The U.S. Patent and Trademark Office (USPTO) has granted a new CRISPR-Cas9 patent covering the use of one or multiple single guide RNAs in any cell type to the regents of the University of California (UC), the University of Vienna, and CRISPR pioneer Emmanuelle Charpentier, PhD, director and scientific member at the Max Planck Institute of Infection Biology, Berlin, UC said today.

U.S. Patent Number 10,227,611, “Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription,” covers the use of single molecule RNA guides and Cas9 protein in any cell, with the aim of creating efficient and effective ways for scientists to target and edit genes.

Charpentier is listed as an inventor on the patent, along with CRISPR pioneer Jennifer Doudna, PhD, of UC Berkeley; Martin Jinek, PhD, of University of Zurich, a onetime postdoctoral student of Doudna; and Krzysztof Chylinski, PhD, of University of Vienna, a onetime postdoctoral student of Charpentier.

The patent covers claims that provide:

  • A DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA.
  • Site-specific modifying polypeptides.
  • Methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA.
  • Methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA.

The newly-granted patent was not at issue in the interference proceeding before the USPTO’s Patent Trial and Appeal Board (PTAB) focused on invention of the gene-editing technology. Citing a pending patent application, the Doudna-Charpentier-UC inventor team challenged 12 patents related to CRISPR technology that listed as inventor Feng Zhang, PhD, of The Broad Institute of MIT and Harvard.

The May 25, 2012 priority application broadly encompassed CRISPR-Cas9 genome-editing technology invented by the Doudna-Charpentier team and its applications in any setting, UC said, including in vitro, and cellular and non-cellular environments, as well as single molecule RNA guides, among other inventions. The Broad’s patents focused on the use of CRISPR for genome editing in eukaryotic cells, such as those in plants and higher animals.

The Doudna-Charpentier team contended that the application of CRISPR to eukaryotic systems covered by the Broad’s patents represented an obvious rather than an inventive invention, and was thus nonpatentable.

The Broad defended its patent and withstood the challenge. A three-judge panel of the PTAB in 2017 unanimously found there was “no interference in fact” between the Broad’s CRISPR-Cas9 patents and the application filed by the Doudna-Charpentier inventor group. In September 2018, the U.S. Court of Appeals for the Federal Circuit upheld the PTAB three-judge panel’s decision, also siding with The Broad.

Third patent issued; Fourth expected

The new patent is the third to be issued to the Doudna-Charpentier inventor team; the other two are U.S. Patents No. 10,000,772 and No. 10,113,167.

Patent No. 10,000,772, which was issued in June 2018, covers methods of using optimized guide RNA formats (including single-guide and dual-guide formats) in certain environments, including eukaryotic cells (such as human, animal, and plant cells). The optimized formats modify the part of a guide RNA that interacts with the CRISPR-Cas9 nuclease.

Patent No. 10,113,167, issued October 30, 2018, covers “Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription.”

In its announcement today, UC also stated that the USPTO is expected to issue the group a fourth patent “in the next several weeks” based on U.S. Patent Application No. 13/842,859, “Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription.” That application covers methods and systems for modifying a target DNA molecule in any setting, including in any cell type as well as in vitro, using one or multiple single guide RNAs.

Together, all four patents would cover CRISPR-Cas9 compositions and methods useful to locate and edit genes in any setting, including within plant, animal, and human cells, UC said.

In addition to the U.S. patents, the Doudna-Charpentier team has been issued patents for the use of CRISPR-Cas9 for gene editing in all types of cells being issued by the European Patent Office, representing more than 30 countries—as well as patent offices in the United Kingdom, China, Japan, Australia, New Zealand, Mexico, and other countries.

“The Doudna-Charpentier team’s invention is changing the future of our world for the better,” Edward Penhoet, PhD, special advisor to UC Berkeley Chancellor Carol T. Christ, PhD, and special assistant to UC President Janet Napolitano, JD, said in a statement. “We are pleased that the USPTO has recognized the unique importance of each of the CRISPR innovations that have been pioneered here at the University of California with its collaborators.”

Both The Broad and UC have said they have worked to ensure wide availability of CRISPR tools. The Broad has noted that it licenses CRISPR IP nonexclusively to companies to use in their own commercial research; and makes CRISPR tools, knowledge, methods, and other IP for genome editing freely available to the academic and nonprofit community.

In 2014, The Broad developed the Inclusive Innovation Model, in which Broad, Harvard, and MIT licensed their CRISPR technology to a primary licensee, Editas Medicine. Editas has an exclusive right to use the technology on targets of its choosing for the development of genomic medicines. However, after an initial period, other companies may apply to license certain CRISPR IP for use against genes of interest not being pursued by Editas.

UC noted today that it has encouraged widespread commercialization of its technology through its exclusive license with Caribou Biosciences. Caribou has sublicensed the UC’s patent family to numerous companies worldwide, including Intellia Therapeutics for certain human therapeutic applications. Additionally, Charpentier has licensed the technology to CRISPR Therapeutics and ERS Genomics.

ERS’ exclusive worldwide license from Charpentier is for foundational intellectual property covering CRISPR-Cas9 for all applications other than use as a human therapeutic. ERS’ foundational IP covers broad and dominant claims covering CRISPR/Cas9 compositions and methods of genome editing in any organism.

“We are pleased that the seminal contribution of Charpentier and her colleagues to CRISPR/Cas9 technology continues to be recognized by patent offices in the United States and around the world,” Eric Rhodes, CEO of ERS Genomics, said in a separate statement issued today by his company.

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