IP Library › Granted Patent US 10,981,982

Granted Patent B2

US 10,981,982 · App. 16/912,085 · Granted Apr 20, 2021

Nucleic acid molecules encoding antibodies 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.

C07K16/241 A61K39/3955 A61K45/06 C07K16/2875 A61K2039/505 A61K2039/54 C07K2317/14 C07K2317/24 C07K2317/33 C07K2317/34 C07K2317/52 C07K2317/56 C07K2317/76 C07K2317/92 C07K2317/94

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Quick Facts

Patent No.: US 10,981,982
App. No.: 16/912,085
Granted: Apr 20, 2021
Kind: B2

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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 (111)

1. A nucleic acid molecule encoding three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) of an anti-A PRoliferation Inducing Ligand (APRIL) antibody molecule,

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, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13; and the LCDR1 comprises the amino acid sequence of SEQ ID NO: 280; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 285, and the LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

wherein the HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 282, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13; and the CDR1 comprises the amino acid sequence of SEQ ID NO: 280; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 285, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16.

2. The nucleic acid molecule of claim 1 , wherein:

(a) the nucleic acid molecule encodes a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 296, 283, 288, 289, 291, 292, 294, or 317, or an amino acid sequence that is at least 85% identical thereto;

(b) the nucleic acid molecule encodes a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85% identical thereto; or

3. The nucleic acid molecule of claim 2 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 296;

(b) the VL comprises the amino acid sequence of SEQ ID NO: 286; or

4. The nucleic acid molecule of claim 1 , wherein the anti-APRIL antibody molecule is a synthetic antibody molecule, an isolated antibody molecule, or a humanized antibody molecule.

5. The nucleic acid molecule of claim 1 , wherein the anti-APRIL 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

6. The nucleic acid molecule of claim 1 , wherein the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2.

7. The nucleic acid molecule of claim 1 , wherein the anti-APRIL antibody molecule comprises a light chain constant region of kappa or lambda light chain.

8. The nucleic acid molecule of claim 1 , wherein the anti-APRIL antibody molecule comprises an Fc region.

9. The nucleic acid molecule of claim 1 , wherein the anti-APRIL antibody molecule comprises two VHs and two VLs, or comprises a Fab, F(ab′)2, Fv, or single chain Fv (scFv) fragment.

10. The nucleic acid 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, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13; and the LCDR1 comprises the amino acid sequence of SEQ ID NO: 280; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 285, and the LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

11. The nucleic acid molecule of claim 1 , wherein the HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 282, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13; and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 285, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16.

12. The nucleic acid molecule of claim 2 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 296, 283, 288, 289, 291, 292, 294, or 317, or an amino acid sequence that is at least 90% identical thereto;

(b) the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 90% identical thereto; or

13. The nucleic acid molecule of claim 2 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 296, 283, 288, 289, 291, 292, 294, or 317, or an amino acid sequence that is at least 95% identical thereto;

(b) the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 95% identical thereto; or

14. The nucleic acid molecule of claim 2 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 296, 283, 288, 289, 291, 292, 294, or 317, or an amino acid sequence that is at least 99% identical thereto;

(b) the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 99% identical thereto; or

15. The nucleic acid molecule of claim 2 , wherein 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.

16. A nucleic acid molecule encoding a heavy chain variable region (VH), a light chain variable region (VL), or both, of an anti-APRIL antibody molecule,

wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

17. The nucleic acid molecule of claim 16 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 296, 283, 288, 289, 291, 292, 294, or 317, or an amino acid sequence that is at least 85% identical thereto;

(b) the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85% identical thereto; or

18. The nucleic acid molecule of claim 16 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 296;

(b) the VL comprises the amino acid sequence of SEQ ID NO: 286; or

19. The nucleic acid molecule of claim 16 , wherein the anti-APRIL antibody molecule is a synthetic antibody molecule, an isolated antibody molecule, or a humanized antibody molecule.

20. The nucleic acid molecule of claim 16 , wherein the anti-APRIL 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

21. The nucleic acid molecule of claim 16 , wherein the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2.

22. The nucleic acid molecule of claim 16 , wherein the anti-APRIL antibody molecule comprises a light chain constant region of kappa or lambda light chain.

23. The nucleic acid molecule of claim 16 , wherein the anti-APRIL antibody molecule comprises an Fc region.

24. The nucleic acid molecule of claim 16 , wherein the anti-APRIL antibody molecule comprises two VHs and two VLs, or comprises a Fab, F(ab′)2, Fv, or single chain Fv (scFv) fragment.

25. A vector comprising the nucleic acid molecule of claim 16 .

26. A cell comprising the nucleic acid molecule of claim 16 .

27. A method of producing an anti-APRIL antibody molecule, the method comprising culturing a cell of claim 26 under conditions that allow production of an antibody molecule, thereby producing the antibody molecule.

28. The nucleic acid molecule of claim 16 , 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, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13; and the LCDR1 comprises the amino acid sequence of SEQ ID NO: 280; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 285, and the LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

29. The nucleic acid molecule of claim 16 , wherein the HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 282, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13; and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 285, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 16.

