生物制药产业的研究现状及趋势

传统化学制药及新化学药品数量在逐年下降,而生物技术药物已成为当今最活跃和发展最迅速的领域。随着生物技术研究的深入,与人、畜疾病发展相关的生物制药产业有着突破性进展。本文从生物制药的概念出发,阐述了抗肿瘤药物、单克隆抗体、仿生药物及孤儿药物的发展现状．对我国生物制药产业的发展趋势进行简要综述,旨在为科研领域及产品开发提供理论参考．推进生物类新药的研制与开发。     

生物技术药物发展态势分析

生物技术药物是指采用现代生物技术,借助某些微生物、植物或动物来生产所需的药品。包括细胞因子、重组蛋白质药物、抗体、疫苗和寡核苷酸药物等,主要用于肿瘤、心血管疾病、传染病、糖尿病、类风湿性关节炎等疾病的预防和治疗,在临床上已开始广泛应用,为制药工业带来了革命性的变化。生物技术药物成为世界医药范围中最活跃、发展最迅速和最令人关注的领域。全球医药市场的发展重心正在逐步从化学药转向生物技术药。从产业角度分析,生物技术药物是全球医药产业的重要组成部分,预计会成为未来增长的重要推动力。因此,本文对生物技术药物的市场现状与趋势、研发状态进行分析,为相关人员提供参考。     

2023年新药研发发展现状与未来趋势

新药研发是制药行业的核心活动之一,成功发现和开发对疾病具有疗效的新药物需要跨学科的合作、大量的投资和对创新的不断追求。近年来全球新药研发竞争格局不断加速演变,我国众多创新药企寻求深层次变革与转型发展,并加快拓展海外市场。2023年,全球获批上市的创新药数量持续增长,同比增长17%,临床研究管线数量亦不断扩大;生物技术和基因疗法的发展日新月异,罕见病药物研发逐渐增多,免疫疗法领域研发取得显著成果。本研究从创新药物的类别和研发新格局等角度出发,对2023年新药研发发展态势进行梳理与总结,并展望未来发展趋势。     

我国生物制药企业发展的几点建议

随着以基因工程为核心的生物技术的迅猛发展,全国生物医药产业进入了一个前所未有的全新发展阶段,并逐渐成为新药研发的主要来源和未来医药产业的方向。但我国生物制药企业在发展中仍存在企业规模小,资源分散,科研投入不足等问题。本文就此提出了几点建议。     

寡核苷酸和小肽类药物筛选方法与新药药物设计技术学习班

(首期第一轮通知 )　　生物医药产业是当今世界发展最为迅速的两大产业之一。生物分子结构信息的研究开发利用 ,已经成为当前生物技术的一个前沿领域和研究热点 ,为各国政府部门、研究机构、高等院校瞩目 ,引起欧美各药物公司的高度重视。我国新药研发体系已由“仿制”向“创新     

生物制药的现状和未来（二）：发展趋势与希望

随着基因组和蛋白质组研究的深入,越来越多的与人类疾病发展相关的靶标被确定,使得我们能够研发更精确的药物来防治这些疾病。这意味着生物制药将有更多机会获得突破性进展,最终将使更多更好的生物技术药物被批准上市。综述了生物制药发展的几个趋势,主要有:(1)哺乳动物细胞表达的产品将在相当长的时间内占统治地位;(2)治疗性抗体将会是生物制药领域第二次创新高潮;(3)越来越多分子量大、结构复杂的功能蛋白将被开发成生物技术药物,尤其是用于治疗遗传性疾病的药物;(4)对已批准上市的生物技术药物的化学修饰尤其是PEG化以改善药物性能;(5)通过某些药物的定点突变获得第二代新生物技术药物,如胰岛素、EPO和t-PA的突变体;(6)组织工程、细胞治疗和基因治疗充满了机遇和挑战。     

多维液相色谱技术在生物大分子分离纯化中的应用

生物技术是当今最活跃的科技领域之一,生物技术革命有助于解决现在人类生存所面临的健康、食品、环境等问题.以单克隆抗体为标志的生物制药是生物技术产业中发展最为迅速的部分.目前,全球己批准35个抗体药物上市,用于癌症、自身免疫、黄斑变性、血液病和感染治疗等.     

