Claims for Patent: 7,247,631

Summary for Patent: 7,247,631

Title:	Pegylated interferon alfa-CCR5 antagonist combination HIV therapy
Abstract:	Methods for treating treatment-naive as well as treatment-experienced adult and pediatric patients having HIV-1 infections as well as patients co-infected with HIV-1 and HCV involving administering a therapeutically effective amount of pegylated interferon-alfa, e.g., pegylated interferon alfa-2b, in association with a therapeutically effective amount of a CCR5 antagonist or preferably further in association with a therapeutically effective amount of at least one of ribavirin, IL-2, IL-12, pentafuside alone or in combination with a therapeutically effective amount of an anti-HIV-1 drug therapy, e.g., HAART are disclosed.
Inventor(s):	Laughlin; Mark A. (Edison, NJ)
Assignee:	Schering Corporation (Kenilworth, NJ)
Application Number:	10/430,370
Patent Claims:	1. A method of treating patients co-infected with [HIV-1] Human Immunodeficiency Virus-1 ("HIV-1") and [HCV] Hepatitis C Virus("HCV") which comprises administering a therapeutically effective amount of pegylated interferon-alfa in association with a therapeutically effective amount of ribavirin and a therapeutically effective amount of [HAART] Highly Active Antiretroviral Therapy and a therapeutically effective amount of a CCR5 antagonist represented by the structural formula I or II or III or IV: ##STR00060## or a pharmaceutically acceptable salt of I or II or II or IV; sufficient to lower HIV-1-RNA and HCV-RNA levels; wherein in the CCR5 antagonist compounds represented by structural formula I: ##STR00061## X is --C(R.sup.13).sub.2--, --C(R.sup.13)(R.sup.19)--, --C(O)--, --O--, --NH--, --N((C.sub.1-C.sub.6)alkyl)-, ##STR00062## R is R.sup.6-phenyl, R.sup.6-pyridyl, R.sup.6-thiophenyl or R.sup.6-naphthyl; R.sup.1 is hydrogen, (C.sub.1-C.sub.6 ) alkyl or (C.sub.2-C.sub.6)alkenyl; R.sup.2 is R.sup.7, R.sup.8, R.sup.9-phenyl; R.sup.7, R.sup.8, R.sup.9-substituted 6-membered heteroaryl; R.sup.7, R.sup.8, R.sup.9-substituted 6-membered heteroaryl N-oxide; R.sup.10, R.sup.11-substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl ##STR00063## R.sup.3 is R.sup.6-phenyl, R.sup.6-heteroaryl or R.sup.6-naphthyl; R.sup.4 is hydrogen, (C.sub.1-C.sub.6) alkyl fluoro-(C.sub.1-C.sub.6 ) alkyl, cyclopropylmethyl, --CH.sub.2CH.sub.2OH, --CH.sub.2CH.sub.2--O--(C.sub.1-C.sub.6 )alkyl, --CH.sub.2C(O)--O--(C.sub.1-C.sub.6)alkyl, --CH.sub.2C(O)NH.sub.2, --CH.sub.2C(O)--NH(C.sub.1-C.sub.6)alkyl or --CH.sub.2C(O)--N((C.sub.1-C.sub.6)alkyl).sub.2; R.sup.5 and R.sup.11 are independently selected from the group consisting of hydrogen and (C.sub.1-C.sub.6)-alkyl; R.sup.6 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, (C.sub.1-C.sub.6) alkyl, C.sub.1-C.sub.6)alkoxy, --CF.sub.3, CF.sub.3O--, CH.sub.3C(O)--, --CN, CH.sub.3SO.sub.2--, CF.sub.3SO.sub.2--, R.sup.14-phenyl, R.sup.14-benzyl, CH.sub.3C(.dbd.NOCH.sub.3)--, CH.sub.3C(.dbd.NOCH.sub.2CH.sub.3)--, ##STR00064## --NH.sub.2, --NHCOCF.sub.3, --NHCONH(C.sub.1-C.sub.6 