Seqirus, Inc. v Translate Bio, Inc - [2025] APO 5

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Seqirus, Inc. v Translate Bio, Inc. [2025] APO 5
Patent Application: 2020202755

Title:Delivery of mRNA for the augmentation of proteins and enzymes in human genetic diseases

Patent Applicant: Translate Bio, Inc.

Opponent:Seqirus, Inc.

Delegate:M. Umehara

Decision Date: 18 February 2025

Hearing Date: 25 November 2024, by video conference

Catchwords: PATENTS – opposition to the grant of a patent under s59 – grounds of novelty, inventive step, clear enough and complete enough disclosure, support and utility – reg 5.23 request refused – lack of novelty and inventive step not established – lack of clear enough and complete enough disclosure and support – claims do not lack utility – costs awarded against applicant.

Representation: Counsel for the applicant: Patrick Flynn
Patent attorney for the applicant: Douglas Horton of Spruson & Ferguson and Andrew Rankine of Spruson & Ferguson Lawyers
Patent attorney for the opponent: Declan McKeveney and Patrick McManamny of FB Rice

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE

Patent Application: 2020202755

Title:Delivery of mRNA for the augmentation of proteins and enzymes in human genetic diseases

Patent Applicant: Translate Bio, Inc.
Date of Decision: 18 February 2025
DECISION

The opposed application lacks clear enough and complete enough disclosure as well as support for all claims.
Translate Bio, Inc. is allowed a period of two months from the date of this decision to propose amendments to overcome this deficiency.
I award costs according to Schedule 8 against Translate Bio, Inc.
REASONS FOR DECISION

Background

Australian patent application 2020202755 (the opposed application) was filed by Shire Human Genetic Therapies (Shire) on 24 April 2020. It is a divisional of 2018203895 (the parent application), which in turn is a divisional of 2016250459, itself a divisional of 2014250713 and the original application is 2010326132, filed on 30 November 2010, claiming priority from US 61/265653 (the priority document) filed on 1 December 2009. The priority claim was challenged and will be discussed below. While nothing turns on this point, all earlier applications have been granted without opposition and 2023201438 has been filed as a further divisional application from the opposed application.
The opposed application was accepted on 21 November 2022 with the notice of acceptance advertised on 8 December 2022. Shire proposed post-acceptance amendments to the specification on 23 December 2022 to correct typographical errors. The amendment was advertised on 19 January 2023 and formally allowed on 27 March 2023.
A notice of opposition to the grant of the opposed application under section 59 of the Patents Act 1990 (the Act) was filed by Kings Patent & Trade Marks Attorneys Pty Ltd on 8 March 2023. The opponent was amended to JLTF Holdings Pty Ltd (JLTF Holdings) on 6 June 2023. A statement of grounds and particulars was filed by JLTF Holdings on 8 June 2023, identifying the following grounds of opposition: entitlement, manner of manufacture, novelty, inventive step, utility, clear enough and complete enough disclosure, best method, support and clarity. JLTF Holdings then filed the evidence in support (EIS) on 7 September 2023. The EIS consisted of a declaration dated 5 September 2023 by Leaf Huang (Huang #1) with supporting exhibits LH-1 to LH-28 and a declaration dated 6 September 2023 by Timothy Fitzgerald (Fitzgerald) with supporting exhibits TF-1, TF-1A, TF-1B, TF-1C, TF-1D, TF-1E, TF-2, TF-2A, TF-3, TF-3A, TF-4, TF-4A, TF-5, TF-5A, TF-6, TF-6A, TF-7 and TF-7A.
On 3 November 2023, an amendment to the patent request was filed, proposing the change of applicant to Translate Bio, Inc (the applicant), and further amendments to the specification were also proposed. The amendment to the patent request was advertised on 25 January 2024 and formally allowed on 2 May 2024. The amendment to the specification was advertised on 22 February 2024 and formally allowed on 6 May 2024. Further references to the specification in this decision relate to the specification as amended.
During this time, the applicant also filed the evidence in answer (EIA) on 7 December 2023. The EIA consisted of a declaration dated 7 December 2023 by Colin William Pouton (Pouton) with supporting exhibits CWP-1 to CWP-32 and a declaration dated 6 December 2023 by Douglas Alexander Horton (Horton) with supporting exhibits DAH-1 to DAH-33.
JLTF Holdings filed the evidence in reply (EIR) on 7 February 2024. The EIR consisted of another declaration by Leaf Huang (Huang #2) dated 2 February 2024 with further supporting exhibits LH-29 to LH-33. Subsequently, the opponent was amended to Seqirus, Inc. (the opponent) on 25 October 2024.
Request for information to be considered under regulation 5.23
A request under reg 5.23 was made by JLTF Holdings on 26 August 2024 to introduce a further document as evidence relevant to at least the grounds of utility, sufficiency and support. A delegate of the Commissioner issued correspondence on 17 September 2024 advising the parties that consideration of the reg 5.23 material should be made at the substantive hearing and to include relevant comments in their submissions.
Reg 5.23 states:
(1) For the purpose of deciding an opposition, the Commissioner may consult a document that:
·     (a) is relevant to the opposition; and
·     (b) has not been filed under this Chapter; and
·     (c) is available in the Patent Office.
(2) If the Commission proposes to rely on the document, the Commissioner must give the parties:
·     (a) notice of the Commissioner’s intention to do so; and
·     (b) a copy of, or access to, the document; and
·     (c) an opportunity to give evidence or make representations about the document.
The material sought to be added was a journal article published in 2019 authored by Hassett K.J. et al. and entitled “Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines” (Hassett).
During the hearing, I queried the opponent as to the probative value of Hassett, particularly as their submissions already referred to alternative documents in relation to the grounds of utility, sufficiency and support. The opponent submitted that the reasons for introducing Hassett under reg 5.23 was to provide an alternative angle, in case the evidence already present was insufficient to make out the grounds. The only reason given for the document not being raised earlier was that they had only recently become aware of it.
The applicant submitted that Hassett was merely repetitive of other material already in evidence and that it could not be said to be crucial to the outcome of the present matter. The applicant noted that Hassett does not provide the nature of the PEG-modified lipid component of the formulations for the lipid nanoparticles and whether they fell within the scope of the claims or not could not be determined. Furthermore, the applicant submitted that they would suffer additional costs of gathering evidence and there would necessarily be delays to the resolution of the present matter, which would go towards considerations of public interest.
I have reviewed the document and am of the opinion that it would not change the outcome of the opposition in any meaningful way. As noted by the applicant, Hassett repeats similar content covered by other documents already in evidence and the PEG-modified lipid component of the lipid nanoparticle formulations cannot be ascertained from reading this document alone. While the opponent sought to provide this information in their written submissions[1], this only highlights the fact that Hassett itself does not contain relevant information. Consequently, I do not see that it is crucial to the outcome of the present proceeding nor that it is necessary for me to consult the material for the purposes of deciding this matter. I refuse the opponent’s request to consult Hassett under reg 5.23.
[1] Opponent submissions in [222] and Annex 3.
Onus and standard of proof
The opposed application was filed after 15 April 2013 and is therefore governed by the Act and Patents Regulations 1991 as amended by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012. Thus, the standard of proof that applies in the present case is the balance of probabilities.
The onus rests with the opponent to satisfy me, on a balance of probabilities, that a ground of opposition to the grant exists. Under subsection 60(3A), if I am satisfied, on the balance of probabilities, that a ground of opposition to the grant of a patent exists, I may refuse the application. I note, however, that, under subsection 60(3B), I must not refuse an application without, where appropriate, giving the applicant a reasonable opportunity to amend the relevant specification to remove any grounds of opposition.
The specification
The specification includes a description, including a sequence listing, followed by 19 claims and 6 drawings. Before construing the specification, I note the comments of Middleton J in Eli Lilly and Company Limited v Apotex Pty Ltd:
“It is well settled that the Court should, from the outset, approach the task of patent construction with a generous measure of common sense. The Court must place itself in the position of a person skilled in the relevant art, being the subject matter of the patent. From this perspective, the patent is to be read as a whole, in the context of the specification and in light of the prevailing common general knowledge and state of the relevant art at the priority date.”[2]
The description
[2] Eli Lilly and Company Limited v Apotex Pty Ltd [2013] FCA 214 at [139].
The field of the invention relates to methods of intracellular delivery of nucleic acids that are capable of correcting genetic defects and/or providing beneficial functions to target cells by transfecting them or having the gene product of interest translated in the target cells.[3] Such strategies are useful in the management and treatment of a large number of diseases which result from protein and/or enzyme deficiencies.[4]
[3] Specification at page 2 lines 25-31.
[4] Specification at page 3 lines 1-3.
The Summary of the Invention section then sets out a number of embodiments and various aspects of the invention. Broadly, the invention is described as “a nucleic acid, a transfer vehicle and an agent to facilitate contact with, and subsequent transfection of a cell.”[5]
[5] Specification at page 3 lines 13-15.
The term ‘nucleic acid’ in the specification refers to genetic material, including both DNA and RNA.[6] Contemplated forms of RNA include mRNA, siRNA, miRNA, snRNA, snoRNA and lincRNA.[7] Furthermore, the nucleic acids should be capable of facilitating the expression of a functional enzyme or protein for the treatment of various genetic or metabolic disorders which involve the non-expression, mis-expression or deficiency of a protein or enzyme.[8] The nucleic acids are introduced into cells or tissues of interest and are capable of being expressed, translated or “otherwise capable of conferring a beneficial property to the target cells or tissues.”[9] For example, the nucleic acid may encode a hormone, enzyme, receptor, peptide or protein of interest, or siRNA.[10]
[6] Specification at page 8 lines 30-31.
[7] Specification at page 8 line 31 – page 9 line 7.
[8] Specification at page 9 lines 6-17.
[9] Specification at page 9 lines 26-30.
[10] Specification at page 9 line 31 – page 10 line 3.
The term ‘transfer vehicle’ is defined as “includ[ing] any of the standard pharmaceutical carriers, diluents, excipients and the like which are generally intended for use in connection with the administration of biologically active agents”.[11] Suitable forms of transfer vehicles include liposomes, nanoliposomes, ceramide-containing nanoliposomes, proteoliposomes, nanoparticulates, calcium phospho-silicate nanoparticulates, calcium phosphate nanoparticulates, silicon dioxide nanoparticulates, nanocrystalline particulates, semiconductor nanoparticulates, poly(D-arginine), nanodendrimers, starch-based delivery systems, micelles, emulsions, niosomes, plasmids, viruses, calcium phosphate nucleotides, aptamers, peptides, other vectorial tags, bionanocapsules, viral capsid protein assemblies, lipid nanoparticles and polymers.[12] In a preferred embodiment, the transfer vehicle is formulated as a lipid nanoparticle.[13]
[11] Specification at page 17 lines 26-28.
[12] Specification at page 18 line 14 – page 19 line 7.
[13] Specification at page 18 lines 24-25.
Of relevance to the present claims, the use of liposomal transfer vehicles to facilitate the delivery of nucleic acids to target cells is discussed in some detail. According to the specification, liposomes are “usually characterized as microscopic vesicles having an interior aqua space sequestered from an outer medium by a membrane of one or more bilayers… typically formed by amphiphilic molecules” such as lipids, polymers and surfactants.[14] It is stated that:
“Ideally, liposomal transfer vehicles are prepared to encapsulate one or more desired nucleic acids (e.g. mRNA encoding a urea cycle enzyme) such that the compositions demonstrate a high transfection efficiency and enhanced stability.”[15]
[14] Specification at page 19 line 23 – page 20 line 2.
[15] Specification at page 20 lines 27-29.
Furthermore, the transfer vehicle may be selected to optimise the delivery of the nucleic acid to the target cell, tissue or organ.[16] For example, if the target cell is a hepatocyte, the properties of the transfer vehicle, such as size, charge and/or pH, may be modified to target the delivery, reduce immune clearance and/or promote retention in the target tissue.[17] Alternatively, if the target is the central nervous system, selection and preparation of the transfer vehicle must consider penetration of the blood-brain barrier or alternate means of direct delivery.[18]
[16] Specification at page 19 lines 8-10.
[17] Specification at page 19 lines 10-13.
[18] Specification at page 19 lines 13-18.
In order to achieve this, the transfer vehicles may be prepared by including multi-component lipid mixtures employing one or more cationic lipids, non-cationic lipids and PEG-modified lipids.[19] The purpose of incorporating nucleic acids into a transfer vehicle is said to be to protect the nucleic acid from an environment which may contain enzymes or chemicals that degrade them or systems or receptors that cause the rapid excretion of the nucleic acids.[20] The use of polycationic copolymers, cationic lipids, cholesterol and polyethylene-modified phospholipids to improve encapsulation, increase transfection efficiency and enhance stability are contemplated.[21]
[19] Specification at page 21 lines 8-10.
[20] Specification at page 20 lines 14-17.
[21] Specification at page 20 line 27 – page 24 line 29
Cationic lipid refers to “any of a number of lipid species that carry a net positive charge at a selected pH, such as physiological pH.”[22] Examples of known cationic lipids include N-[-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA), 5-carboxyspermylglycine-dioctadecylamide (DOGS), 2,3-dioleyloxy-N-[2(spermine-carboxamido)ethyl]-N,N-dimethyl-propanaminium (DOSPA),1,2-dioleoyl-3-dimethylammonium-propane (DODAP), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-distearyloxy-N,N-dimethyl-3-aminopropane (DSDMA), 1,2-dioleyloxy-N,N-dimethyl-3-aminopropane (DODMA), 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA), 1,2-dilinolenyloxy-N,N-dimethyl-3-aminopropane (DLenDMA) and the like.[23] The use of cholesterol-based cationic lipids as well as dialkylamino-based, imidazole-based, and guanidinium-based lipids are also contemplated.[24]
[22] Specification at page 21 lines 6-7.
[23] Specification at page 21 line 10 – page 22 line 9.
[24] Specification at page 22 line 10 – page 23 line 25.
Non-cationic lipid refers to “any neutral, zwitterionic or anionic lipid.”[25] Examples of known non-cationic lipids include distearoyl-phosphatidylcholine (DSPC), dioleoyl-phosphatidylcholine (DOP), dipalmitoyl-phosphatidylcholine (DPPC), dioleoyl-phosphatidylglycerol (DOPG), dipalmitoyl-phosphatidylglycerol (DPPG), dioleoyl-phosphatidylethanolamine (DOPE), palmitoyloleoyl-phosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl-phosphatidylethanolamine (DPPE), dimyristoyl-phosphoethanolamine (DMPE), distearoyl-phosphatidylethanolamine (DSPE), 16-O-monomethyl- phosphatidylethanol-amine, 16-O-dimethyl-phosphatidylethanolamine, 18-1-trans-phosphatidylethanolamine, 1-stearoyl-2-oleoyl-phosphatidylethanolamine (SOPE) and cholesterol.[26]
[25] Specification at page 24 lines 11-13.
[26] Specification at page 24 lines 15-29.
The use of PEG-modified lipids is said to prevent complex aggregation and also increase circulation lifetime, as well as increasing the delivery of the lipid-nucleic acid composition to the target tissues.[27] Suitable PEG-modified lipids include PEG-modified phospholipids, a PEG chain of up to 5 kDa in length covalently attached to a lipid with alkyl chain(s) of C_6-20 length.[28] PEG-ceramides having C_14-18 acyl chains are given as particularly useful options.[29]
[27] Specification at page 24 lines 1-6.
[28] Specification at page 23 line 26 – page 24 line 6.
[29] Specification at page 24 lines 6-7.
It is preferred that the transfer vehicle is prepared by combining multiple components rather than a single lipid.[30] For example, a transfer vehicle may be prepared using about 1-50 % DSPC, about 5-65 % cholesterol, about 5-90 % DODAP and about 1-25 % C₈-PEG 5000.[31] Suggestions of representative combinations include:
·33 % DSPC, 40 % cholesterol, 25 % DODAP and 2 % mPEG-5000
·31 % DSPC, 40 % cholesterol, 25 % DODAP and 4 % C₈-PEG-2000-ceramide
·75-87 % POPC, 3-14 % DODAP and 10 % C₈-PEG-2000-ceramide
·31 % DSPC, 40 % cholesterol, 25 % DOTAP and 4 % C₈-PEG-2000-ceramide [32]
[30] Specification at page 24 lines 30-31.
[31] Specification at page 24 line 31 – page 25 line 1.
[32] Specification at page 25 lines 3-7.
The selection of lipids as well as their relative amounts, requires the consideration of the characteristics of the each of the lipids in the combination, the nature of the intended target cells or tissues and the characteristics of the nucleic acids to be delivered by the transfer vehicle.[33] For example, these considerations will include the size, charge pH, pKa, fusogenicity and toxicity of the selected lipids.[34] Furthermore, the nucleic acid may be associated with the surface of the transfer vehicle and/or encapsulated within the transfer vehicle, depending on the intended use.[35]
[33] Specification at page 25 lines 7-12.
[34] Specification at page 25 lines 12-14.
[35] Specification at page 25 lines 25-28.
The transfer vehicles may also be targeted to specific cells and tissues by passive and/or active targeting means.[36] Passive targeting exploits the natural distribution patterns of a transfer vehicle in vivo.[37] In contrast, active targeting involves the use of targeting ligands to actively facilitate tissue distribution and cellular uptake of the transfer vehicle and/or its contents in the target cells and tissues.[38]
[36] Specification at page 30 lines 1-2.
[37] Specification at page 30 lines 2-8.
[38] Specification at page 30 lines 9-20.
The compositions comprising a transfer vehicle and nucleic acid are broadly applicable to the delivery of nucleic acids to treat diseases or disorders relating to the deficiency of proteins.[39] For example, mRNA encoding hormones and neurotransmitters may be expressed by target cells and secreted into the surrounding extracellular fluid.[40] In another embodiment, mRNA encoding functional enzymes that remain in the cytosol of the target cell can treat metabolic disorders such as urea cycle disorders.[41] Alternatively, the nucleic acids may encode full length antibodies to confer immunity to a subject.[42] The delivery of mRNA, rather than DNA, encoding the required protein avoids the need to deliver the cargo to specific organelles, such as the mitochondria, within a target cell.[43]
[39] Specification at page 34 lines 21-25.
[40] Specification at page 34 lines 25-28.
[41] Specification at page 34 lines 28-30.
[42] Specification at page 35 lines 28-31.
[43] Specification at page 29 lines 27-31.

