Interfering RNA (iRNA) is no interference to manner of manufacture in Australia

Take home message

• In a recent decision the Australian Patent Office (APO) determined that claims directed to a composition comprising double-stranded RNA (dsRNA; so-called “interfering RNA” or “iRNA”) is a manner of manufacture (patent eligible subject matter) in accordance with Section 18(1)(a) of the Patents Act.
• Informational, structural and chemical content of the dsRNA are essential elements to determining patent subject matter eligibility.
• The Myriad decision should be given narrow jurisdiction and should not extend to certain DNA and RNA species.
• This is welcome news as the APO practice to date has been to reject such claims in light of the High Court decision issued last year in D'Arcy v Myriad Genetics Inc (Myriad) [2015] HCA 35.

Background

Following the Australian High Court decision in Myriad, isolated nucleic acid was found not to constitute patent eligible subject matter. The High Court reasoned that although the substance of the claims were formulated as a product, the invention was the “information” embodied in the sequence of nucleotides in the claimed molecule and that the information was an inherent part thereof. The reasoning was thus akin to the USPTO approach of looking at the substance of the claim rather than merely its form. Further, as the invention was not “made” (or involved some manipulation) by human action, it did not define patent eligible subject matter according to the Patents Act. The High Court decision effectively turned established principles of patent eligible subject matter (see the 1959 decision of NRDC¹) concerning DNA/RNA on its head.

The APO subsequently issued guidelines which, in short, stated that in light of the Myriad decision all forms of naturally occurring nucleic acid molecules, such as DNA or RNA, whether human or non-human and whether coding or non-coding are not patent eligible subject matter because they are not considered to have been “made”.

In practise, these guidelines have been rigorously applied by the APO during examination to reject claims to cDNA, synthetic nucleic acids, probes and primers, and isolated interfering/inhibitory nucleic acids where they replicate the genetic information of a naturally occurring organism. Additionally, the guidelines have been applied to reject claims to DNA/RNAs comprising a backbone modification and modified bases such as locked nucleic acids.

Pharmaceutical compositions comprising the above species, without something more beyond a reference to pharmaceutically acceptable excipient have also been rejected by the APO.

The decision

The decision made on 13 October 2016 concerned Australian patent application no. 2013207601 entitled “RNAi-mediated inhibition of spleen tyrosine kinase-related inflammatory conditions” [2016] APO 70. The claims were directed to interfering RNAs (iRNAs) that target spleen tyrosine kinase (Syk) mRNA and interfere with its expression. The iRNAs are useful for treating patients with, or at risk of developing a Syk-related condition.

The method of treatment claims were not at issue and the hearing was confined to the iRNA defined in claims 6-13 of which claims 6 and 11 were independent claims.

Claim 6 is reproduced below:

A composition comprising an interfering RNA, the interfering RNA comprising: a sense nucleotide strand and an antisense nucleotide strand, wherein:

1. the sense nucleotide strand and the antisense nucleotide strand are each 19-49 nucleotides in length;
2. the sense nucleotide strand and the antisense nucleotide strand have a region of at least near perfect contiguous complementarity of at least 19 nucleotides; and
3. the antisense nucleotide strand has a region of at least near-perfect contiguous complementarity to SEQ ID NO: 21-22, 25, 29, 35-39, or 42.

Claim 11 differs from claim 6 only in part in which the words “at least near-perfect complementarity” are replaced with “perfect contiguous complementarity”.

The composition claims comprising iRNA were rejected by the APO for failing to constitute patent eligible subject matter on the basis that “the substance of the claimed compositions is the genetic information contained therein, and said genetic information is not considered made since the information embodied in the iRNA is the same as a sequence of nucleotides from the target sequence which is part of the genome of the organism”.

During the hearing, the Applicant (Arrowhead Research Corporation), argued that neither the iRNA compositions, nor the information conveyed exist in nature and that the mere recitation of a nucleic acid sequence cannot be considered genetic information. Further, that the substance of the claim is not genetic information. Rather, the invention related to economically significant products and compositions with the capacity to attenuate the expression of Syk.

The submissions were accompanied by an expert declaration describing the structural differences between DNA and RNA and the mechanism of RNA interference.

The findings of the Hearing Officer

In arriving at the decision, the Hearing Officer stated that in order to determine the substance of the invention, consideration should also be given to the specification description and how the invention works.

The Hearing Office observed that there was no suggestion that the inventive contribution resides in the tools or techniques used for the selection of target sequences, rather the emphasised placed on the specific target sequences identified suggests that the inventive contribution resides in the sequences themselves. The information embodied in the arrangement of nucleotides within the target sequences is crucial to the invention and can be considered to support the Examiner’s opinion that the substance of the invention is genetic information.

However, turning to how the invention works, the Hearing Officer was persuaded by expert evidence showing that the structural properties of RNA and the mechanism and requirements for RNA interference are also significant to the working of the invention. In particular, the structural and chemical elements of the dsRNA being crucial for recognition and digestion of the molecule by Dicer into small interfering RNAs (siRNAs) which mediate silencing of gene expression.

Thus based on how the invention works, the Hearing Officer determined that the invention related to a pharmaceutical composition that had been “made” rather than the genetic information that is contained in the composition.

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¹National Research and Development Corp v Commissioner of Patents (1959) 102 CLR 252.