Rodent HER2 tumor model
AssigneeGenentech, Inc.
InventorsSharon Erickson, Kathleen King, Ralph Schwall
Life of this patent
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Abstract
The invention concerns HER2-transgenic non-human mammals, animal models for screening drug candidates for the treatment of diseases and disorders associated with the overexpression of HER2. In particular, the invention concerns animal models designed to test drug candidates for the treatment of HER2-overexpressing cancers, including breast cancer, that are not responding or poorly responding to current treatments.
Claims37
A transgenic mouse that produces in its mammary gland cells detectable levels of a native human HER2 protein, wherein said transgenic mouse has stably integrated into its genome a nucleic acid sequence encoding a native human HER2 protein, operably linked to transcriptional regulatory sequences directing its expression to the mammary gland, and develops a mammary tumor that, when transplanted into a suitable rodent recipient, develops into a tumor that does not respond or responds poorly to anti-HER2 antibody treatment.
A rodent model for HER2 expressing tumors comprising a rodent bearing a tumor that developed from a transplanted mouse tumor, wherein said tumor overexpresses HER2 and does not respond or responds poorly to anti-HER2 antibody treatment.
The rodent model of clam 8 wherein said tumor expresses a human HER2 protein in at least about 500,000 copies per cell.
A rodent model for HER2 expressing tumors comprising a rodent bearing a tumor overexpressing HER2 wherein said tumor does not respond or responds poorly to treatment with anti-HER2 antibody 4D5 or a conjugate of said antibody.
A transgene construct comprising a nucleic acid encoding a native human HER2 protein, wherein said nucleic acid is operably linked to transcriptional regulatory sequences directing its expression to the mammary gland.
A stable cell line that expresses HER2 and is established from a HER2 transgenic mouse that has stably integrated into its genome a nucleic acid sequence encoding a native human HER2 protein, wherein said nucleic acid is operably linked to transcriptional regulatory sequences directing its expression to the mammary gland.
The cell line HER-5, deposited with ATCC on Feb. 28, 2001 (Accession Number PTA-3135).
The cell line HER-3081-3-1, deposited with ATCC on Feb. 28, 2001 (Accession Number PTA-3133).
The cell line HER-3081-3-10, deposited with ATCC on Feb. 28, 2001 (Accession Number PTA-3134).
A method of screening drug candidates for the treatment of a disease or disorder characterized by the overexpression of HER2 comprising (a) administering a drug candidate to a transgenic mouse that overexpresses in its mammary gland cells a native human HER2 protein, wherein said transgenic mouse has stably integrated into its genome a nucleic acid sequence encoding a native human HER2 protein, operably linked to transcriptional regulatory sequences directing its expression to the mammary gland, and develops a mammary tumor, or to a rodent bearing a tumor transplanted from said transgenic mouse, wherein said transplanted tumor does not respond or poorly responds to anti-HER2 antibody treatment;
- (b) evaluating Me effect of said drug candidate on said tumor.
The method of claim wherein said disease or disorder is a HER2-overexpressing cancer.
Dependencies are inferred from the claim text.