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Angiogenesis using hepatocyte growth factor

a technology of hepatocyte growth factor and angiogenesis, which is applied in the direction of angiogenin, phosphorous compound active ingredients, peptide/protein ingredients, 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: 2005-11-10
FERRARA NAPOLEONE +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018] Although not being bound by any particular theory, it is presently believed that the HGF can be used to stimulate or enhance angiogenic activity in patients suffering from vascular insufficiency or limb ischemia secondary to arterial occlusive disease.

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

[0036] 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 application is a non-provisional application filed under 37 CFR 1.53(b)(1) and 35 USC 111(a), claiming priority under 35 USC 119 (e) to provisional application No. 60 / 004,816 filed Oct. 5, 1995, the contents of which are incorporated herein 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 al., supra, reported the purification of HGF from the serum of partially hepatectomized rats. Subsequently, HGF was purified from rat platelets, and its subunit structure w...

Claims

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Application Information

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IPC IPC(8): A61K38/18
CPCA61K38/1833A61P9/00
Inventor FERRARA, NAPOLEONEISNER, JEFFREY M.SCHWALL, RALPH H.
Owner FERRARA NAPOLEONE
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