IP Library › Granted Patent US 11,472,866
Granted Patent B2
US 11,472,866 · App. 17/478,645 · Granted Oct 18, 2022

Adeno-associated virus antibodies, fragments thereof and encoding polynucleotides

Inventors: Sohrab Khan (Cambridge, MA); Danielle Griffin (Cambridge, MA); Louise Rodino-Klapac (Cambridge, MA)
Assignee: Sarepta Therapeutics, Inc.
C07K16/08A01K67/027G01N33/54306A01K2217/05
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Quick Facts
Patent No.
US 11,472,866
App. No.
17/478,645
Granted
Oct 18, 2022
Kind
B2
Abstract

The present disclosure relates to an isolated anti-AAV (adeno-associated virus) antibody or an antigen-binding fragment thereof capable of specifically binding an epitope of AAVrh74 capsid protein and uses thereof.

Claims (45)

1. An isolated antibody or antigen-binding fragment thereof that comprises a heavy chain variable region comprising VH CDR1, VH CDR2, and VH CDR3 domains, and a light chain variable region comprising VL CDR1, VL CDR2, and VL CDR3 domains, wherein:

a. the VH CDR1 domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 33, SEQ ID NO: 39, SEQ ID NO: 46, SEQ ID NO: 52, and SEQ ID NO: 58;

b. the VH CDR2 domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 34, SEQ ID NO: 40, SEQ ID NO: 47, SEQ ID NO: 53, and SEQ ID NO: 59;

c. the VH CDR3 domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 35, SEQ ID NO: 41, SEQ ID NO: 48, SEQ ID NO: 54, and SEQ ID NO: 60;

d. the VL CDR1 domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 36, SEQ ID NO: 42, SEQ ID NO: 49, SEQ ID NO: 55, and SEQ ID NO: 61;

e. the VL CDR2 domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 37, SEQ ID NO: 43, SEQ ID NO: 50, SEQ ID NO: 56, and SEQ ID NO: 62; and

f. the VL CDR3 domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 38, SEQ ID NO: 44, SEQ ID NO: 51, SEQ ID NO: 57, and SEQ ID NO: 63.

2. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody comprises a heavy chain variable region that comprises VH CDR1, VH CDR2, and VH CDR3 domains, and a light chain variable region that comprises VL CDR1, VL CDR2, and VL CDR3 domains selected from the group consisting of:

a. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 33, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 34, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 35, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 36, a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 37, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 38;

b. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 39, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 40, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 41, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 42, a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 43, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 44;

c. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 46, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 47, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 48, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 49, a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 50, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 51;

d. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 52, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 53, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 54, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 55 a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 56, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 57; and

e. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 58, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 59, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 60, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 61, a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 62, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 63.

3. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region of the antibody or antigen binding fragment thereof is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 9, and SEQ ID NO: 17.

4. The isolated antibody or antigen-binding fragment thereof of claim 3 , wherein the light chain variable region of the antibody or antigen binding fragment thereof is selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 6, SEQ ID NO: 14, SEQ ID NO: 10, and SEQ ID NO: 18.

5. The isolated antibody or antigen-binding fragment thereof of claim 4 , wherein

a. the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 9, and SEQ ID NO: 17; and

b. the light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 6, SEQ ID NO: 14, SEQ ID NO: 10, and SEQ ID NO: 18.

6. The isolated antibody or antigen-binding fragment thereof of claim 5 , comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 2.

7. The isolated antibody or antigen-binding fragment thereof of claim 5 , comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 5 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 6.

8. The isolated antibody or antigen-binding fragment thereof of claim 5 , comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 13 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 14.

9. The isolated antibody or antigen-binding fragment thereof of 5 , comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 9 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 10.

10. The isolated antibody or antigen-binding fragment thereof of claim 5 , comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 17 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 18.

11. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or binding fragment thereof binds to a capsid protein of AAV8 and/or AAV9 with less affinity as compared to a capsid protein of AAVrh74.

12. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is labeled with a radioactive, enzymatic, or fluorescent group.

13. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a full-length antibody or an antibody fragment selected from the group consisting of Fab, Fab′, Fab′-SH, Fd, Fv, dAb, F(ab′)2, scFv, bispecific single-chain Fv dimers, diabodies, triabodies, and sxFv genetically fused to the same or a different antibody.

14. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a murine antibody, a chimeric murine/human antibody, a human antibody, an engineered antibody, or a humanized antibody.

15. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is a bispecific antibody.

16. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is a multispecific antibody.

17. A polynucleotide comprising a nucleic acid sequence that encodes the isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof comprises:

a. a VH CDR1 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 33, SEQ ID NO: 39, SEQ ID NO: 46, SEQ ID NO: 52, and SEQ ID NO: 58;

b. a VH CDR2 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 34, SEQ ID NO: 40, SEQ ID NO: 47, SEQ ID NO: 53, and SEQ ID NO: 59;

c. a VH CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 35, SEQ ID NO: 41, SEQ ID NO: 48, SEQ ID NO: 54, and SEQ ID NO: 60;

d. a VL CDR1 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 36, SEQ ID NO: 42, SEQ ID NO: 49, SEQ ID NO: 55, and SEQ ID NO: 61;

e. a VL CDR2 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 37, SEQ ID NO: 43, SEQ ID NO: 50, SEQ ID NO: 56, and SEQ ID NO: 62; and

f. a VL CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 38, SEQ ID NO: 44, SEQ ID NO: 51, SEQ ID NO: 57, and SEQ ID NO: 63.

18. The polynucleotide of claim 17 , wherein the polynucleotide comprises a nucleic acid sequence that encodes:

a. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 33, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 34, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 35, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 36, a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 37, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 38;

b. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 39, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 40, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 41, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 42, a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 43, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 44;

c. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 46, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 47, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 48, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 49, a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 50, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 51;

d. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 52, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 53, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 54, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 55 a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 56, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 57; or

e. a VH CDR1 having the amino acid sequence set forth in SEQ ID NO: 58, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO: 59, a VH CDR3 having the amino acid sequence set forth in SEQ ID NO: 60, a VL CDR1 having the amino acid sequence set forth in SEQ ID NO: 61, a VL CDR2 having the amino acid sequence set forth in SEQ ID NO: 62, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO: 63.

19. The polynucleotide of claim 17 , wherein the polynucleotide comprises a nucleic acid sequence that encodes a heavy chain variable region and a nucleic acid sequence that encodes a light chain variable region, wherein:

a. the nucleic acid encoding the heavy chain variable region comprises a nucleotide sequence selected from the group consisting of SEQ ID NO: 3; SEQ ID NO: 7; SEQ ID NO: 15; SEQ ID NO: 11; and SEQ ID NO: 19; and

b. the nucleic acid encoding the light chain variable region comprises a nucleotide sequence selected from the group consisting of SEQ ID NO: 4; SEQ ID NO: 8; SEQ ID NO: 16; SEQ ID NO: 12; and SEQ ID NO: 20.

Assignments (2)
SECURITY INTEREST Recorded May 7, 2025
From: SAREPTA THERAPEUTICS, INC.
To: JPMORGAN CHASE BANK, N.A. AS ADMINISTRATIVE AGENT
Reel/Frame 071218/0445 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2022
From: KHAN, SOHRAB; GRIFFIN, DANIELLE; RODINO-KLAPAC, LOUISE
To: SAREPTA THERAPEUTICS, INC.
Reel/Frame 058622/0585 →