alkyl), --NHCO(C.sub.1-C.sub.6 alkyl), --NHSO.sub.2(C.sub.1 -C.sub.6 alkyl), 5-membered heteroaryland ##STR00065## wherein X.sup.b is --O--, --NH--or --N(CH.sub.3)--; R.sup.7 and R.sup.8 are independently selected from the group consisting of (C.sub.1-C.sub.6)alkyl, halogen, --NR.sup.20R.sup.21, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, and --OCF.sub.3; R.sup.9 is R.sup.7, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.20, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.20)CONR.sup.21 R.sup.22, --NHCONH(chloro-(C.sub.1-C.sub.6)alkyl), --NHCONH((C.sub.3-C.sub.10) -cycloalkyl(C.sub.1-C.sub.6)alkyl), --NHCO(C.sub.1-C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2N((C.sub.1-C.sub.6)alkyl).sub.2, --NHSO.sub.2(C.sub.1-C.sub.6)alkyl, --N(SO.sub.2CF.sub.3).sub.2, --NHCO.sub.2(C.sub.1-C.sub.6)alkyl, C.sub.3-C.sub.10 cycloalkyl, --SR.sup.23, --SOR.sup.23, --SO.sub.2R.sup.23, --SO.sub.2NH(C.sub.1-C.sub.6 alkyl), --OSO.sub.2(C.sub.1-C.sub.6)alkyl, --OSO.sub.2CF.sub.3, hydroxy(C.sub.1-C.sub.6)alkyl, --CON R.sup.20R.sup.21, --CON(CH.sub.2CH.sub.2--O--CH.sub.3).sub.2, --OCONH(C.sub.1-C.sub.6)alkyl, --CO.sub.2R.sup.20, Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2; R.sup.10 is (C.sub.1-C.sub.6)alkyl, --NH.sub.2 or R.sup.12-phenyl; R.sup.12 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1-C.sub.6) alkyl, --CF.sub.3, --CO.sub.2R.sub.20, --CN, (C.sub.1-C.sub.6)alkoxy and halogen; R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and (C.sub.1-C.sub.6)alkyl; R.sup.17 and R.sup.18 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6 alkyl, or R.sup.17 and R.sup.18 together are a C.sub.2-C.sub.5 alkylene group and with the carbon to which they are attached form a Spiro ring of 3 to 6 carbon atoms; R.sup.19 is R.sup.6-phenyl, R.sup.6-heteroaryl, R.sup.6-naphthyl, C.sub.3-C.sub.10 cycloalkyl, (C.sub.3-C.sub.10)cycloalky(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl; R.sup.20, R.sup.21 and R.sup.22 are independently selected from the group consisting of H and C.sub.1-C.sub.6) alkyl; and R.sup.23 is C.sub.1-C.sub.6 alkyl or phenyl; and wherein in the CCR5 antagonist compounds represented by the structural formula II: ##STR00066## or a pharmaceutically acceptable salt thereof, wherein (1) X.sup.a is --C(R.sup.13).sub.2--, --C(R.sup.13)(R.sup.19)--, --C(O)--, --O--, --NH--, --N((C.sub.1-C.sub.6)alkyl)--; ##STR00067## R.sup.a is R.sup.6a-phenyl, R.sup.6a-pyridyl, R.sup.6a-thiophenyl or R.sup.6-naphthyl; R.sup.1 is hydrogen, (C.sub.1-C.sub.6) alkyl or (C.sub.2-C.sub.6) alkenyl; R.sup.2 is R.sup.7, R.sup.8, R.sup.9-phenyl; R.sup.7, R.sup.8, R.sup.9-substituted 6-membered heteroaryl; R.sup.7, R.sup.8, R.sup.9-substituted 6-membered heteroaryl N-oxide; R.sup.10, R.sup.11-substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl ##STR00068## R.sup.3 is