RNAi – patentable subject matter after all

RNAi – patentable subject matter after all

RNAi – patentable subject matter after all

In a decision handed down on 13 October 2016 involving an application in the name of Arrowhead Research Corporation (Arrowhead) the Australian Patent Office has determined that claims directed to dsRNA molecules which trigger RNA interference do constitute patent eligible subject matter following the High Court decision in D’Arcy v Myriad Genetics Inc. (Myriad).

The patent application in question included claims directed to dsRNA molecules that silence expression of SYK. The Examiner objected to these claims on the basis that the dsRNA molecules were not patent eligible subject matter in view of the decision in Myriad. Specifically, the Examiner alleged that the claimed dsRNA molecules only function to attenuate SYK expression due to the sequence encoded by the sense and antisense strands. Furthermore, given that the specific sequences recited by the claims were identical to sequences that occur in nature, the substance of the claims was genetic information that has not been ‘made’. 

Background to RNAi 

In a simplified model, the RNAi pathway comprises a two-step process, mediated by specialised ribonucleases. In the first step, dsRNA is processed into siRNA by the RNaseIII enzyme, Dicer. In the second step, siRNAs are loaded into the effector complex RNA-induced silencing complex (RISC). The siRNA is then unwound in a strand specific manner by the activated RISC. Thereafter, the exposed sequence of the antisense strand binds to the mRNA target by complementary base pairing and gene silencing is effected by nucleolytic degradation of the target mRNA. 

Importantly, it is the physical, double-stranded nature of the claimed dsRNA molecules that initiates the RNAi pathway. The initiation of the RNAi pathway is completely independent from the genetic information of the two strands that comprise the dsRNA. 

IP Australia’s Examination Practice post-Myriad

Following the High Court’s decision in D’Arcy v Myriad Genetics Inc. (Myriad), IP Australia has determined the patentability of claims comprising nucleic acids or genetic information by applying the following key principles:

  1. What is the substance of the claim (not merely its form)?
  2. Has the substance of the claim been ‘made’ or changed by man, or is it ‘artificial’?

Applying these principles, IP Australia had objected to claims directed to dsRNA on the basis that the substance of any such claims is the genetic information of the nucleotide sequences of the dsRNA. In particular, it was the Office’s view that the sequence alone gave the molecule its function, as it is the antisense strand which interacts with the mRNA to bring about the silencing of gene expression. This interpretation, however, ignored the importance of the structure of the dsRNA in triggering the RNAi pathway, which is distinct from the genetic information (if any) contained within the dsRNA. 

Furthermore, the substance of the claim was not considered to be ‘made’ as the genetic information was the same as a sequence that occurred in the genome. Therefore, given that one strand of the dsRNA corresponded to a sequence that occurred in the genome, the synthetic nature of the molecule was not sufficient to confer patentability.

Arrowhead Hearing

In light of continued rejection based on this Patent Office practice Arrowhead requested a hearing to resolve the outstanding objections.  At the Hearing it was submitted that the substance of the claims in issue was not genetic information, but rather economically significant products and compositions with the capacity to attenuate the expression of SYK.

Substance of claim to be determined in view of how the invention works

In considering Arrowhead’s submission, the Delegate recognised that although the subject matter of the claim may be determined by analysing the words of the claim, the substance of the claim is to be determined in view of how the invention actually works. To this end, Arrowhead submitted that the Examiner’s view that the function of the invention was only associated with the sequence of nucleotides of the dsRNA was incorrect. Arrowhead further submitted that the chemical and structural characteristics of dsRNA molecules in the RNAi pathway were at least equally significant in the working of the invention as the nucleotide sequence. 

Substance of the invention was merely genetic information

The Delegate agreed with Arrowhead and held that the “informational, structural and chemical content of the dsRNA molecules may all be considered essential elements of the invention as claimed, and as a result the substance of the invention encompasses each of these elements, not merely the genetic information conveyed by the molecule.” Therefore, the Delegate considered that the substance of the invention as defined by the claims was directed to a pharmaceutical composition, not the genetic information contained within the composition. The Delegate also agreed with Arrowhead that the claimed compositions were economically significant products that meet the requirements for manner of manufacture consistent with the High Court’s decision in Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd [2013] HCA 50. 

Learnings for patent protection for inventions which include genetic information 

The approach applied by the Delegate in Arrowhead will be welcomed by industry as it provides more certainty around patent protection for inventions that incorporate or use RNAi and other nucleic acids which have a function dictated by structure.