Drug – bio-affecting and body treating compositions – Lymphokine – Interferon
Reexamination Certificate
1999-12-16
2004-11-30
Foley, Shanon (Department: 1648)
Drug, bio-affecting and body treating compositions
Lymphokine
Interferon
C424S184100, C424S228100, C514S043000, C530S351000
Reexamination Certificate
active
06824768
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to methods of treating patients having chronic hepatitis C infection by administering a therapeutically effective induction amount of ribavirin and a therapeutically effective induction amount of pegylated interferon-alfa for a first treatment time period sufficient to substantially lower detectable HCV-RNA, followed by (2) administering a therapeutically effective amount of ribavirin and an therapeutically effective amount of pegylated interferon-alfa for a second treatment time period sufficient to eradicate detectable HCV-RNA at least by the end of the second treatment time period and to maintain no detectable HCV-RNA for at least 24 weeks after the end of the second treatment time period.
Chronic infection with hepatitis C virus is an insidious and slow-progressing disease having a significant impact on the quality of life. It can eventually result in cirrhosis of the liver, decompensated liver disease and/or hepatocelluar carcinoma.
International Publication No. WO98/48840 discloses use of pegylated interferon alfa to treat hepatitis C infections.
Nieforth et al. (Clin. Pharmacol. Ther., 1996, 59:636-646) has reported a comparison of the in vivo activity of Roferon®A and a polyethylene glycol-modified Roferon® A in healthy volunteers. The results, however, suggested that the conjugates could not be administered less than twice weekly and therefore offered little therapeutic advantage over the unmodified counterpart.
Co-pending, commonly assigned U.S. patent application Ser. No. 08/742,305 discloses methods of administering polymer-cytokine conjugates to individuals susceptible to treatment with the cytokine, but does not disclose the method of this invention.
Polyethylene glycol modification of other proteins has been reported by Fuertges et al. (Journal of Controlled Release,1990, Vol.11:139-48).
Combination therapy of interferon alfa-2b and ribavirin to treat chronic hepatitis C for 24 weeks is disclosed by Reichard et al. (Lancet 1998; 351;83-87)
T. Poynard et al. (Lancet, 1998, Vol. 352, 1426-1432) disclose that treating chronic hepatitis C patients who had not been treated with interferon or ribavirin with 3 MIU of interferon alfa-2b TIW plus 1000-1200 mg of ribavirin per day for 48 weeks resulted in a sustained virological response at 24 weeks after treatment in 43% of the patients. See also J. G. McHutchinson et al. (N. Engl. J. Med., 1998, 339:1485-1492), G. L. Davis et al. (N. Engl. J. Med. 339:1493-1499) disclose that treating chronic hepatitis C patients who relapsed after treatment with interferon with 3 MIU of interferon alfa 2b Tim plus 100-1200 mg of ribavirin per day for 48 weeks results in higher rates of sustained virologic response than treatment with interferon alone.
There is a need to provide an improved therapy for treating chronic hepatitis C patients to produce a sustained virological response at 24 weeks after treatment in a greater number of patients.
SUMMARY OF THE INVENTION
The present invention provides a method of treating patients having chronic hepatitis C infections which comprises (1) administering a therapeutically effective induction dosing amount of ribavirin and an therapeutically effective induction dosing amount of pegylated interferon-alfa for a first treatment time period sufficient to substantially lower detectable HCV-RNA, followed by (2) administering a therapeutically effective amount of ribavirin and an therapeutically effective amount of pegylated interferon-alfa for a second treatment time period sufficient to eradicate detectable HCV-RNA at least by the end of the second treatment time period and to maintain no detectable HCV-RNA for at least 24 weeks after the end of the second treatment time period.
The present invention also provides a method of treating patients having chronic hepatitis C infections which comprises (1) administering, in a first treatment time period of at least about four weeks, about 400-1200 mg per day of ribavirin and about 1.5 micrograms per kilogram of pegylated interferon-alfa-2b twice a week, followed by (2) administering, in a second treatment time period of up to about forty-four weeks, about 800-1200 mg per day of ribavirin and about 0.5 to 1.5 micrograms per kilogram of pegylated interferon-alfa-2b once a week.
