Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Reexamination Certificate
1999-11-09
2003-07-29
Mosher, Mary E. (Department: 1648)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
C530S402000, C530S413000, C530S810000, C435S239000, C435S308100, C604S005020
Reexamination Certificate
active
06600014
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an adsorbent for removing hepatitis C virus which is capable of selectively adsorbing hepatitis C virus from body fluids such as blood, plasma, etc. to thereby expedite the cure for hepatitis C, an adsorption apparatus including said adsorbent, and an adsorbing method for removing hepatitis C virus.
PRIOR ART
With the successful cloning of the RNA virus genome of hepatitis C virus in 1989 (Q. L. Choo et al.: Science, 244, 359, 1989), it became possible to assay anti-hepatitis C virus antibody using a recombinant protein. As a result, most of the hepatitis termed non-A, non-B hepatitis in the past were found to be hepatitis C. Thus, it is estimated that in Japan today there are about 2,000,000 HCV carriers and, of them, 1,400,000 have chronic hepatitis and 300,000 have cirrhosis (Shiro Iino: Medical Practice in Gastroenterology-2, Hepatitis C, 11-17, 1993).
According to the Ministry of Health and welfare demographic statistics, the number of deaths due to primary liver cancer in 1992 was 27 thousand (1992 Demographic Statistics, Minister of Health and Welfare Statistical Information Bureau, Vol. 1, 1993) and approximately 70% of the casualties were due to hepatocellular carcinoma associated with hepatitis C virus infection and it is by now considered that this cancer ensues following the progression of chronic hepatitis to cirrhosis (S. Kaneko et al.: Intervirology, 37, 108, 1994; Eiki Matsushita et al.: Japanese Journal of Clinics, 53, 727, 1995 Special Issue). Therefore, hepatitis C can be said to be a refractory disease which progresses to cirrhosis to hepatocellular carcinoma.
The conventional therapy of hepatitis C is mostly built around rest cure, dietary thereby, and pharmacotherapy using hepatoprotectants and/or Chinese medicines. However, because the hepatitis virus cannot be removed by such therapeutics, the cure rate is miserably low. This is why, in clinical practice, emphasis has been placed on the arrest of progression of chronic liver disease through palliation of local tissue necrosis. Therefore, as the disease period is prolonged, many patients succumb to hepatocellular carcinoma, the serious outcome, through cirrhosis as mentioned above.
Meanwhile, the mass production of interferons became feasible recently and those proteins were found to show not only antiviral activity against hepatitis C virus and its cognate RNA viruses in vitro (Yasuyuki Ninomiya et al.: The Clinical Report, 19, 231, 1985) but also protective activity in mice infected with RNA viruses (M. Kramer et al.: J. Interferon Res., 3, 425, 1983). Accordingly, the utility of interferons in clinical cases of hepatitis C has come into the focus of attention.
Actually, serum transaminase was normalized in some of the non-A, non-B hepatitis cases which were treated with a recombinant interferon-alpha (J. H. Hoofnagel et al.: N. Eng. J. Med., 315, 1575, 1986) and in the administration of an interferon to patients with hepatitis C, some cases became consistently negative to hepatitis C virus RNA in blood (K. Chayama et al.: Hepatology, 13, 1040, 1991; Hideki Ogiwara et al.: Japanese Journal of Gastroenterology, 88, 1420, 1991). In view of those results, interferons have come to be broadly used in clinical practice. Thus, the therapy of hepatitis C has made a decisive step forward from symptomatic therapy to etiotropic therapy.
However, in the interferon therapies performed in about 200,000 cases of type C chronic active hepatitis during the past several years in Japan, it was only in about 30% of cases that the virus could be eliminated and the disease cured and in the remaining about 70% of cases the virus survived and the therapy either proved ineffective or recurrences were encountered (Migito Yano: Japanese Journal of Clinics, 53, 986, 1995 Special Issue).
