一、项目背景及建设条件

专案背景:艾滋病,全称为获得性免疫缺陷综合症(Acquired immunodeficiency syndrome, AIDS)，是由人类免疫缺陷病毒(Human immunodeficiency virus, HIV) 引起的全身性疾病, 是21世纪危害人类健康和生命最严重的病毒疾病之一。当前最新的抗HIV 复合药物已有了很大的进展,但也只能稳定或减缓艾滋病症状，不能彻底消灭体内病毒；而且药物通常存在着较大的毒副作用，且不能够有效解决日益严重的病毒的耐药性问题等；同时治疗费用昂贵, 数量和效果有限, 绝大部分患者无法承受。因此，研制出艾滋病疫苗是解决这一社会难题的根本途径。

国际上对艾滋病的防治投入了巨大的人力和物力，其中制药公司对艾滋病疫苗研究的经费在10亿美元/年以上。从1987年的国际上第一个艾滋病候选疫苗进入临床试验至今，全球约有30多种侯选疫苗正在临床实验，其中大多处于临床I期和Ⅱ期阶段。

建设条件:项目依托海正药业技术中心生物技术药物实验室，该研发平台已经建立了分子生物学、微生物蛋白表达体系、哺乳动物细胞表达体系、蛋白质纯化体系、微生物的分子操作。建立了2000平方米的中试车间,配置了细胞罐600L，发酵罐 1000L，年产冻干制剂30万支。发展了重组蛋白药物、核酸疫苗药物、单克隆抗体药物三大研发领域。

二、项目进展情况

目前，海正药业已经将治疗性艾滋病疫苗的研究与开发单独立项。课题组在治疗性艾滋病疫苗已经完成临床前有效性实验。其中包括：

嵌合型重组腺病毒载体的研究。

含有艾滋病病毒基因片断的活载体疫苗（Ad5/35-HIV，MVA-HIV）的构建。

治疗性活载体疫苗的扩增以及纯化和制剂的研究与开发。

治疗性活载体疫苗的临床前动物药效实验。

三、项目建设规模和内容

项目建设规模：项目拟投入315万美元，组建符合研发标准的艾滋病疫苗研究实验室、符合GMP标准的中试车间、配套的技术平台；进一步开展艾滋病疫苗的研发及关键技术研究；培养人才队伍，形成标准的管理运行体系。将形成年产活载体疫苗200万支产量的生产规模。

项目建设内容： 项目主要在已完成实验的基础上开展临床前安全性实验及临床批文的报批工作，主要包括：

符合GMP车间的建立，为临床前动物实验和报批提供样品。

治疗性活载体疫苗的前临床动物安性实验。

治疗性活载体疫苗的扩增培养工艺条件的优化。

治疗性活载体疫苗的纯化工艺条件的优化。

治疗性活载体疫苗原液和制剂质量研究和质量分析。

稳定生产三批成品。

四、项目合作方式

项目主要以合资形式，股权比例可以协商，要求外方提供资金或技术支持。

五、项目中方可提供的合作条件

中方企业主要提供现有研究基础内容和一定的固定资产投入，同时负责项目建设等。

六、项目中方情况简介

浙江海正药业股份有限公司（以下简称“公司”）创建于1956年，为国有企业。1998年2月经浙江省人民政府批准成立股份有限公司，2000年7月“海正药业”A股发行上市，2005年被列为国家500强制造业企业，2006年被批准为国家首批创新型试点企业。

公司建有国家认定的企业技术中心和人事部批准设立的博士后科研工作站，建筑面积16438 M²，研科技人员383名。设有生物技术、微生物、创新药物、合成、制剂、现代中药等研发部，50多个单元实验室，以及三个中试车间、动物试验中心、分析检测中心和信息中心等。其中生物技术药物部包括基因蛋白实验室、酶工程实验室、抗体药物实验室、GMP中试车间和质检部等，拥有摇瓶机、生化培养箱、自动化学反应控制系统，全自动控制的实验生化反应器以及分离设备。配备国际先进的分析仪器及设备，核磁共振仪、X－衍射仪、液质联用、气质联用等，检测手段与国外药典检测手段接轨。公司拥有科技人员1296人，占员工总数的49.35%；其中硕士/博士71人，外籍专家10人，留学归国博士5人。博士后科研工作站保持10位左右在站工作。

七、项目联系方式：

联系人姓名：朱康勤

电话：86-576-88827891，传真：86-576-88827887

邮编：318000

通讯地址：浙江省台州市椒江区外沙路46号

电子信箱：zkq@hisunpharm.com。

Project background, ADIS, with a full name of Acquired immunodeficiency syndrome, is a whole body disease caused by Human immunodeficiency virus and one of the most serious virus diseases that threatens the health and life of human beings in the 21^st century. At present, great progress has been made in the latest compound medicine of anti-HIV, yet only capable of stabilizing or releasing the symptom of AIDS without eliminating the virus completely. Usually, there will be harmful side effects coming along, leaving the problems unsolved, such as the increasing anti-medicine capability of virus, etc. Besides, treatment charge is quite high, yet the quantity and effect are limited, which is not affordable for most patients. Therefore, the essential way to solve this social problem is to develop the vaccine of AIDS.