通过RNAi和干细胞来进行筛选打破基因组新药开发的僵局

进行基因组新药的研发不一定就能发明新药。美国大型企业和国立卫生研究院（NIH）的生物技术相关预算一方面在迅速上升：另一方面美国食品与药物管理局批准的新药数量却在减少。解决上述问题的秘诀就在于RNAi和干细胞组合起来的高通量筛选（11ighthroughputscreening，HTS）技术。[第一段]     

重组蛋白药物研发及专利分析

<正>自20世纪90年代以来,全球的重组蛋白药物不断发展,已成为现代生物制药领域最重要的品类之一。截至2014年12月15日,全球至少已对3746个重组蛋白药物进行了研发,文章对这些药物及其相关专利进行分析,以期为研发人员提供参考。     

生物制药发展状况、方向及相关技术平台

自从生物技术应用于医药工业后,生物制药得以迅速发展。生物制药呈现出克隆技术、血管发生、基因治疗、药物基因组学等新的发展方向。基于现阶段基因治疗、基因工程药物、转基因植物、克隆动物、诊断试剂等相关成果和产业,基因组、生物芯片、干细胞、生物信息学、神经科学等相关技术平台的建立和完善将会对生物制药的发展起着重要的作用。     

Drug discovery of the future: the implications of the human genome project

The elucidation of the 3.2-gigabase human genome will have various impacts on drug discovery. The number of drug targets will increase by at least one order of magnitude and target validation will become a high-throughput process. To benefit from these opportunities, a theory-based integration of the vast amount of new biological data into models of biological systems is called for. The skills and knowledge required for genome-based drug discovery of the future go beyond the traditional competencies of the pharmaceutical industry. Cooperation with biotechnology firms and research institutions during drug discovery and development will become even more important.     

2014 年热门生物技术公司的研发动态

FierceBiotech 网站报道了2014 年最热门的16 家生物技术公司,其涉足生物制药、体外诊断以及医疗器械研发等热门医疗领域,其中多家公司与包括葛兰素史克、罗氏、拜耳、默克等公司在内的制药巨头展开合作,值得医疗行业的投资者关注。对这16 家热门生物技术公司的研发重点、主打产品的适应证/ 用途、合作伙伴、并购交易信息进行归纳总结,旨在为新一代生物技术药物的深入研发提供参考。     

Recent Updates on Corals from Nephtheidae

Marine natural products display a wide range of biological activities, which play a vital role in the innovation of lead compounds for the drug development. Soft corals have been ranked at the top in regard to the discovery of bioactive metabolites with potential pharmaceutical applications. Many of the isolated cembranoids revealed diverse biological activities, such as anticancer, antidiabetic and anti‐osteoporosis. Likewise, sterols from soft corals exhibited interesting biological potential as anti‐inflammatory, antituberculosis and anticancer. Consequently, investigating marine soft corals will definitely lead to the discovery of a large number of chemically varied secondary metabolites with countless bioactivities for possible applications in medicine and pharmaceutical industry. This review provides a complete survey of all metabolites isolated from the family Nephtheidae, from 2011 until November 2018, along with their natural sources and biological potential whenever possible.     

