Anti-tissue factor antibodies, antibody-drug conjugates, and related methods

Abstract

The present invention provides an antibody that specifically binds to human tissue factor (TF), an anti-TF antibody drug conjugate (ADC), and a composition comprising the antibody or ADC. [Solution] An isolated human antibody is provided that binds to the extracellular domain of human tissue factor (TF), wherein the isolated human antibody binds to human TF at a human TF binding site separate from the human TF binding site to which human FVIIa binds.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims the interests of U.S. Provisional Applications No. 62 / 613,545, No. 62 / 613,564, No. 62 / 646,788, No. 62 / 646,788, No. 62 / 713,797, and No. 62 / 713,804, filed on 4 January 2018, each of which is incorporated herein by reference in whole.

[0002] Sequence List This application includes a sequence listing submitted via EFS-Web, which is incorporated herein by reference in its entirety. A copy of the ASCII file, 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 series of complex processes that result in clotting. Tissue factor (TF) plays a crucial role in these coagulation processes. TF is the cell surface receptor for serine protease factor VIIa (FVIIa). The TF / FVIIa complex catalyzes the conversion of inactive protease factor X (FX) to active protease factor Xa (FXa). FXa and its cofactor FVa form the prothrombinase complex, which generates thrombin from prothrombin. Thrombin converts soluble fibrinogen into insoluble fibrin chains and also catalyzes many other coagulation-related processes.

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

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

[0006] In one embodiment, the Specified herein provides an isolated human antibody that binds to the extracellular domain of human tissue factor (TF) at a human TF binding site separate from the human TF binding site to which human FVIIa binds.

[0007] In some embodiments, (1) the isolated antibody is determined by a thrombin production assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it does not inhibit human thrombin production, and (2) 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 variant TF containing 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.

[0008] In some embodiments, (1) the isolated antibody is determined by a thrombin production assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 LCompared to a reference antibody containing the sequence, it inhibits human thrombin production to a lower degree, and (2) as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, the binding of the isolated antibody to the extracellular domain of variant TF containing a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding of the isolated antibody to the extracellular domain of TF of the sequence shown in SEQ ID NO:810.

[0009] In some embodiments, (1) the isolated antibody is determined by a thrombin production assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it tolerates human thrombin generation to a greater extent, and (2) as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, the binding of the isolated antibody to the extracellular domain of variant TF containing a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding of the isolated antibody to the extracellular domain of TF of the sequence shown in SEQ ID NO:810.

[0010] In some embodiments, (1) the isolated antibody is determined by a thrombin production assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it inhibits human thrombin production by a smaller amount, and (2) as determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, the binding of the isolated antibody to the extracellular domain of variant TF containing a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding of the isolated antibody to the extracellular domain of TF of the sequence shown in SEQ ID NO:810.

[0011] In some embodiments, (1) the isolated antibody permits more human thrombin generation as determined by a thrombin generation assay (TGA) compared to a reference antibody comprising the V H sequence of SEQ ID NO:821 and the V L sequence of SEQ ID NO:822, and (2) when 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 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.

[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 includes VH-CDR1 containing the sequence described in SEQ ID NO:878, VH-CDR2 containing the sequence described in SEQ ID NO:879, VH-CDR3 containing the sequence described in SEQ ID NO:880, VL-CDR1 containing the sequence described in SEQ ID NO:881, VL-CDR2 containing the sequence described in SEQ ID NO:882, and VL-CDR3 containing the sequence described in SEQ ID NO:883.

[0015] In some embodiments, the isolated antibody is determined by a thrombin production assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 L Compared to reference antibodies containing the sequence, it does not inhibit human thrombin production.

[0016] In some embodiments, the isolated antibody is determined by a thrombin production assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 L Compared to reference antibodies containing the sequence, it inhibits human thrombin production to a lower degree.

[0017] In some embodiments, the isolated antibody is determined by a thrombin production assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it tolerates human thrombin generation to a greater degree.

[0018] In some embodiments, the isolated antibody is determined by a thrombin production assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it inhibits human thrombin production by a smaller amount.

[0019] In some embodiments, when determined by a thrombin generation assay (TGA), the isolated antibody permits human thrombin generation in a greater amount than a reference antibody comprising the V H sequence of SEQ ID NO:821 and the V L sequence of SEQ ID NO:822.

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

[0021] In some embodiments, the antibody binds to human TF at a human TF binding site distinct from the human TF binding site to which human FX binds. In 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, when determined by a thrombin generation assay (TGA), the antibody does not inhibit human thrombin generation, allows human thrombin generation when determined by a thrombin generation assay (TGA), binds to human TF at a human TF binding site 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, when determined by a thrombin generation assay (TGA), the antibody does not inhibit human thrombin generation, does not decrease the endogenous thrombin potential (ETP) compared to an isotype control when determined by the area under the thrombin generation curve, allows human thrombin generation when determined by a thrombin generation assay (TGA), protects the endogenous thrombin potential (ETP) compared to an isotype control when determined by the area under the thrombin generation curve, binds to human TF at a human TF binding site 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 production as determined by thrombin production assay (TGA), does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, does not increase the time from the start of the assay to the thrombin peak on the thrombin production curve (tt peak) compared to isotype controls, does not decrease endogenous thrombin production capacity (ETP) as determined by the area under the thrombin production curve compared to isotype controls, and, as determined by thrombin production assay (TGA), does not inhibit human thrombin production. It allows for the maintenance of the thrombin peak (peak IIa) on the thrombin generation curve compared to isotype controls, maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to isotype controls, protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by the area under the thrombin generation curve, binds to human TF at a human TF binding site 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.

[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 containing 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 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 149 of the sequence shown 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 containing 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 variant TF containing 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 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 of the isolated antibody to 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 of the extracellular domain of a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the isolated antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0031] In some embodiments, the binding of the isolated antibody to the extracellular domain of a human TF in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the isolated antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0032] In some embodiments, the binding of the isolated antibody to the extracellular domain of a 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 a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the isolated antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

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

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

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

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

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

[0038] In some embodiments, the binding of the isolated antibody to the extracellular domain of a rat TF in which amino acid residues 141-194 of the sequence shown in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of a human TF in the sequence shown in SEQ ID NO:810 is greater than 50% of the binding of the isolated antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0039] In some embodiments, when 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 containing 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 the TF of the sequence shown in SEQ ID NO:810, the binding between the isolated antibody and the extracellular domain of a variant TF containing 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, and 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 is less than 50% of 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. The binding between the isolated antibody and the extracellular domain of human TF, in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the rat TF extracellular domain shown in SEQ ID NO:838, is more than 50% of the binding between the isolated antibody and the extracellular domain of 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 rat TF extracellular domain shown in SEQ ID NO:838, is more than 50% of the binding between the isolated antibody and the extracellular domain of 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 rat TF extracellular domain shown in SEQ ID NO:838, is more than 50% of the binding between the isolated antibody and the extracellular domain of TF, in which The binding between the isolated antibody and the extracellular domain of human TF, in which amino acid residues 146-158 of the sequence shown in NO:810 are replaced with amino acid residues 151-163 of the extracellular domain of rat TF shown in SEQ ID NO:838, is as follows:The binding between the isolated antibody and the extracellular domain of the TF of the sequence shown in NO:810 is less than 50%, and 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 with amino acid residues 136-189 of the extracellular domain of human TF 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 the TF of the sequence shown in SEQ ID NO:810. In some embodiments, the mutation at amino acid residue 149 of the sequence shown 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.

[0040] In some embodiments, when 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 containing 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 the TF of the sequence shown in SEQ ID NO: 810, the binding between the isolated antibody and the extracellular domain of a variant TF containing 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, the binding between the isolated antibody and the extracellular domain of a variant TF containing 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, and the binding between the isolated antibody and the extracellular domain of a variant TF containing mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID 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 NO:810 are replaced with amino acid residues 1-76 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838, is more than 50% of the binding between the isolated antibody and the extracellular domain of TF in 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 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838, is more than 50% of the binding between the isolated antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and the binding between the isolated antibody and amino acid residues 94-107 of the sequence shown in SEQ ID The binding between the isolated antibody and the extracellular domain of human TF, where amino acid residues 99-112 in the extracellular domain of rat TF of the sequence shown in NO:838 have been replaced, 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 human TF, in which amino acid residues 146-158 of the sequence shown in NO:810 are replaced with amino acid residues 151-163 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 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 159-219 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-224 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 the sequence shown in SEQ ID NO:810, and the binding between the isolated antibody and amino acid residues 159-189 of the sequence shown in SEQ ID The binding between the isolated antibody and the extracellular domain of human TF, in which amino acid residues 164-194 in the extracellular domain of rat TF of the sequence shown in NO:838 are replaced, 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 human TF, in which amino acid residues 159-174 in the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-179 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, and the binding between the isolated antibody and amino acid residues 167-174 in the sequence shown in SEQ ID The binding between the isolated antibody and the extracellular domain of human TF, in which amino acid residues 172-179 in the extracellular domain of rat TF of the sequence shown in NO:838 have been replaced, 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 amino acid residues 141-194 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 of the sequence shown in SEQ ID NO:810.The binding between the extracellular domain of rat TF, which has been substituted with amino acid residues 136-189 in the extracellular domain of human TF in the sequence shown NO:810, is more than 50% of the binding between the isolated antibody and the extracellular domain of TF in the sequence shown SEQ ID NO:810. In some embodiments, the mutation at amino acid residue 149 of the sequence shown SEQ ID NO:810 is K149N, the mutation at amino acid residue 68 of the sequence shown SEQ ID NO:810 is K68N, and the mutations at amino acid residues 171 and 197 of the sequence shown 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 pig TF.

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

[0043] In some embodiments, the antibody (a) does not inhibit human thrombinogenesis as determined by a thrombinogenesis assay (TGA), and (b) 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 a variant TF containing 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. 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.

[0044] In some embodiments, the antibody permits human thrombin generation when determined by a thrombin generation assay (TGA) and, when 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 a variant TF containing 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. 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.

[0045] In some embodiments, the antibody does not inhibit human thrombin generation when determined by a thrombin generation assay (TGA), and when 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 a variant TF containing 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 the TF of the sequence shown in SEQ ID NO: 810, and when 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 a variant TF containing 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. In some embodiments, the mutation at amino acid residue 149 of the sequence shown 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.

[0046] In some embodiments, the antibody (a) allows 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 containing 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 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, and (c) the binding between the antibody and the extracellular domain of a variant TF containing 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 mutation at amino acid residue 149 of the sequence shown 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.

[0047] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by a thrombin production assay (TGA), (b) binds to cynomolgus monkey TF, (c) the binding between the antibody and the extracellular domain of a variant TF containing 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 the TF in 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 containing 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 in 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 shown 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.

[0048] In some embodiments, the antibody (a) allows 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 containing 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 the TF in 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 containing 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 in 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 shown 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.

[0049] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by a thrombin production assay (TGA), (b) allows human thrombin production as determined by a thrombin production assay (TGA), (c) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (d) does not interfere with TF:FVIIa's ability 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 production as determined by thrombin production assay (TGA), (b) does not reduce endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombin production curve, (c) allows human thrombin production as determined by thrombin production assay (TGA), (d) protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombin production curve, (e) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (f) does not interfere with TF:FVIIa's ability 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 production as determined by thrombin production assay (TGA), (b) does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, (c) does not increase the time from the start of the assay to the thrombin peak (tt peak) on the thrombin production curve compared to isotype controls, (d) does not reduce endogenous thrombin production capacity (ETP) as determined by area under the thrombin production curve compared to isotype controls, (e) allows human thrombin production as determined by thrombin production assay (TGA), and (f) does not increase the time from the start of the assay to the thrombin peak on the thrombin production curve compared to isotype controls. (g) maintains the thrombin peak (peak IIa), maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to isotype controls, (h) protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by the area under the thrombin generation curve, (i) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (j) does not interfere with TF:FVIIa's ability 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 thrombinogenesis as determined by a thrombinogenesis assay (TGA), (b) allows human thrombinogenesis as determined by a thrombinogenesis assay (TGA), (c) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (d) does not interfere with TF:FVIIa's ability 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 angiogenesis (CNV) model.

[0053] In some embodiments, the antibody (a) does not inhibit human thrombinogenesis as determined by thrombinogenesis assay (TGA), (b) does not reduce endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombinogenesis curve, (c) allows human thrombinogenesis as determined by thrombinogenesis assay (TGA), (d) protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombinogenesis curve, (e) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (f) does not interfere with TF:FVIIa's ability 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 angiogenesis (CNV) model.

[0054] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by thrombin production assay (TGA), (b) does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, (c) does not increase the time from the start of the assay to the thrombin peak (tt peak) on the thrombin production curve compared to isotype controls, (d) does not reduce endogenous thrombin production capacity (ETP) as determined by the area under the thrombin production curve compared to isotype controls, (e) allows human thrombin production as determined by thrombin production assay (TGA), (f) maintains the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, and (g) Compared to isotype controls, it maintains the time from assay initiation to the thrombin peak on the thrombin generation curve (tt peak), (h) protects endogenous thrombin production capacity (ETP) compared to isotype controls, as determined by the area under the thrombin generation curve, (i) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (j) does not interfere with TF:FVIIa's ability 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 pig TF, and (q) reduces lesion size in a pig choroidal angiogenesis (CNV) model.

[0055] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by thrombin production assay (TGA), (b) does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin production curve (tt peak) compared to isotype controls, (d) does not decrease endogenous thrombin production capacity (ETP) as determined by area under the thrombin production curve compared to isotype controls, (e) allows human thrombin production as determined by thrombin production assay (TGA), (f) maintains the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, and (g) does not increase the time from the start of the assay to the thrombin production curve compared to isotype controls. (h) when determined by the area under the thrombin production curve, the isolated antibody protects endogenous thrombin production capacity (ETP) compared to isotype controls, (i) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (j) does not interfere with TF:FVIIa's ability 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 pig TF, (q) reduces lesion size in a pig choroidal angiogenesis (CNV) model, and (r) when determined by the median fluorescence intensity of the isolated antibody compared to isotype controls in a live cell staining assay, the isolated antibody and SEQ The binding between the isolated antibody and the extracellular domain of variant TF containing a mutation at amino acid residue 149 of the sequence shown in 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, and (s) when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of variant TF containing a mutation at amino acid residue 68 of the sequence shown in SEQ ID(t) The binding between the isolated antibody and the extracellular domain of a variant TF containing mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is greater than 50%, and when 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 a variant TF containing mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50%, and when 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 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 of the rat TF extracellular domain of the sequence shown in SEQ ID NO:838 (v) The binding between the isolated antibody and the extracellular domain of the TF of the sequence shown in NO:810 is greater than 50%, and the binding between the isolated antibody and the extracellular domain of the human TF in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of the 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 the TF of the sequence shown in SEQ ID NO:810, and (w) The binding between the isolated antibody and amino acid residues 94-107 of the sequence shown in SEQ ID The binding between the extracellular domain of human TF, in which amino acid residues 99-112 in the extracellular domain of rat TF of the sequence shown in NO:838 have been replaced, 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 (x) when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the isolated antibody and SEQ ID(y) When the binding between the isolated antibody and the extracellular domain of human TF, in which amino acid residues 146-158 of the sequence shown in NO:810 are replaced with amino acid residues 151-163 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 the sequence shown in SEQ ID NO:810, and (y) when determined by the median fluorescence intensity of the isolated antibody compared to the 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 159-219 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-224 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 the sequence shown in SEQ ID (z) The binding between the isolated antibody and the extracellular domain of the TF of the sequence shown in NO:810 is less than 50%, and when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of the human TF in which amino acid residues 159-189 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-194 of the rat TF extracellular domain of the sequence shown in SEQ ID NO:838 is less than 50%, and (aa) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of the TF of the sequence shown in SEQ ID NO:810 is less than 50%, and (aa) the binding between the isolated antibody and amino acid residues 159-174 of the sequence shown in SEQ ID The binding between the extracellular domain of human TF, in which amino acid residues 164-179 in the extracellular domain of rat TF of the sequence shown in NO:838 have been replaced, 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 (bb) when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the isolated antibody and amino acid residues 167-174 of the sequence shown in SEQ ID NO:810 are SEQ IDWhen the binding between the isolated antibody and the extracellular domain of human TF, in which amino acid residues 172-179 in the extracellular domain of rat TF of the sequence shown in NO:838 are replaced, 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 when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a (cc) live cell staining assay, the binding between the isolated antibody and the extracellular domain of rat TF, in which amino acid residues 141-194 in the sequence shown in SEQ ID NO:838 are replaced with amino acid residues 136-189 in the extracellular domain of human TF 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.

