台灣藥廠呼應 "走出去" 政策 !!

國際合作 生技新概念 【經濟日報╱記者黃文奇／台北報導】 2012.07.13 04:34 am 生技下半年走勢，第一金投顧研究部經理宋豪麟昨（12）日表示，「國際合作的概念」將是下半年最夯議題，包括永豐餘（1907）轉投資的太景生技，台灣微脂體及東洋等，下半年都將有國際合作進展。 其中，太景生技近期和大陸浙江醫藥合作，將旗下新藥「奈諾沙星」大陸市場授權出去，創下台灣新藥授權大陸首例，太景下半年起將獲得1,400萬美元（約新台幣4.2億元）授權金，最慢後年起搶攻每年人民幣10億元（約新台幣47億元）市場商機，由於永豐餘集團共握有資太景約34%股權，也將同步受惠。台灣微脂體日前也宣布將和全球最大學名藥廠TEVA，及美國安成藥業共同合作，以開發、製造並銷售旗下抗癌藥。法人估，台微體也可望在今年拚轉盈。 根據了解，台微體曾將抗癌藥物Doxisome授權給安成，近期雙方又將此藥物共同授與TEVA銷售，目前預估市場規模約4到5億美元（近新台幣150億元），目前已經在澳洲生產，下半年可望在美國開賣。 宋豪麟提醒，下半年除了國際合作題材外，由於大陸在十八大交班後，「十二五規劃」的挹注下，生技中概族群會繼續加溫，包括前述的太景，還有大陸肝藥通路F-康聯都值得注意。另外，農業生技近期也逐漸獲重視，下半年旺季報到，應有不錯表現。 【2012/07/13 經濟日報】  

Nature Genetics刊登: 單一基因突變(FAN1) 造成慢性腎臟病 (CKD) !!!

Researchers identify new genetic cause for chronic kidney disease  July 10, 2012 in Genetics A new single-gene cause of chronic kidney disease has been discovered that implicates a disease mechanism not previously believed to be related to the disease, according to new research from the University of Michigan.  The research was published July 8 in the journal Nature Genetics. "In developed countries, the frequency of chronic kidney disease is continually increasing for unknown reasons. The disease is a major health burden," says Friedhelm Hildebrandt, M.D., the paper's senior author and professor of pediatrics and of human genetics at C.S. Mott Children's Hospital. Using whole exome sequencing, Hildebrandt and his colleagues studied a model disorder for renal fibrosis, nephronophthisis, and detected a new single-gene cause of CKD that implicates a disease mechanism formerly not related to CKD — DNA damage response signaling (DDR). "Since DNA damage is cause by a whole variety of chemical compounds it may now be important to see whether certain 'genotoxins' may play a role in the increase of CKD," says Hildebrandt who is also an investigator for the Howard Hughes Medical Institute. The researchers identified mutations of Fanconi anemia-associated nuclease 1 (FAN1) as causing karyomegalic interstitial nephritis (KIN) in patients with CKD. Depletion of fan1 in a zebrafish model of disease revealed increased DDR, apoptosis, and kidney cysts akin to nephronophthisis. "Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms of renal fibrosis and CKD," Hildebrandt said. Journal reference: Nature Genetics Provided by University of Michigan Health System  

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair.

Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of nephronophthisis, except for the presence of karyomegaly. The FAN1 protein has nuclease activity and acts in DNA interstrand cross-link (ICL) repair within the Fanconi anemia DNA damage response (DDR) pathway. We show that cells from individuals with FAN1 mutations have sensitivity to the ICL-inducing agent mitomycin C but do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from individuals with Fanconi anemia. We complemented ICL sensitivity with wild-type FAN1 but not with cDNA having mutations found in individuals with KIN. Depletion of fan1 in zebrafish caused increased DDR, apoptosis and kidney cysts. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms contributing to renal fibrosis and CKD.

加速推動旭東海普上市!!!

