US 11,993,648 B2
Screening method for identifying anti-PACAP antibodies or antibody fragments suitable for use in treating or preventing PACAP-associated photophobia or light aversion
Adisa Kuburas, North Liberty, IA (US); Bianca Mason, Iowa City, IA (US); Levi P. Sowers, Iowa City, IA (US); Andrew F. Russo, Iowa City, IA (US); Maria-Cristina Loomis, Bothell, WA (US); Leon F. Garcia-Martinez, Woodinville, WA (US); Benjamin H. Dutzar, Seattle, WA (US); Daniel S. Allison, Lake Forest Park, WA (US); Katherine Lee Hendrix, Renton, WA (US); Ethan W. Ojala, Snohomish, WA (US); Pei Fan, Bothell, WA (US); Jeffrey T. L. Smith, Bellevue, WA (US); John A. Latham, Seattle, WA (US); Charlie Karasek, Seattle, WA (US); Jenny Mulligan, Lake Forest Park, WA (US); Michelle Scalley-Kim, Seattle, WA (US); Erica Stewart, Seattle, WA (US); Vanessa Lisbeth Rubin, Seattle, WA (US); and Jens J. Billgren, Seattle, WA (US)
Assigned to H. LUNDBECK A/S, Valby (DK); and The University of lowa Research Foundation
Filed by H. LUNDBECK A/S, Valby (DK); and The University of Iowa Research Foundation, Iowa City, IA (US)
Filed on Nov. 20, 2020, as Appl. No. 16/953,443.
Application 16/953,443 is a division of application No. 15/130,215, filed on Apr. 15, 2016, granted, now 10,844,116, issued on Nov. 24, 2020.
Claims priority of provisional application 62/148,583, filed on Apr. 16, 2015.
Claims priority of provisional application 62/148,557, filed on Apr. 16, 2015.
Claims priority of provisional application 62/148,643, filed on Apr. 16, 2015.
Claims priority of provisional application 62/148,640, filed on Apr. 16, 2015.
Claims priority of provisional application 62/148,562, filed on Apr. 16, 2015.
Claims priority of provisional application 62/148,596, filed on Apr. 16, 2015.
Claims priority of provisional application 62/148,550, filed on Apr. 16, 2015.
Prior Publication US 2021/0324068 A1, Oct. 21, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/395 (2006.01); A61P 25/06 (2006.01); C07K 16/26 (2006.01); A61K 39/00 (2006.01); A61K 45/06 (2006.01); A61K 49/00 (2006.01); C07K 14/575 (2006.01); C07K 16/42 (2006.01); G01N 33/50 (2006.01); G01N 33/74 (2006.01)
CPC C07K 16/26 (2013.01) [A61K 39/3955 (2013.01); A61P 25/06 (2018.01); A61K 39/39566 (2013.01); A61K 2039/505 (2013.01); A61K 45/06 (2013.01); A61K 49/0004 (2013.01); A61K 49/0008 (2013.01); C07K 14/57536 (2013.01); C07K 14/57563 (2013.01); C07K 16/4241 (2013.01); C07K 2317/21 (2013.01); C07K 2317/24 (2013.01); C07K 2317/33 (2013.01); C07K 2317/34 (2013.01); C07K 2317/40 (2013.01); C07K 2317/50 (2013.01); C07K 2317/54 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01); G01N 33/5088 (2013.01); G01N 33/74 (2013.01); G01N 2333/5757 (2013.01); Y02A 50/30 (2018.01)] 9 Claims
 
1. A method of screening for an antibody or antigen binding fragment 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 subject in need thereof,
which method 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) further administering to the at least one first test subject one or more anti-PACAP antibodies, or an antigen binding fragment of any of the foregoing, wherein said one or more antibodies or antigen binding fragments includes one comprising a variable heavy chain polypeptide having the heavy chain CDRs1-3 of SEQ ID NO: 44, 46 and 48 respectively; and a variable light chain polypeptide having the light chain CDRs1-3 of SEQ ID NO: 64, 66 and 68 respectively; or one comprising the variable heavy chain polypeptide of SEQ ID NO: 42 and the variable light chain polypeptide of SEQ ID NO: 62;
(iv) comparing the response of the at least one first test subject and the at least one second test subject to light; and
(v) based on this comparison, identifying one or more antibodies or antigen binding fragments thereof that yield 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 identifying an antibody or antigen binding fragment 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 subject in need thereof; or
which method 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 one or more anti-PACAP antibodies, or an antigen binding fragment of any of the foregoing, wherein said one or more antibodies or antigen binding fragments thereof includes one comprising a variable heavy chain polypeptide having the heavy chain CDRs1-3 of SEQ ID NO: 44, 46 and 48 respectively; and a variable light chain polypeptide having the light chain CDRs1-3 of SEQ ID NO: 64, 66 and 68 respectively; or one comprising the variable heavy chain polypeptide of SEQ ID NO: 42 and the variable light chain polypeptide of SEQ ID NO: 62;
(iii) 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 the at least one second test subject to light; and
(v) based on this comparison, identifying antibodies or antigen binding fragments that yield decreased photophobia or decreased light aversion in the at least one first test subject as compared with the at least one second test subject, identifying an antibody or antigen binding fragment suitable for use in treating or preventing PACAP-associated photophobia or light aversion, or identifying an antibody or antigen binding fragment suitable for precluding the onset of PACAP-associated photophobia or light aversion, in a subject to be treated in need thereof.