Angiogenesis using hepatocyte growth factor

a technology of hepatocyte growth factor and angiogenesis, which is applied in the direction of angiogenin, peptide/protein ingredients, drug compositions, etc., can solve the problems of complex structure, inability to perform nonsurgical revascularization, and inability to achieve arterial bypass and/or amputation, etc., to stimulate or enhance angiogenic activity

Inactive Publication Date: 2006-09-21
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

HGF stimulates angiogenic activity, enhancing collateral vessel formation and regional perfusion, thereby addressing the limitations of existing treatments for vascular disease and reducing tissue atrophy.

Problems solved by technology

As Takeshita et al., J. Clin. Invest., 93:662-670 (1994), point out, such patients are often refractory to conservative measures and typically unresponsive to drug therapy.
When vascular obstruction is lengthy and / or widespread, nonsurgical revascularization may not be feasible.
Surgical therapy, consisting of arterial bypass and / or amputation, may be complicated by a variable morbidity and mortality, and is often dependent for its efficacy upon short- and long-term patency of the conduit used.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example

[0034] Recombinant human HGF (“rhuHGF”) was produced in CHO cells using a procedure modified from Naka et al., J. Biol. Chem., 267:20114-20119 (1992). rhuHGF-transfected cells were grown in a 400 L bioreactor in medium containing 2% fetal bovine serum for 8 days. Culture supernatant containing rhuHGF was concentrated and clarified, then conditioned by the addition of solid NaCl to 0.3 M. rhuHGF was then purified in a single step using cation exchange chromatography. Conditioned, concentrated culture supernatant was loaded onto a column of S-Sepharose Fast Flow equilibrated in 20 mM Tris, pH 7.5, 0.3 M NaCl. After washing out unbound protein, rhuHGF was eluted in a linear gradient from 20 mM Tris, pH 7.5, 0.3 M NaCl to 20 mM Tris, pH 7.5, 1.2 M NaCl. rhuHGF-containing fractions were pooled based on SDS-PAGE analysis. The S Sepharose Fast Flow pool was concentrated and exchanged into 20 mM Tris, pH 7.5, 0.5 M NaCl by gel filtration on Sephadex G25 to a final concentration of about 3-5...

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Abstract

Methods for enhancing angiogenesis in a mammal using hepatocyte growth factor (“HGF”) are provided. In the methods, HGF can be administered to mammals suffering from, for instance, vascular insufficiency or arterial occlusive disease. Articles of manufacture and kits containing HGF are also provided.

Description

RELATED APPLICATIONS [0001] This is a continuation claiming priority to application Ser. No. 10 / 642664 filed Aug. 19, 2003; which is a continuation of Ser. No. 09 / 610152, filed Jul. 5, 2000, which is a divisional of Ser. No. 09 / 086498 filed May 22, 1998; which is a continuation of Ser. No. 08 / 726110 filed Oct. 4, 1996, claiming priority to provisional Ser. No. 60 / 004816 filed Oct. 5, 1995, the entire disclosure of which is hereby incorporated by reference.FIELD OF THE INVENTION [0002] The invention relates generally to methods and compositions which can be employed for enhancing angiogenesis in mammals. BACKGROUND OF THE INVENTION [0003] Hepatocyte growth factor (“HGF”) functions as a growth factor for particular tissues and cell types. HGF was identified initially as a mitogen for hepatocytes [Michalopoulos et al., Cancer Res., 44:4414-4419 (1984); Russel et al., J. Cell. Physiol., 119:183-192 (1984); Nakamura et al., Biochem. Biophys. Res. Comm., 122:1450-1459 (1984)]. Nakamura et...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K38/18
CPCA61K38/1833A61P9/00
InventorFERRARA, NAPOLEONEISNER, JEFFREY M.SCHWALL, RALPH H.
OwnerGENENTECH INC