 2012/07/11 10:22 精實新聞 2012-07-11 10:22:24 記者 蕭燕翔 報導 東洋(4105)公告，處分香港東洋國際部分股權有效期將展延至今年10月30日，該公司表示，主要是因應策略夥伴匯款交割地點的變更及稅負考量，整體交易預計10月底前完成，匯款可能分三批入帳。法人估計，該處分完成除可挹注東洋逾3億元的處分收益外，也將加速上海旭東海普的上市計畫，有助集團產業布局更趨完整。 東洋去年3月上旬公告，將處分香港東洋國際49.09%股權，價金約1.24億人民幣，折合台幣約5.7億元，扣除成本後，處分利益超過3億台幣，處分完成後，東洋藉香港東洋持有上海旭東海普的股權將降至28%左右。 因應策略夥伴集團佈局的考量，東洋公告將處分香港東洋部分股權的契約有效期延長至10月30日。東洋表示，主要是策略夥伴希望深化在台灣的投資，因而規劃在台設立公司，未來交易款項交割的地點可能由香港轉至台灣，惟在稅負及其他考量下，交易款預計分成三次入帳，除首筆預收款2千萬台幣外，其餘款項預計在10月底前完成交割後認列。 法人估計，若完成交易後，東洋將可認列3.5-3.8億元的處分利得，對每股盈餘的挹注約2.1-2.2元。比較重要的是，該處分完成後，東洋可解決與上海旭東海商業競爭的疑慮，有助於推動在大陸上市，一旦上市後，東洋集團在大中華區製藥供應鏈的佈局會更趨完整。 除上海旭東海普外，東洋在大陸另一重點佈局的東曜，日前已完成第二次增資，資金到位後多數投入新廠興建，內部估計，年底前一期工程可望有部分癌症化學藥試量產，2014年東曜營運可望達損益兩平以上，成為下個十年的集團金雞母。  

Liver stiffness predicts liver failure, cancer and mortality in cirrhotic patients

 July 10, 2012 Researchers from Spain established that liver stiffness, measured by transient elastography (TE), is an independent predictor of liver failure, hepatocellular carcinoma (HCC), and mortality in cirrhotic patients coinfected with the human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS), and hepatitis C virus (HCV). Findings available in the July issue of Hepatology, a journal published by Wiley on behalf of the American Association for the Study of Liver Diseases, also show that measurement of liver stiffness predicts potential recovery and survival in patients with cirrhosis, adding to the prognosis value provided by the Child-Turcotte-Pugh (CTP) or model for end-stage liver disease (MELD) scores. According to the World Health Organization (WHO), chronic HCV affects up to 170 million people worldwide, with more than 350,000 of those dying from HCV-related liver diseases annually. WHO also reports that in 2010 nearly 34 million individuals worldwide were living with HIV. Additionally, a 2008 report from the Centers for Disease Control and Prevention (CDC) found that mortality rates were highest among those infected with HCV at nearly five deaths per 100,000 people. In fact, since 1999 deaths from HCV have steadily increased and now exceed HIV infection mortalities. For the present study Dr. Nicolás Merchante from the Unidad de Enfermedades Infecciosas, Hospital Universitario de Valme in Sevilla, Spain conducted a multicenter prospective study of cirrhotic patients coinfected with HIV and HCV beginning in February 2006. A total of 239 consecutive HIV/HCV patients with a new diagnosis of compensated cirrhosis participated in the study to assess the predictive value of liver stiffness as measured by TE. Participants were followed between nine and 34 months, and 13% of patients developed liver failure (decompensation). The incidence of decompensation was 6.7 cases per 100 person-years. Researchers reported 15 patient deaths with ten due to liver disease, and liver transplant was performed on one patient. In 8% of 181 patients with baseline liver stiffness less than 40 kPa developed liver failure compared with 29% of 58 patients with liver stiffness greater than 40 kPa. Medical evidence shows that end-stage liver disease from chronic HCV is a leading cause of death in HIV-infected individuals living in western countries. "For patients with end-stage liver disease, transplantation is often the only treatment option," said Dr. Merchante. "Earlier recognition of cirrhosis and optimal treatment of cirrhotic patients at the initial stages are critical. Our findings indicate that liver stiffness predicts risk of liver failure and liver-related deaths in patients with compensated cirrhosis who are coinfected with HIV and HCV, providing more advanced detection of disease severity." The authors suggest that future studies should evaluate if liver stiffness is also an independent prognostic marker in decompensated cirrhosis, which then could be used in conjunction with CTP and MELD scores in considering patients referred for liver transplantation. More information: "Liver Stiffness Predicts Clinical Outcome in Hiv/Hcv-Coinfected Patients with Compensated Liver Cirrhosis." Nicolás Merchante, Antonio Rivero-Juárez, Francisco Téllez, Dolores Merino, Maria José Ríos-Villegas, Manuel Márquez-Solero, Mohamed Omar, Juan Macías, Ángela Camacho, Montserrat Pérez-Pérez, Jesús Gómez-Mateos, Antonio Rivero, Juan Antonio Pineda on behalf of the Grupo Andaluz para el Estudio de las Hepatitis Víricas (HEPAVIR) de la Sociedad Andaluza de Enfermedades Infecciosas (SAEI). Hepatology; (DOI: 10.1002/hep.35616); Print Issue Date: July, 2012. Journal reference: Hepatology 

