Antibodies for inhibiting blood coagulation and methods of use thereof
AssigneeSunol Molecular Corporation
InventorsJin-an Jiao, Hing Wong, Jinghai Wen
Life of this patent
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Abstract
Disclosed are antibodies that provide superior anti-coagulant activity by binding native human TF with high affinity and specificity. Also disclosed are methods of using such antibodies to reduce cancer cell tissue factor activity and to detect cancer cells that express TF.
Claims56
An antibody that binds native human tissue factor and does not substantially bind non-native tissue factor.
An antibody having the binding affinity for native human tissue factor about equal to or greater than H36.D2.B7 [ATCC HB-12255].
An antibody having identifying characteristics of H36.D2.B7 [ATCC HB-12255].
An antibody that binds native tissue factor to form a complex whereby factor X binding to the complex is inhibited.
An antibody that comprises a sequence that has at least about 70 percent sequence identity to SEQ ID NO:
- 1.
An antibody that comprises hypervariable regions that have at least 90 percent sequence identity to SEQ ID NOS. 5 through 10 inclusive.
An isolated nucleic acid comprising a sequence encoding at least a portion of an antibody that binds native human tissue factor.
A nucleic acid comprising at least about 100 base pairs and that hybridizes to SEQ ID NO:
- 1 or SEQ ID NO:3 under normal stringency conditions.
A method of inhibiting blood coagulation in a mammal, comprising administering to the mammal an effective amount of an antibody capable of specifically binding native tissue factor and whereby the antibody complexes with native tissue factor, and factor X binding to the complex is inhibited.
A method of reducing tissue factor levels in a mammal comprising:
- administering to the mammal a therapeutically effective amount of an antibody capable of binding native tissue factor, the antibody linked covalently to a cell toxin or an effector molecule to provide complement-fixing ability and antibody-dependent cell-mediated cytotoxicity, the antibody contacting cells expressing tissue factor to reduce tissue factor levels in the mammal.
The method of claim 37, wherein Factor X (FX) or Factor VII/VIIa (FVII/FVIIa) binding to the complex is inhibited.
The method of claim 37, wherein the antibody or fragment has the binding specificity for native human tissue factor about equal to or greater than H36. D2. B7 [ATCC HB12255].
The method of claim 37, wherein the antibody is a monoclonal antibody.
The method of claim 37, wherein the antibody is a single chain antibody.
The method of claim 37, wherein the antibody comprises a sequence that has at least about 70 percent sequence identity to SEQ ID NO:
- 1.
The method of claim 37, wherein the antibody comprises an immunological effector molecule.
The method of claim 37, wherein the antibody is an immunologically active antibody fragment.
The method of claim 37, wherein the FX or FVII/FVIIa binding to the complex is inhibited by at least 80 percent in a standard in vitro binding assay.
The method of claim 37, wherein the FX or FVII/FVIIa binding to the complex is inhibited by at least 90 percent in a standard in vitro binding assay.
The method of claim 37, wherein the FX or FVII/FVIIa binding to the complex is inhibited by at least 95 percent in a standard in vitro binding assay.
Dependencies are inferred from the claim text.