Novavax, Inc. v GlaxoSmithKline Biologicals SA - [2018] APO 84

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Novavax, Inc. v GlaxoSmithKline Biologicals SA [2018] APO 84

Patent Application: 2012211278

Title:RSV immunization regimen

Patent Applicant: GlaxoSmithKline Biologicals SA

Opponent: Novavax, Inc

Delegate: D. S. Triffett

Decision Date: 23 November 2018

Hearing Date: 31 August 2018, in Canberra

Catchwords: PATENTS – section 59 opposition to grant of a patent – manner of manufacture – lack of manner of manufacture not established – novelty – lack of novelty not established – inventive step – evidence does not establish that a person skilled in the art would ascertain patent documents - lack of inventive step not established – full description – lack of full description not established – best method of performance – lack of best method of performance not established

Representation: Counsel for the applicant: Mr Chris Burgess
Patent attorney for the applicant: Mr Steve Gledhill and Dr Lee Miles of FB Rice
Counsel for the opponent: Mr Ian Horak
Patent attorney for the opponent: Dr Tom Gumley and Dr Catherine Windbanks of FPA Patent Attorneys Pty Ltd.

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Patent Application:         2012211278
Title:  RSV immunization regimen
Patent Applicant:            GlaxoSmithKline Biologicals SA.
Date of Decision:            23 November 2018

DECISION

The opposition fails on all grounds. Subject to appeal, I direct that the application proceed to grant.

I award costs according to Schedule 8 against Novovax, Inc.

REASONS FOR DECISION

Background

Patent application 2012211278 in the name of GlaxoSmithKline Biologicals SA (the applicant) was advertised as accepted on 10 November 2016. Novavax, Inc (the opponent) opposed the grant of a patent under s 59 of the Patents Act 1990 (Cth)(the Patents Act).

The opposition

The statement of grounds and particulars identified seven grounds of opposition: manner of manufacture, novelty, inventive step, utility, full description, clarity and fair basis. At the hearing, only four grounds were pressed: manner of manufacture, novelty, inventive step and full description.

The parties relied upon evidence by several declarants. Evidence in support consists of declarations by John Lowenthal (Lowenthal-1 and Lowenthal-2), Nigel Crawford (Crawford-1 and Crawford-2), and Catherine Windbanks (Windbanks). Evidence in answer consists of a declaration by Paul Young (Young). Evidence in reply consists of declarations by John Lowenthal (Lowenthal-3) and Nigel Crawford (Crawford-3).

The request for examination in relation to the patent application was filed on 12 April 2013. As a consequence, the substantive amendments of the Patents Act brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 do not apply to the opposed application. This includes the amendment to s 60(3A) that allows the Commissioner to refuse a patent application if satisfied on the balance of probabilities that a ground of opposition has been made out. Instead, the onus of proof in this opposition proceeding lies with the opponent, who must establish that it is clear that a valid patent cannot be granted.[1]
[1] F. Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283 at [29], [67], 50 IPR 305; Commissioner of Patents v Sherman [2008] FCAFC 182 at [18], [22], 79 IPR 426.

The specification

The opposed application claims priority from US61/436,355 filed on 26 January 2011, the contents of which are incorporated into the present specification by reference. The specification as amended on 20 October 2016 comprises description pages from 1 to 102, claims pages from 103 to 108, drawings page 1/1, and a sequence listing from page 1 to page 10. There are 36 claims, including four independent claims (claims 1, 2, 16 and 17). The claims in full appear in the ANNEX at the end of this decision.

What is the invention as described

Before commencing to construe the specification, I note what Middleton J said in Eli Lilly and Company Limited v Apotex Pty Ltd:[2]

"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] [2013] FCA 214, 100 IPR 451 at [139].

The background to the invention

Respiratory syncytial virus (RSV) is an enveloped non-segmented negative-strand RNA virus in the family Paramyxoviridae, genus Pneumovirus.[3] It is the most common cause of bronchiolitis and pneumonia among children in their first year of life.[4] To infect a host cell, RSV requires fusion of the viral membrane with a host cell's membrane.[5]

[3] Specification at [003].

[4] Specification at [003].

[5] Specification at [004].

The application is titled "RSV immunization regimen". The invention is broadly summarised as follows:

"The invention relates to methods for providing protective immunity against RSV in an infant, comprising (a) administering a first anti-RSV immune response inducing composition to a female during pregnancy; and (b) administering a second anti-RSV immune response inducing composition to the infant that is born from that pregnancy."[6]

"The invention also relates to methods for protecting an infant from disease caused by RSV, comprising administering to an infant an anti-RSV immune response inducing composition, wherein the infant was born to a female to whom an anti-RSV immune response inducing composition was administered during the time when the female was pregnant with the infant."[7]
[6] Specification at [008].
[7] Specification at [009].

The specification further describes anti-RSV immune response inducing compositions,[8] protein formulations,[9] nucleic acid compositions,[10] RNA delivery systems,[11] oil emulsion adjuvants,[12] cytokine-inducing agents,[13] aluminium salt adjuvants,[14] and methods of treatment, use and administration.[15]
[8] Specification at [039] and [0138]-[0148].
[9] Specification at [040]-[070].
[10] Specification at [071]-[095].
[11] Specification at [096]-[0137].
[12] Specification at [0149]-[0156].
[13] Specification at [0157]-[0180].
[14] Specification at [0181]-[0197].
[15] Specification at [0198]-[0209].

Examples

Example 1 describes the effectiveness and immunogenicity of the RSV immunisation regimen by reference to using suitable animal models.[16] In Example 1, female cotton rats are administered an anti-RSV immune response inducing composition before and/or after they are mated to induce the production of anti-RSV antibodies during pregnancy.[17] Furthermore, Example 1 describes that some of the newborn rats are administered an anti-RSV immune response inducing composition one or more times,[18] and the level of protection from RSV conferred by the immunisation regimens is assessed by challenging the infant cotton rats with RSV and assessing titres of virus in the infant cotton rat.[19]

[16] Specification at [0210].

[17] Specification at [0211].

[18] Specification at [0211].

[19] Specification at [0211].

Example 2 describes the preparation of an RSV F subunit vaccine,[20] and testing the efficiency of boosting an immune response with the RSV F subunit vaccine in adult rats and mice previously primed by natural infection.[21] The results of these experiments demonstrated that the RSV F subunit vaccine effectively boosted the serum F-specific IgG and RSV neutralising responses primed by RSV infection in mice and cotton rats.[22]

[20] Specification at [0222].

[21] Specification at [0223]-[0225].

[22] Specification at [0226]; Tables 1 and 2.

Example 3 describes protection by passive transfer of antibody from RSV-infected, F subunit vaccine-boosted cotton rats and mice. In Example 3, cotton rats were injected with serum from 1) naive cotton rats, 2) RSV infected cotton rats, or 3) RSV infected cotton rats that were also vaccinated with the RSV F subunit vaccine.[23] Two days after the serum transfer, all cotton rats and mice were infected intranasally with RSV.[24] The results of Example 3 indicated that rodents that received serum from RSV-infected, F subunit vaccine-immunised donors had the highest serum RSV neutralisation titers after transfer and the lowest lung viral loads after RSV challenge.[25] The results of Example 3 illustrate that passively-transferred serum can protect from RSV challenge, and that the higher the neutralisation titer of the transferred serum, the greater the protection from RSV.[26]

[23] Specification at [0227].

[24] Specification at [0229].

[25] Specification at [0233]; Tables 3 and 4.

[26] Specification at [0233]; Tables 3 and 4; Figures 1A and 1B.

Example 4 describes induction of a protective immune response by the RSV SAM™ (Self Amplifying Message) vaccine in rodents in the presence or absence of passively-transferred RSV-immune serum. The RSV SAM™ vaccine is an RNA replicon vaccine that encodes the full length RSV F protein with a deletion in the fusion peptide region.[27] In Example 4, cotton rats were injected with serum from 1) RSV infected cotton rats boosted with the RSV SAM vaccine, or 2) naïve cotton rats. Half of the animals in each group were further vaccinated with the RSV SAM vaccine on days 2 and 20 of the study, all cotton rats were challenged with RSV on day 49, and 5 days later spleens and lungs were harvested for T cell and viral load analysis.[28] The results of Example 4 indicated that the RSV SAM vaccine was immunogenic and provided almost complete protection from a nasal RSV challenge.[29] The results of Example 4 also demonstrated that the RSV SAM vaccine was able to induce a RSV neutralising response in the presence of passively-transferred immune serum, although the RSV SAM vaccine-induced neutralising response was approximately 10-fold lower in the presence of passive RSV-specific antibody than in the absence of this antibody.[30] Example 4 also demonstrated that, although passively-transferred RSV-specific antibody partially suppressed the RSV SAM-induced antibody response in rodents, it did not suppress the RSV SAM-induced T cell response.[31]

[27] Specification at [0235].

[28] Specification at [0237].

[29] Specification at [0242].

[30] Specification at [0243].

[31] Specification at [0244].

Example 4 further determined whether the RSV SAM vaccine was capable of inducing a protective immune response in the presence of passive antibody from RSV-infected, F subunit vaccine-boosted donors.[32] Cotton rats were inoculated with RSV-immune serum, vaccinated twice with the RSV SAM vaccine, and then infected with RSV 3-4 weeks later.[33] The results of this experiment demonstrate that that the RSV SAM vaccine is able to induce a protective immune response in the presence of passively-transferred RSV-specific antibody, although the protective efficacy of the RSV SAM vaccine was greater in the absence of passive RSV-specific serum.[34]

[32] Specification at [0245].

