Gene editing technology has revolutionized molecular biology, offering unprecedented precision in genetic modifications and a lighter regulatory pathway compared to conventional transgenic approaches. However, the intellectual property landscape surrounding CRISPR has historically been overshadowed with disputes and unexpected developments. A recent and notable twist is the self-revocation of two seminal European patents by the team led by Nobel Laureates Emmanuelle Charpentier and Jennifer Doudna, and assigned to University of California, University of Vienna, and Emmanuelle Charpentier (collectively known as CVC). This move has introduced new uncertainties for companies navigating the complex CRISPR IP landscape.
基因编辑技术彻底革新了分子生物学，在基因修饰方面实现了前所未有的精准度，并且与传统的转基因方法相比，其监管流程也更为简便。然而，一直以来，围绕着CRISPR（基因编辑技术）的知识产权领域都被各种争端和意外发展所笼罩。最近一个值得注意的转折是，诺贝尔奖得主埃马纽埃尔·沙彭蒂耶（Emmanuelle Charpentier）和詹妮弗·杜德纳（Jennifer Doudna）所带领的团队撤回了两项具有开创性意义的欧洲专利，这些专利归属于加利福尼亚大学、维也纳大学以及埃马纽埃尔·沙彭蒂耶（统称为CVC）。这一举动给那些在复杂的CRISPR知识产权领域中摸索前行的公司带来了新的不确定性。
1.史无前例的自我撤销
In an extraordinary decision, CVC requested the European Patent Office (EPO) to revoke two of its foundational patents: EP2800811 (EP '811) and EP3401400 (EP '400). These patents encompassed broad claims covering nearly all methods of modifying target DNA using the CRISPR-Cas9 system. The self-revocation appears to be a strategic response to unfavorable preliminary opinions from the EPO's Opposition Division Board of Appeal, which questioned the sufficiency of the original patent disclosures. Specifically, the Board of Appeal indicated that CVC's earliest patent filing lacked certain key features necessary for other scientists to effectively utilize the technology. This is akin to the U.S. written description requirement, which is referred to as sufficiency of disclosure with the EPO.
一项非同寻常的决定是，CVC向欧洲专利局（EPO）提出撤回其两项基础性专利：欧洲专利第2800811号（EP '811）和欧洲专利第3401400号（EP '400）。这些专利的权利要求范围广泛，涵盖了几乎所有使用CRISPR-Cas9系统修饰目标DNA的方法。此次自我撤回似乎是对EPO异议部门上诉委员会不利初步意见的一种战略性回应，该委员会对原始专利披露内容的充分性提出了质疑。具体而言，上诉委员会指出，CVC最早提交的专利申请缺少某些关键特征，而这些特征是其他科学家有效利用该技术所必需的。这类似于美国的书面描述要求，在EPO则被称为披露充分性要求。
A critical point in the dispute centers on the protospacer adjacent motif (PAM) sequence, essential for CRISPR-Cas9 binding and cleavage. CVC's initial provisional application, filed in May 2012, notably omitted the PAM sequence, which was later included in a subsequent provisional application in October 2012 after their groundbreaking publication in Science. Opponents argued, and the Board of Appeal concurred, that without the PAM sequence, the invention was not sufficiently disclosed, rendering the May 2012 application inadequate to support the later European patents. Consequently, EP '811 and EP '400 lost their priority date entitlement from May 2012, making the June 2012 Science publication invalidating prior art against their own patents. Here, the applicants failed to file a patent application containing the PAM sequences before their own publication in Science disclosing PAM sequences. This violates a basic cardinal rule in patent prosecution: file updated application(s) before publication of any new results that go beyond the priority application. This is also a good reminder of one of the many watchouts for "coversheet provisional" practice, where often a company wants a quick filing with minimal data, to support an upcoming disclosure or meeting with investors. The PAM sequence disclosure issue could have been averted if they sent their patent counsel the draft manuscript before submission, and filed an updated priority application.
