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Summary for Patent: 7,470,506
|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), comprises a macrocyclic ring.|
|Inventor(s):||Erickson; John W. (Frederick, MD), Gulnik; Sergei V. (Frederick, MD), Mitsuya; Hiroaki (Chevy Chase, MD), Ghosh; Arun K. (River Forest, IL)|
|Assignee:||The United States of America as represented by the Department of Health and Human Services (Washington, DC) N/A (Urbana, IL) Board of Trustees of the University of Illinois (|
|Patent Litigation and PTAB cases:||See patent lawsuits and PTAB cases for patent 7,470,506|
1. A method of treating a HIV-infected mammal who has developed resistance to HIV treatments, the method comprising (i) determining whether the mammal has developed
resistance to HIV treatments; (ii) administering to the HIV-infected mammal an effective amount of a compound of the formula: ##STR00035## wherein X is oxygen, R.sup.5 is isobutyl, and Ar is substituted phenyl; and (iii) administering at least one
antiviral agent selected from the group consisting of ritonavir, indinavir, amprenavir and saquinavir; whereby the HIV-infected mammal is treated.
2. The method of claim 1, wherein Ar is a phenyl substituted at the para-position.
3. The method of claim 1, wherein Ar is a phenyl substituted at the meta-position.
4. The method of claim 1, wherein Ar is a phenyl substituted at the ortho-position.
5. The method of claim 1, wherein Ar is selected from the group consisting of para-aminophenyl, para-toluoyl, para-methoxyphenyl, meta-methoxyphenyl, and meta-hydroxymethylphenyl.
6. The method of claim 1, wherein the HIV-infected mammal is infected with a wild-type HIV.
7. The method of claim 1, wherein the HIV-infected mammal is infected by a mutant HIV with least one protease mutation.
8. The method of claim 1, wherein the HIV-infected mammal is infected by a mutant HIV having at least one reverse transcriptase mutation.
9. The method of claim 1, wherein the at least one antiviral agent is ritonavir.
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