[33] Specification at [0245].

[34] Specification at [0245].

The problem

The specification describes the problem as a need for improved RSV immunisation regimens,[35] as previous attempts at RSV vaccines have led to failed clinical trials wherein the vaccine did not protect against infection and in fact was associated with increased risk of severe RSV disease when the vaccinated children become infected.[36] The specification further states that a suitable vaccine for infants against RSV infection is not currently available, but is desired.[37]
[35] Specification at [007].
[36] Specification at [006].
[37] Specification at [005].

The Person Skilled in the Art

The person skilled in the art (PSA) was considered in Root Quality Pty Ltd v Root Control Technologies Pty Ltd:[38]
"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."
[38] [2000] FCA 980; 49 IPR 225 at [70].
However, the PSA is not a real person, but an artificial construct that is used as a tool of analysis which is used to make the determination:

"The notional person is not an avatar for expert witnesses whose testimony is accepted by the court. It is a pale shadow of a real person – a tool of analysis which guides the court in determining, by reference to expert and other evidence, whether an invention as claimed does not involve an inventive step."[39]
[39] AstraZeneca AB v Apotex Pty Ltd [2015] HCA 30; 257 CLR 356 at [23].

At the hearing the opponent submitted that Dr Crawford's evidence should be attributed more weight than Prof Young, as Dr Crawford is a clinician focussed on vaccine administration which is the subject matter of the opposed application, whereas Prof Young is a researcher focussed on drug discovery which is an earlier stage in the development process.
The applicant submits that Professor Young's evidence carries more weight than Dr Lowenthal or Dr Crawford, because Professor Young is the only witness who has actually worked on the problem of providing protective immunity against RSV, including before the priority date.[40] The applicant further submitted at the hearing that Prof Young is more representative of the skilled addressee as the common general knowledge in relation to RSV immunisation of infants at the priority date, was at the drug discovery stage, which involved assessment of RSV antigens and dealing with the problems of maternal antibody immunosuppression and the immature immune system of an infant. The applicant submits that Dr Crawford's expertise as a clinician is more relevant to devising administration regimes of vaccines that have already had regulatory approval.
[40] Applicant's Written Submissions at [15].
I am satisfied that the hypothetical team representing the PSA would comprise both researchers at the drug discovery stage, and clinicians at the administration stage. As stated above, the problem is the need for improved RSV immunisation regimes. In order to solve the problem, the hypothetical team representing the PSA would need to comprise researchers at the drug development stage, such as Dr Lowenthal and Prof Young, to identify appropriate antigens that provide protective immunity and avoid problems such as maternal antibody immunosuppression and the immature immune system of an infant. However, the hypothetical team would also need to include clinicians such as Dr Crawford to optimise vaccination schedules once such antigens have been discovered. As such I will weigh the evidence of the declarants in the usual manner.

Construction

The correct approach to the construction of claims was discussed by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd:[41]

"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."

[41] [2009] FCAFC 70, 81 IPR 228 at [118]-[120].

Construction of claim 1

Claim 1 is the first independent claim. It reads:

"A method for providing protective immunity against respiratory syncytial virus (RSV) in an infant, comprising:
(a) administering a first anti-RSV immune response inducing composition which provides one or more RSV antigens to a female during pregnancy; and
(b) administering a second anti-RSV immune response inducing composition which provides one or more RSV antigens to the infant that is born from the pregnancy, at about 4 months old or younger;
wherein the one or more RSV antigens comprise an RSV F glycoprotein."

"protective immunity"

The specification states at [0019]:

"An used herein, an anti-RSV immune response inducing composition is any composition that is suitable for administration to a mammal and is effective to induce active immunity or boost an immune response, preferably a protective immune response, against RSV."

Paragraph [0019] implies that a "protective immune response" is something more than "active immunity" or any "immune response".

The specification at [033] further illustrates some examples about what constitutes a "protective immune response":

"In some embodiments the immune response is a protective immune response, i.e., the response reduces the risk of RSV infection, delays the onset of RSV infection, reduces the risk of RSV-caused disease, reduced the severity of RSV-caused disease, delays the onset of RSV-caused disease, reduces the frequency of RSV-caused disease, reduces the sequelae of RSV infection or RSV-caused disease, or reduces the risk that an RSV-infected individual will spread RSV to another individual."

Dr Crawford defines describes "protective immunity" as:

"a form of immunity that enables protection from a disease or condition that arises from infection with the relevant pathogen."[42]

[42] Crawford-1 at [23].

Dr Lowenthal defines "protective immunity" as:

"something more than a mere immune response. It is possible to provide an immune response that is not protective. Protective immunity in simple words is immunity, or an immune response, that protects the individual from infection or disease related aspects of infection."[43]
[43] Lowenthal-2 at [38].

Dr Lowenthal further states that he does not "think that protective immunity actually means an immunity that can completely prevent infection or reinfection but rather that the degree of immunity is sufficient to limit any infection such that the infant does not suffer disease."[44]

[44] Lowenthal-2 at [38].

It can be seen that the expert evidence of what constitutes "protective immunity" is broadly consistent with the idea of "protective immunity" implied from the specification. As a result I construe "protective immunity" as broadly defined in the evidence of Dr Crawford and Dr Lowenthal. That is, "protective immunity" is a form of immunity (or immune response) that protects an individual from infection or a disease related aspect of that infection. Some examples of protective immunity are exemplified at paragraph [033] of the specification.

"an infant"

The specification defines an "infant" as an individual under one year of age.[45]
[45] Specification at [018].

"anti-RSV immune response inducing composition"

The specification defines an "anti-RSV immune response inducing composition" as "any composition that is suitable for administration to a mammal and is effective to induce active immunity or boost an immune response, preferably [emphasis added] a protective immune response, against RSV."[46]

[46] Specification at [019].

In my view, the specification is implying that the anti-RSV immune response inducing compositions induce active immunity or boost an immune response, but do not necessarily have to (on their own) provide a "protective" immune response.

The specification goes on to exemplify some example anti-RSV immune response inducing compositions as:

"a subunit composition comprising an RSV protein antigen, a nucleic acid that encodes an RSV protein antigen, a viral replicon particle (VRP) that contains a nucleic acid that encodes an RSV protein antigen, live attenuated viruses, inactivated viruses, virus-like particles (VLP), or recombinant viral vectors."[47]
[47] Specification at [019].

Further, the specification states at [011]:

"In some embodiments, the first anti-RSV immune response inducing composition and the second anti-RSV immune response inducing composition are the same. The anti-RSV immune response inducing compositions can each comprise an RSV subunit composition, a nucleic acid, a viral replicon particle, a live attenuated virus, an inactivated virus particle, a recombinant viral vector, or a virus-like particle. The anti-RSV immune response inducing compositions can each comprise one or more peptides or a virosomal composition."

The specification further outlines a preferred aspect of the invention wherein:

"the first anti-RSV immune response inducing composition that is administered to a female during pregnancy does not replicate in the female after administration, and the second anti-RSV immune response inducing composition that is administered to the infant that is born from the pregnancy does replicate itself or its genome in the infant. For example, the first anti-RSV immune response inducing composition can be, for example, an RSV subunit composition, an RSV virus-like particle (VLP), one or more RSV peptides, an epitope mimetic composition, a virosomal composition, or a killed RSV virion composition, and the second anti-RSV immune response inducing composition can be, for example, a self-replicating nucleic acid (e.g., a self replicating (self-amplifying) RNA), a live attenuated virus, a heterologous live virus (e.g. an RSV-related virus with a non-human primary host), a live viral vector, a chimeric live virus, or a viral replicon particle."[48]
[48] Specification at [013].

I am satisfied that an "anti-RSV immune response inducing composition" must either induce active immunity or boost an immune response, but does not necessarily have to provide a protective immune response on its own. While the compositions exemplified in the paragraphs above are considered "anti-RSV immune response inducing compositions", any composition which induces active immunity or boosts an immune response is also considered an "anti-RSV immune response inducing composition".

"RSV antigens"

The specification states that the RSV antigen can be any desired RSV antigen.[49]

[49] Specification at [019].

The specification at [019] also states that:

"[t]he RSV antigen administered to the pregnant female and the infant may be from different serogroups, different serotypes, different immunotypes, different serovars, different biovars, different strains, different clades, or different species and/or may contain mutations (e.g., deletions). The RSV antigen administered to the pregnant female and the infant may be from different subtypes."

I conclude that the while the "RSV antigens" must comprise an RSV F glycoprotein, they can also include other RSV antigens.

Timing of the administration of one or more RSV antigens

At the hearing there was some discussion regarding the construction of the timing of the administration of RSV antigens in steps (a) and (b).

Step (a) in claim 1 defines:

"administering a first anti-RSV immune response inducing composition which provides one or more RSV antigens to a female during pregnancy"

The opponent's preferred construction of the scope of step (a) was that the first anti-RSV immune response inducing composition could be administered "before" pregnancy as long as the one or more RSV antigens are "provided" to a female during pregnancy. Under this construction, it is only the one or more RSV antigens which need to be provided "during" pregnancy, and compositions administered "before" pregnancy which "provide" the RSV antigens "during" pregnancy would fall within the scope of claim 1.

