Claudin-6 antibodies and drug conjugates

Patent metadata

Field	Value
Publication number	US-2025066469-A1
Application number	US-202418792232-A
Country	US
Kind code	A1
Filing date	Aug 1, 2024
Priority date	Mar 20, 2019
Publication date	Feb 27, 2025
Grant date	—

Abstract

The present disclosure provides antigen-binding proteins which bind to Claudin-6 (CLDN6). In various aspects, the antigen-binding proteins bind to Extracellular Loop 2 (EL2) of the extracellular domain of CLDN6. Related polypeptides, nucleic acids, vectors, host cells, and conjugates are further provided herein. Kits and pharmaceutical compositions comprising such entities are moreover provided. Also provided are methods of making an antigen-binding protein and methods of treating a subject having cancer.

First claim

What is claimed is:

1 . A method of treating a subject with a CLDN6-expressing cancer, comprising administering to the subject an effective amount of a composition comprising a conjugate and a pharmaceutically acceptable carrier, diluent, or excipient, wherein
the conjugate comprises a CLDN6-specific antigen-binding protein and a heterologous moiety; the composition comprises a heterologous moiety-to-antigen-binding protein ratio (HAR) of about 4; the heterologous moiety is monomethyl auristatin E (MMAE); the conjugate comprises the MMAE in the following structure:

wherein in Formula I is a sulfur atom from a cysteine residue of the CLDN6-specific antigen-binding protein; and
the CLDN6-specific antigen-binding protein comprises:
(i) CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 387, and CDR1-3 derived from a light chain variable region of SEQ ID NO: 389;
(ii) CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 387, and CDR1-3 derived from a light chain variable region of SEQ ID NO: 388;
(iii) CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 422, and CDR1-3 derived from a light chain variable region of SEQ ID NO: 389;
(iv) CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 385, and CDR1-3 derived from a light chain variable region of SEQ ID NO: 388;
(v) CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 385, and CDR1-3 derived from a light chain variable region of SEQ ID NO: 389;
(vi) CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 386, and CDR1-3 derived from a light chain variable region of SEQ ID NO: 389; or
(vii) CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 386, and CDR1-3 derived from a light chain variable region of SEQ ID NO: 388.

2 . The method of claim 1 , wherein the antigen-binding protein is an antigen-binding antibody fragment.

3 . The method of claim 2 , wherein the antigen-binding antibody fragment is selected from the group consisting of scFv, F(ab′) 2 , Fab, Fab′, and Fv.

4 . The method of claim 1 , wherein the antigen-binding protein is an antibody.

5 . The method of claim 4 , wherein the antibody is a monoclonal antibody.

6 . The method of claim 5 , wherein the antibody is a human antibody, a humanized antibody, or a chimeric antibody.

7 . The method of claim 4 , wherein the antibody is an IgG.

8 . The method of claim 7 , wherein the IgG is selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

9 . The method of claim 8 , wherein the IgG is IgG1.

Assignees

• Univ California

Inventors

• Conklin Dylan
• Mcdermott Martina S
• O'Brien Neil A
• Palazzolo Michael J
• Slamon Dennis
• Von Euw Erika
• Bowers Peter

Classifications

• G01N33/57575

  involving oncogenic proteins · CPC title

• A61K47/68037

  the drug being a camptothecin [CPT] or derivatives · CPC title

• A61K47/68031

  the drug being an auristatin · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title