Russia through the prism of the world biopharmaceutical market

Trends in the Russian pharmaceutical biotechnology and related fields representing the major sector of domestic biotech are reviewed through the prism of the world biopharmaceuticals market. A special emphasis is placed on biogenerics and follow-on biologics. The revival of national pharmbiotech is seen in close cooperation between private companies and the state, academia and industry. One of the first positive steps toward promoting development of domestic biopharmaceuticals is the Federal Program of subsidized supply of expensive pharmaceuticals (Dopolnitel'- noe Lekarstvennoe Obespechenie). The program allows the Russian government to purchases expensive drugs to be provided free of cost to certain preferential categories of individuals. As an example, production of recombinant human insulin by the largest Russian fundamental biotechnological institute, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry under the trademark Insuran (Insulin produced by the Russian Academy of Science) is reviewed. Some prospects and problems of Russian biotech research related to medical area are briefly discussed.     

Biotechnological studies in the Far-Eastern Region of Russia

Achievements and problems in both the studies on natural bioactive compounds from the Far-Eastern higher plants and marine invertebrates and development of the corresponding biotechnologies concerning new drugs and food supplements, as well as pharmaceutical leads are discussed. Special emphasis is made on recent results from the Far-eastern Institutions belonging to the Russian Academy of Sciences, and their application in both medicine and the food industry, as well as on peculiarities of biological and chemical diversity in the North-Western part of Asia and adjoining seas.     

