Pharmaceutical antibody compositions with resistance to soluble CEA
The present invention relates to pharmaceutical compositions for the treatment of an epithelial tumor in a human, said pharmaceutical composition comprising an IgG1 antibody specifically binding to human CEA, wherein the variable region of said IgG1 antibody comprises at least (i) a CDR-H1 having the amino acid sequence “SYWMH” (SEQ ID NO: 29) and a CDR-H2 having the amino acid sequence “FIRNKANGGTTEYAASVKG” (SEQ ID NO: 28) and a CDR-H3 having the amino acid sequence “DRGLRFYFDY” (SEQ ID NO: 27) or (ii) a CDR-H1 having the amino acid sequence “TYAMH” (SEQ ID NO: 31) and a CDR-H2 having the amino acid sequence “LISNDGSNKYYADSVKG” (SEQ ID NO: 30) and a CDR-H3 having the amino acid sequence “DRGLRFYFDY” (SEQ ID NO: 27). Furthermore, processes for the production of said pharmaceutical compositions as well as medical/pharmaceutical uses for the IgG1 antibody molecules bearing specificities for the human CEA antigen are disclosed.
1. A pharmaceutical composition comprising an IgG1 antibody specifically binding to human CEA, wherein said IgG1 antibody comprises heavy chain variable (V H ) domain and a light chain variable (V L ) domain, wherein the heavy chain variable domain comprises:
(1) a CDR-H1 having the amino acid sequence “TYAMH” (SEQ ID NO. 31);
(2) a CDR-H2 having the amino acid sequence “LISNDGSNKYYADSVKG” (SEQ ID NO. 30); and
(3) a CDR-H3 having the amino acid sequence “DX1X2X3X4FYFDY” (SEQ ID NO. 99), wherein said X1 is F, M, E or T; X2 is Y, A, D or S; X3 is F, M E or T; and; X4 is Y, A, D or S;
and further comprises light chain variable domain CDRs CDR-L1 having the amino acid sequence “TLRRGINVGAYSIY” (SEQ ID NO. 34) and a CDR-L2 having the amino acid sequence “YKSDSDKQQGS” (SEQ ID NO. 33) and a CDR-L3 having the amino acid sequence “MIWHSGASAV” (SEQ ID NO. 32).
2. The pharmaceutical composition of claim 1 , which further comprises pharmaceutically suitable carriers, stabilizers and/or excipients.