The present invention also provides a method method of treating patients having chronic hepatitis C infections which comprises (1) administering, in a first treatment time period of from about four weeks up to about twelve weeks, about 400-1200 mg per day of ribavirin and about 1.5 micrograms/kilogram of pegylated interferon-alfa-2b twice a week followed by (2) administering, in a second time of from about thirty-six to about forty-four weeks, period about 800-1200 mg per day of ribavirin and about 0.5 to about 1.5 micrograms per kilogram of pegylated interferon-alfa-2b once a week basis.
The present invention also provides a method method of treating patients having chronic hepatitis C infections which comprises (1) administering, in a first treatment time period of about four weeks, about 800-1200 mg per day of ribavirin and about 1.5 micrograms/kilogram of pegylated interferon-alfa-2b twice a week, followed by (2) administering, in a second time of about forty-four weeks, about 800-1200 mg per day of ribavirin and about 1.5 micrograms/kilogram of pegylated interferon-alfa2b once a week
REFERENCES:
patent: 5503828 (1996-04-01), Testa et al.
patent: 6172046 (2001-01-01), Albrecht
patent: 6472373 (2002-10-01), Albrecht
patent: 0 707 855 (1996-04-01), None
patent: WO 95/13090 (1995-05-01), None
Chemello et al. 1994. Response to ribavirin and to a combination of both in patients with chronic hepatitis C and its relation to HCV genotypes. Journal of Hepatology. vol. 21. (Suppl. 1), p. S12. Abstract No. GS 5/29.*
Xu et al. 1998. PK/PD modeling approach to support clinical development of a long-acting interferon (RO25-3036) for the treatment of chronic hepatitis C. Clin. Pharmacol. Ther. vol. 63. No. 2, p. 162. Abstract No. Pl-101.*
Lai, et al.,Gastroenterology, Nov. 1996, vol. III, pp. 1307-1312.
Sato, et al., NS5A Region and the Prediction of Interferon Effect, Igaku-no-Ayumi (May 3, 1997), vol. 181, (No. 5) pp. 330-340 (Translation).
Hayashi, N.,Today's Therapy, Chronic Hepatitis, Konnichi-no-Chiryo-Sisin, Jan. 15, 1997, p. 403 (Translation).
Gunther, R., “What is Ribavirin?” and “Combination with Ribavirin for Non-Responders”, Medical Tribune, Nr 22, May 30, 1997, www.hepatitis-c.de/wasriba.htm (in German).
Schalm, SW., et al., Digestive Diseases and Sciences, vol. 41, (No. 12) Dec. 1996, Supplement, pp. 131S to 134S.
Reichard, O.., et al., “Interferon-Alpha and Ribavirin versus Interferon alpha as Therapy for Chronic Hepatitis C—A randomized Double-blind placebo-controlled study.” American Association for the Study of Liver Diseases, 1996 Annual Meeting, www.hepatitis-c.de/riba.htm.
Pol, S., et al., “Ribavirin-Interferon v. Interferon alone in Non-Responders to IFN in Chronic Hepatitis C”, American Association for the Study of Liver Diseases, 1996 Annual Meeting,. www.hepatitis-c.de/riba.htm.
Lurie, Y., et al., “Ribavirin Interferon Combination for chronic HCV”, American Gastroenterology Association Digestive Disease Week meeting in Washington, May 1997, www.hepatitis-c.de/riba.htm.
Bellobuono, A., et al. “Ribavirin and interferon-alph combination therapy v. interferon-alpha alone in the treatment of chronic hepatitis C; A randomized clinical trial;” Journal of Viral Hepat 1997; vol. 4, 185-191.
Weiland, et al., “Combination Treatment with Interferon Alpha-2b and Ribavirin in Patients Suffering from Chronic Hepatitis C Relapsing After, or Not Responding to Earlier Treatment with Interferon,” Translation of Abstract from Lakarstamman (Swedish Physicians' Meeting) Stockholm—Dec. 1993.
El Zayadi, et al., “Combination treatment of alpha interferon-2b and ribavirin in chronic hepatitis C genotype”< Hepatology 22 (4 Pt 2),152A (1995).
Bizollon, et al., “Ribavirin and interferon treatment for Hepatitis C recurre
Albrecht Janice K.
Glue Paul W.
Stalgis Carlos O.
Foley Shanon
Hoffman Thomas D.
Schering Corporation
Zaradic Sandy
LandOfFree
Ribavirin-pegylated interferon alfa induction HCV... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Ribavirin-pegylated interferon alfa induction HCV..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Ribavirin-pegylated interferon alfa induction HCV... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3317778