Methods of determining whether anti-PACAP (adenylate cyclase-activating peptide) antibodies or anti-PACAP antigen binding fragments inhibit PACAP-associated photophobia or light aversion

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 non-human mammalian test subject and at least one second non-human mammalian test subject;

(ii) administering PACAP to the at least one first non-human mammalian test subject and the at least one second non-human mammalian test subject;

(iii) after step (ii), further administering to the at least one first non-human mammalian test subject one or more anti-PACAP antibodies or anti-PACAP antigen-binding fragments comprising a light chain variable region (V L ) comprising a complementarity determining region (CDR)1 consisting of the amino acid sequence of SEQ ID NO: 404, a CDR2 consisting of the amino acid sequence of SEQ ID NO: 406 and a CDR3 consisting of the amino acid sequence of SEQ ID NO: 408; and a heavy chain variable region (V H ) comprising a CDR1 consisting of the amino acid sequence of SEQ ID NO: 424, a CDR2 consisting of the amino acid sequence of SEQ ID NO: 426 and a CDR3 consisting of the amino acid sequence of SEQ ID NO: 428;

(iv) comparing the response of the at least one first non-human mammalian test subject and at least one second non-human mammalian test subject to light in a light aversion or photophobia assay; and

(v) determining whether the anti-PACAP antibodies or anti-PACAP antigen-binding fragments inhibit PACAP-associated photophobia or light aversion based on the comparison of (iv); wherein a decreased light sensitive behavior in the light aversion or photophobia assay in the at least one first non-human mammalian test subject as compared with the at least one second non-human mammalian test subject, indicates that the one or more anti-PACAP antibodies or anti-PACAP antigen-binding fragments yield a decreased light aversion or photophobia, thereby identifying the one or more anti-PACAP antibodies or anti-PACAP antigen-binding fragments as the anti-PACAP antibodies or anti-PACAP antigen binding fragments inhibiting PACAP-associated photophobia or light aversion.

2. A method of determining whether an antibody or antigen binding fragment inhibits Adenylate Cyclase-Activating Peptide (PACAP)-associated photophobia or light aversion, which comprises:

(i) providing at least one first non-human mammalian test subject and at least one second non-human test subject;

(ii) administering to the at least one first non-human mammalian test subject one or more anti-PACAP antibodies or anti-PACAP antigen-binding fragments comprising a light chain variable region (V L ) comprising a complementarity determining region (CDR)1 consisting of the amino acid sequence of SEQ ID NO: 404, a CDR2 consisting of the amino acid sequence of SEQ ID NO: 406 and a CDR3 consisting of the amino acid sequence of SEQ ID NO: 408; and a heavy chain variable region (V H ) comprising a CDR1 consisting of the amino acid sequence of SEQ ID NO: 424, a CDR2 consisting of the amino acid sequence of SEQ ID NO: 426 and a CDR3 consisting of the amino acid sequence of SEQ ID NO: 428;

(iii) after step (ii), administering PACAP to the at least one first non-human mammalian test subject and the at least one second non-human mammalian test subject;

(iv) comparing the response of the at least one first non-human mammalian test subject and at least one second non-human mammalian test subject to light in a light aversion assay; and

(v) determining whether the anti-PACAP antibodies or anti-PACAP antigen-binding fragments inhibit PACAP-associated photophobia or light aversion based on the comparison of (iv); wherein a decreased light sensitive behavior in the light aversion or photophobia assay in the at least one first non-human mammalian test subject as compared with the at least one second non-human mammalian test subject, indicates that the one or more anti-PACAP antibodies or anti-PACAP antigen-binding fragments yield a decreased light aversion or photophobia, thereby identifying the one or more anti-PACAP antibodies or anti-PACAP antigen-binding fragments as the anti-PACAP antibodies or anti-PACAP antigen binding fragments inhibiting PACAP-associated photophobia or light aversion.

3. The method of claim 1 or 2 ,

wherein the at least one first non-human mammalian test subject and the at least one second non-human mammalian test subject is a mouse, monkey, rabbit, rat, guinea pig, dog, or hamster.

4. The method of claim 1 or 2 , wherein the anti-PACAP antibody or anti-PACAP antigen-binding fragment is humanized.

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

6. The method of claim 1 or 2 , wherein the anti-PACAP antigen-binding fragment is selected from scFvs, Fab″ fragments, Fab′ fragments, monovalent antigen-binding fragments, and F(ab′)2 fragments.

7. The method of claim 1 or 2 , wherein the anti-PACAP antibody comprises an Fc region that has been modified to increase at least one of effector function, half-life, proteolysis, or glycosylation.

8. The method of claim 1 or 2 , wherein the anti-PACAP antibody comprises an Fc region that has been modified to decrease at least one of effector function, half-life, proteolysis, or glycosylation.

9. The method of claim 1 or 2 , wherein the anti-PACAP antibody or anti-PACAP antigen-binding fragment lacks N-glycosylation and/or O-glycosylation.

10. The method of claim 1 or 2 , wherein the anti-PACAP antibody or anti-PACAP antigen-binding fragment binds to PACAP with an off-rate (k off ) of less than or equal to 5×10 −4 s −1 .

11. The method of claim 1 or 2 , wherein the anti-PACAP antibody or anti-PACAP antigen-binding fragment binds to human PACAP with a binding affinity (K D ) of less than or equal to 5×10 −10 M.