Caribou Bio’s New CRISPR Patent Isn’t About Gene Editing

Xconomy San Francisco — 

If you ask people who don’t follow biotech too closely what they know about CRISPR, you might get two answers: genetic editing and a big patent fight.

But a new CRISPR patent highlights a lower-profile potential use for the biotechnology: genetic detection and analysis.

The U.S. Patent and Trademark Office granted the patent Tuesday to Caribou Biosciences, the Berkeley, CA-based company cofounded by Jennifer Doudna of the University of California, Berkeley, one of the scientists whose work has been crucial in turning a bacterial defense system into one of this century’s most promising and contentious developments.

At the heart of the technology are DNA strands called CRISPR, short for “clustered regularly interspaced short palindromic repeats,” and a so-called Cas enzyme that cuts DNA. Cas9 borrowed from the bacterium S. pyogenes is the enzyme most studied and used to date, but researchers are exploring CRISPR systems that use other enzymes. For simplicity, we will simply refer to the whole complex as “CRISPR” for the rest of this article.

The patent, first reported by Buzzfeed Tuesday, lists the inventors as Doudna (pictured above), James Berger of the Johns Hopkins School of Medicine, Caribou’s CEO Rachel Haurwitz, CSO Andy May, research associate Paul Donohoue, and bioinformatics specialist Matthew Carter. (May is the first inventor named on the patent.)

The Caribou patent is different than the patents and patent applications at the heart of the ongoing CRISPR patent fight that pits the Broad Institute of MIT and Harvard, in Cambridge, MA, against a group led by Doudna and UC Berkeley.

The underlying dispute there centers on who invented methods to delete, and even replace, bits of DNA within eukaryotic cells—that is, in creatures more complex than bacteria, anything from yeast to plants to humans. In broad strokes, the big patent fight is about gene editing, with an eye on prizes such as major scientific awards or financial stakes in future medicines that use CRISPR to fix a disease-causing gene.

But the new patent issued to Caribou is about using CRISPR not to edit DNA but to detect and analyze it and related genetic material.

As Caribou’s May put it in an email Wednesday, the patent’s claims “describe methods of using nucleoprotein-guided systems for the detection of target nucleic acid proximity.”

When I asked if that means Caribou is claiming the use of CRISPR to do gene analysis, not editing, May wrote, “That’s a fair description.”

In other words, the patent office now says Caribou has exclusive rights to use the CRISPR machinery to locate precise sequences of DNA or RNA that might be of interest to a basic researcher in a lab, to a doctor or surgeon trying to pinpoint cancer in a patient, or to a drug company looking to recruit people for a clinical trial. May used the example of detecting the Philadelphia translocation, a well-known chromosomal abnormality that is the cause of nearly all cases of the blood cancer chronic myeloid leukemia.

There are already blood tests that look for the Philadelphia defect. But there might be improvements using a CRISPR-based diagnostic tool that detects a snippet of mutant DNA and perhaps, for example, lights up with a glowing green protein that is attached to the nucleic acid. (One of the new patent’s claims, in fact, mentions “GFP”—short for green fluorescent protein, which is commonly used in experiments to help researchers track genes that are being turned on or off.)

CRISPR could also theoretically latch on to cancer tissue and show surgeons exactly where to cut, although there would be many hurdles to clear before such a product could be introduced into a patient’s body. (There are also similar products using other technologies that are already deep into development.)

Caribou has made no secret of its ambition to build businesses around CRISPR in the fields of agriculture, diagnostics, therapeutics, and more. It has already granted exclusive license of its technology for human therapeutics to Intellia Therapeutics of Cambridge, MA. (I asked Intellia if the new patent falls under its license but did not receive an answer by press time.)

The new patent—U.S. 9,260,752—is called “Compositions and methods of nucleic acid-targeting nucleic acids.”

Meanwhile, the ramifications of the new Caribou patent on the ongoing patent fight—or vice versa—are unclear. That fight has moved into a special PTO trial called “interference” that could take years to resolve.

The PTO moved the case into interference earlier this year because the Berkeley-Doudna camp, which also includes the University of Vienna and Doudna’s collaborator, the French microbiologist Emmanuelle Charpentier, made a strong case for a head-to-head challenge of the Broad Institute’s patents, which issued in 2014.

Caribou has exclusive license to cofounder Jennifer Doudna’s work at UC Berkeley, which underpins her group’s fight. But the company has also been building on top of that work.

Much of the Broad’s work is licensed to Editas Medicine (NASDAQ: EDIT), the Cambridge, MA-based therapeutics company that went public earlier this month. Charpentier, who controls her rights separately because of the laws in Sweden where she has conducted much of her work, has thrown in with Crispr Therapeutics, which is headquartered in London but has significant R&D in Cambridge, MA.