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

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.

1 . A method of identifying whether a human or humanized antibody or antigen binding fragment that specifically binds to human Pituitary Adenylate Cyclase-Activating Peptide (PACAP) is potentially 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 rodent subject in need thereof, which comprises:
 (i) providing at least one first rodent test subject and at least one second rodent test subject;   (ii) administering PACAP to the at least one first test rodent subject and the at least one second rodent test subject;   (iii) further administering to the at least one first rodent test subject a human or humanized antibody or antigen binding fragment that specifically binds to human PACAP;   (iv) comparing the response of the at least one first rodent test subject and at least one second rodent test subject to light; and   (v) based on this comparison, if the first rodent exhibits increased light aversion than the second rodent thereby identifying that the human or humanized antibody or antigen binding fragment which specifically binds to human PACAP is potentially 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.   
     
     
         2 . A method of identifying whether a human or humanized antibody or antigen binding fragment that specifically binds to human Pituitary Adenylate Cyclase-Activating Peptide (PACAP) is potentially 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, which comprises:
 (i) providing at least one first rodent test subject and at least one second rodent test subject;   (ii) administering to the at least one first rodent test subject a human or humanized antibody or antigen binding fragment that specifically binds to human PACAP;   (iii) administering PACAP to the at least one first rodent test subject and the at least one second rodent test subject;   (iv) comparing the response of the at least one first rodent test subject and at least one second rodent test subject to light; and   (v) based on this comparison, if the first rodent exhibits increased light aversion than the second rodent, thereby identifying that the human or humanized antibody or antigen binding fragment which specifically binds to human PACAP is potentially suitable for precluding the onset of PACAP-associated photophobia or light aversion, in a human subject in need thereof.   
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the efficacy of the identified human or humanized antibody or antigen binding fragment that specifically binds to human PACAP for inhibiting PACAP-associated photophobia or light aversion, or for precluding the onset of PACAP-associated photophobia or light aversion, is confirmed in a human subject. 
     
     
         5 . The method of  claim 2 , wherein the efficacy of the identified human or humanized antibody or antigen binding fragment that specifically binds to human PACAP for inhibiting PACAP-associated photophobia or light aversion, or for precluding the onset of PACAP-associated photophobia or light aversion, is confirmed in a human subject. 
     
     
         6 . The method of  claim 1 , wherein the at least one first rodent test subject and the at least one second rodent test subject is a CD1 mouse. 
     
     
         7 - 51 . (canceled) 
     
     
         52 . A method of identifying whether a human or humanized an antibody or antigen binding fragment that specifically binds to human Pituitary Adenylate Cyclase-Activating Peptide (PACAP) decreases or inhibits light-induced pain signaling through intrinsically photosensitive retinal ganglion cells (“ipRGCs”) in a human subject, which comprises:
 (i) providing at least one first rodent test subject and at least one second rodent test subject; 
 (ii) administering PACAP to the first rodent test subject and the second rodent test subject; 
 (iii) administering to the first rodent test subject a human or humanized an antibody or antigen binding fragment that specifically binds to human PACAP; 
 (iv) comparing the response of the at least one first rodent test subject and at least one second rodent test subject to light; and 
 (v) based on this comparison, identifying if the human or humanized antibody or antigen binding fragment that specifically binds to human PACAP decreases or inhibits light-induced pain signaling through intrinsically photosensitive retinal ganglion cells (“ipRGCs”); and 
 (vi) confirming that said human or humanized antibody or antigen binding fragment that specifically binds to human PACAP decreases or inhibits light-induced pain signaling in a human subject. 
 
     
     
         53 . (canceled) 
     
     
         54 . The method of  claim 2 , wherein the first and second rodent test subjects are a CD1 Mouse. 
     
     
         55 . The method of  claim 52 , wherein the first and second rodent test subjects are a CD1 Mouse. 
     
     
         56 . The method of  claim 1 , wherein the light aversion test is effected in a testing chamber that (i) is partitioned into two zones, (ii) comprises a source of infrared light, wherein (iii) one zone is exposed to the infrared light and the second zone is not exposed to the infrared light, (iv) comprises an opening that permits free movement of a test subject between the two zones and (v) further comprises a means for detecting and recording the movement of the test subject between the first and second zones. 
     
     
         57 . The method of  claim 2 , wherein the light aversion test is effected in a testing chamber that (i) is partitioned into two zones, (ii) comprises a source of infrared light, wherein (iii) one zone is exposed to the infrared light and the second zone is not exposed to the infrared light, (iv) comprises an opening that permits free movement of a test subject between the two zones and (v) further comprises a means for detecting and recording the movement of the test subject between the first and second zones. 
     
     
         58 . The method of  claim 52 , wherein the light aversion test is effected in a testing chamber that (i) is partitioned into two zones, (ii) comprises a source of infrared light, wherein (iii) one zone is exposed to the infrared light and the second zone is not exposed to the infrared light, (iv) comprises an opening that permits free movement of a test subject between the two zones and (v) further comprises a means for detecting and recording the movement of the test subject between the first and second zones.