Gene Editing: CRISPR Patent Dispute Can’t Slow Innovation

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Gene Editing: CRISPR Patent Dispute Can’t Slow Innovation

by David Dittman

CRISPR-Cas9 is the big name in gene-editing technology, and there’s an ongoing patent dispute holding up potentially millions — even billions — in new business. But researchers continue to find new ways to make us better, stronger, faster…

We’re still waiting for a decision that could determine who profits from the most important biotechnology innovation of the century.

The University of California, Berkeley and the Broad Institute of MIT and Harvard conducted oral arguments before a three-judge panel of the U.S. Patent and Trademark Office’s Patent Trial and Appeal Board (PTAB) on December 6, 2016.

At issue is which inventor or inventors were “first to invent” CRISPR (clustered regularly interspaced short palindromic repeats) gene-editing technology by “reducing the concept to practice.”

There’s no telling how the PTAB will rule. We do know that there are hundreds of millions of dollars at stake.

CRISPR — “molecular scissors” that trim unwanted parts of the genome and replace them with new sections of DNA — have almost limitless biomedical, pharmaceutical, and agricultural applications.

Despite this litigation, time marches on.

And CRISPR continue to make big news.

As ScienceDaily reported on January 11, “Scientists have performed the first all-atom molecular dynamics simulations of Cas9-catalyzed DNA cleavage in action. The simulations shed light on the process of Cas9 genome editing and helped resolve controversies about specific aspects of the cutting.”

Equally exciting is news that researchers at the University of California, San Francisco have discovered “a way to inactivate the CRISPR-Cas9 gene-editing system” using “newly identified bacteriophage proteins.”

As reported by Sci-News on January 3:

“The newly discovered anti-CRISPR proteins could help resolve both problems, enabling more precise control in CRISPR applications, but also providing a fail-safe to quickly block any potentially harmful uses of the technology,” said lead author Dr. Joseph Bondy-Denomy, from the Department of Microbiology and Immunology and the Quantitative Biosciences Institute at the University of California, San Francisco

There remains the major, threshold question: Do we really want this type of technology?

It’s a question that Jim Kozubek, author of Modern Prometheus: Editing the Human Genome With Crispr-Cas9 takes up in a January 9 essay for Time.

Kozubek writes:

There are no superior genes. Genes have a long and layered history, and they often have three or four unrelated functions, which balance against each other under selection. Those risky variants that can, in the right scenario, say, make us better at numbers are actually helpful to remain in the population in low frequencies. Indeed, versions of hundreds of genes that predispose us to psychiatric risks remain in the population at stable rates, while autism spectrum disorder and schizophrenia each occur at about 1% — hinting at a tradeoff of risk for advantage.

…

The promise that we can use gene modification, or even data, to eliminate psychiatric disorders is a fool’s errand. Chronic stress matters. And genetic risk variants remain in the population because they’re advantageous to certain people, given the right genetic background or conditions. Those risk variants are speculating — evolution, always and forever, takes chances.

CRISPR is the acronym du jour. But the technique that’s drawn such attention is actually a two-part process: CRISPR and Cas. Cas stands for “CRISPR-associated proteins.”

The CRISPR process includes “proteins that unravel DNA, others that cut the double helix at a specific location, and a guide RNA that can recognize enemy DNA in the cell.”

Cas9, invented by a team led by Jennifer Doudna of UC Berkeley, is the famous one . . .  for now.

There are actually multiple gene-editing alternatives being studied as you read this. Science moves fast.

Feng Zhang, who leads the Broad Institute group that’s squaring off with Doudna’s Berkeley group in that patent interference proceeding, is responsible for CRISPR-Cpf1. Cpf1 is a smaller, simpler alternative to the Cas9 enzyme.

As Heidi Ledford of the journal Nature explains, “The small size makes the enzyme easier to shuttle into mature cells — a crucial destination for some potential therapies.”

Zhang and his team have also identified C2c2, “an RNA-guided enzyme capable of targeting and degrading RNA” that “helps protect bacteria against viral infection.”

The Berkeley team is also hard at work. As GenomeWeb reports, researchers there discovered “two new CRISPR/Cas systems in a variety of uncultivated microbes, opening the door for the development of new versions of the genome-editing technology.”

