Bispecific binding proteins that bind CD40 and mesothelin

Patent metadata

Field	Value
Publication number	US-10233258-B2
Application number	US-201815903812-A
Country	US
Kind code	B2
Filing date	Feb 23, 2018
Priority date	May 27, 2016
Publication date	Mar 19, 2019
Grant date	Mar 19, 2019

Abstract

The present disclosure provides bispecific proteins that bind to two antigens, as well as their compositions, uses, and methods of making.

First claim

The invention claimed is:

1. A bispecific binding protein capable of binding CD40 and capable of binding mesothelin, comprising two polypeptides of formula (II):
scFv X —H—Fc—L—scFv Y   (II),

wherein
L is a polypeptide linker,
H is a hinge region,
Fc comprises CH2 and CH3 regions of an immunoglobulin,
scFv X and ScFv Y are each independently a single chain variable fragment,
scFv X specifically binds a first antigen,
scFv Y specifically binds a second antigen, and
one of the two antigens is CD40 and the other is mesothelin; and

wherein the scFv that binds CD40 comprises a V H having a CDR-H1 according to SEQ ID NO:25, a CDR-H2 according to SEQ ID NO:26, and a CDR-H3 according to SEQ ID NO:27, and a V L having a CDR-L1 according to SEQ ID NO:55, a CDR-L2 according to SEQ ID NO:56, and a CDR-L3 according to SEQ ID NO:57; and
wherein the scFv that binds mesothelin comprises a V H having a CDR-H1 according to SEQ ID NO:241, a CDR-H2 according to SEQ ID NO:242, and a CDR-H3 according to SEQ ID NO:243, and a V L having a CDR-L1 according to SEQ ID NO:244, a CDR-L2 according to SEQ ID NO:245, and a CDR-L3 according to SEQ ID NO:246.

2. The bispecific binding protein of claim 1 , wherein the scFv that binds CD40 comprises a V H according to SEQ ID NO:17 and a V L according to SEQ ID NO:44.

3. The bispecific binding protein of claim 1 , wherein the scFv that binds mesothelin comprises a V H according to SEQ ID NO:120 and a V L according to SEQ ID NO:137.

4. The bispecific binding protein of claim 1 , wherein the scFv that binds CD40 comprises a V H according to SEQ ID NO:17 and a V L according to SEQ ID NO:44, and wherein the scFv that binds mesothelin comprises a V H according to SEQ ID NO:120 and a V L according to SEQ ID NO:137.

5. The bispecific binding protein of claim 1 , wherein the two polypeptides each comprise the amino acid sequence of SEQ ID NO:406.

6. A pharmaceutical composition comprising a bispecific binding protein of claim 5 , and a pharmaceutically acceptable carrier.

7. A bispecific binding protein capable of binding CD40 and capable of binding mesothelin, comprising two polypeptides of formula (III):
Fab—H—Fc—L—scFv Y   (III),

wherein
L is a polypeptide linker,
H is a hinge region,
Fc comprises CH2 and CH3 regions of an immunoglobulin,
Fab is a fragment antigen-binding region,
scFv Y is a single chain variable fragment,
Fab specifically binds a first antigen,
scFv Y specifically binds a second antigen, and
the first antigen is mesothelin and the second antigen is CD40; and

wherein the scFv that binds CD40 comprises a V H having a CDR-H1 according to SEQ ID NO:25, a CDR-H2 according to SEQ ID NO:26, and a CDR-H3 according to SEQ ID NO:27, and a V L having a CDR-L1 according to SEQ ID NO:55, a CDR-L2 according to SEQ ID NO:56, and a CDR-L3 according to SEQ ID NO:57; and
wherein the scFv that binds mesothelin comprises a V H having a CDR-H1 according to SEQ ID NO:241, a CDR-H2 according to SEQ ID NO:242, and a CDR-H3 according to SEQ ID NO:243, and a V L having a CDR-L1 according to SEQ ID NO:244, a CDR-L2 according to SEQ ID NO:245, and a CDR-L3 according to SEQ ID NO:246.

8. A pharmaceutical composition comprising a bispecific binding protein of claim 7 , and a pharmaceutically acceptable carrier.

9. The bispecific binding protein of claim 1 , wherein the first antigen is CD40 and the second antigen is mesothelin.

10. The bispecific binding protein of claim 1 , wherein the first antigen is mesothelin and the second antigen is CD40.

Assignees

• Abbvie Biotherapeutics Inc

Inventors

• Akamatsu Yoshiko
• Culp Patricia
• Forsyth Charles M
• Huang Ping Y
• Powers David
• Wahl Alan F
• Ye Shiming

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K2317/73

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