The description ends with a series of worked examples. Example 1 illustrates a general process for the manufacture of small (<100 nm) liposomal formulations containing mRNA encoding GFP, OTC or Luciferase. Appropriate quantities of DSPC, cholesterol, DODAP and C₈-PEG-2000 ceramide in a molar ratio of 31:40:25:4 were weighed and dissolved in absolute ethanol at 70 °C and added to a citrate buffered mRNA solution to generate multi-lamellar vesicles (MLVs). The MLVs were diluted with 5mM pH 5.0 citrate buffer to generate large unilamellar vesicles (LUVs) by extrusion through three stacked 80 nm polycarbonate filters. Following extrusion, mRNA that was not associated with the liposomes or was associated with the exterior surface of the liposomes was removed by anion exchange to ensure that all remaining associated mRNA was encapsulated in the liposomes. Examples 2-5 prepare similar 4-component liposomes with the following molar ratio of ingredients:

DSPC cholesterol DODAP/DOTAP C₈-PEG2000 ceramide mRNA

Example 2 31 40 25 4 Renilla Luciferase

Example 3 31 40 25 4 Renilla Luciferase

Example 4 31 40 25 4 Firefly Luciferase

Example 5 31 40 [25][44] 4 Murine OTC
[44] Huang #1 at [150].

