Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, DHHS.

ACTION:

Notice.

SUMMARY:

The inventions listed below are owned by agencies 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.

V1 Knockout Mice for Screening New Vaccines Against Streptococcus Pneumoniae

Qing-Sheng Mi, James J. Kenny, Dan L. Longo (NIA)

DHHS Reference No. E-140-00/0

Licensing Contact: Uri Reichman; 301/496-7056 ext. 240; e-mail: reichmau@od.nih.gov

Streptococcus pneumonia (SP) is a bacterial agent found in both mild mucosa and severe systemic infection; it is also often responsible for pneumonia, a disease that takes over one million lives a year. Recent SP strains prove resistant to Penicillin and other antibiotics, making the development of a Pneumococcal vaccine crucial. The existing vaccine is only about eighty percent effective at preventing SP infection in adults, but is much less effective in infants, aged, or immune deficient patients. Antibodies to phosphocholine (PC), an immunodominant epitope in the cell wall of Streptococcus pneumoniae, protect mice from lethal pneumococcal infection. The heavy chain of the PC protecting antibody is encoded by the V1 segment of the S107 V_H gene family. The V1 knockout mice which are available for licensing, cannot produce protective antibodies against the PC epitope of Streptococcus pneumonia. They are however, capable of producing normal antibodies to other cell wall proteins following bacteria immunization and get partial protection against lethal pneumococcal infection. Thus, the V1 knockout mice can facilitate the screening of protective antigens other than PC. This may result in new vaccine candidates against Streptococcus pneumonia. Screening for new vaccine candidates can be done as follows: The V1 knockout mice can be immunized with avirulent SP bacteria. The immune serum will be utilized to detect and isolate the antigenic cell wall proteins, using standard affinity binding procedures. The antigenic proteins will then be cloned, sequenced and purified. Normal mice will be immunized with these proteins and then challenged with virulent SP bacteria to determine whether these proteins have protective function.

Methods and Compositions for Co-Stimulation of Immunological Responses to Peptide Antigens

Samir Khleif, Jay Berzofsky (NCI)

DHHS Reference No. E-128-00/0 filed 15 Mar 2000

Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; e-mail: soukasp@od.nih.gov

This invention relates to peptide vaccines comprising administering a peptide comprising at least one T cell epitope coordinately with a non-viral vector comprising a polynucleotide encoding a T cell co-stimulatory molecule useful for eliciting cellular immune responses. The inventors have found that intradermal vaccination of mice with a DNA vector carrying the mouse co-stimulatory immunoglobulin B7.1 (CD80) in combination with a Human Papilloma Virus (HPV) E7 peptide significantly enhances the E7 specific cytotoxic lymphocyte response. Delivery of the B7.1 molecule as non-replicating DNA with antigenic peptides overcomes the problems of low antigenicity associated with some viral vectors as well as the instability, exogenous presentation and conformational maintenance problems associated with the delivery of full-length protein delivery. Furthermore, polynucleotides encoding the B7.1 construct can potentially be used along with any other form of antigen vaccine delivery systems, including peptides, full proteins and naked DNA antigens and are inexpensive to produce.

Full-Length Infectious cDNA Clones of Tick Borne Flavivirus

Alexander Pletnev, Robert M. Chanock (NIAID)

DHHS Reference No. E-281-98/0 filed 10 Feb 2000

Licensing Specialist: Carol Salata; 301/496-7735 ext. 232; e-mail: salatac@od.nih.gov

The tick-borne encephalitis virus complex of flavivirus family includes tick-borne encephalitis (TBEV), Kyasanur forest disease, Langat, Louping ill, Negishi, Omsk hemorrhagic fever and Povassan viruses. These viruses are endemic throughout most of the Northern Hemisphere and except for Langat, cause human disease of varying severity that can have mortality as high as 20 to 30%. Tick-borne encephalitis remains a pressing public health problem in Eastern Europe and Russia, where 9,000 to 12,000 patients are diagnosed annually and there is a need for a vaccine which can prevent this disease. This invention relates to an infectious full length Langat virus cDNA which has been successfully constructed and can be used to further attenuate this naturally attenuated tick-borne flavivirus. This full length Langat virus can be used as a live attenuated virus vaccine for the prevention of severe, often fatal disease caused by its more virulent tick-borne flavivirus relatives such as tick-borne encephalitis virus.

