本文对新型丙型肝炎病毒(hepatitis C virus,HCV)抑制剂索非布韦在中国的专利申请状况进行分析,重点涉及专利申请的时间分布情况、专利申请人情况、专利申请的法律状态、原研公司的专利布局以及其他申请人有关索非布韦的外围专利申请情...本文对新型丙型肝炎病毒(hepatitis C virus,HCV)抑制剂索非布韦在中国的专利申请状况进行分析,重点涉及专利申请的时间分布情况、专利申请人情况、专利申请的法律状态、原研公司的专利布局以及其他申请人有关索非布韦的外围专利申请情况等,旨在为国内研究机构和制药企业提供有益的研究方向和在专利布局方面的建议。展开更多
Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tre...Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.展开更多
Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an ag...Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.展开更多
In this paper, we take naturally occurring 2-benzylidenebenzofuran-3-ones （aurones） inhibitors of hepatitis C virus （HCV） RNA-dependent RNA polymerase （RdRp） as an example to study the Multi-dimensional scaling ...In this paper, we take naturally occurring 2-benzylidenebenzofuran-3-ones （aurones） inhibitors of hepatitis C virus （HCV） RNA-dependent RNA polymerase （RdRp） as an example to study the Multi-dimensional scaling （MDS） method for structure-activity relationship. By analyzing training set molecules, our MDS method combined with a PROXSCAL algorithm can predict inhibitory activity of most compounds correctly. Thus, a new sample＇s activity can be estimated and judged conveniently, and whether it should be synthesized can be known. The MDS method is applicable to optimize the structure for a compound and to provide suggestions for drug design.展开更多
文摘本文对新型丙型肝炎病毒(hepatitis C virus,HCV)抑制剂索非布韦在中国的专利申请状况进行分析,重点涉及专利申请的时间分布情况、专利申请人情况、专利申请的法律状态、原研公司的专利布局以及其他申请人有关索非布韦的外围专利申请情况等,旨在为国内研究机构和制药企业提供有益的研究方向和在专利布局方面的建议。
基金Supported by Foundation for Liver and Gastrointestinal Research (SLO)The Netherlands Organisation for Scientific Research (NWO), No. VENI-grant 916-13-032 (to Pan Q)
文摘Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.
文摘Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.
文摘In this paper, we take naturally occurring 2-benzylidenebenzofuran-3-ones （aurones） inhibitors of hepatitis C virus （HCV） RNA-dependent RNA polymerase （RdRp） as an example to study the Multi-dimensional scaling （MDS） method for structure-activity relationship. By analyzing training set molecules, our MDS method combined with a PROXSCAL algorithm can predict inhibitory activity of most compounds correctly. Thus, a new sample＇s activity can be estimated and judged conveniently, and whether it should be synthesized can be known. The MDS method is applicable to optimize the structure for a compound and to provide suggestions for drug design.