In Example 6, an imidazole cholesterol ester lipid is prepared and characterised. This lipid is used in preparing nanoparticles in Example 7 comprising a codon-optimised Firefly Luciferase mRNA encapsulated in imidazole cholesterol ester lipid, DOPE and DMG-PEG-2000 (70:25:5 molar ratio).
In Example 8, the Firefly Luciferase mRNA was “packaged and delivered via a lipid transfer vehicle formulation” consisting of cholesterol, DOPE, DLinDMA and DMG-PEG2000. Example 8 does not give a molar ratio for the lipid components and only indicates that the preparation was “in a manner similar to that described supra.” The example immediately preceding it is a lipid nanoparticle formulation and the results discuss the successful in vivo translation of the exogenous mRNA that was delivered in a lipid nanoparticle.[45]
The claims
[45] Specification at page 49 line 31 – page 50 line 1.
The specification as amended includes a total of 19 claims with claim 1 being the only independent claim, which reads as follows:
1. A composition comprising an mRNA encoding a protein or a peptide, encapsulated within a liposome, wherein the liposome has a size less than about 150 nm and comprises
(i)one or more cationic lipids at a molar ratio of 20 % to 70 % of the total lipids in the liposome,
(ii)one or more non-cationic lipids at a molar ratio of 5 % to 90 % of the total lipids in the liposome,
(iii)and one or more PEG-modified lipids at a molar ratio of 1 % to 15 % of the total lipids in the liposome,
wherein the one or more non-cationic lipids consist of cholesterol and another non-cationic lipid selected from distearoylphosphatidylcholine (DSPC) and dioleoylphosphatidylethanolamine (DOPE); and
wherein the mRNA comprises
(i)a 5'-UTR,
(ii)a 3'-UTR,
(iii)a 5' cap structure, and
(iv)a poly A tail; and
wherein the one or more PEG-modified lipids comprise a polyethylene glycol chain of up to 5 kDa in mass covalently attached to a lipid with alkyl chain(s) of C6-C20 length.
Appended claims 2-19 further define the components, molar ratio of the components, size of the liposomes, nature of the mRNA and the incorporation of additional nucleic acids into the liposomes. The mRNA is specified as encoding for an enzyme in claim 14, further as a liver-specific enzyme in claim 15 and specifically selected from mRNA encoding for ornithine transcarbamylase (OTC), carbamyl phosphate synthetase (CPS), argininosuccinate synthetase (ASSI), argininosuccinate lyase (ASL) or arginase (ARG) in claim 16.
The person skilled in the art
The specification is to be construed through the eyes of the person skilled in the art, a notionally non-inventive skilled worker aware of the common general knowledge in the relevant field. In KD Kanopy Australasia Pty Ltd v Insta Image Pty Ltd, Kiefel J identified the person skilled in the art as:
“...a person acquainted with the surrounding circumstances of the state of the art and manufacture at the relevant time...They are likely to have a practical interest in the subject matter of the invention...and may often work in the art with which the invention is connected.”[46]
[46] KD Kanopy Australasia Pty Ltd v Insta Image Pty Ltd [2007] FCA 481 at [16].
In Root Quality Pty Ltd v Root Control Technologies Pty Ltd, Finkelstein J stated:
“He is the person to whom the patent is addressed and who must construe it. He is the person whose knowledge will determine whether a patent is novel. He is the person who will judge whether a patent is obvious.”[47]
[47] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [70].
Finkelstein J went on to say that the hypothetical skilled person works in the field with which the invention is connected and is a non-inventive person or team likely to have a practical interest in the subject matter of the invention.[48] As described by the applicant, the relevant field from which to draw the person skilled in the art relates to “compositions and methods of the in vivo delivery of nucleic acids.”[49]
[48] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [70]-[72].
[49] Applicant submissions at [34].
The key declarants in this matter are Professor Huang for the opponent and Professor Pouton for the applicant. Professor Huang, at the time of his declaration, was the Fred Eshelman Distinguished Professor in the Eshelman School of Pharmacy at the University of North Carolina[50], and has since retired. His area of research related to gene therapy and targeted drug delivery using liposomes.[51] Professor Pouton is a Professor of Pharmaceutical Science at the Monash Institute of Pharmaceutical Sciences with research experience in drug discovery, formulation of medicines, drug delivery and biotechnology.[52] Since 2006, Professor Pouton has focused on in vivo delivery of nucleic acids, especially mRNA.[53]
[50] Huang #1 at [7].
[51] Huang #1 at [8].
[52] Pouton at [6], [8].
[53] Pouton at [25].
The applicant submitted that the opponent’s choice of expert witness and their line of briefing tainted Professor Huang’s evidence. Professor Huang is a pioneer of liposomal delivery of genes, other nucleic acid-based therapies and small molecule drugs.[54] The first task put to Professor Huang was to give his views on “what [he] considered the skillset and knowledgebase to be, of a skilled person or team given the task of providing compositions having a nucleic acid formulated within a liposome, working immediately before the priority date of the Opposed Application.”[55]
“In my view, providing compositions having a nucleic acid formulated within a liposome would require a team including a person with knowledge of how to prepare liposome formulations and their use in delivering nucleic acids. Such a person would be a lipid formulation chemist, who might have a PhD and background in organic chemistry or, like myself, membrane biophysics, and/or a biochemist; and a person having knowledge in the formulation and production of nucleic acid-based protein expression generally, including protein replacement therapies or vaccines.”[56]
[54] Huang #1 at [11].
[55] Huang #1 at [24].
[56] Huang #1 at [25].
The applicant submitted that choosing a liposome specialist and providing features from the claims in the first question, specifically that the nucleic acid is formulated within a liposome, left little room for any alternative to be suggested by Professor Huang.
The applicant submitted that the person skilled in the art should appropriately be characterised as “a person, or a team of persons, having a practical interest in making and using compositions and methods for the in vivo delivery of nucleic acids.”[57] This person, or team, would include the person skilled in the art as described by Professor Huang but further include those with non-liposomal approaches for in vivo delivery of nucleic acids.[58]
[57] Applicant submissions at [35].
[58] Applicant submissions at [36].
Nevertheless, there was general agreement that both Professor Huang and Professor Pouton had relevant qualifications and experience in varying aspects of the field. For example, both key declarants have experience with in vivo delivery of various nucleic acids. While Professor Huang may specialise in liposomal delivery systems, his evidence remains relevant. When asked about the field of mRNA delivery, Professor Huang demonstrated his knowledge of non-liposome delivery strategies.[59] Therefore, I consider that both key declarants have backgrounds that enable them to understand the specification and provide evidence in relation to what a person skilled in the art knew or would have done at the relevant date. Where there is conflicting evidence, I will decide which evidence should be given greater weight in the usual manner.
[59] Huang #1 at [32].
The opponent included evidence by Timothy Fitzgerald, a registered patent attorney, to introduce citation documents and discuss how they are citable with regard to priority dates, publication dates and relevant passages of disclosure therein.
Construction
The correct approach to the construction of claims was discussed by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd:
“the words in a claim should be read through the eyes of the skilled addressee in the context in which they appear...while the claims define the monopoly claimed in the words of the patentee’s choosing, the specification should be read as a whole ... it is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification...terms in the claim which are unclear may be defined or clarified by reference to the body of the specification.”[60]
[60] H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70 at [118]-[120].
Thus, the task of construing the specification is undertaken from the viewpoint of a person skilled in the art and cognisant of the prevailing common general knowledge at the priority date. The Full Court in Airco Fasteners Pty Ltd v Illinois Tool Works Inc. reiterated the principle that experts can give evidence on the meaning which those skilled in the art would give to technical or scientific terms and phrases and on any unusual or special meanings that would be given by skilled addressees to words which might otherwise bear their ordinary meaning. The Court is to place itself in the position of some person acquainted with the surrounding circumstances as to the state of the art and manufacture at the time. However, it is for the Court, not for any witness however expert, to construe the specification.[61] A similar approach is taken in matters before the Commissioner.
mRNA
[61] Airco Fasteners Pty Ltd v Illinois Tool Works Inc. [2023] FCAFC 7 at [48].
Messenger RNA (mRNA) comprises a single strand of RNA which is the complementary transcript from DNA and acts as the template for protein synthesis through translation by ribosomes.[62] Compared to other types of nucleic acids, mRNA has a short half-life in vivo, enabling cells to modify gene expression and protein synthesis rapidly in response to altered environmental or metabolic conditions.[63]
[62] Pouton at [50].
[63] Pouton at [52].
The simple structure of mRNA is linear[64] but it also has extensive secondary structures through folding.[65] The secondary structures adopted by mRNA in vivo are less predictable and more variable in contrast to other types of nucleic acids and they are likely to transition between different secondary structures over time.[66]
[64] Pouton at [210].
[65] Huang #2 at [18].
[66] Pouton at [51].
As noted by Professor Pouton, the claims also require the mRNA to comprise a 5’-UTR, a 3’-UTR, a 5’-cap structure, and a poly A tail, as well as for it to encode a protein or a peptide. The specification explains that:
“In some embodiments the mRNA can comprise one or more modifications that confer stability to the mRNA (e.g., compared to a wild-type or native version of the mRNA) and may also comprise one or more modifications relative to the wild-type which correct a defect implicated in the associated aberrant expression of the protein. For example, the nucleic acids of the present invention may comprise modifications to one or both the 5' and 3' untranslated regions. Such modifications may include, but are not limited to, the inclusion of a partial sequence of a cytomegalovirus (CMV) immediate-early l (IE1) gene, a poly A tail, a Cap 1 structure or a sequence encoding human growth hormone (hGH)).”[67]
[67] Specification at page 3 lines 24 – page 4 line 2.
Professor Huang noted that the 3’-UTRs, 5’-UTRs, 5’-caps and poly A tails are “completely standard components of mRNA”[68] and that they were “well-known at the relevant date.”[69] Provided these modifications are incorporated, the “mRNA can be one that encodes for literally any protein or peptide.”[70] Professor Pouton confirms this and goes further to say that “the compositions disclosed and claimed are suitable generally for the delivery, transfection and expression of mRNA in vivo.”[71] (emphasis in original)
[68] Huang #2 at [110].
[69] Huang #2 at [86].
[70] Huang #1 at [156].
[71] Pouton at [259].
Insofar as the claims require only that the mRNA comprise these structural elements, the mRNA may include further segments in addition to the protein encoding segment and the flanking segments. For example, the specification refers to the incorporation of a second protein encoding segment in order to modify the stability of the first protein.[72] However, mRNA which do not include 3’-UTRs, 5’-UTRs, 5’-cap and poly A tail, non-protein coding mRNAs, and other forms of nucleic acids, such as DNA, siRNA and plasmids, do not fall within the scope of these claims.
Liposome
[72] Specification at page 14 line 26 – page 15 line 3.
The claims are directed to a composition comprising a liposome having a size of less than 150 nm and comprising:
(i)one or more cationic lipids at a molar ratio of 20-70 % of the total lipids;
(ii)one or more non-cationic lipids consisting of cholesterol and one or both of DSPC and DOPE, at a molar ratio of 5-90 % of the total lipids; and
(iii)one or more PEG-modified lipids comprising a PEG chain of up to 5 kDa covalently attached to a lipid with alkyl chain(s) of C_6-20 length at a molar ratio of 1-15% of the total lipids.
The non-cationic lipid component of the liposome requires ‘one or more’ species consisting of cholesterol and one or both of DSPC and DOPE. Given that cholesterol is required along with DSPC and/or DOPE, ‘one or more’ non-cationic lipids necessarily requires at least two species. The combined molar contribution of cholesterol with DSPC and/or DOPE to the total lipids is 5-90 %. Furthermore, as the selection of non-cationic lipids consist of cholesterol, DSPC and DOPE, liposomes containing any other non-cationic lipids are excluded.
According to the specification, liposomes “are usually characterized as microscopic vesicles having an interior aqua space sequestered from an outer medium by a membrane of one or more bilayers.”[73] It is further explained that “Bilayer membranes of liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains”, and a 1998 paper is referenced to corroborate this position.[74] This is consistent with my understanding of liposomes and Professor Huang also stated that “This is consistent with my understanding of classical liposome morphology”.[75]
[73] Specification at page 19 lines 23-29.
[74] Specification at page 19 lines 29-32.
[75] Huang #1 at [139].
Professor Pouton made the observation that particles formed from a combination of cationic lipid, non-cationic lipid, cholesterol and PEG-modified lipids of the kind disclosed in the opposed application are “today often referred to as ‘lipid nanoparticles’ but for the sake of simplicity, I will continue to use the term ‘liposome’ in this declaration.”[76] Rather than simplifying anything, this statement renders it impossible to determine whether Professor Pouton’s declaration relates to a liposome or to a lipid nanoparticle. However, the applicant submitted as follows:
“insofar as is relevant to the present proceedings, the Specification draws no distinction between the ‘liposome’, ‘liposomal transfer vehicle’ and ‘lipid nanoparticle’. Each of the expressions used in the Specification to refer to a transfer vehicle comprising a combination of one or more cationic lipids, non-cationic lipids and/or PEG-modified lipids.”[77]
[76] Pouton at [213].
[77] Applicant submissions at [51].
To clarify the applicant’s position, I asked at the hearing whether they considered liposomes and lipid nanoparticles to be the same. The applicant submitted that the terms ‘liposome’ and ‘lipid nanoparticle’ are used interchangeably throughout the specification and further submitted that that they did not consider the specification to draw any relevant distinction between the two expressions. Following on from this response, I asked whether they would therefore be happy to read ‘liposome’ in the claims as meaning any lipid-based transfer vehicle having the required combination of lipids and particle size of less than about 150nm. The applicant confirmed that was the case.
I agree with the applicant that each of the expression ‘liposome’, ‘liposomal transfer vehicle’ and ‘lipid nanoparticle’ as used in the specification refer to a form of transfer vehicle and the preferred transfer vehicles comprise a combination of cationic lipids, non-cationic lipids and/or PEG-modified lipids. However, any given combination of lipids can be arranged into different vehicle forms by choice of preparation. The examples of the specification show this quite clearly where rapidly injecting ethanolic solution of the lipids into an aqueous mRNA solution results in a suspension from which the lipid nanoparticles are directly filtered. In contrast, liposomes are prepared by mixing the ethanolic solution of the lipids with the aqueous mRNA solution by stirring or vortexing, then adjusting the pH and extruding the resulting multilamellar vesicles through filters to generate unilamellar liposomes.
I appreciate that the description does not draw any relevant distinction between the liposome and lipid nanoparticle embodiments in terms of the outcome to be achieved. That is, both embodiments are capable of encapsulating mRNA within their interior and delivering it. However, I see nothing in the specification that suggests that the terms themselves were used interchangeably. Each represent an embodiment of a broader concept of lipid-based transfer vehicles, but they are distinct from one another.
Furthermore, I do not consider Professor Pouton’s statement to be proffering that the term ‘liposome’ was understood in the art to be synonymous with ‘lipid nanoparticle’ or any other lipid-based systems at the relevant time. Nor does his statement suggest that anything with lipid components were ubiquitously referred to as ‘liposome’ in the art. Instead, faced with the multitude of arrangements possible from the combination of cationic lipid, non-cationic lipid, cholesterol and PEG-modified lipids, I consider that Professor Pouton simply chose to use the language in the claim for convenience. I note that the prior art documents reviewed by Professors Huang and Pouton included many forms of lipid vehicles, as does the opposed application. Other than for convenience’s sake, Professor Pouton did not provide any evidence that the liposomes of Examples 1-5 were indeed any other form of lipid vehicle or that the word ‘liposome’ had any other meaning in the art.

