CD30 bispecific antibodies and method of immunotherapy of CD30+ malignancies

Patent metadata

Field	Value
Publication number	US-11667721-B2
Application number	US-201916580625-A
Country	US
Kind code	B2
Filing date	Sep 24, 2019
Priority date	Sep 24, 2018
Publication date	Jun 6, 2023
Grant date	Jun 6, 2023

Abstract

The present invention provides novel bispecific antibodies that bind to human CD30 and uses thereof. Methods of treating cancer using the bispecific antibodies described herein are also provided.

First claim

The invention claimed is:

1. An isolated bispecific antibody capable of binding human CD30 and to CD3 comprising an anti-CD30 antibody or antigen binding portion thereof and an anti-CD3 antibody or antigen binding portion thereof,
wherein the anti-CD30 antibody or antigen binding portion thereof comprises:
(a) a light chain variable domain comprising a CDRL1 region of SEQ ID NO:2 or a sequence with at least 85% similarity to SEQ ID NO:2, a CDRL2 region of SEQ ID NO:3 or a sequence with at least 85% similarity to SEQ ID NO:3, and a CDRL3 region of SEQ ID NO:4 or a sequence with at least 85% similarity to SEQ ID NO:4 and a heavy chain variable domain comprising a CDRH1 region of SEQ ID NO:6 or a sequence with at least 85% similarity to SEQ ID NO:6, a CDRH2 region of SEQ ID NO:7 or a sequence with at least 85% similarity to SEQ ID NO:7, and a CDRH3 region of SEQ ID NO:8 or a sequence with at least 85% similarity to SEQ ID NO:8;
(b) a light chain variable domain comprising a CDRL1 region of SEQ ID NO:10 or a sequence with at least 85% similarity to SEQ ID NO:10, a CDRL2 region of SEQ ID NO:11 or a sequence with at least 85% similarity to SEQ ID NO:11, and a CDRL3 region of SEQ ID NO:12 or a sequence with at least 85% similarity to SEQ ID NO:12 and a heavy chain variable domain comprising a CDRH1 region of SEQ ID NO:14 or a sequence with at least 85% similarity to SEQ ID NO:14, a CDRH2 region of SEQ ID NO:15 or a sequence with at least 85% similarity to SEQ ID NO:15, and a CDRH3 region of SEQ ID NO:16 or a sequence with at least 85% similarity to SEQ ID NO:16;
(c) a light chain variable domain comprising a CDRL1 region of SEQ ID NO:18 or a sequence with at least 85% similarity to SEQ ID NO:18, a CDRL2 region of SEQ ID NO:19 or a sequence with at least 85% similarity to SEQ ID NO:19, and a CDRL3 region of SEQ ID NO:20 or a sequence with at least 85% similarity to SEQ ID NO:20 and a heavy chain variable domain comprising a CDRH1 region of SEQ ID NO:22 or a sequence with at least 85% similarity to SEQ ID NO:22, a CDRH2 region of SEQ ID NO:23 or a sequence with at least 85% similarity to SEQ ID NO:23, and a CDRH3 region of SEQ ID NO:24 or a sequence with at least 85% similarity to SEQ ID NO:24;
(d) a light chain variable domain comprising a CDRL1 region of SEQ ID NO:26 or a sequence with at least 85% similarity to SEQ ID NO:26, a CDRL2 region of SEQ ID NO:27 or a sequence with at least 85% similarity to SEQ ID NO:27, and a CDRL3 region of SEQ ID NO:28 or a sequence with at least 85% similarity to SEQ ID NO:28and a heavy chain variable domain comprising a CDRH1 region of SEQ ID NO:30 or a sequence with at least 85% similarity to SEQ ID NO:30, a CDRH2 region of SEQ ID NO:31 or a sequence with at least 85% similarity to SEQ ID NO:31, and a CDRH3 region of SEQ ID NO:32 or a sequence with at least 85% similarity to SEQ ID NO:32; or
(e) a light chain variable domain comprising a CDRL1 region of SEQ ID NO:34 or a sequence with at least 85% similarity to SEQ ID NO:34, a CDRL2 region of SEQ ID NO:35 or a sequence with at least 85% similarity to SEQ ID NO:35, and a CDRL3 region of SEQ ID NO:36 or a sequence with at least 85% similarity to SEQ ID NO:36 and a heavy chain variable domain comprising a CDRH1 region of SEQ ID NO:38 or a sequence with at least 85% similarity to SEQ ID NO:38, a CDRH2 region of SEQ ID NO:39 or a sequence with at least 85% similarity to SEQ ID NO:39, and a CDRH3 region of SEQ ID NO:40 or a sequence with at least 85% similarity to SEQ ID NO:40.

