HUMAN ANTIBODIES AGAINST TISSUE FACTOR AND METHODS OF USE THEREOF
Isolated human monoclonal antibodies which bind to human TF and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies, and therapeutic and diagnostic methods for using the antibodies.
1 . A human antibody which binds human Tissue Factor, wherein the antibody comprises:
(a) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:14, 15 and 16 and a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 70, 71 and 72,
(b) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 18, 19, 20 and a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:74, 75 and 76,
(c) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NO:22, 23 and 24 and a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 78, 79 and 80,
(d) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 26, 27 and 28 and a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 82, 83 and 84, or
(e) a variant of any of (a)-(d), wherein said variant has at most 1, 2 or 3 amino-acid modifications.
2 - 66 . (canceled)
67 . A bispecific molecule comprising the antibody of claim 1 and a second binding specificity for a human effector cell, a human Fc receptor or a T cell receptor.
68 . An expression vector comprising a nucleotide sequence encoding one or more of the amino acid sequences of the antibody of claim 1 .
69 . (canceled)
70 . A recombinant eukaryotic or prokaryotic host cell which produces the antibody as defined in claim 1 .
71 . A pharmaceutical composition comprising the antibody as defined in claim 1 or a bispecific molecule comprising the antibody of claim 1 and a second binding specificity, and a pharmaceutically acceptable carrier.
72 - 83 . (canceled)
84 . A method for inhibiting growth and/or proliferation of a tumor cell expressing Tissue Factor, comprising administration, to an individual in need thereof, of an antibody of any of claim 1 or a bispecific molecule comprising the antibody of claim 1 and a second binding specificity.
85 . A method for producing the antibody of claim 1 , said method comprising the steps of
a) culturing a recombinant eukaryotic or prokaryotic host cell which produces the antibody as defined in claim 1 , and
b) purifying the antibody from the culture media.
86 . A diagnostic composition comprising the antibody as defined in claim 1 .
87 . A method for detecting the presence of Tissue Factor in a sample, comprising:
contacting the sample with an antibody of claim 1 , or a bispecific molecule comprising the antibody of claim 1 and a second binding specificity, under conditions that allow for formation of a complex between the antibody or bispecific molecules and Tissue Factor; and
analyzing whether a complex has been formed.
88 . A kit for detecting the presence of Tissue Factor in a sample comprising
an antibody of claim 1 or a bispecific molecule comprising the antibody of claim 1 and a second binding specificity; and
instructions for use of the kit.