Antibody specific for Mucin-1 and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11970546-B2
Application number	US-202117389723-A
Country	US
Kind code	B2
Filing date	Jul 30, 2021
Priority date	Jul 31, 2020
Publication date	Apr 30, 2024
Grant date	Apr 30, 2024

Abstract

The present disclosure provides antibodies specific for Mucin 1. Nucleic acids that encode one or both of the variable chains of an antibody of the present disclosure are also provided, as are cells that include such nucleic acids. Also provided are compositions that include the antibodies of the present disclosure, including in some instances, pharmaceutical compositions. Methods of making and using the antibodies of the present disclosure are also provided. In certain aspects, provided are methods that include administering to an individual having a cell proliferative disorder a therapeutically effective amount of an antibody of the present disclosure, where the antibody is administered to the individual to enhance an immune response, e.g., a T cell response, to abnormally proliferating cells of the cell proliferative disorder. The antibodies are also useful in various diagnostic, and monitoring applications, which are also provided.

First claim

What is claimed is:

1. An antibody or fragment thereof that specifically binds to Mucin-1 (MUC-1), wherein the antibody or fragment thereof comprises:
a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), and a heavy chain complementarity determining region 3 (HCDR3) as set forth in a variable heavy (VH) chain comprising the amino acid sequence of SEQ ID NO: 1; and
a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) as set forth in a variable light (VL) chain comprising the amino acid sequence of any one of SEQ ID NOs: 2, 3, or 4.

2. The antibody or fragment thereof according to claim 1 , comprising:
a VH chain comprising:
an HCDR1 comprising the amino acid sequence DHTMEI (SEQ ID NO: 17);
an HCDR2 comprising the amino acid sequence YFYPRDDSTNYNEKFKG (SEQ ID NO: 18); and
an HCDR3 comprising the amino acid sequence GLRYALDY (SEQ ID NO: 9); and

a VL chain comprising:
a) an LCDR1 comprising the amino acid sequence RASSSVSSSYLY (SEQ ID NO: 10),
an LCDR2 comprising the amino acid sequence GTSNLAS (SEQ ID NO: 11), and
an LCDR3 comprising the amino acid sequence HQYAWSPPT (SEQ ID NO: 12); or

b) an LCDR1 comprising the amino acid sequence RASSSVGSSNLY (SEQ ID NO: 13),
an LCDR2 comprising the amino acid sequence RSTKLAS (SEQ ID NO: 14), and
an LCDR3 comprising the amino acid sequence HQYRWSPPT (SEQ ID NO: 15; or

c) an LCDR1 comprising the amino acid sequence RASSSVSSSYLY (SEQ ID NO: 10),
an LCDR2 comprising the amino acid sequence GTSNLAS (SEQ ID NO: 11), and
an LCDR3 comprising the amino acid sequence HQYSWSPPT (SEQ ID NO: 16).

3. The antibody or fragment thereof according to claim 1 , wherein the VH chain comprises an amino acid sequence having at least 80% identity to the amino acid sequence set forth in SEQ ID NO: 1.

4. The antibody or fragment thereof according to claim 3 , wherein the VL chain comprises an amino acid sequence having at least 80% identity to the amino acid sequence set forth in any one of SEQ ID NO: 2, 3, or 4.

5. The antibody or fragment thereof according to claim 1 , comprising:
(i) an HCDR1 comprising the amino acid sequence DHTMH (SEQ ID NO: 17),
an HCDR2 comprising the amino acid sequence YFYPRDDSTNYNEKFKG (SEQ ID NO: 18),
an HCDR3 comprising the amino acid sequence GLRYALDY (SEQ ID NO: 9),
an LCDR1 comprising the amino acid sequence RASSSVSSSYLY (SEQ ID NO: 10),
an LCDR2 comprising the amino acid sequence GTSNLAS (SEQ ID NO: 11), and
an LCDR3 comprising the amino acid sequence HQYAWSPPT (SEQ ID NO: 12),

as per Kabat definition; or
(ii) an HCDR1 comprising the amino acid sequence GYTFTDH (SEQ ID NO: 7),
an HCDR2 comprising the amino acid sequence YPRDDS (SEQ ID NO: 8),
an HCDR3 comprising the amino acid sequence GLRYALDY (SEQ ID NO: 9),
an LCDR1 comprising the amino acid sequence RASSSVSSSYLY (SEQ ID NO: 10),
an LCDR2 comprising the amino acid sequence GTSNLAS (SEQ ID NO: 11), and
an LCDR3 comprising the amino acid sequence HQYAWSPPT (SEQ ID NO: 12), as per Chothia definition; or

(iii) an HCDR1 comprising the amino acid sequence GYTFTDHT (SEQ ID NO: 34),
an HCDR2 comprising the amino acid sequence FYPRDDST (SEQ ID NO: 44),
an HCDR3 comprising the amino acid sequence ARGLRYALDY (SEQ ID NO: 45),
an LCDR1 comprising the amino acid sequence SSVSSSY (SEQ ID NO: 33),
an LCDR2 comprising the amino acid sequence GT, and
an LCDR3 comprising the amino acid sequence HQYAWSPPT (SEQ ID NO: 12), as per IMGT definition.

