Anti-Tissue Factor Antibodies, Antibody-Drug Conjugates, and Related Methods

Abstract

To provide antibodies that specifically bind to human tissue factor (TF), to provide anti-TF antibody-drug conjugates (ADCs), and to provide compositions comprising the antibody or ADC.SOLUTION: Provided is an isolated human antibody which binds to the extracellular domain of human Tissue Factor (TF), the isolated human antibody binding human TF at a human TF binding site that is distinct from a human TF binding site bound by human FVIIa.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application Nos. 62 / 613,545, filed January 4, 2018, 62 / 613,564, filed January 4, 2018, 62 / 646,788, filed March 22, 2018, 62 / 713,797, filed August 2, 2018, and 62 / 713,804, filed August 2, 2018, each of which is incorporated herein by reference in its entirety.

[0002] Sequence Listing This application contains a Sequence Listing, which has been submitted via EFS-Web and is hereby incorporated by reference in its entirety. The ASCII copy, created on XX / XX / 20XX, is named XXXXXUS_sequencelisting.txt and is X,XXX,XXX bytes in size. [Background technology]

[0003] background Blood coagulation involves a complex series of steps that result in the formation of a blood clot. Tissue factor (TF) plays a key role in these clotting steps. TF is the cell surface receptor for the serine protease factor VIIa (FVIIa). The TF / FVIIa complex catalyzes the conversion of the inactive protease factor X (FX) to the active protease factor Xa (FXa). FXa and its cofactor FVa form the prothrombinase complex, which generates thrombin from prothrombin. Thrombin converts soluble fibrinogen to insoluble fibrin strands and catalyzes many other coagulation-related processes.

[0004] TF is overexpressed on multiple types of solid tumors. In cancer, TF / FVIIa signaling can support angiogenesis, tumor progression, and metastasis. Increased TF expression can also induce inflammation and / or angiogenesis in many other diseases, including wet age-related macular degeneration (AMD) and diabetic retinopathy. Summary of the Invention

[0005] overview Provided herein are antibodies that specifically bind to human tissue factor (TF), anti-TF antibody-drug conjugates, and related methods.

[0006] In one aspect, provided herein is an isolated human antibody that binds to the extracellular domain of human tissue factor (TF), wherein the antibody binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FVIIa binds.

[0007] In some embodiments, (1) the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L and (2) the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0008] In some embodiments, (1) the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 Land (2) the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0009] In some embodiments, (1) the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L and (2) the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0010] In some embodiments, (1) the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L and (2) the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0011] In some embodiments, (1) the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L and (2) the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0012] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:784.

[0013] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:872, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:877.

[0014] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:883.

[0015] In some embodiments, the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L It does not inhibit human thrombin generation compared to a reference antibody containing the sequence.

[0016] In some embodiments, the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L The antibody inhibits human thrombin generation to a lesser extent compared to a reference antibody containing the sequence.

[0017] In some embodiments, the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L The antibody sequence permits human thrombin generation to a greater extent than a reference antibody containing the sequence.

[0018] In some embodiments, the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L The antibody inhibits human thrombin generation by a smaller amount compared to a reference antibody containing the sequence.

[0019] In some embodiments, the isolated antibody has a V nucleotide sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L It allows for greater amounts of human thrombin generation compared to a reference antibody containing the sequence.

[0020] In some embodiments, the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA). In some embodiments, the antibody does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. In some embodiments, the antibody does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control. In some embodiments, the antibody does not reduce endogenous thrombin potential (ETP) as determined by the area under the thrombin generation curve compared to an isotype control. In some embodiments, the antibody tolerates human thrombin generation as determined by a thrombin generation assay (TGA). In some embodiments, the antibody maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. In some embodiments, the antibody maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control. In some embodiments, the antibody protects endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve.

[0021] In some embodiments, the antibody binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, hi some embodiments, the antibody does not interfere with the ability of TF:FVIIa to convert FX to FXa.

[0022] In some embodiments, the antibody does not compete with human FVIIa for binding to human TF.

[0023] In some embodiments, the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), permits human thrombin generation as determined by a thrombin generation assay (TGA), binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, does not interfere with the ability of TF:FVIIa to convert FX to FXa, and does not compete with FVIIa for binding to human TF.

[0024] In some embodiments, the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), does not reduce endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve, permits human thrombin generation as determined by a thrombin generation assay (TGA) and protects endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve, binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, does not interfere with the ability of TF:FVIIa to convert FX to FXa, and does not compete with FVIIa for binding to human TF.

[0025] In some embodiments, the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control, does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control, does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control, and does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA). maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control, maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control, protects endogenous thrombin potential (ETP) compared to an isotype control as determined by the area under the thrombin generation curve, binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, does not interfere with the ability of TF:FVIIa to convert FX to FXa, and does not compete with FVIIa for binding to human TF.

[0026] In some embodiments, the antibody inhibits FVIIa-dependent TF signaling.

[0027] In some embodiments, the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO: 810 is less than 50% of the binding between the isolated antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO: 810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO: 810 is K149N.

[0028] In some embodiments, the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO: 810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of the TF of the sequence shown in SEQ ID NO: 810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 68 of the sequence shown in SEQ ID NO: 810 is K68N.

[0029] In some embodiments, the binding between the isolated antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 is less than 50% of the binding between the isolated antibody and the extracellular domain of the TF of the sequence shown in SEQ ID NO: 810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 are N171H and T197K.

[0030] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 1-77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 1-76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0031] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 39-77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0032] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0033] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146-158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151-163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0034] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-219 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-224 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0035] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-189 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-194 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0036] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0037] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 167-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 172-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0038] In some embodiments, the binding between the isolated antibody and the extracellular domain of rat TF in which amino acid residues 141-194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0039] In some embodiments, the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is more than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; and the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 1-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 1-76 in the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838, as determined by median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 39 to 77 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 38 to 76 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO: 838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 99 to 112 of the extracellular domain of rat TF in which ... Binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146 to 158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151 to 163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is demonstrated.and the binding between the isolated antibody and the extracellular domain of rat TF in which amino acid residues 141-194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO:810 is more than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N and the mutation at amino acid residue 68 of the sequence set forth in SEQ ID NO:810 is K68N.

[0040] In some embodiments, the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is more than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 1 to 77 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 1 to 76 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 39 to 77 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 38 to 76 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 1 to 76 of the extracellular domain of rat ...38 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 1 to 76 of the extracellular domain of rat TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO:838 is the binding between the extracellular domain of human TF having the sequence shown in SEQ ID NO:838 substituted for amino acid residues 99-112 in the extracellular domain of rat TF is more than 50% of the binding between the isolated antibody and the extracellular domain of TF having the sequence shown in SEQ ID NO:810;the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146 to 158 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 151 to 163 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 159 to 219 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 224 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 159 to 189 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 224 of the extracellular domain of rat ... The binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 164 to 194 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 164 to 194 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159 to 174 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 179 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 172 to 179 in the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 172 to 179 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, and the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 141 to 194 in the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 141 to 194 in the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810,The binding between the extracellular domain of rat TF substituted with amino acid residues 136-189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO: 810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO: 810. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO: 810 is K149N, the mutation at amino acid residue 68 of the sequence set forth in SEQ ID NO: 810 is K68N, and the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO: 810 are N171H and T197K.

[0041] In some embodiments, the antibody binds to cynomolgus monkey TF. In some embodiments, the antibody binds to mouse TF. In some embodiments, the antibody binds to rabbit TF. In some embodiments, the antibody binds to porcine TF.

[0042] In some embodiments, the antibody reduces lesion size in a porcine choroidal neovascularization (CNV) model.

[0043] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), and (b) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO: 810 compared to the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO: 810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO: 810 are N171H and T197K.

[0044] In some embodiments, the antibody (a) permits human thrombin generation as determined by a thrombin generation assay (TGA), and (b) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO: 810 compared to the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO: 810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO: 810 are N171H and T197K.

[0045] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (c) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N, and the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K.

[0046] In some embodiments, the antibody (a) permits human thrombin generation as determined by a thrombin generation assay (TGA); (b) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay, and (c) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N, and the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K.

[0047] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) binds to cynomolgus monkey TF; (c) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (d) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N, and the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K.

[0048] In some embodiments, the antibody (a) permits human thrombin generation as determined by a thrombin generation assay (TGA); (b) binds to cynomolgus monkey TF; (c) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (d) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N, and the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K.

[0049] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), (b) permits human thrombin generation as determined by a thrombin generation assay (TGA), (c) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, (d) does not interfere with the ability of TF:FVIIa to convert FX to FXa, (e) does not compete with FVIIa for binding to human TF, (f) inhibits FVIIa-dependent TF signaling, (g) binds to cynomolgus monkey TF, (h) binds to mouse TF, and (i) binds to rabbit TF.

[0050] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), (b) does not reduce endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve, (c) permits human thrombin generation as determined by a thrombin generation assay (TGA), (d) protects endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve, (e) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, (f) does not interfere with the ability of TF:FVIIa to convert FX to FXa, (g) does not compete with FVIIa for binding to human TF, (h) inhibits FVIIa-dependent TF signaling, (i) binds to cynomolgus monkey TF, (j) binds to mouse TF, and (k) binds to rabbit TF.

[0051] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on a thrombin generation curve compared to an isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on a thrombin generation curve (tt peak) compared to an isotype control; (d) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (e) tolerates human thrombin generation as determined by a thrombin generation assay (TGA); and (f) does not increase the thrombin peak on a thrombin generation curve compared to an isotype control. (g) maintains the thrombin peak (peak IIa) on the thrombin generation curve (tt peak) compared to an isotype control; (h) protects endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) does not interfere with the ability of TF:FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibits FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; and (o) binds to rabbit TF.

[0052] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), (b) permits human thrombin generation as determined by a thrombin generation assay (TGA), (c) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, (d) does not interfere with the ability of TF:FVIIa to convert FX to FXa, (e) does not compete with FVIIa for binding to human TF, (f) inhibits FVIIa-dependent TF signaling, (g) binds to cynomolgus monkey TF, (h) binds to mouse TF, (i) binds to rabbit TF, (j) binds to pig TF, and (k) reduces lesion size in a pig choroidal neovascularization (CNV) model.

[0053] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), (b) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control, (c) permits human thrombin generation as determined by a thrombin generation assay (TGA), (d) protects endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control, (e) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, (f) does not interfere with the ability of TF:FVIIa to convert FX to FXa, (g) does not compete with FVIIa for binding to human TF, (h) inhibits FVIIa-dependent TF signaling, (i) binds to cynomolgus monkey TF, (j) binds to mouse TF, (k) binds to rabbit TF, (l) binds to pig TF, and (m) reduces lesion size in a pig choroidal neovascularization (CNV) model.

[0054] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control; (d) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (e) tolerates human thrombin generation as determined by a thrombin generation assay (TGA); (f) maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; and (g) does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control. (h) preserves the time from the start of the assay to the thrombin peak on the thrombin generation curve (ttpeak) compared to an isotype control; (i) protects endogenous thrombin potential (ETP) as determined by the area under the thrombin generation curve compared to an isotype control; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) does not interfere with the ability of TF:FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibits FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; (o) binds to rabbit TF; (p) binds to porcine TF; and (q) reduces lesion size in a porcine choroidal neovascularization (CNV) model.

[0055] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; (c) does not increase the time from the start of the assay to the thrombin peak (tt peak) on the thrombin generation curve compared to an isotype control; (d) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (e) tolerates human thrombin generation as determined by a thrombin generation assay (TGA); (f) maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; and (g) does not increase the time from the start of the assay to the thrombin peak (tt peak) on the thrombin generation curve compared to an isotype control. (h) preserves the time to thrombin peak (tt peak); (i) protects endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (ii) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) does not interfere with the ability of TF:FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibits FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; (o) binds to rabbit TF; (p) binds to porcine TF; (q) reduces lesion size in a porcine choroidal neovascularization (CNV) model; and (r) reduces lesion size in a porcine choroidal neovascularization (CNV) model as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. and (s) the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of a TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.(t) the binding between the isolated antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of a TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control; and (u) the binding between the isolated antibody and the extracellular domain of a human TF in which amino acid residues 1-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 1-76 in the extracellular domain of a rat TF of the sequence shown in SEQ ID NO:838, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. (v) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 39 to 77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38 to 76 in the extracellular domain of rat TF in the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38 to 76 in the extracellular domain of rat ... and (x) the binding between the isolated antibody and the extracellular domain of human TF having amino acid residues 99-112 substituted for those of the extracellular domain of rat TF having the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF having the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.(y) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146 to 158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151 to 163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. (z) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159 to 189 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164 to 194 in the extracellular domain of rat TF in the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 159 to 174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164 to 194 in the extracellular domain of rat ... and (bb) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 167-174 of the sequence set forth in SEQ ID NO:810 have been replaced with amino acid residues 164-179 of the extracellular domain of rat TF having the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF having the sequence set forth in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.and (cc) the binding between the isolated antibody and the extracellular domain of rat TF in which amino acid residues 141-194 of the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 136-189 of the extracellular domain of human TF in which the sequence shown in SEQ ID NO:810 is replaced, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control, is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in which the sequence shown in SEQ ID NO:810 is replaced by amino acid residues 141-194 of the sequence shown in SEQ ID NO:838, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control.

