Aveo Pharmaceuticals, Inc.

Ronan O'Hagan

Alisa C Bell

William M Winston, Jr

Jeno Gyuris

Sandra Abbott

Heidi Okamura

Samantha Perino

Hamid Tissire

Kelly Kreuter

Murray Robinson

Yinghui Zhou

Steven C Clark

Jie Lin

Maria Isabel Chiu

Tyler E Jacks

Lorena Lerner

Joerg Heyer

Ronald A Depinho

William Rideout, Iii

Karuppiah Kannan

Ti Cai

H Heidi Okamura

Jeanine Lorusso

Ronald Depinho

William Iii Rideout

Murray O Robinson

Monoclonal antibodies that bind and inhibit activation of human Notch3 are disclosed. The antibodies can be used to treat cell proliferative diseases and disorders, including certain forms of cancer, associated with activation of Notch3.

Anti-notch3 antibodies

Anti-NOTCH3 antibodies

Anti-Notch3 antibodies

Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

Chimeric cancer models

A method of producing a tumorigenic mouse cell, the tumorigenicity of which depends on a recombinant gene of interest is disclosed. The method involves: (a) providing a conditionally tumorigenic mouse cell containing a recombinant oncogene operably linked to an inducible promoter, wherein (i) expression of the recombinant oncogene is necessary and sufficient for the tumorigenicity of the tumorigenic mouse cell, and (ii) the inducible promoter is in the uninduced state; and (b) introducing into the cell a recombinant gene of interest that functionally complements the oncogene, thereby restoring tumorigenicity without expression of the inducible recombinant oncogene. Also disclosed is a method of testing a compound for anti-tumor effects. The method includes producing tumorigenic mouse cells the tumorigenicity depends on expression of a recombinant gene of interest, implanting the cells in mice and obtaining tumors from the implanted cells, administering test compounds to the mice, and determining anti-tumor effects, if any, of the compounds.

Directed complementation

The disclosure provides a method for identifying cancer tissue sensitive to treatment with an inhibitor of Notch receptor activation. The method comprises determining the level of HeyL gene expression in a sample derived from the cancer tissue, wherein an elevated level of HeyL gene expression alone in the sample indicates sensitivity to the cancer tissue to treatment with an inhibitor of Notch receptor activation.

Identifying cancers sensitive to treatment with inhibitors of notch signaling

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Arlington, MA, United States of America

Ronan O'Hagan