R.sup.10-phenyl, pyridyl, pyrimidyl, pyrazinyl or thiazolyl; R.sup.4 is hydrogen, (C.sub.1-C.sub.6) alkyl, fluoro-(C.sub.1-C.sub.6) alkyl, cyclopropylmethyl, --CH.sub.2CH.sub.2OH, --CH.sub.2CH.sub.2--O--(C.sub.1-C.sub.6)alkyl, --CH.sub.2C(O)--O--(C.sub.1C.sub.6)alkyl, --CH.sub.2C(O)NH.sub.2, --CH.sub.2C(O)--NH(C.sub.1-C.sub.6)alkyl or --CH.sub.2C(O)--N((C.sub.1-C.sub.6)alkyl).sub.2; R.sup.5 and R.sup.11 are independently selected from the group consisting of hydrogen and (C.sub.1-C.sub.6)-alkyl; R.sup.6a is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, --CF.sub.3, CF.sub.3O--, --CN, --CF.sub.3SO.sub.2--, R.sup.12-phenyl, --NHCOCF.sub.3, 5-membered heteroaryl and ##STR00069## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.6 is independently selected from the group consisting of R.sup.6a and CH.sub.3SO.sub.2--; R.sup.7 and R.sup.8 are independently selected from the group consisting of (C.sub.1-C.sub.6)alkyl, halogen, --NR.sup.20R.sup.21, --OH, --CF.sub.3, --OCH.sub.3, --O--acyl, and --OCF.sub.3; R.sup.9 is R.sup.7, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.20, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.20)CONR.sup.21R.sup.22, --NHCONH(chloro-(C.sub.1-C.sub.6)alkyl), --NHCONH((C.sub.3-C.sub.10) -cycloalkyl(C.sub.1-C.sub.6)alkyl), --NHCO(C.sub.1-C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2N((C.sub.1-C.sub.6)alkyl).sub.2, --NHSO.sub.2(C.sub.1-C.sub.6)alkyl, --N(SO.sub.2CF.sub.3).sub.2, --NHCO.sub.2(C.sub.1-C.sub.6)alkyl, C.sub.3-C.sub.10 cycloalkyl, --SR.sup.23, --SOR.sup.23, --SO.sub.2R.sup.23, --SO.sub.2NH(C.sub.1-.sub.6 alkyl), --OSO.sub.2(C.sub.1-C.sub.6)alkyl, --OSO.sub.2CF.sub.3, hydroxy(C.sub.1-C.sub.6)alkyl, --CON R.sup.20R.sup.21, --CON(CH.sub.2CH.sub.2--O--CH.sub.3).sub.2, --OCONH(C.sub.1-C.sub.6)alkyl, --CO.sub.2R.sup.20, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2; R.sup.10 is (C.sub.1-C.sub.6)alkyl, --NH.sub.2 or R.sup.12-phenyl; R.sup.12 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1-C.sub.6) alkyl, --CF.sub.3, --CO.sub.2R.sub.20, --CN, (C.sub.1-C.sub.6)alkoxy and halogen; R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and (C.sub.1-C.sub.6)alkyl; R.sup.17 and R.sup.18 are independently selected from the group consisting of hydrogen and (C.sub.1-C.sub.6) alkyl, or R.sup.17 and R.sup.18 together are a C.sub.2-C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.19 is R.sup.6-phenyl, R.sup.6-heteroaryl, R.sup.6-naphthyl, C.sub.3-C.sub.10 cycloalkyl, (C.sub.3-C.sub.10)cycloalkyl(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl; R.sup.20, R.sup.21 and R.sup.22 are independently selected from the group consisting of H and C.sub.1-C.sub.6) alkyl; and R.sup.23 is C.sub.1-C.sub.6 alkyl or phenyl; or (2): X.sup.a is --C(R.sup.13)(R.sup.19)--, --C(O)--, --O--, --NH--, --N((C.sub.1-C.sub.6)alkyl)--, ##STR00070## R.sup.a is R.sup.6b-phenyl, R.sup.6b-pyridyl or R.sup.6b-thiophenyl; R.sup.4a is fluoro-C.sub.1-C.sub.6 