[0056] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; (c) does not increase the time from the start of the assay to the thrombin peak (tt peak) on the thrombin generation curve compared to an isotype control; (d) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (e) tolerates human thrombin generation as determined by a thrombin generation assay (TGA); (f) maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; and (g) does not increase the time from the start of the assay to the thrombin peak (tt peak) on the thrombin generation curve compared to an isotype control. (h) preserves the time to thrombin peak (tt peak); (i) protects endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (ii) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) does not interfere with the ability of TF:FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibits FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; (o) binds to rabbit TF; (p) binds to porcine TF; (q) reduces lesion size in a porcine choroidal neovascularization (CNV) model; and (r) reduces lesion size in a porcine choroidal neovascularization (CNV) model as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. and (s) the binding between the isolated antibody and the extracellular domain of a variant TF comprising the mutation K149N of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of a TF comprising the mutation K68N of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.(t) the binding between the isolated antibody and the extracellular domain of a variant TF comprising mutations N171H and T197K of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of a TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control; and (u) the binding between the isolated antibody and the extracellular domain of a human TF in which amino acid residues 1-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 1-76 in the extracellular domain of a rat TF of the sequence shown in SEQ ID NO:838, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. (v) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 39 to 77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38 to 76 in the extracellular domain of rat TF in the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38 to 76 in the extracellular domain of rat ... and (x) the binding between the isolated antibody and the extracellular domain of human TF having amino acid residues 99-112 substituted for those of the extracellular domain of rat TF having the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF having the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.(y) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146 to 158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151 to 163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. (z) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159 to 189 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164 to 194 in the extracellular domain of rat TF in the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF in which amino acid residues 159 to 174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164 to 194 in the extracellular domain of rat ... and (bb) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 167-174 of the sequence set forth in SEQ ID NO:810 have been replaced with amino acid residues 164-179 of the extracellular domain of rat TF having the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF having the sequence set forth in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.and (cc) the binding between the isolated antibody and the extracellular domain of rat TF in which amino acid residues 141-194 of the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 136-189 of the extracellular domain of human TF in which the sequence shown in SEQ ID NO:810 is replaced, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control, is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in which the sequence shown in SEQ ID NO:810 is replaced by amino acid residues 141-194 of the sequence shown in SEQ ID NO:838, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control.

[0057] In some embodiments, the antibody competes for binding to human TF with an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0058] In some embodiments, the antibody competes with an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9 for binding to human TF.

[0059] In some embodiments, the antibody competes with an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea for binding to human TF.

[0060] In some embodiments, the antibody binds to the same epitope of human TF as does the antibody designated 25A, the antibody designated 25A3, the antibody designated 25A5, the antibody designated 25A5-T, the antibody designated 25G, the antibody designated 25G1, the antibody designated 25G9, the antibody designated 43B, the antibody designated 43B1, the antibody designated 43B7, the antibody designated 43D, the antibody designated 43D7, the antibody designated 43D8, the antibody designated 43E, or the antibody designated 43Ea.

[0061] In some embodiments, the antibody binds to the same epitope of human TF as the antibody designated 25A, the antibody designated 25A3, the antibody designated 25A5, the antibody designated 25A5-T, the antibody designated 25G, the antibody designated 25G1, or the antibody designated 25G9.

[0062] In some embodiments, the antibody binds to the same epitope of human TF as the antibody designated 43B, the antibody designated 43B1, the antibody designated 43B7, the antibody designated 43D, the antibody designated 43D7, the antibody designated 43D8, the antibody designated 43E, or the antibody designated 43Ea.

[0063] In some embodiments, the antibody comprises all three heavy chain complementary determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, 25G9, 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. In some embodiments, the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering.

[0064] In some embodiments, the antibody comprises all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, an antibody designated as 25A5-T, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9.

[0065] In some embodiments, the antibody comprises all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from the antibody designated 43B, the antibody designated 43B1, the antibody designated 43B7, the antibody designated 43D, the antibody designated 43D7, the antibody designated 43D8, the antibody designated 43E, or the antibody designated 43Ea.

[0066] In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A3. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5-T. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G1. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G9. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B1. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B7. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D7. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D8. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43E. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43Ea.

[0067] In some embodiments, the antibody comprises V of SEQ ID NO:113. H Sequence and V of SEQ ID NO: 114 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:151. HSequence and V of SEQ ID NO: 152 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:189. H Sequence and V of SEQ ID NO: 190 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:836. H Sequence and V of SEQ ID NO:837 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:227. H Sequence and V of SEQ ID NO: 228 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:265. H Sequence and V of SEQ ID NO: 266 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:303. H Sequence and V of SEQ ID NO: 304 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:455. H Sequence and V of SEQ ID NO:456 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:493. H Sequence and V of SEQ ID NO:494 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:531. H Sequence and V of SEQ ID NO:532 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:569. H Sequence and V of SEQ ID NO:570 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:607. H Sequence and V of SEQ ID NO:608 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:645. H Sequence and V of SEQ ID NO:646 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:683. H Sequence and V of SEQ ID NO:684L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:721. H Sequence and V of SEQ ID NO:722 L Contains arrays.

[0068] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 784. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 872, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 877. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 883. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 797, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 798, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 799, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 800, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 801, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 802.

[0069] In some embodiments, the antibody comprises V of SEQ ID NO:763. H Sequence and V of SEQ ID NO:764 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:868. H Sequence and V of SEQ ID NO:869 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:870. H Sequence and V of SEQ ID NO:871 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:769. H Sequence and V of SEQ ID NO:770 L Contains arrays.

[0070] In some embodiments, the antibody comprises an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0071] In some embodiments, the antibody comprises an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9.

[0072] In some embodiments, the antibody comprises an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0073] In some embodiments, the antibody consists of an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0074] In some embodiments, the antibody consists of the antibody designated as 25A, the antibody designated as 25A3, the antibody designated as 25A5, the antibody designated as 25A5-T, the antibody designated as 25G, the antibody designated as 25G1, or the antibody designated as 25G9.

[0075] In some embodiments, the antibody consists of the antibody designated as 43B, the antibody designated as 43B1, the antibody designated as 43B7, the antibody designated as 43D, the antibody designated as 43D7, the antibody designated as 43D8, the antibody designated as 43E, or the antibody designated as 43Ea.

[0076] In another aspect, provided herein is an isolated antibody comprising all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0077] In some embodiments, the antibody is human, humanized, or chimeric.

[0078] In some embodiments, the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering.

[0079] In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A, the antibody designated 25A3, the antibody designated 25A5, the antibody designated 25A5-T, the antibody designated 25G, the antibody designated 25G1, or the antibody designated 25G9.

[0080] In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A3. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5-T. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G1. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G9.

[0081] In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B, the antibody designated 43B1, the antibody designated 43B7, the antibody designated 43D, the antibody designated 43D7, the antibody designated 43D8, the antibody designated 43E, or the antibody designated 43Ea.

[0082] In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B1. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B7. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D7. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D8. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43E. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43Ea.

[0083] In some embodiments, the antibody comprises V of SEQ ID NO:113. H Sequence and V of SEQ ID NO: 114 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:151. H Sequence and V of SEQ ID NO: 152 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:189. H Sequence and V of SEQ ID NO: 190 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:836. H Sequence and V of SEQ ID NO:837 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:227. H Sequence and V of SEQ ID NO: 228 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:265. H Sequence and V of SEQ ID NO: 266 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:303.H Sequence and V of SEQ ID NO: 304 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:455. H Sequence and V of SEQ ID NO:456 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:493. H Sequence and V of SEQ ID NO:494 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:531. H Sequence and V of SEQ ID NO:532 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:569. H Sequence and V of SEQ ID NO:570 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:607. H Sequence and V of SEQ ID NO:608 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:645. H Sequence and V of SEQ ID NO:646 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:683. H Sequence and V of SEQ ID NO:684 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:721. H Sequence and V of SEQ ID NO:722 L Contains arrays.

[0084] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 784. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 872, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 877. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 883. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 797, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 798, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 799, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 800, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 801, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 802.

[0085] In some embodiments, the antibody comprises V of SEQ ID NO:763. H Sequence and V of SEQ ID NO:764 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:868. H Sequence and V of SEQ ID NO:869 LIn some embodiments, the antibody comprises the sequence V of SEQ ID NO:870. H Sequence and V of SEQ ID NO:871 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:769. H Sequence and V of SEQ ID NO:770 L Contains arrays.

[0086] In some embodiments, the antibody comprises an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0087] In some embodiments, the antibody comprises an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9.

[0088] In some embodiments, the antibody comprises an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0089] In some embodiments, the antibody consists of an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0090] In some embodiments, the antibody consists of the antibody designated as 25A, the antibody designated as 25A3, the antibody designated as 25A5, the antibody designated as 25A5-T, the antibody designated as 25G, the antibody designated as 25G1, or the antibody designated as 25G9.

[0091] In some embodiments, the antibody consists of the antibody designated as 43B, the antibody designated as 43B1, the antibody designated as 43B7, the antibody designated as 43D, the antibody designated as 43D7, the antibody designated as 43D8, the antibody designated as 43E, or the antibody designated as 43Ea.

[0092] In another aspect, provided herein is an isolated antibody that competes with an antibody designated 1F, an antibody designated 1G, an antibody designated 29D, an antibody designated 29E, an antibody designated 39A, or an antibody designated 54E for binding to human TF.

[0093] In some embodiments, the antibody is human, humanized, or chimeric.

[0094] In some embodiments, the antibody inhibits FVIIa-dependent TF signaling.

[0095] In some embodiments, the antibody binds to cynomolgus monkey TF.

[0096] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0097] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 78-93 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77-98 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0098] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 78-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0099] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 78-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77-85 and 92-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0100] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, and the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 78-93 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77-98 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay.

[0101] In some embodiments, the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 78-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; and The binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 78-107 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 77-85 and 92-112 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810.

[0102] In some embodiments, the antibody comprises all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated 1F, an antibody designated 1G, an antibody designated 29D, an antibody designated 29E, an antibody designated 39A, an antibody designated 43Ea, or an antibody designated 54E. In some embodiments, the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering.

[0103] In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 1F. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 1G. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 29D. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 29E. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 39A. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 54E.

[0104] In some embodiments, the antibody comprises V of SEQ ID NO:37. H Sequence and V of SEQ ID NO: 38 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:75. H Sequence and V of SEQ ID NO:76 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:341. H Sequence and V of SEQ ID NO: 342 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:379. H Sequence and V of SEQ ID NO: 380 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:417. H Sequence and V of SEQ ID NO:418 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:759. H Sequence and V of SEQ ID NO:760 L Contains arrays.

[0105] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 773, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 774, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 775, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 776, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 777, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 778. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 785, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 786, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 787, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 788, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 789, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 790. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 791, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 792, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 793, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 794, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 795, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 796. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 803, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 804, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 805, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 806, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 807, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 808.

[0106] In some embodiments, the antibody comprises V of SEQ ID NO:761. H Sequence and V of SEQ ID NO:762 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:765. H Sequence and V of SEQ ID NO:766 LIn some embodiments, the antibody comprises the sequence V of SEQ ID NO:767. H Sequence and V of SEQ ID NO:768 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:771. H Sequence and V of SEQ ID NO:772 L Contains arrays.

[0107] In some embodiments, the antibody comprises the antibody designated as 1F, the antibody designated as 1G, the antibody designated as 29D, the antibody designated as 29E, the antibody designated as 39A, or the antibody designated as 54E.

[0108] In some embodiments, the antibody consists of the antibody designated as 1F, the antibody designated as 1G, the antibody designated as 29D, the antibody designated as 29E, the antibody designated as 39A, or the antibody designated as 54E.

[0109] In another aspect, provided herein is an isolated antibody comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:773, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:774, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:775, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:776, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:777, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:778.

[0110] In another aspect, provided herein is an isolated antibody comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:784.

[0111] In another aspect, provided herein is an isolated antibody comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:785, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:786, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:787, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:788, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:789, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:790.

[0112] In another aspect, provided herein is an isolated antibody comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:791, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:792, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:793, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:794, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:795, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:796.

[0113] In another aspect, provided herein is an isolated antibody comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:797, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:798, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:799, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:800, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:801, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:802.

[0114] In another aspect, provided herein is an isolated antibody comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:803, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:804, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:805, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:806, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:807, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:808.

[0115] In another aspect, provided herein is an isolated antibody comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:872, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:877.

[0116] In another aspect, provided herein is an isolated antibody comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:883.

[0117] In some embodiments, the antibody has a K of 50 nM or less, 10 nM or less, 5 nM or less, 1 nM or less, 0.5 nM or less, or 0.1 nM or less as measured by Octet QK384 or Biacore assay. D It binds to human TF.

[0118] In some embodiments, the antibody is a monoclonal antibody.

[0119] In some embodiments, the antibody is multispecific.

[0120] In some embodiments, the antibody is a Fab, Fab', F(ab')2, Fv, scFv, (scFv)2, single-chain antibody molecule, dual variable domain antibody, single variable domain antibody, linear antibody, or V-domain antibody.

[0121] In some embodiments, the antibody comprises a scaffold, optionally the scaffold is Fc, optionally human Fc. In some embodiments, the antibody comprises a heavy chain constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. In some embodiments, the antibody comprises a heavy chain constant region of the IgG class and subclass selected from IgG1, IgG2, IgG3, and IgG4. In some embodiments, the antibody comprises an IgG1 heavy chain constant region.

[0122] In some embodiments, the Fc comprises one or more modifications that result in increased half-life, increased antibody-dependent cellular cytotoxicity (ADCC), increased antibody-dependent cellular phagocytosis (ADCP), increased complement-dependent cytotoxicity (CDC), or decreased effector function compared to the Fc that does not contain the one or more modifications.

[0123] In another aspect, provided herein is an isolated antibody that competes with any of the above antibodies for binding to human TF.

[0124] In another aspect, provided herein is an isolated antibody that binds to an epitope of human TF to which any of the above antibodies binds.

[0125] In another aspect, the present invention provides any of the above antibodies, their V H , that V L Provided is an isolated polynucleotide or set of polynucleotides encoding the antibody, its light chain, its heavy chain, or an antigen-binding portion thereof.

[0126] In another aspect, provided herein is a vector or set of vectors comprising the above-described polynucleotide or set of polynucleotides.

[0127] In another aspect, there is provided herein a host cell comprising the above-described polynucleotide or set of polynucleotides, or the above-described vector or set of vectors.

[0128] In another aspect, provided herein is a method of producing an antibody, the method comprising expressing the antibody by a host cell as described above and isolating the expressed antibody.