The applicant's preferred construction of the scope of step (a) was that the first anti-RSV immune response inducing composition must be administered "during" pregnancy. Under this construction, compositions administered "before" pregnancy fall outside the scope of claim 1 regardless of when the RSV antigens were "provided". The applicant submitted at the hearing, that this was the construction preferred by all three declarants.

The specification under the title of "Summary" states that the invention comprises "administering a first anti-RSV immune response inducing composition to a female during [emphasis added] pregnancy."[50] Various further references can be found in the specification that relate to administering the composition to the female "during" pregnancy.[51]

[50] Specification at [008].

[51] Specification at [010], [013], [015], [016], [017]. [020], [023], [025], [034], [035], [036], [037], [038], [0198], [0200], [0201], [0202], [0207] and [0211].

The only parts of the specification that appear to support the opponent's construction are paragraph [019] which states that the "RSV antigen" (and not the immune response inducing composition) is administered to the pregnant female, and paragraph [0211] which states that:

"female cotton rats may be infected with RSV before and/or after they are mated and boosted with an anti-RSV immune response inducing composition before and/or after they are mated to increase the production of anti-RSV antibodies during pregnancy."

Paragraph [0211] is part of Example 1 which merely introduces the animal models used to test the effectiveness and immunogenicity of the RSV immunisation regimen described. None of the subsequent examples disclose animal models where immunisation is performed "before" pregnancy.

The applicant's construction is also consistent with the views of Prof Young and Dr Lowenthal. Young states that step 1 comprises "immunising the mother during [emphasis added] pregnancy", and step 2 provides the proviso that the mother "when pregnant" and the infant are immunised.[52] Lowenthal-2 states that administration is to the "pregnant mother".[53]

[52] Young at [42].
[53] Lowenthal-2 at [41].
Step (b) in claim 1 defines:

"administering a second anti-RSV immune response inducing composition which provides one or more antigens to the infant that is born from the pregnancy, at about 4 months old or younger"

If the opponent's construction of step (a) was to be preferred, presumably the same construction would also be applied to step (b). That is, it is the RSV antigens that must be provided to the infant at about 4 months old or younger. Under this construction, if the second anti-RSV immune response inducing composition was administered at exactly 4 months, there is a possibility that the RSV antigens may not be provided to the infant until after this time. For example, if there is a delay between administration of the composition and provision of the RSV antigens. To my mind, this would result in a somewhat laboured construction, as it would be difficult to determine the length of time between administering the composition and providing the antigen. The preferred construction, and one that is most consistent with the specification and the evidence, is that that the "anti-RSV immune response inducing composition" must be administered during pregnancy.

"RSV F glycoprotein"

"RSV F" is a conserved fusion protein which fuses the viral and cellular membranes by coupling irreversible protein refolding with juxtaposition of the membranes.[54] In current models based on paramyxovirus studies, the RSV F protein initially folds into a metastable "pre-fusion" conformation.[55] During cell entry, the pre-fusion conformation undergoes refolding and conformational changes to its stable "post-fusion" conformation.[56]

[54] Specification at [004].

[55] Specification at [004].

[56] Specification at [004].

The specification states at [019]:

"The RSV glycoprotein may be in any conformation (e.g., pre-fusion conformation, post-fusion conformation) or a mixture of conformations."

The specification goes on to state that the anti-RSV immune response inducing composition may comprise "an RSV glycoprotein or a portion thereof (e.g., the ectodomain), preferably an RSV F glycoprotein."[57]

[57] Specification at [019].

Example 2 discloses an RSV trimer which is a recombinant protein comprising the ectodomain of RSV F with a deletion in the fusion peptide region preventing association with other trimers.[58] Example 4 discloses an RSV SAM^TM (Self Amplifying Message) vaccine (RNA replicon vaccine) that encodes the full length RSV F protein with a deletion in the fusion peptide region.[59]

[58] Specification at [0222].

[59] Specification at [0235].

As a result, I am satisfied that RSV F glycoprotein can include a portion thereof, such as an RSV F glycoprotein ectodomain.

Construction of claim 2

Claim 2 is the second independent claim. It reads:

"Use of an anti-respiratory syncytial virus (RSV) immune response inducing composition which provides one or more antigens in the preparation of a medicament for inducing an anti-RSV immune response in an infant, wherein inducing the anti-RSV immune response in the infant comprises:
(a) administering a first anti-RSV immune response inducing composition which provides one or more RSV antigens to a female during pregnancy; and
(b) administering a second anti-RSV immune response inducing composition which provides one or more RSV antigens to the infant that is born from the pregnancy, at about 4 months old or younger;
wherein the one or more RSV antigens comprise an RSV F glycoprotein, and at least one of (a) and (b) comprises administering the medicament to administer the anti-RSV immune response inducing composition."

Claim 2 is drafted in the form of a Swiss type claim.[60] Yates J in Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4)[61] at [120] stated:

"In my view, an invention defined by a Swiss type claim is appropriately characterised as a method or process."
[60] The generalised from of a Swiss type claim is "the use of compound X in the manufacture of a medicament for a specified therapeutic use": see Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd [2013] HCA 50, 253 CLR 284 at [248] and Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4) [2015] FCA 634 at [101].
[61] [2015] FCA 634; 113 IPR 191.

The Full Federal Court in Commissioner of Patents v AbbVie Biotechnology Ltd (AbbVie)[62] came to the same conclusion, and provided more detail about the steps of the process:

"Speaking broadly, such claims are, in form, directed to the use of a substance in the manufacture of a medicament to be administered for a specified therapeutic purpose. An invention in this form is appropriately characterised as a 'method or process', not as a 'product': Otsuka at [120]."[63]
"They are method or process claims which, in this connection, exhibit a dual character. First, they are directed to a method or process in which a substance is used to produce a medicament. Secondly, they have an additional method or process element constituted by a specific purpose to which the medication is to be used."[64]
[62] [2017] FCAFC 129 at [15].
[63] AbbVie at [15].
[64] AbbVie at [58].

I accept that Swiss type claims are directed to a method, wherein the method involves the preparation of the medicament with the intention of using it for the specific purpose recited in the claim.

As such, claim 2 defines a method, wherein the method is the manufacture of a medicament (an anti-RSV immune response inducing composition which provides one or more antigens) with an intention to use the medicament to induce an anti-RSV immune response in an infant (comprising steps (a) and (b)), wherein at least one of steps (a) and (b) comprises administering the medicament to administer the anti-RSV immune response inducing composition.
"Anti-RSV immune response"

I note that claim 2 is not limited to an intention to use the medicament to induce "protective immunity" in the infant, but rather the intention is to use the medicament to induce an "anti-RSV immune response." At the hearing, the applicant submitted that from reading claim 2 in context, the feature of "protective immunity" was implicit in the claim, having regard to the purpose for which the medicament is being prepared.
I found previously that "protective immunity" is a form of immunity (or immune response) that protects an individual from infection or a disease related aspect of that infection. I also found previously that an "anti-RSV immune response inducing composition" is a composition that either induces active immunity or boosts an immune response, but does not necessarily have to provide a protective immune response.
While the specification fails to explicitly define an "anti-RSV immune response", the specification does state that an "anti-RSV immune response inducing composition is any composition that … is effective to induce active immunity or boost an immune response, preferably [emphasis added] a protective immune response, against RSV."[65] This paragraph implies that a "protective immune response" against RSV is something more than any "anti-RSV immune response" as the latter is a preferable response as a result of administering the composition.
[65] Specification at [019].
Consistent with my previous construction of an "anti-RSV immune response inducing composition", I consider an "anti-RSV immune response" is an active immune response but does not necessarily rise to the level of a "protective immune response". I see nothing in the evidence to depart from this construction.

Construction of claim 16

Claim 16 is the third independent claim. It reads:

"A method for providing protective immunity against respiratory syncytial virus (RSV) in an infant, comprising administering to an infant at about 4 months old or younger an anti-RSV immune response inducing composition which provides one or more RSV antigens, wherein said infant was born to a female to whom an anti-RSV immune response inducing composition which provides one or more RSV antigens was administered during the time when said female was pregnant with said infant, wherein the one or more RSV antigens comprises an RSV F glycoprotein.

At the hearing there was some discussion as to whether the scope of claim 16 differed from the scope of claim 1. There is a presumption that each appended claim is of differing scope and, where possible, claims should be construed accordingly.[66]

[66] Parkinson v Simon (1894) 11 RPC 493.

The opponent submitted at the hearing that the scope of claim 16 differed from claim 1 due to the fact that claim 16 was restricted to the anti-RSV immune response inducing composition being administered "during" pregnancy, whereas claim 1 was not so limited as it was only the one or more RSV antigens that needed to be provided during the pregnancy. However, I have previously rejected this construction (see paragraph [49]) and construed claim 1 as limited to the administration of the anti-RSV immune response "during" pregnancy.
The applicant submitted at the hearing that the scope of claim 16 differed from claim 1 due to the fact that claim 1 was limited to method steps (a) and (b) being performed by the same practitioner, whereas in claim 16, only the infant needs to be vaccinated by the practitioner working the claim, so long as the mother of that infant was also vaccinated during her pregnancy (whether that vaccination was administered by the same practitioner or not).
While there is a presumption against redundancy for appended claims, this rule is not absolute and invariable, and can bend to other considerations if they are weighty enough.[67] As claim 1 and claim 16 are both independent claims, I consider that the presumption against redundancy bears little weight to my construction of claim 16.
[67] David Kahn Inc v Conway Stewart & Co Ltd [1974] RPC 279 at 308.