30. The nucleic acid molecule of claim 16 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 296, 283, 288, 289, 291, 292, 294, or 317, or an amino acid sequence that is at least 90% identical thereto;

(b) the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 90% identical thereto; or

31. The nucleic acid molecule of claim 16 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 296, 283, 288, 289, 291, 292, 294, or 317, or an amino acid sequence that is at least 95% identical thereto;

(b) the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 95% identical thereto; or

32. The nucleic acid molecule of claim 16 , wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO: 296, 283, 288, 289, 291, 292, 294, or 317, or an amino acid sequence that is at least 99% identical thereto;

(b) the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 99% identical thereto; or

33. The nucleic acid molecule of claim 16 , wherein 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.

34. A nucleic acid molecule comprising:

(i) a first nucleotide sequence encoding a heavy chain variable region (VH) comprising the amino acid sequence of any of SEQ ID NOs: 296, 283, 288, 289, 291, 292, 294, or 317;

(ii) a second nucleotide sequence encoding a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 286; or

(iii) both (i) and (ii).

35. A vector comprising the nucleic acid molecule of claim 34 .

36. A cell comprising the nucleic acid molecule of claim 34 .

37. A method of producing an anti-APRIL antibody molecule, the method comprising culturing a cell of claim 36 under conditions that allow production of an antibody molecule, thereby producing the antibody molecule.

38. A nucleic acid molecule comprising:

(i) a first nucleotide sequence of any of SEQ ID NOs: 73, 304, 307, 308, 309, 310, 311, 313, or 319, or a nucleotide sequence that is at least 85% identical thereto, or differs by no more than 45 nucleotides therefrom;

(ii) a second nucleotide sequence of SEQ ID NO: 306, or a nucleotide sequence that is at least 85% identical thereto, or differs by no more than 45 nucleotides therefrom; or

(iii) both (i) and (ii).

39. The nucleic acid molecule of claim 38 , comprising:

(i) a first nucleotide sequence of any of SEQ ID NOs: 73, 304, 307, 308, 309, 310, 311, 313, or 319;

(ii) a second nucleotide sequence of SEQ ID NO: 306; or

(iii) both (i) and (ii).

40. A vector comprising the nucleic acid molecule of claim 38 .

41. A cell comprising the nucleic acid molecule of claim 38 .

42. A method of producing an anti-APRIL antibody molecule, the method comprising culturing a cell of claim 41 under conditions that allow production of an antibody molecule, thereby producing the antibody molecule.

43. The nucleic acid molecule of claim 38 , comprising:

(i) a first nucleotide sequence of any of SEQ ID NOs: 73, 304, 307, 308, 309, 310, 311, 313, or 319, or a nucleotide sequence that is at least 90% or more identical thereto, or differs by no more than 30 nucleotides therefrom;

(ii) a second nucleotide sequence of SEQ ID NO: 306, or a nucleotide sequence that is at least 90% or more identical thereto, or differs by no more than 30 nucleotides therefrom; or

(iii) both (i) and (ii).

44. The nucleic acid molecule of claim 38 , comprising:

(i) a first nucleotide sequence of any of SEQ ID NOs: 73, 304, 307, 308, 309, 310, 311, 313, or 319, or a nucleotide sequence that is at least 95% or more identical thereto, or differs by no more than 15 nucleotides therefrom;

(ii) a second nucleotide sequence of SEQ ID NO: 306, or a nucleotide sequence that is at least 95% or more identical thereto, or differs by no more than 15 nucleotides therefrom; or

(iii) both (i) and (ii).

45. The nucleic acid molecule of claim 38 , comprising:

(i) a first nucleotide sequence of any of SEQ ID NOs: 73, 304, 307, 308, 309, 310, 311, 313, or 319, or a nucleotide sequence that is at least 99% or more identical thereto, or differs by no more than 6 nucleotides therefrom;

(ii) a second nucleotide sequence of SEQ ID NO: 306, or a nucleotide sequence that is at least 99% or more identical thereto, or differs by no more than 6 nucleotides therefrom; or

(iii) both (i) and (ii).

46. The nucleic acid molecule of claim 38 , comprising:

(i) a first nucleotide sequence of SEQ ID NO: 313, or a nucleotide sequence that is at least 85% identical thereto, or differs by no more than 45 nucleotides therefrom;

(ii) a second nucleotide sequence of SEQ ID NO: 306, or a nucleotide sequence that is at least 85% identical thereto, or differs by no more than 45 nucleotides therefrom; or

(iii) both (i) and (ii).

47. The nucleic acid molecule of claim 38 , comprising a first nucleotide sequence of SEQ ID NO: 313, a second nucleotide sequence of SEQ ID NO: 306, or both.

48. The nucleic acid molecule of claim 38 , comprising a first nucleotide sequence of SEQ ID NO: 313 and a second nucleotide sequence of SEQ ID NO: 306.

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 20200317770A1 · Oct 8, 2020

Cited By (1)

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