[0056] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by thrombin production assay (TGA), (b) does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin production curve (tt peak) compared to isotype controls, (d) does not decrease endogenous thrombin production capacity (ETP) as determined by area under the thrombin production curve compared to isotype controls, (e) allows human thrombin production as determined by thrombin production assay (TGA), (f) maintains the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, and (g) does not increase the time from the start of the assay to the thrombin production curve compared to isotype controls. (h) when determined by the area under the thrombin production curve, the isolated antibody protects endogenous thrombin production capacity (ETP) compared to isotype controls, (i) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (j) does not interfere with TF:FVIIa's ability 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 pig TF, (q) reduces lesion size in a pig choroidal angiogenesis (CNV) model, and (r) when determined by the median fluorescence intensity of the isolated antibody compared to isotype controls in a live cell staining assay, the isolated antibody and SEQ The binding between the isolated antibody and the extracellular domain of the variant TF containing the K149N mutation in the sequence shown in ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of the TF containing the sequence shown in SEQ ID NO:810, and (s) when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of the variant TF containing the K68N mutation in the sequence shown in SEQ ID(t) The binding between the isolated antibody and the extracellular domain of variant TF containing mutations N171H and T197K of the sequence shown in SEQ ID NO:810 is greater than 50%, and when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of variant TF containing 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 TF of the sequence shown in SEQ ID NO:810, and when determined by the median fluorescence intensity of the isolated antibody compared to the 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 1-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 1-76 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 rat TF (v) The binding between the isolated antibody and the extracellular domain of the TF of the sequence shown in NO:810 is greater than 50%, and the binding between the isolated antibody and the extracellular domain of the human TF in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of the 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 the TF of the sequence shown in SEQ ID NO:810, and (w) The binding between the isolated antibody and amino acid residues 94-107 of the sequence shown in SEQ ID The binding between the extracellular domain of human TF, in which amino acid residues 99-112 in the extracellular domain of rat TF of the sequence shown in NO:838 have been replaced, 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 (x) when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the isolated antibody and SEQ ID(y) When the binding between the isolated antibody and the extracellular domain of human TF, in which amino acid residues 146-158 of the sequence shown in NO:810 are replaced with amino acid residues 151-163 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 the sequence shown in SEQ ID NO:810, and (y) when determined by the median fluorescence intensity of the isolated antibody compared to the 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 159-219 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-224 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 the sequence shown in SEQ ID (z) The binding between the isolated antibody and the extracellular domain of the TF of the sequence shown in NO:810 is less than 50%, and when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of the human TF in which amino acid residues 159-189 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-194 of the rat TF extracellular domain of the sequence shown in SEQ ID NO:838 is less than 50%, and (aa) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of the TF of the sequence shown in SEQ ID NO:810 is less than 50%, and (aa) the binding between the isolated antibody and amino acid residues 159-174 of the sequence shown in SEQ ID The binding between the extracellular domain of human TF, in which amino acid residues 164-179 in the extracellular domain of rat TF of the sequence shown in NO:838 have been replaced, 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 (bb) when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the isolated antibody and amino acid residues 167-174 of the sequence shown in SEQ ID NO:810 are SEQ IDWhen the binding between the isolated antibody and the extracellular domain of human TF, in which amino acid residues 172-179 in the extracellular domain of rat TF of the sequence shown in NO:838 are replaced, 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 when determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a (cc) live cell staining assay, the binding between the isolated antibody and the extracellular domain of rat TF, in which amino acid residues 141-194 in the sequence shown in SEQ ID NO:838 are replaced with amino acid residues 136-189 in the extracellular domain of human TF 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.

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

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

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

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

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

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

[0063] In some embodiments, the antibody includes all three heavy chain complementation 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 includes all three heavy chain complementation determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, 25A5-T, 25A3, 25A5, 25G, 25G1, or 25G9.

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

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

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

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

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

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

[0071] In some embodiments, the antibody includes 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 includes 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 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.

[0074] 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.

[0075] 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.

[0076] In another embodiment, an isolated antibody is provided herein that comprises all three heavy chain complementation 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.

[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 an antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9.

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

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

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

[0083] In some embodiments, the antibody is V of SEQ ID NO:113 H Sequence and V of SEQ ID NO:114 L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:151. H Sequence and SEQ ID NO:152 V L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:189 H Sequence and SEQ ID NO:190 V L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:836. H Sequence and V of SEQ ID NO:837 L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:227 H Sequence and SEQ ID NO:228 V L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:265 H Sequence and V of SEQ ID NO:266 L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:303.H Sequence and SEQ ID NO:304 V L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:455. H Sequence and V of SEQ ID NO:456 L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:493. H Sequence and SEQ ID NO:494 V L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO: 531. H Sequence and SEQ ID NO: 532 V L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:569 H Sequence and SEQ ID NO: 570 V L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:607 H Sequence and SEQ ID NO: 608 V L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:645 H Sequence and V of SEQ ID NO:646 L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:683. H Sequence and V of SEQ ID NO:684 L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:721. H Sequence and V of SEQ ID NO:722 L Includes 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 the V of SEQ ID NO:763 H sequence and the V of SEQ ID NO:764 L sequence. In some embodiments, the antibody comprises the V of SEQ ID NO:868 H sequence and the V of SEQ ID NO:869 LIncludes a sequence. In some embodiments, the antibody is V of SEQ ID NO:870 H Sequence and V of SEQ ID NO:871 L Includes a sequence. In some embodiments, the antibody is V of SEQ ID NO:769 H Sequence and SEQ ID NO:770 V L Includes arrays.

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

[0087] In some embodiments, the antibody includes 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 includes 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 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.

[0090] 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.

[0091] 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.

[0092] In another embodiment, isolated antibodies are provided herein that compete for binding to human TF with antibodies designated as 1F, 1G, 29D, 29E, 39A, or 54E.

[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 of the isolated antibody to the extracellular domain of a 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 a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the isolated antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0097] In some embodiments, the binding of the isolated antibody to the extracellular domain of a 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 a rat TF in the sequence shown in SEQ ID NO:838 is less than 50% of the binding of the isolated antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0098] In some embodiments, the binding of the isolated antibody to the extracellular domain of a human TF in which amino acid residues 78-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77-112 of the extracellular domain of a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the isolated antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0099] In some embodiments, the binding of the isolated antibody to the extracellular domain of a human TF in which amino acid residues 78-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77-85 and 92-112 of the extracellular domain of a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the isolated antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0100] In some embodiments, 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 94-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF 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, 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 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 the sequence shown in SEQ ID NO:810.

[0101] In some embodiments, when 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 94-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF 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, 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 with amino acid residues 77-112 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, and the binding between the isolated antibody and SEQ ID 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 NO:810 are replaced with 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 more 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 complementation determining regions (CDRs) and all three light chain CDRs from an antibody designated as 1F, 1G, 29D, 29E, 39A, 43Ea, or 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 the V H sequence of SEQ ID NO:37 and the V L sequence of SEQ ID NO:38. In some embodiments, the antibody comprises the V H sequence of SEQ ID NO:75 and the V L sequence of SEQ ID NO:76. In some embodiments, the antibody comprises the V H sequence of SEQ ID NO:341 and the V L sequence of SEQ ID NO:342. In some embodiments, the antibody comprises the V H sequence of SEQ ID NO:379 and the V L sequence of SEQ ID NO:380. In some embodiments, the antibody comprises the V H sequence of SEQ ID NO:417 and the V L sequence of SEQ ID NO:418. In some embodiments, the antibody comprises the V H sequence of SEQ ID NO:759 and the V L sequence of SEQ ID NO:760.

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

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

[0107] In some embodiments, the antibody includes 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.

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

[0109] In another embodiment, isolated antibodies are provided herein, comprising VH-CDR1 containing the sequence described in SEQ ID NO:773, VH-CDR2 containing the sequence described in SEQ ID NO:774, VH-CDR3 containing the sequence described in SEQ ID NO:775, VL-CDR1 containing the sequence described in SEQ ID NO:776, VL-CDR2 containing the sequence described in SEQ ID NO:777, and VL-CDR3 containing the sequence described in SEQ ID NO:778.

[0110] In another embodiment, isolated antibodies are provided herein, comprising VH-CDR1 containing the sequence described in SEQ ID NO:779, VH-CDR2 containing the sequence described in SEQ ID NO:780, VH-CDR3 containing the sequence described in SEQ ID NO:781, VL-CDR1 containing the sequence described in SEQ ID NO:782, VL-CDR2 containing the sequence described in SEQ ID NO:783, and VL-CDR3 containing the sequence described in SEQ ID NO:784.

[0111] In another embodiment, isolated antibodies are provided herein, comprising VH-CDR1 containing the sequence described in SEQ ID NO:785, VH-CDR2 containing the sequence described in SEQ ID NO:786, VH-CDR3 containing the sequence described in SEQ ID NO:787, VL-CDR1 containing the sequence described in SEQ ID NO:788, VL-CDR2 containing the sequence described in SEQ ID NO:789, and VL-CDR3 containing the sequence described in SEQ ID NO:790.

[0112] In another embodiment, isolated antibodies are provided herein, comprising VH-CDR1 containing the sequence described in SEQ ID NO:791, VH-CDR2 containing the sequence described in SEQ ID NO:792, VH-CDR3 containing the sequence described in SEQ ID NO:793, VL-CDR1 containing the sequence described in SEQ ID NO:794, VL-CDR2 containing the sequence described in SEQ ID NO:795, and VL-CDR3 containing the sequence described in SEQ ID NO:796.

[0113] In another embodiment, isolated antibodies are provided herein, comprising VH-CDR1 containing the sequence described in SEQ ID NO:797, VH-CDR2 containing the sequence described in SEQ ID NO:798, VH-CDR3 containing the sequence described in SEQ ID NO:799, VL-CDR1 containing the sequence described in SEQ ID NO:800, VL-CDR2 containing the sequence described in SEQ ID NO:801, and VL-CDR3 containing the sequence described in SEQ ID NO:802.

[0114] In another embodiment, isolated antibodies are provided herein, comprising VH-CDR1 containing the sequence described in SEQ ID NO:803, VH-CDR2 containing the sequence described in SEQ ID NO:804, VH-CDR3 containing the sequence described in SEQ ID NO:805, VL-CDR1 containing the sequence described in SEQ ID NO:806, VL-CDR2 containing the sequence described in SEQ ID NO:807, and VL-CDR3 containing the sequence described in SEQ ID NO:808.

[0115] In another embodiment, isolated antibodies are provided herein, comprising VH-CDR1 containing the sequence described in SEQ ID NO:872, VH-CDR2 containing the sequence described in SEQ ID NO:873, VH-CDR3 containing the sequence described in SEQ ID NO:874, VL-CDR1 containing the sequence described in SEQ ID NO:875, VL-CDR2 containing the sequence described in SEQ ID NO:876, and VL-CDR3 containing the sequence described in SEQ ID NO:877.

[0116] In another embodiment, isolated antibodies are provided herein, comprising VH-CDR1 containing the sequence described in SEQ ID NO:878, VH-CDR2 containing the sequence described in SEQ ID NO:879, VH-CDR3 containing the sequence described in SEQ ID NO:880, VL-CDR1 containing the sequence described in SEQ ID NO:881, VL-CDR2 containing the sequence described in SEQ ID NO:882, and VL-CDR3 containing the sequence described in SEQ ID NO:883.

[0117] In some embodiments, the antibody, when measured by Octet QK384 or Biacore assay, has a K content 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. D It then 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 Fab, Fab', F(ab')2, Fv, scFv, (scFv)2, a single-chain antibody molecule, a bivariate domain antibody, a single variable domain antibody, a linear antibody, or a V-domain antibody.

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

[0122] In some embodiments, the Fc comprises one or more modifications, which result in an increased half-life, increased antibody-dependent cytotoxicity (ADCC), increased antibody-dependent cell phagocytosis (ADCP), increased complement-dependent cytotoxicity (CDC), or decreased effector function compared to the Fc without the modifications.

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

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

[0125] In another embodiment, as used herein, any of the above antibodies, its V H That V L An isolated polynucleotide or set of polynucleotides is provided, encoding its light chain, its heavy chain, or its antigen-binding moiety.

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

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

[0128] In another embodiment, this specification provides a method for producing an antibody, comprising expressing the antibody in the host cells described above and isolating the expressed antibody.

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

[0130] In another embodiment, the Specified provides a method for treating or preventing a disease or condition in a subject requiring treatment or prevention of such disease or condition, the method comprising administering to the subject an effective amount of any of the above-mentioned antibodies or pharmaceutical compositions.

[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 stomach 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 breast cancer, being estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-). 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 neovascularization. In some embodiments, the disease or condition involving neovascularization is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. In some embodiments, the disease or condition involves vasculitis.

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

[0134] In another embodiment, this specification provides a method for detecting TF in a subject having or suspected to have a disease or condition, 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 one 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 stomach 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 breast cancer, being estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-). 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 neovascularization. In some embodiments, the disease or condition involving neovascularization is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. In some embodiments, the disease or condition involves vasculitis.

[0137] In another embodiment, the Specified Public Service provides a method for detecting TF in a subject having or suspected to have a disease or condition, comprising: (a) administering one of the above-mentioned antibodies to the subject; 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 stomach 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 breast cancer, being estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-). 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 neovascularization. In some embodiments, the disease or condition involving neovascularization is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. In some embodiments, the disease or condition involves vasculitis.

[0140] In another embodiment, a kit is provided herein that includes any of the above-described antibodies or pharmaceutical compositions and instructions for use.

[0141] In another embodiment, this specification provides an antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent conjugated to the antibody, and optionally a linker for conjugating 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 separate from the human TF binding site to which human FVIIa binds.

[0142] In some embodiments, (1) the antibody is determined by a thrombin generation assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it does not inhibit human thrombin production, and (2) as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay, the binding of the antibody to the extracellular domain of variant TF containing a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding of the antibody to the extracellular domain of TF of the sequence shown in SEQ ID NO:810.

