Patent ID: 8586714

Claim:
A binding protein comprising first and second polypeptide chains, each independently comprising VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first variable domain; VD2 is a second variable domain; C is a constant domain; X1 is a linker with the proviso that it is not CH1; X2 is an Fc region; n is 0 or 1; wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site, and wherein the binding protein is capable of binding: (a) methotrexate (MTX) and CD3, wherein (i) the variable domains that form a functional target binding site for MTX comprise: three CDRs from SEQ ID NO: 104 and three CDRs from SEQ ID NO: 105; and (ii) the variable domains that form a functional target binding site for CD3 comprise: three CDRs from SEQ ID NO: 32 and a three CDRs from SEQ ID NO: 33, three CDRs from SEQ ID NO: 68 and three CDRs from SEQ ID NO: 69, or three CDRs from SEQ ID NO: 100 and three CDRs from SEQ ID NO: 101; and (iii) the IC 50 of the binding pair is at most 4.0 nM as measured in a methotrexate neutralization assay; (b) MTX and EGFR, wherein (i) the variable domains that form a functional target binding site for MTX comprise: three CDRs from SEQ ID NO: 104 and three CDRs from SEQ ID NO: 105; and ii) the variable domains that form a functional target binding site for EGFR comprise: three CDRs from SEQ ID NO: 34 and three CDRs from SEQ ID NO: 35, three CDRs from SEQ ID NO: 62 and three CDRs from SEQ ID NO: 63, or three CDRs from SEQ ID NO: 76 and three CDRs from SEQ ID NO: 77; and (iii) the IC 50 of the binding pair is at most 3.9 nM as measured in a methotrexate neutralization assay; or (c) MTX and HER-2, wherein (i) the variable domains that form a functional target binding site for MTX comprise: three CDRs from SEQ ID NO: 104 and three CDRs from SEQ ID NO: 105, and (ii) the variable domains that form a functional target binding site for HER-2 comprise: three CDRs from SEQ ID NO: 36 and three CDRs from SEQ ID NO: 37; or three CDRs from SEQ ID NO: 98 and three CDRs from SEQ ID NO: 99; and (iii) the IC 50 of the binding pair is at most 3.9 nM as measured in a methotrexate neutralization assay.