Professor Huang also had concerns regarding the nature of the invention. He noted that “the particles generated in the Examples have not been fully characterised” but accepted that “Nonetheless, all of the four-lipid liposome formulations did describe the formation of MLVs followed by extrusion to generate LUVs.”[78] LUVs are liposomes having a single lipid bilayer surrounding an aqueous interior and having a diameter greater than 100 nm.[79]
[78] Huang #1 at [156].
[79] Huang #1 at [150].
Given the specific use of ‘liposome’ in the specification as a subset of lipid-based transfer vehicles and the clear definition provided by Professor Huang, I prefer his evidence. I consider ‘liposome’ in the claims to refer to the classical liposome structure having at least one lipid bilayer comprised of the combination of lipids defined above surrounding an aqueous interior and having a size of less than 150 nm.
Encapsulated within
The word ‘encapsulation’ is defined in the description as follows:
“The incorporation of a nucleic acid into liposomes is also referred to herein as ‘encapsulation’ wherein the nucleic acid is entirely contained within the interior space of the liposome.”[80]
[80] Specification at page 20 lines 10-13.
The specification directly compares ‘encapsulation’ to ‘loading’, which refers more generally to incorporating the desired nucleic acid completely or partially in the interior space of the liposome, within the bilayer membrane of the liposome, or associated with the exterior surface of the liposome membrane.[81] Professor Pouton refers to the latter as complexing nucleic acids with liposomes and notes that such structures are “distinctly different” from the structure of the claimed liposomes.[82]
[81] Specification at page 20 lines 8-10.
[82] Pouton at [191] and [212].
Professor Huang expressed dissatisfaction with reading ‘encapsulation’ as appearing in the claims differently to the broader use in the prior art.[83] His concerns stem from the lack of evidence in the specification relating to the exact nature of the composition and the mismatch with prior art documents he was shown prior to seeing the opposed application.[84]
[83] Huang #2 at [51].
[84] Huang #2 at [51]-[52].
However, the specification has endeavoured to provide a clear meaning by distinguishing between ‘loading’ and ‘encapsulation’. In my opinion, the claimed subject matter is further clarified by the mRNA being encapsulated within a liposome, thereby explicitly excluding encapsulation by association, such as a complex.
Therefore, I prefer Professor Pouton’s construction of “the mRNA is entirely contained within the interior space of the liposome.”[85] (emphasis in original) A clear distinction is made between liposomes containing mRNA within its interior space and complexes formed between cationic liposomes and nucleic acids.[86] For instance, Example 1 of the specification illustrating the general process for preparing liposome formulations includes the step of “removing mRNA that was not associated with the liposomes or was associated with the exterior surface of the liposomes”[87] by anion exchange to ensure that all remaining mRNA was encapsulated within the liposomes.
[85] Pouton at [191].
[86] Pouton at [191].
[87] Specification at page 40 lines 23-24.
The applicant sought to add further meaning: “the mRNA is ‘entirely contained within the interior space of the liposome’, so as to be protected against degradation and thus retain its function of ‘encoding a protein or peptide’.”[88] (emphasis in original) However, I do not consider the purpose of the encapsulation to impart any further limitation. Nothing in the specification suggests that anything other than the encapsulation of mRNA within a liposome is required.
[88] Applicant submissions at [114], [173], [180], [213] and [242].
Utility
Subsection 18(1)(c) of the Act requires that the invention, so far as claimed in any claim, is useful. The ground of utility was considered by the Full Court of the Federal Court in H Lundbeck A/S v Alphapharm Pty Ltd., Emmett J stated:
“A claim is bad if it covers means that will not produce the desired result, even if a skilled person would know which means to avoid. That is to say, everything that is within the scope of a claim must be useful, otherwise the claim will fail for inutility.”[89]
[89] H Lundbeck A/S v Alphapharm Pty Ltd. [2009] FCAFC 70; 81 IPR 228 at [247].
In Apotex Pty Ltd v AstraZeneca AB (No 4), Jagot J pointed out that lack of utility requires evidence, not just speculation:
“Ultimately, an asserted lack of utility must be established by appropriate evidence, not be mere speculation that the invention will not work or meet the promise set out in the specification.”[90]
[90] Apotex Pty Ltd v AstraZeneca AB (No 4) [2013] FCA 162 at [352].
A summary of relevant principles was provided by the Full Court of the Federal Court in Artcraft Urban Group v Streetworx:
“It is ‘no objection’ to the validity of an innovation patent granted under the Act that it is ‘commercially impracticable’. The utility of the patent depends upon whether, by following the teaching of the specification, the result claimed is produced...
The ‘basic principle’ of inutility is that if an invention ‘does what it is intended by the patentee to do, and the end attained is itself useful, the invention is a useful invention’... What the invention is ‘intended’ to do is a matter to be gathered from the ‘title and the whole of the specification’.
Put another way, the two questions are: first, what is the promise of the invention derived from the whole of the specification?; second, by following the teaching of the specification, does the invention, as claimed in the patent, attain the result promised for it by the patentee?... Further, ‘everything’ that is within the scope of a claim must be useful, that is, attain the result promised for the invention by the patentee.”[91] (citations omitted)
[91] Artcraft Urban Group Pty Ltd v Streetworx Pty Ltd [2016] FCAFC 29 at [118]- [121].
The Full Federal Court accepted that “it is necessary to follow the teaching of the complete specification to isolate the promise of the invention and determine whether that results in the promise being produced.”[92]
[92] ESCO Corporation v Ronneby Road Pty Ltd [2018] FCAFC 46 at [279].
For completeness, I note that Section 7A states that an invention is taken to not be useful unless a specific, substantial, and credible use for the invention (so far as claimed) is disclosed in the complete specification. However, the opponent submitted that the opposed application fails to meet the promise of the specification across the full scope of the claims.
What is the promise of the invention?
The opponent did not suggest any particular promise of the invention to be derived from the specification. Instead, their submissions stress the breadth of the claims of the opposed application as encompassing embodiments which “simply do not deliver on their intended therapeutic use.”[93]
[93] Opponent submissions at [260].
The applicant suggests the promise of the opposed application is that “the claimed compositions are useful for the in vivo delivery of mRNA, so as to achieve transfection of target cells and expression of the protein or peptide encoded by that mRNA.”[94] The applicant stressed that the promise of delivery, transfection and expression does not necessarily require therapeutic efficacy or specific patient benefit. In contrast, the opponent submitted at the hearing that the expression of the tiniest amounts of a protein would not achieve any clinical effect and the invention would serve no purpose and therefore cannot achieve any promise.

[94] Applicant submissions at [252].

