CRISPR sits in the middle of a costly patent brawl. That hasn’t stopped scientists and venture capitalists from betting on who will win. Business is moving fast with licenses being sold, betting on the USPTO’s decision which recently sided with MIT and the Broad Institute, with possibility for appeal.

When it comes to pharmaceuticals, patents are licensed and traded in the amount of millions of dollars funneled through a 14 to 20-year timer.

While the stakes are high, CRISPR/Cas9 is not the only gene editing technology out there. It was however, the first gene editing technology to be discovered in ancient bacteria, channeling new interest with the hope to discover an unclaimed and more effective gene editing technique.

There are over 20 patents for various aspects of CRISPR technology, the patents are claimed and divvied up between four major companies: Editas with Zhang and MIT (public company, raised $190M), Caribou with Doudna and UC Berkeley (private, ~$42M), Intellia (public, $104M), and CRISPR Therapeutics with Charpentier (private, $154M).

While Doudna and Charpentier are largely touted as first to invent the technology, Zhang was first to file, with MIT paying extra fees for expedited filing services. Filed at the cusp between “first to invent” and “first to file” the patents still hang in limbo. Even though they were recently by-and-large awarded to MIT and the Broad Institute, there is still possibility to appeal.

At the heart of the dispute is the claim that Doudna only applied the patent for bacterial cells - and not for human cells, which are more complicated versions of bacterial cells. The dispute over what is and isn’t obvious, along with timing of filing and evidence of first to discover, could point the patent, and millions of dollars of royalties, to either Doudna or Zhang.

Pharmaceutical companies make money in two ways: drug sales and royalties on intellectual property. Since gene therapeutics are so new and governments haven’t yet decided how to regulate the therapies, there are currently no sales in the U.S. and will likely be no sales for several years. So how do companies based off of CRISPR/Cas9 attract investment and operate?

Investors are betting that gene therapeutics will be profitable, and patents for CRISPR/Cas9 are held until 2033. Usually companies receive single-digit percentage royalties as well as yearly licensing fees on the scale of several hundred thousand dollars. If Editas wins the license, they can passively collect revenue on any drug sales from therapeutics using the Cas9 technology.

These pre-revenue companies also do collaboration with other large pharmaceuticals. Competing in the growing cancer space with chimeric antigen receptor (CAR) T-cells, Editas partnered with Juno Therapeutics receiving an upfront payment of $25M, while Intellia (founded by Caribou) has engaged in a collaboration with Novartis receiving an upfront payment of $10M. Entering the field of inborn metabolic disorders Intellia collaborated with Regeneron in April, receiving $75M upfront.

While there is a Nobel prize floating around, and upfront license payments and collaborations are over $100M with billions to be gained in the coming 18 years, it also might not be that big of a deal in everyday research.

Zhang recently discovered another method in the CRISPR system called Cpf1, which staggers the DNA break and only needs one guide RNA. While the discovery is not revolutionary scientifically, being just one of many in the CRISPR system, and with many others bound to be discovered in the coming years, it does however provide an answer to the patent brawl by simply stepping out of it. Cpf1 can do the same thing, without all the legal hassle. And there’s more where it came from.

How does all this affect day-to-day science? Speaking with Alex Chavez with the Church Lab, who is researching modified CRISPR/Cas9 systems to treat Duchenne’s Muscular Dystrophy (DMD), I ask if the CRISPR patent brawl will affect scientists’ choice in research. Luckily he responded, “I think a lot of people are driven purely by intellectual curiosity, and if [money] comes along, that’s great.”

Should universities be involved in patenting technologies? Does the commercial pressure increase research? Does multiple licensing of the technologies increase cost of development?