Optimized anti-CD30 antibodies

• US 9,574,006 B2
• Filed: 06/17/2011
• Issued: 02/21/2017
• Est. Priority Date: 10/06/2005
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Lazar, Gregory Alan, Desjarlais, John R., Hammond, Philip W., Carmichael, David F., Chen, Bao-lu, Chu, Seung Y., Karki, Sher Bahadur, Kunkel, Lori
• Primary Examiner(s): HADDAD, MAHER M
• Application Number:
  US13/163,465
• Publication Number:
  US 20120014943A1
• Time in Patent Office: 2,076 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/72 Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]

Abstract

An antibody that targets CD30, wherein the antibody comprises at least one modification relative to a parent antibody and the antibody binds with altered affinity to an FcγR or alters effector function as compared to the parent antibody. Also disclosed are methods of using the anti-CD30 antibody.

Claims

1. A method of treating a CD30-expressing cancer comprising administering to a subject in need thereof an anti-CD30 antibody, said antibody comprising:

at least one amino acid substitution in the Fc region at a position selected from the group consisting of 239D and 332E relative to a parent Fc region; and

a heavy chain and a light chain, wherein said heavy chain comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO 11, and wherein said light chain comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO 10, and

said antibody binds with enhanced affinity to FcyRllla as compared to a parent antibody, wherein numbering is according to the EU index as in Kabat.

2. The method of claim 1, wherein a first substitution is 239D.

3. The method of claim 2, wherein a second substitution is 332E.

4. The method of claim 3, wherein said indication is a the CD30-expressing cancer selected from carcinoma, B cell tumor, lymphoma, blastoma, sarcoma (Including liposarcoma), neuroendocrine tumors, mesothelioma, schwanoma, meningioma, adenocarcinoma, melanoma, and leukemia or lymphoid malignancies.

5. The method of claim 4, wherein said indication the CD30-expressing cancer is selected from Hodgkin'"'"'s lymphoma, anaplastic large-cell lymphoma, (ALCL), immunoblastic lymphoma, multiple myeloma, adult T-cell lymphoma leukemia, mycosis fungoides, germ-cell malignancies, chronic lymphocytic leukemia (CLL), follicular B-cell lymphoma, hairy cell leukemia, T-cell lymphoblastic lymphoma, and adult T-cell leukemia lymphoma.

6. The method of claim 5, wherein the CD30-expressing cancer is Hodgkin'"'"'s lymphoma.

7. The method of claim 1, wherein the CD30-expressing cancer is selected from carcinoma, B cell tumor, lymphoma, blastoma, sarcoma (including liposarcoma), neuroendocrine tumors, mesothelioma, schwanoma, meningioma, adenocarcinoma, melanoma, and leukemia or lymphoid malignancies.

8. The method of claim 7, wherein the CD30-expressing cancer is selected from Hodgkin'"'"'s lymphoma, anaplastic large-cell lymphoma, (ALCL), immunoblastic lymphoma, multiple myeloma, adult T-cell lymphoma leukemia, mycosis fungoides, germ-cell malignancies, chronic lymphocytic leukemia (CLL), follicular B-cell lymphoma, hairy cell leukemia, T-cell lymphoblastic lymphoma, and adult T-cell leukemia lymphoma.

9. The method of claim 8, wherein the CD30-expressing cancer is Hodgkin'"'"'s lymphoma.