alkyl, cyclopropylmethyl, --CH.sub.2CH.sub.2OH, --CH.sub.2CH.sub.2--O--(C.sub.1-C.sub.6)alkyl, --CH.sub.2C(O)--O--(C.sub.1-C.sub.6)alkyl, --CH.sub.2C(O)NH.sub.2, --CH.sub.2C(O)--NH--(C.sub.1-C.sub.6)alkyl or --CH.sub.2C(O)--N((C.sub.1-C.sub.6)alkyl).sub.2; R.sup.6b is CH.sub.3SO.sub.2--; and R.sup.1, R.sup.2, R.sup.3, R.sup.5, R.sup.14, R.sup.15, R.sup.16 and R.sup.19 are as defined in II(1); and wherein in the CCR5 antagonist compounds represented by the structural formula III: ##STR00071## R is R.sup.8-phenyl, R.sup.8-pyridyl, R.sup.8-thiophenyl or R.sup.8-naphthyl; R.sup.1 is hydrogen or C.sub.1-C.sub.6 alkyl; R.sup.2 is R.sup.9, R.sup.10, R.sup.11-phenyl; R.sup.9, R.sup.10, R.sup.11-substituted 6-membered heteroaryl; R.sup.9, R.sup.10, R.sup.11-substituted 6-membered heteroaryl N-oxide; R.sup.12, R.sup.13-substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl ##STR00072## R.sup.3 is hydrogen, C.sub.1-C.sub.6 alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.10 cycloalkyl(C.sub.1-C.sub.6)alkyl, R.sup.8-phenyl, R.sup.8-phenyl(C.sub.1-C.sub.6)alkyl, R.sup.8-naphthyl, R.sup.8-naphthyl(C.sub.1-C.sub.6)alkyl, R.sup.8-heteroaryl or R.sup.8-heteroaryl(C.sub.1-C.sub.6)alkyl; R.sup.4, R.sup.5, R.sup.7 and R.sup.13 are independently selected from the group consisting of hydrogen and (C.sub.1-C.sub.6)-alkyl; R.sup.6 is hydrogen, C.sub.1-C.sub.6) alkyl or (C.sub.2-C.sub.6)alkenyl; R.sup.8 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, (C.sub.1-C.sub.6) alkyl, C.sub.1-C.sub.6 alkoxy, --CF.sub.3, CF.sub.3O--, CH.sub.3C(O)--, --CN, CH.sub.3SO.sub.2--, CF.sub.3SO.sub.2--, R.sup.14-phenyl, R.sup.14-benzyl, CH.sub.3C(.dbd.NOCH.sub.3), CH.sub.3C(.dbd.NOCH.sub.2CH.sub.3), ##STR00073## --NH.sub.2, --NHCOCF.sub.3, --NHCONH(C.sub.1-C.sub.6 alkyl), --NHCO(C.sub.1-C.sub.6 alkyl), --NHSO.sub.2(C.sub.1-C.sub.6 alkyl), 5-membered heteroaryl and ##STR00074## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.9 and R.sup.10 are independently selected from the group consisting of (C.sub.1-C.sub.6)alkyl, halogen, --NR.sup.17R.sup.18, --OH, --CF.sub.3, OCH.sub.3, --O--acyl, --OCF.sub.3 and --Si(CH.sub.3).sub.3; R.sup.11 is R.sup.9, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.17, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.17)CONR.sup.18R.sup.19, --NHCONH(chloro-(C.sub.1-C.sub.6)alkyl), --NHCONH((C.sub.3-C.sub.1)cycloalkyl(C.sub.1-.sub.6)alkyl), --NHCO(C.sub.1-C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2N((C.sub.1-C.sub.6)alkyl).sub.2, --NHSO.sub.2(C.sub.1-C.sub.6)alkyl, --N(SO.sub.2CF.sub.3).sub.2, --NHCO.sub.2(C.sub.1-C.sub.6)alkyl, C.sub.3-C.sub.10 cycloalkyl, --SR.sup.20, --SOR.sup.20, --SO.sub.2R.sup.20, --SO.sub.2NH(C.sub.1-C.sub.6 alkyl),--OSO.sub.2(C.sub.1-C.sub.6)alkyl, --OSO.sub.2CF.sub.3, hydroxy(C.sub.1-C.sub.6)alkyl, --CON R.sup.17R.sup.18, --CON(CH.sub.2CH.sub.2--O--CH.sub.3).sub.2, --OCONH(C.sub.1-C.sub.6)alkyl, --CO.sub.2R.sup.17, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2; R.sup.12 