NIH Invention Disclosures, Nov. 15, 1996
Forwarded by NIH for publication in the Federal Register on November 15, 1996.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, DHHS
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.
ADDRESS: Licensing information and a copy of the U.S. patent applications referenced below may be obtained by contacting Joseph Contrera, M.S., J.D., at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804 (telephone 301/496-7056 ext 244; fax 301/402-0220). A signed Confidential Disclosure Agreement will be required to receive a copy of the patent applications.
A Novel Vector for Polynucleotide Vaccines
EL Nelson, PJ Nelson (NCI)
Serial No. 60/023,931 filed 14 Aug 96
This invention is directed to a "humanized" polynucleotide vector vaccine which uses covalent closed circular (CCC) plasmid DNA, "naked DNA," to express target antigens. The vector contains the necessary elements to express mRNA for a target antigen. The plasmids are non-replicating but are capable of extended stable expression of the target sequences in skeletal muscle and professional antigen presenting cells generating an immune response to the target antigen in immunized individuals. The polynucleotide vector is particularly useful in accommodating monomorphic and polymorphic tumor antigens via PCR technology. This invention could be useful in constructing polynucleotide vector cancer vaccines or "naked DNA" vaccines containing one or more tumor antigens.
Heterologous Boosting Immunizations for the Generation of CTL and Anti-Tumor Responses
RS Chamberlain, KR Irvine, SA Rosenberg, NP Restifo (NCI)
Serial No. 60/015,893 filed 22 Apr 96
Description of Invention: A number of recombinant and synthetic vectors expressing tumor associated antigens have been developed which each induce powerful cellular and humoral immune responses that correlated with anti-tumor immunity in murine tumor model systems. Examples of these vectors include 1) recombinant viruses, such as vaccinia, fowlpox and adenovirus, 2) recombinant plasmid DNA, and 3) minimal determinant peptides. This invention involves the use of more than one of these vectors expressing a particular antigen for priming and boosting immunization regimens with the goal of enhancing anti-tumor immunity. Boosting with heterologous vectors induced more powerful primary antigen-specific cytotoxic T lymphocyte responses than boosting with the same vector. These more powerful immune responses induced by subsequent immunization with a different vector than the priming agent also resulted in a significant prolongation in survival of tumor-bearing mice as compared to mice that received two vaccinations with the same vector. Specifically, the combinations that were most efficacious were recombinant vaccinia virus followed by recombinant fowlpox and vice versa and recombinant DNA immunization followed by either recombinant fowlpox or vaccinia virus and vice versa.
Potential Areas of Application: The invention is significant because these heterologous boosting strategies may provide for increased therapeutic potential in the design and development of immunotherapies for cancer treatment. This approach may also be useful in the development of treatments for infectious bacterial and viral diseases.
Main Advantages of Invention: The main advantage of this approach is that it offers an easy method to augment anti-tumor immunity. Repetitive administration of recombinant vectors such as viruses induce anamnestic immune responses against proteins normally expressed by viruses that may abrogate or reduce immunity against the virally produced recombinant protein. A severely reduced immune response against the HIV gp160 protein has been documented in individuals inoculated with a recombinant vaccinia virus encoding HIV gp160 that were previously immunized with wild type vaccinia virus as a smallpox immunization. The approach of boosting with heterologous immunogens will avoid the occurrence of anamnestic immunity and therefore result in augmented anit-tumor immunity.
Stage of Development: Most of these recombinant approaches are being attempted in clinical trials in patients with melanoma. In these studies, each approach is being used individually in Phase I clinical trials to test mainly for safety and dose.
Further Development Required: The main murine study has been completed. Clinical trials are pending once the parameters for each vector have been assessed.
Point Mutated ras Peptides for the Generation of CD8+ Cytotoxic T Lymphocytes
J Schlom, S Abrams (NCI)
Serial No. 08/635,344 filed 19 Apr 96
This invention is directed to a method of inducing a cytotoxic T cell response where the cytotoxic T cells are CD8+ T cells. The CD8+ cytotoxic T cell response is induced by peptides which contain a mutation in the K-ras oncogene at codon 12. The invention discloses 13 mer K-ras peptides spanning position 5-17 of the K-ras gene and which contain a mutation at codon 12. In addition, 9 mer and 10 mer K-ras peptides are also described in which they both span codon 12 and in which codon 12 is mutated. This invention could be useful in cancer vaccines and adoptive immunotherapy.