Mutants of the factor VII epidermal growth factor domain
OwnerMorris Blajchman, Bryan Clarkeinventors
Life of this patent
Estimating the term…
Abstract
The application relates to modified blood coagulation factor, sequencing encoding such modified factors, processes for their production, and related pharmaceutical compositions comprising such factors and their uses. More specifically, the application relates to mutations in the human FVII EGF-1 domain, wherein said mutations were analyzed for clotting activity, amidolytic activity and affinity of binding to full-length, relipidated human TF by competitive ELISA.
Claims23
A modified factor VII/VIIa (mutant FVII/FVIIa) or functional fragment thereof, comprising one or more mutation(s), wherein said mutation(s) is/are in the epidermal growth factor-like (EGF-1) domain and said mutation(s) may be to any amino acid residue that confers enhanced biological activity of said FVII/FVIIa.
A nucleotide sequence comprising a sequence that encodes a modified FVII/FVIIa sequence, wherein said sequence specifically hybridizes to a sequence selected from SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:
- 30 or any degenerate variant thereof.
A nucleotide sequence comprising any one of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 or any degenerate variant thereof wherein said sequence differs from a sequence of human wild-type FVII.
A nucleotide sequence comprising a sequence that encodes a polypeptide comprising a modified FVII/FVIIa amino acid sequence comprising one, more than one or all mutation(s) specified in FIG. 1, or any combinations thereof, wherein said modified FVII/FVIIa sequence confers enhanced FVII/FVIIa biological activity.
A polypeptide comprising the amino acid sequence of any one of SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, or SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20 wherein the amino acid sequence differs from an amino acid sequence of human wild-type FVII.
A culture cell or cell line transfected with a vector according to claim 16, or a progeny of said cell, wherein said culture cell or cell line expresses the modified FVII/FVIIa.
A pharmaceutical composition comprising a modified FVII/FVIIa, or functional fragment thereof, and a pharmaceutically accepted carrier;
- wherein said modified FVII/FVIIa amino acid sequence comprises one, more than one or all mutation(s) specified in FIG. 1 or any combinations thereof.
A method for treating a patient with a blood condition, comprising introducing into the patient an expression vector encoding a modified factor VII protein, or functional fragment thereof, such that an amount of said protein is effective to improve coagulation;
- wherein said modified FVII/FVIIa amino acid sequence comprises one, more than one or all mutation(s) specified in FIG. 1 or any combinations thereof.
A modified factor VII/VIIa (mutant FVII/FVIIa) comprising any one or more mutation(s) in the epidermal growth factor-like (EGF-1) domain, wherein said mutation(s) confer(s) enhanced biological activity of FVII/FVIIa to positively improve blood coagulation.
Dependencies are inferred from the claim text.