河北的韩春雨的论文要被撤搞，大河北的张锋的专利要被无效。

马上到了河北科技大学承诺的一个月的期限，怎么看似乎也无法想象韩春雨能够把他的论文重复，我估计韩春雨的论文被撤搞是不可避免的。经过刚刚公布的自然基金项目，河北科技大学获得的资助达到230多万，显然没有如预期那样好几千万的大钱，看来基金掌舵者没有给予韩春雨特别关照，估计是害怕撤搞后打脸。

另一个重磅消息是，Crispr技术大佬张锋有极大可能失去其通过歪门邪道取得的专利（事后申请，但审查先前发明，钻了一个美国专利法的空子）。我曾经说过，张锋的研究是在Doudna基础的改进或者跟风，并不具有原创性，所以他的专利也在Doudna等人专利之后申请也就没有新颖性（http://blog.sciencenet.cn/blog-683543-989805.html）。

今天看到中文生物学媒体公开了一份一位出自饶毅实验室博士然后进入张锋实验室博士后叫林帅亮发给Doudan类似投名状的信件，该林同学声称如果Doudan能够提供工作可以进一步公开一些张锋等人企图欺骗美国专利局的行为，让张锋失去Crispr专利，而让Doudan获得应得的专利。

这里说明一下，美国专利在2013年之前，施行先发明制度，只要证明申请人的发明是比较靠前的，那么经过自己的专利申请是同类竞争专利之后，也可以争这个先发明权从而使自己后申请的专利获得专利，对手则不能获得。在2013年之后，美国专利法修改和世界其他国家类似的先申请制度。但是，张锋的专利是在2013年这个修改之前，所以依然沿用老政策。张锋的专利也没有进行国际其他国家的申请，Doudan的专利已经通过PCT申请进入了多个国家。

这位林同学的信件和承诺基本保证了Doudan的专利会被授权，而张锋的专利会被无效，因为张锋无法提供真实的先发明证据。

林同学的指证如果成立，张锋不仅丢失了专利，而且会失去部分荣誉，更不可能进入诺奖三人组中。

尽管韩春雨和张锋都是河北人，我们即使不搞地域歧视，也会因为他们可能的欺骗行为想到这两个奇葩。

Beneath the technical and legal jargon in the latest documents filed in the battle over CRISPR patents is a simple argument that, in only slightly exaggerated form, comes down to this:

Any idiot could have turned the rudimentary CRISPR genome-editing technologydescribed by scientists at the University of California in 2012 into the powerful technique that has revolutionized biology. No, going from DNA floating around in a test tube, the UC experiment, to precisely editing genes in humans took the kind of skill wielded only by a scientist in the running for a Nobel Prize — say, the Broad Institute’s Feng Zhang.

The gloves are off.

Key patents on the CRISPR technology were awarded to the Broad and Harvard University based on Zhang’s research developing a CRISPR system that edited mouse and human genes — many of them at the same time, Zhang and his team reported in a 2013 paper. The University of California is challenging those patents on behalf of UC Berkeley biochemist Jennifer Doudna and one of her key collaborators on a seminal 2012 paper, which described editing the test tube DNA using CRISPR.

In one of the more incendiary claims in the hundreds of pages of filings submitted by UC and the Broad this week, UC quotes an email by a former member of Zhang’s lab who asked Doudna for a job. As first reported by MIT Technology Review on Wednesday, graduate student Shuailiang Lin emailed Doudna in February 2015, saying he was the only member of Zhang’s lab working on CRISPR in 2011. The technique “did not work,” the email continued, adding that Lin has lab notebooks and other documentation “of the lab’s failure process.”

That failure turned into success, according to Lin’s email quoted by the UC lawyers, only after Zhang and others saw Doudna’s 2012 paper.

He was telling Doudna this, Lin said, because “I think I may help the CRISPR patent interference process,” referring to UC’s claim that its scientists and not the Broad’s are the true inventors of CRISPR-based genome editing.

