Claims for Patent: 9,266,956

Summary for Patent: 9,266,956

Title:	Methods of inhibiting proliferation of CD40-expressing cancer cells with anti-CD40 antibodies
Abstract:	The present invention provides high affinity anti-CD40 monoclonal antibodies and related compositions, which may be used in any of a variety of therapeutic methods for the treatment of cancer and other diseases.
Inventor(s):	Zhang; Yongke (Palo Alto, CA), Yu; Guo-Liang (Hillsborough, CA), Zhu; Weimin (San Francisco, CA)
Assignee:	Apexigen, Inc. (San Carlos, CA)
Application Number:	14/613,110
Patent Claims:	1. A method for inhibiting proliferation of a CD40-expressing cancer cell in a patient having a cancer, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises (i) a heavy chain variable region comprising the VHCDR1 region set forth in SEQ ID NO:3, the VHCDR2 region set forth in SEQ ID NO:4, and the VHCDR3 region set forth SEQ ID NO:5; and (ii) a light chain variable region comprising the VLCDR1 region set forth in SEQ ID NO:6, the VLCDR2 region set forth in SEQ ID NO:7, and the VLCDR3 region set forth in SEQ ID NO: 8; or a variant of said antibody, or an antigen-binding fragment thereof, comprising heavy and light chain variable regions identical to the heavy and light chain variable regions of (i) and (ii) except for up to 8 amino acid substitutions in said CDR regions. 2. The method of claim 1 wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 3. A method for inhibiting proliferation of a CD40-expressing cancer cell in a patient having a cancer, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:9 and a light chain variable region which comprises an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:10. 4. The method of claim 3, wherein the light chain variable region which comprises the amino acid sequence set forth in SEQ ID NO:10. 5. The method of claim 3, wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 6. A method for inhibiting proliferation of a CD40-expressing cancer cell in a patient having a cancer, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:9 and a light chain variable region which comprises the amino acid sequence set forth in SEQ ID NO:10. 7. The method of claim 6, wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 8. A method for inhibiting growth of a CD40-expressing tumor in a patient having a cancer, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises (i) a heavy chain variable region comprising the VHCDR1 region set forth in SEQ ID NO:3, the VHCDR2 region set forth in SEQ ID NO:4, and the VHCDR3 region set forth SEQ ID NO:5; and (ii) a light chain variable region comprising the VLCDR1 region set forth in SEQ ID NO:6, the VLCDR2 region set forth in SEQ ID NO:7, and the VLCDR3 region set forth in SEQ ID NO: 8; or a variant of said antibody, or an antigen-binding fragment thereof, comprising heavy and light chain variable regions identical to the heavy and light chain variable regions of (i) and (ii) except for up to 8 amino acid substitutions in said CDR regions. 9. The method of claim 8 wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 10. A method for inhibiting growth of a CD40-expressing tumor in a patient having a cancer, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:9 and a light chain variable region which comprises an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:10. 11. The method of claim 10, wherein the light chain variable region which comprises the amino acid sequence set forth in SEQ ID NO:10. 12. The method of claim 10, wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 13. A method for inhibiting growth of a CD40-expressing tumor in a patient having a cancer, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:9 and a light chain variable region which comprises the amino acid sequence set forth in SEQ ID NO:10. 14. The method of claim 13, wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 15. A method for activating antibody dependent cellular cytotoxicity (ADCC) against a CD40-expressing cancer cell in a patient having a cancer, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises (i) a heavy chain variable region comprising the VHCDR1 region set forth in SEQ ID NO:3, the VHCDR2 region set forth in SEQ ID NO:4, and the VHCDR3 region set forth SEQ ID NO:5; and (ii) a light chain variable region comprising the VLCDR1 region set forth in SEQ ID NO:6, the VLCDR2 region set forth in SEQ ID NO:7, and the VLCDR3 region set forth in SEQ ID NO: 8; or a variant of said antibody, or an antigen-binding fragment thereof, comprising heavy and light chain variable regions identical to the heavy and light chain variable regions of (i) and (ii) except for up to 8 amino acid substitutions in said CDR regions. 16. The method of claim 15 wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 17. A method for activating ADCC against a CD40-expressing cancer cell in a patient having a cancer, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:9 and a light chain variable region which comprises an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:10. 18. The method of claim 17, wherein the light chain variable region which comprises the amino acid sequence set forth in SEQ ID NO:10. 19. The method of claim 17, wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 20. A method for activating ADCC against a CD40-expressing cancer cell in a patient having a cancer, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:9 and a light chain variable region which comprises the amino acid sequence set forth in SEQ ID NO:10. 21. The method of claim 20, wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 22. A method for activating an antigen presenting cell in a patient, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises (i) a heavy chain variable region comprising the VHCDR1 region set forth in SEQ ID NO:3, the VHCDR2 region set forth in SEQ ID NO:4, and the VHCDR3 region set forth SEQ ID NO:5; and (ii) a light chain variable region comprising the VLCDR1 region set forth in SEQ ID NO:6, the VLCDR2 region set forth in SEQ ID NO:7, and the VLCDR3 region set forth in SEQ ID NO: 8; or a variant of said antibody, or an antigen-binding fragment thereof, comprising heavy and light chain variable regions identical to the heavy and light chain variable regions of (i) and (ii) except for up to 8 amino acid substitutions in said CDR regions. 23. The method of claim 22, wherein the antigen presenting cell is a B cell, a dendritic cell or a macrophage. 24. A method for activating an antigen presenting cell in a patient, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:9 and a light chain variable region which comprises an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:10. 25. The method of claim 24, wherein the light chain variable region which comprises the amino acid sequence set forth in SEQ ID NO:10. 26. The method of claim 24, wherein the antigen presenting cell is a B cell, a dendritic cell or a macrophage. 27. A method for activating an antigen presenting cell in a patient, comprising administering to the patient a composition comprising a physiologically acceptable carrier and a therapeutically effective amount of an isolated antibody, or an antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:9 and a light chain variable region which comprises the amino acid sequence set forth in SEQ ID NO:10. 28. The method of claim 27 wherein the antigen presenting cell is a B cell, a dendritic cell or a macrophage.

Details for Patent 9,266,956

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2031-04-29
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2031-04-29
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2031-04-29