张锋 CRISPR-Cas9 基因编辑技术 的 专利官司今天出结果了。美国专利局法庭（注一）宣布张锋获胜。

众所周知， Doudna 在2012 年六月发表论文，首次报道运用 CRISPR-Cas9 在试管中实现 DNA片段的切割。6个月后的2013年 一月，张锋的研究小组发表论文，在人类细胞中用 CRISPR-Cas9 实现基因编辑，并很快申请了专利。2016年3月，Doudna 提出专利干扰诉讼，称张锋的发明是在她的专利基础上显然的事情。据报道，双方为了专利诉讼花了千万美元的律师费。

在此之前，我对张锋的了解仅仅是在韩春雨事件中听过其名而已，而且似乎有人对他的名气还存在疑问。在阅读相关资料后，我发现张锋才是 CRISPR -Cas9 技术的集大成者。围绕双方的争议，我写了若干博文。介绍了CRISPR-Cas9 基因编辑技术，也分析了张锋与DOUDNA在 CRISPR-Cas9 的专利官司。相关介绍参见：《张峰专利官司科普及案情发展-叛逃者将被 UC 传讯》《 CRISPR 基因编辑技术及张锋的贡献》《 CRISPR基因编辑技术的显然性分析》《CRISPR基因编辑研究秘辛大起底》《发自张锋实验室的四封CRISPR邮件》。

在 CRISPR 基因编辑技术及张锋的贡献一文中，我结论到 【张锋首次将 CRISPR-Cas9 成功用于高等生物的基因编辑，其主要成果是基于2011年 Charpentier 的 tracrRNA  发现】。在2012年初，也就是 Doudna 论文发表前半年，张锋就已经提交了完整的真核细胞基因编辑设计。张后来的论文结果基本是基于这个设计。

事件中，张锋实验室还出了一个中国留学生背叛者，向  DOUDNA 提供内部消息。但这个学生提供的电子邮件等信息恰恰证明张锋在 2012 年初就开始了相关真核细胞的基因编辑研究，并且明显找到了关键。而  DOUDNA 在 其2012年论文发表之后数个月仍未能成功实现真核细胞的基因编辑，直到张锋合作伙伴 CHURCH 提供了真核编辑的数据之后才获得成功。

根据张锋所在布罗德研究院的声明，美国专利局法庭在 2月15日宣布，Doudna 针对张锋的真核细胞 CRISPR-Cas9 基因编辑技术的专利干扰诉求不成立。美国专利局判决称：

• Doudna 与 Vilnius 的专利申请只是在试管中剪切DNA片段，没有涉及细胞、基因组，也没有基因编辑.（ The applications filed in 2012 by the Vilnius team and the Berkeley team each showed only that purified Cas9 protein and a certain purified RNA could cut a short piece of DNA in a solution in a test tube. In both cases, the applications in 2012 contained no cells, no genomes, and no editing.）

• Vilnius 的专利申请只是自然系统不能申请专利 （专利必须是人脑的创造，自然现象不能申请专利） （The USPTO rejected the Vilnius application as not having significantly more than a study of the natural system and failing to describe invention.）

• 张锋的真核细胞基因编辑专利不受 Doudna 专利影响。

对相关技术感兴趣的读者可以参阅《CRISPR基因编辑技术的显然性分析》等博文。另外，科技时代，科学技术是财富。据报道，去年 Doudna 专利官司启动后，张锋的 EDITAS 公司股价从 $42 开始大跌，最低只有13。今天 EDITAS 大涨 30%，达到  $24。张锋的财富量在10年内可能超过到处捣房地产的美国总统川普家族。

虽然科学研究的目的是为人类文明做贡献，而不是获取，但能用科技智慧创造财富也许更能够激励人们进行科学探索。

科学网的生物学家们都有希望。加油！

注一：读者可能问，专利局怎么有法庭，这个问题我在之前解释过 --  这叫 administrative law court.

附件：美专利局法庭三名ALJ的 50页 判决书 http://www.zzwave.com/zzw/upload/up/2/7b0b1c1.pdf  RICHARD E. SCHAFER, SALLY GARDNER LANE, andDEBORAH KATZ

Administrative Patent Judges.

这判决得有相当生物知识才能看懂，关键证据

【Broad also cites to statements reportedly made by UC inventor Doudna after
2 Jinek 2012 that the publication “was a big success, but there was a problem. We
3 weren’t sure if CRISPR/Cas9 would work in eukaryotes—plant and animal cells.”
4 (Exh. 22078, at 3; see Broad Motion 2, paper 77, at 4:8-11.) In another report,
5 Doudna was quoted as stating that she had experienced “many frustrations” getting
6 CRISPR to work in human cells and that she knew that if she succeeded, CRISPR
7 would be “a profound discovery.” (Exh. 22309, at 3; see Broad Motion 2,
8 Paper 77, at 8:1-4.)】

【9 Broad cites to other statements attributed to Dr. Doudna regarding the
10 difficulties of genetic modification techniques in eukaryotes. (Broad Motion 2,
11 Paper 77, at 9:5-22.) One author quoted Dr. Doudna as saying: “The ability to
12 modify specific elements of an organism’s genes has been essential to advance our
13 understanding of biology, including human health. . . . However, the techniques for
14 making these modifications in animals and humans have been a huge bottleneck in
15 both research and the development of human therapeutics.” (Sanders10, Exh. 2259,
16 at 2.) According to Broad, the contemporaneous statements of the UC inventors
17 demonstrate that one of ordinary skill in the art lacked a reasonable expectation of
18 success. (Broad Motion 2, Paper 77, at 4:14-17.)】

【3 We agree with Broad that the statements by and attributed to the UC
4 inventors do not demonstrate a reasonable expectation of success. Although the
5 statements express an eagerness to learn the results of experiments in eukaryotic
6 cells and the importance of such results, none of them express an expectation that
7 such results would be successful. The contemporaneous commentary by the UC
8 inventors cited by Broad do not indicate that at the time of Jinek 2012 the
9 ordinarily skilled artisan would have reasonably expected the CRISPR-Cas9
10 system to work in eukaryotic cells.
11 UC also argues that the selected quotations from inventors Doudna and Jinek
12 are irrelevant because determination of interference-in-fact is from the viewpoint
13 of a person of ordinary skill, not an inventor. (UC Opp. 2, Paper 652, at 27:12-14.)
14 Although this may be true, UC’s argument only tends to persuade us more because
15 if the inventors themselves were uncertain, it seems that ordinarily skilled artisans
16 would have been even more uncertain.】

【Despite the evidence about the effects of chromatin structure that UC
presents for this proceeding, we are still persuaded by Dr. Carroll’s statement made
contemporaneously to Jinek 2012. (See Carroll, Exh. 1152, at 1660: “There is no
guarantee that Cas9 will work effectively on a chromatin target or that the required
DNA–RNA hybrid can be stabilized in that context. . . . Only attempts to apply the
system in eukaryotes will address these concerns.”) Because the statements Dr.
Greider makes in her declaration are substantially identical to Dr. Carroll’s in his
declaration, we do not give Dr. Greider’s statements more weight than Dr.
Carroll’s.】