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

[0144] In some embodiments, (1) the antibody is determined by a thrombin generation assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 LCompared to a reference antibody containing the sequence, it tolerates human thrombin generation to a greater extent, and (2) as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay, the binding of the antibody to the extracellular domain of variant TF containing a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding of the antibody to the extracellular domain of TF of the sequence shown in SEQ ID NO:810.

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

[0146] In some embodiments, (1) the antibody is determined by a thrombin generation assay (TGA) to be V of SEQ ID NO: 821. H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, the antibody tolerates a greater amount of human thrombin generation, and (2) the binding between the antibody and the extracellular domain of variant TF containing 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.

[0147] In some embodiments, the antibody includes VH-CDR1 containing the sequence described in SEQ ID NO:779, VH-CDR2 containing the sequence described in SEQ ID NO:780, VH-CDR3 containing the sequence described in SEQ ID NO:781, VL-CDR1 containing the sequence described in SEQ ID NO:782, VL-CDR2 containing the sequence described in SEQ ID NO:783, and VL-CDR3 containing the sequence described in SEQ ID NO:784.

[0148] In some embodiments, the antibody includes VH-CDR1 containing the sequence described in SEQ ID NO:872, VH-CDR2 HI containing the sequence described in SEQ ID NO:873, VH-CDR3 containing the sequence described in SEQ ID NO:874, VL-CDR1 containing the sequence described in SEQ ID NO:875, VL-CDR2 containing the sequence described in SEQ ID NO:876, and VL-CDR3 containing the sequence described in SEQ ID NO:877.

[0149] In some embodiments, the antibody includes VH-CDR1 containing the sequence described in SEQ ID NO:878, VH-CDR2 containing the sequence described in SEQ ID NO:879, VH-CDR3 containing the sequence described in SEQ ID NO:880, VL-CDR1 containing the sequence described in SEQ ID NO:881, VL-CDR2 containing the sequence described in SEQ ID NO:882, and VL-CDR3 containing the sequence described in SEQ ID NO:883.

[0150] In some embodiments, the antibody is V of SEQ ID NO:821 when determined by thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L Compared to reference antibodies containing the sequence, it does not inhibit human thrombin production.

[0151] In some embodiments, the antibody is V of SEQ ID NO:821 when determined by thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 LCompared to reference antibodies containing the sequence, it inhibits human thrombin production to a lower degree.

[0152] In some embodiments, the antibody is V of SEQ ID NO:821 when determined by thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it tolerates human thrombin generation to a greater degree.

[0153] In some embodiments, the antibody is V of SEQ ID NO:821 when determined by thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it inhibits human thrombin production by a smaller amount.

[0154] In some embodiments, the antibody is V of SEQ ID NO:821 when determined by thrombin generation assay (TGA). H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it allows for a greater amount of human thrombin production.

[0155] In some embodiments, the antibody does not inhibit human thrombin production as determined by a thrombin production assay (TGA). In some embodiments, the antibody does not reduce the thrombin peak (peak IIa) on the thrombin production 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 production curve (tt peak) compared to an isotype control. In some embodiments, the antibody does not reduce endogenous thrombin production capacity (ETP) as determined by the area under the thrombin production curve compared to an isotype control. In some embodiments, the antibody allows human thrombin production as determined by a thrombin production assay (TGA). In some embodiments, the antibody maintains the thrombin peak (peak IIa) on the thrombin production 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 production curve (tt peak) compared to an isotype control. In some embodiments, the antibody protects endogenous thrombin production capacity (ETP) compared to an isotype control, as determined by the area under the thrombin production curve.

[0156] In some embodiments, the antibody binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds. In 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 production as determined by a thrombin production assay (TGA), allows human thrombin production as determined by a thrombin production assay (TGA), binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, does not interfere with TF:FVIIa's ability 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 production as determined by a thrombin assay (TGA), does not reduce endogenous thrombin production capacity (ETP) compared to isotype controls as determined by the area under the thrombin production curve, allows human thrombin production as determined by a thrombin assay (TGA), protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by the area under the thrombin production curve, binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, does not interfere with TF:FVIIa's ability 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 production as determined by thrombin production assay (TGA), does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, does not increase the time from the start of the assay to the thrombin peak on the thrombin production curve (tt peak) compared to isotype controls, does not decrease endogenous thrombin production capacity (ETP) as determined by the area under the thrombin production curve compared to isotype controls, and, as determined by thrombin production assay (TGA), does not inhibit human thrombin production. It allows for the maintenance of the thrombin peak (peak IIa) on the thrombin generation curve compared to isotype controls, maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to isotype controls, protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by the area under the thrombin generation curve, binds to human TF at a human TF binding site 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.

[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 containing 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 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 149 of the sequence shown in SEQ ID NO:810 is K149N.

[0163] In some embodiments, the binding between the antibody and the extracellular domain of a variant TF containing 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 containing 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 of the antibody to 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 of the extracellular domain of rat TF 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, is greater than 50% of the binding of the antibody to the extracellular domain of TF shown in SEQ ID NO:810.

[0166] In some embodiments, the binding of the antibody to the extracellular domain of a human TF in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0167] In some embodiments, the binding of the antibody to the extracellular domain of a 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 a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

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

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

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

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

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

[0173] In some embodiments, the binding of the antibody to the extracellular domain of a rat TF in which amino acid residues 141-194 of the sequence shown in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of a human TF in the sequence shown in SEQ ID NO:810 is greater than 50% of the binding of the antibody to the extracellular domain of the TF in 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.

[0174] In some embodiments, when 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 a variant TF containing 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 the TF in the sequence shown in SEQ ID NO:810, the binding between the antibody and the extracellular domain of a variant TF containing 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 in the sequence shown in SEQ ID NO:810, and the binding between the 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 in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding between the antibody and the extracellular domain of a human TF in which amino acid residues 1-77 of the sequence shown in SEQ ID The binding between the antibody and the extracellular domain of the rat TF in the sequence shown in NO:810 is more than 50%, and the binding between the antibody and the extracellular domain of the human TF in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the rat TF in the sequence shown in SEQ ID NO:838 is more than 50%, and the binding between the antibody and the extracellular domain of the rat TF in the sequence shown in SEQ ID NO:810 is replaced with amino acid residues 99-112 of the rat TF in the sequence shown in SEQ ID NO:838 is more than 50%, and the binding between the antibody and the extracellular domain of the 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 rat TF in the sequence shown in SEQ ID NO:838 is more than 50%, and the binding between the antibody and amino acid residues 146-158 of the sequence shown in SEQ ID The binding between the antibody and the extracellular domain of human TF, in which amino acid residues 151-163 in the extracellular domain of rat TF of the sequence shown in NO:838 have been replaced, 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 amino acid residues 141-194 in the sequence shown in SEQ ID NO:838 is SEQThe binding between the antibody and the rat TF extracellular domain, which has been substituted with amino acid residues 136-189 in the extracellular domain of the human TF sequence shown in ID NO:810, is more than 50% of the binding between the antibody and the extracellular domain of the TF sequence shown in SEQ ID NO:810. In some embodiments, the mutation at amino acid residue 149 of the sequence shown 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.

[0175] In some embodiments, when 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 a variant TF containing 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 the TF of the sequence shown in SEQ ID NO: 810, the binding between the antibody and the extracellular domain of a variant TF containing 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, the binding between the antibody and the extracellular domain of a variant TF containing 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, and the binding between the antibody and the extracellular domain of a variant TF containing mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID The binding between the antibody and the extracellular domain of human TF, in which amino acid residues 1-77 of the sequence shown in NO:810 are replaced with amino acid residues 1-76 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 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 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 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 the sequence shown in SEQ ID NO:810, and the binding between the antibody and amino acid residues 94-107 of the sequence shown in SEQ ID The binding between the antibody and the extracellular domain of human TF, where amino acid residues 99-112 in the extracellular domain of rat TF of the sequence shown in NO:838 are replaced, 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 amino acid residues 146-158 in the sequence shown in SEQ ID NO:810 isThe binding between the antibody and the extracellular domain of human TF in which amino acid residues 151-163 in the extracellular domain of rat TF in the sequence shown in NO:838 have been replaced is less than 50% of the binding between the antibody and the extracellular domain of TF in 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 159-219 in the sequence shown in SEQ ID NO:810 have been replaced with amino acid residues 164-224 in 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 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 159-189 in the sequence shown in SEQ ID NO:810 have been replaced with amino acid residues 164-194 in 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 human TF in which amino acid residues 159-189 in the sequence shown in SEQ ID NO:810 have been replaced with amino acid residues 164-194 in 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 the TF of the sequence shown in NO:810 is less than 50%, and the binding between the antibody and the extracellular domain of human TF in which amino acid residues 159-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-179 in the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50%, and the binding between the antibody and the extracellular domain of human TF in which amino acid residues 167-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 172-179 in the extracellular domain of rat TF of the sequence shown in SEQ ID NO:838 is less than 50%, and the binding between the antibody and the extracellular domain of human TF in which amino acid residues 141-194 of the sequence shown in SEQ ID NO:838 are SEQ The binding between the antibody and the extracellular domain of rat TF, where amino acid residues 136-189 in the extracellular domain of human TF with the sequence shown in ID NO:810 have been replaced, is more than 50% of the binding between the antibody and the extracellular domain of TF with the sequence shown in SEQ ID NO:810. In some embodiments, SEQ IDThe mutation at amino acid residue 149 of the sequence shown in 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 pig TF.

[0177] In some embodiments, the antibody (a) does not inhibit human thrombinogenesis as determined by a thrombinogenesis assay (TGA), and (b) 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 a variant TF containing 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. 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.

[0178] In some embodiments, the antibody (a) allows human thrombin generation as determined by a thrombin generation assay (TGA), and (b) the binding between the antibody and the extracellular domain of variant TF containing 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 mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 are N171H and T197K.

[0179] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by a thrombin production assay (TGA), (b) 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 a variant TF containing 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 the TF in the sequence shown in SEQ ID NO:810, and (c) 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 a variant TF containing 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 in the sequence shown in SEQ ID NO:810. In some embodiments, the mutation at amino acid residue 149 of the sequence shown 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.

[0180] In some embodiments, the antibody (a) allows 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 containing 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 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, and (c) the binding between the antibody and the extracellular domain of a variant TF containing 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 mutation at amino acid residue 149 of the sequence shown 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.

[0181] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by a thrombin production assay (TGA), (b) binds to cynomolgus monkey TF, (c) the binding between the antibody and the extracellular domain of a variant TF containing 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 the TF in 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 containing 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 in 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 shown 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.

[0182] In some embodiments, the antibody (a) allows 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 containing 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 the TF in 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 containing 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 in 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 shown 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.

[0183] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by a thrombin production assay (TGA), (b) allows human thrombin production as determined by a thrombin production assay (TGA), (c) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (d) does not interfere with TF:FVIIa's ability 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 production as determined by thrombin production assay (TGA), (b) does not reduce endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombin production curve, (c) allows human thrombin production as determined by thrombin production assay (TGA), (d) protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombin production curve, (e) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (f) does not interfere with TF:FVIIa's ability 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 production as determined by thrombin production assay (TGA), (b) does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, (c) does not increase the time from the start of the assay to the thrombin peak (tt peak) on the thrombin production curve compared to isotype controls, (d) does not reduce endogenous thrombin production capacity (ETP) as determined by area under the thrombin production curve compared to isotype controls, (e) allows human thrombin production as determined by thrombin production assay (TGA), and (f) does not increase the time from the start of the assay to the thrombin peak on the thrombin production curve compared to isotype controls. (g) maintains the thrombin peak (peak IIa), maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to isotype controls, (h) protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by the area under the thrombin generation curve, (i) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (j) does not interfere with TF:FVIIa's ability 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 production as determined by a thrombin production assay (TGA), (b) allows human thrombin production as determined by a thrombin production assay (TGA), (c) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (d) does not interfere with TF:FVIIa's ability 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 production as determined by thrombin production assay (TGA), (b) does not reduce endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombin production curve, (c) allows human thrombin production as determined by thrombin production assay (TGA), (d) protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombin production curve, (e) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (f) does not interfere with TF:FVIIa's ability 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 production as determined by thrombin production assay (TGA), (b) does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, (c) does not increase the time from the start of the assay to the thrombin peak (tt peak) on the thrombin production curve compared to isotype controls, (d) does not decrease endogenous thrombin production capacity (ETP) as determined by the area under the thrombin production curve compared to isotype controls, (e) allows human thrombin production as determined by thrombin production assay (TGA), and (f) does not increase the time from the start of the assay to the thrombin peak on the thrombin production curve compared to isotype controls. (g) maintains peak IIa, (h) maintains the time from assay initiation to the thrombin peak on the thrombin generation curve (tt peak) compared to isotype controls, (i) protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by the area under the thrombin generation curve, (j) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (k) does not interfere with TF:FVIIa's ability to convert FX to FXa, (l) does not compete with FVIIa for binding to human TF, (m) inhibits FVIIa-dependent TF signaling, (n) binds to cynomolgus monkey TF, (o) binds to rabbit TF, and (p) binds to pig TF.

[0189] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by thrombin production assay (TGA), (b) does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin production curve (tt peak) compared to isotype controls, (d) does not reduce endogenous thrombin production capacity (ETP) as determined by the area under the thrombin production curve compared to isotype controls, (e) allows human thrombin production as determined by thrombin production assay (TGA), (f) maintains the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, and (g) compared to isotype controls The antibody maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak), (h) protects endogenous thrombin production ability (ETP) compared to isotype controls, as determined by the area under the thrombin generation curve, (i) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (j) does not interfere with TF:FVIIa's ability 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 pig TF, and (q) as determined by the median fluorescence intensity of the antibody compared to isotype controls in a live cell staining assay, the antibody and SEQ The binding between the antibody and the extracellular domain of variant TF containing a mutation at amino acid residue 149 of the sequence shown in 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, and (r) when determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing a mutation at amino acid residue 68 of the sequence shown in SEQ ID(s) The binding between the antibody and the extracellular domain of a variant TF containing mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is greater than 50%, and when 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 a variant TF containing mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 is less than 50%, and when 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 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 of the extracellular domain of a rat TF in the sequence shown in SEQ ID NO:838 (u) The binding between the antibody and the extracellular domain of the rat TF in the sequence shown in NO:810 is greater than 50%, and the binding between the antibody and the extracellular domain of the human TF in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the rat TF in the sequence shown in SEQ ID NO:838, as determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, is greater than 50% of the binding between the antibody and the extracellular domain of the rat TF in the sequence shown in SEQ ID NO:810, and (v) The binding between the antibody and the extracellular domain of the 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 rat TF in the sequence shown in SEQ ID NO:838, as determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, is greater than 50% of the binding between the antibody and the extracellular domain of the rat TF in the sequence shown in SEQ ID The binding between the extracellular domain of the TF of the sequence shown in NO:810 is greater than 50%, and (w) when determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the antibody and amino acid residues 146-158 of the sequence shown in SEQ ID NO:810 are SEQ ID(x) When determined by the median fluorescence intensity of the antibody compared to the 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 151-163 in the extracellular domain of rat TF in the sequence shown in NO:838 are replaced is less than 50% of the binding between the antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and (y) When determined by the median fluorescence intensity of the antibody compared to the 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 159-219 in the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 are replaced is less than 50% of the binding between the antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and (y) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and amino acid residues 159-189 in the sequence shown in SEQ ID (z) When determined by the median fluorescence intensity of the antibody compared to the 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 164-194 in the extracellular domain of rat TF in the sequence shown in NO:838 are replaced with amino acid residues 164-179 in 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 the sequence shown in SEQ ID NO:810 is replaced with amino acid residues 164-179 in 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 the sequence shown in SEQ ID NO:810 is replaced with amino acid residues 167-174 in the sequence shown in SEQ ID The binding between the extracellular domain of human TF, in which amino acid residues 172-179 in the extracellular domain of rat TF of the sequence shown in NO:838 have been replaced, and the antibody and SEQ IDThe binding between the antibody and the extracellular domain of the TF of the sequence shown in NO:810 is less than 50%, and (bb) the binding between the 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 with amino acid residues 136-189 of the extracellular domain of human TF 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.

