Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1999-09-14
2001-11-20
Borin, Michael (Department: 1631)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S002600
Reexamination Certificate
active
06319899
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates broadly to the treatment of inflammatory bowel diseases in a patient. More particularly, the invention relates to treating a patient having an inflammatory bowel disease condition with Hepatocyte Growth Factor (“HGF”).
Chronic Ulcerative Colitis (“CUC”) and Crohn's Disease (“CD”), generally referred to as Inflammatory Bowel Disease (“IBD”), are devastating disorders with an unknown etiology. Current medical therapy can control symptomatic exacerbations of IBD, but does not provide a cure. Progress in understanding the pathogenesis of IBD has been slowed by the lack of availability of animal models that exhibit the chronic, spontaneous, relapsing gastrointestinal (“GI”) inflammation that is symptomatic of human IBD. Numerous murine and rat experimental models exist that possess some but not all of the features of human IBD.
A study has shown that the introduction of HLA-B27 and human &bgr;
2
-microglobulin genes into Fisher (F344) rats induces spontaneous chronic GI inflammation. Hammer et al.,
Cell
63: 1099-1112 (1990). In this model, rats spontaneously develop a chronic inflammatory disease that includes most of the clinical and pathologic features of the B27-associated disorders in humans. The most prevalent site of inflammation in these transgenic rats appears to be localized to the gastro-intestinal tract, and the most persistent finding is diarrhea developing in 100% of the animals at 20 weeks of age. Hammer et al.,
Cell
63: 1099-1112 (1990); Elson et al.,
Gastroenterology
109: 1344-1367 (1995). Because it closely approximates the human disease, as will be described in detail below, this transgenic rat model was used to study the therapeutic benefit of HGF as a treatment for IBD.
In a previous application, application Ser. No. 08/932,391, filed on Sep. 17, 1997, herein specifically incorporated by reference, HGF was shown to increase the intestinal absorptive functions and increase the intestinal tissue mass of the small intestine beyond the normal adaptive response in subjects suffering from Short Bowel Syndrome, a surgical resection of the small intestine or other developmental abnormalities of the small intestine. The subject of the present invention relates to the therapeutic benefits of treating subjects with HGF who are suffering from inflammation of the bowel as in IBD.
SUMMARY OF THE INVENTION
The present invention relates to a method for treating a patient comprising administering an effective dose of HGF wherein the patient has a condition characterized as inflammatory bowel disease.
The condition may be selected from the group consisting of Chronic Ulcerative Colitis, Crohn's Disease, necrotizing enterocolitis, severe acute gastroenteritis, chronic gastroenteritis, cholera, chronic infections of the bowel, immunologic disorders affecting the small intestine, immunodeficiency syndromes affecting the small intestine, and HIV.
Further, the invention relates to a method for treating a patient having intestinal mucosal damage comprising decreasing the mucosal damage of the small intestine by administering an effective dose of HGF to the patient.
Still further, the invention relates to a method for treating a patient having histologic lesions comprising decreasing the histologic lesions of the small intestine by administering an effective dose of HGF to the patient.
Further, the invention includes the systemic lumenal administration of HGF to a patient. The effective dosage range of HGF for the patient is about 30 &mgr;g/kg body weight/day to about 300 &mgr;g/kg body weight/day. Preferably, the effective dose of HGF is about 150 &mgr;g/kg body weight/day.
Further, the invention relates to a composition for treating a patient having a condition characterized as inflammatory bowel disease comprising an effective dose of HGF in a suitable carrier. The suitable carrier may be selected from the group consisting of intravenous fluid and sustained release enteral preparations.
REFERENCES:
patent: 6051557 (2000-04-01), Drucker
patent: 08231418 (1995-02-01), None
Zushi et al. Am. J. Physiol.270, G757-G762, Feb. 1996.*
Halttunen, T. et al Gastroenterology, 111, 1252-1262, Nov. 1996.*
“Importance of fibroblastic support for in vitro differentiation of intestinal endodhermal cells and for their response to glucocorticoids,” by M. Kedinger, P. Simon-Assmann, E. Alexandre and K. Haffen,Cell Differentiation, 20 (1987) 171-182.
“Primary Cultures for Studies of Cell Regulation and Physiology in Intestinal Epithelium,” by G. S. Evans, N. Flint, and C. S. Potten,Annu. Rev. Physiol..(1994) 56: 399-417.
“The development of a method for the preparation of rat intestinal epithelial cell primary cultures,” by G. S. Evans, N. Flint, A. S. Somers, B. Eyden and C. S. Potten,Journal of Cell Science, 101 (1992) 219-231.
“Iron Absorption; Characterization of isolated duodenal epithelial cells along a crypt-villus axis in rats fed diets with different iron content,” by Phillip S. Oates, Carla Thomas and Evan H. Morgan,Journal of Gastroenterology and Hepatology(1997) 12: 829-838.
Borin Michael
McGuireWoods LLP
The Nemours Foundation
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