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AssigneesYale University, The Regents of the University of California, The United States Government as represented by the Department of Veterans Affairs
InventorsJames E. Hansen, Peter M. Glazer, Richard H. Weisbart, Robert N. Nishimura, Grace Chan
Estimating the term…
Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.
A method of inhibiting DNA repair in a neoplastic cell, comprising contacting the cell with a pharmaceutical composition comprising cell-penetrating unconjugated monospecific anti-DNA antibodies or cell-penetrating unconjugated antigen binding fragments thereof, wherein the cell-penetrating unconjugated monospecific anti-DNA antibodies or cell-penetrating unconjugated antigen binding fragments thereof consist of monoclonal antibody 3E10 produced by ATCC Accession No. PTA 2439 hybridoma, or a cell penetrating antigen binding fragment or humanized form thereof.
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The method of claim, wherein the cell-penetrating unconjugated antigen binding fragments comprise a single chain variable fragment of 3E10 (3E10 scFv) or a humanized form thereof.
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A dosage unit comprising cell-penetrating anti-DNA antibodies or fragments thereof in a pharmaceutically acceptable excipient, wherein the antibodies are present in an amount effective to inhibit DNA repair in cancer or virally infected cells with or without intrinsic deficiency in DNA repair.
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A method of determining a subject's sensitivity to a DNA damaging therapy, comprising assaying a sample obtained from the subject for levels of cell-penetrating anti-DNA antibodies, wherein an increase in cell-penetrating anti-DNA antibodies in the sample compared to a control indicates that the subject is sensitive to the DNA damaging therapy.
Dependencies are inferred from the claim text.