[0129] In another aspect, provided herein is a pharmaceutical composition comprising any of the antibodies described above and a pharmaceutically acceptable excipient.

[0130] In another aspect, provided herein is a method for treating or preventing a disease or condition in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the antibodies described above or the pharmaceutical composition described above.

[0131] In some embodiments, the disease or condition is cancer. In some embodiments, the cancer is head and neck cancer. In some embodiments, the cancer is ovarian cancer. In some embodiments, the cancer is gastric cancer. In some embodiments, the cancer is esophageal cancer. In some embodiments, the cancer is cervical cancer. In some embodiments, the cancer is prostate cancer. In some embodiments, the cancer is pancreatic cancer. In some embodiments, the cancer is triple-negative estrogen receptor negative (ER-), progesterone receptor negative (PR-), and HER2 negative (HER2-) breast cancer. In some embodiments, the cancer is glioblastoma. In some embodiments, the cancer is lung cancer. In some embodiments, the cancer is bladder cancer. In some embodiments, the cancer is melanoma. In some embodiments, the cancer is kidney cancer.

[0132] In some embodiments, the disease or condition involves angiogenesis. In some embodiments, the disease or condition involves angiogenesis is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. In some embodiments, the disease or condition involves vascular inflammation.

[0133] In some embodiments, the method further comprises administering one or more additional therapeutic agents to the subject. In some embodiments, the additional therapeutic agent is formulated in the same pharmaceutical composition as the antibody. In some embodiments, the additional therapeutic agent is formulated in a different pharmaceutical composition from the antibody. In some embodiments, the additional therapeutic agent is administered before administering the antibody. In some embodiments, the additional therapeutic agent is administered after administering the antibody. In some embodiments, the additional therapeutic agent is administered simultaneously with the antibody.

[0134] In another aspect, provided herein is a method for detecting TF in a subject having or suspected of having a disease or condition, the method comprising: (a) receiving a sample from the subject; and (b) detecting the presence or level of TF in the sample by contacting the sample with any of the antibodies described above.

[0135] In some embodiments, the disease or condition is cancer. In some embodiments, the cancer is head and neck cancer. In some embodiments, the cancer is ovarian cancer. In some embodiments, the cancer is gastric cancer. In some embodiments, the cancer is esophageal cancer. In some embodiments, the cancer is cervical cancer. In some embodiments, the cancer is prostate cancer. In some embodiments, the cancer is pancreatic cancer. In some embodiments, the cancer is triple-negative estrogen receptor negative (ER-), progesterone receptor negative (PR-), and HER2 negative (HER2-) breast cancer. In some embodiments, the cancer is glioblastoma. In some embodiments, the cancer is lung cancer. In some embodiments, the cancer is bladder cancer. In some embodiments, the cancer is melanoma. In some embodiments, the cancer is kidney cancer.

[0136] In some embodiments, the disease or condition involves angiogenesis. In some embodiments, the disease or condition involves angiogenesis is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. In some embodiments, the disease or condition involves vascular inflammation.

[0137] In another aspect, provided herein is a method for detecting TF in a subject having or suspected of having a disease or condition, the method comprising: (a) administering to the subject any of the antibodies described above; and (b) detecting the presence or level of TF in the subject.

[0138] In some embodiments, the disease or condition is cancer. In some embodiments, the cancer is head and neck cancer. In some embodiments, the cancer is ovarian cancer. In some embodiments, the cancer is gastric cancer. In some embodiments, the cancer is esophageal cancer. In some embodiments, the cancer is cervical cancer. In some embodiments, the cancer is prostate cancer. In some embodiments, the cancer is pancreatic cancer. In some embodiments, the cancer is triple-negative estrogen receptor negative (ER-), progesterone receptor negative (PR-), and HER2 negative (HER2-) breast cancer. In some embodiments, the cancer is glioblastoma. In some embodiments, the cancer is lung cancer. In some embodiments, the cancer is bladder cancer. In some embodiments, the cancer is melanoma. In some embodiments, the cancer is kidney cancer.

[0139] In some embodiments, the disease or condition involves angiogenesis. In some embodiments, the disease or condition involves angiogenesis is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. In some embodiments, the disease or condition involves vascular inflammation.

[0140] In another aspect, provided herein is a kit comprising any of the above antibodies or the above pharmaceutical compositions and instructions for use.

[0141] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody binds to the extracellular domain of human tissue factor (TF) at a human TF binding site that is distinct from the human TF binding site to which human FVIIa binds.

[0142] In some embodiments, (1) the antibody has a V of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L and (2) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0143] In some embodiments, (1) the antibody has a V of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L and (2) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0144] In some embodiments, (1) the antibody has a V of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 Land (2) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0145] In some embodiments, (1) the antibody has a V of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L and (2) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0146] In some embodiments, (1) the antibody has a V of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L and (2) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of a TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0147] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:784.

[0148] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:872, a VH-CDR2 HI comprising the sequence set forth in SEQ ID NO:873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:877.

[0149] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:883.

[0150] In some embodiments, the antibody has a V sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L It does not inhibit human thrombin generation compared to a reference antibody containing the sequence.

[0151] In some embodiments, the antibody has a V sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 LThe antibody inhibits human thrombin generation to a lesser extent compared to a reference antibody containing the sequence.

[0152] In some embodiments, the antibody has a V sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L The antibody sequence permits human thrombin generation to a greater extent than a reference antibody containing the sequence.

[0153] In some embodiments, the antibody has a V sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L The antibody inhibits human thrombin generation by a smaller amount compared to a reference antibody containing the sequence.

[0154] In some embodiments, the antibody has a V sequence similar to that of SEQ ID NO:821 as determined by a thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L It allows for greater amounts of human thrombin generation compared to a reference antibody containing the sequence.

[0155] In some embodiments, the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA). In some embodiments, the antibody does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. In some embodiments, the antibody does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control. In some embodiments, the antibody does not reduce endogenous thrombin potential (ETP) as determined by the area under the thrombin generation curve compared to an isotype control. In some embodiments, the antibody tolerates human thrombin generation as determined by a thrombin generation assay (TGA). In some embodiments, the antibody maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. In some embodiments, the antibody maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control. In some embodiments, the antibody protects endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve.

[0156] In some embodiments, the antibody binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, hi some embodiments, the antibody does not interfere with the ability of TF:FVIIa to convert FX to FXa.

[0157] In some embodiments, the antibody does not compete with human FVIIa for binding to human TF.

[0158] In some embodiments, the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), permits human thrombin generation as determined by a thrombin generation assay (TGA), binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, does not interfere with the ability of TF:FVIIa to convert FX to FXa, and does not compete with FVIIa for binding to human TF.

[0159] In some embodiments, the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), does not reduce endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve, permits human thrombin generation as determined by a thrombin generation assay (TGA) and protects endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve, binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, does not interfere with the ability of TF:FVIIa to convert FX to FXa, and does not compete with FVIIa for binding to human TF.

[0160] In some embodiments, the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control, does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control, does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control, and does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA). maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control, maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control, protects endogenous thrombin potential (ETP) compared to an isotype control as determined by the area under the thrombin generation curve, binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, does not interfere with the ability of TF:FVIIa to convert FX to FXa, and does not compete with FVIIa for binding to human TF.

[0161] In some embodiments, the antibody inhibits FVIIa-dependent TF signaling.

[0162] In some embodiments, the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO: 810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO: 810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO: 810 is K149N.

[0163] In some embodiments, the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO: 810 is greater than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence shown in SEQ ID NO: 810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 68 of the sequence shown in SEQ ID NO: 810 is K68N.

[0164] In some embodiments, the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence shown in SEQ ID NO: 810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 are N171H and T197K.

[0165] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 1-77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 1-76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0166] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 39-77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0167] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 94-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0168] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 146-158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151-163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0169] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159-219 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-224 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0170] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159-189 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-194 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0171] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0172] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 167-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 172-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0173] In some embodiments, the binding between the antibody and the extracellular domain of rat TF in which amino acid residues 141-194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0174] In some embodiments, the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is more than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; and the binding between the antibody and the extracellular domain of human TF in which amino acid residues 1-77 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 1-76 in the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838, as determined by median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. the binding between the antibody and the extracellular domain of human TF in which amino acid residues 39 to 77 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 38 to 76 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO: 838 is greater than 50% of the binding between the antibody and the extracellular domain of TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 99 to 112 of the extracellular domain of rat TF in which amino acid residues 146 to 158 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 156 to 160 of the extracellular domain of rat TF in which amino acid residues 166 to 170 of the extracellular domain of rat TF in which amino acid residues 176 to 180 of the extracellular domain of rat TF in which amino acid residues 186 to 190 of the extracellular domain of rat TF in which amino acid residues 194 to 207 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 199 to 201 of the extracellular domain of rat TF in which amino acid residues 206 to 210 of the extracellular domain of rat TF in which amino acid residues 214 to 220 of the extracellular domain of rat TF in which amino acid residues 226 to 230 of the extracellular domain of rat TF in which amino acid residues 236 to 240 of the extracellular domain of rat TF in which amino acid residues 246 to 250 of the extracellular domain of rat TF in which amino acid residues 256 to 260 of the extracellular domain of rat TF in which amino acid residues 266 to 270 of the extracellular domain of rat TF in which amino acid residues 276 to The binding between the antibody and the extracellular domain of human TF in which amino acid residues 151 to 163 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 151 to 163 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, and the binding between the antibody and the extracellular domain of TF in which amino acid residues 141 to 194 of the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 151 to 163 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810,The binding between the extracellular domain of rat TF substituted with amino acid residues 136-189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO: 810 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO: 810. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO: 810 is K149N and the mutation at amino acid residue 68 of the sequence set forth in SEQ ID NO: 810 is K68N.

[0175] In some embodiments, the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is more than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; and the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. the binding between the antibody and the extracellular domain of human TF in which amino acid residues 1 to 77 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 1 to 76 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is more than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; the binding between the antibody and the extracellular domain of human TF in which amino acid residues 39 to 77 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 38 to 76 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is more than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; The binding between the antibody and the extracellular domain of human TF in which amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 99 to 112 is more than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, and the binding between the antibody and the extracellular domain of TF in which amino acid residues 146 to 158 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 146 to 158 of the sequence shown in SEQ ID NO:810.The binding between the antibody and the extracellular domain of human TF in which amino acid residues 159 to 219 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 224 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF in which amino acid residues 159 to 189 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 194 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838. the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159 to 174 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 164 to 179 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO: 838 is less than 50% of the binding between the antibody and the extracellular domain of TF in which amino acid residues 167 to 174 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 172 to 179 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO: 838 is less than 50% of the binding between the antibody and the extracellular domain of TF in which amino acid residues 141 to 194 of the sequence shown in SEQ ID NO: 838 are replaced by amino acid residues 164 to 179 of the extracellular domain of rat TF in which amino acid residues 167 to 174 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 172 to 179 of the extracellular domain of rat TF in which amino acid residues 141 to 194 of the sequence shown in SEQ ID NO: 838 is less than 50% of the binding between the antibody and the extracellular domain of TF in which amino acid residues 141 to 194 of the sequence shown in SEQ ID NO: 838 are replaced by amino acid residues 164 to 179 of the extracellular domain of rat TF in which amino acid residues 167 to 174 of the sequence shown in SEQ ID NO: 810 are replaced by amino acid residues 167 to 174 of the sequence shown in SEQ ID NO: 810 The binding between the extracellular domain of rat TF having amino acid residues 136-189 substituted for those of the extracellular domain of human TF having the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the antibody and the extracellular domain of TF having the sequence set forth in SEQ ID NO:810.The mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is K149N, the mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is K68N, and the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 are N171H and T197K.

[0176] In some embodiments, the antibody binds to cynomolgus monkey TF. In some embodiments, the antibody binds to mouse TF. In some embodiments, the antibody binds to rabbit TF. In some embodiments, the antibody binds to porcine TF.

[0177] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), and (b) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO: 810 compared to the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO: 810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO: 810 are N171H and T197K.

[0178] In some embodiments, the antibody (a) permits human thrombin generation as determined by a thrombin generation assay (TGA), and (b) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO: 810 compared to the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO: 810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO: 810 are N171H and T197K.

[0179] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (c) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N, and the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K.

[0180] In some embodiments, the antibody (a) permits human thrombin generation as determined by a thrombin generation assay (TGA); (b) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay, and (c) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N, and the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K.

[0181] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) binds to cynomolgus monkey TF; (c) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (d) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N, and the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K.

[0182] In some embodiments, the antibody (a) permits human thrombin generation as determined by a thrombin generation assay (TGA); (b) binds to cynomolgus monkey TF; (c) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (d) exhibits less than 50% of the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. In some embodiments, the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N, and the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K.

[0183] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), (b) permits human thrombin generation as determined by a thrombin generation assay (TGA), (c) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, (d) does not interfere with the ability of TF:FVIIa to convert FX to FXa, (e) does not compete with FVIIa for binding to human TF, (f) inhibits FVIIa-dependent TF signaling, (g) binds to cynomolgus monkey TF, (h) binds to mouse TF, and (i) binds to rabbit TF.

[0184] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), (b) does not reduce endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve, (c) permits human thrombin generation as determined by a thrombin generation assay (TGA), (d) protects endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve, (e) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, (f) does not interfere with the ability of TF:FVIIa to convert FX to FXa, (g) does not compete with FVIIa for binding to human TF, (h) inhibits FVIIa-dependent TF signaling, (i) binds to cynomolgus monkey TF, (j) binds to mouse TF, and (k) binds to rabbit TF.

[0185] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on a thrombin generation curve compared to an isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on a thrombin generation curve (tt peak) compared to an isotype control; (d) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (e) tolerates human thrombin generation as determined by a thrombin generation assay (TGA); and (f) does not increase the thrombin peak on a thrombin generation curve compared to an isotype control. (g) maintains the thrombin peak (peak IIa) on the thrombin generation curve (tt peak) compared to an isotype control; (h) protects endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) does not interfere with the ability of TF:FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibits FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; and (o) binds to rabbit TF.

