IP Library › Granted Patent US 10,968,270
Granted Patent B2
US 10,968,270 · App. 16/912,131 · Granted Apr 6, 2021

Antibody molecules to a proliferation-inducing ligand (APRIL)

Inventors: James R. Myette (Waltham, MA); Zachary Holmes Shriver (Winchester, MA); Karthik Viswanathan (Acton, MA); Andrew M. Wollacott (Milton, MA); Hedy Adari-Hall (Sudbury, MA); Boopathy Ramakrishnan (Braintree, MA); Gregory Babcock (Marlborough, MA)
Assignee: VISTERRA, INC.
C07K16/241A61K39/3955A61K45/06C07K16/2875A61K2039/505A61K2039/54C07K2317/14C07K2317/24C07K2317/33C07K2317/34C07K2317/52C07K2317/56C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 10,968,270
App. No.
16/912,131
Granted
Apr 6, 2021
Kind
B2
Abstract

Antibody molecules that specifically bind to APRIL are disclosed. The antibody molecules can be used to treat, prevent, and/or diagnose disorders, such as IgA nephropathy.

Claims (67)

1. An anti-A PRoliferation Inducing Ligand (APRIL) antibody molecule, comprising:

(i) a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the VH comprises:

an HCDR1 comprising the amino acid sequence of G-Y-T-F-T-D-Y (SEQ ID NO: 11);

an HCDR2 comprising the amino acid sequence of Y-P-L-R-G-S(SEQ ID NO: 12); and

an HCDR3 comprising the amino acid sequence of H-G-A-Y-Y-S-N-A-F-D-Y (SEQ ID NO: 13), and

(ii) a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the VL comprises:

an LCDR1 comprising the amino acid sequence of X1-X2-S-X4S-V-D-N-D-G-I-R-F-X14-H (SEQ ID NO: 327), wherein X1 is R or K; X2 is A or S; X4 is E or Q; and X14 is M or L;

an LCDR2 comprising the amino acid sequence of R-A-S-X4-X5-X6-X7 (SEQ ID NO: 328), wherein X4 is N or T; X5 is L or R; X6 is E or A; and X7 is S or T; and

an LCDR3 comprising the amino acid sequence of Q-Q-S-N-K-D-P-Y-T (SEQ ID NO: 16).

2. The antibody molecule of claim 1 , wherein the LCDR1 comprises the amino acid sequence of any of SEQ ID NOs: 14, 280, or 314, the LCDR2 comprises the amino acid sequence of any of SEQ ID NOs: 15, 281, 285, 293, or 315, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16.

3. The antibody molecule of claim 1 , wherein:

(a) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence of any of SEQ ID NO: 14, the LCDR2 comprises the amino acid sequence of any of SEQ ID NO: 15, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16;

(b) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence of any of SEQ ID NO: 280, the LCDR2 comprises the amino acid sequence of any of SEQ ID NO: 281, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16;

(c) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence of any of SEQ ID NO: 280, the LCDR2 comprises the amino acid sequence of any of SEQ ID NO: 285, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16;

(d) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence of any of SEQ ID NO: 280, the LCDR2 comprises the amino acid sequence of any of SEQ ID NO: 293, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16; or

(e) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence of any of SEQ ID NO: 314, the LCDR2 comprises the amino acid sequence of any of SEQ ID NO: 315, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16.

4. The antibody molecule of claim 1 , wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 14, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 15, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16.

5. The antibody molecule of claim 1 , wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 280, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 281, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16.

6. The antibody molecule of claim 1 , wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 280, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 293, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16.

7. The antibody molecule of claim 1 , wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 314, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 315, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16.

8. The antibody molecule of claim 1 , wherein:

(a) the VH comprises the amino acid sequence of any of SEQ ID NOs: 19, 283, 288, 289, 291, 292, 294, 296, or 317, or an amino acid sequence that is at least 85% identical thereto;

(b) the VL comprises the amino acid sequence of any of SEQ ID NOs: 20, 284, 286, 295, or 316, or an amino acid sequence that is at least 85% identical thereto; or

(c) both (a) and (b).

9. The antibody molecule of claim 1 , wherein:

(a) the VH comprises the amino acid sequence of any of SEQ ID NOs: 19, 283, 288, 289, 291, 292, 294, 296, or 317;

(b) the VL comprises the amino acid sequence of any of SEQ ID NOs: 20, 284, 286, 295, or 316; or

(c) both (a) and (b).

