The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
May. 16, 2000
Filed:
Apr. 10, 1995
Laurence M Melnick, Watertown, MA (US);
Donald L Heefner, Hudson, MA (US);
Sepracor, Inc., Marlborough, MA (US);
Abstract
An in vitro method for predicting the identity of distinct, first-generation, drug-resistant, biologically-active, HIV protease mutants that may emerge in vivo in response to a drug targeted thereagainst. In a preferred embodiment, the in vitro method comprises the steps of (a) preparing, in the presence of the drug, a comprehensive library of all first-generation mutants of the protease differing therefrom by at least one and preferably no more than three amino acid substitutions, each of the protease mutants being generated as part of a polyprotein with the HIV reverse transcriptase protein; (b) isolating, in vitro, first-generation, drug-resistant, biologically-active, mutant proteases from said library by assaying for biological activity of the reverse transcriptase protein; and (c) identifying the distinct, first-generation, biologically-active, mutant proteases so isolated. The present invention also relates to an in vitro method for evaluating the efficacy of a drug against a biologically-active mutant or wild-type form of HIV protease, said method comprising the steps of (a) providing a mutant polyprotein, said mutant polyprotein including a biologically-inactive mutant form of the protease linked to HIV reverse transcriptase by one or more sites cleavable by the biologically-active or wild-type form of the protease; (b) adding the drug to the mutant polyprotein; (c) then, adding the biologically-active or wild-type form of the protease to the mutant polyprotein; and (d) then, assaying for the presence of biological activity for reverse transcriptase, whereby the presence of reverse transcriptase activity indicates that the drug is not efficacious against the biologically-active mutant or wild-type form of the protease tested. The present invention further relates to a kit for evaluating the efficacy of a drug against a biologically-active mutant or wild-type form of HIV protease.