[0186] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), (b) permits human thrombin generation as determined by a thrombin generation assay (TGA), (c) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, (d) does not interfere with the ability of TF:FVIIa to convert FX to FXa, (e) does not compete with FVIIa for binding to human TF, (f) inhibits FVIIa-dependent TF signaling, (g) binds to cynomolgus monkey TF, (h) binds to mouse TF, (i) binds to rabbit TF, and (j) binds to pig TF.

[0187] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), (b) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control, (c) permits human thrombin generation as determined by a thrombin generation assay (TGA), (d) protects endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control, (e) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, (f) does not interfere with the ability of TF:FVIIa to convert FX to FXa, (g) does not compete with FVIIa for binding to human TF, (h) inhibits FVIIa-dependent TF signaling, (i) binds to cynomolgus monkey TF, (j) binds to mouse TF, (k) binds to rabbit TF, and (l) binds to pig TF.

[0188] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on a thrombin generation curve compared to an isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on a thrombin generation curve (tt peak) compared to an isotype control; (d) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (e) tolerates human thrombin generation as determined by a thrombin generation assay (TGA); and (f) does not increase the time from the start of the assay to the thrombin peak on a thrombin generation curve compared to an isotype control. (g) maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (ttpeak) compared to an isotype control; (h) protects endogenous thrombin potential (ETP) compared to an isotype control as determined by the area under the thrombin generation curve; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) does not interfere with the ability of TF:FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibits FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; (o) binds to rabbit TF; and (p) binds to porcine TF.

[0189] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control; (d) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (e) tolerates human thrombin generation as determined by a thrombin generation assay (TGA); (f) maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; and (g) increases the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. (h) protects endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) does not interfere with the ability of TF:FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibits FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; (o) binds to rabbit TF; (p) binds to porcine TF; and (q) as determined by median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. (r) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of a TF of the sequence shown in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.(s) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of a TF having the sequence shown in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control; and (t) the binding between the antibody and the extracellular domain of a human TF in which amino acid residues 1 to 77 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 1 to 76 of the extracellular domain of a rat TF having the sequence shown in SEQ ID NO:838, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. (u) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 39 to 77 of the sequence shown in SEQ ID NO: 810 are replaced with amino acid residues 38 to 76 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO: 838 is greater than 50% of the binding between the antibody and the extracellular domain of TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO: 810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF in which ... determined by median fluorescence intensity of the antibody in a live cell staining assay compared to an isotype control; and (v) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO: 810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF in which sequence shown in SEQ ID NO: 838 is determined by median fluorescence intensity of the antibody in a live cell staining assay compared to an isotype control. and (w) greater than 50% binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.(x) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159 to 219 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 224 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control, and (y) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159 to 189 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 224 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. (z) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159 to 174 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 179 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control; and (aa) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 167 to 174 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 167 to 174 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control. The binding between the antibody and the extracellular domain of human TF, wherein amino acid residues 172 to 179 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 172 to 179 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838.and (bb) the binding between the antibody and the extracellular domain of rat TF in which amino acid residues 141-194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay, is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810.

[0190] In some embodiments, the antibody (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control; (d) does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (e) tolerates human thrombin generation as determined by a thrombin generation assay (TGA); (f) maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; and (g) increases the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. (h) protects endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) does not interfere with the ability of TF:FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibits FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; (o) binds to rabbit TF; (p) binds to porcine TF; and (q) as determined by median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. (r) the binding between the antibody and the extracellular domain of a variant TF comprising the mutation K68N of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of a TF comprising the mutation K149N of the sequence shown in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.(s) the binding between the antibody and the extracellular domain of a variant TF comprising the mutations N171H and T197K of the sequence shown in SEQ ID NO:810 is greater than 50% of the binding between the antibody and the extracellular domain of a TF having the sequence shown in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control; and (t) the binding between the antibody and the extracellular domain of a human TF in which amino acid residues 1 to 77 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 1 to 76 in the extracellular domain of a rat TF having the sequence shown in SEQ ID NO:838, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. (u) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 39 to 77 of the sequence shown in SEQ ID NO: 810 are replaced with amino acid residues 38 to 76 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO: 838 is greater than 50% of the binding between the antibody and the extracellular domain of TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO: 810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF in which ... determined by median fluorescence intensity of the antibody in a live cell staining assay compared to an isotype control; and (v) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO: 810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF in which sequence shown in SEQ ID NO: 838 is determined by median fluorescence intensity of the antibody in a live cell staining assay compared to an isotype control. and (w) greater than 50% binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810 as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.(x) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159 to 219 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 224 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control, and (y) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159 to 189 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 224 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. (z) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159 to 174 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 164 to 179 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control; and (aa) the binding between the antibody and the extracellular domain of human TF in which amino acid residues 167 to 174 of the sequence shown in SEQ ID NO:810 are replaced by amino acid residues 167 to 174 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control. The binding between the antibody and the extracellular domain of human TF, wherein amino acid residues 172 to 179 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 are replaced by amino acid residues 172 to 179 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838.and (bb) the binding between the antibody and the extracellular domain of rat TF in which amino acid residues 141-194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay, is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810.

[0191] In some embodiments, the antibody competes for binding to human TF with an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0192] In some embodiments, the antibody competes with an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9 for binding to human TF.

[0193] In some embodiments, the antibody competes with an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea for binding to human TF.

[0194] In some embodiments, the antibody binds to the same epitope of human TF as does the antibody designated 25A, the antibody designated 25A3, the antibody designated 25A5, the antibody designated 25A5-T, the antibody designated 25G, the antibody designated 25G1, the antibody designated 25G9, the antibody designated 43B, the antibody designated 43B1, the antibody designated 43B7, the antibody designated 43D, the antibody designated 43D7, the antibody designated 43D8, the antibody designated 43E, or the antibody designated 43Ea.

[0195] In some embodiments, the antibody binds to the same epitope of human TF as the antibody designated 25A, the antibody designated 25A3, the antibody designated 25A5, the antibody designated 25A5-T, the antibody designated 25G, the antibody designated 25G1, or the antibody designated 25G9.

[0196] In some embodiments, the antibody binds to the same epitope of human TF as the antibody designated 43B, the antibody designated 43B1, the antibody designated 43B7, the antibody designated 43D, the antibody designated 43D7, the antibody designated 43D8, the antibody designated 43E, or the antibody designated 43Ea.

[0197] In some embodiments, the antibody comprises all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, 25G9, 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. In some embodiments, the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering.

[0198] In some embodiments, the antibody comprises all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9.

[0199] In some embodiments, the antibody comprises all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from the antibody designated 43B, the antibody designated 43B1, the antibody designated 43B7, the antibody designated 43D, the antibody designated 43D7, the antibody designated 43D8, the antibody designated 43E, or the antibody designated 43Ea.

[0200] In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A3. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5-T. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G1. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G9. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B1. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B7. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D7. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D8. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43E. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43Ea.

[0201] In some embodiments, the antibody comprises V of SEQ ID NO:113. H Sequence and V of SEQ ID NO: 114 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:151. HSequence and V of SEQ ID NO: 152 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:189. H Sequence and V of SEQ ID NO: 190 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:836. H Sequence and V of SEQ ID NO:837 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:227. H Sequence and V of SEQ ID NO: 228 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:265. H Sequence and V of SEQ ID NO: 266 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:303. H Sequence and V of SEQ ID NO: 304 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:455. H Sequence and V of SEQ ID NO:456 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:493. H Sequence and V of SEQ ID NO:494 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:531. H Sequence and V of SEQ ID NO:532 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:569. H Sequence and V of SEQ ID NO:570 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:607. H Sequence and V of SEQ ID NO:608 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:645. H Sequence and V of SEQ ID NO:646 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:683. H Sequence and V of SEQ ID NO:684L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:721. H Sequence and V of SEQ ID NO:722 L Contains arrays.

[0202] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 784. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 872, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 877. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 883. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 797, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 798, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 799, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 800, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 801, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 802.

[0203] In some embodiments, the antibody comprises V of SEQ ID NO:763. H Sequence and V of SEQ ID NO:764 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:868. H Sequence and V of SEQ ID NO:869 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:870. H Sequence and V of SEQ ID NO:871 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:769. H Sequence and V of SEQ ID NO:770 L Contains arrays.

[0204] In some embodiments, the antibody comprises an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. In some embodiments, the antibody comprises an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9. In some embodiments, the antibody comprises an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea.

[0205] In some embodiments, the antibody consists of the antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, 25G9, 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. In some embodiments, the antibody consists of the antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9. In some embodiments, the antibody consists of the antibody designated as 43B, the antibody designated as 43B1, the antibody designated as 43B7, the antibody designated as 43D, the antibody designated as 43D7, the antibody designated as 43D8, the antibody designated as 43E, or the antibody designated as 43Ea.

[0206] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody competes with an antibody designated 1F, an antibody designated 1G, an antibody designated 29D, an antibody designated 29E, an antibody designated 39A, or an antibody designated 54E for binding to human TF.

[0207] In some embodiments, the antibody inhibits FVIIa-dependent TF signaling.

[0208] In some embodiments, the antibody binds to cynomolgus monkey TF.

[0209] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 94-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0210] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 78-93 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77-98 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0211] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 78-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0212] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 78-107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77-85 and 92-112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0213] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 94-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, and the binding between the antibody and the extracellular domain of human TF in which amino acid residues 78-93 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77-98 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay.

[0214] In some embodiments, the binding between the antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; the binding between the antibody and the extracellular domain of human TF in which amino acid residues 78 to 107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77 to 112 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810; and the binding between the antibody and the extracellular domain of human TF in which amino acid residues 78 to 107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77 to 112 of the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810. The binding between the extracellular domain of human TF in which amino acid residues 77-85 and 92-112 of the extracellular domain of rat TF having the sequence set forth in SEQ ID NO:838 are replaced is more than 50% of the binding between the antibody and the extracellular domain of TF having the sequence set forth in SEQ ID NO:810.

[0215] In some embodiments, the antibody comprises all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated 1F, an antibody designated 1G, an antibody designated 29D, an antibody designated 29E, an antibody designated 39A, an antibody designated 43Ea, or an antibody designated 54E. In some embodiments, the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering.

[0216] In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 1F. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 1G. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 29D. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 29E. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 39A. In some embodiments, the antibody comprises all three heavy chain CDRs and all three light chain CDRs from the antibody designated 54E.

[0217] In some embodiments, the antibody comprises V of SEQ ID NO:37. H Sequence and V of SEQ ID NO: 38 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:75. H Sequence and V of SEQ ID NO:76 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:341. H Sequence and V of SEQ ID NO: 342 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:379. H Sequence and V of SEQ ID NO: 380 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:417. H Sequence and V of SEQ ID NO:418 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:759. H Sequence and V of SEQ ID NO:760 L Contains arrays.

[0218] In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 773, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 774, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 775, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 776, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 777, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 778. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 785, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 786, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 787, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 788, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 789, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 790. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 791, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 792, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 793, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 794, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 795, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 796. In some embodiments, the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 803, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 804, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 805, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 806, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 807, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 808.

[0219] In some embodiments, the antibody comprises V of SEQ ID NO:761. H Sequence and V of SEQ ID NO:762 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:765. H Sequence and V of SEQ ID NO:766 LIn some embodiments, the antibody comprises the sequence V of SEQ ID NO:767. H Sequence and V of SEQ ID NO:768 L In some embodiments, the antibody comprises the sequence V of SEQ ID NO:771. H Sequence and V of SEQ ID NO:772 L Contains arrays.

[0220] In some embodiments, the antibody comprises the antibody designated as 1F, the antibody designated as 1G, the antibody designated as 29D, the antibody designated as 29E, the antibody designated as 39A, or the antibody designated as 54E. In some embodiments, the antibody consists of the antibody designated as 1F, the antibody designated as 1G, the antibody designated as 29D, the antibody designated as 29E, the antibody designated as 39A, or the antibody designated as 54E.

[0221] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:773, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:774, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:775, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:776, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:777, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:778.

[0222] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:784.

[0223] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:785, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:786, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:787, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:788, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:789, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:790.

[0224] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:791, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:792, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:793, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:794, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:795, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:796.

[0225] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:797, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:798, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:799, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:800, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:801, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:802.

[0226] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:803, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:804, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:805, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:806, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:807, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:808.

[0227] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:872, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:877.

[0228] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:883.

[0229] In some embodiments, the antibody is human, humanized, or chimeric.

[0230] In some embodiments, the antibody has a K of 50 nM or less, 10 nM or less, 5 nM or less, 1 nM or less, 0.5 nM or less, or 0.1 nM or less as measured by Octet QK384 or Biacore assay. D It binds to human TF.

[0231] In some embodiments, the antibody is a monoclonal antibody.

[0232] In some embodiments, the antibody is multispecific.

[0233] In some embodiments, the antibody is a Fab, Fab', F(ab')2, Fv, scFv, (scFv)2, single-chain antibody molecule, dual variable domain antibody, single variable domain antibody, linear antibody, or V-domain antibody.

[0234] In some embodiments, the antibody comprises a scaffold, optionally the scaffold is an Fc, optionally a human Fc. In some embodiments, the antibody comprises a heavy chain constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. In some embodiments, the antibody comprises a heavy chain constant region of an IgG class and subclass selected from IgG1, IgG2, IgG3, and IgG4. In some embodiments, the antibody comprises an IgG1 heavy chain constant region. In some embodiments, the Fc comprises one or more modifications that result in increased half-life, increased antibody-dependent cellular cytotoxicity (ADCC), increased antibody-dependent cellular phagocytosis (ADCP), increased complement-dependent cytotoxicity (CDC), or decreased effector function compared to the Fc without the one or more modifications.

[0235] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody competes with any of the above antibodies for binding to human TF.

[0236] In another aspect, provided herein is an antibody drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody binds to an epitope of human TF to which any of the above antibodies bind.

