COMPOSITIONS COMPRISING CROSS-SPECIES-SPECIFIC ANTIBODIES AND USES THEREOF
The present invention relates to uses of bispecific antibodies exhibiting cross-species specificity for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of the same in non-human species and humans. The present invention moreover relates to methods for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of said bispecific antibodies exhibiting cross-species specificity. The present invention also relates to methods of measuring the biological activity and/or efficacy of such bispecific antibodies exhibiting cross-species specificity. In addition, the present invention relates to pharmaceutical compositions comprising bispecific single chain antibodies exhibiting cross-species specificity and to methods for the preparation of pharmaceutical compositions comprising said bispecific single chain antibodies exhibiting cross-species specificity for the treatment of diseases.
1 - 43 . (canceled)
44 . A nucleic acid comprising a nucleotide sequence encoding a bispecific single chain antibody, the antibody comprising:
(a) a first binding domain which binds to CD3, wherein the first binding domain comprises the amino acid sequence of CDR-L1 (SEQ ID NO: 118), CDR-L2 (SEQ ID NO: 117), and CDR-L3 (SEQ ID NO: 116), and CDR-H1 (SEQ ID NO: 115), CDR-H2 (SEQ ID NO: 114) and CDR-H3 (SEQ ID NO: 112 or 113); and
(b) a second binding domain which binds to a cell surface antigen.
45 . The nucleic acid of claim 44 , wherein the nucleotide sequence encodes a first binding domain comprising a VH region comprising at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 110 and/or a VL region comprising at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 168.
46 . The nucleic acid of claim 44 , wherein the nucleotide sequence encodes a first binding domain comprising a VH region comprising at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 110 and/or a VL region comprising at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 168.
47 . The nucleic acid of claim 44 , wherein the nucleotide sequence encodes a first binding domain comprising a VH region comprising the amino acid sequence of SEQ ID NO: 110 and/or a VL region comprising the amino acid sequence of SEQ ID NO: 168.
48 . The nucleic acid of claim 44 , wherein the nucleotide sequence encodes a first binding domain comprising an scFv comprising at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 170 or 194.
49 . The nucleic acid of claim 44 , wherein the nucleotide sequence encodes a first binding domain comprising an scFv comprising at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 170 or 194.
50 . The nucleic acid of claim 44 , wherein the nucleotide sequence encodes a first binding domain comprising an scFv comprising the amino acid sequence of SEQ ID NO: 170 or 194.
51 . The nucleic acid of claim 44 , wherein the nucleotide sequence encodes a first binding domain comprising an scFv comprising the amino acid sequence of SEQ ID NO: 170.
52 . The nucleic acid of claim 44 , wherein the nucleotide sequence encodes a first binding domain comprising an scFv comprising the amino acid sequence of SEQ ID NO: 194.
53 . The nucleic acid of claim 44 , wherein the nucleic acid encoding the first binding domain comprises a nucleotide sequence comprising at least 90% sequence identity to the nucleotide sequence of SEQ ID NO: 169 or 193.
54 . The nucleic acid of claim 44 , wherein the nucleic acid encoding the first binding domain comprises a nucleotide sequence comprising at least 95% sequence identity to the nucleotide sequence of SEQ ID NO: 169 or 193.
55 . The nucleic acid of claim 44 , wherein the nucleic acid encoding the first binding domain comprises the nucleotide sequence of SEQ ID NO: 169 or 193.
56 . The nucleic acid of claim 44 , wherein the nucleic acid encoding the first binding domain comprises the nucleotide sequence of SEQ ID NO: 169.
57 . The nucleic acid of claim 44 , wherein the nucleic acid encoding the first binding domain comprises the nucleotide sequence of SEQ ID NO: 193.
58 . The nucleic acid of claim 44 , wherein the cell surface antigen is a tumor antigen.
59 . The nucleic acid of claim 44 , wherein the cell surface antigen is EpCAM, EGFR, EGFRvIII or Carboanhydrase IX (MN/CA IX).
60 . A composition comprising the nucleic acid of claim 44 and a carrier, stabilizer, and/or excipient.