Title:
ANTIVIRAL COMBINATIONS OF LAMIVUDINE AND ADEFOVIR
Document Type and Number:
WIPO Patent Application WO2000016755
Kind Code:
A3
Abstract:
The present invention relates to therapeutic combinations comprising (2R, cis) -4-amino-1- (2-hydroxymethyl-1, 3-oxathiolan-5-yl) -pyrimidin-2-one (lamivudine) and a second therapeutic agent selected from (9-[(R) -2-(phosphonomethoxy) ethyl]adenine, (PMEA or adefovir) and bis(pivaloyloxymethyl) (9-[(R) -2- (phosphonomethoxy)ethyl]adenine, (the oral prodrug of PMEA, adefovir dipivoxil) w hich have anti-hepatitis B virus (HBV) activity. The present invention is also concerned with pharmaceutical compositions containing said combinations and their use in the treatment of HBV infections including infections with HBV mutants bearing resistance to nucleoside and/or non-nucleoside inhibitors.
Inventors:
BROWN NATHANIEL A (US)
CONDREAY LYNN D (US)
GRAY DOUGLAS FRASER (GB)
RUBIN MARC (US)
CONDREAY LYNN D (US)
GRAY DOUGLAS FRASER (GB)
RUBIN MARC (US)
Application Number:
PCT/EP1999/006886
Publication Date:
May 25, 2000
Filing Date:
September 17, 1999
Export Citation:
Assignee:
GLAXO GROUP LTD (GB)
BROWN NATHANIEL A (US)
CONDREAY LYNN D (US)
GRAY DOUGLAS FRASER (GB)
RUBIN MARC (US)
BROWN NATHANIEL A (US)
CONDREAY LYNN D (US)
GRAY DOUGLAS FRASER (GB)
RUBIN MARC (US)
International Classes:
A61K31/506; A61K31/52; C07D473/34; A61K31/70; A61P31/20; A61P43/00; C07D411/04; (IPC1-7): A61K31/505; A61K31/52
Domestic Patent References:
| WO1999066936A1 | 1999-12-29 |
Other References:
BARTNOF H. S.: "Preveon shows benefits for patients co-infected with HIV and HBV", HIV AND HEPATITIS.COM, 18 August 1999 (1999-08-18), XP002132867, Retrieved from the Internet [retrieved on 20000313]
PERRILLO: "Gilead Presents Preliminary Clinical Data demostrating activity of adefovir dipivoxil against lamivudine-resistant Hepatitis B virus", GILEAD SCIENCES PRESS RELEASE ARCHIVE, 9 April 1999 (1999-04-09), XP002132868, Retrieved from the Internet [retrieved on 20000313]
THOMPSON M. ET AL: "Randomized Study of Adefovir Dipivoxil (ADV) in combination with Indinavir (IDV) and reverse transcriptase inhibitors for treatment-naive HIV infected patients", ABSTRACTS AND POSTERS IAPAC, 8 November 1998 (1998-11-08), XP002132869, Retrieved from the Internet [retrieved on 20000313]
ONO-NITA, S. K. (1) ET AL: "Susceptibility of lamivudine resistant hepatitis B virus to other antivirals: Adefovir and lobucavir.", HEPATOLOGY, (OCT., 1998) VOL. 28, NO. 4 PART 2, PP. 165A. MEETING INFO.: BIENNIAL SCIENTIFIC MEETING OF THE INTERNATIONAL ASSOCIATION FOR THE STUDY OF THE LIVER AND THE 49TH ANNUAL MEETING AND POSTGRADUATE COURSES OF THE AMERICAN ASSOCIATION FOR THE, XP000890075
MULATO, A.S. ET AL: "Anti-HIV activity of adefovir (PMEA) and PMPA in combination with antiretroviral compounds: in vitro analyses", ANTIVIRAL RES. (1997), 36(2), 91-97, XP000890091