In the context of the opposed application, the promise is to provide mRNA with a transfer vehicle such that it is better than delivering naked mRNA. The very first paragraph of the specification following the divisional references reads as follows:
“Novel approaches and therapies are still needed for the treatment of protein and enzyme deficiencies, particularly strategies and therapies which overcome the challenges and limitations associated with the administration of nucleic acids and the transfection of target cells. Additional approaches which modulate or supplement the expression of a deficient protein or enzyme and thus ameliorate the underlying deficiency would be useful in the development of appropriate therapies for associated disorders.”[95]
[95] Specification at page 1 lines 15-19.
Therapeutic efficacy at a clinically relevant level is obviously desirable, including in a commercial sense. However, therapeutic efficacy is reliant on many other factors, such as the development of an appropriate nucleic acid cargo. The invention described relates to the anterior steps of delivery, transfection, and expression of protein. The promise does not extend to a clinically useful therapy.
Does the claimed invention attain the result promised?
The opponent pressed that “the claims lack utility in that they encompass within their scope embodiments which will not work.”[96] In particular, that downstream effects of mRNA delivery beyond protein expression has not been shown and therefore has not been shown to be therapeutically meaningful.
[96] Opponent submissions at [22] and [260].
Professor Huang was provided with three documents, all published after the earliest priority date, and asked to give his views on these documents.[97] First of these documents, LH-26[98], is a review article on nanomedicines for delivery of mRNA and Professor Huang was directed to section 4.2 relating to protein replacement therapies.[99] In particular, his attention was drawn to the mention of two clinical trials in which synthetic mRNAs formulated in lipid nanoparticles are administered to patients with cystic fibrosis or OTC deficiency. The second document, LH-27[100], is a review article on nanomaterial delivery of mRNA vaccines and Professor Huang was asked about the development of the ionizable cationic lipids for lipid nanoparticles.[101] The final document, LH-28[102], is a patent application by the same applicant as the original applicant for the opposed application and Professor Huang was asked to look at the examples which showed protein secretion in all instances but not necessarily haematocrit increase (therapeutic effect).[103]
[97] Huang #1 at [178].
[98] GOMEZ-AGUADO I. et al.: “Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives”, NANOMATERIALS, 2020, vol. 10, article 364.
[99] Huang #1 at [179].
[100] BUSCHMANN M.D. et al.: “Nanomaterial Delivery Systems for mRNA Vaccines”, VACCINES, 2021, vol. 9, article 65.
[101] Huang #1 at [180].
[102] WO 2012/170930 A1 (SHIRE HUMAN GENETIC THERAPIES, INC) 13 December 2012.
[103] Huang #1 at [181].
With regard to the first two documents, Professor Pouton noted that “there are many reasons why a pharmaceutical or biotechnology company may decide not to proceed with the clinical development of a particular technology (e.g., failure to meet specified milestones).”[104] With regard to the patent document, Professor Pouton pointed to the animal model used in the example being that of healthy mice and the example not being intended to show treatment of anaemia in anyway.[105] The conclusion reached by Professor Pouton was that each of the documents shown to Professor Huang showed delivery, transfection and expression of mRNA encoding a protein.
[104] Pouton at [279].
[105] Pouton at [283].
Given their preference for a broad interpretation of the term ‘liposome’, the applicant did not raise any concerns with the documents Professor Huang was given to consider being directed to lipid nanoparticles. However, I note that none related to liposomes.
Although none of the examples show any activity of the liposome formulations, both parties were in agreement that Example 8 showed something within the scope of the claims was capable of delivering mRNA to the liver, transfection into hepatocytes and expressing the encoded protein.
Conclusion on utility
The opponent has raised doubts and concerns in relation to the ultimate benefit of lipid nanoparticles comprising combinations of cationic lipids, non-cationic lipids, and PEG-modified lipids. However, the evidence provided falls short of showing that liposome compositions as claimed are incapable of achieving any therapeutic effect or even that delivery, transfection and expression of the encoded protein cannot be achieved by any particular embodiment. Consequently, this ground of opposition fails.
Clear enough and complete enough disclosure
Section 40(2)(a) of the Act requires that the complete specification must disclose the invention in a manner which is clear enough and complete enough for the invention to be performed by a person skilled in the relevant art. Such enablement must be across the whole breadth of the claims, without undue burden or the need for further invention. Delegates of the Commissioner have adopted the following stepped approach to assessing whether there is a clear enough and complete enough disclosure:
a)   Construe the claims to determine the scope of the invention as claimed;
b)   Construe the description to determine what it discloses to the person skilled in the art; and
c)   Decide whether the specification provides an enabling disclosure of all the things that fall within the scope of the claims.[106]
1)Is it plausible that the invention can be worked across the full scope of the invention?
2)Can the invention be performed across the full scope of the claims without undue burden?[107]
[106] CSR Building Products Limited v United States Gypsum Company [2015] APO 72.
[107] Evolva SA [2017] APO 57.
These principles have been confirmed by the Federal Court.[108] The opponent also points to the matter in Jusand[109] where the Full Court applied principles entirely consistent with those above, and also considered the concept of a relevant range for the purpose of assessing enablement across the scope of the claims. There it was noted that whether a range is a relevant range is to be:
“...judged against the invention as claimed and, where appropriate, against its essence or core where that is understood to be related to the technical contribution the specification makes to the art and/or its inventive concept.”[110]
Opponent submissions
[108] Cytec Industries Inc. v Nalco Company [2021] FCA 970.
[109] Jusand Nominees Pty Ltd v Rattlejack Innovations Pty Ltd [2023] FCAFC 178 at [217].
[110] Jusand Nominees Pty Ltd v Rattlejack Innovations Pty Ltd [2023] FCAFC 178 at [191].
The gist of the opponent’s submissions was that the invention resides in “the identification of a type of liposomal formulation having the ability to encapsulate and deliver mRNA resulting in the expression of a therapeutically useful protein or peptide – particularly for the treatment of conditions in which the relevant protein or peptide is not expressed or is under expressed.”[111] In the opponent’s opinion, the technical contribution to the art resides in showing that the liposomal compositions of the examples of the opposed application can encapsulate mRNA and deliver the cargo preferentially to the liver.[112]
[111] Opponent submissions at [200].
[112] Opponent submissions at [201].
The opponent highlighted that the only exemplified embodiments relevant to the claims are the liposomal formulations described in Examples 1-5 comprising 31 % DSPC, 40 % cholesterol, 25 % cationic lipid and 4 % C₈-PEG-2000 ceramide, wherein the cationic lipid is either DODAP or DOTAP.[113] Although being uncertain as to the molar ratio of the lipids used, the opponent was satisfied that Example 8 shows something falling within the scope of the claims is able to cause a protein to be expressed in the hepatocytes of treated mice.[114]
[113] Opponent submissions at [202].
[114] Opponent submissions at [205].
The opponent referred to several documents published after the original priority date of the opposed application relating to the successes and failures of later research in the general field of nucleic acid delivery.[115] These documents are said to show that results are highly variable on the basis of the selection of the particular cationic lipid despite the opposed application failing to provide any guidance as to how to select an appropriate lipid formulation.[116]
[115] Opponent submissions at [209].
[116] Opponent submissions at [210].
The opponent further noted that the opposed claims are not limited by the nature of the protein encoded for by the mRNA nor to any delivery target.[117] For example, the later-published documents are said to show: even where some level of protein expression can be confirmed, therapeutic effect has not followed; the lipid formulations encapsulating mRNA do not produce a functional immune response to the protein or peptide being expressed; and the combination of lipids does not allow for alternative targeting other than to the liver.[118]
[117] Opponent submissions at [211].
[118] Opponent submissions at [230]-[234].
In the opponent’s opinion, the opposed claims, by not being limited to the exemplified liposome formulations, mRNA for protein replacement therapy or protein supplementation, and delivery to the liver, exceeded the contribution to the art made in the opposed application. The opponent submitted that “the applicant’s technical contribution to the art does not go beyond the examples due to the high degree of unpredictability and lack of guidance within the opposed application.”[119]
[119] Opponent submissions at [250].
I note that the opponent included submissions relating to proceedings in front of the European Patent Office, as well as to the reg 5.23 material. I have omitted discussions of these documents as they are not proper evidence and I am not bound by proceedings in other jurisdictions. As mentioned above, I have also refused the opponent’s request to take the reg 5.23 material into consideration for the present matter.
Applicant submissions
The applicant submitted that “all claims of the Opposed Application are limited by result.”[120] For example, a composition will fall outside the scope of the claims if the liposome is not capable of encapsulating mRNA.[121] In particular, the applicant stressed that the choice of cationic lipid should be made by the person skilled in the art so as to yield liposomes possessing the characteristics necessary to encapsulate the mRNA and protect it from degradation rather than trying any and all cationic lipids.[122]
[120] Applicant submissions at [213].
[121] Applicant submissions at [214].
[122] Applicant submissions at [215].
Furthermore, the applicant added that the “Specification as a whole, taken together with the CGK” (emphasis in original) should be the basis for assessment of whether a general principle has been disclosed.[123] In this regard, the applicant points to passages from the specification which refers to cationic lipids.[124] Moreover, Professor Huang’s evidence suggested that a person skilled in the art would have had sufficient guidance from the common general knowledge to prepare suitable liposome formulations:
“These four lipid particle components could be formulated in differing relative amounts but within generally understood limits. The cationic lipid (or ionizable cationic lipid) had to be present in a sufficient amount to complex with the nucleic acid but also to be sufficiently available to trigger endosomal release. The neutral lipid and cholesterol could, to a small extent, be balanced with one another but cholesterol was generally present in higher relative amounts. The PEG-lipid couldn’t be present in too high a relative amount as it would otherwise present too much of a steric barrier to contacting the cell membrane for endocytosis and could undesirably affect the physical characteristics of the particle.”[125]
[123] Applicant submissions at [216].
[124] Applicant submissions at [217].
[125] Huang #1 at [40], as referenced in applicant submissions at [217].