Polypeptides That Bind HIV gp120 and Related Nucleic Acids, Antibodies, Compositions, and Methods of Use

Carl Saxinger (NCI)

DHHS Reference No. E-245-99/0 filed 27 Aug 1999

Licensing Contact: J.P. Kim; 301/496-7056 ext. 264; e-mail: kimj@od.nih.gov

The presence of chemokines has been observed to have an inhibitory effect on HIV-1 attachment to, and infection of, susceptible cells. The interaction between gp120 and CD4, or at least one chemokine receptor is obligatory for HIV-1 infection. Reagents which interfere with the binding of gp120 to chemokine receptors and to CD4 are used in the biological and medical arts; however, there remains a need for additional reagents that can compete with one or more proteins of the gp120-CD4-chemokine-receptor complex to assist in the development of HIV therapeutics.

The present invention relates to such polypeptides with homology to domains of the human chemokine receptors CCR5, CXCR4, and STRL33, as well as domains of CD4 that bind with human immunodeficiency virus (HIV), in particular the HIV-1 glycoprotein 120 (gp120) envelope protein. These receptor polypeptides were identified through the application of a recent technological advance in the design and synthesis of synthetic peptide arrays (see Saxinger, WC: An automated peptide design and synthesis; U.S. Patent 6,031,074 issued 29 Feb 2000). The binding of gp120 to receptor peptide arrays was highly linearly correlated with structure/activity relationships between biological receptors and HIV infectivity in vitro (r=>95%, p<=0.03). The binding of gp120 by active receptor polypeptides was unrestricted by viral or receptor strain or subtype suggesting that the polypeptides participated in an early stage of infection common to multiple virus strains, thus potentially addressing problems of virus variation and multiple virus strains. The invention further provides for nucleic acids encoding such polypeptides, antibodies, compositions comprising such polypeptides, nucleic acids or antibodies, and methods of use thereof, such as in therapeutics and vaccine design.

System and Method for Simulating a Two-Dimensional Radiation Intensity Distribution of Photon or Electron Beams

J van de Geijn, H Xie (NCI)

Serial No. 08/368,589 filed 06 Jan 1995; U.S. Patent No. 5,526,395 issued 11 Jun 1996

Licensing Contact: NIHOTT@od.nih.gov

The present invention provides a method for computer-assisted, interactive 3-dimensional radiation treatment planning and optimization. The computerized system is capable of processing and analyzing data obtained from x-ray, CT, MRI, PET, SPECT, and gammacamera devices. Hence, the system can be used as a training device, alleviating the need for training centers to purchase each of these devices. The computerized system comprises a fast, versatile, and user-friendly software package and computer components which are commercially available and which can be used without significant modification. Because the hardware costs of this system are much lower than the cost of systems of comparable ability, this invention ought to be particularly attractive to smaller radiation oncology facilities which seek a powerful treatment planning system. The low cost of the system is also particularly advantageous for medical training facilities, including medical schools. The invention also has potential use as a monitor for clinical quality assurance.

Combination Therapies for Viral Infection

Lori et al. (NCI); Malley & Vila

Serial Nos. 08/065,814 filed 21 May 1993; 08/245,259 filed 17 May 1994; 08/169,253 filed 20 Dec 1993; 08/378,219 filed 25 Jan 1995; 08/401,488 filed 08 Mar 1995; 08/577,322 filed 22 Dec 1995; 08/617,421 filed 18 Mar 1996; 09/497,700 filed 03 Feb 2000

Licensing Contact: J.P. Kim; 301/496-7056 ext. 264; e-mail: kimj@od.nih.gov

The subject inventions provide for formulations and methods for inhibiting replication of reverse transcription dependent viruses in animals cells comprising administering a compound that depletes the intracellular pool of deoxyribonucleoside phosphate, and further comprising administering a compound that serves to inhibit replication of the virus by terminating DNA chain elongation.