[0190] In some embodiments, the antibody (a) does not inhibit human thrombin production as determined by thrombin production assay (TGA), (b) does not reduce the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, (c) does not increase the time from the start of the assay to the thrombin peak on the thrombin production curve (tt peak) compared to isotype controls, (d) does not reduce endogenous thrombin production capacity (ETP) as determined by the area under the thrombin production curve compared to isotype controls, (e) allows human thrombin production as determined by thrombin production assay (TGA), (f) maintains the thrombin peak (peak IIa) on the thrombin production curve compared to isotype controls, and (g) compared to isotype controls The antibody maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak), (h) protects endogenous thrombin production ability (ETP) compared to isotype controls, as determined by the area under the thrombin generation curve, (i) binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, (j) does not interfere with TF:FVIIa's ability 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 pig TF, and (q) as determined by the median fluorescence intensity of the antibody compared to isotype controls in a live cell staining assay, the antibody and SEQ The binding between the antibody and the extracellular domain of the variant TF containing the K149N mutation in the sequence shown in ID NO:810 is less than 50% of the binding between the antibody and the extracellular domain of the TF containing the sequence shown in SEQ ID NO:810, and (r) when determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of the variant TF containing the K68N mutation in the sequence shown in SEQ ID(s) The binding between the antibody and the extracellular domain of variant TF containing mutations N171H and T197K of the sequence shown in SEQ ID NO:810 is greater than 50%, and when determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing mutations N171H and T197K of the sequence shown in SEQ ID NO:810 is less than 50%, and when determined by the median fluorescence intensity of the antibody compared to the 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 1-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 1-76 of the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 (u) The binding between the antibody and the extracellular domain of the rat TF in the sequence shown in NO:810 is greater than 50%, and the binding between the antibody and the extracellular domain of the human TF in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the rat TF in the sequence shown in SEQ ID NO:838, as determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, is greater than 50% of the binding between the antibody and the extracellular domain of the rat TF in the sequence shown in SEQ ID NO:810, and (v) The binding between the antibody and the extracellular domain of the 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 rat TF in the sequence shown in SEQ ID NO:838, as determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, is greater than 50% of the binding between the antibody and the extracellular domain of the rat TF in the sequence shown in SEQ ID The binding between the extracellular domain of the TF of the sequence shown in NO:810 is greater than 50%, and (w) when determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the antibody and amino acid residues 146-158 of the sequence shown in SEQ ID NO:810 are SEQ ID(x) When determined by the median fluorescence intensity of the antibody compared to the 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 151-163 in the extracellular domain of rat TF in the sequence shown in NO:838 are replaced is less than 50% of the binding between the antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and (y) When determined by the median fluorescence intensity of the antibody compared to the 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 159-219 in the extracellular domain of rat TF in the sequence shown in SEQ ID NO:838 are replaced is less than 50% of the binding between the antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and (y) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and amino acid residues 159-189 in the sequence shown in SEQ ID (z) When determined by the median fluorescence intensity of the antibody compared to the 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 164-194 in the extracellular domain of rat TF in the sequence shown in NO:838 are replaced with amino acid residues 164-179 in 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 the sequence shown in SEQ ID NO:810 is replaced with amino acid residues 164-179 in 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 the sequence shown in SEQ ID NO:810 is replaced with amino acid residues 167-174 in the sequence shown in SEQ ID The binding between the extracellular domain of human TF, in which amino acid residues 172-179 in the extracellular domain of rat TF of the sequence shown in NO:838 have been replaced, and the antibody and SEQ IDThe binding between the antibody and the extracellular domain of the TF of the sequence shown in NO:810 is less than 50%, and (bb) the binding between the 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 with amino acid residues 136-189 of the extracellular domain of human TF 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.

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

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

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

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

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

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

[0197] In some embodiments, the antibody includes all three heavy chain complementation 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 complementation determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9.

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

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

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

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

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

[0204] In some embodiments, the antibody includes 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 antibody includes an antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9. In some embodiments, the antibody includes 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 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.

[0206] In another embodiment, this specification provides an antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent conjugated to the antibody, and optionally a linker for conjugating the antibody to the cytotoxic agent, wherein the antibody competes for binding to human TF with antibodies designated as 1F, 1G, 29D, 29E, 39A, or 54E.

[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 of the antibody to the extracellular domain of a 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 a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0210] In some embodiments, the binding of the antibody to the extracellular domain of a 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 a rat TF in 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, is less than 50% of the binding of the antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0211] In some embodiments, the binding of the antibody to the extracellular domain of a human TF in which amino acid residues 78-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77-112 of the extracellular domain of a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0212] In some embodiments, the binding of the antibody to the extracellular domain of a human TF in which amino acid residues 78-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77-85 and 92-112 of the extracellular domain of a rat TF in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the antibody to the extracellular domain of the TF in the sequence shown in SEQ ID NO:810.

[0213] In some embodiments, as determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay, the binding of the antibody to 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 in the sequence shown in SEQ ID NO:838 is greater than 50% of the binding of the antibody to the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and the binding of the antibody to 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 in the sequence shown in SEQ ID NO:838 is less than 50% of the binding of the antibody to the extracellular domain of TF in the sequence shown in SEQ ID NO:810.

[0214] In some embodiments, when 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 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 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 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 78-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77-112 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 antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and the binding between the antibody and amino acid residues 78-107 of the sequence shown in SEQ ID NO:810 is greater than 50% of the binding between the antibody and the extracellular domain of TF in 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 77-85 and 92-112 in the extracellular domain of rat TF with the sequence shown NO:838 have been replaced, is more than 50% of the binding between the antibody and the extracellular domain of TF with the sequence shown SEQ ID NO:810.

[0215] In some embodiments, the antibody comprises all three heavy chain complementation determining regions (CDRs) and all three light chain CDRs from an antibody designated as 1F, 1G, 29D, 29E, 39A, 43Ea, or 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 contains all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 1F. In some embodiments, the antibody contains all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 1G. In some embodiments, the antibody contains all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 29D. In some embodiments, the antibody contains all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 29E. In some embodiments, the antibody contains all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 39A. In some embodiments, the antibody contains all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 54E.

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

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

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

[0220] In some embodiments, the antibody includes 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. In some embodiments, the antibody consists 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.

[0221] In another embodiment, this specification provides 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 VH-CDR1 containing the sequence described in SEQ ID NO:773, VH-CDR2 containing the sequence described in SEQ ID NO:774, VH-CDR3 containing the sequence described in SEQ ID NO:775, VL-CDR1 containing the sequence described in SEQ ID NO:776, VL-CDR2 containing the sequence described in SEQ ID NO:777, and VL-CDR3 containing the sequence described in SEQ ID NO:778.

[0222] In another embodiment, this specification provides 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 VH-CDR1 containing the sequence described in SEQ ID NO:779, VH-CDR2 containing the sequence described in SEQ ID NO:780, VH-CDR3 containing the sequence described in SEQ ID NO:781, VL-CDR1 containing the sequence described in SEQ ID NO:782, VL-CDR2 containing the sequence described in SEQ ID NO:783, and VL-CDR3 containing the sequence described in SEQ ID NO:784.

[0223] In another embodiment, this specification provides an antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent conjugated to the antibody, and optionally a linker for conjugating the antibody to the cytotoxic agent, wherein the antibody comprises VH-CDR1 containing the sequence described in SEQ ID NO:785, VH-CDR2 containing the sequence described in SEQ ID NO:786, VH-CDR3 containing the sequence described in SEQ ID NO:787, VL-CDR1 containing the sequence described in SEQ ID NO:788, VL-CDR2 containing the sequence described in SEQ ID NO:789, and VL-CDR3 containing the sequence described in SEQ ID NO:790.

[0224] In another embodiment, this specification provides an antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent conjugated to the antibody, and optionally a linker for conjugating the antibody to the cytotoxic agent, wherein the antibody comprises VH-CDR1 containing the sequence described in SEQ ID NO:791, VH-CDR2 containing the sequence described in SEQ ID NO:792, VH-CDR3 containing the sequence described in SEQ ID NO:793, VL-CDR1 containing the sequence described in SEQ ID NO:794, VL-CDR2 containing the sequence described in SEQ ID NO:795, and VL-CDR3 containing the sequence described in SEQ ID NO:796.

[0225] In another embodiment, this specification provides an antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent conjugated to the antibody, and optionally a linker for conjugating the antibody to the cytotoxic agent, wherein the antibody comprises VH-CDR1 containing the sequence described in SEQ ID NO:797, VH-CDR2 containing the sequence described in SEQ ID NO:798, VH-CDR3 containing the sequence described in SEQ ID NO:799, VL-CDR1 containing the sequence described in SEQ ID NO:800, VL-CDR2 containing the sequence described in SEQ ID NO:801, and VL-CDR3 containing the sequence described in SEQ ID NO:802.

[0226] In another embodiment, this specification provides an antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent conjugated to the antibody, and optionally a linker for conjugating the antibody to the cytotoxic agent, wherein the antibody comprises VH-CDR1 containing the sequence described in SEQ ID NO:803, VH-CDR2 containing the sequence described in SEQ ID NO:804, VH-CDR3 containing the sequence described in SEQ ID NO:805, VL-CDR1 containing the sequence described in SEQ ID NO:806, VL-CDR2 containing the sequence described in SEQ ID NO:807, and VL-CDR3 containing the sequence described in SEQ ID NO:808.

[0227] In another embodiment, this specification provides an antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent conjugated to the antibody, and optionally a linker for conjugating the antibody to the cytotoxic agent, wherein the antibody comprises VH-CDR1 containing the sequence described in SEQ ID NO:872, VH-CDR2 containing the sequence described in SEQ ID NO:873, VH-CDR3 containing the sequence described in SEQ ID NO:874, VL-CDR1 containing the sequence described in SEQ ID NO:875, VL-CDR2 containing the sequence described in SEQ ID NO:876, and VL-CDR3 containing the sequence described in SEQ ID NO:877.

[0228] In another embodiment, this specification provides 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 VH-CDR1 containing the sequence described in SEQ ID NO:878, VH-CDR2 containing the sequence described in SEQ ID NO:879, VH-CDR3 containing the sequence described in SEQ ID NO:880, VL-CDR1 containing the sequence described in SEQ ID NO:881, VL-CDR2 containing the sequence described in SEQ ID NO:882, and VL-CDR3 containing the sequence described in SEQ ID NO:883.

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

[0230] In some embodiments, the antibody, when measured by Octet QK384 or Biacore assay, has a K content 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. D It then 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 Fab, Fab', F(ab')2, Fv, scFv, (scFv)2, a single-chain antibody molecule, a bivariate domain antibody, a single variable domain antibody, a linear antibody, or a V-domain antibody.

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

[0235] In another embodiment, this specification provides an antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent conjugated to the antibody, and optionally a linker for conjugating the antibody to the cytotoxic agent, wherein the antibody competes with any of the above antibodies for binding to human TF.

[0236] In another embodiment, this specification provides an antibody-drug conjugate comprising an anti-human tissue factor (anti-hTF) antibody, a cytotoxic agent conjugated to the antibody, and optionally a linker for conjugating the antibody to the cytotoxic agent, wherein the antibody conjugates to a human TF epitope to which any of the above antibodies conjugate.

[0237] In some embodiments, the cytotoxic agent includes angiogenesis inhibitors, apoptosis promoters, mitotic inhibitors, kinase inhibitors, alkylating agents, hormones, hormone agonists, hormone antagonists, chemokines, drugs, prodrugs, toxins, enzymes, antimetabolites, antibiotics, alkaloids, or radioisotopes. In some embodiments, the cytotoxic agent includes at least one of calicheamicin, camptothecan, carboplatin, irinotecan, SN-38, carboplatin, camptothecan, cyclophosphamide, cytarabine, dacarbazine, docetaxel, dactinomycin, daunorubicin, doxorubicin, etoposide, idarubicin, topotecan, vinca alkaloids, mytansinoids, mytansinoid analogs, pyrrolobenzodiazepines, taxoids, duocalmycin, drastatin, and auristatin.

[0238] In some embodiments, the linker includes an unstable linker, an acid-unstable linker, a photo-unstable 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 an incleavable linker.

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

[0240] In another embodiment, the Specified provides a method for treating or preventing a disease or condition in a subject requiring treatment or prevention of such disease or condition, the method comprising administering to the subject an effective amount of any of the above-described antibody-drug conjugates or pharmaceutical compositions.

[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 stomach 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 breast cancer, being estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-). 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 includes administering one or more additional therapeutic agents to the subject. In some embodiments, the additional therapeutic agents are formulated in the same pharmaceutical composition as the antibody-drug conjugate. In some embodiments, the additional therapeutic agents are formulated in a different pharmaceutical composition than the antibody-drug conjugate. In some embodiments, the additional therapeutic agent is administered before the administration of the antibody-drug conjugate. In some embodiments, the additional therapeutic agent is administered after the administration of the antibody-drug conjugate. In some embodiments, the additional therapeutic agent is administered simultaneously with the antibody-drug conjugate.

