Tissue factor compositions and ligands for the specific coagulation of vasculature
AssigneesThe Scripps Research Institute, Board of Regents, The University of Texas System
InventorsPhilip E. Thorpe, Thomas S. Edgington
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Abstract
Disclosed are various compositions and methods for use in achieving specific blood coagulation. This is exemplified by the specific in vivo coagulation of tumor vasculature, causing tumor regression, through the site-specific delivery of a coagulant using a bispecific antibody.
Claims100
A binding ligand comprising:
- (a) a first binding region that binds to a tumor cell, a component of tumor-associated vasculature or a component of tumor-associated stroma;
- the first binding region operatively linked to
- (b) a Tissue Factor construct or a second binding region that binds to a Tissue Factor construct, wherein said second binding region comprises an antibody or an antigen binding region of an antibody.
A binding ligand comprising a first antibody or antigen binding region of an antibody that binds to a tumor cell, a component of tumor-associated vasculature or a component of tumor-associated stroma;
- the first binding region operatively linked to a Tissue Factor construct.
A binding ligand comprising a first antibody or antigen binding region of an antibody that binds to a tumor cell, a component of tumor-associated vasculature or a component of tumor-associated stroma;
- the first binding region operatively linked to a second antibody or antigen binding region of an antibody that binds to a Tissue Factor construct.
A bispecific antibody comprising:
- (a) a first antibody or antigen binding region of an antibody that binds to a tumor cell, a component of tumor-associated vasculature or a component of tumor-associated stroma;
- the first antibody or antigen binding region operatively linked to
- (b) a second antibody or antigen binding region of an antibody that binds to a Tissue Factor construct.
A binding ligand comprising a first binding region that binds to a surface-expressed, surface-accessible or surface-localized marker of intratumoral blood vessels of a vascularized tumor, the first binding region operatively linked to a Tissue Factor construct or to an antibody, or antigen binding region thereof, that binds to a Tissue Factor construct.
A binding ligand comprising a first antibody, or antigen binding region thereof, that binds to a surface-expressed surface-accessible or surface-localized marker of intratumoral blood vessels of a vascularized tumor, the first antibody or antigen binding region operatively linked to a Tissue Factor construct or to a second antibody, or antigen binding region thereof, that binds to a Tissue Factor construct.
A Tissue Factor construct comprising an operatively linked first, second and third Tissue Factor construct or truncated Tissue Factor construct.
A Tissue Factor construct comprising a first Tissue Factor or truncated Tissue Factor construct operatively linked to a second Tissue Factor or truncated Tissue Factor construct wherein at least one of said Tissue Factor or truncated Tissue Factor constructs is a mutant Tissue Factor deficient in the ability to activate Factor VII.
Dependencies are inferred from the claim text.