I note that claim 16 defines the administration of the one or more RSV antigens during the pregnancy of the female in past tense by using the word "administered" as opposed to the current tense of "administering" in claim 1. I consider this difference in wording does not change the scope of claim 16. In the two-step regime defined in claims 1 and 16, the pregnant female would necessarily be administered the one or more RSV antigens at a time prior to the administration of the RSV antigens to the infant. That is, the method of claim 1 would necessarily be performed at two different points in time, despite the use of the current tense word "administering" with regard to the pregnant female.

As a result, I also reject the applicant's construction of claim 16 above. The plain meaning of the words of claims 1 and 16 provide no such limitation on which practitioner needs to perform steps (a) and (b) of claims 1 and 16.

Construction of claim 17

Claim 17 is the fourth independent claim. It reads:

"Use of an anti-respiratory syncytial virus (RSV) immune response inducing composition which provides one or more respiratory syncytial virus (RSV) antigens in the preparation of a medicament for inducing an anti-RSV immune response in an in [sic] infant, wherein inducing the anti-RSV immune response in the infant comprises administering to the infant at about 4 months old or younger the medicament, wherein said infant was born to a female to whom an anti-RSV immune response inducing composition which provides one or more RSV antigens was administered during the time when said female was pregnant with said infant, wherein the one or more RSV antigens comprises an RSV F glycoprotein."

Consistent with my construction of claim 2 above, claim 17 defines a method, wherein the method is the manufacture of a medicament (an anti-RSV immune response inducing composition which provides one or more RSV antigens) with an intention to use the medicament to induce an anti-RSV immune response in an infant (comprising administering to the infant at about 4 months or younger the medicament), wherein said infant was born to a female to whom an anti-RSV immune response inducing composition which provides one or more RSV antigens was administered during the time when said female was pregnant with said infant, and wherein the one or more RSV antigens comprises an RSV F glycoprotein.

Novelty

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 Aicken 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 and infringement."[68]
[68] Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19; 137 CLR 228 at 235.

This test is satisfied if the alleged anticipation discloses all the essential features of the invention claimed.[69]
[69] Nicaro Holdings Pty Ltd v Martin Engineering Company [1990] FCA 40; 16 IPR 545 at 549.
To meet this requirement, the prior art must contain "clear and unmistakable directions to do what the patentee claims to have invented… A signpost, however clear, upon the road to the patentee's invention will not suffice. The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee."[70]

[70] The General Tire & Rubber Company v The Firestone Tyre and Rubber Company Limited [1972] RPC 457 at 485-

A prior disclosure will only invalidate a claim if, after having read it, the skilled addressee would, rather than could, have produced all the essential features of the claim. As stated in Canadian General Electric Co., Ltd v Fada Radio Ltd:[71]

"Where the question is solely one of prior publication, it is not enough to prove that an apparatus described in an earlier specification could have been used to produce this or that result. It must also be shown that the specifications contain clear and unmistakable directions to use it."
[71] (1930) 47 RPC 69, 90.

Furthermore:

"If … 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 that would not do so, the patentee's claim will not be anticipated."[72]

[72] General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd [1972] RPC 457, 485-486; See also AstraZeneca AB v Apotex Pty Ltd [2014] FCAFC 99 (12 August 2014) at [293].

US 5149650

US 5149650 (designated D1) was published on 22 September 1993. Consequently it is part of the prior art base.

D1 is titled "Vaccines for Human Respiratory Virus". D1 discloses compositions of DNA and proteins that are useful for preparing vaccines against human respiratory syncytial virus [HRSV].[73] In addition D1 discloses vaccines made from the native structural viral proteins or immunogenic fragments as well as methods for protecting humans by inoculation with these vaccines.[74]

[73] D1 at column 1, lines 13-15; Abstract.

[74] D1 at column 1, lines 20-23.

D1 further discloses a DNA sequence coding for human respiratory syncytial virus structural proteins selected from the group consisting of F protein, G protein, 22K protein, 9.5K protein, N protein and immunogenic fragments thereof,[75] and vaccines and methods of using these vaccines comprising these polypeptides.[76] D1 also discloses the G and F glycoproteins and immunogenic fragments thereof are the most preferred.[77]

[75] D1 at column 4, lines 32-37; claim 1.

[76] D1 at column 4, lines 52-57.

[77] D1 at column 4, lines 37-38 and 57-58.

Example 1 discloses the cloning of HRSV Glycoproteins F and G, Example 2 discloses expression of glycoproteins F and G of HRSV in CHO cells, Example 3 discloses the expression of HRSV GPF using Bovine Papilloma Virus (BPV), Example 4 discloses the expression of HRSV GPF using Baculovirus Virus, and Example 5 discloses the preparation of a vaccine for HRSV.

Example 5 further discloses that:

"The vaccine can be administered to pregnant women or to women of child-bearing age to stimulate material [sic] HRSV antibodies.[78] The female can be revaccinated as needed. Infants can be vaccinated at 2 to 3 months of age and revaccinated as necessary, preferably at 6 to 9 months of age. Babies born to unvaccinated mothers can be vaccinated at 2 to 3 months of age."[79]
[78] Lowenthal-1 states at [101] with regard to the reference to Example 5: "I believe "material" should be "maternal" because "material antibody" doesn't mean anything to me".
[79] D1 at column 20, lines 60-66.

The opponent submits that the teaching of D1 indicates that all pregnant mothers can be vaccinated, and that all infants can be vaccinated at 2 to 3 months of age.[80]

[80] Opponent's Written Submissions at [79].

The applicant submits that D1 does not disclose the two step regimen claimed for two reasons. Firstly, D1 does not disclose what antigens "the vaccine" of Example 5 provides, and it cannot be inferred that the vaccine of Example 5 necessarily provides an antigen that comprises an RSV-F glycoprotein, as Example 5 appears in the context of the broad disclosure of D1, which includes DNA sequences, compositions and vaccines based upon each of the F protein, the G protein, the 22K protein, the 9.5K protein or the N protein.[81] Secondly, D1 does not disclose the claimed two-step regimen, as the permissive language "can be" (on line 60, column 20) allows vaccinating mothers outside of pregnancy, vaccinating children born to mothers who were vaccinated outside of pregnancy, and vaccinating children who were born to unvaccinated mothers.[82]

[81] Applicant's Written Submissions at [102]-[103].

[82] Applicant's Written Submissions at [106].

The opponent responds by submitting that the teaching of D1 is explicit when the passage in Example 5 is read in context.[83] The opponent argues that the passage also suggests that "babies to unvaccinated mothers can be vaccinated at 2 to 3 months of age" highlights that the earlier sentence, in contradistinction, is teaching that vaccination is about vaccinating the infant born from the vaccinated mother, and to interpret the language otherwise would render the sentence referring to "babies born to unvaccinated mothers" meaningless.[84]
[83] Opponent's Written Submissions at [81].
[84] Opponent's Written Submissions at [81].

Dr Lowenthal reads Example 5 as disclosing vaccination of women of child bearing age to stimulate maternal HRSV antibodies, boosting either before or during pregnancy,[85] and vaccination of infants of either vaccinated or unvaccinated mothers at 2 to 3 months of age.[86]

[85] Lownethal-1 at [101].

[86] Lowenthal-1 at [103].

Prof Young's interpretation of D1 is that "D1 does not appear to describe an immunisation regimen which is the same as that defined in the claims of the opposed application"[87] as "there is no explicit teaching of the two-step regimen described in, e.g., claim 1 of the opposed application."[88]

[87] Young at [72].

[88] Young at [72].

In my view, D1 fails to disclose clear and unmistakable directions for a PSA to perform the claimed two-step regimen. D1 fails to disclose what antigens the vaccine of Example 5 delivers. D1 discloses five possible polypeptides that can be used in the vaccine including the F protein, the G protein, the 22K protein, the 9.5K protein and the N protein.[89] Notwithstanding the reference in D1 that states that the F protein and the G protein are most preferred,[90] in my opinion, D1 falls short of providing clear and unmistakable directions to use an RSV F glycoprotein antigen in the vaccination of a pregnant female, and to subsequently use an RSV F glycoprotein antigen in the vaccination of an infant born from that female. As a result, I am not satisfied that any of the claims lack novelty in view of D1.
[89] D1 at column 4, lines 52-57; claim 1.
[90] D1 at column 4, lines 57-58.

Sales and Wang (2003)

Sales, V. and Wang, E. EL., Paediatric Child Health, 2003, Vol. 8, No. 10, pages 605-608 (designated D2) was published on 1 December 2003. Consequently it is part of the prior art base.

D2 is titled "Respiratory syncytial virus vaccine: Is it coming?". D2 discloses that protein-based vaccines have been evaluated in clinical trials and are promising candidates for RSV-primed populations or for maternal vaccination to provide early life protection.[91]

[91] D2 - Abstract.

D2 further discloses that:

"hospitalization for RSV-bronchiolitis peaks in the first two months of age during the RSV season. Illness is also more severe in this age group. Thus, vaccination programs must be designed to induce protection in very young infants."[92]
[92] D2 at page 606, left hand column, first dot point.

D2 discloses two main approaches to vaccine development against RSV that have led to clinical trials, a live-attenuated vaccine in young infants and a subunit vaccine approach in other populations.[93] In addition D2 discloses that live-attenuated viruses are developed for intranasal administration to very young infants (one-month-old) and are expected to confer protection against severe RSV-bronchiolitis and hospitalization within the first six months of age.[94] D2 further discloses that subunit vaccines are targeted to older populations, including children with underlying pulmonary disease such as asthma and cystic fibrosis, or immunocompromised children.[95]

[93] D2 at page 606, left hand column, last paragraph.