In the success or failure of a therapy, the hepatitis C virus gene type, the viral population in blood, and the stage of liver disease are important factors but, of all the factors involved, the viral population in blood is the most important factor. For example, when the amount of the virus in 1 ml of the patient's blood was less than 1,000,000 copies, the virus could be eliminated from the body and the disease cured by administration of an interferon in about 80% of cases but when the amount of the virus was over 1,000,000 copies, the cure rate was as low as about 9% (Fumio Imazeki et al.: Japanese Journal of Clinics, 53, 1017, 1995).
In addition to the above-mentioned amount of the virus, the inventors of the present invention found that the mode of existence of viral particles in blood is also an important factor modifying the effect of an interferon therapy. Thus, it has been reported that hepatitis C virus particles in blood can be classified according to their suspension density in blood into low-density particles with high infectivity and high-density particles with low infectivity. Therefore, the inventors studied the relationship of those viral particles varying in density to the severity of illness and the interferon therapy and found that whereas the interferon therapy resulted in cure in 75% of patients with the ratio of low-density viral particles to high-density viral particles is 10:1, the cure rate in patients with the ratio of 1:10 was as low as 13%.
It was also found that in blood, the low-density virus particles is bound to lipoprotein and the high-density virus particles to immunoglobulin, thus existing as immune complexes (Akihito Sakai et al.: Japanese Journal of Gastroenterology, 92 (Special Issue), 1488, 1995).
It is, therefore, clear that the contemporary interferon therapy has the drawback that the lower the blood viral population is or the lower the immune-complex virus population is, the higher is the therapeutic response and conversely the higher the viral population is or the hither the immune-complex virus population is, the much lower is the therapeutic response.
SUMMARY OF THE INVENTION
The present invention has for its object to provide an adsorbent for removing hepatitis C virus which has the ability to adsorb hepatitis C virus particles, particularly immune-complex hepatitis C virus particles, from a patient's body blood safely and with high efficiency and high selectivity for enhancing the efficacy of interferon therapy, an hepatitis C virus adsorption apparatus including said adsorbent, and an adsorbing method for removing hepatitis C virus.
For accomplishing the above object, the inventors of the present invention made an intensive exploration for a compound which, when immobilized on a water-insoluble carrier and brought into contact with a patient's blood, should exhibit a high adsorbing affinity for hepatitis C virus but not for such proteins as albumin. As a result, the inventors found that an adsorbent fabricated by immobilizing a compound capable of adsorbing hepatitis C virus, particularly a compound having a binding affinity for immunoglobulin and/or immune complex, on a water-insoluble carrier displays a remarkably high hepatitis C virus-adsorbing performance. The present invention has been developed on the basis of the above finding.
The present invention, therefore, is directed to an adsorbent for removing hepatitis C virus which comprises a compound capable of adsorbing hepatitis C virus as immobilized on a water-insoluble carrier.
REFERENCES:
patent: 4576928 (1986-03-01), Tani et al.
patent: 4681870 (1987-07-01), Balint, Jr. et al.
patent: 5037649 (1991-08-01), Balint, Jr. et al.
patent: 5846735 (1998-12-01), Stapleton et al.
patent: 6133431 (2000-10-01), Yasuda et al.
patent: 6358692 (2002-03-01), Jindal et al.
patent: 0752425 (1997-01-01), None
patent: 09033530 (1997-02-01), None
patent: WO 90/09237 (1990-08-01), None
Sigma Immuno Chemicals. Sigma Chemical Co., St. Louis MO, p. 302-311, 1995.*
Pierce Immuno Technology Catalog & Handbook, Pierce Chemical Co., Rockford IL, p. B22-B25, B28-33, 1992.*
Vola et al. Journal of Chromatography B 668:209-218, 1995.*
Gazitt et al. Immunology Letters 11:1-8, 1995.*
Goetzl et al. Immunology
Asahi Takashi
Kaneko Shuichi
Nomura Michio
Ogino Eiji
Sakai Akito
Connolly Bove & Lodge & Hutz LLP
Kaneka Corporation
Mosher Mary E.
LandOfFree
Adsorbent for eliminating hepatitis C virus, adsorber, and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Adsorbent for eliminating hepatitis C virus, adsorber, and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Adsorbent for eliminating hepatitis C virus, adsorber, and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3070214