Antibody molecules to PD-1 and uses thereof

Patent metadata

Field	Value
Publication number	US-10752687-B2
Application number	US-201715727456-A
Country	US
Kind code	B2
Filing date	Oct 6, 2017
Priority date	Jan 24, 2014
Publication date	Aug 25, 2020
Grant date	Aug 25, 2020

Abstract

Antibody molecules that specifically bind to PD-1 are disclosed. The anti-PD-1 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious conditions and disorders.

First claim

What is claimed is:

1. A nucleic acid molecule comprising a first nucleotide sequence that encodes a heavy chain variable region (VH), or a second nucleotide sequence that encodes a light chain variable region (VL), or both, of an antibody molecule capable of binding to human Programmed Death-1 (PD-1), wherein the antibody molecule comprises:
(a) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 4, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 33;
(b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 1; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 32;
(c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 224, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 33; or
(d) a VHCDR1 amino acid sequence of SEQ ID NO: 224; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 32.

2. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 1; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 32.

3. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 224, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 33.

4. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 224; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 32.

5. A nucleic acid molecule comprising a first nucleotide sequence that encodes a VH, or a second nucleotide sequence that encodes a VL, or both, of a bispecific antibody molecule having a first binding specificity for PD-1 and a second binding specificity for TIM-3, LAG-3, CEACAM-1, CEACAM-5, PD-L1 or PD-L2, wherein the bispecific antibody molecule comprises:
(a) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 4, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 33;
(b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 1; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 32;
(c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 224, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 33; or
(d) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 224; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 32.

6. The nucleic acid molecule of claim 1 , wherein the first and the second nucleotide sequences are in the same nucleic acid molecule.

7. The nucleic acid molecule of claim 1 , wherein the first and the second nucleotide sequences are in separate nucleic acid molecules.

8. The nucleic acid molecule of claim 5 , wherein the first and the second nucleotide sequences are in the same nucleic acid molecule.

9. The nucleic acid molecule of claim 5 , wherein the first and the second nucleotide sequences are in separate nucleic acid molecules.

10. An expression vector comprising the nucleic acid molecule of claim 1 .

11. An expression vector comprising the nucleic acid molecule of claim 5 .

12. A host cell comprising the nucleic acid molecule of claim 1 .

13. A host cell comprising the nucleic acid molecule of claim 5 .

14. A method of producing an antibody molecule, comprising culturing the host cell of claim 12 under conditions suitable for gene expression.

15. A method of producing an antibody molecule, comprising culturing the host cell of claim 13 under conditions suitable for gene expression.

16. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 4, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 33.

17. The nucleic acid molecule of claim 1 , wherein the first nucleotide sequence encodes a VH comprising an amino acid sequence at least 85% identical to any of SEQ ID NOs: 38, 50, 82, or 86.

18. The nucleic acid molecule of claim 1 , wherein the first nucleotide sequence encodes a VH comprising the amino acid sequence of SEQ ID NO: 38, 50, 82, or 86.

19. The nucleic acid molecule of claim 1 , wherein the second nucleotide sequence encodes a VL comprising an amino acid sequence at least 85% identical to any of SEQ ID NOs: 42, 46, 54, 58, 62, 66, 70, 74, or 78.

20. The nucleic acid molecule of claim 1 , wherein the second nucleotide sequence encodes a VL comprising the amino acid sequence of SEQ ID NO: 42, 46, 54, 58, 62, 66, 70, 74, or 78.

21. The nucleic acid molecule of claim 1 , wherein the first nucleotide sequence and the second nucleotide sequence encode, respectively:
(a) a VH comprising the amino acid sequence of SEQ ID NO: 38 and a VL comprising the amino acid sequence of SEQ ID NO: 54;
(b) a VH comprising the amino acid sequence of SEQ ID NO: 38 and a VL comprising the amino acid sequence of SEQ ID NO: 42;
(c) a VH comprising the amino acid sequence of SEQ ID NO: 38 and a VL comprising the amino acid sequence of SEQ ID NO: 66;
(d) a VH comprising the amino acid sequence of SEQ ID NO: 38 and a VL comprising the amino acid sequence of SEQ ID NO: 70;
(e) a VH comprising the amino acid sequence of SEQ ID NO: 50 and a VL comprising the amino acid sequence

Assignees

• Novartis Ag
• Dana-Farber Cancer Institute Inc
• Harvard College

Inventors

• Freeman Gordon James
• Sharpe Arlene Helen
• Blattler Walter A
• Mataraza Jennifer Marie
• Sabatos-Peyton Catherine Anne
• Chang Hwai Wen
• Frey Gerhard Johann

Classifications

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• G01N2333/70596

  Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705 · CPC title

• G01N33/6854

  Immunoglobulins · CPC title

• G01N33/566

  using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds} · CPC title

• C07K2317/74

  Inducing cell proliferation · CPC title