罗氏12亿美元合作协议：开发DARPin毒剂偶联药物

　　罗氏（Roche）和Molecular Partners公司12月4日宣布，双方已达成了一项研究合作及授权协议，发现、开发、商业化数个将Molecular Partner的DARPin生物制剂与罗氏开发的毒性制剂偶联而成的抗癌药物。

　　DARPin-药物偶联物将成为令人激动的新一类药物，与现有疗法相比，有望提供增强的疗效，并为患者带来实质性的临床益处。

　　DARPins是一组并非基于抗体的小分子蛋白，该组蛋白中的可变区域已被设计为靶向结合。小分子尺寸及高结合亲和力，使这些分子能够深入渗透至实体肿瘤。因此，DARPins是理想的靶向药物，可用于向肿瘤递送毒性制剂，以杀死癌细胞。由于DARPins与抗体所结合的表位（epitope）不同，而且可在同一时间并联结合多个表位或靶标，与其他生物制剂（包括抗体偶联药物）相比，DARPins被认为对肿瘤细胞具有更高的选择性。

　　根据协议条款，罗氏将有权开发和商业化数个基于DARPin的产品。Molecular Partners将有资格获得一笔5500万瑞士法郎（约合6100万美元）的预付款和起始款项。同时，Molecular Partners将获得研究经费，在所有潜在产品均达到开发、销售里程碑后，更将获得高达10亿瑞士法郎（约合11亿美元）的里程碑款项。此外，Molecular Partners还将获得所合作产品在未来销售的特许权使用费。

　　除罗氏外，Molecular Partners早在2008年就与强生（JNJ）旗下杨森（Janssen）达成了DARPins药物研发合作，双方在2011年新增11亿美元合作项目，开发DARPin药物用于治疗免疫性疾病。

　　此外，Molecular Partners于2011年与艾尔建（Allergan）达成了4亿美元的DARPins药物研发合作，双方在2012年新增15亿美元项目，开发MP0112用于视网膜疾病。MP0112是一种DARPin蛋白，可特异性针对VEGF进行治疗。

　　关于DARPin平台：

　　DARPins（Designed Ankyrin Repeat Proteins）为新一代的靶标-结合蛋白，由天然存在的锚定重复序列蛋白（Ankyrin Repeat Proteins）设计而来，这类蛋白已自然演变为对靶标具有高度亲和结合，通常这些蛋白与另一种蛋白通过融合结构域连接，将后者锚定至一个特定的位点。

　　DARPin的成功，最有可能归因于一个事实，即这些蛋白已自然进化出具有卓越的靶向结合能力，包括多特异性。

　　关于锚蛋白重复序列（ankyrinrepeat，ANK）：

　　ANK是广泛存在于生物体中的一种蛋白质序列模体(motif)，ANK模体在ANK结构域中折叠成β2α2结构，在空间上则形成L型结构。数目不等的ANK串联起来，依靠氢键和疏水相互作用，组成紧密、稳定的结构域，并且形成了种类众多但功能各异的ANK蛋白质分子。

　　ANK结构域介导蛋白质-蛋白质的相互作用，它能够与多种配体结合，实现纷繁复杂的生物功能。

　　英文原文：

Roche and Molecular Partners enter into alliance to develop new cancer treatments

　　Roche and Molecular Partners enter into alliance to develop new cancer treatments

　　Partnership will combine novel biologics (DARPins) with Roche drug-conjugate technology

　　Roche (SIX: RO, ROG； OTCQX: RHHBY) and Molecular Partners AG today announced that they have entered into a research collaboration and licensing agreement to discover, develop and commercialize several proprietary therapeutics incorporating Molecular Partners’ DARPin? biologics conjugated to toxic agents developed at Roche for the treatment of cancer.

　　DARPin-drug conjugates would be an exciting new class of drugs offering the potential of enhanced efficacy with substantial patient benefit over existing therapies.

　　DARPins are non-antibody-based small proteins where a variable region has been engineered for target binding. Their small size and high binding affinity enable them to hone in on and penetrate deep into solid tumors. DARPins are thus ideal targeting agents to deliver toxic agents to tumors to kill cancer cells. As a result of their ability to bind to different epitopes than antibodies, and by binding to multiple epitopes or targets in parallel at the same time, DARPins are believed to have a higher selectivity for tumor cells compared to other biologics including antibody drug conjugates.

　　“We are excited about this collaboration as the DARPin platform is truly complementary to our internal capabilities in the large molecule space,” Sylke Poehling, Head of Large Molecule Research at Roche commented. “In the field of drug conjugates, we have identified an excellent opportunity to combine our expertise with the leading company in non-antibody scaffold technology to develop transformative cancer medicines.”

　　Christian Zahnd, Ph.D., Chief Executive Officer of Molecular Partners, added, “Roche is one of the top players in oncology and specifically the toxic payload field. By combining its technical and commercial expertise with our DARPin R&D expertise, we can rapidly develop a pipeline of highly differentiated products offering a novel approach to treating patients far more quickly than we could do independently, offering new hope for patients with unmet medical need. The DARPin-drug conjugate is an exciting new product direction for us alongside our internal proprietary DARPins and our existing partnerships in ophthalmology and immunology.”

　　Under the terms of the agreement, Roche has rights to develop and commercialize several DARPin-based products. Molecular Partners is entitled to receive upfront and initiation payments up to CHF 55 million. Furthermore, Molecular Partners will receive research funding and can earn more than CHF 1 billion if all development and sales milestones are met for all potential products. In addition Molecular Partners will receive tiered royalties on any future product sales into the double-digit percentage range.

　　About Molecular Partners AG

　　Molecular Partners is a privately-owned biotech company focusing on the research, development and commercialization of a novel class of biological drugs known as DARPins. The company is committed to create medicines for diseases with unmet medical need and to dramatically improve existing therapies. DARPins combine the high specificity, selectivity and safety of monoclonal antibodies with many advantages of small molecules, including high stability and low-cost production.

　　Molecular Partners has established a strong DARPin pipeline which is well differentiated from standard therapeutic approaches. Next to ophthalmology, Molecular Partners is focusing on DARPin drugs in inflammation, oncology and other disease areas. The internal pipeline is expanded by partnered programs with leading pharmaceutical companies. Molecular Partners has established alliances with Allergan and Janssen and other pharmaceutical companies. The company is backed by a strong syndicate of investors and holds a strong patent estate covering all DARPin applications.

　　About Roche

　　Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, infectious diseases, inflammation, metabolism and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2012 Roche had over 82,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 45.5 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.