[94] D2 at page 606, right hand column, first full paragraph.

[95] D2 at page 606, right hand column, first paragraph under "Subunit RSV Vaccines".

In relation to subunit RSV vaccines, D2 discloses that:

"Maternal immunization with such vaccines to protect their infants has also been proposed to increase neutralizing antibody titres in infants transplacentally. This route circumvents poor immune responses of infants to vaccination and affords protection of term or near term infants within the first six months of life."[96]
[96] D2 at page 606, right hand column, first paragraph under heading "Subunit RSV Vaccines".

Table 1 discloses preventative strategies for paediatric RSV disease. For the "Patient Population" of "Infants born at term" the "RSV prophylactic options" are described as:
"Maternal vaccination in third trimester. May be followed by live-attenuated vaccine to protect beyond maternal antibody decay."[97]

[97] D2 - Table 1.

The opponent submits that D2 "discloses maternal vaccination in the third trimester … and then administration of a live attenuated vaccine for the 'infants born at term'",[98] and that "[i]t is without argument that an infant born at term is not an infant that is older than 4 months old."[99]

[98] Opponent's Written Submissions at [87].

[99] Opponent's Written Submissions at [87].

The applicant submits that D2 does not disclose the two step regimen claimed for four reasons. Firstly, D2 does not provide clear and unmistakable directions to administer an anti-RSV immune response inducing composition to infants, as the word "may" in Table 1 teaches that infants born at term may, or may not, be vaccinated.[100] Secondly, D2 does not disclose when any live attenuated vaccine should be administered to infants born at term.[101] Thirdly, the words "[m]ay be followed by live attenuated vaccine to protect beyond maternal antibody decay" in Table 1 are likely to be understood as contemplating the possibility of infant vaccination after the first six months of life, when maternal antibodies have decayed.[102] Finally, D2 does not provide clear and unmistakable directions to administer to both mother and infant, an anti-RSV immune response inducing composition that will provide RSV antigens that comprise an RSV F glycoprotein, as D2 discusses vaccines providing each of F, G and M proteins.[103]

[100] Applicant's Written Submissions at [114].

[101] Applicant's Written Submissions at [115].

[102] Applicant's Written Submissions at [118].

[103] Applicant's Written Submissions at [119].

There was some discussion at the hearing about the disclosure in Table 1 relating to the timing of the live-attenuated vaccine to infants born at term to protect beyond maternal antibody decay. The opponent's preferred construction was that this vaccine was administered to infants while maternal antibodies were present in order to provide "protection" beyond maternal antibody decay. The applicant's preferred construction was that this vaccine was "administered" to infants after (or beyond) the decay of maternal antibodies.

Dr Crawford reads Table 1 as:

"Those born at term are said to be protected first by vaccinating the mother in the third trimester, and then vaccinating with a live virus, before [emphasis added] maternal antibody from the vaccination decays."[104]
[104] Crawford-1 at [135].

Dr Crawford reads Table 1 as indicating that infants are given live-attenuated vaccine at term.[105] Dr Crawford goes on to state that the word "may" in "may be followed by live-attenuated vaccine" at "a stretch … [is taken as] … meaning that the infant vaccine may follow the maternal vaccination or the mother may not be vaccinated."[106]

[105] Crawford-3 at [35].

[106] Crawford-1 at [137].

Prof Young also states that the word "may" in "may be followed by live-attenuated vaccine" means that the infant "may or may not be vaccinated."[107] Furthermore, Prof Young's opinion is that Table 1 of D2 discloses nothing about timing of infant vaccination if it is to occur.[108] His view is that as D2 is suggesting vaccination of an infant with a attenuated live virus, this would imply that the infant would likely be older than 4 months of age when vaccinated given (1) the well-known issue of maternal antibody suppression, and (2) infants <= 4 months of age would likely mount a poor immune response to an attenuated live vaccine because of the immaturity of the immune system.[109] Prof Young concludes that it would be more reasonable to vaccinate the infant at a later age (i.e. after maternal antibodies have decayed) as D2 states that vaccination of pregnant women "affords protection of term or near term infants within the first six months of life."[110]

[107] Young at [75].

[108] Young at [75].

[109] Young at [75].

[110] D2 at page 606, right hand column, first paragraph under heading "Subunit RSV Vaccines"; Young at [75].

In my view, D2 fails to disclose clear and unmistakable directions for a PSA to perform the claimed two-step regimen. I come to this view for several reasons. Firstly, D2 fails to disclose what antigens the RSV prophylactic options disclosed in Table 1 deliver. D2 discloses the use of live-attenuated RSV vaccines as well as subunit RSV vaccines based on F proteins,[111] F, G and M proteins,[112] and G protein fragments.[113] Secondly, D2 does not explicitly disclose when the live-attenuated vaccine is to be delivered to an infant, if at all. I construe Table 1 as disclosing an RSV prophylactic option for infants born at term which comprises maternal vaccination of the infant's mother during the third trimester, and optionally vaccinating the infant with a live attenuated vaccine at a point in time near the end of maternal antibody decay. D2 discloses that maternal administration of subunit RSV vaccines affords protection of term or near term infants within the "first six months of life."[114] This disclosure in D2 adds weight to the construction of Table 1, wherein the live-attenuated vaccine is administered to infants at or around 6 months in order to protect beyond the passive immunity acquired transplacentally. I construe the reference in D2 to live-attenuated vaccines being designed for administration to very young infants (one-month old), as relating to a stand-alone, single vaccination strategy of infants within the first six months of life who are not protected by passive maternal antibodies and are otherwise at risk of infection. This construction is also consistent with the view of Prof Young and the broadest possible interpretation given by Dr Crawford. This construction is consistent with the teaching in the last paragraph of D2 which considers a live-attenuated vaccine and a maternal immunisation program are alternative strategies rather than a combined strategy. As a result, I am not satisfied that any of the claims lack novelty in view of D2.

[111] D2 at page 606, right hand column, last paragraph.

[112] D2 at page 607, left hand column, first full paragraph.

[113] D2 at page 607, left hand column, second full paragraph.

[114] D2 at page 606, right hand column, first paragraph under heading "Subunit RSV Vaccines".

WO 2009/042794

WO 2009/042794 (designated D3) was published on 2 April 2009. Consequently it is part of the prior art base.

D3 is titled "Vaccine for RSV and MPV". D3 discloses alphavirus vectored vaccine constructs encoding paramyxovirus proteins that find use in the prevention of respiratory syncytial virus.[115] In addition D3 discloses that F and G proteins have been used separately or in combination in many experimental RSV vaccines, and that purified F protein alone or F protein expressed from a recombinant viral vector such as vaccinia virus induces RSV-specific neutralising antibodies, CD8+ cytotoxic T lymphocytes and protection against subsequent RSV challenge in mice or cotton rats.[116]

[115] D3 - Abstract.

[116] D3 at page 2, lines 22-26.

More specifically, D3 discloses a method of inducing an immune response in an animal comprising administering to said animal an infectious virus particle comprising a viral replicon comprising (a) a Venezuelan equine encephalitis virus (VEE) positive-sense RNA genome lacking at least one functional gene for an VEE structural gene; and (b) a paramyxovirus surface glycoprotein coding region under the control of a promoter active in eukaryotic cells.[117] D3 further discloses that the paramyoxovirus surface glycoprotein coding region may be from respiratory syncytial virus, such as RSV F or G, or from human metapneumovirus (hMPV), such as hMPV F.[118] Furthermore D3 discloses administering the infectious virus particle three times,[119] and that the animal receiving the infectious virus particle may be a human "neonate comprising maternal antibodies."[120]

[117] D3 at page 5, lines 20-25.

[118] D3 at page 5, lines 25-27.

[119] D3 at page 6, lines 1-2.

[120] D3 at page 6, line 5.

The opponent submits that D3 teaches multiple injections (of either RSV G or RSV F) and, in context, teaches that the maternal antibodies that are being discussed may come from a vaccinated mother.[121] The applicant submits that D3 does not disclose the vaccination of an infant's mother, let alone vaccination during pregnancy.[122] The applicant further argues that the presence of antibodies of maternal origin disclosed in D3, does not imply vaccination of the infant's mother because the target population of D3 is young infants, almost all mothers to newborns are going to have some level of circulating antibodies against RSV, and at the time of publication of D3 there was no approved vaccine for RSV that could be administered to a mother.[123]

[121] Opponent's Written Submissions at [91].

[122] Applicant's Written Submissions at [121].

[123] Applicant's Written Submissions at [122].

Dr Lowenthal identifies three circumstances a pregnant woman could have antibodies to RSV which are that the woman has RSV infection, has recently been infected with RSV, or has been vaccinated for RSV.[124] With regard to the source of the maternal antibodies disclosed in D3, Dr Lowenthal states that such antibodies could either come from a woman who has been vaccinated with RSV or a woman who has RSV infection, "although perhaps more likely" it means from a vaccinated mother.[125] Furthermore, Dr Lowenthal considers that D3 discloses "the use of the RSV G protein as a vaccine antigen and that their overall strategy is to induce a mucosal IgA response after vaccination."[126]

[124] Lowenthal-1 at [97].

[125] Lowenthal-1 at [98].

[126] Lowenthal-1 at [95].

