Methods of determining whether anti-PACAP antibodies inhibit PACAP-associated photophobia or light aversion

Patent metadata

Field	Value
Publication number	US-10981984-B2
Application number	US-201816217567-A
Country	US
Kind code	B2
Filing date	Dec 12, 2018
Priority date	Apr 16, 2015
Publication date	Apr 20, 2021
Grant date	Apr 20, 2021

Abstract

This invention relates to methods of screening for anti-PACAP antibodies, or anti-PACAP receptor antibodies, and antigen binding fragments thereof, for potential use in treating or preventing PACAP-associated photophobia or light aversion, and therapeutic compositions containing and methods of using anti-PACAP antibodies, or anti-PACAP receptor antibodies, and antigen binding fragments thereof.

First claim

What is claimed is:

1. A method of determining whether an antibody or antigen binding fragment inhibits Pituitary Adenylate Cyclase-Activating Peptide (PACAP)-associated photophobia or light aversion, which comprises:
(i) providing at least one first test subject and at least one second test subject;
(ii) administering PACAP to the at least one first test subject and the at least one second test subject;
(iii) after step (ii) further administering to the at least one first test subject an anti-PACAP antibody or antigen binding fragment comprising
(a) a heavy chain variable region (VH) comprising a complementarity determining region 1 (CDR1) sequence consisting of the amino acid sequence of SEQ ID NO: 444, a complementarity determining region 2 (CDR2) sequence consisting of the amino acid sequence of SEQ ID NO: 446, and a complementarity determining region 3 (CDR3) sequence consisting of the amino acid sequence of SEQ ID NO: 448 and
(b) a light chain variable region (VL) comprising a CDR1 sequence consisting of the amino acid sequence of SEQ ID NO: 464, a CDR2 sequence consisting of the amino acid sequence of SEQ ID NO: 466, and a CDR3 sequence consisting of the amino acid sequence of SEQ ID NO: 468;

(iv) comparing the response of the at least one first test subject and at least one second test subject to light; and
(v) based on the comparison in (iv), identifying whether the anti-PACAP antibody or antigen binding fragment yields a decreased light aversion or decreased photophobia in the at least one first test subject as compared with the at least one second test subject, thereby determining whether the anti-PACAP antibody or antigen binding fragment inhibits PACAP-associated photophobia or light aversion.

2. A method of determining whether an antibody or antigen binding fragment inhibits Pituitary Adenylate Cyclase-Activating Peptide (PACAP)-associated photophobia or light aversion, which comprises:
(i) providing at least one first test subject and at least one second test subject;
(ii) administering to the at least one first test subject an anti-PACAP antibody or antigen binding fragment comprising
(a) a VH comprising a CDR1 sequence consisting of the amino acid sequence of SEQ ID NO: 444, a CDR2 sequence consisting of the amino acid sequence of SEQ ID NO: 446, and CDR3 sequence consisting of the amino acid sequence of SEQ ID NO: 448 and
(b) a VL comprising a CDR1 sequence consisting of the amino acid sequence of SEQ ID NO: 464, a CDR2 sequence consisting of the amino acid sequence of SEQ ID NO: 466, and a CDR3 sequence consisting of the amino acid sequence of SEQ ID NO: 468;

(iii) after step (ii) further administering PACAP to the at least one first test subject and the at least one second test subject;
(iv) comparing the response of the at least one first test subject and at least one second test subject to light; and
(v) based on the comparison in (iv), identifying whether the anti-PACAP antibody or antigen binding fragment yields a decreased light aversion or decreased photophobia in the at least one first test subject as compared with the at least one second test subject, thereby determining whether the anti-PACAP antibody or antigen binding fragment inhibits PACAP-associated photophobia or light aversion.

3. The method of claim 1 or 2 , wherein:
(I) the VH comprises the amino acid sequence of SEQ ID NO: 442;
(II) the VL comprises the amino acid sequence of SEQ ID NO: 462; or
(III) the VH comprises the amino acid sequence of SEQ ID NO: 442 and the VL comprises the amino acid sequence of SEQ ID NO: 462.

4. The method of claim 1 or 2 , wherein said anti-PACAP antibody or antigen binding fragment comprises:
(I) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 441;
(II) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 461; or
(III) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 441 and a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 461.

5. The method of claim 1 or 2 , wherein said anti-PACAP antibody or antigen binding fragment is humanized or chimeric.

6. The method of claim 1 or 2 , wherein said anti-PACAP antibody or antigen binding fragment comprises an antigen binding fragment selected from a single chain antibody, fragment antigen binding (“Fab”) fragment, Fab′ fragment, monovalent antibody fragment, and a F(ab′)2 fragment of the antibody.

7. The method of claim 1 or 2 , wherein said anti-PACAP antibody or antigen binding fragment comprises—(a) a VH comprising a CDRI sequence consisting of the amino acid sequence of SEQ ID NO: 444, a CDR2 sequence consisting of the amino acid sequence of SEQ ID NO: 446, and a CDR3 sequence consisting of the amino acid sequence of SEQ ID NO: 448; (b) a VL comprising a CDRI sequence consisting of the amino acid sequence of SEQ ID NO: 464, a CDR2 sequence consisting of the amino acid sequence of SEQ ID NO: 466, and a CDR3 sequence consisting of the amino acid sequence of SEQ ID NO: 468; and (c) a human Fc region of a human IgG which is selected from a human IgG1, IgG2, IgG3, or IgG4.

8. The method of claim 7 , wherein the amino acid sequence of the Fc region of the human IgG selected from the human IgG1, IgG2, IgG3, or IgG4 comprises a mutation to eliminate: (i) at least one N-glycosylation; (ii) at least one O-glycosylation; or (iii) at least one N-glycosylation and at least O-glycosylation.

9. The method of claim 1 or 2 , wherein said anti-PACAP antibody or antigen binding fragment entirely lacks:
(i) N-glycosylation;
(ii) O-glycosylation; or
(iii) N-glycosylation and O-glycosylation.

Assignees

• Alder Biopharmaceuticals Inc
• The Univ Of Iowa Research Foundation
• H Lundbeck As

Inventors

• Kuburas Adisa
• Mason Bianca
• Sowers Levi P
• Russo Andrew F
• Loomis Maria-Cristina
• Garcia-Martinez Leon F
• Dutzar Benjamin H
• Allison Daniel S
• Hendricks Katherine Lee
• Ojala Ethan W
• Fan Pei
• Smith Jeffrey T L
• Latham John A
• Karasek Charlie
• Mulligan Jenny
• Scalley-Kim Michelle
• Stewart Erica
• Rubin Vanessa Lisbeth
• Billgren Jens J

Classifications

• A61K49/0008

  Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure · CPC title

• A61K49/0004

  Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions · CPC title

• C07K16/4241

  against anti-human or anti-animal Ig · CPC title

• A61K39/39566

  against immunoglobulins, e.g. anti-idiotypic antibodies · CPC title

• G01N33/74

  involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors} · CPC title