[0237] In some embodiments, the cytotoxic agent comprises an angiogenesis inhibitor, a proapoptotic agent, a mitotic inhibitor, a kinase inhibitor, an alkylating agent, a hormone, a hormone agonist, a hormone antagonist, a chemokine, a drug, a prodrug, a toxin, an enzyme, an antimetabolite, an antibiotic, an alkaloid, or a radioisotope. In some embodiments, the cytotoxic agent comprises at least one of a calicheamicin, a camptothecin, a carboplatin, an irinotecan, an SN-38, a carboplatin, a camptothecan, a cyclophosphamide, a cytarabine, a dacarbazine, a docetaxel, a dactinomycin, a daunorubicin, a doxorubicin, an etoposide, an idarubicin, a topotecan, a vinca alkaloid, a maytansinoid, a maytansinoid analog, a pyrrolobenzodiazepine, a taxoid, a duocarmycin, a dolastatin, and an auristatin.

[0238] In some embodiments, the linker comprises a labile linker, an acid-labile linker, a photolabile linker, a charged linker, a disulfide-containing linker, a peptidase-sensitive linker, a β-glucuronide linker, a dimethyl linker, a thio-ether linker, or a hydrophilic linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker is a non-cleavable linker.

[0239] In another aspect, provided herein is a pharmaceutical composition comprising any of the antibody drug conjugates described above and a pharmaceutically acceptable excipient.

[0240] In another aspect, provided herein is a method for treating or preventing a disease or condition in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the antibody drug conjugates described above or the pharmaceutical composition described above.

[0241] In some embodiments, the disease or condition is cancer. In some embodiments, the cancer is head and neck cancer. In some embodiments, the cancer is ovarian cancer. In some embodiments, the cancer is gastric cancer. In some embodiments, the cancer is esophageal cancer. In some embodiments, the cancer is cervical cancer. In some embodiments, the cancer is prostate cancer. In some embodiments, the cancer is pancreatic cancer. In some embodiments, the cancer is triple-negative estrogen receptor negative (ER-), progesterone receptor negative (PR-), and HER2 negative (HER2-) breast cancer. In some embodiments, the cancer is glioblastoma. In some embodiments, the cancer is lung cancer. In some embodiments, the cancer is bladder cancer. In some embodiments, the cancer is melanoma. In some embodiments, the cancer is kidney cancer.

[0242] In some embodiments, the method further comprises administering one or more additional therapeutic agents to the subject. In some embodiments, the additional therapeutic agent is formulated in the same pharmaceutical composition as the antibody drug conjugate. In some embodiments, the additional therapeutic agent is formulated in a different pharmaceutical composition from the antibody drug conjugate. In some embodiments, the additional therapeutic agent is administered before administering the antibody drug conjugate. In some embodiments, the additional therapeutic agent is administered after administering the antibody drug conjugate. In some embodiments, the additional therapeutic agent is administered simultaneously with the antibody drug conjugate.

[0243] In another aspect, provided herein is a method for detecting TF in a subject having or suspected of having a disease or condition, the method comprising: (a) administering to the subject any of the antibody drug conjugates described above; and (b) detecting the presence or level of TF in the subject.

[0244] In some embodiments, the disease or condition is cancer. In some embodiments, the cancer is head and neck cancer. In some embodiments, the cancer is ovarian cancer. In some embodiments, the cancer is gastric cancer. In some embodiments, the cancer is esophageal cancer. In some embodiments, the cancer is cervical cancer. In some embodiments, the cancer is prostate cancer. In some embodiments, the cancer is pancreatic cancer. In some embodiments, the cancer is triple-negative estrogen receptor negative (ER-), progesterone receptor negative (PR-), and HER2 negative (HER2-) breast cancer. In some embodiments, the cancer is glioblastoma. In some embodiments, the cancer is lung cancer. In some embodiments, the cancer is bladder cancer. In some embodiments, the cancer is melanoma. In some embodiments, the cancer is kidney cancer.