SHAW, T. ET AL: "Synergistic inhibition of in vitro hepadnaviral replication by PMEA and penciclovir or lamivudine.", ANTIVIRAL RESEARCH, (1997) VOL. 34, NO. 2, PP. A51. MEETING INFO.: MEETING OF THE INTERNATIONAL SOCIETY FOR ANTIVIRAL RESEARCH AND THE TENTH INTERNATIONAL CONFERENCE ON ANTIVIRAL RESEARCH ATLANTA, GEORGIA, USA APRIL 6-11, 1997, XP000890096
DE CLERCQ E: "Perspectives for the treatment of hepatitis B virus infections.", INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, (1999 JUL) 12 (2) 81-95. REF: 72, XP000890077
PESSOA M.G. ET AL: "Update on clinical trials in the treatment of hepatitis B.", JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, (1999) 14/SUPPL. (S6-S11)., XP000890090
PETERS M G ET AL: "Fulminant hepatic failure resulting from lamivudine -resistant hepatitis B virus in a renal transplant recipient: durable response after orthotopic liver transplantation on adefovir dipivoxil and hepatitis B immune globulin.", TRANSPLANTATION, (1999 DEC 27) 68 (12) 1912-4., XP000890081
PERRILLO: "Gilead Presents Preliminary Clinical Data demostrating activity of adefovir dipivoxil against lamivudine-resistant Hepatitis B virus", GILEAD SCIENCES PRESS RELEASE ARCHIVE, 9 April 1999 (1999-04-09), XP002132868, Retrieved from the Internet
THOMPSON M. ET AL: "Randomized Study of Adefovir Dipivoxil (ADV) in combination with Indinavir (IDV) and reverse transcriptase inhibitors for treatment-naive HIV infected patients", ABSTRACTS AND POSTERS IAPAC, 8 November 1998 (1998-11-08), XP002132869, Retrieved from the Internet
ONO-NITA, S. K. (1) ET AL: "Susceptibility of lamivudine resistant hepatitis B virus to other antivirals: Adefovir and lobucavir.", HEPATOLOGY, (OCT., 1998) VOL. 28, NO. 4 PART 2, PP. 165A. MEETING INFO.: BIENNIAL SCIENTIFIC MEETING OF THE INTERNATIONAL ASSOCIATION FOR THE STUDY OF THE LIVER AND THE 49TH ANNUAL MEETING AND POSTGRADUATE COURSES OF THE AMERICAN ASSOCIATION FOR THE, XP000890075
MULATO, A.S. ET AL: "Anti-HIV activity of adefovir (PMEA) and PMPA in combination with antiretroviral compounds: in vitro analyses", ANTIVIRAL RES. (1997), 36(2), 91-97, XP000890091
SHAW, T. ET AL: "Synergistic inhibition of in vitro hepadnaviral replication by PMEA and penciclovir or lamivudine.", ANTIVIRAL RESEARCH, (1997) VOL. 34, NO. 2, PP. A51. MEETING INFO.: MEETING OF THE INTERNATIONAL SOCIETY FOR ANTIVIRAL RESEARCH AND THE TENTH INTERNATIONAL CONFERENCE ON ANTIVIRAL RESEARCH ATLANTA, GEORGIA, USA APRIL 6-11, 1997, XP000890096
DE CLERCQ E: "Perspectives for the treatment of hepatitis B virus infections.", INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, (1999 JUL) 12 (2) 81-95. REF: 72, XP000890077
PESSOA M.G. ET AL: "Update on clinical trials in the treatment of hepatitis B.", JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, (1999) 14/SUPPL. (S6-S11)., XP000890090
PETERS M G ET AL: "Fulminant hepatic failure resulting from lamivudine -resistant hepatitis B virus in a renal transplant recipient: durable response after orthotopic liver transplantation on adefovir dipivoxil and hepatitis B immune globulin.", TRANSPLANTATION, (1999 DEC 27) 68 (12) 1912-4., XP000890081
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