Variants of vascular endothelial cell growth factor having altered pharmacological properties, and recombinant methods of production

An isolated nucleic acid molecule comprising a sequence that encodes a vascular endothelial cell growth factor (VEGF) variant wherein said variant differs from native VEGF comprising a heparin binding domain by comprising a C-terminus heparin binding domain structural alteration resulting in modified pharmacokinetic properties from said native VEGF, wherein said VEGF variant binds heparin at a lower affinity than said native VEGF, and wherein said structural alteration is a truncation of said heparin binding domain.

An isolated nucleic acid molecule comprising a sequence that encodes a vascular endothelial cell growth factor (VEGF) variant wherein said variant differs from native VEGF by containing a C-terminus heparin binding domain structural alteration such that said domain binds heparin at a lower affinity than native VEGF comprising a heparin binding domain resulting in said variant having a reduced clearance rate compared with native VEGF, and wherein said structural alteration is a truncation of said heparin binding domain.

An isolated nucleic acid molecule comprising a sequence that encodes a vascular endothelial cell growth factor (VEGF) variant wherein said variant differs from native VEGF by comprising a structural alteration of the C-terminus heparin binding domain, wherein said VEGF variant binds heparin at a lower affinity than said native VEGF, and wherein said structural alteration comprises at least one internal cleavage within said heparin binding domain.

An isolated nucleic acid molecule comprising a sequence that encodes a vascular endothelial cell growth factor (VEGF) variant wherein said variant differs from native VEGF comprising a heparin binding domain by comprising a C-terminus heparin binding domain structural alteration resulting in modified pharmacokinetic properties from said native VEGF, wherein said VEGF variant binds heparin at a lower affinity than said native VEGF, and wherein said structural alteration comprises at least one internal cleavage within said heparin binding domain.

An isolated nucleic acid molecule comprising a sequence that encodes a vascular endothelial cell growth factor (VEGF) variant wherein said variant differs from native VEGF by containing a C-terminus heparin binding domain structural alteration such that said domain binds heparin at a lower affinity than said native VEGF comprising a heparin binding domain resulting in said variant having a reduced clearance rate compared with said native VEGF, and wherein said structural alteration comprises at least one internal cleavage within said heparin binding domain.

Host cells transformed with a vector according to claim, 13.

A purified vascular endothelial cell growth factor (VEGF) variant wherein said variant differs from native VEGF comprising a heparin binding domain by comprising a C-terminus heparin binding domain structural alteration resulting in modified pharmacokinetic properties from said native VEGF, wherein said VEGF variant binds heparin at a lower affinity than said native VEGF, and wherein said structural alteration is a truncation of said heparin binding domain.

A purified vascular endothelial cell growth factor (VEGF) variant wherein said variant differs from native VEGF by containing a C-terminus heparin binding domain structural alteration such that said domain binds heparin at a lower affinity than native VEGF, resulting in said variant having a reduced clearance rate compared with native VEGF, and wherein said structural alteration is a truncation of said heparin binding domain.

A purified vascular endothelial cell growth factor (VEGF) variant wherein said variant differs from native VEGF by comprising a C-terminus heparin binding domain structural alteration resulting in modified pharmacokinetic properties from said native VEGF, wherein said VEGF variant binds heparin at a lower affinity than said native VEGF, and wherein said structural alteration comprises at least one internal cleavage within said heparin binding domain.

(NEW) A purified vascular endothelial cell growth factor (VEGF) variant wherein said variant differs from native VEGF by comprising a C-terminus heparin binding domain structural alteration such that said domain binds heparin at a lower affinity than said native VEGF, resulting in said variant having a reduced clearance rate compared with native VEGF, and wherein said structural alteration comprises at least one internal cleavage within said heparin binding domain.