这场争端的一个关键要点集中在原间隔区相邻基序（PAM）序列上，该序列对于CRISPR-Cas9的结合和切割至关重要。CVC于2012年5月提交的最初临时申请中，明显遗漏了PAM序列，而在他们于《科学》杂志上发表了具有开创性的论文之后，PAM序列才被纳入2012年10月提交的后续临时申请中。反对者提出，并且上诉委员会也表示认同，即如果没有PAM序列，这项发明就没有得到充分的公开，这使得2012年5月的申请不足以支持后来的欧洲专利。因此，EP '811和EP '400两项专利失去了其从2012年5月起的优先权日资格，这使得2012年6月发表在《科学》杂志上的文章成为了可使他们自己的专利无效的现有技术。在这种情况下，申请人未能在他们自己发表披露PAM序列的《科学》杂志文章之前，提交一份包含PAM序列的专利申请。这违反了专利申请过程中的一条基本重要规则：在发表任何超出优先权申请内容的新成果之前，提交更新后的申请。这也很好地提醒了人们 “封面临时申请” 做法中众多需要注意的事项之一，通常公司希望以最少的数据快速提交申请，以支持即将进行的披露或与投资者的会面。如果他们在提交（论文）之前将手稿草稿发送给他们的专利律师，并提交一份更新后的优先权申请，PAM序列披露的问题本是可以避免的。
Rather than relinquishing control over their CRISPR IP in Europe, CVC's self-revocation aims to prevent a final adverse decision that could negatively impact the entire patent family and future patent prospects in Europe. In a submission accompanying the revocation request, CVC's legal representatives stated: "The Patentees cannot be expected to expose the Nobel Prize-winning invention protected by the present patent to the repercussions of a decision handed down under such circumstances, when other members of this family... are still at a stage where the Patentees can procedurally ensure that they will ultimately be fully heard by the Board on all substantive issues."
CVC撤回自身专利并非是要放弃对其在欧洲的CRISPR知识产权的控制权，其目的是为了避免出现最终的不利裁决，因为这样的裁决可能会对整个专利系列以及未来在欧洲的专利前景产生负面影响。在随撤回请求一同提交的文件中，CVC的法律代表称：“不能指望专利权人在这种情况下，让受本专利保护的、荣获诺贝尔奖的发明承受（不利）裁决的后果，尤其是该专利系列的其他专利……仍处于专利权人能够通过程序确保就所有实质性问题最终得到上诉委员会充分听证的阶段。”
By revoking these patents, CVC seemingly seeks to shield other family members from an adverse final decision and to leverage pending applications within the same patent family to secure new patents. However, this self-revocation strategy does not rectify the foundational issue of the May 2012 application's insufficiency. Future patents stemming from pending applications are likely to encounter similar challenges when faced with challenges to written description or sufficiency of disclosure.
通过撤回这些专利，CVC似乎试图保护同一专利系列中的其他专利不受到不利的最终裁决影响，并利用该专利系列内尚未审结的申请来获取新的专利。然而，这种自我撤回专利的策略并不能纠正2012年5月申请存在的根本性问题，即申请内容不充分。未来，源于这些尚未审结申请的专利在面临书面描述或披露充分性方面的质疑时，很可能会遇到类似的挑战。
2.更广泛的趋势和未来展望
CVC's self-revocation is not an isolated incident. Sigma-Aldrich just recently employed a similar tactic, revoking its own European CRISPR patents to avoid unfavorable rulings.
CVC撤回自身专利并非个例。西格玛奥德里奇公司（Sigma-Aldrich）最近也采用了类似的策略，撤回了其在欧洲的CRISPR专利，以避免出现不利的裁决。
In this twist nobody saw coming, less than two months after CVC revoked two of its foundational European CRISPR patents, Sigma-Aldrich has jumped on a similar "self-revocation" bandwagon approach.
在这一谁都未曾预料到的转折中，就在CVC撤回其两项基础性欧洲CRISPR专利后不到两个月，西格玛奥德里奇公司也跟风采取了类似的“自我撤回”策略。
Sigma-Aldrich's move involves two significant patents, EP3138911 (EP '911) and EP3360964 (EP '964), which broadly cover methods and compositions for editing chromosomal sequences in eukaryotic cells using RNA-guided endonucleases like CRISPR/Cas proteins with nuclear localization signals.
