Claims
- 1. A heterodimeric vascular endothelial growth factor II said heterodimer comprising an A subunit and a B subunit wherein said A subunit and said B subunit are encoded by different genes, with said growth factor being substantially free of other proteins.
- 2. A heterodimeric mammalian vascular endothelial growth factor II with an apparent non-reduced molecular mass of about 49,500 daltons, with said heterodimer made up of an A monomer having an apparent reduced molecular mass of about 27,000 daltons and a B monomer having an apparent reduced molecular mass of about 31,000 daltons wherein said A monomer and said B monomer are encoded by different genes, with said vascular endothelial growth factor substantially free of impurities.
- 3. The vascular endothelial growth factor II of claim 1 wherein the factor is mitogenic for mammalian vascular endothelial cells.
- 4. The vascular endothelial growth factor II of claim 2 wherein the factor is mitogenic for mammalian vascular endothelial cells.
- 5. Mammalian vascular endothelial growth factor comprising a homodimer comprising two B subunits with said endothelial growth factor substantially free of impurities and mitogenic for mammalian vascular endothelial cells.
- 6. Mammalian vascular endothelial growth factor II comprising an A subunit wherein said A subunit is selected from a group consisting of a 190 amino acid form, a 164 amino acid form, a 135 amino acid form, and a 120 amino acid form, and a B subunit encoded by the nucleotide sequence as shown in FIG. 6 or FIG. 7 and forms thereof which are mitogenic for human vascular endothelial cells, substantially free of impurities.
- 7. Vascular endothelial growth factor comprising two B subunits encoded by the nucleotide sequence as shown in FIG. 6 or FIG. 7 and forms thereof which are biologically active, substantially free of impurities.
- 8. A process for isolating mammalian heterodimeric vascular endothelial growth factor II in substantially pure form which comprises:
a. isolating conditioned growth media containing VEGF II; b. cation exchange chromatography; c. lectin affinity chromatography; d. cation exchange high performance liquid chromatography; e. repeated reverse-phase high performance liquid chromatography; and f. collecting the substantially pure vascular endothelial growth factor II.
- 9. The process of claim 8 for the isolation of vascular endothelial growth factor II from GS-9L cell culture fluid.
- 10. A pharmaceutical composition comprising a pharmaceutical carrier and an effective tissue repairing amount of the purified vascular endothelial growth factor II of claim 1.
- 11. A pharmaceutical composition comprising a pharmaceutical carrier and an effective tissue repairing amount of the purified vascular endothelial growth factor II of claim 2.
- 12. A pharmaceutical composition comprising a pharmaceutical carrier and an effective tissue repairing amount of the purified vascular endothelial growth factor of claim 7.
- 13. A method of promoting tissue repair which comprises the administration to a patient in need of such treatment of an effective tissue repairing amount of the vascular endothelial growth factor II of claim 1.
- 14. A method of promoting tissue repair which comprises the administration to a patient in need of such treatment of an effective tissue repairing amount of the vascular endothelial growth factor II of claim 2.
- 15. A method of promoting tissue repair which comprises the administration to a patient in need of such treatment of an effective tissue repairing amount of the vascular endothelial growth factor of claim 7.
- 16. A method for stimulating growth of vascular endothelial cells which comprises treating vascular endothelial cells in a nutrient medium with vascular endothelial growth factor II at a concentration of about 0.1-100 ng/ml.
- 17. A method for stimulating growth of vascular endothelial cells which comprises treating vascular endothelial cells in a nutrient medium with vascular endothelial growth factor of claim 7 at a concentration of about 1-1000 ng/ml.
- 18. The method of claim 16 wherein cells from a vascular explant are grown on a surface of a synthetic polymeric vessel for implanting in a host.
- 19. The method of claim 16 wherein endothelial cells from a vascular explant are grown on an interior surface of a biocompatible tubular mesh support and smooth muscle cells are grown on an external surface of the tubular mesh support for implanting in a host.
- 20. A method for preparing synthetic vessels comprising treating synthetic polymeric vessels with vascular endothelial growth factor II and implanting into a patient in need of such treatment after said implantation endothelial cells migrate into and grow on the artificial surface.
- 21. A method for the stimulation of the growth of vascular endothelial cells which comprises the administration to a patient in need of such treatment an effective growth promoting amount of vascular endothelial growth factor II whereby either vascular repair, neovascularization, or both is promoted.
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of copending application Ser. No. 08/000,834 filed Jan. 5, 1993, which is a continuation of application Ser. No. 07/586,631 filed Sep. 21, 1990, abandoned.
Divisions (2)
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Number |
Date |
Country |
Parent |
09038199 |
Mar 1998 |
US |
Child |
09326879 |
Jun 1999 |
US |
Parent |
08299185 |
Aug 1994 |
US |
Child |
09038199 |
Mar 1998 |
US |
Continuations (2)
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Number |
Date |
Country |
Parent |
09326879 |
Jun 1999 |
US |
Child |
10071370 |
Feb 2002 |
US |
Parent |
07586638 |
Sep 1990 |
US |
Child |
08000834 |
Jan 1993 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
08000834 |
Jan 1993 |
US |
Child |
08299185 |
Aug 1994 |
US |