Ticagrelor

PRINCETON, N.J., June 24, 2024 (GLOBE NEWSWIRE) -- CytoSorbents, Inc. (NASDAQ: CTSO), a leader in the treatment of life-threatening conditions in the intensive care unit and cardiac surgery using blood purification via its proprietary polymer adsorption technology, announces the regulatory approval of CytoSorb® in Taiwan by the Taiwan Food and Drug Administration (TFDA). The approved indications include the extracorporeal removal of cytokines (e.g. cytokine storm, sepsis), bilirubin (e.g. liver disease), and myoglobin (e.g. trauma) from a patient’s circulating blood. The removal of the antithrombotic drugs Brilinta® (ticagrelor, AstraZeneca) and Xarelto® (rivaroxaban, Janssen/Bayer) during cardiothoracic surgery is also approved, with the goal of reducing perioperative bleeding. CytoSorb will be distributed throughout Taiwan by Hemoscien Corporation. Ms. Bettina Sabisch, Vice President of International Distributor Sales at CytoSorbents stated, “We are thrilled to announce this milestone which underscores the value and efficacy of our CytoSorb therapy and was achieved after navigating a long and complex approval process. We look forward to collaborating with Hemoscien and leveraging their long-standing customer relationships in Taiwan to bring this innovative therapy to patients in need.” Mr. Tom Juan, Managing Director of Hemoscien Corporation emphasized, “There is an ongoing critical need for more effective therapies to combat infections and to prevent or treat organ failure. I firmly believe that advanced blood purification devices such as CytoSorb® can complement the limitations of traditional pharmaceuticals by restoring peripheral blood homeostasis and balance. Given the widespread and successful application of CytoSorb therapy in numerous countries to treat life-threatening critical illnesses, we are confident in our ability to take what has been learned and to market and support CytoSorb in Taiwan's ICU sectors through our deep critical care network to help save the lives of severely ill patients.” In addition to Taiwan, CytoSorb is approved in the European Union and distributed in 75 countries worldwide. It is an extracorporeal cytokine adsorber that reduces “cytokine storm” or “cytokine release syndrome” in common critical illnesses such as sepsis and septic shock, trauma, acute respiratory distress syndrome, burn injury, pancreatitis, and others that can lead to massive inflammation, organ failure and patient death. CytoSorb is also used as an extracorporeal liver support therapy in acute liver disease (e.g. acute on chronic liver failure, alcoholic hepatitis) and removes both liver toxins, such as bilirubin and bile acids, as well as cytokines. It is also used to treat rhabdomyolysis (e.g. trauma) and the removal of