美国麻省生物技术公司（GTC Biotherapeutics）利用转基因动物技术开发、生产和商业化治疗用蛋白质。ATryn是GTC生物治疗公司开发的一种人抗凝血酶重组蛋白，它是第一个在世界上得到认可的转基因动物生产的蛋白。GTC生物治疗公司正在开发从人类血浆蛋白的重组蛋白，同时开发单克隆抗体。这些产品可能应用于血液学、肿瘤学和自身免疫疾病。  重大事件：  2006年1月，美国GTCBiotherapeutics公司收到美国专利商标局有关覆盖从转基因动物的乳汁中分泌、精制治疗用蛋白质生产法的专利申请的审查通知。  2006年2月，欧洲药品管理局宣布，因为临床试验不充分等原因，美国GTC公司生产的世界上第一种源自转基因动物的药品不能在欧盟上市。 2006年6月宣布，美国GTC公司用转基因山羊生产的人抗凝血酶“ATryn”（α-antithrombin）获得欧洲药品评价局（EMEA）人用药品委员会（CHMP）的批准推荐。  2007年7月，美国GTC公司开发了获取精对苯二甲酸(PTA)较简易又高效的方法。  2009年2月，FDA首次批准由转基因动物生产药物上市。

美国食品和药物管理局刚批准首个转基因动物表达的药 ATryn（α-antithrombin），人类终于有了第一个转基因动物生产的药物上市用于临床。该药品是从经过基因修饰奶山羊分泌出的羊奶中提取纯化，它是用于治疗一种被称为遗传性抗凝血酶缺乏症的疾病。

这种药物是由美国一家生物技术公司GTC Biotherapeutics ，这种药物的上市标志着转基因动物药物真正迈入产业化时代。记得20年前，笔者在做博士论文时，就看到当时这家美国生物技术公司类似试验获得成功的报道，当时觉得非常惊讶和兴奋，动物居然可以成为活的生物反应器，为人类生产昂贵的药物。生物技术太神奇了。没想到从实验动物的初步成功到药物上市，走了二十多年漫长的路。这家公司就在离自己做论文的实验室10多英里处，后来还有同学去那家公司工作。公司是Genezye旗下的公司，为了分担风险和募集资金，母公司还特意剥离了这家公司单独在NASDAQ单独上市。尽管后来这家公司花费巨大财力物力，不断取得工艺突破和临床研究进展，但公司的产品就是迟迟上不了市。因为全世界没有这种先例，用转基因动物来替代生物发酵和细胞培养的大工厂化生产生物药。正因为缺乏操作和审批指南，使得该产品的研制过程格外艰难曲折。

几个星期前，美国食品和药物管理局遗传工程动物制药相关问题发布了一套规章和报批指南。使得审批这类药物有章可循，有了明显的审批和操作的程序和方向，给转基因动物生产药物带来美好的前景。欧洲药监部门的专家本周刚逆转过去持否定态度，也开始推荐 ATryn（α-antithrombin）药物的上市，看来GTC Biotherapeutics 在经历这么多年曲折，终于要扬眉吐气后，开始腾飞了。下周的股票一定会攀升。

纽约时报最近列举了几个正在开发中的通过转基因动物手段生产的药物：一家名为Pharming药业的公司正计划申请一种批准的药物，是在转基因兔的奶中表达和提取的，用于治疗某种遗传性蛋白质缺陷症；而另一家公司也在研制一种转基因山羊表达的药物，用于治疗神经毒气中毒的患者。

