CRISPR: The Final Interference
CRISPR (“Clustered regularly interspaced shorty palindromic repeats”), also known as CRISPR-Cas9, is a recent advancement in biotechnology that allows for genetic manipulation. This monumental discovery is currently at the center of a heated patent interference proceeding that started earlier this year.
CRISPR naturally occurs in some bacteria, providing them with a means to defend against viruses. There are two main components involved in this system: Cas9 enzyme and a small RNA molecule. The RNA molecule directs the Cas9 enzyme to cut a specific sequence of DNA. In nature, the native DNA repair system can mend the cut but often with mistakes. However, scientists have modified the CRISPR process to be able to more accurately cut and paste together DNA sequences. This technology can alter the genomes of anything from plants to mammals, and has limitless applications in areas such as medicine, agriculture, and industrial biotechnology.
Who is involved?
There are two different groups involved with the patent interference dispute. On one side is a team led by Dr. Jennifer Doudna at the University of California, Berkeley and Dr. Emmanuelle Charpentier, who works at Umeå University in Sweden and at the Max Planck Institute for Infection Biology in Berlin. In August 2012, their research team published a paper showing that the Cas9 enzyme can be directed to cut specific sites in isolated DNA. Later that same year, they initiated a patent application and subsequently filed it on March 15, 2013.
The opposing party is a team led by Dr. Feng Zhang at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts. Dr. Zhang initiated a patent application in December 2012 and filed it by October 2013. That same year, Dr. Zhang published a paper showing the application of CRISPR-Cas9 in mammalian cells.
Though Dr. Doudna and her team filed their patent application first, Dr. Zhang filed his patent through an expedited review process and was awarded a CRISPR patent in April 2014. After Dr. Zhang was granted the patent, Dr. Doudna and her team requested patent interference, which was the granted by the US Patent and Trademark Office (USPTO) in January 2016. The Broad Institute is maintaining a detailed timeline of the proceedings.
What is patent interference?
Dr. Doudna filed her CRISPR patent the day before the effective date of the Leahy-Smith America Invents Act (AIA). Therefore, this patent dispute is governed by the “first to invent” patent system, which was altered by the passage of the AIA.
Under this system, a party could request that the USPTO initiate a process called interference in the event of a dispute, which in turn was governed by 35 U.S.C. § 135 (2012). In considering the requests that fall under the old “first to invent” system, the director of the USPTO must first decide if one patent application interferes with an unexpired patent or with another pending patent application.
In determining whether interference exists, the director decides “if the subject matter of a claim of one party would, if prior art, have anticipated or rendered obvious the subject matter of a claim of the opposing party and vice versa.” 37 C.F.R. § 41.203(a). This is called the two-way test, articulated in Winter v. Fujita. 1999 WL 1327616, at *11 (P.T.O. Nov. 16, 1999). If interference is found then the request is approved and the USPTO’s Patent Trial and Appeals Board (PTAB) determines priority, which is then granted to the patent applicant who was “first to invent” and reduce the invention to practice.
During a CRISPR hearing, a panel of USPTO patent judges considers evidence presented from both sides to determine who invented the application of CRISPR for gene editing. The judges could decide that there is no interference-in-fact, meaning the patents don’t actually interfere with each other and could be separately patentable, as they did in Rolls-Royce, PLC v. United Techs. Corp.
Patent interferences are uncommon, costly, and complex so there is not a clear-cut path to victory. There are two ways that a party can prevail. First, they can prove that they were first to conceive and reduce the invention to practice. Second, if the party was first to conceive but last to reduce to practice then they can instead show reasonable diligence, dating back prior to the opposing party’s conception. 35 U.S.C. §102(g) (2012).
In the second case, the determination of reasonable diligence is a factual question, as delineated in Brown v. Barbacid. A variety of evidence will be considered such as written documentation or testimony from the inventors. If the inventor decides to testify about her diligence, it must be corroborated as indicated in In re Jolley. But what constitutes sufficient corroboration?
In Brown, the court determined that evidence from the inventor and the laboratory technician was sufficient to establish diligence. In Scott v. Koyama, the appellants established diligence by showing intent to build a manufacturing plant needed for large scale production of the invented process at issue. In Bey v. Kollonitsch, an attorney’s work in preparing the patent application was sufficient to establish diligence.
However, commercial activity alone does not amount to reasonable diligence. Antoshkiw v. Pevsner, 224 U.S.P.Q. (BNA) ¶ 1049 (Jan. 17, 1983). The main question is, based on the evidence presented, did the inventor conduct reasonable continuing activity to reduce the invention to practice? Brown, 436 F.3d at 1380.
This dispute will be resolved under the previous “first to invent” system but it was replaced by the “first to file” system under the AIA, which went into effect on March 16, 2013. This Act also replaced the patent interference process with a process called derivation proceeding, which is conducted at PTAB to ensure that the inventor who is first to file is the true inventor of the disputed subject matter. The patent fight over CRISPR may have been an easier dispute to settle after the effective date of AIA. Since Dr. Doudna’s team filed first, they would have likely been awarded the patent (given that their patent application was sufficient and they could show that they didn’t derive their idea from Dr. Zhang’s research). Because the change in systems used to determine priority of a patent occurred during the dispute at hand, this is likely the last patent interference case that the USPTO will oversee.
Yasmin Amin-Reimer is a J.D. candidate, 2018, at NYU School of Law.