myoglobin. In these diseases, the risk of death can be extremely high, and there are few, if any, effective or practical treatments. CytoSorb is also used during and after cardiothoracic surgery to remove antithrombotic drugs and inflammatory mediators that can lead to postoperative complications, including severe bleeding and multiple organ failure. As of March 31, 2024, more than 237,000 CytoSorb devices have been used cumulatively around the world. Taiwan, with approximately 24 million inhabitants, offers universal coverage to its citizens through its National Health Insurance System and serves them through a network of nearly 400 medical centers and regional hospitals. With rising medical standards, use of advanced technology to increase administrative and provider efficiency, and access to high quality healthcare, Taiwan boasts one of the most progressive healthcare systems globally. Like many other parts of the world, critical illness including sepsis is a major problem in Taiwan. For example, there are 150,000 estimated new cases of sepsis reported each year in Taiwan with mortality rates as high as 30%, driven by diseases such as pneumonia, which is the third leading cause of death in Taiwan. About Hemoscien Corporation Hemoscien Corporation, a specialized hemo-epuration service provider, was established in 2008 as a spinoff from Smile Group Corp., originally founded in 1980. Since 1998, Hemoscien has maintained a strong partnership with Infomed S.A., a respected ICU hemo-therapy platform developer, achieving over 50% market share. The company is dedicated to its mission of addressing unmet medical needs in ICU care, as well as advancing regenerative medicine and other immune therapies. About CytoSorbents Corporation (NASDAQ: CTSO) CytoSorbents Corporation is a leader in the treatment of life-threatening conditions in the intensive care unit and in cardiac surgery through blood purification. CytoSorb, the Company’s flagship product, was originally launched in the European Union under CE mark as the first cytokine adsorber. In addition to the description in the text above, CytoSorb also received FDA Emergency Use Authorization in the United States for use in adult critically ill COVID-19 patients with impending or confirmed respiratory failure. CytoSorbents’ purification technologies are based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and surface adsorption. Its technologies have received non-dilutive grant, contract, and other funding of approximately $50 million from DARPA, the U.S. Department of Health and Human Services (HHS), the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), the U.S. Army, the U.S. Air Force, U.S. Special Operations Command (SOCOM), Air Force Material Command (USAF/AFMC), and others. The Company has numerous