With regard to the choice of mRNA, the applicant submitted that Professor Huang’s concerns were limited to his analysis of the specification rather than being based on “any technical or scientific basis to consider that the ability of a PSA, armed with the Specification and the CGK, to perform the invention would vary depending upon the identity of the protein or peptide encoded by the mRNA”.[126] Instead, the applicant pointed to Professor Pouton’s evidence indicating that “the compositions disclosed and claimed are suitable generally for the delivery, transfection and expression of mRNA in vivo.”[127] (emphasis in original)
[126] Applicant submissions at [224].
[127] Pouton at [259].
The applicant submitted that the technical contribution to the art is the disclosure of the claimed compositions.[128] Examples 1-8 describe the preparation of compositions as claimed while the body of the description provides additional information such as the need for enrichment with additional components for targeting tissues or cells, selecting appropriate size of the transfer vehicle for the target cell or tissue and further considerations for passive or active targeting.[129]
Conclusion on clear enough and complete enough disclosure
[128] Applicant submissions at [242].
[129] Applicant submissions at [245].
Both parties are in agreement that Examples 1-5 provide plausible and workable examples of liposome compositions which fall within the scope of the present claims. Both parties also agree that these liposomes comprising DSPC, cholesterol, cationic lipid and C₈-PEG-2000 ceramide in molar ratios of 31:40:25:4, wherein the cationic lipid is either DODAP or DOTAP, are capable of encapsulating and delivering mRNA and transfecting cells to cause the target protein or peptide to be expressed.
The question remains whether applicant’s contribution to the art extends to the general principle of encapsulating mRNA within the full breadth of the claimed liposomes and whether this has been enabled. If not, the applicant’s contribution to the art would reside in having identified certain combinations of lipids in a certain ratio to successfully encapsulate mRNA for delivery, transfection and expression.
Professor Huang explained the “generally understood limits” mentioned above in greater detail for each liposome component. The cationic lipids bind nucleic acid molecules during loading and are involved in endosomal membrane fusion event for release into the cytoplasm and tend to be used in 25-30 % range.[130] Cationic lipids in very low amounts, such as below 20 %, would not be sufficient to bind the nucleic acid and still be available to trigger endosomal release, while very high amounts, such as 70 %, would not leave sufficient room for the neutral lipid and cholesterol to form stable particles with the desired morphology.[131] The neutral lipid and cholesterol may compensate for one another to some degree but Professor Huang considers that less than 30 % of cholesterol in a 4-component liposome would be at a high risk of not having the appropriate particle architecture for nucleic acid encapsulation and delivery.[132] Finally, the PEG-lipid plays a number of roles such as conferring appropriate colloidal stability to the liposomal formulation, reducing particle aggregation, influencing the size of the particle and increasing the circulation time.[133] Again, a sufficient amount of PEG-lipids is required to achieve stability but too much, such as at levels approaching 20 %, creates a high degree of steric hindrance on the particle surface and the particle becomes unstable.[134] According to Professor Huang, he would not have considered adding a PEG-modified lipid at levels above 4-5 %.[135]
[130] Huang #1 at [159].
[131] Huang #1 at [159] and [162].
[132] Huang #1 at [166].
[133] Huang #1 at [163]-[164].
[134] Huang #1 at [164].
[135] Huang #1 at [164].
In contrast, Professor Pouton suggested adopting a practical, common-sense approach to the specification and claims should resolve all of Professor Huang’s concerns.[136] According to Professor Pouton, “using the information supplied in the Specification, and starting from the examples of suitable lipids and lipid ratios identified in the passages of the Specification…, a scientist having even modest experience in the development of delivery systems for nucleic acids could, by routine methods and trial-and-error experimentation, have identified additional lipids and lipid ratios suitable for use in compositions of the kind disclosed and claimed”.[137] However, it was Professor Pouton who also said that even within the general limits, the resulting properties of a liposome prepared from any given combination could not be predicted and empirical testing was required.[138]
[136] Pouton at [263], [270] and [271].
[137] Pouton at [265].
[138] Pouton at [221], [233] and [449].
The work suggested by Professor Pouton appears to fit well with the generally understood limits described by Professor Huang. When asked about the general skill in the art, Professor Huang had suggested that “at that time a skilled graduate student could perform the encapsulation and formulation tasks. The formulations, in terms of molar ratios, and a number of individual lipids within each lipid class which had been shown to form lipid particles were described in the literature and generally fell within well-defined ranges.”[139] Therefore, I am satisfied that a person skilled in the art would have been able to prepare 4-component liposomes within the generally understood limits and make suitable adjustments to cater for a mRNA cargo within this range.
[139] Huang #1 at [43].
However, the generally understood limits do not extend to 20-70 % cationic lipids, 5-90 % cholesterol with DSPC and/or DOPE, and 1-15 % PEG-modified lipids. At best, 25-30 % cationic lipids, greater than 30 % cholesterol and non-cationic lipids, and 4-5 % PEG-modified lipid appears to be the extent of the generally understood limits workable by adopting a practical, common-sense approach. Despite this, based on the passages of the specification pointed out by the applicant and the evidence provided by both experts, I understand that significant empirical testing is required to successfully produce a liposome capable of encapsulating mRNA and getting the target protein expressed following delivery.
Therefore, rather than a principle of general application that would enable substantially the entire scope of the claims, the specification enables a more limited range of specific embodiments. I therefore agree with the opponent that the applicant’s contribution to the art resides in having identified certain combinations of lipids in a certain ratio to successfully encapsulate mRNA for delivery, transfection and expression. This cannot be extrapolated to further embodiments which are wholly reliant on supplementation of information from the common general knowledge or further research to identify alternatives within the broad range.
The applicant’s view of excluding unworkable embodiments by relying on the functional requirement of the mRNA being encapsulated within the liposome does not, in my view, provide any information on how to proceed in case of failure. If anything, the reliance on a functional limitation would suggest that the applicant accepts that not everything within the range of liposomes as claimed are actually capable of encapsulating mRNA, delivering it and causing expression of a target protein. The person skilled in the art is therefore no closer to a workable standard by having the failures excluded from the claimed invention.
With regard to the enablement of the cationic lipid as a general class of liposome component, I note that DOTAP and DODAP are structurally similar with only one methyl group being the difference. In contrast, the opposed application contemplates many more cationic lipids which share no structural similarity to DOTAP or DODAP. The choice of cationic lipid impacts on surface charge as well as membrane structure, which in turn dictates the liposome’s ability to encapsulate its cargo and how it interacts with target cells.[140] The non-cationic lipids, cholesterol and PEG-modified lipids are added to fine-tune the liposome.[141] It is not plausible that the person skilled in the art would be able to work the invention across the full breadth of cationic lipids, even when attempting to work the invention rather than seeking for non-workable alternatives.
[140] Huang #1 at [33].
[141] Pouton at [221].
As well as the general liposome formulation itself, the opponent was also concerned by the nature of the protein encoded by the mRNA and the ability of the liposome to deliver to targets other than the liver. However, I do not consider these aspects to be relevant ranges, as expressed in Jusand. In the context of the opposed application, the ability of the liposome to deliver mRNA, so as to achieve transfection and expression of the protein or peptide encoded by that mRNA is relevant. However, what the expressed protein or peptide is capable of achieving in the body is not. The opposed application does not purport to have invented new proteins or peptides expressed by a new mRNA.
Similarly, the ability for the liposomes to target various tissues and cells preferentially over others is also not a relevant range, as expressed in Jusand. Importantly, the claims do not include any functional features for targeting various tissues or cells. The specification includes discussions of selective delivery by both passive and active targeting means.[142] However, this does not mean that the claims must necessarily include this feature. There is no indication that liposomes without specific targeting means cannot encapsulate or deliver mRNA.
[142] Specification at page 30 line 1 – page 31 line 24.
Overall, while the claims do encompass enabled embodiments, I agree with the opponent that the opposed application does not provide a clear enough and complete enough disclosure for the full breadth of the claimed subject matter to be performed by a person skilled in the art.
Support
Section 40(3) of the Act requires that the claims must be supported by matter disclosed in the specification. At the heart of this consideration is the principle that the “extent of the patent monopoly, as defined by the claims, should correspond to the technical contribution to the art in order for it to be supported, or justified.”[143]
[143] EXXON/Fuel Oils (T409/91) [1994] OJ EPO 653.
The Full Federal Court considered issues of support and sufficiency and noted:
“In many cases these obligations may tend to be the same since they are describing the same relationship although viewed from the differing perspectives of the claims and the specification. As Burley J has observed in Merck Sharp & Dohme Corporation v Wyeth LLC (No 3) [2020] FCA 1477; 155 IPR 1 (‘Merck Sharp’) at [543], they may often be viewed as two sides of the same coin. But they may nevertheless sometimes differ as Birss J (as his Lordship then was) explained in Illumina Cambridge Ltd v Latvia MGI Tech SIA [2021] EWHC 57 (Pat); RPC 12 (‘Illumina’) at [255].”[144]
[144] Jusand Nominees Pty Ltd v Rattlejack Innovations Pty Ltd [2023] FCAFC 178 at [155].
The opponent’s submissions for support were substantially the same as those discussed above for sufficiency. Given my determination under the ground of sufficiency and the overlap in the issues in dispute, I consider that I can deal with this fairly briefly.
For the reasons given above, the applicant’s contribution to the art resides in having identified certain combinations of lipids in a certain ratio to successfully encapsulate mRNA for delivery, transfection and expression. The exemplified liposomes comprising DSPC, cholesterol, cationic lipid and C₈-PEG-2000 ceramide in molar ratios of 31:40:25:4, wherein the cationic lipid is either DODAP or DOTAP, are capable of delivering mRNA and transfecting cells to cause the target protein or peptide to be expressed.
I do not suggest that the only way to enable an embodiment is through worked examples. I do not consider that there is any requirement for a patentee/applicant to demonstrate every embodiment within the scope of the claims have been tried, tested, and proven to have been enabled to be made in the specification. However, where the specification does not provide a principle of general application for something broader, the worked examples may be the only enabled embodiments.
I am satisfied that the full breadth of the claimed subject matter exceeds the applicant’s contribution to the art. None of the claims are limited to the enabled embodiments. Consequently, claims 1-19 of the opposed application lack support.
Priority
In TCT Group Pty Ltd v Polaris IP Pty Ltd, Burley J outlined the relevant principles concerning priority dates of divisional applications:
“Section 43(1) of the Patents Act provides that each claim of a specification must have a priority date. If s 43(2A) applies to a claim, the priority date is the date determined under the Regulations: s 43(2)(a). Otherwise the priority date of a claim is the date of the filing of the specification: s 43(2)(b).
Section 43(2A) provides for a presently relevant exception:
(2A) This subsection applies to a claim if:
(a)prescribed circumstances apply in relation to the invention defined in the claim; and
(b)a prescribed document discloses, or a prescribed set of prescribed documents considered together disclose, the invention in the claim in a manner that is clear enough and complete enough for the invention to be performed by a person skilled in the relevant art.
Chapter 3, Pt 1, Div 2 of the Regulations determines the priority date of a claim for s 43(2)(a) of the Patents Act: reg 3.12(1). Regulation 3.13D(4)(a), which falls within this part of the Regulations, provides that a prescribed circumstance within s 43(2A) of the Patents Act includes where the ‘specification containing the claim that defines the invention was filed for (i) a divisional application under s 79B’.
By reg 3.13D(4)(b), ‘the document mentioned in paragraph 1(b) is a prescribed document’. Paragraph (1)(b) says ‘the specification mentioned in subsection 79B(1) of the Act (the earlier specification) clearly discloses the invention in the claim’.
It follows that to be a prescribed document, the earlier specification (here, the parent) must (a) be an earlier specification mentioned in s 79B(1) of the Patents Act; and (b) ‘clearly disclose’ the invention in the claim.
Regulation 3.12(4) provides:
In this Division, a document, or a set of documents considered together, clearly discloses an invention if the document, or set of documents, discloses the invention in a manner that is clear enough, and complete enough, for the invention to be performed by a person skilled in the relevant art.”[145] (emphasis in original)
[145] TCT Group Pty Ltd v Polaris IP Pty Ltd [2022] FCA 1493 at [142]-[147].
In ToolGen Incorporated v Fisher (No 2), Nicholas J considered the disclosure requirement in the context of a claim to priority to a PCT application and provided the following explanation:
“Section (40)(2)(a) requires that the complete specification make the necessary disclosure. Since the claims form part of the complete specification they may contribute to the disclosure. However, for the purposes of s 43(2A), the claims in the complete specification, although defining the invention, do not contribute to the disclosure. They serve only to define the invention which must be disclosed in the priority document ‘… in a manner that is clear enough and complete for the invention to be performed by a person skilled in the relevant are’. That said, the language used in s 40(2)(a) and s 43(2A)(b) is essentially the same: in both cases the invention must be disclosed in a manner that is clear enough and complete enough for the invention to be performed by a person skilled in the relevant art. Section 43(2A)(b) expresses the disclosure obligation by reference to the invention ‘in the claim’. In my view, nothing turns on the absence of the words ‘in the claims’ in s 40(2)(a). The disclosure obligation imposed by s 40(2)(a) of the Act relates to the invention as claimed.”[146]
The opposed application
[146] ToolGen Incorporated v Fisher (No 2) [2023] FCA 794 at [166].
The opponent pressed that the claimed earliest priority of 1 December 2009 was invalid and that the opposed claims were only entitled to a priority date of 30 November 2010, being the filing date of the PCT application. According to the opponent, the original priority document does not disclose the “invention as claimed in each of opposed claims 1-19 in a manner that is clear enough and complete enough to be performed by a person skilled in the relevant art.”[147]
[147] Opponent submissions at [32], [33] and [53].
The applicant submitted that the priority date should instead be tested under fair basis, as was the law when the priority application was filed.[148] The applicant further noted the absence of any expert evidence on the disclosures of the priority document. It is their submission that, in the absence of any expert evidence in relation to what would have been disclosed to a person skilled in the art, I am “not in a position to make finding as to what would have been disclosed to a PSA by US 653 at any date relevant to the proceedings.”[149]
[148] Applicant submissions at [76]-[77].
[149] Applicant submissions at [80].
It is then fortunate that, for the present matter, I do not need to consider what the priority document would or would not have disclosed to anyone at any date under whichever test. Given that the description for the parent application is the same as that for the opposed application, my conclusions on clear enough and complete enough disclosure of the claimed invention in the opposed application would apply equally to the consideration of priority from the parent application. Consequently, the claims cannot take priority from the parent application.
The opposed application was filed on 24 April 2020, claiming divisional status from the parent application, 2018203895. The opposed application does not directly derive priority from 2010326132 or the priority application US 61/265653. If the opposed application is not entitled to claim priority from the parent application, it will also not be entitled to claim divisional status and the earliest possible priority date will become the filing date of 24 April 2020.
Conclusion on priority
In accordance with the above, I find that there is no claim that is eligible to take the priority date of the parent application. It follows that the opposed application is not entitled to claim priority from the parent application. Consequently, it is not entitled to a divisional status under section 79B. Accordingly, the correct priority date for the claimed invention is 24 April 2020.
While the shift in priority is over 10 years, I note that the same examples for the liposomes were present in the parent and the earlier applications. The priority document also included Examples 1-5 identical to that of the opposed application. The opponent did not make any submissions suggesting that the exemplified embodiments lacked sufficiency. As the present application has lost its connection to the original priority date, the earlier applications could be raised against the current claims. However, the opponent did not press any of the earlier applications as prior art. Furthermore, given the nature of amendments required to address my findings in relation to sufficiency and support, consideration of the earlier applications as prior art appears unnecessary. Therefore, very little turns on the actual priority date of the present claims, be it 2020, 2010 or 2009.
Novelty
For the purposes of subsection 7(1) of the Patents Act, an invention is to be taken to be novel when compared with the prior art base unless it is not novel in the light of any one of the pieces of prior art information. It is well established that the general test for anticipation is the reverse infringement test. The classic formulation of this test is that given by Aickin J:
“The basic test for anticipation or want of novelty is the same as that for infringement and generally one can properly ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement.”[150]
[150] Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1997] HCA 19 at 20.