Follow-on Biologics: A New Play for Big Pharma: Healthcare 2010

The U.S. pharmaceutical industry plays a vital role in shaping the face of American healthcare. As an industry rooted in innovation, its continued evolution is inherent. With major patent expirations looming and thin product pipelines, the industry now must consider new directions to maintain growth and stability. Follow-on biologics, derived from living organisms and marketed after the patent expiration of similar therapies, represent a growing opportunity for big pharmaceutical firms, as discussed during Yale’s Healthcare 2010 conference in April. Key characteristics of follow-on biologics make them a worthwhile investment for big pharma companies: They command high prices, will likely have fewer entrants than generics due to high barriers to entry, and play to the existing strengths of big pharma firms. With the recent healthcare legislation providing the way for consistent Food and Drug Administration (FDA) regulation, the timing seems right to continue the push into this new and growing market.At a time when healthcare issues are on the mind of every American, it would serve us well to consider the future of one of the most influential players in the sector: pharmaceutical companies. National health expenditures for pharmaceutical products are hovering around 10 percent, meaning that one out of every 10 dollars that we, as a nation, spend on healthcare goes toward drugs. These drugs regulate our cholesterol levels, promote the growth of white blood cells in cancer patients, manage our restless leg syndrome, help us sleep better at night, and provide myriad other benefits to our health and well-being. Yet, for all the benefits that the pharmaceutical industry provides, it is also criticized by many for the expense of its products and the high profit margins that these products command. The growing popularity of biologics — treatments derived from living organisms, such as antibodies and interleukins — has particularly increased the price of drugs in the United States. The current price of the average biologic is more than 20 times that of a traditional, chemically synthesized small-molecule drug. There is a trade-off between high prices and innovative new therapies. Moreover, pharmaceutical companies themselves argue justifiably that prices account not only for the price of production, but also for the research and development (R&D) for that therapy as well as numerous others that did not make it all the way through the regulatory process and to the clinic.In recent years, we have witnessed the breakdown of the well-oiled innovation machinery of the traditional big pharma company. While R&D departments spent more and more (well over $1B per drug), they did not see promising results in the form of late-stage drug candidates [1]. Over time, this led to a strategic shift in portfolio management within big pharma companies toward an acquisition-heavy plan to build up their pipeline of drugs. In-house R&D projects were cut, and layoffs of scientific staff were rampant. This phenomenon continues, with 2009 bearing witness to the most mergers and acquisitions in the pharmaceutical industry to date. Industry-wide consolidation aimed to find complementary development projects and synergies in manufacturing and emerging markets. What has been the effect of all of this? The answer is not as hopeful as the pharmaceutical industry would have liked. A giant “patent cliff” still persists, referring to a number of blockbuster drugs that will go off patent over the next two years and cause a dramatic decrease in sales for big pharma firms. Without a strong pipeline to fill in the valley with new product sales, big pharma companies have begun scrambling to find new ways to generate revenue.Meanwhile, the biotech industry’s foray into therapeutics has been a wild success story. From the 1980s to the present, biologics have reshaped the face of medicine in many disease areas. The spawn of highly innovative, nimble biotech firms, biologic drugs are large, complex molecules grown in living cells rather than synthesized chemically like small molecules. For example, Enbrel is a fusion protein that acts as a tumor necrosis factor (TNF) inhibitor to stop inflammation. This drug is being widely prescribed for rheumatoid arthritis as well as psoriasis, among other indications, with sales last year reaching $5.9 billion, up 9.3 percent from 2008 [2]. Enbrel was first developed by Immunex and released in 1998. Immunex was acquired by a rival biotech firm, Amgen, in 2001 [3], and subsequent marketing of the drug in the United States was jointly undertaken by Amgen and Wyeth (now taken over by Pfizer in the mega-merger of 2009). Enbrel’s is the classic story of the modern biologic: a novel therapy developed at a small biotech firm and acquired or licensed up the food chain to feed bigger firms’ appetites for late-stage assets.Enbrel is by no means unique; there are many blockbuster biologics on the market. Like Enbrel, many of them will reach the end of their patent life soon. Enbrel’s patent expiration is set for 2012, at which time it will be exposed to potential competition from generic versions. Therefore, though there are many novel biologics therapies that can provide new ways of treating patients, there is also a huge opportunity for generic versions of biologics that did not exist even one decade ago. This opportunity is hard to quantify, but one recent estimate shows that biologics responsible for $20B in annual sales will go off patent by 2015 [4]. Unsurprisingly, small-molecule generics firms are flocking to this space. Teva, the world’s largest generics manufacturer, has partnered with the Lonza Group to make and sell so-called follow-on biologics. These treatments are similar, but not identical, to preceding biologics whose patents expired. Meanwhile, Novartis’s generics arm, Sandoz, has increased capacity in biomanufacturing to ramp up its efforts. Big pharma itself has made motions of interest in the business of follow-on biologics, as witnessed by the dedicated division of Merck, BioVentures, established in late 2008 for the development of follow-on biologics. Interestingly, even Pfizer is testing a follow-on version of Enbrel, now in phase 2 clinical trials [5]. With a big market opportunity and a number of firms interested, follow-on biologics will surely play an important role in shaping the future of the pharma industry.For large pharmaceutical firms, what is needed is a way to diversify and mitigate risk, a way to supplement their rollercoaster sales figures year after year. Follow-on biologics may be a smart play for big pharma companies. Like their generic cousins, biologics manufacturing has strong economies of scale that big pharma firms can leverage. But unlike generics, there are higher barriers to entry because of the technical challenges of manufacturing biologics and the necessary clinical proofs of equivalency. Pharmaceutical companies already are practiced at navigating the global clinical-trials arena and should be able to exercise a significant competitive advantage in this area, especially over the existing generics manufacturers attempting a play in the follow-on biologics market. It has been estimated that the investment necessary to bring a follow-on biologic to market is eight to 10 years and will cost $100-$200M [6]. This investment of time and capital is substantial and tends to favor larger firms with significant R&D budgets. However, to put the investment into perspective, this is only one-tenth of the cost of developing a full-scale innovative pharmaceutical product and has less associated risk of failure — a proposition that the big pharma industry should find appealing. Additionally, the trend for current follow-on biologics on the market in the European Union (EU) and United States has been to use traditional detailing and marketing practices to compete with branded products. This, too, puts big pharma at a competitive advantage over other players lacking an army of detailing pharmaceutical reps, who can use their established relationships with doctors and medical personnel to promote new follow-on biologics.One counter-argument to the case for a move into follow-on biologics is that the new healthcare reform, the Patient Protection and Affordable Care Act (PPACA), passed in March of this year will harm any would-be generic biologics makers with its 12-year exclusivity for branded biologics. However, while this length of time is significantly longer than the proposed five years that generics proponents pushed for, the surety of a secure path forward through the FDA for follow-on biologics outweighs the downside of lengthy biologics exclusivity. It is reasonable to hope that within two to three years, the FDA will have functional guidelines for the regulation of this nascent market. Now more than at any other time in the past, the ambiguity associated with government regulation is manageable. And if big pharma becomes more intentional about entering the follow-on biologics market, its powerful lobby, PhRMA, could influence the way that the details of the FDA regulations are written.If the pharma industry does find the follow-on biologics market appealing and makes a bet on it for supplementary revenue, what can we expect from the patient perspective? It could mean greater access at cheaper prices, but the dynamics are much more nuanced. The economics of the small-molecule generics market likely will not be transferrable to the follow-on biologics market. High barriers to entry, high fixed costs of manufacturing, and marketing expenses will more likely manifest themselves in a market that has a small number of firms with relatively small price drops upon introduction of follow-on therapies. In small-molecule generics, the price typically decreases by about 80 percent from the original branded drug price after one year of generic competition. However, in current follow-on markets in the EU, this has not been the case. Since its introduction of biosimilars regulation in 2004, the EU has successfully introduced numerous follow-on biologics for three classes of branded drugs. The results hint at what might be expected for U.S. firms: By 2008 in Germany, biosimilars had captured an estimated 14 percent to 30 percent market share and discounted prices by 25 percent [7]. The U.S. story of follow-on biologics will likely mirror that of EU biosimilars rather than that of small-molecule generics.With healthcare legislation passed and the inevitable refocusing on bending the cost curve in healthcare expenditures, big pharma firms may be able to boost their reputation with the public as well as their bottom line with a continued push into follow-on biologics. The decreased risk of approval and steady returns will help diversify pharmaceutical companies’ volatile revenue streams, while concurrently winning favorable public opinion by promoting price reductions for some of the most expensive drugs available. The cost savings to consumers will increase access for patients as FDA regulation is finalized and more and more follow-on biologics enter the market. This could be a win-win scenario for big pharma and for patients.     

