Neuropilin antagonists
Novel anti-NRP1 antibodies and variants thereof having unique structural and functional characteristics are disclosed. Also provided are uses of the antibodies in research, diagnostic and therapeutic applications.
1. An anti-neuropilin-1 (NRP1) antibody capable of inhibiting at least one neuropilin (NRP) mediated biological activity, which comprises a light chain variable domain comprising the following CDR amino acid sequences: CDRL1 (RASQYFSSYLA; SEQ ID NO:129), CDRL2 (GASSRAS; SEQ ID NO:130) and CDRL3 (QQYLGSPPT; SEQ ID NO:131).
2. The antibody of claim 1 , which comprises a light chain variable domain sequence of SEQ ID NO:5.
3. The antibody of claim 1 , which comprises a heavy chain variable domain comprising the following CDR amino acid sequences: CDRH1 (GFTFSSYAMS; SEQ ID NO:132), CDRH2 (SQISPAGGYTNYADSVKG; SEQ ID NO:133) and CDRH3 (ELPYYRMSKVMDV; SEQ ID NO:134).
4. The antibody of claim 3 , which comprises a heavy chain variable domain sequence of SEQ ID NO:6.
5. The antibody of claim 1 , which is the YW107.4.87 antibody comprising a light chain variable domain sequence of SEQ ID NO:5 and a heavy chain variable domain sequence of SEQ ID NO:6.
6. The antibody according to claim 1 , wherein the antibody is capable of binding to both murine NRP1 and human NRP1.
7. The antibody according to claim 1 , wherein the antibody is a monoclonal antibody.
8. The antibody according to claim 1 , wherein the antibody is a bispecific antibody.
9. The antibody according to claim 1 , wherein the antibody is a synthetic antibody.
10. The antibody of claim 3 , which comprises a heavy chain variable domain sequence which differs from SEQ ID NO:6 only by the insertion of a glycine residue between the arginine residue at Kabat position 94 and the glutamate residue at Kabat position 95.
11. The antibody of claim 10 , which comprises a light chain variable domain sequence of SEQ ID NO:5.