Bispecific anti-CD28 × anti-CD22 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-11396544-B2
Application number	US-201916719015-A
Country	US
Kind code	B2
Filing date	Dec 18, 2019
Priority date	Dec 19, 2018
Publication date	Jul 26, 2022
Grant date	Jul 26, 2022

Abstract

The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human CD-22. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD-22, such as B-cell lymphomas. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.

First claim

What is claimed is:

1. An isolated bispecific antigen binding molecule comprising:
a) a first antigen-binding domain (D1) that binds human CD28 and comprises a heavy chain variable region (HCVR) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) comprising amino acid sequences of SEQ ID NOs: 28, 30, 32, and a light chain variable region (LCVR) comprising three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) comprising amino acid sequences of SEQ ID NOs: 12, 14, 16; and
b) a second antigen-binding domain (D2) that specifically binds human CD22 on a target tumor cell and comprises HCVR CDRs comprising amino acid sequences of SEQ ID NOs: 4, 6, 8, and LCVR CDRs comprising amino acid sequences of SEQ ID NOs: 12, 14, 16.

2. The isolated bispecific antigen binding molecule of claim 1 , wherein the second antigen-binding domain (D2) binds an epitope on human CD22 comprising one or more amino acids of SEQ ID NO:57, SEQ ID NO:58, and/or SEQ ID NO:59.

3. The isolated bispecific antigen binding molecule of claim 1 , wherein the bispecific antigen binding molecule has a property selected from the group consisting of:
(a) binds human CD22 with a K D of less than about 15 nM as measured by surface plasmon resonance at 25° C.;
(b) binds Macaca fascicularis CD22 with a K D of less than about 60 μM as measured by surface plasmon resonance at 25° C.;
(c) binds human CD28 with a K D of less than about 45 μM as measured by surface plasmon resonance at 25° C.;
(d) binds to the surface of cells expressing human CD28 with an EC 50 of less than about 1×10 −8 M as measured by an in vitro FACS binding assay;
(e) binds to the surface of cells expressing human CD22 with an EC 50 of less than about 1×10 −8 M as measured by an in vitro FACS binding assay; and
(f) demonstrates a costimulatory effect when used in conjunction with an anti-CD20×CD3 bispecific antibody.

4. The isolated bispecific antigen-binding molecule of claim 1 , wherein the first antigen-binding domain comprises a HCVR/LCVR pair comprising the amino acid sequences of SEQ ID NOs: 26/10.

5. The isolated bispecific antigen-binding molecule of claim 1 , wherein the second antigen-binding domain comprises a HCVR/LCVR pair
comprising the amino acid sequences of SEQ ID NO: 2/10.

6. The isolated bispecific antigen-binding molecule of claim 1 , comprising:
a) a first antigen binding domain that comprises a HCVR/LCVR pair comprising amino acid sequences of SEQ ID NOs:26/10; and
b) a second antigen binding domain that comprises a HCVR/LCVR pair comprising amino acid sequences of SEQ ID NOs: 2/10.

7. A pharmaceutical composition comprising the bispecific antigen-binding molecule of claim 1 , and a pharmaceutically acceptable carrier or diluent.

8. A nucleic acid molecule comprising a nucleotide sequence encoding the bispecific antigen binding molecule of claim 1 .

9. An expression vector comprising the nucleic acid of claim 8 .

10. A host cell comprising the expression vector of claim 9 .

Assignees

• Regeneron Pharma

Inventors

• Murphy Andrew J
• Skokos Dimitris
• Waite Janelle
• Ullman Erica
• Hermann Aynur
• Smith Eric
• Olson Kara
• Wei Joyce
• Yancopoulos George D

Classifications

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K16/2887

  against CD20 · CPC title