Fragment-based approaches in drug discovery and chemical biology

Fragment-based approaches to finding novel small molecules that bind to proteins are now firmly established in drug discovery and chemical biology. Initially developed primarily in a few centers in the biotech and pharma industry, this methodology has now been adopted widely in both the pharmaceutical industry and academia. After the initial success with kinase targets, the versatility of this approach has now expanded to a broad range of different protein classes. Herein we describe recent fragment-based approaches to a wide range of target types, including Hsp90, β-secretase, and allosteric sites in human immunodeficiency virus protease and fanesyl pyrophosphate synthase. The role of fragment-based approaches in an academic research environment is also examined with an emphasis on neglected diseases such as tuberculosis. The development of a fragment library, the fragment screening process, and the subsequent fragment hit elaboration will be discussed using examples from the literature.     

The development, regulation and use of biopesticides for integrated pest management

Over the past 50 years, crop protection has relied heavily on synthetic chemical pesticides, but their availability is now declining as a result of new legislation and the evolution of resistance in pest populations. Therefore, alternative pest management tactics are needed. Biopesticides are pest management agents based on living micro-organisms or natural products. They have proven potential for pest management and they are being used across the world. However, they are regulated by systems designed originally for chemical pesticides that have created market entry barriers by imposing burdensome costs on the biopesticide industry. There are also significant technical barriers to making biopesticides more effective. In the European Union, a greater emphasis on Integrated Pest Management (IPM) as part of agricultural policy may lead to innovations in the way that biopesticides are regulated. There are also new opportunities for developing biopesticides in IPM by combining ecological science with post-genomics technologies. The new biopesticide products that will result from this research will bring with them new regulatory and economic challenges that must be addressed through joint working between social and natural scientists, policy makers and industry.