Anti-EFNA4 antibody-drug conjugates
AssigneesPfizer Inc., Abbvie Stemcentrx LLC
InventorsMarc Isaac Damelin, Kiran Manohar Khandke, Puja Sapra, Alexander John Bankovich, Scott J. Dylla
Life of this patent
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Abstract
The present invention provides for anti-EFNA4 antibody-drug conjugates and methods for preparing and using the same.
Claims25
A method of treating an EFNA-associated neoplastic disorder comprising administering a therapeutically effective amount of a composition comprising an antibody-drug conjugate of the formula Ab-(L-D) to a subject in need thereof, wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, that binds to EFNA4 and comprises a heavy chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 15, 19, and 23 and a light chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 29, 33, and 35;
- and
- (b) L-D is a linker-drug moiety, wherein L is a linker and D is a drug, and wherein D is a calicheamicin or calicheamicin derivative.
A method of reducing the frequency of tumor initiating cells in a tumor cell population in vivo, the method comprising contacting a tumor cell population with an antibody-drug conjugate of the formula Ab-(L-D), wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, that binds to EFNA4 and comprises a heavy chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 15, 19, and 23 and a light chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 29, 33, and 35;
- and
- (b) L-D is a linker-drug moiety, wherein L is a linker and D is a drug, and wherein D is a calicheamicin or calicheamicin derivative;
- and
- whereby the frequency of tumor initiating cells in the tumor cell population is reduced.
A method of treating an EFNA-associated ovarian cancer comprising administering a therapeutically effective amount of a composition comprising an antibody-drug conjugate of the formula Ab-(L-D) to a subject in need thereof, wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, that binds to EFNA4 and comprises a heavy chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 15, 19, and 23 and a light chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 29, 33, and 35;
- and (b) L-D is a linker-drug moiety, wherein L is a linker and D is a drug, and wherein D is a calicheamicin or calicheamicin derivative.
A method of treating an EFNA-associated breast cancer comprising administering a therapeutically effective amount of a composition comprising an antibody-drug conjugate of the formula Ab-(L-D) to a subject in need thereof, wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, that binds to EFNA4 and comprises a heavy chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 15, 19, and 23 and a light chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 29, 33, and 35;
- and (b) L-D is a linker-drug moiety, wherein L is a linker and D is a drug, and wherein D is a calicheamicin or calicheamicin derivative.
A method of treating an EFNA-associated lung cancer comprising administering a therapeutically effective amount of a composition comprising an antibody-drug conjugate of the formula Ab-(L-D) to a subject in need thereof, wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, that binds to EFNA4 and comprises a heavy chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 15, 19, and 23 and a light chain variable region comprising three CDRs set forth as SEQ ID NOs:
- 29, 33, and 35;
- and (b) L-D is a linker-drug moiety, wherein L is a linker and D is a drug, and wherein D is a calicheamicin or calicheamicin derivative.
Dependencies are inferred from the claim text.