The Broad immediately pushed back on the Lin email. The student visited the Broad “for a brief period from a Peking University/Tsinghua University joint program,” it said in a statement Wednesday, working for Zhang on CRISPR projects from October 2011 to June 2012. His visa was set to expire on March 1, 2015, the Broad added, and because he was not hired by the Broad — something he learned in late February 2015 — he needed another employer to sponsor him. Lin’s email to Doudna, said the Broad in a statement, had the subject line, “The Broad CRISPR patent and Apply for a position in your lab.”

Whatever claims Lin made, said the Broad, there is no “evidence to support them.” Last year, Zhang and Le Cong, the junior scientist who did the most work on what became Zhang’s key 2013 paper, told STAT that they began trying to make CRISPR-Cas9 edit genomes in early 2011, which would contradict Lin’s claim that he was the only member of Zhang’s lab working on CRISPR-Cas9. By the spring of 2012, Zhang said, they had enough results for a paper, but not one he thought good enough to submit to a journal.

“I didn’t want to submit the paper just because the result was publishable,” he told STAT then, explaining that he wanted to wait until they had “a paper that can make a significant difference, not just to be first with something.”

When the US Patent and Trademark Office announced in January that it was reopening its decision to award key CRISPR-Cas9 patents to the Broad (technically, “declaring an interference proceeding”), many legal experts expected the case to turn on who made the key discoveries and inventions first. In fact, said intellectual property expert Jacob Sherkow of New York Law School, it may turn on something even more basic: whether the Doudna and Zhang CRISPR inventions are for the same thing, as almost everyone assumed.

In simplified terms, UC’s original application for a patent on Doudna’s work described DNA editing in simple organisms. The Broad’s described such editing in eukaryotes, animals like mice and people whose cells have a genome-containing nucleus.

UC, in its legal filings this week, argues that parlaying Doudna’s discoveries into a technique that would work in eukaryotes was “obvious.” That is, soon after Doudna’s discovery “became known,” UC argued, “Broad was just one of many groups that quickly confirmed, using conventional techniques, that [CRISPR] could be readily used in eukaryotic cells.”

Crucially, scientists of “ordinary skill in the art” — not off-the-charts brilliance — parlayed Doudna’s work in test-tube DNA into something that worked in higher-order cells, UC said in the filings. Neither Zhang’s nor other discoveries of how to make CRISPR-Cas9 work in eukaryotic cells “required any unusual reagents or techniques, but rather used conventional techniques in conventional ways to produce predictable and expected results.”

“They’re saying that, given what [Doudna] reported, any molecular biologist could do it in eukaryotes,” Sherkow said. “Broad is saying, no, this was actually a big cognitive and technical leap. It’s like, I’ve given you the recipe for a Western omelet; how good a chef do you have to be to use that to make a souffle?” According to UC, any hash slinger could have done it; ergo, any patent claims on the eukaryotic advance are without merit. According to the Broad, only a superstar like Zhang could have done it, so the the Broad and Harvard deserve the patents awarded based on his work.

It won’t be easy for the patent office judges to decide just how obvious it was to move from Doudna’s editing of DNA in a test tube to Zhang’s doing it in eukaryotic cells. “That leads me to believe this will be much harder to resolve than I thought,” Sherkow said.

「随便一个白痴就可以将加州大学科学家在2012年的不成熟CRISPR基因编辑技术转化成强大的革命性工具吗？不可能，只有诺贝尔奖级的科学家才能（将CRISPR基因编辑技术）从试管里转化成可以在人体内精确完成基因编辑的技术。」博德研究所的张锋在最新的一份CRISPR专利大战的文件里略显夸张地说。

