Compositions and methods for diagnosing and treating cancer
AssigneeOncoMed Pharmaceuticals, Inc.
InventorsAustin Gurney, Fumiko Axelrod, Tim Hoey, Sanjeev Satyal
Life of this patent
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Abstract
An isolated antibody that specifically binds to an extracellular domain of human DLL4 and affects growth of a tumor comprising cancer stem cells is described. Also described is a method of treating cancer comprising administering a therapeutically effective amount of an anti-DLL4 antibody.
Claims56
An isolated antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), wherein the antibody affects growth of a tumor comprising cancer stem cells.
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11-12. (canceled)
14-18. (canceled)
An antibody that competes for specific binding to human DLL4 with an antibody produced by hybridoma deposited with ATCC on Sep. 28, 2007 and having ATCC deposit no. PTA-8670.
A humanized antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), wherein the antibody comprises:
- (i) a heavy chain variable region comprising a nonhuman antigen determination region and a human heavy chain variable framework region, and (ii) a light chain variable region comprising a nonhuman antigen determination region and a human light chain variable framework region.
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26-27. (canceled)
30-31. (canceled)
An isolated antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), wherein the antibody inhibits DLL4 binding to a Notch receptor.
A pharmaceutical composition comprising:
- i. an isolated antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), wherein the antibody affects growth of a tumor comprising cancer stem cells;
- and
- ii. a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising:
- i. an isolated antibody that competes for specific binding to human DLL4 with an antibody produced by hybridoma deposited with ATCC on Sep. 28, 2007 and having ATCC deposit no. PTA-8670.
- ii. a pharmaceutically acceptable carrier.
An isolated polynucleotide vector encoding an antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), wherein the antibody affects growth of a tumor comprising cancer stem cells.
An isolated polynucleotide vector encoding a heavy chain variable region of an antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), wherein the antibody affects growth of a tumor comprising cancer stem cells.
An isolated polynucleotide vector encoding a light chain variable region of an antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), wherein the antibody affects growth of a tumor comprising cancer stem cells.
A host cell comprising one or more polynucleotide vectors encoding an antibody, wherein said antibody specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), wherein the antibody affects growth of a tumor comprising cancer stem cells.
A method of treating cancer comprising administering to a patient a therapeutically effective amount of an antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27).
A method of treating cancer comprising administering to a patient a therapeutically effective amount of a humanized antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), wherein the antibody comprises:
- (i) a heavy chain variable region comprising a nonhuman antigen determination region and a human heavy chain variable framework region, and (ii) a light chain variable region comprising a nonhuman antigen determination region and a human light chain variable framework region.
A method of treating cancer comprising administering to a patient a therapeutically effective amount of an antibody that specifically to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27) in combination with a second therapeutic agent.
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56-57. (canceled)
A method of diagnosing cancer comprising contacting a patient sample with an antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), and diagnosing cancer based on the localization of DLL4 expression in the patient sample.
A method of manufacturing an antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), the method comprising:
- i. transforming host cells with a polynucleotide expression vector or vectors encoding the antibody;
- ii. culturing the host cells under conditions permitting expression of the antibody;
- and
- iii. purifying the antibody from the culture medium.
A transformed cell line expressing an antibody that specifically binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27).
A hybridoma that secretes antibody 21M18 deposited with ATCC on Sep. 28, 2007 and having ATCC deposit no. PTA-8670.
A method of producing antibody 21M18 by culturing a hybridoma deposited with ATCC on Sep. 28, 2007 and having ATCC deposit no. PTA-8670.
A monoclonal antibody produced by hybridoma deposited with ATCC on Sep. 28, 2007 and having ATCC deposit no. PTA-8670.
A kit comprising a container and a composition contained therein, wherein the composition comprises an antibody that binds to a human DLL4 epitope comprising amino acids within human DLL4 N-terminal region (SEQ ID NO:
- 27), and further comprises a package insert indicating that the composition can be used to treat cancer.
Dependencies are inferred from the claim text.