這聽起來像是科幻小說——借助新的基因編輯技術(shù)，科學(xué)家可以精確定位并截取細(xì)菌、動(dòng)物甚至人類活體細(xì)胞中的一小段DNA。不過，CRISPR這種基因編輯技術(shù)可是貨真價(jià)實(shí)的。它有可能在未來的某一天治愈細(xì)胞性貧血等與基因相關(guān)的疾病，種出更好的莊稼，或者帶來大量可供移植的器官。難怪《科學(xué)》雜志將這一技術(shù)評為2015年科學(xué)“年度突破”。

但現(xiàn)在，誰擁有并控制著這項(xiàng)革命性技術(shù)也正式成為一個(gè)問題，頂尖科學(xué)家和科研機(jī)構(gòu)為此爭執(zhí)不下。

2016年1月，美國專利商標(biāo)局宣布，有兩位科學(xué)家的專利申請存在“沖突”，從而正式拋出了一個(gè)問題，那就是誰首先發(fā)明了CRISPR技術(shù)，進(jìn)而擁有這項(xiàng)蘊(yùn)含著巨大價(jià)值的技術(shù)。本次專利糾紛不僅將決定相關(guān)名譽(yù)的歸屬，還將決定哪位科學(xué)家和哪所科研機(jī)構(gòu)將獲得這項(xiàng)潛在價(jià)值達(dá)數(shù)十億美元的專利權(quán)。

加利福尼亞大學(xué)伯克利分校生物化學(xué)家詹妮弗?杜德納于2012年5月就核心CRISPR技術(shù)申請專利。2012年12月，麻省理工-哈佛大學(xué)布羅德研究所生物學(xué)家張鋒提交了類似申請。但他申請了快速授權(quán)，并在2014年4月正式取得專利權(quán)。現(xiàn)在，專利商標(biāo)局正式啟動(dòng)了“沖突”解決程序，三名專利法官組成的小組將決定張鋒是否應(yīng)該繼續(xù)擁有CRISPR專利以及其他與此項(xiàng)技術(shù)有關(guān)的專利。

對兩位科學(xué)家和他們所在的科研機(jī)構(gòu)來說，這牽涉到大筆財(cái)富，因?yàn)槭澜绺鞯氐难芯空吆推髽I(yè)都已經(jīng)開始把這項(xiàng)技術(shù)用于新的應(yīng)用之中。紐約法學(xué)院法律和技術(shù)創(chuàng)新中心副教授雅各布?沙爾蔻說：“所有人都試圖算清楚那些應(yīng)用會(huì)值多少錢。這方面有各種說法，但都達(dá)到了數(shù)十億美元的水平?！?/p>

CRISPR被喻為基因編輯技術(shù)的“圣杯”。它能夠精準(zhǔn)地對活體組織中的基因進(jìn)行編輯。這項(xiàng)技術(shù)利用核糖核酸（RNA）導(dǎo)向分子進(jìn)入某些細(xì)胞中，然后把Cas9核酸內(nèi)切酶附著在DNA上，Cas9會(huì)像微型剪刀一樣把DNA切斷。這種辦法既可以只移除有缺陷的DNA，也可以用一個(gè)沒有缺陷的基因序列來代替前者。

已經(jīng)開始融資的公司

目前，市場上已有多家生物科技初創(chuàng)利用這項(xiàng)技術(shù)推出了新的治療方法，并有可能治愈重大基因疾病和免疫疾病，甚至能讓盲人重見光明。波士頓咨詢公司提供的數(shù)據(jù)顯示，包括張鋒的Editas Medicine和杜德納的Caribou Bioscience在內(nèi)，這些公司在過去兩年中已經(jīng)吸引了逾10億美元風(fēng)險(xiǎn)投資。沙爾蔻說：“人們的想法是，無論這些公司得到了多少投資，都只是這些專利估值的粗略體現(xiàn)。至少，在倍數(shù)范圍內(nèi)確實(shí)如此?！?/p>

在初創(chuàng)公司中，Editas Medicine已經(jīng)和生物醫(yī)藥公司Juno Therapeutics聯(lián)手研發(fā)抗癌藥物，平均每個(gè)項(xiàng)目的階段性付款為2.3億美元。據(jù)彭博報(bào)道，杜德納在維也納大學(xué)的合作伙伴埃馬努埃爾?夏龐蒂埃建立的Crispr Therapeutics正在和制藥公司Vertex Pharmaceuticals合作，每個(gè)項(xiàng)目都將獲得最高4.2億美元的階段性付款。