is (C.sub.1-C.sub.6)alkyl, --NH.sub.2 or R.sup.14-phenyl; R.sup.14 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1-C.sub.6) alkyl, --CF.sub.3, --CO.sub.2R.sub.17, --CN, (C.sub.1-C.sub.6)alkoxy and halogen; R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6) alkyl, or R.sup.15 and R.sup.16 together are a C.sub.2-C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.17, R.sup.18 and R.sup.19 are independently selected from the group consisting of H and (C.sub.1-C.sub.6) alkyl; and R.sup.20 is (C.sub.1-C.sub.6) alkyl or phenyl; and wherein in the CCR5 antagonist compounds represented by the structural formula IV: ##STR00075## or a pharmaceutically acceptable salt thereof, wherein (1) R.sup.a is R.sup.8a-phenyl, R.sup.8b-pyridyl, R.sup.8b-thiophenyl or R.sup.8-naphthyl; R.sup.1 is hydrogen or (C.sub.1-C.sub.6) alkyl; R.sup.2 is R.sup.9, R.sup.10, R.sup.11-phenyl; R.sup.9, R.sup.10, R.sup.11-substituted 6-membered heteroaryl; R.sup.9, R.sup.10, R.sup.11-substituted 6-membered heteroaryl N-oxide; R.sup.12, R.sup.13-substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl, ##STR00076## R.sup.3 is hydrogen, (C.sub.1-C.sub.6) alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.10 cycloalkyl(C.sub.1-C.sub.6)alkyl, R.sup.8-phenyl, R.sup.8-phenyl(C.sub.1 -C.sub.6)alkyl, R.sup.8-naphthyl, R.sup.8naphthyl(C.sub.1-C.sub.6)alkyl, R.sup.8-heteroaryl or R.sup.8-heteroaryl(C.sub.1-C.sub.6)alkyl; R.sup.4, R.sup.5, R.sup.7 and R.sup.13 are independently selected from the group consisting of hydrogen and (C.sub.1-C.sub.6)-alkyl; R.sup.6 is hydrogen, (C.sub.1-C.sub.6) alkyl or (C.sub.2-C.sub.6)alkenyl; R.sup.8 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6) alkyl, C.sub.1-C.sub.6 alkoxy, --CF.sub.3, CF.sub.3O--, CH.sub.3C(O)--, --CN, CH.sub.3SO.sub.2--, CF.sub.3SO.sub.2--, R.sup.14-phenyl, R.sup.14-benzyl, CH.sub.3C(.dbd.NOOH.sub.3), CH.sub.3C(.dbd.NOCH.sub.2CH.sub.3), ##STR00077## --NH.sub.2, --NHCOOF.sub.3, --NHCONH(C.sub.1-C.sub.6 alkyl), --NHCO(C.sub.1-C.sub.6 alkyl), --NHSO.sub.2(C.sub.1-C.sub.6 alkyl), 5-membered heteroaryl and ##STR00078## wherein X.sup.b is --O--, --NH--or --N(CH.sub.3)--; R.sup.8a is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, --CF.sub.3, CF.sub.3O--, --CN, CF.sub.3SO.sub.2--, R.sup.14-phenyl, --NHCOCF.sub.3, 5-membered heteroaryl and ##STR00079## wherein X.sup.b is as defined above; R.sup.8b is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, --CF.sub.3, CF.sub.3O--, CH.sub.3C(O)--, --CN, CF.sub.3SO.sub.2--, R.sup.14-benzyl, CH.sub.3C(.dbd.NOCH.sub.3), CH.sub.3C(.dbd.NOCH.sub.2CH.sub.3), ##STR00080## --NHCOCF.sub.3, 5-membered heteroaryl and ##STR00081## wherein X.sup.b is as defined above; R.sup.9 and R.sup.10 are independently selected from the group consisting of (C.sub.1-C.sub.6)alkyl, halogen, --NR.sup.17R.sup.18, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, --OCF.sub.3 and --Si(CH.sub.3).sub.3; R.sup.11 