羅氏12億美元合作協議：開發DARPin毒劑偶聯藥物

　　羅氏（Roche）和Molecular Partners公司12月4日宣布，雙方已達成了一項研究合作及授權協議，發現、開發、商業化數個將Molecular Partner的DARPin生物制劑與羅氏開發的毒性制劑偶聯而成的抗癌藥物。

　　DARPin-藥物偶聯物將成為令人激動的新一類藥物，與現有療法相比，有望提供增強的療效，并為患者帶來實質性的臨床益處。

　　DARPins是一組并非基于抗體的小分子蛋白，該組蛋白中的可變區域已被設計為靶向結合。小分子尺寸及高結合親和力，使這些分子能夠深入滲透至實體腫瘤。因此，DARPins是理想的靶向藥物，可用于向腫瘤遞送毒性制劑，以殺死癌細胞。由于DARPins與抗體所結合的表位（epitope）不同，而且可在同一時間并聯結合多個表位或靶標，與其他生物制劑（包括抗體偶聯藥物）相比，DARPins被認為對腫瘤細胞具有更高的選擇性。

　　根據協議條款，羅氏將有權開發和商業化數個基于DARPin的產品。Molecular Partners將有資格獲得一筆5500萬瑞士法郎（約合6100萬美元）的預付款和起始款項。同時，Molecular Partners將獲得研究經費，在所有潛在產品均達到開發、銷售里程碑后，更將獲得高達10億瑞士法郎（約合11億美元）的里程碑款項。此外，Molecular Partners還將獲得所合作產品在未來銷售的特許權使用費。

　　除羅氏外，Molecular Partners早在2008年就與強生（JNJ）旗下楊森（Janssen）達成了DARPins藥物研發合作，雙方在2011年新增11億美元合作項目，開發DARPin藥物用于治療免疫性疾病。

　　此外，Molecular Partners于2011年與艾爾建（Allergan）達成了4億美元的DARPins藥物研發合作，雙方在2012年新增15億美元項目，開發MP0112用于視網膜疾病。MP0112是一種DARPin蛋白，可特異性針對VEGF進行治療。

　　關于DARPin平臺：

　　DARPins（Designed Ankyrin Repeat Proteins）為新一代的靶標-結合蛋白，由天然存在的錨定重復序列蛋白（Ankyrin Repeat Proteins）設計而來，這類蛋白已自然演變為對靶標具有高度親和結合，通常這些蛋白與另一種蛋白通過融合結構域連接，將后者錨定至一個特定的位點。

　　DARPin的成功，最有可能歸因于一個事實，即這些蛋白已自然進化出具有卓越的靶向結合能力，包括多特異性。

　　關于錨蛋白重復序列（ankyrinrepeat，ANK）：

　　ANK是廣泛存在于生物體中的一種蛋白質序列模體(motif)，ANK模體在ANK結構域中折疊成β2α2結構，在空間上則形成L型結構。數目不等的ANK串聯起來，依靠氫鍵和疏水相互作用，組成緊密、穩定的結構域，并且形成了種類眾多但功能各異的ANK蛋白質分子。

　　ANK結構域介導蛋白質-蛋白質的相互作用，它能夠與多種配體結合，實現紛繁復雜的生物功能。

　　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.