History of Intellectual Property in Synthetic Biology

Gene patents date back to 1976, when Stanford and the University of California filed a patent application for recombinant DNA. Two years later, the IPA granted universities the right to own all inventions arising from research as long as they complied with physical and biological containment standards in NIH guidelines and allowed the government to receive a free non-exclusive license to use the results. Opposing arguments claimed that since research is publicly funded, it should therefore be property of the US government.

The Human Genome project fueled the fire of whether DNA is patentable or not. Since DNA sequences are discoveries and not inventions, they are not patentable or copyrightable. However, in 1991 Craig Venter and NIH applied for patents of 337 partial cDNA sequences of unknown function, as a part of his project to isolate all cDNA sequences of the human brain genes. This was seen as a movement towards a cDNA arms race- the exact opposite of the collaboration and cooperativity that was expected from the Human Genome Project. While the goal of the NIH is rapid dissemination of products to be used to treat disease, this move directly contradicts the open-source access that it claims to support. Venter’s push to patent cDNA sequences would have granted him access to the entire coding sequence, complementary sequence, allelic sequence, and ultimately, the encoded proteins from a cDNA, although this was unknown to him at the time. The patent was ultimately rejected, creating a precedent for the future of synthetic biology.

Current

More recently, a series of Supreme Court cases have brought the world of synthetic biology to the public eye. Sangamo Biosciences Inc., a clinical stage biopharmaceutical company, holds the vast majority of zinc finger intellectual property. Purchasing zinc fingers from Sangamo rings up a hefty price of $15,000 for a single functioning zinc finger nuclease, which only work in pairs. Using purchased zinc fingers, it is impossible to do open source research due to licensing and high costs. Sangamo’s monopoly over the zinc finger industry prompted the synthetic biology community to develop an open source alternative so that research would not be hindered.

In June 2013, the Supreme Court unanimously decided that genes are not patent eligible after Myriad Genetics claimed the rights to two isolated genes that greatly increase the risk of ovarian and breast cancer when mutated. This decision ruled that genomic DNA is a product of nature and cannot be patented solely because it is isolated. However, cDNA, or DNA with the introns removed, is patent-eligible.

Benefits of a patent for a biotech industry vs. copyrights and trademarks

The broad use of the term “intellectual property” has blurred the lines between patents, copyrights, and trademarks, all which carry important distinguishing features when considering their uses in synthetic biology. By definition, copyrights apply to a work of art, while patents cover inventions and methods. Trademarks,which are less common in the synthetic biology industry, essentially label a certain researcher’s creation. By putting a watermark on a product, such as when Craig Venter put his name into DNA sequence, the manufacturer has claimed exclusive control over that product, protecting the credibility and quality of its source. However, trademarks do not protect an idea, and allow other researchers to produce similar, or even identical, products, thus reducing the chances for a monopolistic industry. Therefore, in an effort to maintain control over a product, researchers are less likely to use trademarks over copyrights or patents.

One major topic of discussion is whether to treat synthetic biology as a copyrightable or patentable entity. Arguments have been made to pull emerging synthetic biology to follow in the footsteps of either the software industry or biotechnology. To be copyrightable, engineered products such as proteins and DNA must be deemed as “original works of art”. This qualification has been made in the software industry for codes, which are copyrightable. However, methods are not copyrightable, allowing for protocols to be adapted and used in the building of new synthetic parts. In addition, copyrights do not carry much enforceability.

The other side of this spectrum pushes synthetic biology towards the biotechnology industry, with a race to patent both methods and products. A patent is issued by the government and confers to the applicant the exclusive rights to a method or product. To qualify for a patent, a method or product must be novel, non-obvious, and have utility. Determining the extent to which these qualifications cover has even been taken up in the Supreme Court.

For biotech startups, investing in heftily priced patents allows researchers to accrue royalties by licensing their products. Patents encourage the commercialization and development of the industry by providing incentives for researchers.

Enforcement of patents and licensing in consideration of academia

Efforts have been made to create a balance between patents and open-source technologies regarding the respective users of new technologies. Intellectual property management must take into account private companies versus academic researchers, and all in between.