[0243] In another embodiment, the Specified Public Service provides a method for detecting TF in a subject having or suspected to have a disease or condition, comprising: (a) administering one of the above-mentioned antibody-drug conjugates to the subject; 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 stomach 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 breast cancer, being estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-). 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 embodiment, a kit is provided herein that includes any of the above-described antibody-drug conjugates or pharmaceutical compositions and instructions for use. [Invention 1001] An isolated human antibody that binds to the extracellular domain of human tissue factor (TF), wherein the isolated human antibody binds to human TF at a human TF binding site separate from the human TF binding site to which human FVIIa binds. [Invention 1002] (1) When the isolated antibody is determined by the thrombin generation assay (TGA), the V of SEQ ID NO:821 H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it does not inhibit human thrombin production, and (2) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of variant TF containing 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. Isolated human antibody of the present invention 1000. [Invention 1003] Isolated human antibodies according to Invention 1000 or 1002, comprising VH-CDR1 containing the sequence described in SEQ ID NO:779, VH-CDR2 containing the sequence described in SEQ ID NO:780, VH-CDR3 containing the sequence described in SEQ ID NO:781, VL-CDR1 containing the sequence described in SEQ ID NO:782, VL-CDR2 containing the sequence described in SEQ ID NO:783, and VL-CDR3 containing the sequence described in SEQ ID NO:784. [Invention 1004] An isolated human antibody according to any of invention 1000 to 1003, comprising VH-CDR1 containing the sequence described in SEQ ID NO:872, VH-CDR2 containing the sequence described in SEQ ID NO:873, VH-CDR3 containing the sequence described in SEQ ID NO:874, VL-CDR1 containing the sequence described in SEQ ID NO:875, VL-CDR2 containing the sequence described in SEQ ID NO:876, and VL-CDR3 containing the sequence described in SEQ ID NO:877. [Invention 1005] An isolated human antibody according to any of invention 1000 to 1003, comprising VH-CDR1 containing the sequence described in SEQ ID NO:878, VH-CDR2 containing the sequence described in SEQ ID NO:879, VH-CDR3 containing the sequence described in SEQ ID NO:880, VL-CDR1 containing the sequence described in SEQ ID NO:881, VL-CDR2 containing the sequence described in SEQ ID NO:882, and VL-CDR3 containing the sequence described in SEQ ID NO:883. [Invention 1006] When determined by thrombinogenesis assay (TGA), SEQ ID NO: 821 V H Sequence and V of SEQ ID NO:822 L An isolated human antibody of the present invention 1000 that does not inhibit human thrombin production compared to a reference antibody containing the sequence. [Invention 1007] The present invention provides 1000 isolated human antibodies that do not inhibit human thrombin production, as determined by a thrombin production assay (TGA). [Invention 1008] An isolated human antibody of the present invention 1007 that does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. [Invention 1009] An isolated human antibody of the present invention 1007 or 1008 that 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 1010] An isolated human antibody according to any of the Invention 1007-1009, which, as determined by the area under the thrombin production curve, does not reduce endogenous thrombin production capacity (ETP) compared to an isotype control. [Invention 1011] An isolated human antibody from any of the prior art inventions that allows human thrombin production as determined by a thrombin production assay (TGA). [Invention 1012] An isolated human antibody of the present invention 1011 that maintains the thrombin peak (peak IIa) on the thrombin generation curve compared to an isotype control. [Invention 1013] An isolated human antibody of the present invention 1011 or 1012 that 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. [Invention 1014] An isolated human antibody according to any of the invention 1011-1013, which protects endogenous thrombin production ability (ETP) compared to an isotype control, as determined by the area under the thrombin production curve. [Invention 1015] An isolated human antibody from either of the prior art inventions that binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds. [Invention 1016] An isolated human antibody from any of the prior art inventions in which TF:FVIIa does not interfere with the ability of FX to convert to FXa. [Invention 1017] An isolated human antibody from the prior art that does not compete with human FVIIa for binding to human TF. [Invention 1018] An isolated human antibody from the prior invention, which, as determined by a thrombinogenesis assay (TGA), does not inhibit human thrombinogenesis, as determined by a thrombinogenesis assay (TGA), allows human thrombinogenesis, binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, does not interfere with TF:FVIIa's ability to convert FX to FXa, and does not compete with FVIIa for binding to human TF. [Invention 1019] An isolated human antibody from the prior invention which, as determined by thrombinogenesis assay (TGA), does not inhibit human thrombinogenesis, does not reduce endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombinogenesis curve, allows human thrombinogenesis as determined by thrombinogenesis assay (TGA), protects endogenous thrombin production capacity (ETP) compared to isotype controls as determined by area under the thrombinogenesis curve, binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds, does not interfere with TF:FVIIa's ability to convert FX to FXa, and does not compete with FVIIa for binding to human TF. [Invention 1020] When determined by the Thrombin Generation Assay (TGA), it does not inhibit human thrombin generation, does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to the 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 the isotype control, when determined by the area under the thrombin generation curve, it does not decrease endogenous thrombin production capacity (ETP) compared to the isotype control, when determined by the Thrombin Generation Assay (TGA), it allows human thrombin generation, compared to the isotype control An isolated human antibody from the prior invention that maintains the thrombin peak (peak IIa) on the thrombin generation curve, maintains the time from the start of the assay to the thrombin peak (tt peak) on the thrombin generation curve compared to an isotype control, protects endogenous thrombin production ability (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 separate from the human TF binding site to which human FX binds, does not interfere with TF:FVIIa's ability to convert FX to FXa, and does not compete with FVIIa for binding to human TF. [Invention 1021] An isolated human antibody from the prior art that inhibits FVIIa-dependent TF signaling. [Invention 1022] An isolated human antibody from any of the prior art inventions, wherein, 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 a variant TF containing 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 the TF of the sequence shown in SEQ ID NO:810. [Invention 1023] An isolated human antibody of the present invention 1022, wherein the mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is K149N. [Invention 1024] An isolated human antibody from the prior art, wherein, 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 a variant TF containing 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. [Invention 1025] An isolated human antibody of the present invention 1024, wherein the mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is K68N. [Invention 1026] An isolated human antibody from any of the prior art, wherein, 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 a variant TF containing 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. [Invention 1027] An isolated human antibody of the present invention 1026, wherein the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 are N171H and T197K. [Invention 1028] An isolated human antibody from the prior art, determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, wherein 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 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1029] An isolated human antibody from the prior art, determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, wherein the binding between the isolated antibody and the extracellular domain of a human TF in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1030] An isolated human antibody from the prior art, determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, wherein the binding between the isolated antibody and the extracellular domain of a 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 a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1031] An isolated human antibody from the prior art, determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, wherein the binding between the isolated antibody and the extracellular domain of a human TF in which amino acid residues 146-158 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 151-163 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1032] An isolated human antibody from any of the prior art, wherein, 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 a human TF in which amino acid residues 159-219 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-224 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1033] An isolated human antibody from the prior art, determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, wherein the binding between the isolated antibody and the extracellular domain of a human TF in which amino acid residues 159-189 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-194 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1034] An isolated human antibody from the prior art, determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, wherein the binding between the isolated antibody and the extracellular domain of a human TF in which amino acid residues 159-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-179 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1035] An isolated human antibody from any of the prior art, wherein, 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 a human TF in which amino acid residues 167-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 172-179 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1036] An isolated human antibody from the prior art, determined by the median fluorescence intensity of the isolated antibody compared to an isotype control in a live cell staining assay, wherein the binding between the isolated antibody and the extracellular domain of a rat TF in which amino acid residues 141-194 of the sequence shown in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of a human TF in 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 in the sequence shown in SEQ ID NO:810. [Invention 1037] When 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 variant TF containing 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 variant TF containing 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 1-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 1-76 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 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 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 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 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 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 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. The binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146-158 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 151-163 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 the sequence shown in SEQ ID NO:810, and The binding between the isolated antibody and the extracellular domain of rat TF, in which amino acid residues 141-194 of the sequence shown in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of human TF shown in SEQ ID NO:810, is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF shown in SEQ ID NO:810. An isolated human antibody from any of the prior art inventions. [Invention 1038] The mutation at amino acid residue 149 of the sequence shown 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. Isolated human antibody according to Invention 1037. [Invention 1039] When 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 variant TF containing 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 variant TF containing 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 variant TF containing 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 1-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 1-76 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 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 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 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 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 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 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. The binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 146-158 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 151-163 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 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 159-219 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-224 of the extracellular domain of rat TF shown 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 shown in SEQ ID NO:810. The binding between the isolated antibody and the extracellular domain of human TF in which amino acid residues 159-189 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-194 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 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 159-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-179 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 isolated antibody and the extracellular domain of TF in 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 167-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 172-179 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 isolated antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and The binding between the isolated antibody and the extracellular domain of rat TF, in which amino acid residues 141-194 of the sequence shown in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of human TF shown in SEQ ID NO:810, is greater than 50% of the binding between the isolated antibody and the extracellular domain of TF shown in SEQ ID NO:810. An isolated human antibody from any of the prior art inventions. [Invention 1040] 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. Isolated human antibody according to Invention 1039. [Invention 1041] An isolated human antibody from any of the prior art inventions that binds to cynomolgus monkey TF. [Invention 1042] An isolated human antibody from any of the prior art inventions that binds to mouse TF. [Invention 1043] An isolated human antibody from any of the prior art inventions that binds to rabbit TF. [Invention 1044] An isolated human antibody from any of the prior art inventions that binds to porcine TF. [Invention 1045] An isolated human antibody from any of the prior art inventions that reduces lesion size in a porcine choroidal angiogenesis (CNV) model. [Invention 1046] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production, and (b) When 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 variant TF containing 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. An isolated human antibody from any of the prior art inventions. [Invention 1047] An isolated human antibody of the present invention 1046, wherein the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 are N171H and T197K. [Invention 1048] (a) When determined by the thrombin generation assay (TGA), it is permissible to human thrombin generation, and (b) When 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 variant TF containing 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. An isolated human antibody from any of the prior art inventions. [Invention 1049] An isolated human antibody of the present invention 1048, wherein the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 are N171H and T197K. [Invention 1050] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing 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, and (c) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing 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. An isolated human antibody from any of the prior art inventions. [Invention 1051] The mutation at amino acid residue 149 of the sequence shown 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. Isolated human antibody of the present invention 1050. [Invention 1052] (a) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (b) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing 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, and (c) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing 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. An isolated human antibody from any of the prior art inventions. [Invention 1053] The mutation at amino acid residue 149 of the sequence shown 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. Isolated human antibody according to Invention 1052. [Invention 1054] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) Binds to cynomolgus macaque TF, (c) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing 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, and (d) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing 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. An isolated human antibody from any of the prior art inventions. [Invention 1055] The mutation at amino acid residue 149 of the sequence shown 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. Isolated human antibody according to Invention 1054. [Invention 1056] (a) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (b) Binds to cynomolgus macaque TF, (c) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing 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, and (d) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing 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. An isolated human antibody from any of the prior art inventions. [Invention 1057] The mutation at amino acid residue 149 of the sequence shown 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. Isolated human antibody according to Invention 1056. [Invention 1058] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (c) Human TF binds to a human TF binding site separate 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) Inhibit FVIIa-dependent TF signaling, (g) Binds to cynomolgus macaque TF, (h) Binds to mouse TF, (i) Bind to rabbit TF, An isolated human antibody from any of the prior art inventions. [Invention 1059] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) When determined by the area under the thrombin production curve, it does not reduce endogenous thrombin production capacity (ETP) compared to isotype controls. (c) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (d) When determined by the area under the thrombin production curve, compared to isotype controls, protect endogenous thrombin production capacity (ETP), (e) Human TF binds to a human TF binding site separate from the human TF binding site to which human FX binds, (f)TF:FVIIa does not interfere with the ability 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 macaque TF, (j) Binds to mouse TF, (k) Binds to rabbit TF, An isolated human antibody from any of the prior art inventions. [Invention 1060] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) Compared to isotype controls, the thrombin peak (peak IIa) on the thrombin generation curve is not reduced. (c) Compared to isotype controls, the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) was not increased. (d) When determined by the area under the thrombin production curve, compared to isotype controls, without reducing endogenous thrombin production capacity (ETP), (e) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (f) Compared to isotype controls, maintain the thrombin peak (peak IIa) on the thrombin generation curve. (g) Compared to isotype controls, maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak), (h) When determined by the area under the thrombin production curve, compared to isotype controls, the endogenous thrombin production capacity (ETP) is protected. (i) Human TF binds to a human TF binding site separate from the human TF binding site to which human FX binds, (j)TF:FVIIa does not interfere with the ability 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 macaque TF, (n) Binds to mouse TF, and (o) Bind to rabbit TF, An isolated human antibody from any of the prior art inventions. [Invention 1061] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (c) Human TF binds to a human TF binding site separate 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) Inhibit FVIIa-dependent TF signaling, (g) Binds to cynomolgus macaque TF, (h) Binds to mouse TF, (i) Combine with rabbit TF, (j) Binds to pig TF, and (k) Reduce lesion size in a porcine choroidal angiogenesis (CNV) model. An isolated human antibody from any of the prior art inventions. [Invention 1062] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) When determined by the area under the thrombin production curve, it does not reduce endogenous thrombin production capacity (ETP) compared to isotype controls. (c) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (d) When determined by the area under the thrombin production curve, compared to isotype controls, protect endogenous thrombin production capacity (ETP), (e) Human TF binds to a human TF binding site separate from the human TF binding site to which human FX binds, (f)TF:FVIIa does not interfere with the ability 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 macaque TF, (j) Binds to mouse TF, (k) Bind to rabbit TF, (l) Binds to pig TF, and (m) Reduce lesion size in a porcine choroidal angiogenesis (CNV) model. An isolated human antibody from any of the prior art inventions. [Invention 1063] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) Compared to isotype controls, the thrombin peak (peak IIa) on the thrombin generation curve is not reduced. (c) Compared to isotype controls, the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) was not increased. (d) When determined by the area under the thrombin production curve, compared to isotype controls, without reducing endogenous thrombin production capacity (ETP), (e) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (f) Compared to isotype controls, maintain the thrombin peak (peak IIa) on the thrombin generation curve. (g) Compared to isotype controls, maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak), (h) When determined by the area under the thrombin production curve, compared to isotype controls, the endogenous thrombin production capacity (ETP) is protected. (i) Human TF binds to a human TF binding site separate from the human TF binding site to which human FX binds, (j)TF:FVIIa does not interfere with the ability 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 macaque TF, (n) Binds to mouse TF, (o) Combine with rabbit TF, (p) Binds to pig TF, and (q) Reduce lesion size in a porcine choroidal angiogenesis (CNV) model. An isolated human antibody from any of the prior art inventions. [Invention 1064] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) Compared to isotype controls, the thrombin peak (peak IIa) on the thrombin generation curve is not reduced. (c) Compared to isotype controls, the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) was not increased. (d) When determined by the area under the thrombin production curve, compared to isotype controls, without reducing endogenous thrombin production capacity (ETP), (e) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (f) Compared to isotype controls, maintain the thrombin peak (peak IIa) on the thrombin generation curve. (g) Compared to isotype controls, maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak), (h) When determined by the area under the thrombin production curve, compared to isotype controls, the endogenous thrombin production capacity (ETP) is protected. (i) Human TF binds to a human TF binding site separate from the human TF binding site to which human FX binds, (j)TF:FVIIa does not interfere with the ability 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 macaque TF, (n) Binds to mouse TF, (o) Combine with rabbit TF, (p) Binds to pig TF, (q) Reduce lesion size in a porcine choroidal angiogenesis (CNV) model, (r) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of variant TF containing 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. (s) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of variant TF containing 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. (t) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of variant TF containing 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. (u) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 1-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 1-76 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 the sequence shown in SEQ ID NO:810. (v) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 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 the sequence shown in SEQ ID NO:810. (w) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 94-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF 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. (x) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 146-158 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 151-163 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 the sequence shown in SEQ ID NO:810. (y) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 159-219 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-224 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 the sequence shown in SEQ ID NO:810. (z) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 159-189 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-194 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 the sequence shown in SEQ ID NO:810. (aa) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 159-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-179 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 isolated antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810. (bb) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 167-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 172-179 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 isolated antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and (cc) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, 