CRISPR-Cas9, the "gene scissors", who should belong to?
In response to this protracted "tug-of-war", the USPTO made the latest ruling -
Zhang Feng's team beat the Nobel Laureates with priority.
In other words, the verdict acknowledges that Zhang's Broad team was the first to invent CRISPR-Cas9 to edit human cells and use it to make drugs.
The CVC team, which is at the forefront of the competition, even with two Nobel laureates (Jennifer Doudna and Emmanuelle Charpentier) in the seat, still lost the verdict.
You know, they previously won the 2020 Nobel Prize in Chemistry for their outstanding contributions to CRISPR-Cas9.
At that time, many people lamented that Zhang Feng did not win the Nobel Prize.
But this time, the reason given by the USPTO is:
The CVC failed to provide sufficient, strong evidence that they were ahead of the Broad team.
Therefore, the CVC's argument about unfair conduct is rejected, and the claims referred to by the CVC in this lawsuit are rejected.
This means that Editas Medicine, a gene editing company founded by Zhang Feng, can obtain gene editing patents for CRISPR-Cas9 and CRISPR-Cas12a covering all human cells in the United States.
By contrast, the ruling was a disastrous cost to the University of California, Berkeley, where the CVC team is located.
Foreign media commented on this:
Its licensing revenue in the U.S. could lose $100 million to $100 million.
"Gene scissors", why was it awarded to Zhang Feng?
Let's take a look at the specific contents of the patent judgment.
The Appeals Board ruled that the CVC team no longer had patent rights to the patent "Application of CRISPR-Cas9 in Eukaryotic Cells" to nine technologies associated with it.
The verdict said the debate focused on "who first invented the unidirectional RNA in eukaryotic cell applications in the CRISPR-Cas9 system."
This unidirectional RNA carries an enzyme that is key to targeting DNA editing and influencing gene expression.
More importantly, gene editing in eukaryotic cells has a profound impact on the development of human drugs, which is one of the reasons why the patent dispute has attracted widespread attention.
For example, the treatment of genetic diseases such as hypertrophic cardiomyopathy and sickle cell anemia is affected by CRISPR technology.
Many biotechnology and pharmaceutical companies around the world are using CRISPR as a core technology to develop new therapies.
As a result, affected by this patent dispute, many companies that previously obtained patent use rights from CVC will have to re-sign agreements with Board.
It would be a huge loss. Because these companies have made breakthroughs in previous clinical trials, the patent licensing fees may rise later.
And, of course, the most immediate impact at the moment – stock prices.
For example, Intellia, which has partnerships with Novartis and Regeneration, has previously obtained patent licenses with CVC, and their stock prices have fallen by 19.22%.
But if you had previously "bet" on the Board team, the situation would have been a different form:
Idols Medicine Inc., a biotech company licensed to Board, rose 17 percent ahead of Monday's close.
However, this long patent dispute has only come to an end temporarily.
Because this victory only means that the CVC team cannot interfere with Board's patent use rights in the United States, and who the patents in other regions belong to have not yet been settled.
In fact, the CVC team may be slightly better in Europe.
As of 2018, the European Patent Office has officially granted two patents on CRISPR-Cas9 to Emmanuelle Charpentier, where CVC sits.
A "patent war" that lasted for years
One of the core technologies around this "patent war" is CRISPR-Cas9.
CRISPR is an abbreviation for Clustered Regularly Interspaced Short Palindromic Repeats.
Simply put, CRISPR is a natural "immune system" in the microbial body, and when a virus invades a bacterium, it can produce "memories" through it.
CRISPR was first discovered by Japanese scientists in the 1980s.
It wasn't until Emmanuelle Charpentier and Jennifer Doudna discovered cas9, the enzyme used by Streptococcus for immune defense, that the enormous potential of its genome editing tools was tapped.
That's because enzymes, in the process of gene editing, are the equivalent of a "molecular scissors" that can cut off double-stranded DNA at specific sites.
After a DNA break, the cell repairs the break site.
But before that, scientists often encountered a pain point in this process, that is, every time a gene was modified, a new protein needed to be designed for the DNA sequence they wanted to modify.
Cas9, on the other hand, uses RNA to guide itself and "scans" the DNA until it finds the right site.
So they came up with this idea:
These RNA molecules can be engineered into a gRNA.
