Site-directed mutagenesis modified glycoprotein hormones and methods of use
AssigneeApplied Research Systems ARS Holding N.V.
InventorsScott C. Chappel, Edward G. Bernstine
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AssigneeApplied Research Systems ARS Holding N.V.
InventorsScott C. Chappel, Edward G. Bernstine
Estimating the term…
Described are new glycoprotein hormones capable of competing with natural hormones for the normal receptor binding sites but substantially incapable of effecting post receptor activities. The glycoprotein hormones of the present invention have had specific (rather than all) oligosaccharide chains removed so as to effectively diminish biologic activity while not significantly reducing plasma half-life, thus improving the molecules effectiveness as an antagonist compared with conventionally-produced molecules. The preferred glycoprotein hormones are ideally obtained by site-directed mutagenesis to selectively deglycosylate the protein. Also described are therapeutic treatments comprising the administration of the recombinant glycoprotein hormones of the present invention as hormone antagonists.
A method for treating the overproduction of a dimeric glycoprotein hormone selected from the group consisting of luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone, and human chorionic gonadotropin, comprising administering a therapeutically effective dose of a corresponding hormone which has at least one N-linked oligosaccharide chain entirely removed so as to be capable of competing with the corresponding natural hormone for binding to a natural receptor molecule but incapable of stimulating post receptor biological activity, and having a plasma half-life approximately equal to that of the corresponding natural hormone.
Dependencies are inferred from the claim text.