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EPO Rejects Benitec Patent Application; Company Considers Abandoning Filing

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The European Patent Office last month rejected a Benitec patent application covering its core RNAi technology, RNAi News has learned, delivering the latest blow to the Australian company's intellectual property estate since it initiated a campaign of patent infringement litigation early last year.

The rejection also marks the latest development in ongoing legal maneuverings between Benitec and RNAi rival Nucleonics.

"We are pleased that the European Patent Office has reaffirmed what Nucleonics has believed all along, that this patent application is not allowable for a variety of reasons including: lack of novelty, citing prior art submitted by Nucleonics; lack of inventiveness; and failure to reduce to practice the claimed invention," Nucleonics CEO Robert Towarnicki told RNAi News in an e-mail in response to the EPO ruling.

Sally Brashears, vice president of intellectual property at Benitec, told RNAi News this week that while the company will likely appeal the ruling, it is also considering abandoning the patent application in order to focus on another one currently under EPO review.


The EPO said Benitec's patent application lacked an inventive step and failed to sufficiently disclose the invention clearly and completely. The office also objected to a "lack of novelty [that] was raised in view of one of the documents submitted with the [third] party observations."

The rejected patent application, No. 1071762, is entitled "Control of Gene Expression." As originally filed with the EPO in early 1999, the application essentially claims a method of repressing, delaying, or reducing the expression of a target gene in an animal cell, tissue, or organ by introducing nucleic acid molecules "comprising tandem copies of a nucleotide sequence which is substantially identical to the nucleotide sequence of … [the] target gene or a region thereof."

As it made its way through the EPO, the IP ran aground in January 2004 when the patent office rejected the application's claims because "they [extended] the claimed subject matter beyond the content of the application as originally filed." The EPO also noted that amendments Benitec made previously to its patent application in order to resolve earlier deficiencies appeared to "have been carried out in a haphazard way without any regard to the context of the passages that allegedly serve as basis for said amendments."

According to documents on file with the EPO, Benitec then submitted an amended set of claims, but these too extended beyond the content of the application. After a meeting in September 2004 with EPO officials to discuss how to resolve the problems, the company submitted newly amended claims for the patent application, as well as a declaration comprising technical data from Mick Graham, Benitec's principal research scientist and one of the inventors listed on the patent application.

While the EPO was reviewing Benitec's latest claims early this year, rival Nucleonics submitted to the EPO a number of examples of prior art that it said demonstrated why Benitec's application should not be awarded. Nucleonics made the move as part of its effort to fight off patent-infringement litigation initiated by Benitec's former Chairman and CEO John McKinley (see RNAi News, 4/2/2004).

Excepts from the Convention on the
Grant of European Patents
Article 54
Novelty: An invention shall be considered to be new if it does not form part of the state of the art. The state of the art shall be held to comprise everything made available to the public by means of a written or oral description, by use, or in any other way, before the date of the filing of the European patent application. Additionally, the content of the European patent application as filed, of which the dates of filing are prior to the date of [the patent application itself] and which were published … on or after that date, shall be considered as comprised in the state of the art.
Article 56
Inventive step: An invention shall be considered as having an inventive step if, having regard to the state of the art, it is not obvious to a person skilled in the art.
Article 83
Disclosure of the invention: The European patent application must disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.
SOURCE European Patent Office

Aside from filing counterclaims in the patent suit, Nucleonics also asked US, Australian, and Polish patent officials to re-examine Benitec's ddRNAi patent and patent applications (see RNAi News, 9/10/2004, 10/8/2004, and 3/11/2005). In January this year Nucleonics also submitted to the EPO so-called third party observations on Benitec's patent application (see RNAi News, 1/14/2005).

While the EPO's track record with Benitec's patent application would seem to indicate that a refusal of the IP was already a real possibility, Nucleonics' input didn't help the situation. As the patent office stated in a recent filing, while its examining division determined on its own that Benitec's patent application lacked an inventive step and failed to sufficiently disclose the invention clearly and completely, "an objection on lack of novelty was raised in view of one of the documents submitted with the [third] party observations."

Despite making numerous adjustments to its patent application, and despite trying to prop up the IP with additional declaration by Graham and Stanford University researcher Mark Kay, who founded the RNAi drug firm and eventual Benitec acquisition Avocel (see RNAi News, 5/21/2004), the EPO in June rejected Benitec's patent application, primarily for failing to comply with articles 54, 56, and 83 of the EPO's convention on the grant of European patents (see sidebar).

While the EPO noted that its decision is open to appeal, Brashears said that "possibly what we'll do is abandon [the application] in favor of another pending case. You get so many bites at the apple, and if you start out slowly like we did [with the rejected patent application], your goodwill points with the examiner go away.

"And that's where we are with the examiner," she added. If Benitec focuses all its attention on its other application that's under review, and takes into account the reasons its other application was refused, the company expects to make more headway in getting a patent.

— Doug Macron ([email protected])

 

Reasons for the Decision
In a July filing, the EPO provided a number of reasons why it refused to award Benitec a patent. A selection of key reasons are listed below:
The EPO found that "the application as originally filed discloses a number of plasmid constructs" designed to trigger gene-silencing. While the application includes "two methods whereby introduction of such constructs into mammalian cells would presumably reduce gene expression of the target sequence … no evidence was presented in the application as filed of any effect of the disclosed constructs on gene expression in animal cells."
The EPO also notes that the subject matter of one of Benitec's key claims is "not distinguishable" from certain disclosures in a US patent, No. 5,272,065, awarded in December 1993. That patent's abstract notes that "gene expression in a cell can be regulated or inhibited by incorporating into or associating with the genetic material of the cell a non-native nucleic acid sequence which is transcribed to produce an mRNA which is complementary to and capable of binding to the mRNA produced by the genetic material of said cell."
The EPO stated that since the constructs detailed in Benitec's patent application "comprise coding sequences of variable length and varied identity to the target sequence in combination with the sketchy outline of two methods whereby such constructs are introduced into mammalian cells, and the lack of any evidence in the application as filed that the use of any of the disclosed constructs leads to reduction of gene expression, the sum of the information disclosed in the application indicates the application discloses an unfinished invention. As such, it appears that the skilled person is expected to carry out unlimited experimentation until he arrives at the desired effect without having any assertion that said technical effect may be achieved at all.
"Furthermore … the effectiveness of each of the suggested constructs in achieving reduction of gene expression is under serious doubt substantiated by the teachings of the state of the art." The EPO noted that at the time the application was filed, "it was known that only a limited number of specific nucleic acids are suitable [to achieve gene expression reduction] … [and] that introduction of double-stranded RNA in mammalian cells cause apoptosis rather than targeted gene repression. Thus, the skilled person reading the application … not only has no assertion of success, but on the contrary knows that constructs generation double-stranded RNA may induce apoptosis. Thus, he is led to think that only limited, special type of constructs or conditions should apply for gene expression to be reduced by double-stranded RNA. These special constructs or conditions are not revealed in the application. … In view of the unconventional nature of the method of the application, more than a vague technical disclosure is necessary in the application as originally filed in order for the requirement of sufficiency of disclosure to be satisfied."
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