中國造埃博拉藥物挽救生命 卻捲入專利糾紛

After a nurse who contracted Ebola in Sierra Leone was discharged Wednesday from a Rome hospital, a doctor there described the experimental treatments the patient had received as “absolutely miraculous.”

在塞拉利昂感染埃博拉病毒的一位護士週三從羅馬一家醫院出院，該院一位醫生形容病患接受的試驗治療的效果“絕對如奇蹟一般”。

They included MIL77, a product from China that was also given to a British Army nurse who recovered from Ebola at a London hospital in March. It is a near copy of what many believed was the most promising Ebola therapy: a cocktail of antibodies known as ZMapp, the result of a collaboration between the United States and Canada.

治療中使用了中國生產的MIL77，倫敦一家醫院在三月也用這個藥品治療了一位感染埃博拉的英國陸軍護士，現已治癒。該藥幾乎原樣複製了最被人看好的埃博拉療法，也就是被稱作ZMapp的抗體綜合劑，後者是美國與加拿大合作的成果。

While ZMapp was mired in production delays last fall and winter and quickly became unavailable, a small private Chinese company, Beijing Mabworks, raced ahead, helping produce about 100 doses of MIL77. That means more potentially lifesaving treatments for desperate patients. But it has also led to patent infringement concerns by American officials, and to disagreements over when experimental Ebola therapies should be offered to patients only in carefully controlled studies and when they should be made more available for compassionate reasons.

ZMapp的生產在去年秋冬陷入困難，很快就斷供了，一家叫作“北京天廣實生物技術有限公司”的小型中國民營公司因此迎頭趕上，製造了100劑MIL77。這意味着有更多絕望的病人可以得到挽救生命的治療。但侵犯專利權的問題已經引起美國官員注意，而實驗性的埃博拉療法何時應該僅限於在嚴格管控的研究中施用，何時應該基於同情心提供給更多人，各方的看法也存在分歧。

Feng Li, chief executive of Beijing Mabworks, said his company was motivated to fight a global emergency and had made a licensing agreement with ZMapp’s intellectual property rights holder. “People think international collaboration could easily happen between the U.S. and Canada,” he said, “but these days, China could play a role” by making emergency response drugs “better and faster in some cases.”

天廣實的首席執行官李鋒表示，公司是希望去應對一場全球急難，並且與ZMapp的知識產權持有者簽署了授權協議。“人們認爲美加之間易於發展國際合作，”他說，“但如今，中國也可以在其中發揮作用”，有時能在應急藥品的製作上“達成更好、更快的結果”。

ZMapp is being tested in a clinical trial in the United States and Sierra Leone, where the government reported nine new cases of Ebola on Thursday, one of the highest daily totals in months.

ZMapp在美國與塞拉利昂進行臨牀試驗，後者的政府在週四有九起新病例，是數個月來單日最多的一天。

Last summer, when Ebola was raging out of control, ZMapp raised hopes after it was given to two American aid workers with the disease. Both recovered. Scientists had already shown that ZMapp could save monkeys injected with what would have been a lethal dose of the virus.

埃博拉病毒在去年夏天失控。但受到感染的兩位美國救援工作者獲得ZMapp後都已痊癒，因此喚起一線希望。科學家發現，ZMapp可以讓注射了致死病毒量的猴子存活。

Tobacco plants were engineered to produce ZMapp, a mixture of three antibodies designed to attach to the covering of the virus, neutralize it and attract killer immune cells. That was an unusual production method, chosen in part to meet the requirements of an American government grant that promotes innovation. However, there were no facilities capable of producing large amounts of the treatment.

ZMapp使用經過改造的菸葉植物進行生產，它混合了三種抗體，可以附着在病毒令其失去效力，然後吸引殺手免疫細胞發揮效果。用菸葉製作抗體的生產方法並不常見，選擇它的其中一個原因是，研發獲得了美國政府的一項鼓勵創新資金，因此要符合該撥款的要求。然而，現在沒有設施適合製作大量藥劑。

Then China jumped in. The scarcity of ZMapp was “a spark, like lightning to me,” said Boyan Zhang, chief scientific officer at Beijing Mabworks. Supported by Chinese government grants, the company had developed mammalian cells capable of quickly producing antibodies targeted against cancer and viral diseases in humans, and its leaders decided to use the same process to develop an Ebola remedy.