In response to the disclosure in D3 of vaccination of a neonate "comprising maternal antibodies", Prof Young states at [77]:

"the maternal antibodies could have been raised in the mother as a result of vaccination before or during pregnancy, by infection of the mother during pregnancy, or as a result of previous infection with RSV."
…

"[a] more sensible conclusion is that the antibodies were acquired by the pregnant mother as a result of existing or past RSV infection."

Prof Young goes on to conclude:

"The authors show that their vaccine delivery system could avoid any deleterious effects of maternally derived antibodies, but there is no teaching towards vaccination of maternal antibodies or discussion of the merits of such a strategy; merely that maternal antibodies can be a problem for incoming vaccines."[127]
[127] Young at [78].

In my view, D3 fails to disclose clear and unmistakable directions for a PSA to perform the claimed two-step regimen. D3 fails to disclose vaccination of a female during pregnancy. While D3 does reference vaccinating a neonate comprising maternal antibodies, there is no disclosure that the source of these maternal antibodies is from maternal "vaccination", let alone maternal vaccination of a mother "during" pregnancy. Dr Lowenthal only considered that it was only "perhaps more likely" that the maternal antibodies came from a vaccinated mother, and to the contrary, Prof Young's evidence was that the maternal antibodies were acquired by the pregnant mother as a result of natural RSV infection. Moreover, the only experiment in D3 relating to immunogenicity in the presence of passively-acquired antibodies, related to transferring serum from mice that had been infected with RSV and not vaccinated.[128] This experiment in D3 is in contrast to the opposed application which involved assessing maternal antibody immunosuppression by infecting mice naturally with RSV and subsequently boosting these mice with an RSV vaccine, before transferring immune serum to naïve mice. I consider this disclosure in D3 adds weight to Prof Young's evidence that the maternal antibodies disclosed in D3 are likely to come from natural infection of the mother. Furthermore, D3 fails to disclose a two-step regimen comprising administration of an F glycoprotein. D3 discloses that the paramyoxovirus surface glycoprotein may be RSV F or G, or hMPV F. Dr Lowenthal's evidence suggests that D3 teaches the use of the RSV G protein as a vaccine antigen to induce a mucosal IgA response after vaccination. As a result, I am not satisfied that any of the claims lack novelty in view of D3.
[128] D3 at page 53, lines 12-16.

WO 2008/133663

WO 2008/133663 (designated D4) was published on 6 November 2008. Consequently it is part of the prior art base.

D4 is titled "Codon Modified Immunogenic Compositions and Methods of Use". D4 discloses immunogenic compositions comprising codon modified genes that encode viral proteins and/or glycoproteins or fragments.[129] The immunogenic compositions disclosed in D4 are useful in various methods of treatment, such as preventing or treating viral infection.[130] In addition D4 discloses that the immunogenic compositions of the invention include codon-modified genes or fragments thereof that encode viral surface proteins such as fusion (F), membrane anchored attachment (Gr), matrix (M) or (M2), small hydrophobic (SH), nucleoprotein (N), surface (HN) glycoproteins, or fragments.[131]

[129] D4 - Abstract.

[130] D4 - Abstract.

[131] D4 at page 53, lines 28-33.

D4 discloses the use of vector-based gene delivery for RSV, including the use of adenoviral vectors such as Ad5 and Ad35.[132] D4 further discloses the delivery of Ad35 as a first priming dose at birth, followed by an Ad5 boost at 6 months of age.[133] D4 goes on to state:

"The prime-boost regimen is especially advantageous to practice in a young animal, as it allows vaccination or immunization at an early age, for instance, the first administration in the prime-boost regimen when practiced on a young animal can be at an age at which the young animal has maternal antibodies."[134]
[132] D4 at page 30, line 7 – page 31, line 2.
[133] D4 at page 52, lines 31-32.
[134] D4 at page 53, lines 1-4.

D4 further states that it is advantageous to employ the prime-boost regimen in pregnant females or females prior to giving birth, laying, or insemination.[135]

[135] D4 at page 52, lines 18-19.

The opponent submits that the evidence of Dr Lowenthal supports the construction of a young animal having maternal antibodies as having the maternal antibodies provided by vaccination of the mother with the same vaccine.[136] The applicant submits that D4 is not an anticipation for similar reasons to D3, with the additional reason that D4 discloses a broad range of immunogenic proteins or fragments of the RSV Gr, M, M2, SH, N, HN and F proteins, and there is no clear and unmistakable directions in D4 to vaccinate specifically with the RSV F glycoprotein, as distinct from a different kind of antigen.[137]

[136] Opponent's Written Submissions at [93]; Lowenthal-1 at [94].

[137] Applicant's Written Submissions at [124] and [125].

Lowenthal-1 states at [94]:

"In my view, the detectable maternal antibodies that are referred to under the "Prime Boosting" subheading at page 52 are most likely antibodies that result from the vaccination of the mother."

Dr Lowenthal goes on to state that maternal antibodies arising from a mother naturally infected with RSV is less likely because the majority of women will not have an active RSV infection at the time of pregnancy.[138]

[138] Lowenthal-1 at [94].

In my view D4 fails to disclose clear and unmistakable directions for a PSA to perform the claimed two-step regimen. Similarly to D3, D4 fails to disclose vaccination of a female during pregnancy. Although D4 does disclose that a prime-boost regimen can be practiced on a young animal at an age at which the young animal has maternal antibodies, there is no explicit disclosure of these maternal antibodies arising from vaccination of the mother during pregnancy, nor can such a disclosure be inferred. D4 discloses that the prime-boost regimen can be employed in pregnant females or females prior to giving birth, laying or insemination. This disclosure implies that a prime and a boost must be given to either a pregnant female or a female before becoming pregnant. Vaccination of a pregnant female and subsequent vaccination of an infant born from that female would not be considered a prime-boost regimen but rather a prime in the mother and a prime in the infant. Furthermore D4 discloses that seven possible antigens, one of which being the RSV F antigen, could be used in the disclosed DNA vaccine. As a result, I am satisfied that D4 fails to provide clear and unmistakable directions to specifically perform a two-step vaccination regimen, with two vaccinations of the RSV F glycoprotein wherein the first vaccination is provided to a mother during pregnancy and the second vaccination is provided to an infant born from that pregnancy at about 4 months old or younger. Therefore, I am not satisfied that any of the claims lack novelty in view of D4.

Martinez et al (1999)

Martinez, X. et al., European Journal of Immunology, 1999, Vol. 29, pages 3390-3400 (designated D19) was published on 8 October 1999. Consequently it is part of the prior art base.

D19 is titled "Combining DNA and protein vaccines for early life immunization against respiratory syncytial virus in mice". D19 discloses the study of early life responses to respiratory syncytial virus (RSV)-F DNA and RSV-F protein immunisation in murine models of neonatal immunisation.[139] In addition D19 discloses the immunisation of female BALB/C mice three times with alum-adsorbed RSV-A prior to mating, so as to induce high levels of anti-RSV-A Ab,[140] which resulted in significant titres of RSV-F specific maternal antibody which were efficiently transferred to their offspring.[141] D19 further discloses that two-week-old pups from immune and control mothers were bled and immunised with either the RSV-F protein or DNA vaccine.[142]

[139] D19 - Abstract.

[140] D19 at page 3392, right hand column, 2.2.

[141] D19 at page 3392, right hand column, 2.2.

[142] D19 at page 3392, right hand column, 2.2.

The opponent submits that D19 discloses an immunisation regime involving the combination of maternal immunisation and immunisation of offspring for protection against RSV.[143] The applicant submits that there is no disclosure in D19 that mothers should be vaccinated for the purpose of conferring protective immunity against RSV to infants.[144]

[143] Opponent's Written Submissions at [95].

[144] Applicant's Written Submissions at [130].

Lowenthal-1 at [100] states:

"In one part of the study, pregnant female mice were immunized with RSV-A in alum before mating. The resulting progeny were immunized at 2 weeks of age with RSV-F DNA or RSV F protein or both."

Young at [80], in relation to D19 states:

"It does not, however, describe an immunisation regimen involving maternal immunisation and immunisation of an infant at <= 4 months of age as defined in the claims of the opposed application."

Dr Lowenthal disagrees with Professor Young's assessment of D19, submitting that D19 describes the vaccination of female mice, the generation of RSV antibodies and the maternal transfer of these antibodies to the offspring.[145] To support his assessment, Dr Lowenthal references an extract of D19 which states that "[f]emale BALB/c mice were immunized three times with alum-adsorbed RSV-A prior to mating [emphasis added]".[146]

[145] Lowenthal-3 at [18].

[146] Lowenthal-3 at [18]; D19 at page 3392, right hand column, 2.2.

In my view D19 fails to disclose clear and unmistakable directions for a PSA to perform the claimed two-step regimen. Similarly to D3 and D4, D19 fails to disclose vaccination of a female during pregnancy. Dr Lowenthal contradicts himself in his first declaration where he states that "pregnant" female mice were immunised, but then goes on to say in the same sentence that the female mice were immunised before mating.[147] I think it clear that D19 does not disclose vaccination of a pregnant female, as the document explicitly discloses immunisation prior to mating. As a result, I am not satisfied that any of the claims lack novelty in view of D19.
[147] Lowenthal-1 at [100].
Conclusion on novelty
This ground of opposition fails. The opponent has not shown that the claims are not novel in light of their evidence.