marketed products and products under development based upon this unique blood purification technology protected by many issued U.S. and international patents and registered trademarks, and multiple patent applications pending, including ECOS-300CY®, CytoSorb-XL™, HemoDefend-RBC™, HemoDefend-BGA™, VetResQ®, K+ontrol™, DrugSorb™, ContrastSorb, and others. For more information, please visit the Company’s websites at and or follow us on Facebook and X. Forward-Looking Statements This press release includes forward-looking statements intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, statements about our plans, objectives, future targets and outlooks for our business, statements about potential exposures resulting from our cash positions, representations and contentions, and are not historical facts and typically are identified by use of terms such as “may,” “should,” “could,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue” and similar words, although some forward-looking statements are expressed differently. You should be aware that the forward-looking statements in this press release represent management’s current judgment and expectations, but our actual results, events and performance could differ materially from those in the forward-looking statements. Factors which could cause or contribute to such differences include, but are not limited to, the risks discussed in our Annual Report on Form 10-K, filed with the SEC on March 14, 2024, as updated by the risks reported in our Quarterly Reports on Form 10-Q, and in the press releases and other communications to shareholders issued by us from time to time which attempt to advise interested parties of the risks and factors which may affect our business. We caution you not to place undue reliance upon any such forward-looking statements. We undertake no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, other than as required under the Federal securities laws. Please Click to Follow Us on Facebook and X U.S. Company Contact: Kathleen Bloch, CFO 305 College Road East Princeton, NJ 08540 +1 (732) 398-5429 kbloch@cytosorbents.com Investor Relations Contact: Eric Ribner LifeSci Advisors, LLC 250 W 55th St, #3401 New York, NY 10019 +1 (646) 751-4363 ir@cytosorbents.com

实际工作中如何找到我们的发明点或者如何挖掘创新点申请专利保护呢？首先我们要了解一下什么是专利挖掘，专利挖掘是指从现有研发项目或技改项目中提炼出具有创新点的技术方案，并将所提炼的技术方案用专利化的语言进行描述并申请专利以获得专利保护。 仿制药的药学研究包括原料药、制剂和分析研发三大块，前面已经介绍了原料药和制剂研发过程中的专利挖掘，本文主要阐述分析方法研发过程的专利挖掘。 分析是项目研发人员的眼睛，用于判断项目研发的好坏，分析方法建立的成功与否很大程度上影响着整个项目的进展，因此在整个项目研发中占有绝对的地位。分析方法虽然在项目研发中很重要，但研发人员往往缺少专利挖掘的意识，很多研发成果没有形成专利。下文将结合案例具体探讨分析方法研发过程的可专利点。 有关物质检测 不论是原料还是制剂，分析方法研发的重点和难点基本都在有关物质。有关物质分析方法开发的过程简单的说就是解决如何准确定量目标物中潜在杂质的问题，这就要求方法分离度好、灵敏度高、重现性好、易于操作等，解决这些问题的过程也就是形成我们专利发明点的过程。 一种测定鲁比前列酮供试品有关物质的分析方法专利，申请人为南京正大天晴制药，申请号为201811580995.8。