This test is satisfied if the alleged anticipation discloses all of the essential features of the invention as claimed with clear and unmistakable directions to do what the patentee claims to have invented:
“If the prior inventor’s publication contains a clear description of, or clear instructions to do or make, something that would infringe the patentee’s claim if carried out after the grant of the patentee’s patent, the patentee’s claim will have been shown to lack the necessary novelty, that is to say, it will have been anticipated. … if carrying out the directions contained in the prior inventor’s publication will inevitably result in something being made or done which, if the patentee’s patent were valid, would constitute an infringement of the patentee’s claim, this circumstance demonstrates that the patentee’s claim has in fact been anticipated.
If, on the other hand, the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee’s claim, but would be at least as likely to be carried out in a way which would not do so, the patentee’s claim will not have been anticipated … To anticipate the patentee’s claim the prior publication must contain clear and unmistakeable directions to do what the patentee claims to have invented.” [151]
The nature of the submitted prior art
[151] The General Tire & Rubber Company v The Firestone Tyre and Rubber Company Limited [1972] RPC 457 at 485-486
At the hearing, the opponent pressed that each claim of the opposed application lacked novelty in view of each of the following citations:
WO 2005/120152 A2 (PROTIVA BIOTHERAPEUTICS, INC.)
published 22 December 2005 (D1)
WO 2009/086558 A1 (TEKMIRA PHARMACEUTICALS CORPORATION et al.)
published 9 July 2009 (D2)
WO 2010/129687 A1 (ALNYLAM PHARMACEUTICALS, INC)
published 11 November 2010 (D5)
I have determined that the correct priority date for the claims is 24 April 2020. Consequently, D1, D2 and D5 all form part of the prior art base.
The opponent submitted that each of these documents disclose lipid formulations with a typical mean diameter of about 50-150 nm for the delivery of nucleic acids. The lipid formulations disclosed in these documents may comprise one or more of cationic lipids, non-cationic lipids, PEG-modified lipids, other components and combinations thereof. The opponent pointed to D1 disclosing a lipid composition of 20 % DSPC, 48 % cholesterol, 2 % PEG-C-DMA, 30 % cationic lipid; D2 disclosing lipid compositions of 20-60 % Dlin-K-DMA, 5-25 % neutral lipid, 25-55 % cholesterol, and 0.5-15 % PEG-modified lipid; and D5 disclosing 25-35 % cationic lipid, 25-35 % neutral lipid, 35-45 % sterol, and 1-2 % PEG-modified lipid.[152] The worked examples in all instances are stable nucleic acid lipid particles (SNALPs) carrying siRNA.
[152] Opponent submissions at [70], [77] and [90].
Professor Huang explained that SNALPs are a type of lipid vehicle akin to liposomes and named according to their siRNA cargo.[153] Although Professor Pouton suggested that expressions such as ‘SPLP’ (stabilised plasmid lipid particle), ‘SNALP’ and ‘SALP’ (stabilised antisense lipid particle) were not in common use at the priority date,[154] they were nevertheless used in the cited documents where D1 was published in 2005 and D2 in 2009. Irrespective of whether they were in common use, they were clearly in use at the time and had clear meaning associated therewith.
[153] Huang #1 at [29].
[154] Pouton at [205].
The opponent further pointed to where mRNA is mentioned in these documents. In all instances, mRNA is mentioned as a possible alternative or included within the general list of nucleic acids. The opponent submitted that mRNA for delivery in the above documents would inherently possess a 5’-UTR, a 3’-UTR, a 5’-cap structure and a poly A tail. However, the applicant submitted that while these modifications were well known in the art, Professor Pouton had indicated that whether or not such features are incorporated into any mRNA for delivery depends entirely on the choices made by the scientists responsible for manufacturing these compositions.[155]
[155] Applicant submissions at [106].
Each of D1, D2 and D5 disclose lipid vehicles for delivering nucleic acids. Each of D1, D2 and D5 include explicit disclosures of SNALPs with lipid components falling within the scope of the present claims. Each of D1, D2 and D5 mention mRNA as a possible nucleic acid. None of D1, D2 and D5 explicitly disclose mRNA encapsulated within a liposome.
Therefore, while it is possible to extract features from each of these prior art documents, whether a person skilled in the art carrying out the instructions disclosed therein would arrive at the specific combination of features as claimed is not necessarily inevitable.
Conclusion on novelty
I agree with the applicant that none of the cited documents provide a clear and unmistakable direction for the claimed liposome composition having the required combination of lipid components, encapsulating within its interior mRNA having the required structure, and a size of less than about 150 nm. Consequently, this ground of opposition fails.
Inventive step
Subsection 7(2) states that an invention is taken to involve an inventive step unless it would have been obvious to a person skilled in the art in light of the common general knowledge (whether in or out of the patent area) before the priority date of the relevant claim when considered alone or together with the information mentioned in subsection 7(3).
Nicholas J provided a succinct statement of principles relevant to assessing inventive step:
“Section 7(2) of the Act uses the word ‘obvious’ in the course of describing what must be established before an invention can be held not to involve an inventive step. Something may be ‘obvious’ in light of the common general knowledge, or the common general knowledge coupled with the relevant s 7(3) information, if it is ‘plain or open to the eye or mind, something which is perfectly evident to the person thinking on the subject’ or something which ‘would at once occur to anyone acquainted with the subject and desirous of accomplishing the end’.
An invention may also be obvious in light of the common general knowledge if the person skilled in the art faced with the same problem as the inventor would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not or (using the language of the ‘modified Cripps question’) if the person skilled in the art would be directly led as a matter of course to take such steps in the expectation that doing so might well produce a useful or better alternative to the prior art. However, a claimed invention is not obvious merely because the person skilled in the art would consider that it was ‘worthwhile to try’.”[156]
[156] Hood v Bush Pharmacy Pty Ltd [2020] FCA 1686 at [116]-[117] (citations omitted).
Furthermore, the Full Court noted that:
“The reformulated Cripps question does not require certainty of outcome. It requires that the skilled addressee be directly led as a matter of course to try the claimed invention in the expectation that a particular research path ‘might well produce’ a useful result. It does not require the skilled addressee to know that the steps will produce a useful result.”[157]
The problem
[157] Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] FCAFC 116 at [502] (citations omitted).
The opponent posed the relevant problem addressed by the invention defined in claim 1 to be:
“the ability to encapsulate any mRNA encoding for a protein or peptide, the mRNA
[158] Opponent submissions at [115].
having claimed features (i) to (iv), within a liposome of the claimed size and lipid composition.”[158]
As noted by the applicant, this incorporates the solution as part of the problem and necessarily brings about hindsight.[159] Instead, the applicant poses the problem as a need for delivering mRNA to target cells in vivo to achieve transfection of those cells and expression of the protein or peptide encoded by the mRNA.[160]
[159] Applicant submissions at [13].
[160] Applicant submissions at [136].
I agree with the applicant that the claims themselves cannot form the basis for the very problem they aim to solve. I also agree with the applicant’s formulation of the problem.
Common general knowledge
Common general knowledge is the background knowledge and experience available to all those working in the relevant art. In Minnesota Mining and Manufacturing Co v Beiersdorf (Aust) Ltd, Aickin J stated:
“The notion of common general knowledge itself involves the use of that which is known or used by those in the relevant trade. It forms the background knowledge and experience which is available to all in the trade in considering the making of new products, or the making of improvements in old, and it must be treated as being used by an individual as a general body of knowledge.”[161]
[161] Minnesota Mining and Manufacturing Co v Beiersdorf (Aust) Ltd [1980] HCA 9 at [115].
However, it is not enough that information is recorded in a document, even if that document is widely circulated. Middleton J explained in Ranbaxy Laboratories Limited v AstraZeneca AB, that it is only part of the common general knowledge when it is generally known and accepted in the art:
“…information does not constitute common general knowledge merely because it might be found, for example, in a journal, even if widely read by persons in the art … Reference in this regard is made to the words of Luxmoore J in British Acoustic Films (1936) 53 RPC 221 at 250, cited by Lehane J in Aktiebolaget Hässle v Alphapharm Pty Ltd (1999) 44 IPR 593; [1999] FCA 628 at 605 [39]:
In my judgment it is not sufficient to prove common general knowledge that a particular disclosure is made in an article, or series of articles, in a scientific journal, no matter how wide the circulation of that journal may be, in the absence of any evidence that the disclosure is accepted generally by those who are engaged in the art to which the disclosure relates. A piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated. Such a piece of knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in the particular art; in other words, when it becomes part of their common stock of knowledge relating to the art.”[162]
[162] Ranbaxy Laboratories Limited v AstraZeneca AB [2013] FCA 368 at [217].
Professor Huang gave evidence on what was common general knowledge in the field of liposomal delivery of nucleic acids, mRNA delivery, cationic lipids, lipid delivery formulations immediately prior to 1 December 2009.[163] Professor Pouton was asked to describe the common general knowledge relating to the delivery of nucleic acids in vivo before 1 December 2009.[164] Both experts were also asked to point out any material change in common general knowledge in the art between 1 December 2009 and 30 November 2010, if any. The relevant common general knowledge as of 1 December 2009 was:
[163] Huang #1 at [26]-[46].
[164] Pouton at [38]-[68].
·   Nucleic acids could be delivered in vivo in their naked form as a direct injection without any transfection medium or using electroporation techniques;
·   Nucleic acids could be delivered in vivo in formulations for gene-guns, viral delivery vehicles, polymer-based delivery systems, peptide-based delivery systems, lipid-based delivery systems and ex vivo transfection techniques;
·   Lipid delivery technologies included micelles, vesicles, liposomes, lipoplexes and lipid nanoparticles composed of one or more types of lipids
othere were a number of commercially available cationic lipids that were typically used,
othe development of the ionisable cationic lipid was important in allowing for complexation with a nucleic acid while charged at an acidic pH while then becoming neutral at physiological pH to improve lipid particle circulation, delivery and, importantly, endosomal release,
othe role of certain neutral helper lipids, cholesterol and PEG-lipids in forming and stabilising an appropriately sized lipid particles were being investigated;
·   Chemical and structural modifications to nucleic acids were known to enhance delivery
oknown chemical and structural modifications to mRNA included capping, tails, untranslated regions, and modified nucleotides.
I have no evidence as to the state of common general knowledge as at the filing date of the opposed application, 24 April 2020. As amendments to overcome sufficiency of disclosure issues that I have found above would necessarily also restore the earliest priority date, I will proceed on the basis that common general knowledge was the same between 2009 and 2020.
Inventive step in light of common general knowledge
Professor Huang noted that lipid delivery platforms had proven successful in DNA and siRNA delivery and early research also showed that mRNA could be encapsulated within a cationic liposome, delivered and expressed.[165] However, at the hearing, the applicant stressed that the briefing process for Professor Huang was tainted by the very first question being to describe the skillset required for providing compositions having a nucleic acid formulated within a liposome. Thereafter, being asked to provide the common general knowledge in the field, Professor Huang gave answers relating to liposome development. Although he was also asked about the state of knowledge in the field of mRNA delivery, the very first statement is “In simple terms, the principle was well-known to lipid formulation chemists.”[166]
[165] Huang #1 at [30].
[166] Huang #1 at [32].
In any event, even if these questions were leading Professor Huang to the claimed subject matter, his evidence falls short of pointing to the combination. Indeed, Professor Huang himself noted that there were many laboratories working on nucleic acid delivery approaches.[167] This would indicate that the field was developing and accumulating knowledge but does not point to the claimed subject matter being obvious to those skilled in the art in the absence of hindsight.
[167] Huang #1 at [29].
At the hearing, it was also stressed by the applicant that the inventive step consideration should not be generalised to whether it would have been obvious to formulate mRNA with liposomes. The claims are limited to a specific combination of lipids forming a liposome within which is encapsulated a protein encoding mRNA with the specified structural modifications. Nothing in the evidence points to this combination being obvious to a person skilled in the art in light of common general knowledge alone.
At best, the evidence suggests that a person skilled in the art would have contemplated formulating mRNA with liposomes. However, whether the liposome would have encapsulated or merely formed complexes with the mRNA, what liposome formulation would have been used or what structural modifications may have been carried out on the mRNA remain unanswered. If given the liposome formulation and told to encapsulate a protein-encoding mRNA with 5’-UTR, 3’-UTR, 5’-cap and a poly A tail, I would expect that a person skilled in the art would have been able to perform this. However, that would be hindsight.
Each feature appearing the claims, individually on their own, were known in the art. However, as noted above, where there is a combination of features, it is the combination that must be obvious.[168] Consequently, the claimed subject matter is inventive over the common general knowledge.
Inventive step in light of common general knowledge plus documents raised
[168] Minnesota Mining and Manufacturing Co v Beiersdorf (Aust) Ltd [1980] HCA 9 at [116].
The opponent pressed the following documents for inventive step in light of common general knowledge considered alone or together with one or more of the following items of prior art:
(i)WO 2005/120152 A2 (D1);
(ii)WO 2009/086558 A1 (D2);
(iii)WO 2004/002453 A1 (D3);
(iv)WO 1998/051278 A2 (D4);
(v)WO 2010/129687 A1 (D5);
(vi)Maurer N., “Spontaneous entrapment of polynucleotides upon electrostatic interaction with ethanol-destabilized cationic liposomes”, Biophysical Journal, 2001, vol. 80, pp. 2310-2326 (D13);
(vii)Martinon et al., “Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA”, European Journal of Immunology, 1993, vol. 23, pp. 1719-1722 (D14);
(viii)Pascolo, S. (2008). “Vaccination with Messenger RNA (mRNA)”. In: Bauer, S., Hartmann, G. (eds) Toll-Like Receptors (TLRs) and Innate Immunity. Handbook of Experimental Pharmacology, vol 183. Springer, Berlin, Heidelberg (D15);
(ix)Fenske, D.B. et al. “Liposomal Nanomedicines: An emerging field”, Toxicologic Pathology, 2008, vol. 36, no. 1, pp. 21-29 (D17);
(x)WO 1990/011092 A1 (D19);
(xi)WO 2007/024708 A2 (LH-6); Karikó et al., “Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability”, Molecular Therapy, 2008, vol. 16, no. 11, pp. 1833-1840 (LH-7); and Karikó et al., “In vivo protein expression from mRNA delivered into adult rat brain”, Journal of Neuroscience Methods, 2001, vol. 105, no. 1, pp. 77-86 (LH-8) (The ‘Karikó’ documents).
D1 and D2 relate to improved cationic lipids for use in lipid vehicles. D3 relates to an apparatus for producing liposomes. D4 relates to therapeutic agents encapsulated in lipid vesicles. D5 relates to the delivery of nucleic acid-based agents to immune cells. D13, D14, D17 and D19 discuss liposome-entrapped genetic drugs. D15 is a book chapter on mRNA-based vaccines and describes direct injection, liposomal delivery and needless delivery with gold particles.
D1-D5, D13 and D17 disclose lipid vehicle components which fall within the scope of the claimed liposome. However, the worked examples encapsulated siRNA in the liposomes. Given the problem of delivering mRNA to target cells in vivo to achieve transfection of those cells and expression of the protein or peptide encoded by the mRNA, would the person skilled in the art have considered delivering mRNA in the same vehicle as siRNA?
Interestingly, D17 separately describes lipid vehicles for small molecule drugs, plasmid DNA, antisense oligonucleotides and siRNA. The progression in the art is described as starting with plasmid DNA encapsulated in a liposome composed of a cationic lipid (such as DODAC), DOPE, and PEG ceramides. This approach was used as a guide for antisense oligonucleotides, replacing DODAC with DODAP and changing the co-solubiliser from a detergent to ethanol. For the development of siRNA liposomes, further modification to lipid selection for DSPC, DODMA, cholesterol and PEG-S-distearoylglycerol and enhancing encapsulation by the use of a peristaltic pump with dual pump heads to achieve mixing of lipids and siRNA.
On the other hand, D14 is specific to liposome encapsulation of mRNA but the liposome comprised only cholesterol, DPPC, and phosphatidylserine in a 5:4:1 molar ratio. DPPC and phosphatidylserine are phospholipids. Alternative liposome formulations, such as the claimed 4- component liposomes, are not taught in D14.
According to Professor Huang, each of the above documents would have taught a person skilled in the art that lipid-based carrier systems can be used to deliver any nucleic acid.[169] Professor Pouton did not share the same level of optimism due to “the very significant chemical, structural and biological differences between mRNA, on the one hand, and other types of nucleic acids”.[170] I also note that, Professor Huang admits to having exercised impermissible hindsight:
“If a document describes most features of an invention, then I would certainly give it due consideration and think about whether what is missing would have been difficult to add or would have suggested itself to me.”
[169] Huang #1 at [60], [67], [73], [81], [86], [96], [99], [106], [118] and [129].
[170] Pouton at [216].

