IP Library › Granted Patent US 11,312,783

Granted Patent B2

US 11,312,783 · App. 16/014,744 · Granted Apr 26, 2022

Antibody molecules to CD73 and uses thereof

Inventors: Bianka Prinz (Lebanon, NH); Jerry M. Thomas (Lebanon, NH); Ansgar Brock (San Diego, CA); Scott Chappel (Cambridge, MA); Andrew Lake (Cambridge, MA); Alison Paterson (Cambridge, MA); Rachel W. O'Connor (Cambridge, MA); Michael Warren (Cambridge, MA); Pamela Holland (Cambridge, MA); Dirksen Bussiere (Emeryville, CA); Mikias Woldegiorgis (Oakland, CA); Wei Shu (Danville, CA); John Delmas Venable (San Diego, CA); Michael Gladstone (Cambridge, MA); Jonathan Hill (Cambridge, MA); Christine Miller (Cambridge, MA)

Assignees: Novartis AG; SURFACE ONCOLOGY, INC.

C07K16/2896 A61K31/495 A61K39/395 A61K39/3955 A61K39/39533 A61K39/40 A61K45/06 A61P35/00 C07K16/2818 G01N33/68 A61K2039/505 A61K2039/507 A61K2039/545 C07K2317/34 C07K2317/76 C07K2317/90 C07K2317/92 C07K2317/94 G01N2333/70596

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Quick Facts

Patent No.: US 11,312,783
App. No.: 16/014,744
Granted: Apr 26, 2022
Kind: B2

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USPTO Patent Center↗ Full Patent PDF↗

Abstract

Antibody molecules that bind to CD73 are disclosed. The anti-CD73 antibody molecules can be used to treat, prevent and/or diagnose cancer.

Claims (75)

1. An antibody molecule that binds to human CD73, comprising:

(a) (i) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (VHCDR1) amino acid sequence of SEQ ID NO: 88, a VHCDR2 amino acid sequence of SEQ ID NO: 89, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and

(ii) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (VLCDR1) amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50; or

(b) (i) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 189, a VHCDR2 amino acid sequence of SEQ ID NO: 89, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and

(ii) a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50.

2. The antibody molecule of claim 1 , comprising:

(i) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 38, a VHCDR2 amino acid sequence of SEQ ID NO: 36, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(ii) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 72, a VHCDR2 amino acid sequence of SEQ ID NO: 71, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(iii) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 38, a VHCDR2 amino acid sequence of SEQ ID NO: 71, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(iv) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 137, a VHCDR2 amino acid sequence of SEQ ID NO: 136, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(v) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 137, a VHCDR2 amino acid sequence of SEQ ID NO: 146, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(vi) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 137, a VHCDR2 amino acid sequence of SEQ ID NO: 154, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(vii) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 190, a VHCDR2 amino acid sequence of SEQ ID NO: 36, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(viii) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 191, a VHCDR2 amino acid sequence of SEQ ID NO: 71, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(ix) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 192, a VHCDR2 amino acid sequence of SEQ ID NO: 71, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(x) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 193, a VHCDR2 amino acid sequence of SEQ ID NO: 136, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(xi) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 194, a VHCDR2 amino acid sequence of SEQ ID NO: 146, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50; or

(xii) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 195, a VHCDR2 amino acid sequence of SEQ ID NO: 154, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50.

3. The antibody molecule of claim 1 , wherein:

(i) the antibody molecule is a human antibody, a full length antibody, a bispecific antibody, Fab, F(ab′)2, Fv, or a single chain Fv fragment (scFv);

(ii) the antibody molecule comprises a heavy chain constant region selected from IgG1, IgG2, IgG3, and IgG4, and a light chain constant region chosen from the light chain constant regions of kappa or lambda; or

(iii) the antibody molecule comprises a heavy chain constant region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 92-103, 119, and 120, and/or a light chain constant region comprising the amino acid sequence of SEQ ID NO: 104.

4. A composition comprising a plurality of the antibody molecules of claim 1 , wherein the antibody molecules bind to a human CD73 dimer, said dimer consisting of a first CD73 monomer and a second CD73 monomer, each monomer comprising the amino acid sequence of residues 27-547 of SEQ ID NO: 105, wherein when the antibody molecules in the plurality each comprises the same first antigen binding domain and the same second antigen binding domain,

(i) at least 30%, 35%, or 40% of the antibody molecules in said composition bind to the CD73 dimer to form a complex, wherein each of said complex consists of one antibody molecule and one CD73 dimer; or

(ii) at most 60%, 65%, or 70% of the antibody molecules in said composition bind to the CD73 dimer to form a complex, wherein each of said complex comprises two or more antibody molecules and two or more CD73 dimers.

5. A pharmaceutical composition comprising the antibody molecule of claim 1 and a pharmaceutically acceptable carrier, excipient or stabilizer.

6. The antibody molecule of claim 1 , comprising a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 38, a VHCDR2 amino acid sequence of SEQ ID NO: 36, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50.

7. The antibody molecule of claim 1 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 44 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55.

8. The antibody molecule of claim 1 , comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 46, wherein residue 451 of SEQ ID NO: 46 is K, and a light chain comprising the amino acid sequence of SEQ ID NO: 57.

9. The antibody molecule of claim 1 , comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 114, wherein residue 451 of SEQ ID NO: 114 is K, and a light chain comprising the amino acid sequence of SEQ ID NO: 57.

10. The antibody molecule of claim 1 , wherein the antibody molecule comprises a heavy chain constant region of IgG4 and a light chain constant region of kappa.

