Screening strategies for the identification of binders

1. A method to identify antigen-binding moieties which bind to an epitope of a polypeptide, wherein said polypeptide comprises an enzymatic activity, said method comprising

(a) screening a library of antigen-binding moieties against a polypeptide comprising the epitope and having the enzymatic activity and isolating those members of said library that bind to said polypeptide,

(b) counter-screening the members of the library isolated in step (a) against a variant of the polypeptide, wherein said variant polypeptide comprises a mutated epitope and is devoid of enzymatic activity, and

(c) isolating those members that do not bind to said variant polypeptide, therein identifying those members that bind to the epitope of the polypeptide.

2. The method of claim 1 , wherein said variant polypeptide is an epitope mutant of the wild type polypeptide.

3. The method of claim 1 , wherein said epitope of the polypeptide only exists within one or more isoforms of the polypeptide.

4. The method of claim 1 , wherein said epitope of the polypeptide only exists in the monomeric, multimeric or heteromeric form of the polypeptide.

5. The method of claim 1 , wherein said polypeptide is a protease.

6. The method of claim 5 , wherein said protease is a viral protease.

7. The method according to claim 1 , further comprising

(d) testing if the antigen-binding moieties isolated in step (c) inhibit the enzymatic activity of the polypeptide.

8. The method of claim 6 , wherein said viral protease is the NS2B-NS3 protease of West Nile Virus.

9. The method of claim 1 , wherein the epitope is mutated by removal or the substitution of an amino acid.