SIVAKUMAR, PALLAVUR V.,GILBERTSON, DEBRA G.,SNAVELY, MARSHALL D.,MABRY, GEORGE R.,YI, EUGENE C.,YAO, YUE,PRESNELL, SCOTT R.
申请号：
ES09724060
公开号：
ES2456296T3
申请日:
2009.03.27
申请国别(地区):
ES
年份:
2014
代理人:
摘要：
A bispecific antibody that neutralizes both PDGFRb and VEGF-A, said bispecific antibody comprising: (I) a first antigen binding region that specifically binds to the extracellular domain of PDGFRb and neutralizes PDGFRb activity, wherein said PDGFRb binding region It comprises a VL domain (VL-PDGFR) comprising the CDR LCDR1PDGFR, LCDR2PDGFR and LCDR3PDGFR and a VH domain (VH-PDGFR) comprising the CDR HCDR1PDGFR, HCDR2PDGFR and HCDR3PDGFR, where: shown, respectively, in residues 24-40, residues 56-62 and residues 95-103 of SEQ ID NO: 46； and HCDR1PDGFR, HCDR2PDGFR and HCDR3PDGFR have the amino acid sequences shown, respectively, in residues 31-35, residues 50-66, and residues 99-111 of SEQ ID NO: 48； and (II) a second antigen binding region that specifically binds VEGF-A and neutralizes VEGF-A activity, wherein said VEGF-A binding region comprises a VL domain (VL-VEGF) comprising the CDRs LCDR1VEGF, LCDR2VEGF and LCDR3VEGF and a VH domain (VHVEGF) comprising the HCDR1VEGF, HCDR2VEGF and HCDR3VEGF CDRs, where: LCDR1VEGF, LCDR2VEGF and LCDR3VEGF have the amino acid sequences shown, respectively, in the remainder 24-34 56 and residues 89-97 of SEQ ID No. 278； and HCDR1VEGF, HCDR2VEGF and HCDR3VEGF have the amino acid sequences shown, respectively, in residues 31-35, residues 50-66 and residues 99-110 of SEQ ID No. 280； wherein said first antigen binding region and said second antigen binding region each show a binding affinity (Ka) of 108 M-1 or greater.Un anticuerpo biespecífico que neutraliza tanto PDGFRb como VEGF-A, comprendiendo dicho anticuerpo biespecífico: (I) una primera región de unión a antígeno que se une específicamente al dominio extracelular de PDGFRb y neutraliza la actividad PDGFRb, en donde dicha región de unión a PDGFRb comprende un dominio VL (VL-PDGFR) que comprende las CDR LCDR1PDGFR, LCDR2PDGFR y LCDR3PDGFR y un dominio VH (VH-PDGFR) que comprende las CDR HCDR1PDGFR, HCDR2PDGFR y HCDR3PDGFR, en donde: LCDR1PDGFR, LCDR2PDGFR y LCDR3PDGFR tienen las
