Arrowhead Research Corporation
[2016] APO 70
•13 October 2016
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Arrowhead Research Corporation [2016] APO 70
Patent Application: 2013207601
Title:RNAi-mediated inhibition of spleen tyrosine kinase-related inflammatory conditions
Patent Applicant: Arrowhead Research Corporation
Delegate: S. Calanni
Decision Date: 13 October 2016
Hearing Date: 14 July 2016 in Canberra
Catchwords: PATENTS – examiner objection – manner of manufacture – determination of the substance of the invention – substance of the invention is a pharmaceutical composition – claims are directed to a manner of manufacture
Representation: Patent attorney for the applicant: Grant Shoebridge of Shelston IP
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2013207601
Title:RNAi-mediated inhibition of spleen tyrosine kinase-related inflammatory conditions
Patent Applicant: Arrowhead Research Corporation
Date of Decision: 13 October 2016
DECISION
Claims 6, 7, and 9-13 are directed to a manner of manufacture.
Pursuant to regulation 13.4(1)(g), the application will not lapse for failure to gain acceptance until 3 months from the date of this decision. The only impediment to the application being accepted is the postponement of acceptance that is currently in place.
REASONS FOR DECISION
Patent application 2013207601 was filed by Arrowhead Research Corporation (Arrowhead) on 17 July 2013. The application is a divisional application of 2007238027.
Arrowhead requested examination of the application on 21 May 2014.
The Commissioner issued a first examination report on the application on 6 October 2015. Arrowhead provided amendments addressing the matter raised in the first examination report, however the examiner issued a second report with an additional objection relating to the requirement of manner of manufacture with respect to a subset of the claims directed to interfering RNAs that target Syk mRNA and thereby interfere with Syk mRNA expression. Specifically, in view of the High Court decision in D'Arcy v Myriad Genetics Inc (Myriad) [2015] HCA 35, it was held that those claims were not for a manner of manufacture.
A third and fourth report maintained the same objection, at which point the Applicant requested to be heard on the matter. Written submissions were filed on 6 June 2016 and a hearing was held on 14 July 2016.
The Application
The application is entitled "RNAi-mediated inhibition of spleen tyrosine kinase-related inflammatory conditions". The invention is described as follows [0002]:
"The present invention relates to the field of interfering RNA compositions for silencing spleen tyrosine kinase (Syk) and for treatment of a Syk-related inflammatory condition. Such conditions include allergic conjunctivitis, ocular inflammation, dermatitis, rhinitis, asthma, allergy, or mast-cell disease, for example."
In describing the problem to be solved, the application at [0005] –[0007] states that:
"Additional agents and treatment methods would be desirable for targeting the Syk tyrosine kinase, thereby blocking the action of endogenous mast cell degranulation, and release of histamine and other pro-inflammatory mediators while avoiding the side effect of systemic antihistamine treatment. Embodiments of the present invention address the need in the art for such agents and treatment methods.
Embodiments of the present invention overcome these and other drawbacks of the prior art by providing highly potent and efficacious treatment, prevention or intervention of a Syk-related inflammatory condition. In one aspect, methods of the invention include treating a subject having a Syk-related inflammatory condition or at risk of developing a Syk-related inflammatory condition by administering interfering RNAs that silence expression of Syk mRNA, thus interfering with PLCg and PI3K signalling pathways and preventing a cascade of events related to mast cell degranulation, and release of histamine and other pro-inflammatory mediators in a Syk-related inflammatory condition.
The present invention is directed to interfering RNAs that target Syk mRNA and thereby interfere with Syk mRNA expression. The interfering RNAs of the invention are useful for treating patients with a Syk-related condition or at risk of developing a Syk-related condition."
The specification describes a number of compositions comprising different interfering RNA (iRNA) molecules. These iRNA are defined in claims 6-13. Claims 6 and 11 are the independent claims that are in dispute in the present matter. Claim 6 is reproduced below:
"6. A composition comprising an interfering RNA, the interfering RNA comprising:
a sense nucleotide strand and an antisense nucleotide strand, wherein:
a) the sense nucleotide strand and the antisense nucleotide strand are each 19-49 nucleotides in length;
b) 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
c) 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 in part c) only which instead defines an antisense strand which has a region of perfect contiguous complementarity to the target sequences represented by SEQ ID NO: 21-22, 25, 29, 35-39, or 42.
