Anti-Ly6G6D antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-11845799-B2
Application number	US-202017119753-A
Country	US
Kind code	B2
Filing date	Dec 11, 2020
Priority date	Dec 13, 2019
Publication date	Dec 19, 2023
Grant date	Dec 19, 2023

Abstract

Provided herein are anti-Ly6G6D (lymphocyte antigen 6 complex, locus G61) antibodies and methods of using the same.

First claim

What is claimed is:

1. A bispecific antibody that binds to lymphocyte antigen 6 family member G6D (LY6G6D) and cluster of differentiation 3 (CD3), wherein the bispecific antibody comprises: a LY6G6D binding domain comprising a heavy chain polypeptide (H1) and a light chain polypeptide (L1) and a CD3 binding domain comprising a heavy chain polypeptide (H2) and a light chain polypeptide (L2), wherein each H1 and H2 comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH1) and each L1 and L2 comprises a light chain variable domain (VL) and a light chain constant domain (CL), wherein:
(a) the LY6G6D binding domain comprises the following six CDRs:
(i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4;
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5;
(iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6;
(iv) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1;
(v) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 2; and
(vi) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 3; and

(b) the CD3 binding domain comprises the following six CDRs:
(i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 15;
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 16;
(iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17;
(iv) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 12;
(v) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 13; and
(vi) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 14.

2. The bispecific antibody of claim 1 , wherein:
(a) the CH1 of H1 comprises an amino acid substitution at S183 (EU numbering) and the CL of L1 comprises an amino acid substitution at V133 (EU numbering) and/or the CH1 of H2 comprises an amino acid substitution at S183 (EU numbering) and the CL of L2 comprises an amino acid substitution at V133 (EU numbering); and
(b) the VH of H1 comprises an amino acid substitution at position Q39 and the VL of L1 comprises an amino acid substitution at position Q38 and/or the VH of H2 comprises an amino acid substitution at position Q39 and the VL of L2 comprises an amino acid substitution at position Q38 (all Kabat numbering).

3. The bispecific antibody of claim 1 , wherein:
(a) H1 comprises the amino acid sequence of SEQ ID NO: 7;
(b) L1 comprises the amino acid sequence of SEQ ID NO: 9;
(c) H2 comprises the amino acid sequence of SEQ ID NO: 18; and
(d) L2 comprises the amino acid sequence of SEQ ID NO: 19.

4. The bispecific antibody of claim 1 , wherein:
(a) H1 comprises the amino acid sequence of SEQ ID NO: 64;
(b) L1 comprises the amino acid sequence of SEQ ID NO: 65;
(c) H2 comprises the amino acid sequence of SEQ ID NO: 69; and
(d) L2 comprises the amino acid sequence of SEQ ID NO: 70.

5. The bispecific antibody of claim 1 , wherein:
(a) H1 comprises the amino acid sequence of SEQ ID NO: 8;
(b) L1 comprises the amino acid sequence of SEQ ID NO: 9;
(c) H2 comprises the amino acid sequence of SEQ ID NO: 67; and
(d) L2 comprises the amino acid sequence of SEQ ID NO: 19.

6. The bispecific antibody of claim 1 , wherein:
(a) H1 comprises the amino acid sequence of SEQ ID NO: 66;
(b) L1 comprises the amino acid sequence of SEQ ID NO: 65;
(c) H2 comprises the amino acid sequence of SEQ ID NO: 68; and
(d) L2 comprises the amino acid sequence of SEQ ID NO: 70.

7. A bispecific antibody that binds to LY6G6D and CD3, wherein the bispecific antibody comprises: a LY6G6D binding domain comprising an H1 and an L1 and a CD3 binding domain comprising a heavy chain polypeptide (H2) and a light chain polypeptide (L2), wherein each H1 and H2 comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH1) and each L1 and L2 comprises a light chain variable domain (VL) and a light chain constant domain (CL), wherein:
(a) the LY6G6D binding domain comprises the following six CDRs:
(i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4;
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5;
(iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6;
(iv) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1;
(v) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 2; and
(vi) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 3; and

(b) the CD3 binding domain comprises the following six CDRs:
(i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 15;
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 16;
(iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17;
(iv) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 12;
(v) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 50; and
(vi) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 51.

8. The bispecific antibody of claim 7 , wherein:
(a) the CH1 of H1 comprises an amino acid substitution at S183 (EU numbering) and the CL of L1 comprises an amino acid substitution at V133 (EU numbering) and/or the CH1 of H2 comprises an amino acid substitution at S183 (EU numbering) and the CL of L2 comprises an amino acid substitution at V133 (EU numbering); and
(b) the VH of H1 comprises an amino acid substitution at position Q39 and the VL of L1 comprises an amino acid substitution at position Q38 and/or the VH of H2 comprises an amino acid substitution at position Q39 and the VL of L2 comprises an amino acid substitution at position Q38 (all Kabat numbering).

9. The bispecific antibody of claim 7 , wherein:
(a) H1 comprises the amino acid sequence of SEQ ID NO: 7;
(b) L1 comprises the amino acid sequence of SEQ ID NO: 9;
(c) H2 comprises the amino acid sequence of SEQ ID NO: 18; and
(d) L2 comprises the amino acid sequence of SEQ ID NO: 57.

10. The bispecific antibody of claim 7 , wherein:
(a) H1 comprises the amino acid sequence of SEQ ID NO: 64;
(b) L1 comprises the amino acid sequence of SEQ ID NO: 65;
(c) H2 comprises the amino acid sequence of SEQ ID NO: 69; and
(d) L2 comprises the amino acid sequence of SEQ ID NO: 73.

11. The bispecific antibody of claim 7 , wherein:
(a) H1 comprises the amino acid sequence of SEQ ID NO: 8;
(b) L1 comprises the amino acid sequence of SEQ ID NO: 9;
(c) H2 comprises the amino acid sequence of SEQ ID NO: 67; and
(d) L2 comprises the amino acid sequence of SEQ ID NO: 57.

12. The bispecific antibody of claim 7 , wherein:
(a) H1 comprises the amino acid sequence of SEQ ID NO: 66;
(b) L1 comprises the amino acid sequence of SEQ ID NO: 65;
(c) H2 comprises the amino acid sequence of SEQ ID NO: 68; and
(d) L2 comprises the amino acid sequence of SEQ ID NO: 73.

13. One or more isolated nucleic acids encoding the antibody of claim 1 or 7 , or a portion thereof comprising a binding domain that binds to LY6G6D.

14. A composition comprising the antibody of claim 1 or 7 .

15. The bispecific antibody of claim 1 or 7 , wherein:
(a) the CH1 of H1 comprises an amino acid substitution at position S183 and the CL of L1 comprises an amino acid substitution at position V133 and/or the CH1 of H2 comprises an amino acid substitution at position S183 and the CL of L2 comprises an amino acid substitution at position V133 (all EU numbering), wherein the substituted residue at position S183 in the CH 1 of H 1 forms a charge pair with the substituted residue at position V133 in the CL of L1 and/or the substituted residue at position S183 in the CH1 of H2 forms a charge pair with the substituted residue at position V133 in the CL of L2; and
(b) the VH of H 1 comprises an amino acid substitution

Assignees

• Genentech Inc

Inventors

• Lin Weiyu
• Spiess Christoph
• Sun Liping
• Wu Yan
• Chiu Cecilia P C
• Darbonne Walter Christian
• Dillon Michael Andrew

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/57535

  of the large intestine, e.g. colon, rectum or anus · CPC title

• C07K16/2824 Primary

  against CD58 · CPC title

• C07K16/2809

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

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title