IP Library › Granted Patent US 12,643,957
Granted Patent B2
US 12,643,957 · App. 17/843,777 · Granted Jun 2, 2026

Antibodies to plasminogen activator inhibitor-1 (PAI-1) and uses thereof

Inventors: Alla Pritsker (Bridgewater, NJ); Patrick Grailhe (Paris, FR); Alexey Rak (Paris, FR); Magali Mathieu (Paris, FR); Christopher Ryan Morgan (Bridgewater, NJ); Nicolas Baurin (Paris, FR); Bruno Poirier (Paris, FR); Cyril Daveu (Paris, FR); Francis Duffieux (Paris, FR); Han Li (Yardley, PA); Dorothea Kominos (Millington, NJ); Philip Janiak (Paris, FR)
Assignee: Sanofi
C07K16/38A61K2039/505C07K2317/24C07K2317/32C07K2317/34C07K2317/56C07K2317/565C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 12,643,957
App. No.
17/843,777
Granted
Jun 2, 2026
Kind
B2
Abstract

The invention provides antibodies that specifically bind to Plasminogen Activator inhibitor type-1 (PAI-1), The invention also provides pharmaceutical compositions, as well as nucleic acids encoding anti-PAI-1 antibodies, recombinant expression vectors and host cells for making such antibodies, or fragments thereof. Methods of using antibodies to modulate PAI-1 activity or detect PAI-1, either in vitro or in vivo, are also provided. The disclosure further provides methods of making antibodies that specifically bind to PAI-1 in the active conformational state.

Claims (65)

1 . An isolated nucleic acid encoding an amino acid sequence of an antibody, or an antigen-binding fragment thereof, that binds specifically to PA1-1, comprising:

(a) a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 34, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 33, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 32; and a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 37, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 145 or SEQ ID NO: 36, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 35; or

(b) a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 22, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 21, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 20; and a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 25, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 24, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 23; or

(c) a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 28, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 27, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 26; and a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 31, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 30, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 29; or

(d) a heavy chain variable region comprising a heavy chain CDR1region comprising the amino acid sequence of SEQ ID NO: 40, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 39, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 38; and a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 43, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 42, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 41; or

(e) a heavy chain variable region comprising a heavy chain CDR 1region comprising the amino acid sequence of SEQ ID NO: 46, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 45, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 44; and a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 49, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 48, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 47; or

(f) a heavy chain variable region comprising a heavy chain CDR1region comprising the amino acid sequence of SEQ ID NO: 52, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 51, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 50; and a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 55, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 54, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 53; or

(g) a heavy chain variable region comprising a heavy chain CDR 1region comprising the amino acid sequence of SEQ ID NO: 58, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 57, and heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 56; and a light chain variable region comprising a light chain CDR1region comprising the amino acid sequence of SEQ ID NO: 61, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 60, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 59; or

(h) a heavy chain variable region comprising a heavy chain CDR1region comprising the amino acid sequence of SEQ ID NO: 64, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 63, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 62; and a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 67, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 66, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 65; or

(i) a heavy chain variable region comprising a heavy chain CDR1region comprising the amino acid sequence of SEQ ID NO: 70, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 69, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 68; and a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 73, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 72, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 71; or

(j) a heavy chain variable region comprising a heavy chain CDR1region comprising the amino acid sequence of SEQ ID NO: 76, heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 75, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 74; and a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 79, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 78, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 77.

2 . A recombinant expression vector comprising the nucleic acid of claim 1 .

3 . A host cell comprising the recombinant expression vector of claim 2 .

4 . A method of producing an antibody, or an antigen binding fragment thereof, that binds specifically to PAI-1, comprising culturing the host cell of claim 3 under conditions such that the antibody, or antigen binding fragment thereof, that binds specifically to PAI-1 is produced by the host cell.

5 . The method of claim 4 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 34, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 33, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 32; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 37, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 145 or the amino acid sequence of SEQ ID NO: 36, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 35.

6 . The method of claim 5 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 22, a heavy chain CDR2 region comprising SEQ ID NO: 21, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 20; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 25, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 24, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 23.

7 . The method of claim 4 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 28, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 27, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 26; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 31, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 30, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 29.

8 . The method of claim 4 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 40, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 39, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 38; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 43, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 42, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 41.

9 . The method of claim 4 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 46, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 45, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 44; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 49, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 48, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 47.

10 . The method of claim 4 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 52, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 51, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 50; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 55, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 54, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 53.

11 . The method of claim 4 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 58, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 57, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 56; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 61, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 60, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 59.

12 . The method of claim 4 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 64, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 63, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 62; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 67, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 66, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 65.

13 . The method of claim 4 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 70, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 69, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 68; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 73, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 72, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 71.

14 . The method of claim 4 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain variable region comprising a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 76, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 75, and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 74; and

a light chain variable region comprising a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 79, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 78, and a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 77.

15 . An isolated nucleic acid encoding an amino acid sequence of an antibody, or an antigen-binding fragment thereof, that binds specifically to PA1-1, comprising:

(a) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 82, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 91; or

(b) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 83, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 92; or

(c) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 84, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 93; or

(d) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 85, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 91; or

(e) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 85, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 93; or

(f) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 86, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 94; or

(g) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 87, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 95; or

(h) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 88, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 96; or

(i) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 89, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 97; or

(j) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 90, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 98; or

(k) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 86, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 95; or

(l) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 89, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 93; or

(m) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 89, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 95; or

(n) a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 86, and a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 93.

16 . A recombinant expression vector comprising the nucleic acid of claim 15 .

17 . A host cell comprising the recombinant expression vector of claim 16 .

18 . A method of producing an antibody, or an antigen binding fragment thereof, that binds specifically to PAI-1, comprising culturing the host cell of claim 17 under conditions such that the antibody, or antigen binding fragment thereof, that binds specifically to PAI-1 is produced by the host cell.

19 . The method of claim 18 , wherein the antibody or antigen binding fragment thereof comprises:

a heavy chain having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 86; and

a light chain having a light chain variable region comprising the amino acid sequence of SEQ ID NO: 93.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 7, 2024
From: JANIAK, PHILIP; MORGAN, CHRISTOPHER RYAN; BAURIN, NICOLAS; GRAILHE, PATRICK; POIRIER, BRUNO; RAK, ALEXEY; MATHIEU, MAGALI; DAVEU, CYRIL; DUFFIEUX, FRANCIS; PRITSKER, ALLA; LI, HAN; KOMINOS, DOROTHEA
To: SANOFI
Reel/Frame 068211/0722 →
CHANGE OF ADDRESS Recorded Jul 3, 2024
From: SANOFI
To: SANOFI
Reel/Frame 068105/0767 →
Priority Claims (1)
EP 14305757 · May 22, 2014 · regional
Continuity (5)
Continuation 16533048 · Aug 6, 2019
Continuation 15809935 · Nov 10, 2017
Continuation 14911429
Provisional Application 61865451 · Aug 13, 2013
Related Publication 20230015181A1 · Jan 19, 2023
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