6. The antibody or fragment thereof according to claim 1 , comprising:
(i) an HCDR1 comprising the amino acid sequence DHTMH (SEQ ID NO: 17),
an HCDR2 comprising the amino acid sequence YFYPRDDSTNYNEKFKG (SEQ ID NO: 18),
an HCDR3 comprising the amino acid sequence GLRYALDY (SEQ ID NO: 9),
an LCDR1 comprising the amino acid sequence RASSSVGSSNLY (SEQ ID NO: 13),
an LCDR2 comprising the amino acid sequence RSTKLAS (SEQ ID NO: 14), and
an LCDR3 comprising the amino acid sequence HQYRWSPPT (SEQ ID NO: 15),

as per Kabat definition, or
(ii) an HCDR1 comprising the amino acid sequence GYTFTDH (SEQ ID NO: 7),
an HCDR2 comprising the amino acid sequence YPRDDS (SEQ ID NO: 8),
an HCDR3 comprising the amino acid sequence GLRYALDY (SEQ ID NO: 9),
an LCDR1 comprising the amino acid sequence RASSSVGSSNLY (SEQ ID NO: 13),
an LCDR2 comprising the amino acid sequence RSTKLAS (SEQ ID NO: 14), and
an LCDR3 comprising the amino acid sequence HQYRWSPPT (SEQ ID NO: 15), as per Chothia definition; or

(iii) an HCDR1 comprising the amino acid sequence GYTFTDHT (SEQ ID NO: 34),
an HCDR2 comprising the amino acid sequence FYPRDDST (SEQ ID NO: 44),
an HCDR3 comprising the amino acid sequence ARGLRYALDY (SEQ ID NO: 45),
an LCDR1 comprising the amino acid sequence SSVGSSN (SEQ ID NO: 46),
an LCDR2 comprising the amino acid sequence RS, and
an LCDR3 comprising the amino acid sequence HQYRWSPPT (SEQ ID NO: 15), as per IMGT definition.

7. The antibody or fragment thereof according to claim 1 , comprising:
(i) an HCDR1 comprising the amino acid sequence DHTMH (SEQ ID NO: 17),
an HCDR2 comprising the amino acid sequence YFYPRDDSTNYNEKFKG (SEQ ID NO: 18);
an HCDR3 comprising the amino acid sequence GLRYALDY (SEQ ID NO: 9),
an LCDR1 comprising the amino acid sequence RASSSVSSSYLY (SEQ ID NO: 10),
an LCDR2 comprising the amino acid sequence GTSNLAS (SEQ ID NO: 11), and
an LCDR3 comprising the amino acid sequence HQYSWSPPT (SEQ ID NO: 16),

as per Kabat definition or
(ii) an HCDR1 comprising the amino acid sequence GYTFTDH (SEQ ID NO: 7),
an HCDR2 comprising the amino acid sequence YPRDDS (SEQ ID NO: 8),
an HCDR3 comprising the amino acid sequence GLRYALDY (SEQ ID NO: 9),
an LCDR1 comprising the amino acid sequence RASSSVSSSYLY (SEQ ID NO: 10),
an LCDR2 comprising the amino acid sequence GTSNLAS (SEQ ID NO: 11), and
an LCDR3 comprising the amino acid sequence HQYSWSPPT (SEQ ID NO: 16), as per Chothia definition; or

(iii) an HCDR1 comprising the amino acid sequence GYTFTDHT (SEQ ID NO: 34),
an HCDR2 comprising the amino acid sequence FYPRDDST (SEQ ID NO: 44),
an HCDR3 comprising the amino acid sequence ARGLRYALDY (SEQ ID NO: 45),
an LCDR1 comprising the amino acid sequence SSVSSSY (SEQ ID NO: 33),
an LCDR2 comprising the amino acid sequence GT, and
an LCDR3 comprising the amino acid sequence HQYSWSPPT (SEQ ID NO: 16), as per IMGT definition.

8. The antibody or fragment thereof according to claim 1 , wherein the antibody is a humanized antibody or a chimeric antibody.

9. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof is selected from the group consisting of: an IgG, Fv, single chain antibody, scFv, Fab, F(ab′)2, or Fab′.

10. The antibody or fragment thereof according to claim 9 , wherein the antibody is an IgG1 or a bispecific antibody.

11. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof is detectably labeled.

12. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof comprises a covalently linked lipid or fatty acid moiety.

13. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof is linked to a contrast agent.

14. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof is immobilized on a solid support.

15. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragm

Assignees

• Scherer Technologies Llc R P

Inventors

• Rabuka David
• Drake Penelope M
• Kim Yun Cheol
• Barfield Robyn M
• Bauzon Maxine
• Ogunkoya Ayodele

Classifications

• C07K16/3076 Primary

  against structure-related tumour-associated moieties · CPC title

• A61K47/6911

  the form being a liposome · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/3092 Primary

  against tumour-associated mucins · CPC title