Inventive Step

The test for whether an invention is obvious is to ask whether it would have been a matter of routine to proceed to the claimed invention. In Wellcome Foundation Ltd v V. R. Laboratories (Aust.) Pty Ltd[148] Aickin J stated:

"The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they are the steps of the inventor or not."
[148] [1981] HCA 12 at [45]; 148 CLR 262 at 286.

More recently, the High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd[149] referred with approval to this approach and further held:

"That way of approaching the matter has an affinity with the reformulation of the ‘Cripps question’ by Graham J in Olin Mathieson Chemical Corporation v BiorexLaboratories Ltd [1970] RPC 157. This court had been referred to Olin in the argument in Wellcome Foundation. Graham J had posed the question:
'Would the notional research group at the relevant date in all the circumstances directly be led as a matter of course to try [the claimed invention] in the expectation that it might well produce [the desired result]?'
[149] [2002] HCA 59; 56 IPR 129 at 142-143.

That approach should be accepted."
Common general knowledge

Common general knowledge (CGK) is the background knowledge and experience available to all those working in the relevant art:

"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."[150]

Administering a RSV F glycoprotein

[150] Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd [1980] HCA 9; 144 CLR 253 at 292.

The opponent submits that F proteins were well known to induce production of neutralising antibodies in a host infected with virus or vaccinated with F protein.[151]
[151] Opponent's Written Submissions at [42]; Lowenthal-1 at [24].
The applicant submits that, at the priority date, industry and research groups were working on a range of different RSV vaccine candidates, including subunit proteins (e.g. the RSV F, RSV G and RSV M proteins), inactivated virion, live-attenuated virion and DNA-based immunogens.[152]
[152] Applicant's Written Submissions at [26]; Young at [67].
Dr Lowenthal's evidence suggests that the RSV-F protein was the favoured candidate for use in a RSV vaccine, as the alternative RSV-G was not considered safe.[153] Dr Lowenthal provides evidence that F proteins were well known to induce production of neutralizing antibodies in a host infected with virus or vaccinated with F protein.[154] Dr Lowenthal also states that at 2011, it was known that an F protein could be presented in a vaccine or immune stimulating composition in a number of ways for the induction of protective immunity.[155] Dr Lowenthal further states that:
"[i]f there was a suspicion that the G protein was unsafe, then that's all the more reason to keep on with the RSV F protein, or other forms of vaccine, that people had been working on since the mid-90s."[156]
[153] Lowenthal-3 at [17].
[154] Lowenthal-1 at [24].
[155] Lowenthal-1 at [17].
[156] Lowenthal-3 at [17].
Prof Young's evidence states that there were a number of vaccine candidates other than the F glycoprotein being evaluated (e.g. RSV G protein, RSV M protein, live attenuated virus) at the priority date of the opposed application.[157] However Prof Young also states that that there was renewed interest in the industry on subunit vaccines (mainly based on the fusion, F protein) which were generally considered to be safer than live inactivated virus, and many groups, including his, have continued to focus on the F-protein.[158] In relation to the G protein, Prof Young's evidence provides that "in 2011 there was a body of work that showed that certain RSV proteins, in particular the viral surface G-protein, may not be safe".[159]
[157] Young at [67].
[158] Young at [20].
[159] Young at [28].
On the evidence before me, I consider the preference for the use of the F protein in a sub-unit vaccine for RSV to be part of the CGK, due to the ability of the F protein to induce protective immunity, and the lingering safety concerns surrounding the G protein.
Administering a RSV F glycoprotein to a female during pregnancy

The opponent submits that pregnancy was not an absolute contraindication for the use of vaccines,[160] and examples of vaccination regimes based on placental transfer of maternal antibody that had been widely used in Australia include DTPa and seasonal influenza.[161]

[160] Opponent's Written Submissions at [31]; Crawford-1 at [81].

[161] Opponent's Written Submissions at [35]; Crawford-1 at [82].

The applicant submits that Dr Crawford's view that vaccinating both (1) pregnant mothers and (2) infants at 2 months old for acellular pertussis using the dTpa vaccine,[162] is not the generally accepted and assimilated vaccination practices as set out in The Australian Immunisation Handbook (9^th ed, 2008)(Handbook)[163] and The National Immunisation Program Schedule (valid 1 July 2007)(National Schedule).[164] The applicant submits that the Handbook recommends vaccinating pregnant women with dTpa vaccine only if the pregnant woman is "in close contact with infants e.g. childcare, neonatal units."[165] The Handbook goes on to state that "[a]ll women who are planning pregnancy should be encouraged to receive a single dose of dTpa before [emphasis added] pregnancy; if not given before pregnancy, it should be given as soon as possible after delivery."[166]

[162] Crawford-1 at [86].

[163] The Australian Immunisation Handbook (9^th ed, 2008)(Exhibit NC1-6).

[164] The National Immunisation Program Schedule (valid 1 July 2007)(Exhibit NC1-3).

[165] Handbook at page 87.

[166] Handbook at page 87.

The applicant submits that the Handbook recommends that most other vaccines were "not usually recommended"[167] during pregnancy, and the CGK practice was to vaccinate prospective mothers before pregnancy if this was necessary and appropriate, having regard to their vaccination history and the applicable risk profile.[168] The applicant further submits that no routine practice existed of vaccinating women while pregnant,[169] and that the influenza vaccine is only recommended during pregnancy if the woman's pregnancy included a second or third trimester during the influenza season.[170] Furthermore, the evidence of Prof Young states that "maternal immunisation would have been one of the strategies considered in 2011 for protecting infants",[171] indicating that strategies other than vaccinating the mother, such as vaccinating the infant only would have also been considered.
[167] Handbook at page 85.
[168] Applicant's Written Submissions at [43].
[169] Applicant's Written Submissions at [44]; National Schedule at [31]-[35].
[170] Applicant's Written Submissions at [45]; Handbook, at page 88.
[171] Young at [61].
The opponent relies on the evidence of Dr Lowenthal who states that RSV was known to be a major problem in children younger than 4 months, so infants of this age were being considered for vaccination, and vaccines were being developed for the purposes of generating transplacental antibody which could protect children younger than 4 months at the time when they are susceptible to RSV infection.[172] Dr Lownethal concludes that "if a vaccine had been available, it would have inevitably been used in pregnant women and in infants younger than 4 months".[173]
[172] Lowenthal-3 at [16].
[173] Lowenthal-3 at [16].

On the evidence before me, I do not consider that routine vaccination of females during pregnancy with RSV-F glycoprotein was part of the CGK. While DTPa and influenza vaccines have been administered to pregnant women in Australia, these vaccines are only administered to pregnant women in certain circumstances. DTPa vaccine is only routinely administered to pregnant women if the pregnant woman is in close contact with infants, for example by working in childcare or in a neonatal unit.[174] Similarly, the influenza vaccination is only routinely administered to pregnant women if the woman's pregnancy included a second or third trimester during the influenza season.[175] Given Prof Young's evidence that no single regimen in the CGK was appropriate for all pathogens or vaccine types,[176] and the evidence that the administration of vaccines during pregnancy was "not usually recommended",[177] I do not consider it would be CGK for a PSA to administer the RSV F glycoprotein to a pregnant women, as the majority of vaccines administered in Australia are not administered to pregnant women, and the few that are, are administered only in certain circumstances.

Administering a RSV F glycoprotein to an infant at about 4 months old or younger

[174] Handbook at page 87.

[175] Handbook at page 88.

[176] Young at [59].

[177] Handbook at page 85.

The opponent submits that a significant factor in the timing of a regimen comes down to when the individual is likely to encounter the relevant pathogen.[178] The opponent submits that infancy was not an absolute contraindication for the use of vaccines in Australia,[179] and examples of vaccination of neonates and infants less than 4 months old that were practiced routinely across Australia include hepB, DTPa, Hib, IPV, 13vPCV and Rotavirus.[180] The opponent also submits that if the vaccination was shown to be useful by partially priming a neonate to a pathogen then the PSA would vaccinate even if sub optimal protection is obtained.[181] The opponent further submits that RSV is a virus which was known to be of particular concern to neonates and pre-term infants.[182]
[178] Opponent's Written Submissions at [30]; Crawford-1 at [45].
[179] Opponent's Written Submissions at [36]; Crawford-1 at [50].
[180] Opponent's Written Submissions at [38]; Crawford-1 at [56].
[181] Opponent's Written Submissions at [40]; Crawford-1 at [67], [72], [73], [75], [76], [80], [93] and [94].
[182] Opponent's Written Submissions at [41].
The applicant submits that infants are particularly at risk of RSV infection in the first 6 months of life,[183] and there is no regulatory approved RSV vaccine available anywhere in the world.[184]
[183] Applicant's Written Submissions at [23].
[184] Applicant's Written Submissions at [23]; Young at [18].

Maternal antibody immunosuppression results from maternal antibodies circulating in an infant which can neutralise incoming vaccines by binding to the antigen provided by the vaccine, and, therefore, rendering the vaccination of the infant less effective or ineffective.[185]

[185] Applicant's Written Submissions at [30].

The opponent submits that maternal immune suppression was considered to be more of an academic interest rather than a factor relevant to development or implementation of a vaccination regimen in the sense that it did not prevent the vaccination of neonates at birth from various vaccines.[186] Dr Lowenthal is of the view that maternal immune suppression has never been a factor in the design of a vaccine or regimen for its use, with the focus being on obtaining maximum immunogenicity.[187] Furthermore, with regard to maternal antibody immunosuppression, Dr Crawford's evidence suggests that medical practitioners would have administered a vaccine even if that vaccine might otherwise have been suboptimal,[188] as the alternative path of not vaccinating at all at less than 4 months, would be undesirable in circumstances where neonates would be exposed to RSV at a young age.[189]

[186] Opponent's Written Submissions at [46]; Crawford-1 at [64].

