Antithrombin H-helix mutants
AssigneeWiSys Technology Foundation, Inc.
InventorsTimothy Walston, Scott Cooper, Alireza Rezaie
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Abstract
Mutant antithrombin modified to carry a more positive charge in the H-helix is provided. The modified antithrombin modulates the activities of thrombin, and extends the bioavailability of factor VIII.
Claims24
An amino acid sequence comprising antithrombin having an H-helix, wherein at least one amino acid of the H-helix is modified to have a more positive charge than an H-helix of non-modified antithrombin.
A modified antithrombin protein having one or more amino acids in the region of amino acids 304-314 modified to have a more positive charge than non-modified antithrombin.
A nucleic acid sequence encoding a modified antithrombin having at least one nucleic acid modified to encode at least one modified amino acid of the antithrombin H-helix, such that the H-helix has a more positive charge than a H-helix of non-modified antithrombin.
A method for inhibiting the activity of thrombin bound to thrombomodulin (T-TM) in a patient, comprising administering to said patient an effective inhibitory amount of a modified antithrombin, wherein at least one amino acid of the antithrombin H-helix is modified to carry a more positive charge than a H-helix of non-modified antithrombin.
A method for inhibiting the activation of Protein C by thrombin bound to thrombomodulin (T-TM) in an animal, comprising contacting said T-TM with an effective inhibitory amount of a modified antithrombin, wherein at least one amino acid of the antithrombin H-helix is modified to carry a more positive charge than a H-helix of non-modified antithrombin.
A method for inhibiting Activated Protein C degradation of one or more of Coagulation Factors V, VIII, or X in an animal, comprising contacting said sample with an effective inhibitory amount of a modified antithrombin, wherein at least one amino acid of the antithrombin H-helix is modified to carry a more positive charge than a H-helix of non-modified antithrombin.
A method for treating coagulation deficiency in a patient comprising administering to said patient an effective procoagulant amount of a modified antithrombin, wherein at least one amino acid of the antithrombin H-helix is modified to carry a more positive charge than a H-helix of non-modified antithrombin.
A method for extending the bioavailability of Factor VIII in a patient, comprising administering to the patient an effective amount of a modified antithrombin, wherein at least one amino acid of the antithrombin H-helix is modified to carry a more positive charge than a H-helix of non-modified antithrombin, and wherein said amount is effective to inhibit degradation of Factor VIII.
Dependencies are inferred from the claim text.