The objection
As noted earlier, the only remaining objection is that a subset of the claims directed to compositions comprising an iRNA are not for a manner of manufacture. Specifically, the examiner maintained that the compositions defined by claims 6, 7 and 9-13 do not satisfy the requirement of a manner of manufacture because, according to the principles set forth in Myriad, 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. As argued in the fourth examination report,
"It is considered that the iRNA of the claims embodies or conveys genetic information that is important to the utility of the claimed invention. The way the invention works is solely dependent on the sequence of nucleotides in the iRNA. Attenuation of Syk expression by RNA interference is only possible because the sequence of nucleotides is the same to that which occurs in the genome. In other words, the claimed iRNA would not function to attenuate Syk expression if not for the sequence contain therein. The specific sequences recited in the claims reproduces an identical sequence of nucleotides which occurs in nature. As such, the utility lies in the sequence itself, and the substance of the product is information.
..."In essence, the sequences of the iRNA recited in the claims are based on the sequence of the Syk gene, as such the genetic information embodied in the iRNA does exist in nature. If the specific sequence of nucleotides that make up the iRNA did not exist in nature, then no RNA interference would occur. The mere act of synthesis of the iRNA is not sufficient to confer patentability, as the genetic information conveyed by the nucleic acid molecule of the claims has not been changed from that which occurs in nature. As set forth at [6] of Myriad, the information has not been made by human action, but merely discerned."
The law
10. Section 18(1)(a) of the Act requires that the invention, so far as claimed in any claim, must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies. In Myriad at[18] the High Court confirmed that the question posed by the application of s 18(1)(a) may be framed as in National Research Development Corporation (NRDC)[1959] HCA 67 at [14] and [25]; [1959] HCA 67; 102 CLR 252 at 269:
“Is this a proper subject of letters patent according to the principles which have been developed for the application of s 6 of the Statute of Monopolies?”
11. In considering this question, the decision in Research Affiliates LLC v Commissioner of Patents[2014] FCAFC 150 at [106], the Full Federal Court stated that:
“The determination whether the claimed invention is truly “an artificially created state of affairs” in satisfaction of NRDC is made not by some mechanistic application of the criterion of artificiality or physical effect, but by an understanding of the claimed invention itself. The invention is to be understood as a matter of substance and not merely as a matter of form.”
12. The need to consider the substance of the claimed invention was reiterated by the High Court in Myriad where it was observed at [94]:
“Although it may be said in a formal sense that the invention as claimed, referring to isolated nucleic acids, embodies a product created by human action, that is not sufficient to support its characterization as a manner of manufacture. The substance of the invention as claimed and the considerations flowing from its substance militate against that characterization.”
13. Thus it is clear that any consideration of manner of manufacture must look beyond the form of words used in the claim to determine the substance of the claimed invention in the context of the specification as a whole.
14. In Myriad the majority found at [6] and [89-92] that although the claims were formulated as a class of products, the substance of the claims was information embodied in the nucleic acid sequence. The High Court found that the genetic information is discerned, not made by human action, and as a consequence, the claims did not define a manner of manufacture (at [6], [91]).
The applicant's submissions
15. Arrowhead provided written submissions for the hearing presenting various lines of argument, including that:
a.the iRNA compositions do not exist in nature (section 9 of the written submissions),
b.the information conveyed by the iRNA does not exist in nature (section 12 of the written submissions),
c.the mere recitation of a nucleic acid sequence cannot be considered genetic information (section 10 of the written submissions), and
d.the substance of the claim is not genetic information (section 11 of the written
submissions).
16. In addition to the written submissions a declaration by Professor Thomas Preiss (Preiss declaration), dated 5 June 2016, was submitted describing the structural differences between DNA and RNA and the mechanism of RNA interference (RNAi; Appendix C).
17. I note that the submissions are in general focused on the consideration of the substance of the claimed invention (c. and d. above) and whether the claimed matter can be considered made (a. and b. above).
18. First, I will consider and address the applicant's specific submissions relevant to my consideration of the substance of the invention.
What is the substance of the claimed invention?
19. The examiner identified the substance of the invention as genetic information.
"In the present application, it is considered that the iRNA of the claims embodies or conveys genetic information that is important to the utility of the claimed invention. The way the invention works is solely dependent on the sequence of nucleotides in the iRNA. Attenuation of Syk expression by RNA interference is only possible because the sequence of nucleotides is the same to that which occurs in the genome. In other words, the claimed iRNA would not function to attenuate Syk expression if not for the sequence contained therein. The specific sequences recited in the claims reproduces an identical sequence of nucleotides which occurs in nature. As such, the utility lies in the sequence itself, and the substance of the product is information."(Examination Report No. 4 dated 16 April 2016).
20. Arrowhead submitted that the substance of the invention was not genetic information but rather economically significant products and compositions with the capacity to attenuate the expression of Syk (see for example Section 11 of the written submissions).
