Last month, the US Patent and Trademark Office addressed for the first time the issues surrounding the patenting of RNAi at its Biotechnology and Chemical Pharmaceutical Customer Partnership conference.
The meetings, which are events where practitioners and lawyers can hook up with USPTO officials to talk shop, have been running for years, John LeGuyader, supervisory patent examiner of Art Unit 6135 (which oversees antisense-based technologies), told RNAi News. But it wasn’t until Feb. 3 that a session specifically focused on RNAi was added.
“It’s a hot area in biotech,” LeGuyader told RNAi News, and “practitioners that had been attending the customer partnership meetings had expressed some interest … in seeing a presentation” on RNAi. “In general, practitioners enjoy these kinds of presentations because it gives them an opportunity to hear how we approach examining in specific technologies, like RNAi, [and] about how [we] approach patent law.”
LeGuyader said that at that February conference he addressed the four main areas of patent law “that we find important when we’re examining RNAi” — these include utility, enablement, written description, and prior art.
“For RNAi, per se, it has utility — it meets the criteria for utility,” LeGuyader explained. “So, we generally don’t make utility rejections unless we have reason to, based on the particular gene that is going to be inhibited.”
He said that if there isn’t sufficient understanding about what a gene does, a patent application covering RNAi silencing of that gene might not pass muster.
“Simply saying: ‘We want to inhibit the gene to understand what the gene does … because we don’t really understand the underlying biological mechanism for what it’s involved in’ — that would be problematic,” LeGuyader said. “If we don’t know enough about the function of the gene, we’re going to raise the utility issue.”
This is not something that comes up often, he noted. “Typically, what we see are people that are trying to get RNAi [patents] based on genes where there is some biology. Ultimately, what they are going to try to do is claim pharmaceuticals that would be useful in treatment.”
This carries over into the issue of enablement, LeGuyader said, because “while antisense-based technologies like RNAi have advanced greatly over the years, they are nonetheless highly unpredictable when you try to deliver them in vivo.”
To make a patent claim concerning an in vivo RNAi application stick, “we need to have an adequate amount of [supportive] evidence,” LeGuyader said, adding that the USPTO looks on RNAi in much the same way it does traditional gene therapy — as highly unpredictable and handled on a case-by-case basis.
“Due to the unpredictability in the art, we need the requisite evidence to give those kinds of [in vivo] claims,” he noted. The patent office doesn’t set any requirements on what this evidence needs to be, he added, but “typically, cell culture data isn’t going to be sufficient because of the unpredictability — there’s generally little correlation between how a nucleic acid functions in vitro in a cell culture and how it behaves in vivo.”
So, LeGuyader said, the more data a practitioner has regarding the in vivo use of RNAi, “the more potential you can get — and that’s true also with written description.”
In terms of written description, the USPTO concerns itself with the scope of the coverage claimed by a particular patent application, he said.
“Sometimes we see very broad claims and sometimes we see very narrow claims,” LeGuyader said. “For example, sometimes we see a claim [for] an interfering nucleic acid targeted to gene X, where [the applicant doesn’t] reference where the gene is from. If that gene isn’t very well characterized in a number of different species and it’s not highly conserved among those species, then there’s potentially going to be a written description issue.”
Conversely, he said that a claim covering “an interfering nucleic acid targeting human gene X is much narrower and is less likely to raise written description-type issues.”
Finally, in regards to prior art, LeGuyader said that rejections of patent claims can be based on two areas: Anticipation and obviousness.
“Typically, to find a reference that anticipates, the reference has got to teach everything that’s being claimed,” he said. That is, for a rejection based on anticipation to be applicable, a claim must be explicitly detailed in the prior art.
LeGuyader said that obviousness often comes into play with very broad claims, such as one for “an RNAi [molecule] targeted to human gene X … because, in view of the progression of the technology, one would expect it to be obvious to find RNAi sequences for a particular gene, if there is a reason to want to inhibit the gene. We’d have to provide that reason,” he said.
“The upshot is that specific sequences, very likely, are going to be free of the prior art, unless we find that explicit sequence” claimed elsewhere,” LeGuyader added.
Words to the Wise
LeGuyader said that there is no one particular area of the patent landscape that appears to be more of a stumbling block for RNAi practitioners than others, adding that “it’s difficult to tell people what they should or shouldn’t be patenting — I don’t know that that’s necessarily my job. However, there are things practitioners can do to improve their chances, he said.
“We like to see lots of data on targets spanning a gene,” he said. “If people are trying to get a broad … claim for RNAi spanning a full-length gene, then we’re going to want to see data spanning across the gene.” LeGuyader cautioned, however, that if a practitioner is “claiming RNAi sequences in the untranslated regions [and] they don’t have any examples of accessible regions that inhibit [gene expression], then they’re likely not going to be entitled” to their claim.
Additionally, the USPTO’s patent examiners look for objective evidence supporting arguments against enablement, written description, or utility issues, LeGuyader said. “Oftentimes, people will file expert opinion declarations, but they won’t support those opinions with objective evidence … [such as] case law, journal articles, or experimental data … that we can go through and critique.”
In the end, dealing with the USPTO should be a very straightforward issue. “We have very specific guidelines — utility guidelines, written description guidelines, enablement guidelines, as well as prior art that we have to follow and do follow,” LeGuyader said.
“The office is very transparent in what all these guidelines are,” USPTO spokeswoman Brigid Quinn told RNAi News. “They are up on our web site, [and] people go out all the time and make presentations.”
She noted that these guidelines can be found at http://www.uspto.gov/web/offices/com/sol/notices/utilexmguide.pdf and at http://www.uspto.gov/web/offices/com/sol/notices/writdesguide.pdf.
LeGuyader said he also spoke on patenting RNAi at a Feb. 27 meeting at the Suffolk University School of Law, adding that he is currently not scheduled to present his talk again.
—DM