Patent Evaluation: TGF-β as a potential antihypertensive agent
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AntihypertensivelTGF-P antagonist 185 Patent Evaluation W09119513 : Bnstol-Myers Squibb Co TGF-P as a potential antihypertensive agent Current Opinion in Therapeutic Patents February 1992 Summary Novelty: Novel methods for the modulation of blood pressure, using transforming growth factor-P (TGF-P) and TGF-P antagonists are disclosed. The TGFs are potentially useful as antihypertensive agents. Biology: In vivo cynomolgous monkey studies are described. Blood pressure is monitored via arterial catheratization. Recombinant mature TGF-P 1. isolated and transferred from Chinese hamster ovary cells, induces significant and sustained decreases in BP on injection of rTGF- Pl in doses of 0.51 mgkg. No significant fluctuation in BP is observed in the control. Chemistry: Transforming growth factors may be obtained from natural sources. They can also be produced via conventional recombinant DNA or chemical techniques. Preparative references are presented. Evaluation Therapeutic Numerous endogenous vasoactive peptides are now known. An examination of their functions reveals a variety of vasoregulatory activities. "kansforming growth factor+ (TGF-P) is a multifunctional growth factor with the ability to regulate the migration, growth and differentiation of many of the cell types involved in tissue repair, TGF-P1 and the more recently discovered and closely related TGF-P2 are known to play a role in tissue damage and may accelerate repair if administered at the site of myocardial infarction. This application describes in general terms the blood pressure lowering effects of a number of naturally occurring or recombinantly produced TGF-Ps when administered iv to cynomolgous monkeys, in particular the use of recombinant mature rTGF-Pl. A single dose of 0.51 mgkgiv for one to three days results in significant side-effects leading, in some cases, to the need for euthanasia. The isolation and sequencing of various TGFs is well documented in the literature and includes recombinant DNA techniques; practical details are not provided in this appli- cation. The possible use of TGF-P antagonists as pressor agents is also suggested in very general terms but again, the application provides little hard information. The data, while of undoubted interest, provide little insight in to the possibility of the development of practical antihypertensive agents based on TGF-P agents and, more particularly, the question of selectivity and safety factors involved. The implication is that the date of a possible successful outcome to this type of approach could be well into the future. 0 Current Patents Ltd ISSN 0962-2594 Expert Opin. Ther. Patents Downloaded from informahealthcare.com by Cornell University on 11/06/14 For personal use only.
Transcript of Patent Evaluation: TGF-β as a potential antihypertensive agent
AntihypertensivelTGF-P antagonist 185
Patent Evaluation W09119513 : Bnstol-Myers Squibb Co
TGF-P as a potential antihypertensive agent Current Opinion in Therapeutic Patents February 1992
Summary Novelty: Novel methods for the modulation of blood pressure, using transforming growth factor-P (TGF-P) and TGF-P antagonists are disclosed. The TGFs are potentially useful as antihypertensive agents.
Biology: In vivo cynomolgous monkey studies are described. Blood pressure is monitored via arterial catheratization. Recombinant mature TGF-P 1. isolated and transferred from Chinese hamster ovary cells, induces significant and sustained decreases in BP on injection of rTGF- P l in doses of 0.51 mgkg. No significant fluctuation in BP is observed in the control.
Chemistry: Transforming growth factors may be obtained from natural sources. They can also be produced via conventional recombinant DNA or chemical techniques. Preparative references are presented.
Evaluation
Therapeutic Numerous endogenous vasoactive peptides are now known. An examination of their functions reveals a variety of vasoregulatory activities. "kansforming growth factor+ (TGF-P) is a multifunctional growth factor with the ability to regulate the migration, growth and differentiation of many of the cell types involved in tissue repair, TGF-P1 and the more recently discovered and closely related TGF-P2 are known to play a role in tissue damage and may accelerate repair if administered at the site of myocardial infarction.
This application describes in general terms the blood pressure lowering effects of a number of naturally occurring or recombinantly produced TGF-Ps when administered iv to cynomolgous monkeys, in particular the use of recombinant mature rTGF-Pl. A single dose of 0.51 mgkgiv for one to three days results in significant side-effects leading, in some cases, to the need for euthanasia.
The isolation and sequencing of various TGFs is well documented in the literature and includes recombinant DNA techniques; practical details are not provided in this appli- cation. The possible use of TGF-P antagonists as pressor agents is also suggested in very general terms but again, the application provides little hard information. The data, while of undoubted interest, provide little insight in to the possibility of the development of practical antihypertensive agents based on TGF-P agents and, more particularly, the question of selectivity and safety factors involved. The implication is that the date of a possible successful outcome to this type of approach could be well into the future.
0 Current Patents Ltd ISSN 0962-2594
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1 86 Patent Evaluations
Key References 1. WOLLBERG Z et al.: Biophys. Res. Commun. (1990) 167:203.
BiblioaraDhic data
Cardiovasculars
Title: Methods of modulating blood pressure using TGF-P and antagonists thereof. Assignee: Bristol-Myers Squibb Co Inventors: Oleson,FB;Comereski,CR. Priority data: 20 Jun 90, US 541221 Filing date: 20 Jun 91
Publication date: 26 Dec 91 Publication no: W09119513 IPC no: A61K-37/36 Contracting states: AT BE CA CH DE DK ES FR GB GR HU IT JP KR LU NL SE Current Patents listing: CV5130
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