11. The antibody molecule of claim 1 , comprising:

(i) a human IgG4 heavy chain constant region with a mutation at position 228 according to EU numbering;

(ii) a human IgG4 heavy chain constant region with a Serine to Proline mutation at position 228 according to EU numbering; or

(iii) a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 92 or 93.

12. The antibody molecule of claim 1 , comprising:

(i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 44, 77, 84, 142, 151, or 159, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity to SEQ ID NO: 44, 77, 84, 142, 151, or 159;

(ii) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity to SEQ ID NO: 55;

(iii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 46, 79, 86, 114, 116, or 117, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity to SEQ ID NO: 46, 79, 86, 114, 116, or 117;

(iv) a light chain comprising the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity to SEQ ID NO: 57;

(v) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 44, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(vi) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 77, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain variable region comprising the amino acid sequence or SEQ ID NO: 55, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(vii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 84, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(viii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 142, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(ix) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 151, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(x) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 159, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto; or

(xi) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 44 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55.

13. The antibody molecule of claim 1 , comprising:

(i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 46, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain comprising the amino acid sequence of SEQ ID NO: 57, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 114, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain comprising the amino acid sequence of SEQ ID NO: 57, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(iii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 79, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain comprising the amino acid sequence of SEQ ID NO: 57, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(iv) a heavy chain comprising the amino acid sequence of SEQ ID NO: 116, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain comprising the amino acid sequence of SEQ ID NO: 57, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(v) a heavy chain comprising the amino acid sequence of SEQ ID NO: 86, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain comprising the amino acid sequence of SEQ ID NO: 57, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;

(vi) a heavy chain comprising the amino acid sequence of SEQ ID NO: 117, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto, and a light chain comprising the amino acid sequence of SEQ ID NO: 57, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto; or

(vii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 46 and a light chain comprising the amino acid sequence of SEQ ID NO: 57.

14. An antibody molecule that binds to human CD73, comprising:

(a) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (VHCDR1) amino acid sequence of SEQ ID NO: 38, a VHCDR2 amino acid sequence of SEQ ID NO: 36, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (VLCDR1) amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 35, a VHCDR2 amino acid sequence of SEQ ID NO: 36, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50;

(c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 39, a VHCDR2 amino acid sequence of SEQ ID NO: 40, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 51, a VLCDR2 amino acid sequence of SEQ ID NO: 52, and a VLCDR3 amino acid sequence of SEQ ID NO: 53;

(d) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 41, a VHCDR2 amino acid sequence of SEQ ID NO: 42, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 54, a VLCDR2 amino acid sequence of SEQ ID NO: 52, and a VLCDR3 amino acid sequence of SEQ ID NO: 50; or

(e) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 190, a VHCDR2 amino acid sequence of SEQ ID NO: 36, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50.

15. The antibody molecule of claim 14 , comprising a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 38, a VHCDR2 amino acid sequence of SEQ ID NO: 36, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50.

16. The antibody molecule of claim 14 , comprising a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 35, a VHCDR2 amino acid sequence of SEQ ID NO: 36, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50.

17. The antibody molecule of claim 14 , comprising a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 39, a VHCDR2 amino acid sequence of SEQ ID NO: 40, and a VHCDR3 amino acid sequence of SEQ ID NO: 37; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 51, a VLCDR2 amino acid sequence of SEQ ID NO: 52, and a VLCDR3 amino acid sequence of SEQ ID NO: 53.

18. The antibody molecule of claim 14 , comprising a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 41, a VHCDR2 amino acid sequence of SEQ ID NO: 42, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 54, a VLCDR2 amino acid sequence of SEQ ID NO: 52, and a VLCDR3 amino acid sequence of SEQ ID NO: 50.

19. The antibody molecule of claim 14 , comprising a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 190, a VHCDR2 amino acid sequence of SEQ ID NO: 36, and a VHCDR3 amino acid sequence of SEQ ID NO: 43; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 48, a VLCDR2 amino acid sequence of SEQ ID NO: 49, and a VLCDR3 amino acid sequence of SEQ ID NO: 50.

20. The antibody molecule of claim 14 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 44, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55.

21. The antibody molecule of claim 14 , comprising:

(i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 46, wherein residue 451 of SEQ ID NO: 46 is K, and a light chain comprising the amino acid sequence of SEQ ID NO: 57; or

(ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 114, wherein residue 451 of SEQ ID NO: 114 is K, and a light chain comprising the amino acid sequence of SEQ ID NO: 57.

22. A pharmaceutical composition comprising the antibody molecule of claim 14 and a pharmaceutically acceptable carrier, excipient, or stabilizer.

23. An antibody molecule that binds to human CD73, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 44, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55.

24. A pharmaceutical composition comprising the antibody molecule of claim 23 and a pharmaceutically acceptable carrier, excipient, or stabilizer.

25. An antibody molecule that binds to human CD73, comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 46, wherein residue 451 of SEQ ID NO: 46 is K, and a light chain comprising the amino acid sequence of SEQ ID NO: 57.

26. A pharmaceutical composition comprising the antibody molecule of claim 25 and a pharmaceutically acceptable carrier, excipient, or stabilizer.

Assignments (10)

SECURITY INTEREST Recorded May 8, 2024

From: COHERUS BIOSCIENCES, INC.; COHERUS INTERMEDIATE CORP.; INTEKRIN THERAPEUTICS INC.; SURFACE ONCOLOGY, LLC; COHERUS ONCOLOGY SUPPORTIVE CARE LLC

To: ANKURA TRUST COMPANY, LLC

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