituted aryl, (alkyl-substituted aryl)alkyl, hydroxy-substituted alkyl, hydroxy-substituted aryl, or (hydroxy-substituted aryl)alkyl.

Dated: July 19, 2005.

Steven M. Ferguson,

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