Don't ignore these inventions

Release date: 2016-06-02

Medical Valley Editor's Note: Recently, the team headed by Han Chunyu discovered the first “China-created” cutting-edge gene editing technology NgAgo-gDNA, which is known as the fourth-generation gene editing technology and broke the patent monopoly of foreign gene editing technology. It has reached the international first-class level. Some insiders say that it may surpass the CRISPR-Cas9 technology, but in addition to the advanced technology, we may also need to pay attention to some aspects of the technology.

Talking about the Han Chunyu Nobel Prize Project: Talking about the Importance of Patent

Text / Science Network Blog Sha Chen

In recent days, Associate Professor Han Chunyu’s report on the major original achievements of Nature Biotech has captured the headlines of many media and praised everyone. Many researchers believe that the NgAgo-gDNA technology reported by Han Chunyu is more suitable for human genome editing and will likely surpass the CRISPR-Cas9 technology. For professional interest, the author searched Han Chunyu's patent and found some problems, which were proposed for researcher's reference.

Han Chunyu and John van der Oost both published papers in nature

Let's take a look at Han Chunyu's entire process from producing research ideas to "Nature Biotech".

Han Chunyu's research on NgAgo was inspired by the article "DNA-guided DNA interference by a paokaryotic Argonaute" published by John van der Oost of Wageningen University (Netherlands) in the journal Nature. The article introduces TtAgo. (Thermus thermophilus Argonaute) can cut DNA using DNA as a template.

Inspired by van der Oost, the Han Chunyu team started experimenting in the first half of 2014. Two months later, NgAgo was able to do genetic editing tools. After the initial results of the experiment, Han Chunyu submitted a contribution to the journal Science. During the review of Science, Han Chunyu's research team continued to improve the experimental results. In the fall of 2014, Zhejiang University Shen Xiao also began to participate in this work. After a half-year review by Science magazine, Han Chunyu’s submission was eventually rejected. It is estimated that this time is about October. After supplementing the experimental content, the experimental paper was changed to "Nature Biotechnology" on June 3, 2015. After 9 months, the article was accepted in February 2016, and was published online on May 2, 2016. From the beginning of the study, to the publication of the paper, about two years before and after.

Also, let me introduce John van der Oost.

John van der Oost is currently working at Wageningen University in the Netherlands. He began researching the CRISPR field in 2005. He is a research member of the early CRISPR, working with both Zhang Feng and Jennifer Doudna. The latest public patent shows John van der Oost also at Caribou Biosciences. Among the inventors' list, the company was founded by Jennifer Doudna.

John van der Oost's article "DNA-guided DNAinterference by a paokaryotic Argonaute", submitted on July 30, 2013, was published on February 16, 2014.

Both Han Chunyu and John van der Oost applied for a patent.

First look at John van der Oost's patents filed around TtAgo:

Look at the patents applied by Han Chunyu:

Also in the field of genetic editing, the same results are published in the world's top journals. However, the protection of technological achievements is surprising. Han Chunyu's results were better than van der Oost's results. However, it was not until the second submission that he applied for a patent. There were two patent inventors, and the first inventor was Zhejiang University, and he did not apply for foreign patents. In contrast, van der Oost applied for a patent before submitting the manuscript, and then applied for a PCT international application. I think there should be no one in the field of genetic editing about the ownership of CRISPR-Cas9. In this case, such important results still have no active patent layout. This reflects that the attitudes and concepts of Chinese researchers on scientific research results remain in the laboratory, without considering the market application and what benefits the results can bring to society and humanity.

So be reminded :

1. Publishing a paper does not mean that you own the ownership of the technology. Artemisinin drugs discovered by our country's Nobel Prize winner Tu Yu are world-famous, but the drug has only been published in the paper, and there is no patent protection. International pharmaceutical companies can use artemisinin technology for profit. There is no patent regulation here. Please remember that if you have good technology, please protect the patent first.

2. Despite the application for patents, the patents written by different patent writers are uneven. Regardless of the unreasonable layout of the rights, compared to the more than 20 claims of van der Oost, there are only eight claims for the invention of Han Chunyu. I participated in the genetic drug investment project in 2011, and it is similar to foreign countries. With hundreds of claims, it is not enough to have only eight claims for such an important technology. The quality of patents is crucial for subsequent implementation and rights protection.

3. For cooperative R&D, the parties must agree on the ownership issue. For the patents applied by Han Chunyu team, the inventors come from two colleges, but there is only one applicant. If there is no agreement, it may affect the subsequent implementation. And how the patent licensing fees are distributed is an issue that needs to be discussed.