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 with amino acid residues 136-189 of the extracellular domain of human TF in 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 in the sequence shown in SEQ ID NO:810. An isolated human antibody from any of the prior art inventions. [Invention 1065] (a) When determined by thrombin production assay (TGA), it does not inhibit human thrombin production. (b) Compared to isotype controls, the thrombin peak (peak IIa) on the thrombin generation curve is not reduced. (c) Compared to isotype controls, the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) was not increased. (d) When determined by the area under the thrombin production curve, compared to isotype controls, without reducing endogenous thrombin production capacity (ETP), (e) When determined by thrombin generation assay (TGA), human thrombin generation is permitted, (f) Compared to isotype controls, maintain the thrombin peak (peak IIa) on the thrombin generation curve. (g) Compared to isotype controls, maintain the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak), (h) When determined by the area under the thrombin production curve, compared to isotype controls, the endogenous thrombin production capacity (ETP) is protected. (i) Human TF binds to a human TF binding site separate from the human TF binding site to which human FX binds, (j)TF:FVIIa does not interfere with the ability 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 macaque TF, (n) Binds to mouse TF, (o) Combine with rabbit TF, (p) Binds to pig TF, (q) Reduce lesion size in a porcine choroidal angiogenesis (CNV) model, (r) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of variant TF containing the K149N mutation in 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 in the sequence shown in SEQ ID NO:810. (s) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of variant TF containing the K68N mutation in 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 in the sequence shown in SEQ ID NO:810. (t) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, the binding between the isolated antibody and the extracellular domain of variant TF containing the sequence mutations N171H and T197K shown in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF shown in SEQ ID NO:810. (u) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 1-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 1-76 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 the sequence shown in SEQ ID NO:810. (v) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 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 the sequence shown in SEQ ID NO:810. (w) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 94-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF 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. (x) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 146-158 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 151-163 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 the sequence shown in SEQ ID NO:810. (y) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 159-219 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-224 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 the sequence shown in SEQ ID NO:810. (z) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 159-189 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-194 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 the sequence shown in SEQ ID NO:810. (aa) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 159-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-179 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 isolated antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810. (bb) When determined by the median fluorescence intensity of the isolated antibody compared to the 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 167-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 172-179 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 isolated antibody and the extracellular domain of TF in the sequence shown in SEQ ID NO:810, and (cc) When determined by the median fluorescence intensity of the isolated antibody compared to the isotype control in a live cell staining assay, 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 with amino acid residues 136-189 of the extracellular domain of human TF in 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 in the sequence shown in SEQ ID NO:810. An isolated human antibody from any of the prior art inventions. [Invention 1066] An isolated human antibody from the prior invention that competes with the antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, 25G9, 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea for binding to human TF. [Invention 1067] An isolated human antibody of the present invention 1064 that competes with antibodies designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9 for binding to human TF. [Invention 1068] An isolated human antibody of Invention 1064 that competes with antibodies designated as 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea for binding to human TF. [Invention 1069] An isolated human antibody from the prior art that binds to the same human TF epitope, to which the antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, 25G9, 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea binds. [Invention 1070] Isolated human antibodies of the present invention 1069 that bind to the same human TF epitope to which antibodies designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9 bind. [Invention 1071] Isolated human antibodies of Invention 1069 that bind to the same human TF epitope to which antibodies designated as 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea bind. [Invention 1072] An isolated human antibody from any of the prior art inventions, comprising all three heavy chain complementation 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. [Invention 1073] Isolated human antibodies of the present invention 1072, wherein the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering. [Invention 1074] An isolated human antibody according to Invention 1072 or 1073, comprising all three heavy chain complementation determining regions (CDRs) and all three light chain CDRs from an antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9. [Invention 1075] An isolated human antibody according to Invention 1072 or 1073, comprising all three heavy chain complementation determining regions (CDRs) and all three light chain CDRs from an antibody designated as 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. [Invention 1076] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A. [Invention 1077] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A3. [Invention 1078] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A5. [Invention 1079] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A5-T. [Invention 1080] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25G. [Invention 1081] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25G1. [Invention 1082] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25G9. [Invention 1083] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43B. [Invention 1084] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43B1. [Invention 1085] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43B7. [Invention 1086] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43D. [Invention 1087] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43D7. [Invention 1088] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43D8. [Invention 1089] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43E. [Invention 1090] An isolated human antibody of the present invention 1072 or 1073, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43Ea. [Invention 1091] SEQ ID NO:113 V H Sequence and V of SEQ ID NO:114 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1092] SEQ ID NO:151 V H Sequence and SEQ ID NO:152 V L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1093] SEQ ID NO:189 V HSequence and SEQ ID NO:190 V L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1094] SEQ ID NO: 836 V H Sequence and V of SEQ ID NO:837 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1095] SEQ ID NO:227 V H Sequence and SEQ ID NO:228 V L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1096] SEQ ID NO:265 V H Sequence and V of SEQ ID NO:266 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1097] SEQ ID NO:303 V H Sequence and SEQ ID NO:304 V L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1098] SEQ ID NO:455 V H Sequence and V of SEQ ID NO:456 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1099] SEQ ID NO:493 V H Sequence and SEQ ID NO:494 V L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1100] SEQ ID NO: 531 V H Sequence and SEQ ID NO: 532 V L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1101] SEQ ID NO: 569 V H Sequence and SEQ ID NO: 570 V L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1102] SEQ ID NO: 607 V H Sequence and SEQ ID NO: 608 V L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1103] SEQ ID NO: 645 V H Sequence and V of SEQ ID NO:646 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1104] SEQ ID NO: 683 V H Sequence and V of SEQ ID NO:684 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1105] SEQ ID NO:721 V H Sequence and V of SEQ ID NO:722 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1106] Isolated human antibodies according to any of the Invention 1000 to 1073, comprising VH-CDR1 containing the sequence described in SEQ ID NO:779, VH-CDR2 containing the sequence described in SEQ ID NO:780, VH-CDR3 containing the sequence described in SEQ ID NO:781, VL-CDR1 containing the sequence described in SEQ ID NO:782, VL-CDR2 containing the sequence described in SEQ ID NO:783, and VL-CDR3 containing the sequence described in SEQ ID NO:784. [Invention 1107] Isolated human antibodies according to any of invention 1000 to 1073, comprising VH-CDR1 containing the sequence described in SEQ ID NO:872, VH-CDR2 containing the sequence described in SEQ ID NO:873, VH-CDR3 containing the sequence described in SEQ ID NO:874, VL-CDR1 containing the sequence described in SEQ ID NO:875, VL-CDR2 containing the sequence described in SEQ ID NO:876, and VL-CDR3 containing the sequence described in SEQ ID NO:877. [Invention 1108] Isolated human antibodies according to any of the Invention 1000 to 1073, comprising VH-CDR1 containing the sequence described in SEQ ID NO:878, VH-CDR2 containing the sequence described in SEQ ID NO:879, VH-CDR3 containing the sequence described in SEQ ID NO:880, VL-CDR1 containing the sequence described in SEQ ID NO:881, VL-CDR2 containing the sequence described in SEQ ID NO:882, and VL-CDR3 containing the sequence described in SEQ ID NO:883. [Invention 1109] Isolated human antibodies according to any of invention 1000 to 1073, comprising VH-CDR1 containing the sequence described in SEQ ID NO:797, VH-CDR2 containing the sequence described in SEQ ID NO:798, VH-CDR3 containing the sequence described in SEQ ID NO:799, VL-CDR1 containing the sequence described in SEQ ID NO:800, VL-CDR2 containing the sequence described in SEQ ID NO:801, and VL-CDR3 containing the sequence described in SEQ ID NO:802. [Invention 1110] SEQ ID NO:763 V H Sequence and V of SEQ ID NO:764 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1111] SEQ ID NO:868 V H Sequence and V of SEQ ID NO:869 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1112] SEQ ID NO: 870 V H Sequence and V of SEQ ID NO:871 L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1113] SEQ ID NO:769 V H Sequence and SEQ ID NO:770 V L An isolated human antibody comprising any of the sequences 1000 to 1073 of the present invention. [Invention 1114] An isolated human antibody from any of the prior art inventions, comprising an antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, 25G9, 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. [Invention 1115] Isolated human antibodies according to Invention 1114, comprising antibodies designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9. [Invention 1116] Isolated human antibodies according to Invention 1114, comprising antibodies designated as 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. [Invention 1117] An isolated human antibody from any of the prior art inventions, comprising an antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, 25G9, 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. [Invention 1118] Isolated human antibodies according to Invention 1117, comprising antibodies designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9. [Invention 1119] Isolated human antibodies according to Invention 1117, comprising antibodies designated as 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. [Invention 1120] Isolated antibodies containing all three heavy chain complementation determining regions (CDRs) and all three light chain CDRs from antibodies designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, 25G9, 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. [Invention 1121] An isolated antibody of the present invention 1120, which is human, humanized, or chimeric. [Invention 1122] Isolated antibodies of the present invention 1120 or 1121, wherein the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering. [Invention 1123] An isolated antibody according to any of the Invention 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A, 25A3, 25A5, 25A5-T, 25G, 25G1, or 25G9. [Invention 1124] An isolated antibody according to any of the inventions 1120-1122, containing all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A. [Invention 1125] An isolated antibody according to any of the inventions 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A3. [Invention 1126] An isolated antibody according to any of the inventions 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A5. [Invention 1127] An isolated antibody according to any of the inventions 1120 to 1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25A5-T. [Invention 1128] An isolated antibody according to any of the Invention 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25G. [Invention 1129] An isolated antibody according to any of the inventions 1120-1122, containing all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25G1. [Invention 1130] An isolated antibody according to any of the inventions 1120-1122, containing all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 25G9. [Invention 1131] An isolated antibody according to any of Invention 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43B, 43B1, 43B7, 43D, 43D7, 43D8, 43E, or 43Ea. [Invention 1132] An isolated antibody according to any of the inventions 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43B. [Invention 1133] An isolated antibody according to any of the inventions 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43B1. [Invention 1134] An isolated antibody according to any of the inventions 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43B7. [Invention 1135] An isolated antibody according to any of the inventions 1120-1122, containing all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43D. [Invention 1136] An isolated antibody according to any of the inventions 1120-1122, containing all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43D7. [Invention 1137] An isolated antibody according to any of the inventions 1120-1122, containing all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43D8. [Invention 1138] An isolated antibody according to any of the inventions 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 43E. [Invention 1139] An isolated antibody according to any of the inventions 1120-1122, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody denoted as 43Ea. [Invention 1140] SEQ ID NO:113 V H Sequence and V of SEQ ID NO:114 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1141] SEQ ID NO:151 V H Sequence and SEQ ID NO:152 V L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1142] SEQ ID NO:189 V H Sequence and SEQ ID NO:190 V L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1143] SEQ ID NO: 836 V H Sequence and V of SEQ ID NO:837 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1144] SEQ ID NO:227 V H Sequence and SEQ ID NO:228 V L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1145] SEQ ID NO:265 V H Sequence and V of SEQ ID NO:266 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1146] SEQ ID NO:303 V H Sequence and SEQ ID NO:304 V L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1147] SEQ ID NO:455 V H Sequence and V of SEQ ID NO:456 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1148] SEQ ID NO:493 V H Sequence and SEQ ID NO:494 V L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1149] SEQ ID NO: 531 V H Sequence and SEQ ID NO: 532 V L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1150] SEQ ID NO: 569 V H Sequence and SEQ ID NO: 570 V L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1151] SEQ ID NO: 607 V H Sequence and SEQ ID NO: 608 V L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1152] SEQ ID NO: 645 V H Sequence and V of SEQ ID NO:646 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1153] SEQ ID NO: 683 V H Sequence and V of SEQ ID NO:684 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1154] SEQ ID NO:721 V H Sequence and V of SEQ ID NO:722 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1155] An isolated antibody according to any of the inventions 1120 to 1122, comprising VH-CDR1 containing the sequence described in SEQ ID NO:779, VH-CDR2 containing the sequence described in SEQ ID NO:780, VH-CDR3 containing the sequence described in SEQ ID NO:781, VL-CDR1 containing the sequence described in SEQ ID NO:782, VL-CDR2 containing the sequence described in SEQ ID NO:783, and VL-CDR3 containing the sequence described in SEQ ID NO:784. [Invention 1156] An isolated antibody according to any of the inventions 1120 to 1122, comprising VH-CDR1 containing the sequence described in SEQ ID NO:872, VH-CDR2 containing the sequence described in SEQ ID NO:873, VH-CDR3 containing the sequence described in SEQ ID NO:874, VL-CDR1 containing the sequence described in SEQ ID NO:875, VL-CDR2 containing the sequence described in SEQ ID NO:876, and VL-CDR3 containing the sequence described in SEQ ID NO:877. [Invention 1157] An isolated antibody according to any of the inventions 1120 to 1122, comprising VH-CDR1 containing the sequence described in SEQ ID NO:878, VH-CDR2 containing the sequence described in SEQ ID NO:879, VH-CDR3 containing the sequence described in SEQ ID NO:880, VL-CDR1 containing the sequence described in SEQ ID NO:881, VL-CDR2 containing the sequence described in SEQ ID NO:882, and VL-CDR3 containing the sequence described in SEQ ID NO:883. [Invention 1158] An isolated antibody according to any of the inventions 1120 to 1122, comprising VH-CDR1 containing the sequence described in SEQ ID NO:797, VH-CDR2 containing the sequence described in SEQ ID NO:798, VH-CDR3 containing the sequence described in SEQ ID NO:799, VL-CDR1 containing the sequence described in SEQ ID NO:800, VL-CDR2 containing the sequence described in SEQ ID NO:801, and VL-CDR3 containing the sequence described in SEQ ID NO:802. [Invention 1159] SEQ ID NO:763 V H Sequence and V of SEQ ID NO:764 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1160] SEQ ID NO:868 V H Sequence and V of SEQ ID NO:869 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1161] SEQ ID NO: 870 V H Sequence and V of SEQ ID NO:871 L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1162] SEQ ID NO:769 V H Sequence and SEQ ID NO:770 V L An isolated antibody according to any of invention 1120 to 1122, containing the sequence. [Invention 1163] An isolated antibody according to any of the Invention 1120 to 1162, comprising an antibody denoted as 25A, an antibody denoted as 25A3, an antibody denoted as 25A5, an antibody denoted as 25A5-T, an antibody denoted as 25G, an antibody denoted as 25G1, an antibody denoted as 25G9, an antibody denoted as 43B, an antibody denoted as 43B1, an antibody denoted as 43B7, an antibody denoted as 43D, an antibody denoted as 43D7, an antibody denoted as 43D8, an antibody denoted as 43E, or an antibody denoted as 43Ea. [Invention 1164] An isolated antibody according to any of Invention 1163, comprising an antibody denoted as 25A, an antibody denoted as 25A3, an antibody denoted as 25A5, an antibody denoted as 25A5-T, an antibody denoted as 25G, an antibody denoted as 25G1, or an antibody denoted as 25G9. [Invention 1165] An isolated antibody according to any of Invention 1163, comprising an antibody denoted as 43B, an antibody denoted as 43B1, an antibody denoted as 43B7, an antibody denoted as 43D, an antibody denoted as 43D7, an antibody denoted as 43D8, an antibody denoted as 43E, or an antibody denoted as 43Ea. [Invention 1166] An isolated antibody according to any of the Invention 1120 to 1163, comprising an antibody denoted as 25A, an antibody denoted as 25A3, an antibody denoted as 25A5, an antibody denoted as 25A5-T, an antibody denoted as 25G, an antibody denoted as 25G1, an antibody denoted as 25G9, an antibody denoted as 43B, an antibody denoted as 43B1, an antibody denoted as 43B7, an antibody denoted as 43D, an antibody denoted as 43D7, an antibody denoted as 43D8, an antibody denoted as 43E, or an antibody denoted as 43Ea. [Invention 1167] An isolated antibody according to any of Invention 1166, comprising an antibody denoted as 25A, an antibody denoted as 25A3, an antibody denoted as 25A5, an antibody denoted as 25A5-T, an antibody denoted as 25G, an antibody denoted as 25G1, or an antibody denoted as 25G9. [Invention 1168] An isolated antibody according to any of Invention 1166, comprising an antibody denoted as 43B, an antibody denoted as 43B1, an antibody denoted as 43B7, an antibody denoted as 43D, an antibody denoted as 43D7, an antibody denoted as 43D8, an antibody denoted as 43E, or an antibody denoted as 43Ea. [Invention 1169] Isolated antibodies that compete with antibodies designated as 1F, 1G, 29D, 29E, 39A, or 54E for binding to human TF. [Invention 1170] An isolated antibody of the present invention 1169, which is human, humanized, or chimeric. [Invention 1171] An isolated antibody of Invention 1169 or 1170 that inhibits FVIIa-dependent TF signaling. [Invention 1172] An isolated antibody according to any of the inventions 1169-1171 that binds to cynomolgus monkey TF. [Invention 1173] An isolated antibody according to any of the Invention 1169-1172, wherein, 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 a 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 a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1174] An isolated antibody according to any of the Invention 1169-1172, wherein, 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 a 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 a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1175] An isolated antibody according to any of the Invention 1169-1172, wherein, 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 a human TF in which amino acid residues 78-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77-112 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1176] An isolated antibody according to any of the Invention 1169-1172, wherein, 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 a human TF in which amino acid residues 78-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 77-85 and 92-112 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1177] When determined by the median fluorescence intensity of the isolated antibody compared to the 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 94-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF 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, 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 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. An isolated antibody according to any of invention 1169 to 1172. [Invention 1178] When determined by the median fluorescence intensity of the isolated antibody compared to the 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 94-107 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 99-112 of the extracellular domain of rat TF 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. 