2. The isolated bispecific antibody of claim 1 , wherein the anti-CD30 antibody or antigen binding portion thereof comprises a heavy and a light chain selected from the group consisting of:
(a) a light chain comprising SEQ ID NO:1 or a sequence with at least 85% similarity to SEQ ID NO:1, and a heavy chain comprising SEQ ID NO:5 or a sequence with at least 85% similarity to SEQ ID NO:5;
(b) a light chain comprising SEQ ID NO:9 or a sequence with at least 85% similarity to SEQ ID NO:9, and a heavy chain comprising SEQ ID NO:13 or a sequence with at least 85% similarity to SEQ ID NO:13;
(c) a light chain comprising SEQ ID NO:17 or a sequence with at least 85% similarity to SEQ ID NO:17, and a heavy chain comprising SEQ ID NO:21 or a sequence with at least 85% similarity to SEQ ID NO:21;
(d) a light chain comprising SEQ ID NO:25 or a sequence with at least 85% similarity to SEQ ID NO:25, and a heavy chain comprising SEQ ID NO:29 or a sequence with at least 85% similarity to SEQ ID NO:29; and
(e) a light chain comprising SEQ ID NO:33 or a sequence with at least 85% similarity to SEQ ID NO:33, and a heavy chain comprising SEQ ID NO:37 or a sequence with at least 85% similarity to SEQ ID NO:37.

3. The isolated bispecific antibody of claim 1 , wherein the anti-CD30 antibody or antigen binding portion thereof is directly or indirectly conjugated to the T cell surface antigen antibody or antigen binding portion thereof.

4. The isolated bispecific antibody of claim 3 , wherein the anti-CD30 antibody or antigen binding portion thereof is directly conjugated to the T cell surface antigen antibody or antigen binding portion thereof.

5. The isolated bispecific antibody of claim 4 , wherein the anti-CD30 antibody or antigen binding portion thereof is directly conjugated to the T cell surface antigen antibody or antigen binding portion thereof via a linker.

6. The isolated bispecific antibody of claim 1 , wherein the anti-CD3 antibody is a monoclonal antibody.

7. The isolated bispecific antibody of claim 6 , wherein the anti-CD3 antibody is OKT3 made by the hybridoma with ATCC accession number CRL 8001.

8. A pharmaceutical composition comprising the isolated bispecific antibody of claim 1 and a pharmaceutically acceptable carrier.

9. A method of treating a patient having a CD30+ cancer, the method comprising
(a) administering a therapeutically effective amount of the bispecific antibody of claim 1 to reduce or inhibit CD30+ cancer growth.

10. The method of claim 9 , wherein the CD30+ cancer is Hodgkin's lymphoma or AML.

11. The method of claim 9 , wherein the method further comprises administering an effective amount of a cancer treatment.

12. A method of inhibiting growth of a tumor cell expressing CD30, comprising contacting the tumor cell with an effective amount of the antibody or antigen binding fragment thereof of claim 1 such that the growth of the cell is inhibited.

13. A method of enhancing a T cell-mediated immune response against a CD30+ tumor cell, the method comprising administering a therapeutically effective amount of the bispecific antibody of claim 1 to increase the T cell-mediated immune response as compared to treatment without the bispecific antibody.

14. An isolated bispecific antibody capable of binding human CD30 and to a NK cell surface antigen, the bispecific antibody comprising an anti-CD30 antibody or antigen binding portion thereof and an anti-NK cell surface antigen antibody or antigen binding portion thereof,
wherein the anti-NK cell surface antigen antibody or antigen binding portion thereof is an anti-CD16 antibody, and
wherein the anti-CD30 antibody or antigen binding portion thereof comprises:
(a) a light chain variable domain comprising a CDRL1 region of SEQ ID NO:2, a CDRL2 region of SEQ ID NO:3, and a CDRL3 region of SEQ ID NO:4 and a heavy chain variable domain comprising a CDRH1 region of SEQ ID NO:6, a CDRH2 region of SEQ ID NO:7, and a CDRH3 region of SEQ ID NO:8;
(b) a light chain variable domain comprising a CDRL1 region of SEQ ID NO:10, a CDRL2 region of SEQ ID NO:11, and a CDRL3 region of SEQ ID NO:12 and a heavy chain variable domain comprising a CDRH1 regi

Assignees

• Medical College Of Wisconsin Inc
• Univ Virginia Patent Foundation

Inventors

• Medin Jeffrey A
• Lum Lawrence G
• Oldham Robyn A A
• Thakur Archana

Classifications

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K16/2878 Primary

  against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K16/2809

  against the T-cell receptor (TcR)-CD3 complex · CPC title