Methods and Monitoring of Treatment with a DLL4 Antagonist
AssigneeOncoMed Pharmaceuticals, Inc.
InventorsSTEVEN EUGENE BENNER, ROBERT JOSEPH STAGG, JAKOB DUPONT
Life of this patent
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Abstract
Methods for treating diseases such as cancer comprising administering a DLL4 antagonist, either alone or in combination with other anti-cancer agents, and monitoring for cardiovascular side effects and/or toxicity.
Claims22
(canceled)
A method of detecting the development of a cardiovascular side effect and/or toxicity in a subject receiving treatment with an antibody that specifically binds human delta-like protein 4 (DLL4), comprising:
- (a) determining the level of B-type natriuretic peptide (BNP) in a sample from the subject;
- (b) comparing the level of BNP in the sample to a predetermined level of BNP;
- and
- (c) administering to the subject a therapeutically effective amount of an ACE inhibitor and/or a β-blocker if the level of BNP is above the predetermined level of BNP;
- wherein the antibody comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISSYNGATNYNQKFKG (SEQ ID NO:3), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5), and a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:6), a light chain CDR2 comprising AASNQGS (SEQ ID NO:7), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:8).
A method of identifying a subject as eligible for treatment with an antibody that specifically binds human delta-like protein 4 (DLL4), comprising:
- (a) determining the level of B-type natriuretic peptide (BNP) in a sample from the subject prior to treatment;
- (b) identifying the subject as eligible for treatment with the antibody if the level of BNP is below a predetermined level;
- and
- (c) administering the antibody that specifically binds DLL4 to the subject, wherein the antibody comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISSYNGATNYNQKFKG (SEQ ID NO:3), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5), and a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:6), a light chain CDR2 comprising AASNQGS (SEQ ID NO:7), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:8).
A method for reducing a cardiovascular side effect and/or toxicity in a subject receiving treatment with an antibody that specifically binds human delta-like protein 4 (DLL4), comprising:
- (a) determining the level of B-type natriuretic peptide (BNP) in a sample from the subject;
- (b) comparing the level of BNP in the sample to a predetermined level of BNP;
- and
- (c) administering to the subject a therapeutically effective amount of an ACE inhibitor and/or a β-blocker if the level of BNP in the sample is higher than the predetermined level of BNP,
- and wherein the antibody comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISSYNGATNYNQKFKG (SEQ ID NO:3), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5), and a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:6), a light chain CDR2 comprising AASNQGS (SEQ ID NO:7), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:8).
A method of preventing or attenuating the development of a cardiovascular side effect and/or toxicity in subject receiving treatment with an antibody that specifically binds human delta-like protein 4 (DLL4), comprising:
- (a) determining the level of B-type natriuretic peptide (BNP) in a sample from the subject prior to treatment;
- (b) comparing the level of BNP in the sample to a predetermined level of BNP;
- (c) administering to the subject a therapeutically effective amount of an ACE inhibitor and/or a β-blocker, if the level of BNP in the sample is higher than the predetermined level of BNP;
- and
- (d) administering to the subject the antibody that specifically binds DLL4, wherein the antibody comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISSYNGATNYNQKFKG (SEQ ID NO:3), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5), and a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:6), a light chain CDR2 comprising AASNQGS (SEQ ID NO:7), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:8).
A method of screening a subject for the risk of a cardiovascular side effect and/or toxicity from treatment with an antibody that specifically binds human delta-like protein 4 (DLL4), comprising:
- (a) determining the level of B-type natriuretic peptide (BNP) in a sample from the subject;
- (b) comparing the level of BNP in the sample to a predetermined level of BNP, wherein if the level of BNP in the sample is higher than the predetermined level of BNP then the subject is at risk for a cardiovascular side effect and/or toxicity;
- and
- (c) administering a therapeutically effective amount of an ACE inhibitor and/or a β-blocker prior to treatment with the antibody if the subject is at risk for a cardiovascular side effect and/or toxicity;
- and wherein the antibody comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:1), a heavy chain CDR2 comprising YISSYNGATNYNQKFKG (SEQ ID NO:3), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:5), and a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:6), a light chain CDR2 comprising AASNQGS (SEQ ID NO:7), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:8).
Dependencies are inferred from the claim text.