Huge human and material resources have been put into the prevention and treatment of AIDS internationally, among which investment on AIDS vaccine research by pharmaceutical companies is as high as USD1 billion annually. Since the clinic test of the fist AIDS vaccine of the world in 1987, there have been around over 30 vaccine species under clinic test, most of which are in Clinic Phase I or Clinic Phase II.

Construction conditions: the project is based on the medicine laboratory of biological technologies at the technology center of Hisun Pharmaceutical. The research platform has established expression system of molecule biology, microorganism protein and mammal cell, protein purification system, molecule operation of microorganism, and a middle test workshop of 2000 m², equipped with cell tank 600L and zymolysis tank 1000L, the annual output is 0.3 million pieces of lyophilized preparation. The three research fields of recomposed protein medicine, nucleic acid vaccine medicine and monoclonal antibody medicine.

    Hisun Pharmaceutical has independently established the R&D project of therapeutic AIDS vaccine. The project group has completed the pre-clinic effectiveness experiment of therapeutic AIDS vaccine, including the followings:

Research on table-style recomposed carrier of adenovirus.

Living carrier vaccine containing gene section of AIDS virus. （Ad5/35-HIV，MVA-HIV）

R&D of expansion, purification and preparation of therapeutic living carrier vaccine.

Pre-clinic medical effect experiment on animals for therapeutic living carrier vaccine.

Project construction scale: with an estimated investment of USD3.15 million, the project will build a laboratory of therapeutic AIDS vaccines in accordance with the R&D standard, a middle-stage test workshop that meets GMP standard, and a supporting technique platform, with an effort to further carry on the R&D of therapeutic AIDS vaccines and research of key technologies, by cultivating a team of talented to form the functioning system standard management. The production scale of 2 million live carrier vaccines annually will be achieved.

Project construction content, pre-clinic safety experiment and application for clinic approval documents shall be conducted based on the experiment completion, mainly including the following,

GMP workshop will be established to supply samples of pre-clinic animal experiment and approval application.

Pre-clinic safety experiment on animal of therapeutic living carrier vaccine.

Optimization of technical condition for expansion cultivation of therapeutic living carrier vaccine.

Optimization of purification technical condition of therapeutic living carrier vaccine.

Quality research and analysis of solution and preparation of therapeutic living carrier vaccine.

Stable production of three batches of finished products.

The project is mainly planned to be jointly-funded, with negotiable investment proportion and foreign parties are estimated to provide capital or technology support.

The Chinese party mainly supplies basic content of current research and a certain amount of fixed asset investment, and takes charge of the project construction, etc.

Zhejiang Hisun Pharmaceutical Co., Ltd (hereafter referred to as “the company”) is a state-owned enterprise established in 1956. In Feb., 1998, with the approval of Zhejiang Provincial Government, it became an incorporated company; in July, 2000, “Hai Zheng Yao Ye” A-shares were issued in the stock market; in 2005, the company was named as the national top 500 manufacturers; and in 2006, it was awarded as one of the first national batch of innovation experimental enterprises.

The company is equipped with an enterprise technology center verified by the state and a scientific research station of post doctorate authorized by Ministry of Personnel, with a construction area of 16438 m² and 383 specialists of research, science and technology. There are R&D departments covering biological technology, microorganism, creative medicine, synthesis, preparation, modern TCM and so on, together with more than 50 unit laboratories, three middle test workshops, animal experiment center, analysis examination center, information center, etc. Among them, the medicine department of biological technology includes laboratory of gene protein, laboratory of enzyme project, laboratory of antibody medicine, GMP middle test workshop and inspection department, equipped with shaking bed, bio-chemical cultivation box, automatic control system of chemical interaction, bio-chemical reactor and separation equipment automatically controlled for experiments. The examination method is connected with the pharmacopoeia examination overseas by applying to internationally advanced analysis instruments and equipment, nuclear magnetic resonance instruments, X-diffraction instruments, liquid chromatography, gas chromatography, etc. The company has 1296 staff engaged in the field of science and technology, occupying 49.35% of the total workforce, 71 of which have master’s / doctor’s degree, and 10 foreign specialists, 5 doctors returned after overseas education. Around 10 people are maintained to work in the scientific research station of post doctorate.

Contact person：Zhu Kangqin

Tel：86-576-88827891，Fax：86-576-88827887

PC：318000

Address：No. 46, Waisha Road, Jiaojiang District, Taizhou City, Zhejiang Province

E-mail：zkq@hisunpharm.com