肝臟纖維掃描儀對肝纖維化的非侵襲性評估

高偉育、蘇建維、侯明志（臨床醫學 2009; 64: 133-40） 肝臟纖維掃描儀（transient elastography (TE, FibroScan?）是一種非侵襲性的新方法，可藉由測量肝硬度（liver stiffness）來評估慢性肝病病患肝纖維化（liver fibrosis）的情形。肝臟纖維掃描儀是一種快速且容易操作的技術，可用於門診或在住院病人的床邊，立即得到結果並有很好的重現性（reproducibility）。約有5%的病例會測量失敗，主要是在肥胖的病人。肝臟纖維掃描儀在慢性C型肝炎患者診斷肝纖維化方面，與肝臟切片結果相較，二者有良好的相關性，合併肝臟纖維掃描儀和血清標記檢驗更可增加診斷的準確性，這樣可避免使用肝切片來對慢性C型肝炎做初期的評估。這個策略可再用於評估其他病因造成的慢性肝疾病。此外，肝臟纖維掃描儀在早期偵測肝硬化及其預後方面，似乎也是一個出色的工具。肝臟纖維掃描儀容易被病人所接受，因此可使用於監測個別病例的肝纖維化惡化和改善之情形。但在臨床上廣泛使用肝臟纖維掃描儀做為診療常規，仍尚需等待更多應用的研究數據以及指導方針來佐證。 

東洋: 全球癌症針劑中心(80萬劑) !!!!

東洋抗癌針劑 擴產1倍  【經濟日報╱記者黃文奇／台北報導】 2012.07.13 03:59 am 台灣東洋（4105）董事長林榮錦昨（12）日表示，公司投資的中壢癌症針劑廠，投資金額將從原本的2億元加碼到5億元，產能再擴充1倍以上達80萬劑，並趕在今年10月底前投產，以打造全球癌症針劑中心。 台灣東洋指出，該廠投產後將結合美國大藥廠，共同生產癌症針劑，並可望拿下台灣第一個打進美國癌症用藥市場的機會。東洋昨日股價收112元，下跌1元。 據了解，未來東洋將以旗下微脂體包覆技術，和美國大藥廠合作抗癌針劑製造，雙方將以結盟方式搶進美洲抗癌藥物市場。東洋表示，未來該廠投產後，不僅會和美國藥廠合作，還將申請全球衛生單位認證，並釋出合作機會，林榮錦企圖心強，喊出「東洋要做全球癌症針劑中心」。 據了解，未來東洋在美洲銷售的抗癌針劑，將以乳癌、骨癌等適應症為主；法人估，該類藥品目前美洲市場規模約30億美元（約新台幣900億元），若以最大產能80萬劑估算，東洋每年獲利可望增加4到8億元。 至於結盟對象，法人圈則傳出，東洋合作對象就是美國嬌生（Johnson & Johnson）藥廠。 對此林榮錦不願證實，他僅表示，「一切都還在進行中，不便透露」；分析師表示，以建廠進度來說，目前應大抵完成硬體設備，近期美國食品藥物管理局（FDA）將來台查廠。 林榮錦說，由於規模擴大，去年原本預估的2億元預算，後來經過幾次追加，已經約達5億元，產能並從原本規劃的40萬劑，擴充到80萬劑。因此，原本預定今年9月前就會投產的時程，稍微延宕了一下，但會趕在今年10月底前投產。 此外，東洋近期也公告，將在10月底前處分香港東洋國際部分股權約49.09%，價金約人民幣1.24億元（約新台幣5.7億元），扣除成本後將挹注東洋約3億元的獲利，款項將分三批入帳。完成股權處分後，上海旭東海普可望加速在大陸的上市計畫。 【2012/07/13 經濟日報】