This story has been updated to include comments from Benitec's CEO.
By Doug Macron
The US Patent and Trademark Office last week issued a notice of intent to issue an ex parte re-examination certificate for Benitec's US patent No. 6,573,099, a move that will essentially end a years-long re-examination process that nearly overturned the cornerstone of the company's expressed RNAi intellectual property portfolio.
"The long re-examination process reflects the importance of this patent in the global field of gene silencing using RNA interference," Benitec CEO Peter French said in a statement. "This notice … [clears] the way for us to leverage our dominant patent estate globally."
According to French, the re-exam process "sidelined" Benitec from striking potentially lucrative partnerships deals over the past several years. But with the matter settled, "we can now start to negotiate, look for partnering, [and] look for further licensing opportunities. Those potential partners we will be talking to would have their previous uncertainty [about the company's IP] overcome.
"It really is the re-start of the Benitec program," he told Gene Silencing News this week.
Still, Benitec's IP troubles aren't quite over. Last week, the Australian firm disclosed that the UK Intellectual Property Office has received an application to revoke its UK patent No. 2,353,282, which is related to the '099 patent.
The application, the company noted, was filed by a UK-based patent law firm, "which may be acting on behalf of a third party … not disclosed in the application."
French said in a statement that the company is "very confident" of its ability to defend the UK patent, "particularly in light of the recent decision by the US Patent and Trademark Office."
Although it was one of the earliest players in the RNAi therapeutics space, Benitec is perhaps best known for being one of the most litigious.
In 2004, under previous leadership, the company sued three companies — Nucleonics, Ambion, and GenScript — for infringing the '099 patent, which essentially claims the knockdown of gene expression using DNA that transcribes double-stranded RNA (GSN 4/2/2004).
To end the litigation, Ambion and GenScript took licenses to the patent. However, Nucleonics chose to fight back, and asked the court hearing the case to rule Benitec's patent invalid and unenforceable. It later expanded its defense to include requests for re-examination of Benitec's IP in the US and abroad.
The cost of the litigation on both Benitec's finances and reputation eventually led to the ouster of Benitec's Chairman and CEO John McKinley, who was replaced by COO Sara Hall (GSN 1/21/2005).
Under Hall, Benitec worked to settle the matter, requesting that the court dismiss the case on the grounds of a Supreme Court ruling upholding a statutory patent exemption termed 35 U.S.C. 271 (e)(1), which gives drug makers the right to use other companies' patented technology to develop new human therapeutics (GSN 10/7/2005).
Nucleonics appealed the dismissal, however, as it sought to undermine the IP of its chief rival (GSN 3/16/2006). The appeal was ultimately rejected and the lawsuit laid to rest, but the damage was done; in mid-2006, Benitec buckled under the weight of legal costs and shuttered its US operations in order to regroup in Australia as a much smaller firm (GSN 4/20/2006 & 6/29/2006).
Meanwhile, Nucleonics' request to the USPTO for a re-examination of the '099 patent proceeded, and claims in the IP were repeatedly rejected, though the patent office's decisions were never final (GSN 4/24/2008).
Benitec continued to defend its patent, but by early last year it seemed that the company's efforts were falling short (GSN 4/2/2009). And while Benitec suffered another setback in January with the USPTO rejecting certain claims within the patent (GSN 1/10/2010), in September the company announced that it had successfully petitioned to have all previous claim rejections reversed, effectively ending the opposition to the IP (GSN 9/302010).
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In light of that ruling by the USPTO, the issuance of notice of intent last week was widely expected.
What was not expected, however, was the opposition encountered in the UK.
Benitec said that after an initial review of the request to revoke the '282 patent, it "believes that the application … merely reiterates old arguments based on the antisense literature. These arguments have been successfully overcome in other jurisdictions including the US, the EU, and Australia.
"The revocation application also alleges obviousness of the invention over various references, and again similar representations have been dealt with elsewhere," it noted. "Consequently, Benitec believes that the revocation application is without merit."
The firm added that it will defend the patent and should "further significant information" come to light through an attorney review, it will provide additional updates.
Despite the situation in the UK, Benitec is keeping its focus on moving forward as a drug developer with an IP position no longer in doubt.
French said that the company is now working on demonstrating the efficacy of its expressed RNAi technology in order to lure partners and licensees, primarily by advancing three in-house programs.
The first is in lung cancer, which is being conducted in collaboration with the University of New South Wales, is developing an expressed RNAi drug targeting the beta III isoform of tubulin in order to increase the sensitivity of tumors to chemotherapy. French said that Benitec could begin clinical testing of this drug within the next two years.
The company is also working with China's Biomics Biotechnologies to develop a hepatitis B therapy. "We're looking to focus much of [this] work in China, where there is a very big population with chronic hepatitis B infection," he noted.
Lastly, Benitec has a program in cancer- and chronic disease-associated pain. Last month, the company announced it is working with the University of Queensland to test a number of RNAi constructs in pain models to "determine which specific target sequences have the strongest effect on reducing neuropathic pain from a single injection."
Because the regulatory requirements to look at long-term effects of a drug in a terminal patient population would be lower than with non-life-threatening conditions, French said that Benitec might be able to fast-track the pain program, making it the firm's "flagship program to demonstrate the efficacy and advantage of using our technology."
With these efforts advancing, "we feel that we are poised, within the next 24 months, to be able to bring one or more programs to the clinic," he added.
"I believe once we get proof of concept in the clinic through a phase I/II program, this will transform the company's position. With a robust IP [position] … and some validation in the clinic, I think Benitec will be a very different company from what it is today," he said.
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