中國因此投入生產。天廣實的首席科學顧問張博彥表示，ZMapp的稀缺“讓我靈光乍現”。在中國政府的支持下，這家公司先前研發出一種哺乳類細胞，可以快速製造對抗癌症與病毒性疾患的抗體。公司高層決定利用同一方法開發埃博拉的療法。

China, highly attuned to infectious diseases since the outbreak of severe acute respiratory syndrome in 2003, had many citizens working in West Africa. “The entire country was mobilized,” Mifang Liang of the Chinese Center for Disease Control and Prevention said at the China-U.S. Relations Conference in Houston last month.

經歷2003年嚴重急性呼吸綜合症爆發後對傳染病有深刻了解的中國，有許多國民在西非工作。“整個國家都動員起來，”中國疾病預防控制中心研究員樑米芳上個月在休斯頓的中美關係研討會(China-U.S. Relations Conference)上表示。

The Chinese government issued a directive last summer that helped inspire the production not only of MIL77 but also of an Ebola vaccine, which is currently in human safety studies; rapid Ebola diagnostic tests; and copies of antiviral drugs made by companies in other countries. Dr. Zijian Feng, deputy general director of the China C.D.C., said involvement in emergency public health assistance served to “elevate our presence in the international stage and also elevate our capabilities.”

中國政府去年夏天發佈的一項命令，不僅鼓勵了MIL77的製作，還促成埃博拉疫苗的研發（目前已經進展到人體安全的研究）、埃博拉病毒快速診斷測試、以及仿造其他國家藥廠的抗病毒藥物。疾病預防控制中心副主任馮子健表示，參與公共衛生急難協助可以“提升我們在國際層面的知名度，並提升我們的能力”。

Within three months, using information in ZMapp’s patent, Dr. Li and his colleagues had copied the active part of ZMapp and used the company’s specialized cells to produce the antibodies. A month later, with the help of the Chinese pharmaceutical company Hisun, they had 100 doses.

李鋒和他的同事利用ZMapp專利的信息，在三個月內複製了ZMapp的有效部分，然後利用公司的特製細胞製造抗體。一個月後，在中國藥廠海正藥業的幫助下，已經生產出100劑。

But some American officials expressed concern. The United States government holds a patent on one of the antibodies in ZMapp, which was developed with support from American and Canadian military research agencies, a legacy of fears that Ebola could be used as a biological weapon by the Soviet Union or, later, by terrorists.

但是部分美國官員表達了他們的顧慮。美國政府持有ZMapp中的一種抗體的專利，其研發獲得了美國和加拿大軍方研究機構的支持，因爲擔心埃博拉可能被早前的蘇聯或之後的恐怖分子用作生化武器。

“If you use it, you’re supposed to get permission to do it, even for research purposes,” said Robin Robinson, director of the Biomedical Advanced Research and Development Authority, part of the United States Department of Health and Human Services. He said the Chinese scientists might have infringed patents if they tried to sell MIL77 outside China without an agreement with Mapp Biopharmaceutical, the small American company with intellectual property rights to ZMapp.

“如果你使用它，你就應該獲得許可，甚至是爲了研究目的”，美國衛生與公共服務部(Department of Health and Human Services)屬下的生物醫學高級研究和發展管理局(Biomedical Advanced Research and Development Authority)局長羅賓·羅賓遜(Robin Robinson)說道。他說，如果中國科學家試圖在中國以外地區銷售MIL77，卻沒有與擁有ZMapp知識產權的美國小型公司Mapp生物製藥(Mapp Biopharmaceutical)達成協議的話，他們或許已經侵犯了專利。

Larry Zeitlin, president of Mapp, said the Chinese scientists had reached out to him after creating MIL77 and had been collaborative.

Mapp公司總裁拉里·澤特林(Larry Zeitlin)表示中國科學家已經在研製出MIL77之後與他接洽，並表現得願意合作。

Dr. Robinson said his agency had worked with Mapp and larger companies — including Regeneron in Tarrytown, N.Y., and Genentech in South San Francisco — to use methods similar to the Chinese researchers’ to increase production of ZMapp and other antibody-based treatments for Ebola.