该专利主要解决的技术问题是提供一种能准确测定鲁比前列酮供试品有关物质含量的高效液相色谱分析方法。本发明建立的检测方法，溶剂不干扰杂质检测，鲁比前列酮5个已知杂质可以准确定量，主峰与相邻杂质峰的分离度≥1.2、各杂质间的分离度≥1.5，方法专属性良好，且该检测方法简便、快速、准确、灵敏度高、重复性好、准确度好。 异构体检测 手性药物是指分子结构中含有手性中心（也叫不对称中心）的药物。由于手性药物的不同立体异构体在药效、药代及毒理等方面都可能存在差异，因此在质量研究中要重点关注。因为手性药物不同异构体特殊的结构特点，特别是对于光学异构体，其和主药成分为映像关系，同主峰分离非常困难，建立准确可靠的检测方法是一项非常具有挑战性的工作。 一种替格瑞洛对映异构体、非对映异构体的分离检测方法的发明专利，申请人为江苏恒瑞医药，申请号为201611087850.5，主要保护一种替格瑞洛对映异构体、非对映异构体的分离检测方法。现有技术报道了分离检测替格瑞洛非对映异构体的方法，但该方法存在对替格瑞洛对映异构体的分离度不好，载量性差，结果重现性差等问题。本发明所提供的一种替格瑞洛对映异构体、非对映异构体检测方法，以纤维素衍生物为填充剂的色谱柱为手性色谱柱，低级烷烃与低级醇混合液为流动相，通过高效液相色谱法对替格瑞洛对映异构体、非对映异构体进行分离测定。该检测方法具有较高的准确度和精密度，耐用性强，适合医药工业上替格瑞洛异构体的检查及质量控制。 基因毒质检测 基因毒性杂质（genotoxic impurities，GTI）又称遗传毒性杂质，是指化合物本身能直接或间接损伤细胞DNA，产生基因突变或体内诱变，具有致癌可能或者倾向。近年来随着制药行业接连从缬沙坦、雷尼替丁、二甲双胍等药物中发现亚硝胺类基因毒杂质残留，监管部门对基因毒杂质的监管越来越严格。因基因毒性杂质能改变人体DNA、自身反应性强的特点，对其限度控制往往比较低。检测过程受基质干扰大，对仪器的灵敏度高，如何保证检测结果的准确性也成了分析时需要解决的问题。 一种拉莫三嗪潜在基因毒性杂质的分析方法的专利申请，申请人为浙江华海药业，申请号为202110035529.7，主要保护一种拉莫三嗪潜在基因毒性杂质的分析方法。在拉莫三嗪的合成工艺中，有1个可能属于潜在基因毒性杂质，按照每日摄入量限度为1.5微克/天计算其在成品中限度指标为2.14ppm，使用常规的紫外检测器灵敏度无法达到要求。采用GC‑MS或LC‑MS方法检测时，发现由于检测灵敏度不够，或是在高温下发生分解或聚合等原因，无法在2ppm限度内对该杂质进行准确定量。本发明开发了拉莫三嗪样品中微量潜在基毒杂质分析方法，采用检测前先用可离子化或质子化的胺类衍生试剂对该潜在基因毒性杂质进行柱前衍生，然后在酸性检测条件下用LC‑MS方法进行检测，可以使该杂质的检测灵敏度达到0.2ppm以下。该方法抗干扰能力强，操作简单，并且灵敏度高，线性范围宽，可以快速有效地检测拉莫三嗪或其中间体样品中微量潜在基毒杂质二氯苯甲酰腈的含量，有利于有效的控制拉莫三嗪药品中潜在基毒杂质的残留，保护患者的用药安全。 残留溶剂 药物中的残留溶剂系指在原料药或辅料的生产中、以及在制剂制备过程中使用或产生而又未能完全去除的有机溶剂。根据国际化学品安全性纲要，以及美国环境保护机构、世界卫生组织等公布的研究结果，很多有机溶剂对环境、人体都有一定的危害，因此，为保障药物的质量和用药安全，以及保护环境，需要对残留溶剂进行研究和控制。实际方法开发中经常面临灵敏度低、干扰峰、峰形不好或重复性差等问题。 一种利用顶空气相色谱法检测罗库溴铵中残留溶剂的方法专利，申请人为江苏盈科生物制药有限公司，申请号为201810517861.5。在现有技术中，关于罗库溴铵产品中残留溶剂的气相检测，顶空方法多采用DMSO、DMF等溶剂，方法不够环保。与现有技术相比，本发明的检测罗库溴铵中残留溶剂的方法具有环保、便捷的独特优势。同时本发明方法灵敏度高、专属性强、检测结果准确可靠的优点，可以准确评价罗库溴铵的产品质量。 其他检测方法 虽然分析方法开发难点多在药品杂质方面，专利申请也多集中在以上几个方面，但也不是说其他分析方法就不能申请专利，只要方法有创新性、解决了特定的技术问题都可以形成专利进行保护。 一种稳定的非离子型碘造影剂的含量测定方法，申请人为南京正大天晴制药，申请号为202010196316.8。碘帕醇是一种非离子低渗透单体，显影作用良好，是一种临床广泛应用的造影剂。但是由于其黏度大，对于其制剂中的碘含量进行测定一直是困扰技术领域人员的难点，现有的测定法有滴定法和高效液相色谱法，但是，由于其测定时间长，操作复杂，非常受限于操作人员的经验水平。本发明采用密度值作为测定参数，数据采集方便快捷，分析结果准确，可克服常规滴定以及高效液相分析方法操作繁琐，过程耗时，重复性差等缺点；而且本发明方法也不需准备和使用任何化学试剂，环保，高效。 一种难溶注射剂细菌内毒素的检测方法专利申请，申请人为浙江华海药业，申请号为201911118605.X。细菌内毒素是热原的主要代表物质，是注射用药物的重点控制项目。凝胶法是2015版中国药典收录的细菌内毒素检查法之一，使用鲎试剂来定性检测内毒素。这种检测方法易操作、准确性好、实用性较强。采用凝胶法检测难溶注射剂中的细菌内毒素时，因难溶注射剂粉末不溶于细菌内毒素检查用水，难溶注射剂粉末中包裹的细菌内毒素无法提取出来，导致无法准确检测产品中内毒素含量。本发明方法采用二氯甲烷等有机溶剂将难溶注射剂粉末溶解后，再使用细菌内毒素检查用水萃取有机溶剂中的细菌内毒素进行检测，该方法可以有效提取难溶性注射剂中的细菌内毒素，实现难溶性注射剂细菌内毒素检测，而且采用的有机溶剂不干扰检测，避免了现有技术中有机溶剂干扰检测的问题，方法操作简便，准确性高，重现性好，对保证注射剂的安全性具有非常重要的意义。 小结：综上结合案例对分析方法研发中可专利性挖掘进行了梳理，可见即使是做仿制药在仿的过程中仍然会遇到很多问题，仍然有很多创新点，仍然可以形成自己的知识产权。分析方法专利挖掘的关键是要找准发明所要解决的技术问题，解决该技术问题所采用的技术手段，以及相比现有技术采用本发明技术手段所带来的技术效果。当以上几点弄明白之后，我们的专利框架基本也就确定了。 参考文献： 1、 国家知识产权局专利数据库 2、 化学药物杂质研究的技术指导原则 3、 手性药物质量控制研究技术指导原则 4、 朱文泉, 马健, 李敏. 基因毒性杂质的挑战与控制策略——从ICH指导纲领到实际操作层面[J]. 中国食品药品监管, 2020(12):16. 5、 化学药物残留溶剂研究的技术指导原则 药事纵横投稿须知：稿费已上调，欢迎投稿