Patent ID: 11866508
Assignee: AMGEN INC.
Field: Pharmaceuticals (Chemistry)
Classification: CPC C  A  G | IPC A  C  G

Claim 16:
17. A method of determining if a subject has mesothelin expressing tumor cells, comprising
contacting a tumor sample from the subject with a bispecific single chain antibody, the bispecific single chain antibody comprising a cluster of differentiation 3 (CD3) binding domain and a mesothelin (MSLN) binding domain, wherein the variable heavy chain regions (VH) and the variable light chain regions (VL) regions of the bispecific antibody are arranged, from N-terminus to C-terminus, in the order, VH(MSLN)-VL(MSLN)-VH(CD3)-VL(CD3), VH(CD3)-VL(CD3)-VH(MSLN)-VL(MSLN), VL(MSLN)-VH(MSLN)-VH(CD3)-VL(CD3), VH(CD3)-VL(CD3)-VL(MSLN)-VH(MSLN), VL(MSLN)-VH(MSLN)-VL(CD3)-VH(CD3), VL(CD3)-VH(CD3)-VL(MSLN)-VH(MSLN), VH(MSLN)-VL(MSLN)-VL(CD3)-VH(CD3), or VL(CD3)-VH(CD3)-VH(MSLN)-VL(MSLN),
wherein the VH(MSLN) and VL(MSLN) comprise three heavy chain CDRs and three light chain CDRs with sequences selected from the group consisting of:
a) SEQ ID NOs: 45, 46, and 47 of the heavy chain and SEQ ID NOs: 9, 10, and 11 of the light chain;
b) SEQ ID NOs: 48, 49, and 50 of the heavy chain and SEQ ID NOs: 12, 13, and 14 of the light chain;
c) SEQ ID NOs: 51, 52, and 53 of the heavy chain and SEQ ID NOs: 15, 16, and 17 of the light chain;
d) SEQ ID NOs: 51, 52, and 53 of the heavy chain and SEQ ID NOs: 18, 19, and 20 of the light chain;
e) SEQ ID NOs: 54, 55, and 56 of the heavy chain and SEQ ID NOs: 21, 22, and 23 of the light chain;
f) SEQ ID NOs: 57, 58, and 59 of the heavy chain and SEQ ID NOs: 24, 25, and 26 of the light chain;
g) SEQ ID NOs: 60, 61, and 62 of the heavy chain and SEQ ID NOs: 27, 28, and 29 of the light chain;
h) SEQ ID NOs: 63, 64, and 65 of the heavy chain and SEQ ID NOs: 30, 31, and 32 of the light chain;
i) SEQ ID NOs: 63, 64, and 65 of the heavy chain and SEQ ID NOs: 33, 34, and 35 of the light chain;
j) SEQ ID NOs: 63, 64, and 65 of the heavy chain and SEQ ID NOs: 36, 37, and 38 of the light chain, and
k) any one of (a)-(j), wherein each of the CDRs are identical to or comprise 1, 2, or 3 amino acid residue substitutions relative to their specified sequence; and
detecting binding of the antibody, antigen binding protein, or fragment thereof to the sample, wherein an increase in binding of the antibody, antigen binding protein, or fragment thereof to the sample as compared to binding of the antibody, antigen binding protein, or fragment thereof to a control sample identifies the subject as having mesothelin expressing tumor cells.