21. There is no question that the subject matter (or form of words) of the present claims is a composition that comprises double stranded RNA (dsRNA). The composition comprises a sense strand (passenger strand) and an antisense strand (guide strand), which are characterised by the features set out in parts (a)-(c) of the claim.
22. However, analysis of the subject matter of the claim merely represents the determination of the form of the words of the claim, not its substance. To determine the substance of the invention, consideration should also be given to the description and how the invention works (Manual of Practice and Procedure (MPP) at 2.9.2.6).
23. Turning to the description, it is apparent that the inventive contribution provided by the claimed invention resides in the identification of specific target sequences. At [0052]-[0053] the specification describes the selection of target sequences using available design tools and techniques. [0078]-[0080] similarly describe the production of iRNA using well established techniques of the art. As such, there is no suggestion that the inventive contribution resides in the tools or techniques used. Rather, the strong emphasis placed on the specific target sequences identified (see for example Tables 1 and 2, [0054]-[0058]) suggests that the inventive contribution resides in the sequences themselves. Clearly, 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.
24. In considering how the invention works, the applicant submitted that the examiner's view that the manner in which the invention works is solely dependent on the sequence of nucleotides in the iRNA is not correct. Importantly, the structural properties of RNA and the mechanism and requirements for RNAi are also of significance to the working of the invention.
25. Specifically, the chemical and structural characteristics imparted by RNA, as set out in paragraphs [14]-[16] of the Preiss declaration are important to the functionality of the molecules. The fact that RNA is typically single-stranded allows it to fold into complex 3-dimensional shapes and makes it much more flexible in function (Preiss declaration at 15). As a consequence, RNA is more versatile than DNA, capable of performing numerous diverse tasks in an organism. For example, RNA can function as a carrier of genetic information, but it can also act as a catalyst of biochemical reactions, an adapter molecule in protein synthesis, and a structural molecule in cellular organelles.
26. As described in [37] of the specification, RNAi is the process by which dsRNA silences gene expression. Gene silencing is effected by a three-step process that involves:
(1)degradation of dsRNA into small interfering RNAs (siRNAs), 21 to 25 nucleotides long, by the RNase III-like activity of the Dicer enzyme;
(2)incorporation of one strand of the siRNA (the guide strand) into a ribonucleoprotein complex known as the RNase RNA-induced silencing complex (RISC) and the degradation of the second (passenger strand); and
(3)targeting and cleavage of the target mRNA following identification of mRNA molecules at least partially complementary to incorporated siRNA strand.
27. While siRNA ultimately functions as single strands (see for example [83] of the specification), the first two critical steps in RNAi are RNA sequence-independent (12.4 of the written submissions, [20] Preiss declaration). This suggests that while the arrangement of nucleotides, or genetic information, conveyed by the siRNA incorporated in the RISC complex is an important element of the claimed invention, the manner in which the invention works in not solely dependent on the sequence of nucleotides in the iRNA.
28. When considering the invention as a whole, the dsRNA architecture of the claimed compositions is at least equally significant to the working of the invention, with the chemical and structural elements of the dsRNA being crucial for the recognition and digestion of the molecule by Dicer ([22] Preiss declaration). As a consequence, 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.
29. Thus, based on a consideration of how the invention works the substance of the claimed invention is more than genetic information alone. It is the interfering RNA molecules that target Syk mRNA and thereby interfere with Syk mRNA expression. These molecules are more than a "step along the way to an artificially created state of affairs of economic significance" as described in Myriad at [85]: they are the invention described in the application. Thus, from this perspective it is reasonable to view the substance of the invention defined by claims 6-13 as a product, namely a pharmaceutical composition comprising interfering RNA.
30. Having considered the inventive contribution of the claimed invention and the manner in which the invention works I have determined that the substance of the invention can be considered to be either genetic information or a pharmaceutical composition. On balance, I find the factors supporting the proposition that the substance of the invention is a pharmaceutical composition more persuasive. Accordingly, I consider the substance of the invention to be pharmaceutical composition not the genetic information that is contained in the composition.
31. Having determined that the substance of the invention defined in claims 6-13 is appropriately drawn to a pharmaceutical composition, I agree with Arrowhead's submission that consistent with the High Court decision in Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd [2013] HCA 50 at [143] the claimed iRNA compositions are economically significant products that meet the requirements of manner of manufacture.
Conclusion
32. I conclude that the objection of manner of manufacture in relation to the present application has been overcome. Pursuant to regulation 13.4(1)(g), the application will not lapse for failure to gain acceptance until 3 months from the date of this decision. I note that the only impediment to the application being accepted is the postponement of acceptance that is currently in place.
Sophina Calanni
Delegate of the Commissioner of Patents
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