10. The antibody molecule of claim 1 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 19 and the VL comprises the amino acid sequence of SEQ ID NO: 20;

(b) the VH comprises the amino acid sequence of SEQ ID NO: 292 and the VL comprises the amino acid sequence of SEQ ID NO: 284;

(c) the VH comprises the amino acid sequence of SEQ ID NO: 289 and the VL comprises the amino acid sequence of SEQ ID NO: 284;

(d) the VH comprises the amino acid sequence of SEQ ID NO: 289 and the VL comprises the amino acid sequence of SEQ ID NO: 286;

(e) the VH comprises the amino acid sequence of SEQ ID NO: 291 and the VL comprises the amino acid sequence of SEQ ID NO: 286;

(f) the VH comprises the amino acid sequence of SEQ ID NO: 317 and the VL comprises the amino acid sequence of SEQ ID NO: 284;

(g) the VH comprises the amino acid sequence of SEQ ID NO: 288 and the VL comprises the amino acid sequence of SEQ ID NO: 284;

(h) the VH comprises the amino acid sequence of SEQ ID NO: 288 and the VL comprises the amino acid sequence of SEQ ID NO: 286;

(i) the VH comprises the amino acid sequence of SEQ ID NO: 294 and the VL comprises the amino acid sequence of SEQ ID NO: 295;

(j) the VH comprises the amino acid sequence of SEQ ID NO: 294 and the VL comprises the amino acid sequence of SEQ ID NO: 284;

(k) the VH comprises the amino acid sequence of SEQ ID NO: 294 and the VL comprises the amino acid sequence of SEQ ID NO: 316;

(l) the VH comprises the amino acid sequence of SEQ ID NO: 283 and the VL comprises the amino acid sequence of SEQ ID NO: 284;

(m) the VH comprises the amino acid sequence of SEQ ID NO: 283 and the VL comprises the amino acid sequence of SEQ ID NO: 286;

(n) the VH comprises the amino acid sequence of SEQ ID NO: 283 and the VL comprises the amino acid sequence of SEQ ID NO: 316; or

(o) the VH comprises the amino acid sequence of SEQ ID NO: 296 and the VL comprises the amino acid sequence of SEQ ID NO: 286.

11. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 19 and the VL comprises the amino acid sequence of SEQ ID NO: 20.

12. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 292 and the VL comprises the amino acid sequence of SEQ ID NO: 284.

13. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 289 and the VL comprises the amino acid sequence of SEQ ID NO: 284.

14. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 289 and the VL comprises the amino acid sequence of SEQ ID NO: 286.

15. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 291 and the VL comprises the amino acid sequence of SEQ ID NO: 286.

16. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 317 and the VL comprises the amino acid sequence of SEQ ID NO: 284.

17. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 288 and the VL comprises the amino acid sequence of SEQ ID NO: 284.

18. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 288 and the VL comprises the amino acid sequence of SEQ ID NO: 286.

19. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 294 and the VL comprises the amino acid sequence of SEQ ID NO: 295.

20. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 294 and the VL comprises the amino acid sequence of SEQ ID NO: 284.

21. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 294 and the VL comprises the amino acid sequence of SEQ ID NO: 316.

22. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 283 and the VL comprises the amino acid sequence of SEQ ID NO: 284.

23. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 283 and the VL comprises the amino acid sequence of SEQ ID NO: 286.

24. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 283 and the VL comprises the amino acid sequence of SEQ ID NO: 316.

25. The antibody molecule of claim 1 , wherein the antibody molecule is a synthetic antibody molecule, an isolated antibody molecule, or a humanized antibody molecule.

26. The antibody molecule of claim 1 , wherein the antibody molecule comprises:

(a) a heavy chain constant region of IgG1, IgG2, IgG3, or IgG4;

(b) a light chain constant region of kappa or lambda light chain; or

(c) both (a) and (b).

27. The antibody molecule of claim 1 , wherein the antibody molecule comprises an Fc region.

28. The antibody molecule of claim 1 , which comprises two VHs and two VLs, or comprises a Fab, F(ab′)2, Fv, or single chain Fv (scFv) fragment.

29. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of any of SEQ ID NOs: 19, 283, 288, 289, 291, 292, 294, 296, or 317 and the VL comprises the amino acid sequence of any of SEQ ID NOs: 20, 284, 286, 295, or 316.

30. A pharmaceutical composition comprising the antibody molecule of claim 1 and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 29, 2020
From: MYETTE, JAMES R.; SHRIVER, ZACHARY HOLMES; VISWANATHAN, KARTHIK; WOLLACOTT, ANDREW M.; ADARI-HALL, HEDY; RAMAKRISHNAN, BOOPATHY; BABCOCK, GREGORY
To: VISTERRA, INC.
Reel/Frame 054767/0136 →
Continuity (8)
Division 16456810 · Jun 28, 2019
Division 16212957 · Dec 7, 2018
Division 15360145 · Nov 23, 2016
Provisional Application 62422848 · Nov 16, 2016
Provisional Application 62399087 · Sep 23, 2016
Provisional Application 62313684 · Mar 25, 2016
Provisional Application 62259897 · Nov 25, 2015
Related Publication 20200331995A1 · Oct 22, 2020
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