In a paper published December 22, 2016, Doudna and her colleagues write:

Current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving untapped the vast majority of enzymes from organisms that have not been cultured. Metagenomics, the sequencing of DNA extracted from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identified novel CRISPR-Cas systems…

CRISPR aren’t the only tool for gene editing, though the efficacy of an alternative based on the Argonaute protein from Natronobacterium gregoryi (NgAgo) is in question.

As Nature’s David Cyranoski writes:

Three months ago, Han Chunyu, a biologist at Hebei University of Science and Technology in Shijiazhuang, reported that the enzyme NgAgo can be used to edit mammalian genes. Now an increasing number of scientists are complaining that they cannot replicate Han’s results — although one researcher has told Nature that he can. Nature Biotechnology, which published the research, is investigating the matter.

Gene-editing technology could — and probably will — change the world.

As Kozubek notes, despite the fact that questions of ethics “will only get more fraught,” “the method is here to last” and “ideas on how to use” CRISPR “change hourly.”

Fasten your seat belts.

Upticks, Downticks

The Russell 2000 gapped up at the open on Friday and held onto its gains sufficiently enough to end another week in the green. The small-cap index added 0.3% during the five trading sessions that ended January 13 and is now up 1.1% in this very young year.

The Chicago Board Options Exchange Volatility Index (VIX) — also known as the market’s “fear gauge” — crept up from 11.32 at the close on Friday, January 6, to as high as 12.60 last week but settled at 11.23 on Friday. That puts the VIX in all-time-low territory.

Small-business owners are hyped by the potential of a Trump administration. As Bloomberg reports, “Optimism among America’s small businesses soared in December by the most since 1980 as expectations about the economy’s prospects improved dramatically in the aftermath of the presidential election.” The National Federation of Independent Business’ Index of Small Business Optimism added 7.4 points last month, to 105.8, the highest reading since 2004, fueled by “a stratospheric 38-point jump in the number of owners who expect better business conditions.”

“They’re getting away with murder,” said President-elect Donald Trump during a January 11 press conference at his eponymous tower. And with that, the Nasdaq Biotechnology Index shed 3% and the S&P 500 Pharmaceuticals, Biotechnology, & Life Sciences Index fell 1.7%. “Pharma has a lot of lobbyists and a lot of power and there is very little bidding,” he added. “We’re the largest buyer of drugs in the world, yet we don’t bid properly… and we’re going to save billions of dollars.”

Eddy Elfenbein of Crossing Wall Street reports on a fascinating bit of market trivia: “The S&P 500 tech sector is closing in on its all-time highs set in March 2000. It only took 17 years, and we’re still not quite there yet. This isn’t unprecedented. The Dow didn’t take out its 1929 high for 25 years.”

Reuters reports on Bitcoin and big trouble in the Middle Kingdom: “China’s central bank launched spot checks on leading Bitcoin exchanges in Beijing and Shanghai, ratcheting up pressure on potential capital outflows and knocking the price of the cryptocurrency down more than 12% against the dollar.”

The U.S. Department of Labor’s Bureau of Labor Statistics reported January 10 that the number of job openings on the last business day of November 2016 totaled 5.522 million, up from 5.451 million in October and more than the consensus forecast of 5.5 million openings. The Labor Department also reported that seasonally adjusted initial claims for unemployment insurance were up 10,000, to 247,000, below a consensus forecast of 255,000, while the four-week moving average declined by 1,750, to 256,500.

President-elect Donald Trump is in historically low territory when it comes to Gallup polling. According to Gallup, 51% of Americans disapprove of how he’s managing the transition, while 44% approve. In December, 48% disapproved and 48% approved of Trump’s post-election efforts to establish his administration. President Obama enjoyed 83%-to-12% approval-disapproval at a similar stage, while President George W. Bush, who, like Trump, lost the popular vote but won the Electoral College and thus the White House, stood at 61% approval, 25% disapproval.

So proud of my fellow Virginian: “Virginia Man Spends $1,000 to Deliver 300,000 Pennies to Lebanon DMV.” Sounds like a (great) case of stick-it-to-the-man-eosis. I mean, who hasn’t fantasized about doing the very same?

William Peter Blatty, who wrote The Exorcist, both the novel and the screenplay, died aged 88 last week.

Smart Investing,

David Dittman
Editorial Director, Wall Street Daily

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By David Dittman