Use of anti-pacap antibodies and antigen binding fragments thereof for treatment, prevention, or inhibition of photophobia

Patent metadata

Field	Value
Publication number	US-10844116-B2
Application number	US-201615130215-A
Country	US
Kind code	B2
Filing date	Apr 15, 2016
Priority date	Apr 16, 2015
Publication date	Nov 24, 2020
Grant date	Nov 24, 2020

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 putatively determining whether an antibody or antigen binding fragment is suitable for use in treating or preventing Pituitary Adenylate Cyclase-Activating Peptide (PACAP)-associated photophobia or light aversion, or precluding the onset of PACAP-associated photophobia or light aversion, in a human subject in need thereof, which method comprises:
(i) providing at least one first non-human test subject and at least one non-human second test subject;
(ii) first administering PACAP to the at least one first non-human test subject and the at least one second non-human test subject;
(iii) subsequently administering to the at least one first non-human test subject who has been administered PACAP an anti-PACAP antibody or an antigen binding fragment thereof;
(iv) comparing the response of the at least one first non-human test subject and at least one second non-human test subject to light; and
(v) if said first at least one non-human test subject exhibits decreased light aversion or decreased photophobia as compared with the at least one second non-human test subject, identifying said antibody or antigen binding fragment as being putatively suitable for use in treating or preventing PACAP-associated photophobia or light aversion, or precluding the onset of PACAP-associated photophobia or light aversion in a human subject in need thereof;
wherein said anti-PACAP antibody or antigen binding fragment comprises an immunoglobulin variable heavy chain having the CDR1 sequence of SEQ ID NO: 44; a CDR2 sequence of SEQ ID NO: 46; and a CDR3 sequence of SEQ ID NO: 48; and/or an immunoglobulin variable light chain having the CDR1 sequence of SEQ ID NO: 64; a CDR2 sequence of SEQ ID NO: 66; and a CDR3 sequence of SEQ ID NO: 68.

2. A method of screening for an antibody or antigen binding fragment thereof suitable for use in treating or preventing Pituitary Adenylate Cyclase-Activating Peptide (PACAP)-associated photophobia or light aversion, or precluding the onset of PACAP-associated photophobia or light aversion, in a human subject in need thereof, which comprises:
(i) providing at least one first non-human test subject and at least one second non-human test subject;
(ii) first administering to the at least one first non-human test subject an anti-PACAP antibody or an antigen binding fragment thereof;
(iii) subsequently administering PACAP to the at least one first non-human test subject and the at least one second non-human test subject, wherein said first subject has previously been administered said anti-PACAP antibody or an antigen binding fragment thereof;
(iv) comparing the response of the at least one first non-human test subject and at least one second non-human test subject to light; and
(v) if said first at least one non-human test subject exhibits decreased light aversion or decreased photophobia as compared with the at least one second non-human test subject, identifying said antibody or antigen binding fragment as being putatively suitable for use in treating or preventing PACAP-associated photophobia or light aversion, or precluding the onset of PACAP-associated photophobia or light aversion in a human subject in need thereof;
wherein said anti-PACAP antibody or antigen binding fragment comprises an immunoglobulin variable heavy chain having the CDR1 sequence of SEQ ID NO: 44; a CDR2 sequence of SEQ ID NO: 46; and a CDR3 sequence of SEQ ID NO: 48; and/or an immunoglobulin variable light chain having the CDR1 sequence of SEQ ID NO: 64; a CDR2 sequence of SEQ ID NO: 66; and a CDR3 sequence of SEQ ID NO: 68.

3. The method of claim 1 or 2 , wherein the efficacy of said anti-PACAP antibody or antigen binding fragment thereof for putatively inhibiting PACAP-associated photophobia or light aversion, or precluding the onset of PACAP-associated photophobia or light aversion in a human subject in need thereof, is confirmed by administering said anti-PACAP antibody or antigen binding fragment to a human subject who comprises or chronically experiences photophobia or light aversion caused by a chronic condition associated with photophobia or light aversion and determining in said subject whether said anti-PACAP antibody or antigen binding fragment thereof inhibits PACAP-associated photophobia or light aversion, or precludes the onset or the frequency of onset of PACAP-associated photophobia or light aversion in said human subject who comprises or chronically experiences photophobia or light aversion caused by a condition associated with photophobia or light aversion.

4. The method of claim 1 or 2 , which comprises determining whether said anti-PACAP antibody or fragment thereof inhibits or diminishes light aversion behavior in a first rodent administered PACAP and said anti-PACAP antibody or antigen binding fragment thereof, as compared to a second rodent administered PACAP which is not administered said anti-PACAP antibody or antigen binding fragment thereof.

5. The assay of claim 1 or 2 wherein said anti-PACAP antibody is full-length.

6. The assay of claim 1 or 2 wherein said anti-PACAP antibody is humanized.

7. The assay of claim 1 or 2 wherein said anti-PACAP antibody comprises a human IgG1, IgG2, IgG3 or IgG4 constant region.

8. The assay of claim 1 or 2 wherein said anti-PACAP antibody comprises a human IgG1 constant region.

9. The assay of claim 1 or 2 wherein said anti-PACAP antibody is non-glycosylated.

Assignees

• Alderbio Holdings Llc
• The Univ Of Iowa Research Foundation
• H Lundbeck As

Inventors

• Kuburas Adisa
• 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
• Mason Bianca
• Sowers Levi P
• Russo Andrew F
• Loomis Maria-Cristina
• Garcia-Martinez Leon F
• Dutzar Benjamin H
• Allison Daniel S
• Hendrix Katherine Lee

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