西格玛奥德里奇公司的这一举措涉及两项重要专利，即欧洲专利第3138911号（EP '911）和欧洲专利第3360964号（EP '964），这些专利广泛涵盖了使用带有核定位信号的诸如CRISPR/Cas蛋白之类的RNA引导核酸内切酶，对真核细胞中的染色体序列进行编辑的方法和组合物。
Unlike CVC's patents, Sigma's patents had already faced setbacks: the EPO's Opposition Division previously revoked them for lacking inventive step, citing the June 2012 Science publication by Nobel Laureates Emmanuelle Charpentier and Jennifer Doudna. Attempting to salvage their patents on appeal of the opposition decision, Sigma introduced new arguments and auxiliary requests, only to have them rejected by the Board of Appeal for being submitted too late. Sigma then moved to terminate the appeal proceedings, giving up its effort to overturn the Opposition Division's revocation decisions of both EP '911 and EP '964 patents.
与CVC的专利不同，西格玛公司的专利此前就已遭遇挫折：欧洲专利局异议部门先前以缺乏创造性为由撤销了这些专利，理由是诺贝尔奖得主埃马纽埃尔·沙彭蒂耶和詹妮弗·杜德纳在2012年6月发表于《科学》杂志上的文章。西格玛公司试图就异议决定上诉以挽救其专利，提出了新的论据和辅助请求，但由于提交时间过晚而被上诉委员会驳回。随后，西格玛公司采取行动终止了上诉程序，放弃了推翻异议部门对欧洲专利第3138911号（EP '911）和欧洲专利第3360964号（EP '964）两项专利的撤销决定的努力。
3. 战略意义
Why are major patent holders resorting to these tactics? Both Sigma and CVC seemingly aim to shield their other patent family members from the fallout of an unfavorable final decision and preserve their ability to secure future European patents. Yet, Sigma faces an uphill battle because its patents were already revoked once, complicating efforts to reposition future patent claims.
为什么主要的专利持有者要采取这些策略呢？西格玛公司和CVC似乎都旨在保护其专利系列中的其他专利不受到不利最终裁决的影响，并保留他们未来在欧洲获得专利的能力。然而，西格玛公司面临着一场艰难的斗争，因为其专利已经被撤销过一次，这使得重新调整未来专利权利要求的工作变得更加复杂。
This growing trend of patent holders preemptively dropping pursuit of their claims before a final decision is generating a lot of questions within both scientific and legal communities – I have fielded a lot of questions in the past several months about the potential implications (with the biggest one being – "Why?").
专利持有者在最终裁决作出之前就抢先放弃对其权利主张的追求，这一日益增长的趋势在科学界和法律界引发了诸多疑问——在过去几个月里，我收到了许多关于其潜在影响的问题（其中最主要的一个问题是“为什么要这样做？”）。
As the CRISPR IP landscape continues to evolve, companies should keep up to date and seek IP and regulatory guidance for their specific product development pathway, to bring products to market. In addition to the new patent applications published and issued patents granted for gene editing technology each week, ongoing opposition and litigation proceedings remain.
随着CRISPR知识产权格局的持续演变，企业应当及时了解最新动态，并就其特定的产品开发路径寻求知识产权和监管方面的指导，以便将产品推向市场。除了每周都会有新的基因编辑技术专利申请公布以及相关专利获批之外，现有的异议程序和诉讼程序仍在进行中。
For companies and researchers in the gene-editing field looking to protect their innovations, these developments underscore the importance of meticulous patent drafting and comprehensive disclosure. Ensuring that all critical components of an invention are adequately described is paramount to secure a priority date that will withstand legal scrutiny.
对于基因编辑领域中希望保护自身创新成果的企业和研究人员而言，这些发展情况凸显了精心起草专利文件以及进行全面信息披露的重要性。确保对一项发明的所有关键组成部分都进行充分描述，这对于获得一个能够经受住法律审查的优先权日来说至关重要。