[0245] In another aspect, provided herein is a kit comprising any of the above antibody drug conjugates or the above pharmaceutical composition and instructions for use. [The present invention 1001] An isolated human antibody that binds to the extracellular domain of human tissue factor (TF), wherein the antibody binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FVIIa binds. [The present invention 1002] (1) the isolated antibody has a V of SEQ ID NO:821 as determined by a thrombin generation assay (TGA); H Sequence and V of SEQ ID NO:822 L does not inhibit human thrombin generation compared to a reference antibody containing the sequence, and (2) the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; 1000 isolated human antibodies of the present invention. [The present invention 1003] An isolated human antibody of the present invention 1000 or 1002, comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:784. [The present invention 1004] An isolated human antibody according to any one of claims 1000 to 1003 of the present invention, comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 872, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 877. [The present invention 1005] An isolated human antibody according to any one of claims 1000 to 1003 of the present invention, comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 883. [The present invention 1006] V of SEQ ID NO:821 as determined by thrombin generation assay (TGA) H Sequence and V of SEQ ID NO:822 L 1000 isolated human antibodies of the present invention that do not inhibit human thrombin generation compared to a reference antibody comprising the sequence. [The present invention 1007] 1000 isolated human antibodies of the present invention that do not inhibit human thrombin generation as determined by a thrombin generation assay (TGA). [The present invention 1008] 1007. An isolated human antibody of the present invention which does not reduce the thrombin peak (peak IIa) on a thrombin generation curve compared to an isotype control. [The present invention 1009] The isolated human antibody of the present invention 1007 or 1008, which does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control. [The present invention 1010] An isolated human antibody according to any of claims 1007 to 1009, which does not reduce endogenous thrombin generation potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve. [The present invention 1011] Any of the isolated human antibodies of the preceding invention that permit human thrombin generation as determined by a thrombin generation assay (TGA). [The present invention 1012] 1011. An isolated human antibody of the invention that maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. [The present invention 1013] 10 11 or 10 12 isolated human antibodies of the invention, which maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control. [The present invention 1014] Any of 10 11 to 10 13 isolated human antibodies of the invention that protect endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve. [The present invention 1015] Any of the isolated human antibodies of the preceding invention which bind to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds. [The present invention 1016] Any isolated human antibody of the preceding invention, which does not interfere with the ability of TF:FVIIa to convert FX to FXa. [The present invention 1017] Any isolated human antibody of the preceding invention that does not compete with human FVIIa for binding to human TF. [The present invention 1018] Any of the isolated human antibodies of the preceding invention, which does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), allows human thrombin generation as determined by a thrombin generation assay (TGA), binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, does not interfere with the ability of TF:FVIIa to convert FX to FXa, and does not compete with FVIIa for binding to human TF. [The present invention 1019] Any of the preceding isolated human antibodies of the present invention, which does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), does not reduce endogenous thrombin potential (ETP) as determined by the area under the thrombin generation curve compared to an isotype control, allows human thrombin generation as determined by a thrombin generation assay (TGA) and protects endogenous thrombin potential (ETP) as determined by the area under the thrombin generation curve compared to an isotype control, binds to human TF at a human TF binding site that is separate from the human TF binding site to which human FX binds, does not interfere with the ability of TF:FVIIa to convert FX to FXa, and does not compete with FVIIa for binding to human TF. [The present invention 1020] does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control; does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control; does not reduce endogenous thrombin potential (ETP) as determined by the area under the thrombin generation curve compared to an isotype control; and permits human thrombin generation as determined by a thrombin generation assay (TGA) compared to an isotype control. Any of the preceding isolated human antibodies of the present invention, which maintain the thrombin peak (Peak IIa) on the thrombin generation curve, maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt Peak) compared to an isotype control, protect endogenous thrombin potential (ETP) compared to an isotype control as determined by the area under the thrombin generation curve, bind to human TF at a human TF binding site that is separate from the human TF binding site to which human FX binds, do not interfere with the ability of TF:FVIIa to convert FX to FXa, and do not compete with FVIIa for binding to human TF. [The present invention 1021] Any of the isolated human antibodies of the preceding invention that inhibit FVIIa-dependent TF signaling. [The present invention 1022] Any of the isolated human antibodies of the preceding invention, wherein the binding between said isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between said isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of said isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1023] 1022. The isolated human antibody of the present invention, wherein the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N. [The present invention 1024] Any of the isolated human antibodies of the preceding invention, wherein the binding between said isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is greater than 50% of the binding between said isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by the median fluorescence intensity of said isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1025] 1024. The isolated human antibody of the present invention, wherein said mutation at amino acid residue 68 of the sequence set forth in SEQ ID NO:810 is K68N. [The present invention 1026] Any of the isolated human antibodies of the preceding invention, wherein the binding between said isolated antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between said isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by the median fluorescence intensity of said isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1027] 1026. An isolated human antibody of the present invention, wherein said mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K. [The present invention 1028] Any of the isolated human antibodies of the preceding invention, wherein the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 1-77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 1-76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1029] Any of the isolated human antibodies of the preceding invention, wherein the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 39-77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1030] Any of the isolated human antibodies of the preceding invention, wherein the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1031] Any of the isolated human antibodies of the preceding invention, wherein the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146-158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151-163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1032] Any of the isolated human antibodies of the preceding invention, wherein the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-219 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-224 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1033] Any of the isolated human antibodies of the preceding invention, wherein the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-189 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-194 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1034] Any of the isolated human antibodies of the preceding invention, wherein the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. [This invention 1035] Any of the isolated human antibodies of the preceding invention, wherein the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 167-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 172-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. [The present invention 1036] Any of the isolated human antibodies of the preceding invention, wherein the binding between the isolated antibody and the extracellular domain of rat TF in which amino acid residues 141-194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. [This invention 1037] as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO: 810 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO: 810; the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO: 810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO: 810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 1 to 77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 1 to 76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 39 to 77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38 to 76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146 to 158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151 to 163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; and the binding between the isolated antibody and the extracellular domain of rat TF in which amino acid residues 141 to 194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136 to 189 of the extracellular domain of human TF in the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in the sequence set forth in SEQ ID NO:810; Any isolated human antibody of the preceding invention. [The present invention 1038] the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N; and the mutation at amino acid residue 68 of the sequence shown in SEQ ID NO: 810 is K68N; An isolated human antibody of the present invention. [This invention 1039] as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay. the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO: 810 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO: 810; the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence shown in SEQ ID NO: 810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO: 810; the binding between the isolated antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO: 810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 1 to 77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 1 to 76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 39 to 77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38 to 76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146 to 158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151 to 163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159 to 219 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164 to 224 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159 to 189 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164 to 194 of the extracellular domain of rat TF in the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF in the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159 to 174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164 to 179 of the extracellular domain of rat TF having the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF having the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 167-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 172-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; and the binding between the isolated antibody and the extracellular domain of rat TF in which amino acid residues 141 to 194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136 to 189 of the extracellular domain of human TF in the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in the sequence set forth in SEQ ID NO:810; Any isolated human antibody of the preceding invention. [The present invention 1040] the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO: 810 is K149N; the mutation at amino acid residue 68 of the sequence set forth in SEQ ID NO:810 is K68N; and the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 are N171H and T197K; 1039. An isolated human antibody of the present invention. [This invention 1041] Any isolated human antibody of the preceding invention that binds to cynomolgus monkey TF. [The present invention 1042] Any isolated human antibody of the preceding invention that binds to mouse TF. [This invention 1043] Any isolated human antibody of the preceding invention that binds to rabbit TF. [This invention 1044] Any isolated human antibody of the preceding invention that binds to porcine TF. [This invention 1045] Any of the isolated human antibodies of the preceding invention that reduces lesion size in a porcine choroidal neovascularization (CNV) model. [The present invention 1046] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); and (b) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; Any isolated human antibody of the preceding invention. [This invention 1047] 1046. An isolated human antibody of the present invention, wherein said mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K. [This invention 1048] (a) permits human thrombin generation as determined by a thrombin generation assay (TGA); and (b) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; Any isolated human antibody of the preceding invention. [This invention 1049] 1048. The isolated human antibody of the present invention, wherein the mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 are N171H and T197K. [The present invention 1050] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (c) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; Any isolated human antibody of the preceding invention. [This invention 1051] the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N; and the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 are N171H and T197K; 1050. An isolated human antibody of the present invention. [This invention 1052] (a) permits human thrombin generation as determined by a thrombin generation assay (TGA); (b) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (c) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; Any isolated human antibody of the preceding invention. [This invention 1053] the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N; and the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 are N171H and T197K; 1052. An isolated human antibody of the present invention. [This invention 1054] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) binds to cynomolgus monkey TF; (c) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (d) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; Any isolated human antibody of the preceding invention. [This invention 1055] the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N; and the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 are N171H and T197K; An isolated human antibody of the present invention. [The present invention 1056] (a) permits human thrombin generation as determined by a thrombin generation assay (TGA); (b) binds to cynomolgus monkey TF; (c) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; and (d) the binding between the antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; Any isolated human antibody of the preceding invention. [This invention 1057] the mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is K149N; and the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO: 810 are N171H and T197K; 1056. An isolated human antibody of the present invention. [This invention 1058] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) permits human thrombin generation as determined by a thrombin generation assay (TGA); (c) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (d) TF:FVIIa does not interfere with the ability to convert FX to FXa; (e) does not compete with FVIIa for binding to human TF; (f) inhibiting FVIIa-dependent TF signaling; (g) binds to cynomolgus monkey TF; (h) binds to mouse TF; and (i) binds to rabbit TF; Any isolated human antibody of the preceding invention. [This invention 1059] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (c) permits human thrombin generation as determined by a thrombin generation assay (TGA); (d) protect endogenous thrombin potential (ETP) compared to isotype control as determined by area under the thrombin generation curve; (e) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (f) TF: does not interfere with the ability of FVIIa to convert FX to FXa; (g) does not compete with FVIIa for binding to human TF; (h) inhibiting FVIIa-dependent TF signaling; (i) binds to cynomolgus monkey TF; (j) binds to mouse TF; and (k) binds to rabbit TF; Any isolated human antibody of the preceding invention. [The present invention 1060] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to the isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (ttpeak) compared to the isotype control; (d) does not reduce endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (e) permits human thrombin generation as determined by a thrombin generation assay (TGA); (f) maintenance of the thrombin peak (peak IIa) on the thrombin generation curve compared to the isotype control; (g) maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to the isotype control; (h) protects endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) TF: does not interfere with the ability of FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibiting FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF, and (o) binds to rabbit TF; Any isolated human antibody of the preceding invention. [This invention 1061] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) permits human thrombin generation as determined by a thrombin generation assay (TGA); (c) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (d) TF:FVIIa does not interfere with the ability to convert FX to FXa; (e) does not compete with FVIIa for binding to human TF; (f) inhibiting FVIIa-dependent TF signaling; (g) binds to cynomolgus monkey TF; (h) binds to mouse TF; (i) binds to rabbit TF; (j) binds to porcine TF; and (k) reducing lesion size in a porcine choroidal neovascularization (CNV) model; Any isolated human antibody of the preceding invention. [The present invention 1062] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (c) permits human thrombin generation as determined by a thrombin generation assay (TGA); (d) protect endogenous thrombin potential (ETP) compared to isotype control as determined by area under the thrombin generation curve; (e) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (f) TF: does not interfere with the ability of FVIIa to convert FX to FXa; (g) does not compete with FVIIa for binding to human TF; (h) inhibiting FVIIa-dependent TF signaling; (i) binds to cynomolgus monkey TF; (j) binds to mouse TF; (k) binds to rabbit TF; (l) binds to porcine TF; and (m) reducing lesion size in a porcine choroidal neovascularization (CNV) model; Any isolated human antibody of the preceding invention. [The present invention 1063] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to the isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (ttpeak) compared to the isotype control; (d) does not reduce endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (e) permits human thrombin generation as determined by a thrombin generation assay (TGA); (f) maintenance of the thrombin peak (peak IIa) on the thrombin generation curve compared to the isotype control; (g) maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to the isotype control; (h) protects endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) TF: does not interfere with the ability of FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibiting FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; (o) binds to rabbit TF; (p) binds to porcine TF; and (q) Reduces lesion size in a porcine choroidal neovascularization (CNV) model; Any isolated human antibody of the preceding invention. [The present invention 1064] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to the isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (ttpeak) compared to the isotype control; (d) does not reduce endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (e) permits human thrombin generation as determined by a thrombin generation assay (TGA); (f) maintenance of the thrombin peak (peak IIa) on the thrombin generation curve compared to the isotype control; (g) maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to the isotype control; (h) protects endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) TF: does not interfere with the ability of FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibiting FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; (o) binds to rabbit TF; (p) binds to porcine TF; (q) Reduces lesion size in a porcine choroidal neovascularization (CNV) model; (r) the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (s) the binding between the isolated antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 68 of the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (t) the binding between the isolated antibody and the extracellular domain of a variant TF comprising mutations at amino acid residues 171 and 197 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (u) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 1 to 77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 1 to 76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (v) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 39-77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (w) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (x) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146-158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151-163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (y) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-219 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-224 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (z) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-189 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-194 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (aa) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (bb) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 167-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 172-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; and (cc) the binding between the isolated antibody and the extracellular domain of rat TF in which amino acid residues 141 to 194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136 to 189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; Any isolated human antibody of the preceding invention. [This invention 1065] (a) does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA); (b) does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to the isotype control; (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (ttpeak) compared to the isotype control; (d) does not reduce endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (e) permits human thrombin generation as determined by a thrombin generation assay (TGA); (f) maintenance of the thrombin peak (peak IIa) on the thrombin generation curve compared to the isotype control; (g) maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to the isotype control; (h) protects endogenous thrombin potential (ETP) compared to an isotype control, as determined by area under the thrombin generation curve; (i) binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds; (j) TF: does not interfere with the ability of FVIIa to convert FX to FXa; (k) does not compete with FVIIa for binding to human TF; (l) inhibiting FVIIa-dependent TF signaling; (m) binds to cynomolgus monkey TF; (n) binds to mouse TF; (o) binds to rabbit TF; (p) binds to porcine TF; (q) Reduces lesion size in a porcine choroidal neovascularization (CNV) model; (r) the binding between the isolated antibody and the extracellular domain of a variant TF comprising the mutation K149N of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (s) the binding between the isolated antibody and the extracellular domain of a variant TF comprising the mutation K68N of the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (t) the binding between the isolated antibody and the extracellular domain of a variant TF comprising the mutations N171H and T197K of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (u) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 1 to 77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 1 to 76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (v) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 39-77 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (w) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (x) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146-158 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 151-163 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (y) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-219 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-224 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (z) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-189 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-194 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (aa) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 164-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; (bb) the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 167-174 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 172-179 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; and (cc) the binding between the isolated antibody and the extracellular domain of rat TF in which amino acid residues 141 to 194 of the sequence set forth in SEQ ID NO:838 are replaced with amino acid residues 136 to 189 of the extracellular domain of human TF of the sequence set forth in SEQ ID NO:810 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay; Any isolated human antibody of the preceding invention. [The present invention 1066] Any of the preceding isolated human antibodies of the invention that competes with an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea for binding to human TF. [This invention 1067] An isolated human antibody of the present invention 1064 that competes with an antibody designated 25A, an antibody designated 25A3, an antibody designated 25A5, an antibody designated 25A5-T, an antibody designated 25G, an antibody designated 25G1, or an antibody designated 25G9 for binding to human TF. [The present invention 1068] 1064. An isolated human antibody of the present invention that competes with an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea for binding to human TF. [This invention 1069] Any of the preceding isolated human antibodies of the present invention, which binds to the same epitope of human TF as does an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [The present invention 1070] An isolated human antibody of the present invention 1069 that binds to the same epitope of human TF as the antibody designated 25A, the antibody designated 25A3, the antibody designated 25A5, the antibody designated 25A5-T, the antibody designated 25G, the antibody designated 25G1, or the antibody designated 25G9. [This invention 1071] An isolated human antibody of the present invention 1069 that binds to the same epitope of human TF as the antibody designated 43B, the antibody designated 43B1, the antibody designated 43B7, the antibody designated 43D, the antibody designated 43D7, the antibody designated 43D8, the antibody designated 43E, or the antibody designated 43Ea. [This invention 1072] Any of the preceding isolated human antibodies of the present invention, comprising all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [This invention 1073] 1072. An isolated human antibody of the invention, wherein the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering. [This invention 1074] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9. [This invention 1075] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [This invention 1076] An isolated human antibody of the invention 1072 or 1073 comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A. [This invention 1077] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A3. [This invention 1078] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5. [This invention 1079] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5-T. [The present invention 1080] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G. [This invention 1081] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G1. [This invention 1082] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G9. [This invention 1083] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B. [This invention 1084] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B1. [This invention 1085] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B7. [The present invention 1086] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D. [This invention 1087] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D7. [This invention 1088] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D8. [This invention 1089] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43E. [The present invention 1090] An isolated human antibody of the invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43Ea. [This invention 1091] SEQ ID NO: 113V H Sequence and V of SEQ ID NO: 114 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1092] SEQ ID NO: 151V H Sequence and V of SEQ ID NO: 152 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1093] SEQ ID NO: 189V HSequence and V of SEQ ID NO: 190 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1094] SEQ ID NO:836V H Sequence and V of SEQ ID NO:837 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1095] SEQ ID NO:227V H Sequence and V of SEQ ID NO: 228 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1096] SEQ ID NO:265V H Sequence and V of SEQ ID NO: 266 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1097] SEQ ID NO: 303V H Sequence and V of SEQ ID NO: 304 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1098] SEQ ID NO: 455V H Sequence and V of SEQ ID NO:456 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1099] SEQ ID NO:493V H Sequence and V of SEQ ID NO:494 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [The present invention 1100] SEQ ID NO:531V H Sequence and V of SEQ ID NO:532 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [The present invention 1101] SEQ ID NO:569V H Sequence and V of SEQ ID NO:570 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [The present invention 1102] SEQ ID NO:607V H Sequence and V of SEQ ID NO:608 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [The present invention 1103] SEQ ID NO:645V H Sequence and V of SEQ ID NO:646 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [The present invention 1104] SEQ ID NO:683V H Sequence and V of SEQ ID NO:684 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1105] SEQ ID NO:721V H Sequence and V of SEQ ID NO:722 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [The present invention 1106] An isolated human antibody according to any one of claims 1000 to 1073 of the present invention, comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:784. [This invention 1107] An isolated human antibody according to any one of claims 1000 to 1073 of the present invention, comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 872, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 877. [This invention 1108] An isolated human antibody according to any one of claims 1000 to 1073 of the present invention, comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 883. [This invention 1109] An isolated human antibody according to any one of claims 1000 to 1073 of the present invention, comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:797, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:798, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:799, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:800, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:801, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:802. [The present invention 1110] SEQ ID NO:763V H Sequence and V of SEQ ID NO:764 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [The present invention 1111] SEQ ID NO:868V H Sequence and V of SEQ ID NO:869 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [The present invention 1112] SEQ ID NO:870V H Sequence and V of SEQ ID NO:871 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [The present invention 1113] SEQ ID NO:769V H Sequence and V of SEQ ID NO:770 L An isolated human antibody according to any one of claims 1000 to 1073, comprising the sequence: [This invention 1114] Any of the isolated human antibodies of the preceding invention, including the antibody designated as 25A, the antibody designated as 25A3, the antibody designated as 25A5, the antibody designated as 25A5-T, the antibody designated as 25G, the antibody designated as 25G1, the antibody designated as 25G9, the antibody designated as 43B, the antibody designated as 43B1, the antibody designated as 43B7, the antibody designated as 43D, the antibody designated as 43D7, the antibody designated as 43D8, the antibody designated as 43E, or the antibody designated as 43Ea. [This invention 1115] An isolated human antibody of the present invention 1114, including an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9. [The present invention 1116] An isolated human antibody of the present invention 1114, including an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [This invention 1117] Any of the isolated human antibodies of the preceding invention consisting of an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [This invention 1118] An isolated human antibody of the present invention 1117, consisting of an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9. [This invention 1119] An isolated human antibody of the present invention 1117, consisting of an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [The present invention 1120] An isolated antibody comprising all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [This invention 1121] The isolated