Methods for Treating Melanoma
AssigneeOncoMed Pharmaceuticals, Inc.
InventorsTimothy C. Hoey, Lucia Beviglia
Life of this patent
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Abstract
Methods of inhibiting melanoma tumor growth, methods of treating melanoma and metastatic melanoma, and methods of reducing the frequency of tumor initiating cells (or cancer stem cells) in melanoma tumors are described. The methods described comprise administering a DLL4 antagonist (e.g., an antibody that specifically binds the extracellular domain of human DLL4) to a subject. Related polypeptides and polynucleotides, compositions comprising the DLL4 antagonists, and methods of making the DLL4 antagonists are also described.
Claims26
1-75. (canceled)
A method of inhibiting growth of a melanoma tumor comprising administering a therapeutically effective amount of a delta like ligand-4 (DLL4) antagonist to a human subject in need thereof, wherein the DLL4 antagonist is an antibody comprising:
- (a) a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISCYNGATNYNQKFKG (SEQ ID NO:2), YISSYNGATNYNQKFKG (SEQ ID NO:3), or YISVYNGATNYNQKFKG (SEQ ID NO:4), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5);
- and/or
- (b) a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:9), a light chain CDR2 comprising AASNQGS (SEQ ID NO:10), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:11).
A method of treating melanoma in a human subject, comprising:
- (a) determining if the melanoma comprises a mutation in the MAPK pathway, and
- (b) administering to the subject a therapeutically effective of a DLL4 antagonist, wherein the DLL4 antagonist is an antibody comprising:
- (i) a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISCYNGATNYNQKFKG (SEQ ID NO:2), YISSYNGATNYNQKFKG (SEQ ID NO:3), or YISVYNGATNYNQKFKG (SEQ ID NO:4), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5);
- and/or
- (ii) a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:9), a light chain CDR2 comprising AASNQGS (SEQ ID NO:10), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:11).
A method of reducing tumor initiating cell frequency in a melanoma tumor, comprising contacting the melanoma tumor with an effective amount of a DLL4 antagonist, wherein the DLL4 antagonist is an antibody comprising:
- (a) a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISCYNGATNYNQKFKG (SEQ ID NO:2), YISSYNGATNYNQKFKG (SEQ ID NO:3), or YISVYNGATNYNQKFKG (SEQ ID NO:4), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5);
- and/or
- (b) a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:9), a light chain CDR2 comprising AASNQGS (SEQ ID NO:10), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:11).
A method of inhibiting metastases in a human subject who has melanoma, comprising administering to the subject a therapeutically effective amount of a DLL4 antagonist, wherein the DLL4 antagonist is an antibody comprising:
- (a) a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISCYNGATNYNQKFKG (SEQ ID NO:2), YISSYNGATNYNQKFKG (SEQ ID NO:3), or YISVYNGATNYNQKFKG (SEQ ID NO:4), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5);
- and/or
- (b) a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:9), a light chain CDR2 comprising AASNQGS (SEQ ID NO:10), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:11).
A method of inhibiting growth of a melanoma tumor comprising administering a therapeutically effective amount of a DLL4 antagonist to a human subject in need thereof, wherein the DLL4 antagonist is an antibody that specifically binds an epitope within amino acids 27-217 of the extracellular domain of human DLL4 (SEQ ID NO:14).
A method of treating a human subject who has melanoma which is substantially non-responsive to at least one B-raf inhibitor, comprising administering to the subject a therapeutically effective amount of a DLL4 antagonist, wherein the DLL4 antagonist is an antibody comprising:
- (a) a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISCYNGATNYNQKFKG (SEQ ID NO:2), YISSYNGATNYNQKFKG (SEQ ID NO:3), or YISVYNGATNYNQKFKG (SEQ ID NO:4), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5);
- and/or
- (b) a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:9), a light chain CDR2 comprising AASNQGS (SEQ ID NO:10), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:11).
Dependencies are inferred from the claim text.