羅賓遜博士表示他的機構已經與Mapp和一些更大的公司合作，包括位於紐約州塔裏敦(Tarrytown)的Regeneron和舊金山南部的美國基因工程技術公司(Genentech)，以使用與中國研究人員類似的方法增加ZMapp和其他基於抗體的埃博拉藥物的生產。

But aid groups treating patients in West Africa had trouble getting information on those efforts, said Dr. Annick Antierens, coordinator of research partnerships for Doctors Without Borders. So they began to explore using Chinese-made MIL77.

但是救援組織在救治西非的病人時，在獲得有關這些努力的信息方面有困難，無國界醫生組織(Doctors Without Borders)的研究夥伴關係協調員安妮克·安蒂倫斯博士(Annick Antierens)表示。所以他們開始嘗試使用中國製造的MIL77。

“We said, ‘You have people dying like flies, and there’s a product that seems to be O.K.,’ ” Dr. Antierens said. But as the number of Ebola patients declined in West Africa with the waning epidemic and ZMapp finally became available, she said, American officials and scientists expressed concerns that the use of MIL77 could interfere with the clinical testing and licensing of ZMapp.

“我們說，‘人們像蒼蠅一般死去，而有一種藥物似乎有效’”，安蒂倫斯博士表示。但西非的埃博拉病人數量隨着傳播的減弱和ZMapp變得可獲取而減少，她說，美國官員和科學家表達了他們對使用MIL77可能干擾了ZMapp的臨牀試驗和批准的顧慮。

Doctors Without Borders and some other aid groups have balked at participating in the ZMapp trial because it is randomized and patients only have a 50 percent chance of receiving the treatment. That is a standard procedure in many trials so that researchers can compare patient outcomes and determine whether the treatment was effective and not harmful.

無國界醫生組織和其他救援組織已經在是否參加ZMapp試用上猶豫不決，因爲這是隨機化的而且病人只有50%的機會得到治療。這是許多藥物測試的標準流程，這樣研究人員才能比較病人的結果，並確定治療是否是有效而無害的。

At Royal Free Hospital in London several months ago, two healthy workers with serious exposure to Ebola were given MIL77. Neither of the workers ended up developing the disease, said Dr. Michael Jacobs, who treated them.

幾個月前在倫敦皇家自由醫院(Royal Free Hospital)，兩位健康的但密集接觸埃博拉的工作人員被注射了MIL77。兩人最終都沒有感染埃博拉，治療他們的邁克爾·雅各布博士(Michael Jacobs)說。

When the British Army nurse, Cpl. Anna Cross, tested positive for Ebola in March, she also agreed to receive MIL77, which had shown promising results in guinea pigs and nonhuman primates at the Public Health Agency of Canada.

當英國陸軍護士，安娜·克羅斯下士(Anna Cross)在三月的埃博拉測試中呈陽性時，她也同意接受MIL77治療。而在加拿大公共衛生局(Public Health Agency of Canada)，MIL77已經在豚鼠和非人類靈長類動物上顯示了令人滿意的結果。

The London hospital has since decided not to join the American-run clinical trial of ZMapp because of the randomizing requirement. It has opted instead to keep a supply of MIL77 for use in any Ebola patients treated in Britain or the European Union.

這家倫敦醫院因此決定不加入由美國進行的Zmapp臨牀測試，原因是其隨機化的要求。作爲代替，其決定保持MIL77的供應，用以所有英國和歐盟內的埃博拉病人的治療。

“We’ve challenged ourselves about whether that is the right decision or not,” Dr. Jacobs said. “In the end, I have to do my best for the patient in front of me.”

“我們已經在這是否是個正確決定的問題上質疑了自己，”雅各布博士說，“最後，我必須爲我面前的病人做到最好。”

But Dr. H. Clifford Lane, clinical director at the National Institute of Allergy and Infectious Diseases, said it was important to test ZMapp properly to determine whether using antibodies to treat Ebola really works.

但是國家過敏和傳染病研究所(National Institute of Allergy and Infectious Diseases)臨牀主任克利福德·萊恩博士(Clifford Lane)表示，用合適的手段測試ZMapp以確定使用抗體治療埃博拉是否有效是至關重要的。

“There are interventions that look so logical, that should be effective, that prove not to be,” he said. “Without randomization, you have no way to control for all the different variables that come into play when you’re dealing with a patient.”

“有一些干預看起來很符合邏輯，應該是有效的，但被證明並不是，”他說。“沒有隨機化，你在治療病人時就無法控制所有不同的、有影響的變量”。