A system of one protein and one gRNA is enough to be a powerful tool for genetic modification.
Through experiments, their vision was a real success — successfully implementing CRISPR gene editing in test tubes and bacteria.
So in 2012, Charpentier and Doudna made crispr-Cas9 research public in Science.
Perhaps with their strength, it is only a matter of time before they can achieve the gene editing of CRISPR in animals.
As soon as it rises to the animal level, this technology can be fully expanded and expanded in medical treatment (exploring the treatment of AIDS, Alzheimer's disease, schizophrenia and other diseases), scientific research, agriculture and other fields.
In other words, it will be difficult for others to tap into CRISPR's core interests.
At this time, the team led by Zhang Feng also published a paper in Science in 2013, and declared:
Successfully edited animal genes using the CRISPR system.
That is, the former parses how it works, while the latter applies it to mammals.
The work done by both of them has had a sensational impact on the industry.
However, in terms of awards, Zhang Feng's team belongs to the more "frustrated" side.
For example, the 2020 Nobel Prize in Chemistry was awarded to Charpentier and Doudna, and Zhang Feng had no connection with them.
Earlier, such as the 2020 Wolf Prize in Biology, the 2016 Alpert Prize, and the 2015 Scientific Breakthrough Prize, were also awarded to Charpentier and Doudna.
However, Zhang Feng's team obtained very different results in patents.
Charpentier and Doudna filed a patent application in May 2012, while Zhang's team filed in December of the same year.
After all, the commercial value behind CRISPR-Cas9 is immeasurable, and this "patent tug-of-war" has gradually begun.
In 2014, the U.S. Patent and Trademark Office first approved the patent application of Zhang Feng's team.
At this point, Charpentier and Doudna's CVC team was not happy - "the CRISPR-Cas9 we found first, the patent was also filed first."
So in 2016, the CVC team appealed to the U.S. federal court, but the result was rejected.
In 2017, the USPTO gave Zhang Feng's team an extremely crucial judgment in this "tug-of-war":
No changes are made to the approved patent.
To this day, the latest ruling of the USPTO is still biased in favor of Zhang Feng's team.
……
It can be said that although Zhang Feng's team is "frustrated" in the award, it is a "proud" party in terms of patents.
Who is Zhang Feng?
So who is the protagonist of this incident, Zhang Feng?
Zhang Feng, born in 1982 in Shijiazhuang, Hebei Province, moved to the United States with his family at the age of 11.
In 2004, Feng Zhang graduated from Harvard University with a bachelor's degree, and in 2009 received his Ph.D. in chemical and biological engineering from Stanford University under the tutelage of Carl Dicelós, the father of optogenetics.
In graduate school, he worked with his team to develop techniques that use light to activate neurons in the brain, revealing the root causes of diseases such as schizophrenia and bipolar disorder.
The most prestigious is, of course, his work on CRISPR.
In 2011, at an academic conference, Zhang Feng heard about crispr research, and at that time, there was not much literature on the technology, focusing on whether CRISPR could help produce better yogurt.
In a later interview, Zhang Feng revealed that he thought at the time:
Can we make it work in human cells?
Thus began Zhang Feng's years of exploration in CRISPR.
In 2013, his famous industry-famous achievement "Multiple Genome Engineering Using CRISPR/Cas Systems" was published in Science.
The following year, he was named one of Nature's "Top Ten Scientific People of the Year 2013". It was later known in the industry as one of the CRISPR Big Three.
When Charpentier and Doudna won the Nobel Prize for their outstanding contributions to gene editing, many people regretted Zhang Feng's failure.
In 2021, Zhang Feng was elected a member of the National Academy of Medical Sciences.
The rationale for the selection was: the discovery of novel microbial enzymes and systems and their developments as molecular technologies such as optogenetics and CRISPR gene editing, revolutionizing molecular biology and driving a transformative leap forward in the ability to research and treat human diseases, as well as providing excellent guidance and professional services to them.
Finally, it remains to be seen how the overall outcome of this "patent war" will develop.
Reference Links:
[1]https://www.mercurynews.com/2022/02/28/uc-berkeley-loses-crispr-gene-editing-patent-case/
[2]https://www.scribd.com/document/561762623/106-115-Decision-on-Priority
[3]https://mp.weixin.qq.com/s/glN5z7oj-m2fWUpKZ4eO_w