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 with amino acid residues 77-112 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, 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 with amino acid residues 77-85 and 92-112 of the extracellular domain of rat TF 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. An isolated antibody according to any of invention 1169 to 1172. [Invention 1179] An isolated antibody according to any of Invention 1169-1178, comprising all three heavy chain complementarity determining regions (CDRs) and all three light chain CDRs from an antibody designated as 1F, 1G, 29D, 29E, 39A, 43Ea, or 54E. [Invention 1180] The isolated antibody of Invention 1179, wherein the three heavy chain CDRs and the three light chain CDRs are determined using Kabat, Chothia, AbM, Contact, or IMGT numbering. [Invention 1181] An isolated antibody of Invention 1179 or 1180, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 1F. [Invention 1182] An isolated antibody of Invention 1179 or 1180, containing all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 1G. [Invention 1183] An isolated antibody of Invention 1179 or 1180, containing all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 29D. [Invention 1184] An isolated antibody of Invention 1179 or 1180, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 29E. [Invention 1185] An isolated antibody of Invention 1179 or 1180, containing all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 39A. [Invention 1186] An isolated antibody of Invention 1179 or 1180, comprising all three heavy chain CDRs and all three light chain CDRs from an antibody designated as 54E. [Invention 1187] SEQ ID NO:37 V H Sequence and V of SEQ ID NO:38 L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1188] SEQ ID NO:75 V H Sequence and V of SEQ ID NO:76 L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1189] SEQ ID NO:341 V H Sequence and SEQ ID NO:342 V L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1190] SEQ ID NO:379 V HSequence and SEQ ID NO:380 V L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1191] SEQ ID NO:417 V H Sequence and SEQ ID NO:418 V L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1192] SEQ ID NO:759 V H Sequence and SEQ ID NO:760 V L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1193] An isolated antibody according to any of the Invention 1169 to 1180, comprising VH-CDR1 containing the sequence described in SEQ ID NO:773, VH-CDR2 containing the sequence described in SEQ ID NO:774, VH-CDR3 containing the sequence described in SEQ ID NO:775, VL-CDR1 containing the sequence described in SEQ ID NO:776, VL-CDR2 containing the sequence described in SEQ ID NO:777, and VL-CDR3 containing the sequence described in SEQ ID NO:778. [Invention 1194] An isolated antibody according to any of the Invention 1169 to 1180, comprising VH-CDR1 containing the sequence described in SEQ ID NO:785, VH-CDR2 containing the sequence described in SEQ ID NO:786, VH-CDR3 containing the sequence described in SEQ ID NO:787, VL-CDR1 containing the sequence described in SEQ ID NO:788, VL-CDR2 containing the sequence described in SEQ ID NO:789, and VL-CDR3 containing the sequence described in SEQ ID NO:790. [Invention 1195] An isolated antibody according to any of the Invention 1169 to 1180, comprising VH-CDR1 containing the sequence described in SEQ ID NO:791, VH-CDR2 containing the sequence described in SEQ ID NO:792, VH-CDR3 containing the sequence described in SEQ ID NO:793, VL-CDR1 containing the sequence described in SEQ ID NO:794, VL-CDR2 containing the sequence described in SEQ ID NO:795, and VL-CDR3 containing the sequence described in SEQ ID NO:796. [Invention 1196] An isolated antibody according to any of Invention 1169 to 1180, comprising VH-CDR1 containing the sequence described in SEQ ID NO:803, VH-CDR2 containing the sequence described in SEQ ID NO:804, VH-CDR3 containing the sequence described in SEQ ID NO:805, VL-CDR1 containing the sequence described in SEQ ID NO:806, VL-CDR2 containing the sequence described in SEQ ID NO:807, and VL-CDR3 containing the sequence described in SEQ ID NO:808. [Invention 1197] SEQ ID NO:761 V H Sequence and V of SEQ ID NO:762 L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1198] SEQ ID NO:765 V H Sequence and V of SEQ ID NO:766 L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1199] SEQ ID NO:767 V H Sequence and V of SEQ ID NO:768 L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1200] SEQ ID NO:771 V H Sequence and V of SEQ ID NO:772 L An isolated antibody comprising any of the present invention 1169 to 1180, including the sequence. [Invention 1201] An isolated antibody according to any of Invention 1169 to 1200, comprising an antibody denoted as 1F, an antibody denoted as 1G, an antibody denoted as 29D, an antibody denoted as 29E, an antibody denoted as 39A, or an antibody denoted as 54E. [Invention 1202] An isolated antibody according to any of Invention 1169 to 1201, comprising an antibody denoted as 1F, an antibody denoted as 1G, an antibody denoted as 29D, an antibody denoted as 29E, an antibody denoted as 39A, or an antibody denoted as 54E. [Invention 1203] Isolated antibodies comprising VH-CDR1 containing the sequence described in SEQ ID NO:773, VH-CDR2 containing the sequence described in SEQ ID NO:774, VH-CDR3 containing the sequence described in SEQ ID NO:775, VL-CDR1 containing the sequence described in SEQ ID NO:776, VL-CDR2 containing the sequence described in SEQ ID NO:777, and VL-CDR3 containing the sequence described in SEQ ID NO:778. [Invention 1204] Isolated antibodies comprising VH-CDR1 containing the sequence described in SEQ ID NO:779, VH-CDR2 containing the sequence described in SEQ ID NO:780, VH-CDR3 containing the sequence described in SEQ ID NO:781, VL-CDR1 containing the sequence described in SEQ ID NO:782, VL-CDR2 containing the sequence described in SEQ ID NO:783, and VL-CDR3 containing the sequence described in SEQ ID NO:784. [Invention 1205] Isolated antibodies comprising VH-CDR1 containing the sequence described in SEQ ID NO:785, VH-CDR2 containing the sequence described in SEQ ID NO:786, VH-CDR3 containing the sequence described in SEQ ID NO:787, VL-CDR1 containing the sequence described in SEQ ID NO:788, VL-CDR2 containing the sequence described in SEQ ID NO:789, and VL-CDR3 containing the sequence described in SEQ ID NO:790. [Invention 1206] Isolated antibodies comprising VH-CDR1 containing the sequence described in SEQ ID NO:791, VH-CDR2 containing the sequence described in SEQ ID NO:792, VH-CDR3 containing the sequence described in SEQ ID NO:793, VL-CDR1 containing the sequence described in SEQ ID NO:794, VL-CDR2 containing the sequence described in SEQ ID NO:795, and VL-CDR3 containing the sequence described in SEQ ID NO:796. [Invention 1207] Isolated antibodies comprising VH-CDR1 containing the sequence described in SEQ ID NO:797, VH-CDR2 containing the sequence described in SEQ ID NO:798, VH-CDR3 containing the sequence described in SEQ ID NO:799, VL-CDR1 containing the sequence described in SEQ ID NO:800, VL-CDR2 containing the sequence described in SEQ ID NO:801, and VL-CDR3 containing the sequence described in SEQ ID NO:802. [Invention 1208] Isolated antibodies comprising VH-CDR1 containing the sequence described in SEQ ID NO:803, VH-CDR2 containing the sequence described in SEQ ID NO:804, VH-CDR3 containing the sequence described in SEQ ID NO:805, VL-CDR1 containing the sequence described in SEQ ID NO:806, VL-CDR2 containing the sequence described in SEQ ID NO:807, and VL-CDR3 containing the sequence described in SEQ ID NO:808. [Invention 1209] Isolated antibodies comprising VH-CDR1 containing the sequence described in SEQ ID NO:872, VH-CDR2 containing the sequence described in SEQ ID NO:873, VH-CDR3 containing the sequence described in SEQ ID NO:874, VL-CDR1 containing the sequence described in SEQ ID NO:875, VL-CDR2 containing the sequence described in SEQ ID NO:876, and VL-CDR3 containing the sequence described in SEQ ID NO:877. [Invention 1210] Isolated antibodies comprising VH-CDR1 containing the sequence described in SEQ ID NO:878, VH-CDR2 containing the sequence described in SEQ ID NO:879, VH-CDR3 containing the sequence described in SEQ ID NO:880, VL-CDR1 containing the sequence described in SEQ ID NO:881, VL-CDR2 containing the sequence described in SEQ ID NO:882, and VL-CDR3 containing the sequence described in SEQ ID NO:883. [Invention 1211] When measured by Octet QK384 or Biacore assay, K levels 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. D An isolated antibody from any of the prior art inventions that binds to human TF. [Invention 1212] A monoclonal antibody, isolated from any of the prior art inventions. [Invention 1213] A multispecific, isolated antibody from any of the prior art inventions. [Invention 1214] An isolated antibody from the prior art, which is Fab, Fab', F(ab')2, Fv, scFv, (scFv)2, a single-chain antibody molecule, a bivariate domain antibody, a single variable domain antibody, a linear antibody, or a V-domain antibody. [Invention 1215] An isolated antibody from any of the prior art inventions, wherein the antibody includes a scaffold, and optionally the scaffold is Fc, or optionally human Fc. [Invention 1216] An isolated antibody of the present invention 1215 comprising a heavy chain constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. [Invention 1217] An isolated antibody according to the present invention 1216, comprising a heavy chain constant region of the IgG class and a subclass selected from IgG1, IgG2, IgG3, and IgG4. [Invention 1218] An isolated antibody of the present invention 1217, containing the heavy chain constant region of IgG1. [Invention 1219] An isolated antibody according to any of the Invention 1215 to 1218, wherein the Fc comprises one or more modifications, and the one or more modifications result in an increased half-life, increased antibody-dependent cytotoxicity (ADCC), increased antibody-dependent cell phagocytosis (ADCP), increased complement-dependent cytotoxicity (CDC), or decreased effector function compared to the Fc without the one or more modifications. [Invention 1220] An isolated antibody that competes with any of the prior art antibodies for binding to human TF. [Invention 1221] An isolated antibody that binds to the epitope of the human TF to which any antibody from the prior art of the present invention binds. [Invention 1222] Any antibody from the prior art, its V H That V L an isolated polynucleotide or set of polynucleotides encoding its light chain, its heavy chain, or its antigen-binding moiety. [Invention 1223] A vector or set of vectors comprising a polynucleotide or set of polynucleotides according to Invention 1222. [Invention 1224] A host cell comprising a polynucleotide or set of polynucleotides according to Invention 1222, or a vector or set of vectors according to Invention 1223. [Invention 1225] A method for producing an antibody, comprising the steps of expressing the antibody using host cells of the present invention 1224, and isolating the expressed antibody. [Invention 1226] A pharmaceutical composition comprising an antibody according to any of invention 1000 to 1221 and a pharmaceutically acceptable excipient. [Invention 1227] A method for treating or preventing a disease or condition in a subject that requires such treatment, comprising the step of administering to the subject an effective amount of any antibody according to Invention 1000 to 1221 or a pharmaceutical composition according to Invention 1226. [Invention 1228] The method of the present invention 1227, wherein the disease or condition is cancer. [Invention 1229] The method of the present invention 1228, wherein the cancer is head and neck cancer. [Invention 1230] The method of the present invention 1228, wherein the cancer is ovarian cancer. [Invention 1231] The method of the present invention 1228, wherein the cancer is gastric cancer. [Invention 1232] The method of the present invention 1228, wherein the cancer is esophageal cancer. [Invention 1233] The method of the present invention 1228, wherein the cancer is cervical cancer. [Invention 1234] The method of the present invention 1228, wherein the cancer is prostate cancer. [Invention 1235] The method of the present invention 1228, wherein the cancer is pancreatic cancer. [Invention 1236] The method of the present invention 1228, wherein the cancer is a triple-negative breast cancer that is estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-). [Invention 1237] The method of the present invention 1228, wherein the cancer is glioblastoma. [Invention 1238] The method of the present invention 1228, wherein the cancer is lung cancer. [Invention 1239] The method of the present invention 1228, wherein the cancer is bladder cancer. [Invention 1240] The method of the present invention 1228, wherein the cancer is melanoma. [Invention 1241] The method of the present invention 1228, wherein the cancer is kidney cancer. [Invention 1242] The method of the present invention 1227, wherein the aforementioned disease or condition is accompanied by angiogenesis. [Invention 1243] The method of the present invention 1242, wherein the disease or condition accompanied by neovascularization is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. [Invention 1244] The method of the present invention 1227, wherein the aforementioned disease or condition is accompanied by vascular inflammation. [Invention 1245] Any method of the present invention 1227 to 1244, further comprising the step of administering one or more additional therapeutic agents to the subject. [Invention 1246] The method of the present invention 1245, wherein the additional therapeutic agent is formulated in the same pharmaceutical composition as the antibody. [Invention 1247] The method of the present invention 1245, wherein the additional therapeutic agent is formulated in a pharmaceutical composition different from the antibody. [Invention 1248] The method of the present invention 1245, wherein the additional therapeutic agent is administered before the administration of the antibody. [Invention 1249] The method of the present invention 1245, wherein the additional therapeutic agent is administered after the administration of the antibody. [Invention 1250] The method of the present invention 1245, wherein the additional therapeutic agent is administered simultaneously with the antibody. [Invention 1251] A method for detecting TF in a subject having or suspected to have a disease or condition, 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 an antibody according to any of the present invention 1000 to 1221. [Invention 1252] The method of the present invention 1251, wherein the disease or condition is cancer. [Invention 1253] The method of the present invention 1252, wherein the cancer is head and neck cancer. [Invention 1254] The method of the present invention 1252, wherein the cancer is ovarian cancer. [Invention 1255] The method of the present invention 1252, wherein the cancer is gastric cancer. [Invention 1256] The method of the present invention 1252, wherein the cancer is esophageal cancer. [Invention 1257] The method of the present invention 1252, wherein the cancer is cervical cancer. [Invention 1258] The method of the present invention 1252, wherein the cancer is prostate cancer. [Invention 1259] The method of the present invention 1252, wherein the cancer is pancreatic cancer. [Invention 1260] The method of the present invention 1252, wherein the cancer is a triple-negative breast cancer that is estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-). [Invention 1261] The method of the present invention 1252, wherein the cancer is glioblastoma. [Invention 1262] The method of the present invention 1252, wherein the cancer is lung cancer. [Invention 1263] The method of the present invention 1252, wherein the cancer is bladder cancer. [Invention 1264] The method of the present invention 1252, wherein the cancer is melanoma. [Invention 1265] The method of the present invention 1252, wherein the cancer is kidney cancer. [Invention 1266] The method of the present invention 1251, wherein the aforementioned disease or condition is accompanied by angiogenesis. [Invention 1267] The method of the present invention 1266, wherein the disease or condition accompanied by angiogenesis is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. [Invention 1268] The method of the present invention 1251, wherein the aforementioned disease or condition is accompanied by vascular inflammation. [Invention 1269] A method for detecting TF in a subject having or suspected to have a disease or condition, comprising the steps of (a) administering an antibody according to any of the present invention 1000 to 1221 to the subject, and (b) detecting the presence or level of TF in the subject. [Invention 1270] The method of the present invention 1269, wherein the disease or condition is cancer. [Invention 1271] The method of the present invention 1270, wherein the cancer is head and neck cancer. [Invention 1272] The method of the present invention 1270, wherein the cancer is ovarian cancer. [Invention 1273] The method of the present invention 1270, wherein the cancer is gastric cancer. [Invention 1274] The method of the present invention 1270, wherein the cancer is esophageal cancer. [Invention 1275] The method of the present invention 1270, wherein the cancer is cervical cancer. [Invention 1276] The method of the present invention 1270, wherein the cancer is prostate cancer. [Invention 1277] The method of the present invention 1270, wherein the cancer is pancreatic cancer. [Invention 1278] The method of the present invention 1270, wherein the cancer is a triple-negative breast cancer that is estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-). [Invention 1279] The method of the present invention 1270, wherein the cancer is glioblastoma. [Invention 1280] The method of the present invention 1270, wherein the cancer is lung cancer. [Invention 1281] The method of the present invention 1270, wherein the cancer is bladder cancer. [Invention 1282] The method of the present invention 1270, wherein the cancer is melanoma. [Invention 1283] The method of the present invention 1270, wherein the cancer is kidney cancer. [Invention 1284] The method of the present invention 1269, wherein the aforementioned disease or condition is accompanied by angiogenesis. [Invention 1285] The method of the present invention 1284, wherein the disease or condition accompanied by angiogenesis is age-related macular degeneration (AMD), diabetic retinopathy, or cancer. [Invention 1286] The method of the present invention 1269, wherein the aforementioned disease or condition is accompanied by vascular inflammation. [Invention 1287] A kit comprising an antibody according to any of Invention 1000 to 1221 or a pharmaceutical composition according to 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 separate from the human TF binding site to which human FVIIa binds. [Invention 1289] (1) When the antibody is determined by the thrombin generation assay (TGA), SEQ ID NO: 821 V H Sequence and V of SEQ ID NO:822 L Compared to a reference antibody containing the sequence, it does not inhibit human thrombin production, and (2) When determined by the median fluorescence intensity of the antibody compared to the isotype control in a live cell staining assay, the binding between the antibody and the extracellular domain of variant TF containing 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 antibody-drug conjugate of the present invention 1288. [Invention 1290] An antibody-drug conjugate according to Invention 1288 or 1289, wherein the antibody comprises VH-CDR1 containing the sequence described in SEQ ID NO:779, VH-CDR2 containing the sequence described in SEQ ID NO:780, VH-CDR3 containing the sequence described in SEQ ID NO:781, VL-CDR1 containing the sequence described in SEQ ID NO:782, VL-CDR2 containing the sequence described in SEQ ID NO:783, and VL-CDR3 containing the sequence described in SEQ ID NO:784. [Invention 1291] An antibody-drug conjugate according to any of the present invention 1288 to 1290, wherein the antibody comprises VH-CDR1 containing the sequence described in SEQ ID NO:872, VH-CDR2 HI containing the sequence described in SEQ ID NO:873, VH-CDR3 containing the sequence described in SEQ ID NO:874, VL-CDR1 containing the sequence described in SEQ ID NO:875, VL-CDR2 containing the sequence described in SEQ ID NO:876, and VL-CDR3 containing the sequence described in SEQ ID NO:877. [Invention 1292] An antibody-drug conjugate according to any of the present invention 1288 to 1290, wherein the antibody comprises VH-CDR1 containing the sequence described in SEQ ID NO:878, VH-CDR2 containing the sequence described in SEQ ID NO:879, VH-CDR3 containing the sequence described in SEQ ID NO:880, VL-CDR1 containing the sequence described in SEQ ID NO:881, VL-CDR2 containing the sequence described in SEQ ID NO:882, and VL-CDR3 containing the sequence described in SEQ ID NO:883. [Invention 1293] When the aforementioned antibody is determined by thrombin generation assay (TGA), SEQ ID NO: 821 V H Sequence and V of SEQ ID NO:822 L The antibody-drug conjugate of the present invention 1288, which does not inhibit human thrombin production compared to a reference antibody containing the sequence. [Invention 1294] The antibody-drug conjugate of the present invention 1288, wherein the antibody does not inhibit human thrombin production as determined by a thrombin production assay (TGA). [Invention 1295] The antibody-drug conjugate of the present invention 1294, wherein the antibody does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to the isotype control. [Invention 1296] The antibody-drug conjugate of the present invention 1294 or 1295, wherein 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 the isotype control. [Invention 1297] An antibody-drug conjugate according to any of the present invention 1294 to 1296, wherein the antibody does not reduce endogenous thrombin production capacity (ETP) compared to an isotype control, as determined by the area under the thrombin production curve. [Invention 1298] An antibody-drug conjugate according to any of the present invention 1288-1297, wherein the antibody allows human thrombin production when determined by a thrombin production assay (TGA). [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. [Invention 1300] The antibody-drug conjugate of the present invention 1298 or 1299, wherein the antibody maintains the time from the start of the assay to the thrombin peak on the thrombin generation curve (tt peak) compared to the isotype control. [Invention 1301] An antibody-drug conjugate according to any of the present inventions 1298-1300, wherein the antibody protects endogenous thrombin production ability (ETP) compared to an isotype control, when the antibody is determined by the area under the thrombin production curve. [Invention 1302] An antibody-drug conjugate according to any of the present invention 1288 to 1301, wherein the antibody binds to human TF at a human TF binding site separate from the human TF binding site to which human FX binds. [Invention 1303] The antibody-drug conjugate according to any of the Invention 1288-1302, wherein the antibody does not interfere with the ability of TF:FVIIa to convert FX to FXa. [Invention 1304] An antibody-drug conjugate according to any of the present invention 1288 to 1303, wherein the antibody does not compete with human FVIIa for binding to human TF. [Invention 1305] An antibody-drug conjugate according to any of the present invention 1288 to 1304, wherein the antibody does not inhibit human thrombin production as determined by a thrombin production assay (TGA), permits human thrombin production as determined by a thrombin production assay (TGA), binds to human TF at a human TF binding site 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. [Invention 1306] An antibody-drug conjugate according to any of the Invention 1288-1305, wherein the antibody does not inhibit human thrombin production as determined by a thrombin production assay (TGA), does not reduce endogenous thrombin production capacity (ETP) compared to an isotype control as determined by the area under the thrombin production curve, allows human thrombin production as determined by a thrombin production assay (TGA), protects endogenous thrombin production capacity (ETP) compared to an isotype control as determined by the area under the thrombin production curve, binds to human TF at a human TF binding site 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. [Invention 1307] When the antibody is determined by a thrombin generation assay (TGA), it does not inhibit human thrombin generation, does not reduce the thrombin peak (peak IIa) on the thrombin generation curve compared to the 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 the isotype control, when determined by the area under the thrombin generation curve, it does not decrease endogenous thrombin production capacity (ETP) compared to the isotype control, when determined by a thrombin generation assay (TGA), it allows human thrombin generation, and compared to the isotype control, An antibody-drug conjugate according to any of the Invention 1288-1306, which maintains the thrombin peak (peak IIa) on the thrombin generation curve, 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 production capacity (ETP) compared to an isotype control, protects human TF at a human TF binding site 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. [Invention 1308] The antibody-drug conjugate according to any of the present invention 1288 to 1307, wherein the antibody inhibits FVIIa-dependent TF signaling. [Invention 1309] An antibody-drug conjugate according to any of the Invention 1288-1308, wherein, 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 a variant TF containing 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 the TF of the sequence shown in SEQ ID NO:810. [Invention 1310] The antibody-drug conjugate of the present invention 1309, wherein the mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is K149N. [Invention 1311] An antibody-drug conjugate according to any of the present inventions 1288 to 1310, wherein, 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 a variant TF containing 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. [Invention 1312] The antibody-drug conjugate of the present invention 1311, wherein the mutation at amino acid residue 68 of the sequence shown in SEQ ID NO:810 is K68N. [Invention 1313] An antibody-drug conjugate according to any of the Invention 1288-1312, wherein, 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 a variant TF containing 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. [Invention 1314] The antibody-drug conjugate of the present invention 1313, wherein the mutations at amino acid residues 171 and 197 of the sequence shown in SEQ ID NO:810 are N171H and T197K. [Invention 1315] An antibody-drug conjugate according to any of the Invention 1288-1314, wherein, 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 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 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1316] An antibody-drug conjugate according to any of the Invention 1288-1315, wherein, 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 a human TF in which amino acid residues 39-77 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 38-76 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1317] An antibody-drug conjugate according to any of the Invention 1288-1316, wherein, 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 a 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 a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1318] An antibody-drug conjugate according to any of the Invention 1288-1317, wherein, 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 a human TF in which amino acid residues 146-158 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 151-163 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1319] An antibody-drug conjugate according to any of the Invention 1288-1318, wherein, 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 a human TF in which amino acid residues 159-219 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-224 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1320] An antibody-drug conjugate according to any of the Invention 1288-1319, wherein, 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 a human TF in which amino acid residues 159-189 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-194 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1321] An antibody-drug conjugate according to any of the Invention 1288-1320, wherein, 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 a human TF in which amino acid residues 159-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 164-179 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1322] An antibody-drug conjugate according to any of the Invention 1288-1321, wherein, 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 a human TF in which amino acid residues 167-174 of the sequence shown in SEQ ID NO:810 are replaced with amino acid residues 172-179 of the extracellular domain of a 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 the TF in the sequence shown in SEQ ID NO:810. [Invention 1323] An antibody-drug conjugate according to any of the Invention 1288-1322, wherein, 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 a rat TF in which amino acid residues 141-194 of the sequence shown in SEQ ID NO:838 are replaced with amino acid residues 136-189 of the extracellular domain of a human TF in 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 in the sequence shown in SEQ ID NO:810. [Invention 1324] When determined by the median fluorescence intensity of the antibody compared to an isotype control in a live cell staining assay, The binding between th...

