Claims for Patent: 9,889,115

Summary for Patent: 9,889,115

Title:	Fitness assay and associated methods
Abstract:	The present invention provides an assay for determining the biochemical fitness of a biochemical species in a mutant replicating biological entity relative to its predecessor. The present invention further provides a continuous fluorogenic assay for measuring the anti-HIV protease activity of protease inhibitor. The present invention also provides a method of administering a therapeutic compound that reduces the chances of the emergence of drug resistance in therapy. The present invention also provides a compound of formula (I) or a pharmaceutically acceptable salt, a prodrug, a composition, or an ester thereof, wherein A is a group of formulas (A), (B), (C) or (D); R.sup.1, R.sup.2, R.sup.3, R.sup.5 or R.sup.6 is H, or an optionally substituted and/or heteroatom-bearing alkyl, alkenyl, alkynyl, or cyclic group; Y and/or Z are CH.sub.2, O, S, SO, SO.sub.2, amino, amides, carbamates, ureas, or thiocarbonyl derivatives thereof, optionally substituted with an alkyl, alkenyl, or alkynyl group; n is from 1 to 5; X is a bond, an optionally substituted methylene or ethylene, an amino, O or S; Q is C(O), C(S), or SO.sub.2; m is from 0 to 6; R.sup.4 is OH, .dbd.O (keto), NH.sub.2, or alkylamino, including esters, amides, and salts thereof; and W is C(O), C(S), S(O), or SO.sub.2. Optionally, R.sup.5 and R.sup.6, together with the N--W bond of formula (I), comprise a macrocyclic ring. ##STR00001##
Inventor(s):	Erickson; John W. (Potomac, MD), Gulnik; Sergei V. (Frederick, MD), Mitsuya; Hiroaki (Chevy Chase, MD), Ghosh; Arun E. (West Lafayette, IN)
Assignee:	Board of Trustees of the University of Illinois (Urbana, IL) The United States of America, as represented by the Secretary, Department of Health and Human Services (Washington, DC)
Application Number:	13/933,319
Patent Claims:	1. A method of preventing the development of protease inhibitor resistance in an HIV-infected mammal, the method comprising administering to the HIV-infected mammal a protease inhibitor resistance-inhibiting effective amount of a compound selected from: ##STR00036## wherein the protease inhibitor resistance-inhibiting effective amount is an amount sufficient to produce an in vivo protease inhibitor concentration or level in which a mutant virus that is capable of evolving from the HIV virus infecting the mammal has lower fitness, relative to the HIV virus infecting the mammal, in the presence of the compound. 2. The method of claim 1, which comprises further administration of at least one other antiviral agent selected from the group consisting of ritonavir, indinavir, amprenavir and saquinavir. 3. The method of claim 2, wherein the one other antiviral agent is ritonavir. 4. A method of preventing the development of protease inhibitor resistance in an HIV-infected mammal, the method comprising administering to the HIV-infected mammal a protease inhibitor resistance-inhibiting effective amount of a compound of the formula: ##STR00037## wherein the protease inhibitor resistance-inhibiting effective amount is an amount sufficient to produce an in vivo protease inhibitor concentration or level in which a mutant virus that is capable of evolving from the HIV virus infecting the mammal has lower fitness, relative to the HIV virus infecting the mammal, in the presence of the compound, and wherein the method comprises further administration of at least one antiviral agent selected from the group consisting of ritonavir, indinavir, amprenavir and saquinavir. 5. The method of claim 1, wherein the compound is: ##STR00038## 6. The method of claim 4, wherein the compound is: ##STR00039##