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US 10,870,693 B2Granted
Therapeutic combination and methods of treatment with a DLL4 antagonist and an anti-hypertensive agent
AssigneeOncoMed Pharmaceuticals, Inc.
InventorsRobert Joseph Stagg, Steven Eugene Benner
Life of this patent
Estimating the term…
Abstract
Methods for treating cancer comprising administering a DLL4 antagonist and one or more anti-hypertensive agents are described. Also described are pharmaceutical compositions comprising a DLL4 antagonist and one or more anti-hypertensive agents, and kits comprising the same.
Claims22
A method of treating cancer, comprising:
- (i) administering to a subject in need thereof an antibody that specifically binds delta like ligand-4 (DLL4);
- wherein the antibody comprises a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:6, and wherein the heavy chain variable region comprises a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3, and the heavy chain variable region comprises one or more of a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:1, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:5;
- and
- wherein the antibody comprises a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:10, and wherein the light chain variable region comprises a light chain CDR1, a light chain CDR2, and a light chain CDR3, and the light chain variable region comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:7, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:8, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:9;
- and
- (ii) administering a therapeutically effective amount of one or more anti-hypertensive agents to the subject to control hypertension related to the antibody.
3 more elements
A method of ameliorating hypertension in a patient receiving treatment with an antibody that specifically binds DLL4, comprising administering to the patient a therapeutically effective amount of one or more anti-hypertensive agents to control hypertension related to the antibody;
- wherein the antibody comprises a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:6, and wherein the heavy chain variable region comprises a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3, and the heavy chain variable region comprises one or more of a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:1, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:5;
- and
- wherein the antibody comprises a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:10, and wherein the light chain variable region comprises a light chain CDR1, a light chain CDR2, and a light chain CDR3, and the light chain variable region comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:7, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:8, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:9.
A method of reducing hypertension in a patient receiving treatment with an antibody that specifically binds DLL4, comprising administering to the patient a therapeutically effective amount of one or more anti-hypertensive agents to control hypertension related to the antibody;
- wherein the antibody comprises a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:6, and wherein the heavy chain variable region comprises a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3, and the heavy chain variable region comprises one or more of a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:1, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:5;
- and
- wherein the antibody comprises a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:10, and wherein the light chain variable region comprises a light chain CDR1, a light chain CDR2, and a light chain CDR3, and the light chain variable region comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:7, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:8, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:9.
A method of monitoring a subject for the development of hypertension related to an antibody that specifically binds DLL4, comprising:
- (i) administering to the subject an antibody that specifically binds DLL4;
- wherein the antibody comprises a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:6, and wherein the heavy chain variable region comprises a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3, and the heavy chain variable region comprises one or more of a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:1, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:5;
- and
- wherein the antibody comprises a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:10, and wherein the light chain variable region comprises a light chain CDR1, a light chain CDR2, and a light chain CDR3, and the light chain variable region comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:7, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:8, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:9;
- (ii) measuring blood pressure of the subject after receiving treatment with the antibody;
- and
- (iii) administering a therapeutically effective amount of one or more anti-hypertensive agents to the subject to control hypertension related to the antibody.
4 more elements
Dependencies are inferred from the claim text.