antibody of the invention 1120, which is human, humanized, or chimeric. [This invention 1122] 1120 or 1121, an isolated antibody of the invention, wherein the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering. [This invention 1123] An isolated antibody of any of the present inventions 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9. [This invention 1124] 25A. An isolated antibody according to any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A. [Invention 1125] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A3. [The present invention 1126] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5. [This invention 1127] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25A5-T. [This invention 1128] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G. [This invention 1129] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G1. [The present invention 1130] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 25G9. [This invention 1131] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [This invention 1132] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B. [This invention 1133] 11. The isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B1. [This invention 1134] 11. The isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43B7. [This invention 1135] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D. [This invention 1136] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D7. [This invention 1137] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43D8. [This invention 1138] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43E. [This invention 1139] An isolated antibody of any of claims 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 43Ea. [This invention 1140] SEQ ID NO: 113V H Sequence and V of SEQ ID NO: 114 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1141] SEQ ID NO: 151V H Sequence and V of SEQ ID NO: 152 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1142] SEQ ID NO: 189V H Sequence and V of SEQ ID NO: 190 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1143] SEQ ID NO:836V H Sequence and V of SEQ ID NO:837 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1144] SEQ ID NO:227V H Sequence and V of SEQ ID NO: 228 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [Invention 1145] SEQ ID NO:265V H Sequence and V of SEQ ID NO: 266 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [Invention 1146] SEQ ID NO: 303V H Sequence and V of SEQ ID NO: 304 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1147] SEQ ID NO: 455V H Sequence and V of SEQ ID NO:456 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [Invention 1148] SEQ ID NO:493V H Sequence and V of SEQ ID NO:494 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1149] SEQ ID NO:531V H Sequence and V of SEQ ID NO:532 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1150] SEQ ID NO:569V H Sequence and V of SEQ ID NO:570 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1151] SEQ ID NO:607V H Sequence and V of SEQ ID NO:608 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1152] SEQ ID NO:645V H Sequence and V of SEQ ID NO:646 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1153] SEQ ID NO:683V H Sequence and V of SEQ ID NO:684 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1154] SEQ ID NO:721V H Sequence and V of SEQ ID NO:722 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1155] An isolated antibody of any of claims 1120 to 1122 of the present invention, comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:779, a VH-CDR2 having the sequence set forth in SEQ ID NO:780, a VH-CDR3 having the sequence set forth in SEQ ID NO:781, a VL-CDR1 having the sequence set forth in SEQ ID NO:782, a VL-CDR2 having the sequence set forth in SEQ ID NO:783, and a VL-CDR3 having the sequence set forth in SEQ ID NO:784. [Invention 1156] An isolated antibody of any of claims 1120 to 1122 of the present invention, comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:872, a VH-CDR2 having the sequence set forth in SEQ ID NO:873, a VH-CDR3 having the sequence set forth in SEQ ID NO:874, a VL-CDR1 having the sequence set forth in SEQ ID NO:875, a VL-CDR2 having the sequence set forth in SEQ ID NO:876, and a VL-CDR3 having the sequence set forth in SEQ ID NO:877. [This invention 1157] An isolated antibody of any of claims 1120 to 1122 of the present invention, comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:878, a VH-CDR2 having the sequence set forth in SEQ ID NO:879, a VH-CDR3 having the sequence set forth in SEQ ID NO:880, a VL-CDR1 having the sequence set forth in SEQ ID NO:881, a VL-CDR2 having the sequence set forth in SEQ ID NO:882, and a VL-CDR3 having the sequence set forth in SEQ ID NO:883. [This invention 1158] An isolated antibody of any of claims 1120 to 1122 of the present invention, comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:797, a VH-CDR2 having the sequence set forth in SEQ ID NO:798, a VH-CDR3 having the sequence set forth in SEQ ID NO:799, a VL-CDR1 having the sequence set forth in SEQ ID NO:800, a VL-CDR2 having the sequence set forth in SEQ ID NO:801, and a VL-CDR3 having the sequence set forth in SEQ ID NO:802. [This invention 1159] SEQ ID NO:763V H Sequence and V of SEQ ID NO:764 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [The present invention 1160] SEQ ID NO:868V H Sequence and V of SEQ ID NO:869 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1161] SEQ ID NO:870V H Sequence and V of SEQ ID NO:871 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1162] SEQ ID NO:769V H Sequence and V of SEQ ID NO:770 L An isolated antibody according to any one of claims 1120 to 1122, comprising the sequence: [This invention 1163] An isolated antibody of any of the present inventions 1120 to 1162, including an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [Invention 1164] Any of the isolated antibodies of the present invention 1163, including the antibody designated as 25A, the antibody designated as 25A3, the antibody designated as 25A5, the antibody designated as 25A5-T, the antibody designated as 25G, the antibody designated as 25G1, or the antibody designated as 25G9. [This invention 1165] Any of the isolated antibodies of the present invention 1163, including the antibody designated as 43B, the antibody designated as 43B1, the antibody designated as 43B7, the antibody designated as 43D, the antibody designated as 43D7, the antibody designated as 43D8, the antibody designated as 43E, or the antibody designated as 43Ea. [Invention 1166] An isolated antibody of any of the present inventions 1120 to 1163, consisting of an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, an antibody designated as 25G9, an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [This invention 1167] Any of the isolated antibodies of the present invention 1166, consisting of an antibody designated as 25A, an antibody designated as 25A3, an antibody designated as 25A5, an antibody designated as 25A5-T, an antibody designated as 25G, an antibody designated as 25G1, or an antibody designated as 25G9. [Invention 1168] Any of the isolated antibodies of the present invention 1166, consisting of an antibody designated as 43B, an antibody designated as 43B1, an antibody designated as 43B7, an antibody designated as 43D, an antibody designated as 43D7, an antibody designated as 43D8, an antibody designated as 43E, or an antibody designated as 43Ea. [This invention 1169] An isolated antibody that competes with an antibody designated 1F, an antibody designated 1G, an antibody designated 29D, an antibody designated 29E, an antibody designated 39A, or an antibody designated 54E for binding to human TF. [This invention 1170] The isolated antibody of the invention 1169, which is human, humanized, or chimeric. [This invention 1171] The isolated antibody of the invention 1169 or 1170, which inhibits FVIIa-dependent TF signaling. [This invention 1172] An isolated antibody according to any one of claims 1169 to 1171 of the present invention, which binds to cynomolgus monkey TF. [This invention 1173] The isolated antibody of any of claims 1169 to 1172, wherein the binding between said isolated antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between said isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of said isolated antibody compared to an isotype control in a live cell staining assay. [This invention 1174] The isolated antibody of any of claims 1169 to 1172, wherein the binding between said isolated antibody and the extracellular domain of human TF in which amino acid residues 78 to 93 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77 to 98 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between said isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of said isolated antibody compared to an isotype control in a live cell staining assay. [This invention 1175] 1169 to 1172. The isolated antibody of any of claims 1169 to 1172, wherein the binding between said isolated antibody and the extracellular domain of human TF in which amino acid residues 78 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between said isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of said isolated antibody compared to an isotype control in a live cell staining assay. [Invention 1176] 1169 to 1172. The isolated antibody of any of claims 1169 to 1172, wherein the binding between said isolated antibody and the extracellular domain of human TF in which amino acid residues 78 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77 to 85 and 92 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between said isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of said isolated antibody compared to an isotype control in a live cell staining assay. [This invention 1177] as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; and the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 78-93 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77-98 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; An isolated antibody according to any one of claims 1169 to 1172 of the present invention. [This invention 1178] as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay. the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 94 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 99 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 78 to 107 of the sequence set forth in SEQ ID NO:810 are replaced with amino acid residues 77 to 112 of the extracellular domain of rat TF of the sequence set forth in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence set forth in SEQ ID NO:810; and the binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 78 to 107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77 to 85 and 92 to 112 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810; An isolated antibody according to any one of claims 1169 to 1172 of the present invention. [This invention 1179] An isolated antibody of any of claims 1169 to 1178, comprising all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 1F, an antibody designated as 1G, an antibody designated as 29D, an antibody designated as 29E, an antibody designated as 39A, an antibody designated as 43Ea, or an antibody designated as 54E. [This invention 1180] 1179. An isolated antibody of the invention, wherein said three heavy chain CDRs and said three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering. [This invention 1181] An isolated antibody of the invention 1179 or 1180 comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 1F. [This invention 1182] An isolated antibody of the invention 1179 or 1180 comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 1G. [This invention 1183] An isolated antibody of the invention 1179 or 1180 comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 29D. [This invention 1184] An isolated antibody of the invention 1179 or 1180 comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 29E. [This invention 1185] An isolated antibody of the invention 1179 or 1180 comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 39A. [Invention 1186] An isolated antibody of the invention 1179 or 1180 comprising all three heavy chain CDRs and all three light chain CDRs from the antibody designated 54E. [This invention 1187] SEQ ID NO: 37V H Sequence and V of SEQ ID NO: 38 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [This invention 1188] SEQ ID NO: 75V H Sequence and V of SEQ ID NO:76 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [This invention 1189] SEQ ID NO: 341V H Sequence and V of SEQ ID NO: 342 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [This invention 1190] SEQ ID NO:379V HSequence and V of SEQ ID NO: 380 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [This invention 1191] SEQ ID NO: 417V H Sequence and V of SEQ ID NO:418 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [This invention 1192] SEQ ID NO:759V H Sequence and V of SEQ ID NO:760 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [This invention 1193] An isolated antibody according to any one of claims 1169 to 1180 of the present invention, comprising a VH-CDR1 comprising the sequence set forth in SEQ ID NO:773, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:774, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:775, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:776, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:777, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:778. [This invention 1194] An isolated antibody of any of claims 1169 to 1180 of the present invention, comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:785, a VH-CDR2 having the sequence set forth in SEQ ID NO:786, a VH-CDR3 having the sequence set forth in SEQ ID NO:787, a VL-CDR1 having the sequence set forth in SEQ ID NO:788, a VL-CDR2 having the sequence set forth in SEQ ID NO:789, and a VL-CDR3 having the sequence set forth in SEQ ID NO:790. [This invention 1195] An isolated antibody of any of claims 1169 to 1180 of the present invention, comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:791, a VH-CDR2 having the sequence set forth in SEQ ID NO:792, a VH-CDR3 having the sequence set forth in SEQ ID NO:793, a VL-CDR1 having the sequence set forth in SEQ ID NO:794, a VL-CDR2 having the sequence set forth in SEQ ID NO:795, and a VL-CDR3 having the sequence set forth in SEQ ID NO:796. [This invention 1196] An isolated antibody of any of claims 1169 to 1180 of the present invention, comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:803, a VH-CDR2 having the sequence set forth in SEQ ID NO:804, a VH-CDR3 having the sequence set forth in SEQ ID NO:805, a VL-CDR1 having the sequence set forth in SEQ ID NO:806, a VL-CDR2 having the sequence set forth in SEQ ID NO:807, and a VL-CDR3 having the sequence set forth in SEQ ID NO:808. [This invention 1197] SEQ ID NO:761V H Sequence and V of SEQ ID NO:762 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [This invention 1198] SEQ ID NO:765V H Sequence and V of SEQ ID NO:766 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [This invention 1199] SEQ ID NO:767V H Sequence and V of SEQ ID NO:768 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [The present invention 1200] SEQ ID NO:771V H Sequence and V of SEQ ID NO:772 L An isolated antibody according to any one of claims 1169 to 1180, comprising the sequence: [The present invention 1201] An isolated antibody of any of claims 1169 to 1200, including an antibody designated as 1F, an antibody designated as 1G, an antibody designated as 29D, an antibody designated as 29E, an antibody designated as 39A, or an antibody designated as 54E. [This invention 1202] An isolated antibody of any of the present inventions 1169 to 1201, consisting of an antibody designated as 1F, an antibody designated as 1G, an antibody designated as 29D, an antibody designated as 29E, an antibody designated as 39A, or an antibody designated as 54E. [This invention 1203] An isolated antibody comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:773, a VH-CDR2 having the sequence set forth in SEQ ID NO:774, a VH-CDR3 having the sequence set forth in SEQ ID NO:775, a VL-CDR1 having the sequence set forth in SEQ ID NO:776, a VL-CDR2 having the sequence set forth in SEQ ID NO:777, and a VL-CDR3 having the sequence set forth in SEQ ID NO:778. [The present invention 1204] An isolated antibody comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:779, a VH-CDR2 having the sequence set forth in SEQ ID NO:780, a VH-CDR3 having the sequence set forth in SEQ ID NO:781, a VL-CDR1 having the sequence set forth in SEQ ID NO:782, a VL-CDR2 having the sequence set forth in SEQ ID NO:783, and a VL-CDR3 having the sequence set forth in SEQ ID NO:784. [This invention 1205] An isolated antibody comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:785, a VH-CDR2 having the sequence set forth in SEQ ID NO:786, a VH-CDR3 having the sequence set forth in SEQ ID NO:787, a VL-CDR1 having the sequence set forth in SEQ ID NO:788, a VL-CDR2 having the sequence set forth in SEQ ID NO:789, and a VL-CDR3 having the sequence set forth in SEQ ID NO:790. [This invention 1206] An isolated antibody comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:791, a VH-CDR2 having the sequence set forth in SEQ ID NO:792, a VH-CDR3 having the sequence set forth in SEQ ID NO:793, a VL-CDR1 having the sequence set forth in SEQ ID NO:794, a VL-CDR2 having the sequence set forth in SEQ ID NO:795, and a VL-CDR3 having the sequence set forth in SEQ ID NO:796. [This invention 1207] An isolated antibody comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:797, a VH-CDR2 having the sequence set forth in SEQ ID NO:798, a VH-CDR3 having the sequence set forth in SEQ ID NO:799, a VL-CDR1 having the sequence set forth in SEQ ID NO:800, a VL-CDR2 having the sequence set forth in SEQ ID NO:801, and a VL-CDR3 having the sequence set forth in SEQ ID NO:802. [This invention 1208] An isolated antibody comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:803, a VH-CDR2 having the sequence set forth in SEQ ID NO:804, a VH-CDR3 having the sequence set forth in SEQ ID NO:805, a VL-CDR1 having the sequence set forth in SEQ ID NO:806, a VL-CDR2 having the sequence set forth in SEQ ID NO:807, and a VL-CDR3 having the sequence set forth in SEQ ID NO:808. [This invention 1209] An isolated antibody comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:872, a VH-CDR2 having the sequence set forth in SEQ ID NO:873, a VH-CDR3 having the sequence set forth in SEQ ID NO:874, a VL-CDR1 having the sequence set forth in SEQ ID NO:875, a VL-CDR2 having the sequence set forth in SEQ ID NO:876, and a VL-CDR3 having the sequence set forth in SEQ ID NO:877. [The present invention 1210] An isolated antibody comprising a VH-CDR1 having the sequence set forth in SEQ ID NO:878, a VH-CDR2 having the sequence set forth in SEQ ID NO:879, a VH-CDR3 having the sequence set forth in SEQ ID NO:880, a VL-CDR1 having the sequence set forth in SEQ ID NO:881, a VL-CDR2 having the sequence set forth in SEQ ID NO:882, and a VL-CDR3 having the sequence set forth in SEQ ID NO:883. [The present invention 1211] K of 50 nM or less, 10 nM or less, 5 nM or less, 1 nM or less, 0.5 nM or less, or 0.1 nM or less as measured by Octet QK384 or Biacore assay D 2. Any of the preceding isolated antibodies of the present invention that bind to human TF at [The present invention 1212] Any isolated antibody of the preceding invention that is a monoclonal antibody. [This invention 1213] Any of the isolated antibodies of the preceding invention that are multispecific. [This invention 1214] Any of the isolated antibodies of the preceding invention, which is a Fab, Fab', F(ab')2, Fv, scFv, (scFv)2, single-chain antibody molecule, dual variable domain antibody, single variable domain antibody, linear antibody, or V domain antibody. [This invention 1215] The isolated antibody of any of the preceding inventions, wherein said antibody comprises a scaffold, and optionally said scaffold is an Fc, optionally a human Fc. [This invention 1216] 1215. An isolated antibody of the present invention comprising a heavy chain constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. [This invention 1217] 1216. An isolated antibody of the present invention, comprising a heavy chain constant region of the IgG class and a subclass selected from IgG1, IgG2, IgG3, and IgG4. [This invention 1218] 1217. An isolated antibody of the present invention, comprising a heavy chain constant region of IgG1. [This invention 1219] The isolated antibody of any of claims 1215 to 1218, wherein the Fc comprises one or more modifications, which result in increased half-life, increased antibody-dependent cellular cytotoxicity (ADCC), increased antibody-dependent cellular phagocytosis (ADCP), increased complement-dependent cytotoxicity (CDC), or decreased effector function compared to the Fc not comprising said one or more modifications. [The present invention 1220] An isolated antibody that competes with any of the preceding antibodies of the invention for binding to human TF. [This invention 1221] An isolated antibody that binds to the epitope of human TF to which any of the preceding antibodies of the present invention binds. [The present invention 1222] Any of the preceding antibodies of the invention, H , that V L , its light chain, its heavy chain, or an antigen-binding portion thereof. [This invention 1223] A vector or set of vectors comprising a polynucleotide or set of polynucleotides of the present invention 1222. [This invention 1224] A host cell comprising a polynucleotide or set of polynucleotides of the invention 1222 or a vector or set of vectors of the invention 1223. [This invention 1225] A method for producing an antibody, comprising expressing said antibody by a host cell of the invention 1224 and isolating said expressed antibody. [This invention 1226] A pharmaceutical composition comprising any one of the antibodies of the present invention 1000 to 1221 and a pharmaceutically acceptable excipient. [This invention 1227] A method for treating or preventing a disease or pathological condition in a subject in need thereof, the method comprising the step of administering to the subject an effective amount of any one of the antibodies of the present inventions 1000 to 1221 or the pharmaceutical composition of the present invention 1226. [This invention 1228] 1227. The method of claim 1227, wherein said disease or condition is cancer. [This invention 1229] The method of claim 1228, wherein the cancer is head and neck cancer. [This invention 1230] 1228. The method of claim 1228, wherein the cancer is ovarian cancer. [This invention 1231] The method of claim 1228, wherein the cancer is gastric cancer. [This invention 1232] The method of claim 1228, wherein the cancer is esophageal cancer. [This invention 1233] The method of claim 1228, wherein the cancer is cervical cancer. [This invention 1234] The method of claim 1228, wherein the cancer is prostate cancer. [This invention 1235] The method of claim 1228, wherein the cancer is pancreatic cancer. [This invention 1236] The method of claim 1228, wherein the cancer is estrogen receptor negative (ER-), progesterone receptor negative (PR-), and HER2 negative (HER2-) triple-negative breast cancer. [This invention 1237] The method of claim 1228, wherein the cancer is glioblastoma. [This invention 1238] The method of claim 1228, wherein the cancer is lung cancer. [This invention 1239] The method of claim 1228, wherein the cancer is bladder cancer. [This invention 1240] The method of claim 1228, wherein the cancer is melanoma. [This invention 1241] The method of claim 1228, wherein the cancer is renal cancer. [This invention 1242] 1227. The method of claim 1227, wherein the disease or condition involves angiogenesis. [This invention 1243] 1242. The method of claim 1242, wherein said disease or condition involving angiogenesis is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. [This invention 1244] 1227. The method of claim 1227, wherein said disease or condition involves vascular inflammation. [Invention 1245] The method of any of claims 1227 to 1244, further comprising the step of administering to said subject one or more additional therapeutic agents. [Invention 1246] The method of claim 1245, wherein said additional therapeutic agent is formulated in the same pharmaceutical composition as said antibody. [Invention 1247] The method of claim 1245, wherein said additional therapeutic agent is formulated in a different pharmaceutical composition than said antibody. [Invention 1248] 1245. The method of claim 1245, wherein said additional therapeutic agent is administered prior to administering said antibody. [Invention 1249] The method of claim 1245, wherein said additional therapeutic agent is administered after administering said antibody. [This invention 1250] The method of claim 1245, wherein said additional therapeutic agent is administered simultaneously with said antibody. [This invention 1251] A method for detecting TF in a subject having or suspected of having a disease or pathological condition, the method comprising: (a) receiving a sample from the subject; and (b) detecting the presence or level of TF in the sample by contacting the sample with any one of the antibodies 1000 to 1221 of the present invention. [This invention 1252] 1251. The method of claim 1251, wherein said disease or condition is cancer. [This invention 1253] 1252. The method of claim 1252, wherein the cancer is head and neck cancer. [Invention 1254] 1252. The method of claim 1252, wherein the cancer is ovarian cancer. [Invention 1255] 1252. The method of claim 1252, wherein the cancer is gastric cancer. [Invention 1256] 1252. The method of claim 1252, wherein the cancer is esophageal cancer. [Invention 1257] The method of claim 1252, wherein the cancer is cervical cancer. [Invention 1258] 1252. The method of claim 1252, wherein the cancer is prostate cancer. [Invention 1259] 1252. The method of claim 1252, wherein the cancer is pancreatic cancer. [This invention 1260] The method of claim 1252, wherein the cancer is estrogen receptor negative (ER-), progesterone receptor negative (PR-), and HER2 negative (HER2-) triple-negative breast cancer. [This invention 1261] 1252. The method of claim 1252, wherein the cancer is glioblastoma. [This invention 1262] 1252. The method of claim 1252, wherein the cancer is lung cancer. [This invention 1263] 1252. The method of claim 1252, wherein the cancer is bladder cancer. [Invention 1264] 1252. The method of claim 1252, wherein the cancer is melanoma. [Invention 1265] 1252. The method of claim 1252, wherein the cancer is renal cancer. [Invention 1266] 1251. The method of claim 1251, wherein said disease or condition involves angiogenesis. [Invention 1267] 1266. The method of claim 1266, wherein said disease or condition involving angiogenesis is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. [Invention 1268] 1251. The method of claim 1251, wherein said disease or condition involves vascular inflammation. [Invention 1269] A method for detecting TF in a subject having or suspected of having a disease or pathological condition, the method comprising the steps of: (a) administering to the subject any one of antibodies 1000 to 1221 of the present invention; and (b) detecting the presence or level of TF in the subject. [Invention 1270] 1269. The method of claim 1269, wherein said disease or condition is cancer. [This invention 1271] 1270. The method of claim 1270, wherein said cancer is head and neck cancer. [Invention 1272] 1270. The method of claim 1270, wherein said cancer is ovarian cancer. [This invention 1273] 1270. The method of claim 1270, wherein said cancer is gastric cancer. [Invention 1274] 1270. The method of claim 1270, wherein said cancer is esophageal cancer. [Invention 1275] 1270. The method of claim 1270, wherein said cancer is cervical cancer. [Invention 1276] 1270. The method of claim 1270, wherein said cancer is prostate cancer. [Invention 1277] 1270. The method of claim 1270, wherein said cancer is pancreatic cancer. [Invention 1278] 1270. The method of claim 1270, wherein the cancer is estrogen receptor negative (ER-), progesterone receptor negative (PR-), and HER2 negative (HER2-) triple-negative breast cancer. [Invention 1279] 1270. The method of claim 1270, wherein the cancer is glioblastoma. [This invention 1280] 1270. The method of claim 1270, wherein said cancer is lung cancer. [This invention 1281] 1270. The method of claim 1270, wherein said cancer is bladder cancer. [This invention 1282] 1270. The method of claim 1270, wherein said cancer is melanoma. [This invention 1283] 1270. The method of claim 1270, wherein said cancer is renal cancer. [Invention 1284] 1269. The method of claim 1269, wherein the disease or condition involves angiogenesis. [Invention 1285] 1284. The method of claim 1284, wherein said disease or condition involving angiogenesis is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. [Invention 1286] 1269. The method of claim 1269, wherein said disease or condition involves vascular inflammation. [Invention 1287] A kit comprising the antibody of any one of the present inventions 1000 to 1221 or the pharmaceutical composition of the present invention 1226, and instructions for use. [Invention 1288] An antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent linked to the antibody, and optionally a linker linking the antibody to the cytotoxic agent, wherein the antibody binds to the extracellular domain of human tissue factor (TF) at a human TF binding site that is distinct from the human TF binding site to which human FVIIa binds. [This invention 1289] (1) the antibody has a V of SEQ ID NO:821 as determined by a thrombin generation assay (TGA); H Sequence and V of SEQ ID NO:822 L does not inhibit human thrombin generation compared to a reference antibody containing the sequence, and (2) the binding between the antibody and the extracellular domain of a variant TF comprising a mutation at amino acid residue 149 of the sequence set forth in SEQ ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF of the sequence set forth in SEQ ID NO:810, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay; The antibody-drug conjugate of the present invention. [This invention 1290] The antibody drug conjugate of the present invention 1288 or 1289, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO:779, a VH-CDR2 comprising the sequence set forth in SEQ ID NO:780, a VH-CDR3 comprising the sequence set forth in SEQ ID NO:781, a VL-CDR1 comprising the sequence set forth in SEQ ID NO:782, a VL-CDR2 comprising the sequence set forth in SEQ ID NO:783, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO:784. [This invention 1291] The antibody-drug conjugate of any of claims 1288 to 1290, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 872, a VH-CDR2 H1 comprising the sequence set forth in SEQ ID NO: 873, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 874, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 875, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 876, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 877. [This invention 1292] The antibody-drug conjugate of any of claims 1288 to 1290, wherein the antibody comprises a VH-CDR1 comprising the sequence set forth in SEQ ID NO: 878, a VH-CDR2 comprising the sequence set forth in SEQ ID NO: 879, a VH-CDR3 comprising the sequence set forth in SEQ ID NO: 880, a VL-CDR1 comprising the sequence set forth in SEQ ID NO: 881, a VL-CDR2 comprising the sequence set forth in SEQ ID NO: 882, and a VL-CDR3 comprising the sequence set forth in SEQ ID NO: 883. [This invention 1293] The antibody has a V of SEQ ID NO:821 as determined by thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L An antibody drug conjugate of the present invention 1288 that does not inhibit human thrombin generation compared to a reference antibody comprising the sequence. [Invention 1294] The antibody drug conjugate of the present invention 1288, wherein said antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA). [This invention 1295] The antibody drug conjugate of the present invention 1294, wherein said antibody does not reduce the thrombin peak (peak IIa) on a thrombin generation curve compared to an isotype control. [Invention 1296] The antibody drug conjugate of claim 1294 or 1295, wherein said antibody does not increase the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control. [Invention 1297] The antibody-drug conjugate of any of claims 1294 to 1296, wherein the antibody does not reduce endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve. [Invention 1298] The antibody-drug conjugate of any of claims 1288 to 1297, wherein the antibody allows human thrombin generation as determined by a thrombin generation assay (TGA). [This invention 1299] The antibody drug conjugate of the present invention 1298, wherein the antibody maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. [The present invention 1300] The antibody drug conjugate of the present invention 1298 or 1299, wherein said antibody maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to an isotype control. [This invention 1301] 13. The antibody drug conjugate of any of claims 1298 to 1300, wherein said antibody protects endogenous thrombin potential (ETP) compared to an isotype control as determined by area under the thrombin generation curve. [This invention 1302] The antibody-drug conjugate of any one of 1288 to 1301 of the present invention, wherein the antibody binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds. [This invention 1303] The antibody-drug conjugate of any of claims 1288 to 1302, wherein the antibody does not interfere with the ability of TF:FVIIa to convert FX to FXa. [The present invention 1304] The antibody-drug conjugate of any of claims 1288 to 1303, wherein the antibody does not compete with human FVIIa for binding to human TF. [This invention 1305] An antibody-drug conjugate of any of the present inventions 1288 to 1304, wherein the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), allows human thrombin generation as determined by a thrombin generation assay (TGA), binds to human TF at a human TF binding site that is distinct from the human TF binding site to which human FX binds, does not interfere with the ability of TF:FVIIa to convert FX to FXa, and does not compete with FVIIa for binding to human TF. [Invention 1306] The antibody-drug conjugate of any of the present inventions 1288 to 1305, wherein the antibody does not inhibit human thrombin generation as determined by a thrombin generation assay (TGA), does not reduce endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control, permits human thrombin generation as determined by a thrombin generation assay (TGA), protects endogenous thrombin potential (ETP) as determined by area under the thrombin generation curve compared to an isotype control, binds to human TF at a human TF binding site that is distinct from the human...

