US 2022/0195022 A1 · PAC1 ANTIBODIES AND USES THEREOF

Abstract

The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.

Claims24

Dependent claims

An isolated antibody or antigen-binding fragment thereof that specifically binds to human pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1)(SEQ ID NO:

1), wherein the antibody or antigen-binding fragment thereof comprises:
(i) a light chain variable region in which the amino acid at position 29 according to AHo numbering is a basic amino acid that interacts with amino acids Glu120 or Asp121 of human PAC1, and (ii) a heavy chain variable region in which the amino acid at position 61 according to AHo numbering is a hydrophobic, basic, or neutral hydrophilic amino acid that interacts with amino acids Asn60 or Ile61 of human PAC1, and wherein the antibody or antigen-binding fragment thereof inhibits PACAP-induced activation of human PAC1 with an IC50 less than 500 pM as measured by a cell-based cAMP assay.

An isolated antibody or antigen-binding fragment thereof that specifically binds to human PAC1, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising complementarity determining regions CDRL1, CDRL2, and CDRL3 and a heavy chain variable region comprising complementarity determining regions CDRH1, CDRH2, and CDRH3, wherein CDRL1 comprises a sequence selected from SEQ ID NOs:

5-25;
CDRL2 comprises a sequence selected from SEQ ID NOs:
26-35;
CDRL3 comprises a sequence selected from SEQ ID NOs:
36-51;
CDRH1 comprises a sequence selected from SEQ ID NOs:
88-105;
CDRH2 comprises a sequence selected from SEQ ID NOs:
106-170;
and CDRH3 comprises a sequence selected from SEQ ID NOs:
171-190.

8 more elements

An isolated antibody that specifically binds to human PAC1, wherein the antibody comprises a light chain and a heavy chain, wherein:

(a) the light chain comprises the sequence of SEQ ID NO:
506 and the heavy chain comprises the sequence of SEQ ID NO:
521;
(b) the light chain comprises the sequence of SEQ ID NO:
506 and the heavy chain comprises the sequence of SEQ ID NO:
522;
(c) the light chain comprises the sequence of SEQ ID NO:
504 and the heavy chain comprises the sequence of SEQ ID NO:
523;
(d) the light chain comprises the sequence of SEQ ID NO:
504 and the heavy chain comprises the sequence of SEQ ID NO:
524;
(e) the light chain comprises the sequence of SEQ ID NO:
506 and the heavy chain comprises the sequence of SEQ ID NO:
525;
(f) the light chain comprises the sequence of SEQ ID NO:
504 and the heavy chain comprises the sequence of SEQ ID NO:
526;
(g) the light chain comprises the sequence of SEQ ID NO:
506 and the heavy chain comprises the sequence of SEQ ID NO:
523;
(h) the light chain comprises the sequence of SEQ ID NO:
507 and the heavy chain comprises the sequence of SEQ ID NO:
527;
(i) the light chain comprises the sequence of SEQ ID NO:
507 and the heavy chain comprises the sequence of SEQ ID NO:
528;
(j) the light chain comprises the sequence of SEQ ID NO:
508 and the heavy chain comprises the sequence of SEQ ID NO:
529;
(k) the light chain comprises the sequence of SEQ ID NO:
510 and the heavy chain comprises the sequence of SEQ ID NO:
531;
(l) the light chain comprises the sequence of SEQ ID NO:
511 and the heavy chain comprises the sequence of SEQ ID NO:
532;
(m) the light chain comprises the sequence of SEQ ID NO:
512 and the heavy chain comprises the sequence of SEQ ID NO:
533;
(n) the light chain comprises the sequence of SEQ ID NO:
513 and the heavy chain comprises the sequence of SEQ ID NO:
534;
(o) the light chain comprises the sequence of SEQ ID NO:
514 and the heavy chain comprises the sequence of SEQ ID NO:
535;
(p) the light chain comprises the sequence of SEQ ID NO:
515 and the heavy chain comprises the sequence of SEQ ID NO:
535;
(q) the light chain comprises the sequence of SEQ ID NO:
516 and the heavy chain comprises the sequence of SEQ ID NO:
532;
(r) the light chain comprises the sequence of SEQ ID NO:
517 and the heavy chain comprises the sequence of SEQ ID NO:
536;
(s) the light chain comprises the sequence of SEQ ID NO:
509 and the heavy chain comprises the sequence of SEQ ID NO:
532;
or
(t) the light chain comprises the sequence of SEQ ID NO:
518 and the heavy chain comprises the sequence of SEQ ID NO:
530.

58 more elements

Dependencies are inferred from the claim text.

Pac1 antibodies and uses thereof

Life of this patent

Pac1 antibodies and uses thereof

Life of this patent

Abstract

Claims24