US 12,643,957 B2 · Antibodies to plasminogen activator inhibitor-1 (PAI-1) and uses thereof

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.

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.

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

Life of this patent

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

Life of this patent

Abstract

Claims19