罕見的專利爭議

從歷史上看，專利沖突案例很少見。2013年美國修訂專利法以來，這種情況基本上就沒有再出現(xiàn)過?，F(xiàn)行的專利權(quán)授予的基本原則是“先申請者得”。但在2013年之前，這個(gè)標(biāo)準(zhǔn)是“先發(fā)明者得”。也就是說，誰能證明自己首先提出了相關(guān)想法，誰就能取得專利權(quán)。由于杜德納和張鋒申請專利的時(shí)間在專利法修訂之前，此案將按“先發(fā)明者得”的標(biāo)準(zhǔn)進(jìn)行審理。沙爾蔻指出，以前這樣的專利糾紛會(huì)在一年內(nèi)結(jié)案。但鑒于此項(xiàng)專利價(jià)值巨大，敗訴一方提起上訴的可能性很大。而上訴有可能拖上好幾年。

與此同時(shí)，研究者和初創(chuàng)公司仍將繼續(xù)借助CRISPR技術(shù)來推進(jìn)自己的工作。而源于這項(xiàng)技術(shù)的潛在治療手段和應(yīng)用，估計(jì)仍需要幾年時(shí)間才會(huì)成為現(xiàn)實(shí)，但愿在此期間，我們能夠解決這項(xiàng)核心技術(shù)的歸屬問題。（財(cái)富中文網(wǎng)）

譯者：Charlie

校對：詹妮

It sounds like the stuff of science fiction: A new gene-editing technology allows scientists to precisely locate and cut out bits of DNA from live cells in bacteria, animals, and even humans. But CRISPR is very real, with the potential, one day, to cure genetically-linked diseases like sickle cell anemia, produce better crops, and create a huge supply of organs for transplant. No wonder it was namedScience’s 2015 Breakthrough of the Year.

But who owns and controls this revolutionary technology also is now officially in question, pitting leading scientists and research institutions against each other.

In January 2016, the U.S. Patent and Trademark Office declared an “interference” between two scientists’ patent applications, which officially opens up the question of who first invented–and thus owns the lucrative rights to the foundational CRISPR technology, which stands for Clustered Regularly-Interspaced Short Palindromic Repeats. The patent dispute will determine not only who gets credit but who lays claim to the royalties, which could be worth “billions” of dollars for the scientist and research institution.

Biochemist Jennifer Doudna from the University of California, Berkeley submitted her patent application for the core CRISPR technology in May 2012. Biologist Feng Zheng from the Broad Institute of Harvard and MIT submitted a similar patent application in December 2012, but he requested a fast-track process and received the official patent in April 2014. Now, with an official “interference” proceeding underway, a panel of three patent judges will determine whether Zhang should hold onto the rights to the foundational CRISPR patent, as well as other patents related to the technology.

There is a lot of money at stake for both the creators and their institutions, as researchers and companies around the world start using the technology for new applications. “Everyone is trying to figure out how much those applications are going to be worth,” said Jacob Sherkow, an associate professor at the Innovation Center for Law and Technology at the New York Law School. “Numbers have been bandied about, but we’re talking billions with a ‘B’.”

CRISPR is considered to be the “holy grail” of gene-editing technology. It is able to edit genes accurately and precisely within a living organism by leveraging an RNA “guide” molecule to enter in specific cells; a specific protein, called Cas9, attaches to the DNA and cuts it like a pair of tiny scissors. That process can either simply remove a faulty gene or replace a gene with a good strand of DNA.

Companies already raising money

A number of biotechnology startups have been leveraging the technology to bring new treatments to market that could solve devastating genetic diseases, autoimmune illnesses, and even blindness. These companies, including Zhang’s Editas Medicine and Doudna’s Caribou Bioscience, have attracted more than $1 billion in venture investment over the past two years, according to the Boston Consulting Group. “The thinking is that however much money these companies are getting, it’s a very rough approximation of what the patents are worth,” said Sherkow. “It’s at least true within a couple of multiples.”

For starters, Editas has teamed up with Juno Therapeuticsto help create cancer treatments with milestone payments of $230 million per program. Crispr Therapeutics, which was created by Doudna’s partner Emmanuelle Charpentier at the University of Vienna, stands to make up to $420 million in milestone payments per program in partnership with Vertex Pharmaceuticals, reported Bloomberg.

A rare kind of patent dispute

Patent interference cases are historically rare; but they’ve become basically non-existent since a change in the patent law in 2013. Today, patents are awarded on a “first to file” basis. However, prior to 2013, patents were granted on a “first to invent” basis, meaning whoever could prove they invented the idea first would have rights to the patent. Since Doudna’s and Zhang’s patents were filed before the switch went into effect, the case falls under the “first to invent” standard. In the past, patent interference cases like this were concluded within a year, Sherkow said, but given the value of this patent, it seems more than likely that the losing party will appeal the decision. That process could stretch out for years.

In the meantime, researchers and startups are moving ahead, working on advancements using the CRISPR technology. The potential treatments and uses that may stem from the CRISPR method still remain a few years off–hopefully long enough to solve who gets the final ownership on the core technology.