基于张峰利用CRISPR编辑小鼠和人类的基因的研究，CRISPR关键技术专利授予了博德研究所和哈佛大学。然而，加利福尼亚大学却对张峰拥有CRISPR技术的专利权表示质疑，加州大学伯克利分校的一个生物化学家Jennifer Doudna和她的合作者在2012年发表了一篇开创性的论文，文中描述了利用CRISPR编辑试管中的DNA。本周，加利福尼亚大学和博德提交了一份几百页言辞激烈的文件中，加利福尼亚大学引用了一位想要在Doudna实验室工作、张峰实验室前成员的一封邮件。正如本周三MIT科技评论首次报道中说的那样，研究生Shuailiang Lin在2015年2月给Doudna发了一封邮件：他说自己是张峰实验室2011年期间唯一一名负责研究CRISPR的成员。当时张峰实验室里CRISPR实验并没成功，而且 Shuailiang Lin说他手里有实验室记录以及记录「实验失败过程」的其他文件。

加利福尼亚大学的律师引用了Shuailiang Lin在邮件说的话：「只有在2012年张峰和实验室里其他人看到了Doudna2012年发表的那篇论文后，张峰CRISPR实验才成功了。」

Lin表示，他之所以跟Doudna说这些事情，是因为「我想我可以帮助CRISPR专利干涉过程（I think I may help the CRISPR patent interference process）」，之前加州大学声称该校的科学家才是CRISPR基因编辑技术的真正发明人，博德研究所的不是。

博德研究所本周三立即对Lin的邮件做了回应，这个学生「是通过清华和北大的一个联合项目在博德研究所待了一段时间」，在2011年10月到2012年6月在张锋实验室做CRISPR项目，他的签证是2015年3月1日到期。

博德研究所申明，无论林说了什么，没有「证据支持他们」。去年，张锋和Le Cong告诉STAT他们在2011年就开始开始尝试使用CRISPR-Cas9编辑基因组，然而Lin在邮件中说，他是张锋实验室唯一研究CRISPR-Cas9的人，张锋的描述与Lin在邮件中描述的不相符。2012年春，张锋说，他们已经获得了足够的数据，但是还不够好。

「我不想递交只是因为这些结果已经被发表了，」他告诉STAT，然后解释说，他想等到他们”能弄出一篇与其他研究显著不同的论文，而不是仅仅成为第一。

当美国专利和商标局在1月份宣布，它将重启将CRISPR-Cas9关键专利授予博德研究所的决定（专业说法，「宣告干扰程序」），许多法律专家预计这个事件将会搞清楚谁才是CRISPR-Cas9的发现和发明者。其实，纽约法学院知识产权专家Jacob Sherkow说，它将开启一些更基本的东西：Doudna和张锋在CRISPR上的发明到底是不是一样的。

简单的说，加州大学的Doudna开始的一项专利主要用于简单的生物体DNA编辑。博德研究所申请的是在真核细胞中的基因编辑，如小鼠和人等动物的细胞。

加州大学在本周的法律文件认为，将Doudna的发现转化为在真核细胞生物体内使用的一种技术是「显而易见的」。Doudna的发现为世人所知后不久，「博德研究所只是众多快速证实该技术的团队之一，使用常规技术，可以轻而易举地在真核细胞中使用[CRISPR]。」

加州大学认为，重要的是，「该领域技术平平」的科学家也在高级细胞中复制了Doudna研究。张锋和其他科学家在将CRISPR-Cas9用于真核细胞时，「没有使用任何不寻常的技术和试剂，仅仅是采用了CRISPR-Cas9的常规方法，得到了预期的结果而已。」

「他们说，将Doudna的研究报告交给任何一个生物学家，他们都可以在真核细胞中做出来，」Sherkow说，「博德研究所说，不，这需要一个很大的认知和技术飞跃。这就像，我已经给你了西方煎蛋食谱；要按照它做出蛋奶酥，你得有一个多么优秀的厨师？」在加州大学看来，这是连服务员都可以做的事情，因此，任何关于真核细胞的专利都是没有法律依据的。在博德研究所看来，只有张锋这样的超级巨星能做出来，因此基于张锋的工作，博德和哈佛应该获得专利。

从试管到人体究竟有多难，专利局法官很难去判断。Sherkow说，「我认为，这个官司比我想象的更难判决。」

《MIT科技评论》公布的Shuailiang Lin写给Jennifer Doudna的邮件（3）：