Working backwards from the claimed solution would make most inventions obvious. However, without the benefit of hindsight, a person skilled in the art may be led down many different paths where some may be obvious and others not. Consequently, I prefer the evidence and concerns of Professor Pouton on this point.
I can accept that numerous liposomes had been prepared for the delivery of various therapeutic agents, including nucleic acids. As a general concept, this is not contested by either party. However, I cannot accept that a person skilled in the art faced with the problem of formulating mRNA for delivery, transfection and protein expression and armed with any one of D1, D2, D3, D4, D5, D13, D14, D15, D17 or D19 would arrive at the claimed invention as a matter of routine.
As described in D17, even where an existing concept is used, alterations to the lipid composition and preparation steps are required when trying a different form of nucleic acid. The 3-component liposome encapsulated mRNA formulation of D14 points in another direction to the claimed solution. Consequently, I do not consider it possible that, in the absence of hindsight, a person skilled in the art would have arrived at the solution of preparing a protein-encoding mRNA comprising a 5’-UTR, 3’-UTR, 5’-cap and poly A tail and encapsulating it within a liposome comprising 20-70% cationic lipids, 5-90% DSPC and/or DOPE with cholesterol, and 1-15% PEG-modified C_6-20 lipids and having a size less than 150nm.
Accordingly, lack of inventive step in light of any one of D1, D2, D3, D4, D5, D13, D14, D15, D17 or D19 is not made out. The reasoning leads to a conclusion that further combinations of these documents together would also not deprive the claims of inventive step.
With regard to the ‘Karikó’ documents, they were brought into evidence as part of describing the common general knowledge. The applicant submitted that these documents should not be relied upon under section 7(3) as they were not included in the SGP for such purpose.[171] In any event, these documents only disclose modified nucleosides and their incorporation into RNA, including mRNA, and delivery by complexing with cationic lipids. The ‘Karikó’ documents therefore do not address any of the shortcomings of any one of D1, D2, D3, D4, D5, D13, D14, D15, D17 or D19 with regard to inventive step. Consequently, whether they are raised now for inventive step purposes or not is irrelevant.
Conclusion on inventive step
[171] Applicant submissions at [18] and [181].
The opponent has not established that the claims lack inventive step in light of the common general knowledge, alone or in combination with any of the identified prior art documents.
Conclusion
The opposition is successful. The opposed application lacks clear enough and complete enough disclosure as well as support for all claims. I will allow the applicant an opportunity to propose amendments to overcome this finding.
Costs
The normal approach is that costs should follow the event. I see no reason to depart from this approach. The opposition is successful. Accordingly, I award costs in accordance with Schedule 8 against the applicant, Translate Bio, Inc.
M. Umehara
Delegate of the Commissioner of Patents

DSPC	cholesterol	DODAP/DOTAP	C₈-PEG2000 ceramide	mRNA
Example 2	31	40	25	4	Renilla Luciferase
Example 3	31	40	25	4	Renilla Luciferase
Example 4	31	40	25	4	Firefly Luciferase
Example 5	31	40	[25][44]	4	Murine OTC