is R.sup.9, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.17, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.17)CONR.sup.18R.sup.19, --NHCONH(chloro-(C.sub.1-C.sub.6)alkyl), --NHCONH((C.sub.3-C.sub.1)cycloalkyl(C.sub.1-C.sub.6)alkyl), --NHCO(C.sub.1-C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2N((C.sub.1-C.sub.6)alkyl).sub.2, --NHSO.sub.2(C.sub.1-C.sub.6)alkyl, --N(SO.sub.2CF.sub.3).sub.2, --NHCO.sub.2(C.sub.1-C.sub.6)alkyl, C.sub.3-C.sub.10 cycloalkyl, --SR.sup.20, --SOR.sup.20, SO.sub.2R.sup.20, --SO.sub.2NH(C.sub.1-C.sub.6 alkyl), --OSO.sub.2(C.sub.1-C.sub.6)alkyl, --OSO.sub.2CF.sub.3, hydroxy(C.sub.1-C.sub.6)alkyl, --CON R.sup.17R.sup.18, --CON(CH.sub.2CH.sub.2--O--CH.sub.3).sub.2, --OCONH(C.sub.1-C.sub.6)alkyl, --CO.sub.2R.sup.17, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2; R.sup.12 is (C.sub.1-C.sub.6)alkyl, --NH.sub.2 or R.sup.14-phenyl; R.sup.14 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1-C.sub.6) alkyl, --CF.sub.3, --CO.sub.2R.sub.17, --CN, (C.sub.1-C.sub.6)alkoxy and halogen; R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6 alkyl, or R.sup.15 and R.sup.16 together are a C.sub.2-C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.17, R.sup.18 and R.sup.19 are independently selected from the group consisting of H and C.sub.1-C.sub.6 alkyl; and R.sup.20 is (C.sub.1-C.sub.6) alkyl or phenyl; or (2) R.sup.a is R.sup.8-phenyl, R.sup.8-pyridyl or R.sup.8-thiophenyl; R.sup.2 is fluorenyl, diphenylmethyl, ##STR00082## and R.sup.1, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19 and R.sup.20 are as defined in IV(1). 2. The method of claim 1, wherein the patients are treatment-naive patients. 3. The method of claim 1, wherein the patients are treatment-experienced patients. 4. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.5 to about 3.0 micrograms per kilogram in a single dose QW or divided doses BIW. 5. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.75 to about 1.5 micrograms per kilogram in a single dose QW or divided doses BIW. 6. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.5 to about 3.0 micrograms per kilogram in a single dose QW. 7. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.25 to about 1.5 micrograms per kilogram BIW. 8. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.75 to about 1.5 micrograms per kilogram in a single dose QW. 9. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is about 1.5 micrograms per kilogram in a single dose QW. 10. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.375 to about 1.5 micrograms per kilogram BIW.

Details for Patent 7,247,631

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2019-05-04
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2019-05-04
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2019-05-04
Hoffmann-la Roche Inc.	PEGASYS COPEGUS COMBINATION PACK	peginterferon alfa-2a and ribavirin		125083	06/04/2004		2019-05-04