ONYX-015. Onyx Pharmaceuticals.

ONYX-015 (CI-1042), an adenovirus modified selectively to replicate in and kill cells that harbor p53 mutations, is under development by Onyx Pharmaceuticals for the potential treatment of various solid tumors, including head and neck, gastrointestinal and pancreatic tumors. It is a recombinant adenovirus that carries a loss-of-function mutation at the E1B locus, the product of which is a 55 kDa protein that binds to and inactivates the p53 tumor suppressor protein. Wild-type adenoviruses must disable this gene before viral replication can occur. This, the ONYX-015 adenovirus will leave normal cells unaffected. Mutations in the p53 tumor suppressor gene are the most common type of genetic abnormality in cancer, occurring in more than half of all major cancer types. Thus, these cells are susceptible to the virus, which will readily replicate and cause cell death. ONYX-015 is in ongoing phase III trials for the treatment of recurrent head and neck cancer, phase II trials for colorectal, ovary, pancreas and mouth tumors, and phase I trials for digestive disease, esophagus and liver tumors. Onyx Pharmaceuticals was granted US-05677178 covering methods for the treatment of p53-related cancers in October 1997. The patent specifically covers the use of modified adenoviruses and other DNA viruses, which lack viral proteins that bind to p53, for the treatment of cancer patients whose tumors lack p53 function. The USPTO awarded Onyx Pharmaceuticals US-05846945 in December 1998, covering methods for treating cancer using replicating adenoviral therapy in combination with chemotherapy. In April 1999, the company also received EP-094910177.8 covering the technology in Europe.

ONYX - 015（CI - 1042）是一种经过选择性改造的腺病毒，它能在携带p53突变的细胞中复制并杀死这些细胞，由Onyx制药公司研发，用于多种实体瘤的潜在治疗，包括头颈部、胃肠道和胰腺肿瘤。它是一种重组腺病毒，在E1B位点携带一个功能缺失突变，该位点的产物是一种55kDa的蛋白质，它能与p53肿瘤抑制蛋白结合并使其失活。野生型腺病毒在病毒复制发生之前必须使该基因失活。因此，ONYX - 015腺病毒不会影响正常细胞。p53肿瘤抑制基因的突变是癌症中最常见的基因异常类型，在所有主要癌症类型中超过一半都有发生。因此，这些细胞易受该病毒影响，病毒会轻易复制并导致细胞死亡。ONYX - 015正在进行用于治疗复发性头颈部癌症的Ⅲ期试验，用于结直肠、卵巢、胰腺和口腔肿瘤的Ⅱ期试验，以及用于消化系统疾病、食管和肝脏肿瘤的Ⅰ期试验。1997年10月，Onyx制药公司获得了美国专利US - 05677178，涵盖了治疗p53相关癌症的方法。该专利特别涵盖了使用经过改造的腺病毒和其他DNA病毒（这些病毒缺乏与p53结合的病毒蛋白）来治疗肿瘤缺乏p53功能的癌症患者。1998年12月，美国专利商标局授予Onyx制药公司美国专利US - 05846945，涵盖了使用复制性腺病毒疗法联合化疗治疗癌症的方法。1999年4月，该公司还在欧洲获得了EP - 094910177.8，涵盖了相关技术。