ATryn® market authorization transferred to LEO Pharma A/S

The market authorization of ATryn® has been transferred to LEO Pharma A/S who also conduct and fund a phase II study in 2007. GTC Biotherapeutics, Inc. announced 3 January 2007 that the market authorization of ATryn® for the prophylaxis of venous thromboembolism in surgery of patients with congenital antithrombin deficiency has been transferred to its distribution and development partner, LEO Pharma A/S, following approval by the European Commission. ATryn® is a recombinant form of human antithrombin. Antithrombin is normally found in human plasma and has both anticoagulant and anti-inflammatory properties. The approval of the transfer of the market authorization enables LEO to enter into negotiation of reimbursement rates as part of preparing for the commercial launch of ATryn® in Europe on a country-by-country basis. The initial launch is being planned for around the end of the second quarter 2007. Further studies in Europe In addition, LEO is conducting a phase II study of ATryn® in Europe for the treatment of disseminated intravascular coagulation, or DIC, associated with severe sepsis. LEO has initiated the regulatory approval procedures to enable the opening of clinical sites and recruitment of patients into the study. GTC is continuing to supply the product to LEO to conduct this study.     ATryn® (Photo: Business Wire).  Financial details Meeting these objectives in the development of the ATryn® program supports GTC’s previous guidance that pro-forma cash and marketable securities at the end of 2006 will be approximately $50 million. While actual cash and marketable securities at the end of 2006 will be approximately $43.9 million, the pro-forma amount includes the scheduled completion in early January of the third and final tranche of the previously announced $25 million total investment by LFB Biotechnologies, as well as scheduled payments for delivery of a portion of the phase II clinical supply to LEO in January that was begun in late 2006. GTC expects to use $26 to 29 million of cash in 2007 on a pro-forma basis. This forecast is net of cash received from operations, but excludes the items included in the 2006 year end pro-forma cash balance. The net cash use for 2007 includes forecasted sales of ATryn® in the approved indication as well as to LEO for the DIC study. This forecast also reflects lower debt service payments due to refinancing of the loan with GE Capital in the last week of December 2006. This debt refinancing extended the amortization period from three to ten years and provided an additional $2.8 million of proceeds to GTC. US phase III study of the hereditary deficiency indication The 2007 cash use forecast includes planned support for completion of GTC’s phase III study of ATryn® in the hereditary deficiency indication for the United States, the filing of a Biologics License Application in the United States, development of the recombinant human factor VIIa production system with LFB Biotechnologies, and preclinical activities in GTC’s recombinant human alpha-1 antitrypsin and CD137 monoclonal antibody programs. The phase II DIC study activities in 2007 will be conducted and funded by LEO. Background on the ATryn® DIC Study DIC often develops as a result of severe sepsis. This is a large unmet medical need with approximately 220,000 cases in Europe and 250,000 cases in the United States with 50% mortality. Analysis of previous clinical experience indicates that treatment with antithrombin, without the concomitant use of heparin, has the potential to reduce the rate of mortality. LEO Pharma’s phase II study is based on Scientific Advice received from the European Medicines Agency. Approximately 200 patients are planned to be included in this study which is intended to define the optimum dosage and design for use in a subsequent phase III study. Recruitment into the phase II study is expected to take approximately 12 months. About GTC Biotherapeutics, Inc. GTC Biotherapeutics develops, produces, and commercializes therapeutic proteins through transgenic animal technology. In August 2006, ATryn®, GTC’s recombinant form of human antithrombin, was approved by the European Commission for use in patients with hereditary antithrombin deficiency undergoing surgical procedures. This was the first approval anywhere in the world of a therapeutic protein produced from a transgenic animal. ATryn® is in phase III studies to support a filing in the United States requesting approval in the hereditary deficiency indication. In addition, GTC established a strategic collaboration with LFB Biotechnologies of France to jointly develop recombinant forms of human plasma proteins and monoclonal antibodies. The first program of the collaboration will be to develop recombinant human factor VIIa as a potential treatment for hemophilia in patients with antibodies to other coagulation factors. GTC has also recently been granted a patent in the United States through 2021 for the production of any therapeutic protein in the milk of any transgenic mammal. GTC’s transgenic production platform is particularly well suited to enabling cost effective development of proteins that are difficult to express in traditional recombinant production systems as well as those that are required in large volumes. Additional information is available on the GTC website www.gtc-bio.com. Forward-looking statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the planned completion of LFB Biotechnologies’ investment in GTC, the anticipated cash payments receivable upon delivery of clinical supplies of ATryn® to LEO, the expected commercial launch of ATryn® in Europe, GTC’s projected pro-forma cash balance at the end of 2006 and its projected net cash use for 2007. Such forward-looking statements are subject to a number of risks, uncertainties and other factors that could cause actual results to differ materially from future results expressed or implied by such statements. Factors that may cause such differences include, but are not limited to, the risks and uncertainties discussed in GTC's most recent Annual Report on Form 10-K and its other periodic reports filed with the Securities and Exchange Commission, including the risks and uncertainties associated with the development of therapeutic proteins and dependence upon the actions of strategic partners and regulatory agencies. GTC cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this document, and GTC undertakes no obligation to update or revise the statements, except as may be required by law. About LEO Pharma A/S LEO Pharma is an independent research-based company with headquarters in Ballerup, Denmark, and affiliates and regional offices in more than 40 countries. LEO Pharma is 100% owned by the LEO Foundation and employs approximately 3,300 people. The group is one of the world's leading companies in topical dermatology and parenteral treatment of thromboembolic disorders. LEO Pharma products are marketed in more than 90 countries. Additional information is available in the News Room of this website. Contact GTC Biotherapeutics, Inc. Thomas E. Newberry Vice President Corporate Communications +1 (508) 370-5374 LEO Pharma contact information.   Read more about ATryn®