4. The use of patent conversion is not simple, but it is very complicated and costly. Many researchers are not only reluctant to invest enough energy and expenses in patent application, but are also less willing to invest human, material and financial resources in patent conversion. In fact, the requirements for patent conversion are very high. Not only do they require relevant professional knowledge, but also many knowledge and skills such as communication, management, negotiation, etc., and there are few such talents in research institutes and universities. Therefore, it is not a good technology to transform, to find a professional team.

Can NgAgo surpass CRISPR?

Text / Science Network blog Zhu Mengjin

Can NgAgo surpass CRISPR? Not only domestic, but also some foreigners are more concerned about this issue. The world's laboratories for genome editing methods and applications almost all have a mature technology platform for CRISPR-Cas9. The CRISPR-Cas9 editing system is a well-recognized mature genome editing tool, and the advantages of CRISPR technology can not be underestimated. It has a big cow to support it. Its development and improvement have gathered the resources of the genome editing laboratory all over the world. The year of development is amazing. Can NgAgo come back later and go beyond CRISPR?

From the point of view of the number of individual subjective comments, foreign attention to NgAgo does not seem to be as hot as domestic. A simple search, I found that most of the comments are objectively describing the results of the article or introducing the NgAgo and CRISPR principles in parallel, and the comments with personal subjective colors are not particularly high. The following extracts, organizes, and processes some comments with personal subjective colors. In his comments, David believes that this is an interesting editing system. The article is also worth reading. Although there is no strict comparison for editing efficiency, judging from the information given in the article, NgAgo and Cas9 should be in editing efficiency. At the same level, as to whether NgAgo can replace CRISPR, it is still uncertain. The only certainty is that this is not the final progress of genetic editing. Paul's answer in his comment is: From any angle, it is impossible for the time being - "not going to immediately race ahead of CRISPR...not yet any way", but he has to admit that NgAgo has indeed attracted people's attention. . He quoted the four characteristics summarized in Han Chunyu's article. If it is as good as 4 points in the article, then NgAgo may be more concise than CRISPR, and according to Korean article 5, NgAgo editing efficiency is indeed a bit of a cow. However, he believes that because of the large number of articles supported by CRISPR, NgAgo is far from being able to explain the problem with this article alone, and more articles and data are needed for the conclusion of NgAgo. It makes people feel that there is a so-called "too good to be true" acid taste. Finally, he said let us look around, there will be a lot of follow-up articles in the next few months.

So the onlookers really came -

Passerby A - whoever is dead, is not yet known, but everyone must compete in a fair environment. (A look at the guy who knows the unspoken rules of the industry, so many of the big cows doing the CRISPR, it seems that the prospect of NgAgo is not good, so you can open the fight, but be fair! Fair! Fair!)

The death loyalty of CRISPR has also come, and the sniper has been launched for the 4 points of the Korean article summary - I am not awkward, I am based on Betteridge's law (this law means that for any question ending with a question mark, you can use no To answer) NgAgo said no: (1) Church Lab's iPSC genome sequencing results show that CRISPR also has Low tolerance for mismatch, and (2) misguiding? This is the most funny proposition I have heard about genomic engineering problems, and phosphorylated ssDNA is not called DNA at all, it can only be seen as DNA damage or infection, both (DNA damage and DNA infection). It is unpopular for genome manipulation; (3) I never remember that someone actually saw that sgRNA was replaced from Cas9. Is there wood? (4) Who said that sgRNAs are not well designed and synthesized? It must be said that this has not been done by the genome editor; (5) Do you not help the landlord? I can see that the editing efficiency of HEK293T cells in Figure 5 is not good enough, ok?

Passerby B - You don't think this tool is very bullish, can you use it to edit the genes of adults? (This brain hole is a bit big)

Passerby C - Don't you think that it is an advantage to not need PAM? Deaf people think that the labs and companies that have not yet established the CRISPR platform, it is not a good thing to choose NgAgo. However, from the rhythm of "the waves are beaten by the waves", the development speed of genome editors is dazzling, NgAgo will never be the last tool, and I will be better tools will come out within the year. Are you gambling? Two loft magazines!

Passerby Ding - You silly X, why do you have to find the enzyme gene from nature, don't you know that the artificially designed enzyme is more than N times? I firmly believe that the end of the waste of taxpayers, you must be artificially designed enzymes. (very angry)

Passerby - for investing a lot of time and resources on the CRISPR, will not easily go to NgAgo, unless you encounter 100% can not solve the PAM problem, you may try NgAgo. (Looks more rational)

Passerby X——5′-P ssDNA cannot be produced by plasmids, meaning that it cannot be transmitted by plasmid or virus, only synthesis and transfection, and transfection is uncontrollable, which is a big problem of NgAgo.

Source: Science Network Blog Medical Valley Comprehensive

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