Nucleotide sequences encoding VEGF antagonist compositions of FLT-1 and uses thereof
AssigneeGenzyme Corporation
InventorsJames Stefano, Clark Pan, Huawei Qiu, Michael O'Callaghan, Gloria Matthews
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Abstract
The invention provides compositions and methods for treating a disease or disorder associate with vascular endothelial growth factor (VEGF). Specifically, the invention relates to an oligomerized VEGF binding domain to provide VEGF antagonism, and thereby treat diseases associated thereof.
Claims13
A nucleotide sequence comprising a coding sequence encoding a monomer that comprises the second VEGF binding domain (D2) of FMS-like tyrosine kinase-1 (FLT-1), wherein said monomer comprises the amino acid sequence of SEQ ID NO:1, or an amino acid sequence with at least 95% sequence identity thereto;
- wherein the monomer further comprises one or more cysteine residues;
- wherein the one or more cysteine residues are C-terminal to the amino acid sequence of SEQ ID NO:1;
- wherein at least two of said monomer can form an oligomer;
- wherein the oligomer exhibits enhanced stability compared to soluble FLT-1 (sFLT01).
A method of producing a VEGF antagonist oligomer wherein said oligomer comprises a plurality of monomers linked to each other, wherein each monomer comprises the second VEGF binding domain (D2) of FMS-like tyrosine kinase-1 (FLT-1), wherein each monomer further comprises one or more cysteine residues, wherein the one or more cysteine residues are C-terminal to the second VEGF binding domain of FLT-1;
- said method comprising:
- (a) providing host cells comprising an expression vector that comprises a coding sequence encoding said monomer, wherein said monomer comprises the amino acid sequence of SEQ ID NO:
- 1, or an amino acid sequence with at least 95% sequence identity thereto;
- (b) culturing the host cells under conditions whereby the monomer encoded by the coding sequence present in the expression vector is expressed;
- (c) recovering one or more monomers from the host cells;
- and
- (d) linking said monomers to produce the oligomer;
- wherein the oligomer exhibits enhanced stability compared to soluble FLT-1 (sFLT01).
Dependencies are inferred from the claim text.