Claims

1. An antibody that binds to the extracellular domain of human tissue factor (TF), The antibody VH-CDR1, VH-CDR2, and VH-CDR3 each containing the amino acid sequence of VH-CDR1, the amino acid sequence of VH-CDR2, and the amino acid sequence of VH-CDR3 shown in VH comprising the amino acid sequence of SEQ ID NO: 151; VL-CDR1, VL-CDR2, and VL-CDR3, each comprising the amino acid sequence of VL-CDR1, the amino acid sequence of VL-CDR2, and the amino acid sequence of VL-CDR3 set forth in SEQ ID NO: 152, respectively; Including, the VH-CDR1, the VH-CDR2, the VH-CDR3, the VL-CDR1, the VL-CDR2, and the VL-CDR3 are determined by the Kabat numbering scheme, the Chothia numbering scheme, the AbM numbering scheme, the Contact numbering scheme, or the IMGT numbering scheme; The antibody.

2. An antibody that binds to the extracellular domain of human TF, comprising VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3, (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 115, VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 116, VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 117, VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 118, VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 119, and VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 120; (ii) VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 121, VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 122, VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 123, VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 124, VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 125, and VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 126; (iii) VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 127, VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 128, VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 129, VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 130, VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 131, and VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 132; (iv) VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 133, VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 134, VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 135, VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 136, VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 137, and VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 138; (v) VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 139, VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 140, VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 141, VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 142, VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 143, and VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 144; or (vi) VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 145, VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 146, VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 147, VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 148, VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 149, and VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 150; The antibody.

3. The antibody of claim 1, comprising the VH sequence of SEQ ID NO: 151 and the VL sequence of SEQ ID NO:

152.

4. The antibody according to any one of claims 1 to 3, which is a monoclonal antibody.

5. The antibody of any one of claims 1 to 4, which is a Fab, Fab', F(ab')2, Fv, scFv, (scFv)2, single-chain antibody molecule, dual variable domain antibody, or linear antibody.

6. The antibody of any one of claims 1 to 4, comprising an Fc region.

7. The antibody of any one of claims 1 to 4, comprising a heavy chain constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.

8. The antibody of any one of claims 1 to 4, comprising a heavy chain constant region of the IgG class and a subclass selected from IgG1, IgG2, IgG3, and IgG4.

9. An isolated polynucleotide or set of polynucleotides encoding the antibody or antigen-binding portion thereof of any one of claims 1 to 8.

10. A vector or set of vectors comprising the polynucleotide or set of polynucleotides of claim 9.

11. A host cell comprising the polynucleotide or set of polynucleotides of claim 9.

12. 12. A method for producing an antibody, comprising expressing the antibody by the host cell of claim 11 and isolating the expressed antibody.

13. A pharmaceutical composition comprising the antibody of any one of claims 1 to 8 and a pharmaceutically acceptable excipient.

14. (i) an antibody according to any one of claims 1 to 8; (ii) Instructions for use; Includes a kit.

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