Open source is very effective in the software industry because of its modularity. Many people can contribute bits of code to a common domain so that others can utilize selected pieces to build new systems, which can then be integrated together. The same is true for synthetic biology. As new parts are characterized and submitted to the common domain, other researchers can build on these parts to create new systems. In two of our interviews with Arti Rai and Robert Cook-Deegan, we discussed the intrinsic and extrinsic motivations driving the open source model for synthetic biology. In the software industry, once developers create code to solve their specific problem, there is usually no reason to keep the information from being freely accessible. In two of our interviews with Arti Rai and Robert Cook-Deegan, we discussed the motivations driving the open source model for synthetic biology. It is interesting to note the different positions on the topic of access for academic versus commercial institutions. For academic institutions, it is clearly beneficial to maintain an open source registry modeled after the software industry so that parts can be freely shared between researchers. However, it can be argued that when these parts are taken up into the commercial sector, companies should pay appropriate royalties. Support for this argument stems from the fact that companies would then be commercializing parts that were publicly funded.

Sequence patents or methods patents

Craig Venture’s attempt to patent all cDNA sequences in the human brain exposed a possible threat to the future of synthetic biology commons. With the rapid design and building of TALEs, it is hypothetically possible for someone to create every possible combination of repeat variable diresidues and patent those TALES, effectively placing a lock on the industry. To avoid something of this nature, it is important to prevent methods patents in synthetic biology. Patent applications must have a clear written description of use and enablement. Patents would not be granted for parts without a known functionality.

*do we want to talk about Sangamo here?

Guidelines and practice standards for the Biobrick community

In 2007, a group of universities adopted the “9 Points to Consider.” This list illustrates the suggested standards for universities when granting licenses to outside institutions and applying for patents that may limit research at other institutions. The “9 Points” emphasizes that the primary goal of research is to promote improvements for society, and warns against the use of patents which could hinder any advancement.

9 Points:

1. Universities should reserve the right to practice licensed inventions, and to allow other nonprofit and governmental organizations to do so.
2. Exclusive licenses should be structured in a manner that encourages technology development and use.
3. Strive to minimize the licensing of ``future improvements.``
4. Universities should anticipate and help to manage technology transfer related conflicts of interest.
5. Ensure broad access to research tools.
6. Enforcement action should be carefully considered.
7. Be mindful of export regulations.
8. Be mindful of the implications of working with patent aggregators.
9. Consider including provisions that address unmet needs, such as those of neglected patient populations or geographic areas, giving particular attention to improved therapeutics, diagnostics and agricultural technologies for the developing world.

Preventing Against Patent Trolling

It is important to note that there are BioBrick parts in the registry that infringe on patents already. Most companies do not take action against academic institutions, but this can serve as an eye opener to the danger of upstream patent thickets.

• kind of ties into the section above.
  
  
  

References

1. Belt, H van den: Synthetic biology, patenting, health and global justice. Syst Synth Biol. 2012.
2. Chandrasekharan S, Kumar S, Valley C, Rai A: Proprietary science, open science and the role of patent disclosure: the case of zinc-finger proteins. Nature 2009. 27: 140-144.
3. Cook-Deegan, Robert: Law and Science Collide Over Human Gene Patents. Science 2012. 338.
4. Cook-Deegan R, Heaney C: Patents in Genomics and Human Genetics. ARI 2010. 17: 1-36.
5. DeFrancesco, Laura: Move over ZFNs. Nature 2011. 29: 681-684.
6. Genome Patent Fight Erupts. Science. 245: 184-186.
7. Kumar S, Rai A. Synthetic Biology: The Intellectual Property Puzzle. Texas Law Review 85: 17 45-1768.
8. Ledford, Heidi: Bioengineers look beyond patents. Nature 2013. 499: 16-17.
9. Marshall, Eliot: Companies Rush to Patent DNA. Science 1997. 275:780-781.
10. Rai A, Boyle J: Synthetic biology: Caught between property rights, the public domain and the commons. PLoS Biol 2007. 5(3): e58. doi:10.1371/journal.pbio.0050058.
11. Rai A, Cook-Deegan R: Moving Beyond “Isolated” Gene Patents. Science 2013.
12. Scott C: The zinc finger nuclease monopoly. Nature 2005. 23: 915-923.
13. Universities can patent recombinant DNA results. Nature 1978. 272: 199.
14. Zinder N: Patenting cDNA 1993: efforts and happenings. Gene 1993. 135: 295-298.

Extra headers
IP management
Parallel open-source technologies
Taking the risk-Pogge and the Health Impact Fund/prize funds
Patent pooling

Extra
Since BioBrick parts only use four restriction sites, these limitations impose on the modularity desired in building compatible systems. Open registries with fewer restrictions increase the diversity of standard parts that can be shared between systems. Each category of parts, such as promoters, reporters, and genes, could be submitted on unique backbones for each part. However, there are scientific concerns with how these parts would be made. When performing PCR to isolate multiple parts in different backbones, extraneous bits of DNA may become an issue with compatibility.