Claims

1. An antibody that binds to the extracellular domain of human tissue factor (TF), The aforementioned antibody VH-CDR1, VH-CDR2, and VH-CDR3 each contain the amino acid sequences of VH-CDR1, VH-CDR2, and VH-CDR3, respectively, which are represented by VH containing the amino acid sequence of SEQ ID NO:

151. VL-CDR1, VL-CDR2, and VL-CDR3 each contain the amino acid sequences of VL-CDR1, VL-CDR2, and VL-CDR3, respectively, as shown in the VL containing the amino acid sequence of SEQ ID NO:

152. Includes, The VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 are determined by the Kabat numbering scheme, Chothia numbering scheme, AbM numbering scheme, Contact numbering scheme, or IMGT numbering scheme. The antibody.

2. An antibody comprising VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 that binds to the extracellular domain of human TF, (i) VH-CDR1 contains the amino acid sequence of SEQ ID NO: 115, VH-CDR2 contains the amino acid sequence of SEQ ID NO: 116, VH-CDR3 contains the amino acid sequence of SEQ ID NO: 117, VL-CDR1 contains the amino acid sequence of SEQ ID NO: 118, VL-CDR2 contains the amino acid sequence of SEQ ID NO: 119, and VL-CDR3 contains the amino acid sequence of SEQ ID NO:

120. (ii) VH-CDR1 contains the amino acid sequence of SEQ ID NO: 121, VH-CDR2 contains the amino acid sequence of SEQ ID NO: 122, VH-CDR3 contains the amino acid sequence of SEQ ID NO: 123, VL-CDR1 contains the amino acid sequence of SEQ ID NO: 124, VL-CDR2 contains the amino acid sequence of SEQ ID NO: 125, and VL-CDR3 contains the amino acid sequence of SEQ ID NO:

126. (iii) VH-CDR1 contains the amino acid sequence of SEQ ID NO: 127, VH-CDR2 contains the amino acid sequence of SEQ ID NO: 128, VH-CDR3 contains the amino acid sequence of SEQ ID NO: 129, VL-CDR1 contains the amino acid sequence of SEQ ID NO: 130, VL-CDR2 contains the amino acid sequence of SEQ ID NO: 131, and VL-CDR3 contains the amino acid sequence of SEQ ID NO:

132. (iv) VH-CDR1 contains the amino acid sequence of SEQ ID NO: 133, VH-CDR2 contains the amino acid sequence of SEQ ID NO: 134, VH-CDR3 contains the amino acid sequence of SEQ ID NO: 135, VL-CDR1 contains the amino acid sequence of SEQ ID NO: 136, VL-CDR2 contains the amino acid sequence of SEQ ID NO: 137, and VL-CDR3 contains the amino acid sequence of SEQ ID NO:

138. (v) VH-CDR1 contains the amino acid sequence of SEQ ID NO: 139, VH-CDR2 contains the amino acid sequence of SEQ ID NO: 140, VH-CDR3 contains the amino acid sequence of SEQ ID NO: 141, VL-CDR1 contains the amino acid sequence of SEQ ID NO: 142, VL-CDR2 contains the amino acid sequence of SEQ ID NO: 143, and VL-CDR3 contains the amino acid sequence of SEQ ID NO: 144, or (vi) VH-CDR1 contains the amino acid sequence of SEQ ID NO: 145, VH-CDR2 contains the amino acid sequence of SEQ ID NO: 146, VH-CDR3 contains the amino acid sequence of SEQ ID NO: 147, VL-CDR1 contains the amino acid sequence of SEQ ID NO: 148, VL-CDR2 contains the amino acid sequence of SEQ ID NO: 149, and VL-CDR3 contains the amino acid sequence of SEQ ID NO:

150. The antibody.

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

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

7. An antibody according to 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. An antibody according to 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 its antigen-binding portion according to any one of claims 1 to 8.

10. A vector or a set of vectors comprising a polynucleotide or a set of polynucleotides as described in claim 9.

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

12. A method for producing an antibody, comprising the steps of expressing the antibody using a host cell as described in claim 11, and isolating the expressed antibody.

13. A pharmaceutical composition comprising an antibody according to 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 and A kit that includes this.

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