[187] Lowenthal-1 at [38].

[188] Crawford-3 at [25].

[189] Crawford-1 at [73] and [74].

The applicant submits that maternal antibodies generally circulate in an infant between about 4-8 months, depending on the antibody type, and for some pathogens (e.g. measles), maternal antibodies can circulate for substantially longer (e.g. 10 to 12 months).[190] Prof Young submits that maternal antibody immunosuppression is one important consideration when devising a method for immunising an infant, for example, the vaccination for measles is not given until the infant is 12 months old.[191] According to Prof Young, other important considerations for devising a vaccination regime for an infant include the vaccine type, the disease epidemiology (e.g. period of peak incidence or likelihood that the infant will encounter the pathogen at a young age) and the risk that infection poses to the infant.[192] The applicant further submits that a number of strategies have been identified for overcoming maternal antibody immunosuppression including alterations to vaccine dose, mucosal immunisation, vectored vaccines, ISCOM vaccination, plasmid DNA vaccines and maternal immunisation alone.[193]
[190] Applicant's Written Submissions at [29].
[191] Young at [29] and [30].
[192] Young at [35] and [55].
[193] Applicant's Written Submissions at [33].

On the evidence before me, I do not consider that administering an RSV F glycoprotein to an infant at about 4 months old or younger was part of the CGK. While a significant factor in the timing of a regimen is when the individual is likely to encounter the relevant pathogen, which is infancy in the case of RSV, the evidence suggests that maternal antibody immunosuppression is, at the very least, a "consideration" when devising a method of immunising an infant. Although Prof Young's evidence suggests that it is now known that maternal antibody immunosuppression is considered less of a concern for protein-based vaccines, there was no evidence that this was CGK at the priority date of the opposed application.[194] If the mother of an infant was vaccinated while pregnant, the infant could be vaccinated at an early age while maternal antibodies are still circulating resulting in suboptimal protection, or alternatively, vaccination of the infant could be delayed until the protection from maternal derived antibodies had waned, as is the case with measles. I think the latter is the more likely course. I do not consider it would be CGK for a person skilled in the art to administer the RSV F glycoprotein to an infant at about 4 months old or younger, due to the potential of maternal antibody immunosuppression.
[194] Young at [29].
Inventive step in light of the common general knowledge
The question is whether a notional research group, as of 2011, in all the circumstances would be directly led as a matter of course to try the claimed regimen in the expectation that it might well produce a useful result?

The opponent submits that this question would be answered in the positive in circumstances where it was known that vaccines using the RSV-F protein were under development and those vaccines could be used in pregnant women and infants.[195] The opponent further submits that it would be expected that infants under 4 months would have the vaccine administered in circumstances where RSV is a significant disease in neonates with disastrous consequences.[196]
[195] Opponent's Written Submissions at [106].
[196] Opponent's Written Submissions at [106].
The applicant submits that there was no infant vaccination, for any disease, that was implemented using a "two step" method that involved (1) vaccinating the mother while pregnant and then (2) vaccinating the infant shortly after birth.[197] The applicant submits that the opponent's submission that RSV-F protein vaccines under development could be used in pregnant women and infants do not form part of the CGK.[198]
[197] Applicant's Written Submissions at [36]; Young at [59].
[198] Applicant's Written Submissions at [157]-[160].
The relevant question in this case is, in light of the CGK alone, would a PSA be directly led as a matter of course to (a) administer a composition comprising an RSV F glycoprotein to a female during pregnancy, and (b) administer an RSV F glycoprotein to an infant born from that pregnancy at about 4 months old or younger, with the expectation that this method may result in providing the infant protective immunity against RSV?
I found above that it would not have been CGK for a PSA to vaccinate an expectant mother with an RSV F glycoprotein, and it also would not have been CGK for a PSA to vaccinate an infant at about 4 months or less. It follows that I do not consider that a PSA, in light of the CGK alone, would have been directly led as a matter of course to vaccinate a pregnant woman with an RSV F glycoprotein and vaccinate at about 4 months or less, the infant born from that mother with an RSV F glycoprotein. As such, I am not satisfied that any of the claims lack inventive step in light of the CGK alone.
Would the PSA have ascertained, understood and regarded as relevant prior art documents D1-D4, D10, D18 and D19?

Section 7(3) of the Patents Act as it was at 12 April 2013 states:

"The information for the purposes of subsection (2) is:
Any single piece of information; or
A combination of any 2 or more pieces of prior art information;
Being information that the skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood, regarded as relevant and, in the case of information mentioned in paragraph (b), combined as mentioned in that paragraph."

Section 7(3) says that before information in a document can be considered for the purposes of inventive step, it is necessary to decide whether the PSA “could, before the priority date of the relevant claim, be reasonably expected to have ascertained” the information.
The opponent submits that each of the documents (D1-D4, D10, D18 and D19) would be ascertained, understood and regarded as relevant because there is no evidence led by the applicant that these documents would not be ascertained, and each of these documents would be considered relevant because they relate to a vaccine for RSV which is in the same technical field as the opposed application.[199]
[199] Opponent's Written Submissions at [117].
The applicant submits that the opponent has led no evidence that establishes any prior art document could reasonably be expected to have been ascertained by the hypothetical skilled person seeking to solve the problem,[200] rather the prior art documents appear to simply have been given to the opponent's witness, Dr Lowenthal, by the opponent's legal representatives.[201] The applicant further submits that in the context of an opposition, the expectation is that the opponent will provide evidence to support their case on ascertainment.[202]
[200] Applicant's Written Submissions at [185].
[201] Applicant's Written Submissions at [187].
[202] Applicant's Written Submissions at [188]; Sanofi-Aventis Healthcare Pty Limited v Reckitt Benckiser Healthcare (UK) Limited [2018] APO 11 at [134].
In Delnorth Pty Ltd v Commissioner of Patents[203], Nicholas J emphasises at [33] that:
"[w]hether or not a particular document that forms part of the prior art base meets the requirements of s 7(3) of the Act is something that must usually be determined by evidence."
[203] (2013) 100 IPR 175.
The opponent refers to the evidence of Prof Young that appears to confirm that some of D1-D4, D10, D18 and D19 would likely be consulted as they were part of "literature available before 2011 describing the continued investigation into potential RSV vaccines" and this literature provided a "background against which continued general discussion about vaccine regimens, such as this, occurred."[204] In particular, I consider that this evidence of Prof Young is sufficient to establish that a PSA would have at least ascertained the relevant non-patent literature (D2, D18 and D19). I further consider that a PSA would understand D2, D18 and D19 and regard them as relevant, as D2, D18 and D19 are in the same technical field of the opposed application.
[204] Young at [42].
The applicant refers to Alphapharm Pty Ltd v Yeda Research & Development Co Ltd (Yeda)[205]as supporting the proposition that the opponent has not discharged its onus of proving the relevant documents are available under s 7(3). However, in Yeda there was evidence that a PSA would not have searched patent literature,[206] rather than the evidence being silent as to whether a PSA would have searched patent literature, as is the case here.
[205] [2017] APO 41 at [121].
[206] Yeda at [118].
The Patent Manual of Practice and Procedure states at 2.5.2.5.1 that:
“Examiners should generally proceed on the basis that it could be reasonably expected that the person skilled in the art would conduct a search of the patent literature, including patent specifications of major countries and that … any patent document located in a patentability search would reasonably be expected to be ascertained by the person skilled in the art."
In Commissioner of Patents v Emperor Sports Pty Ltd[207], the Full Court affirmed the general correctness of the above practice. However, it also noted that this may not be universally applicable and there may be situations where it would not be reasonable to have such expectation.
[207] [2006] FCAFC 26; 67 IPR 488.
However, in an opposition proceeding, as opposed to examination, the question of whether a PSA would have ascertained patent literature needs to be established by the evidence. In the current opposition, the evidence fails to establish that a PSA, in trying to solve the problem of improving RSV vaccination regimens, would perform a search of the patent literature. None of the witnesses provide evidence that they would search any particular patent database, or any database that would contain patent information. While it would not be surprising if a PSA did consult patent documents, in the absence of any evidence to support such a conclusion the opponent has not established that patent documents would be ascertained.

Inventive step in light of the prior art

Sales and Wang (2003) (D2). The disclosure of D2 was discussed above.
While Table 1 of D2 does disclose a two-step regime, Table 1 fails to disclose what vaccine type or what antigens are delivered to the pregnant female in the third trimester. D2 discusses maternal immunisation strategies under the heading "Subunit RSV Vaccines", so in my view, a PSA would be directly led as a matter of course to perform the maternal vaccination disclosed in Table 1 with a sub-unit vaccine. This construction is consistent with the fact that D2 states that subunit vaccines are targeted to older populations.
D2 further discloses the development of subunit vaccines based on the F, G and M proteins. I found previously that on the evidence before me, I consider the preference for the use of the F protein in a sub-unit vaccine for RSV to be part of the CGK, due to the ability of the F protein to induce protective immunity, and the lingering safety concerns surrounding the G protein. It follows that I am satisfied that a PSA reading D2, in light of the CGK, would be directly led to use the RSV F glycoprotein in the subunit maternal vaccination strategy disclosed in Table 1.
It is inherent that the live-attenuated vaccine delivered to infants to protect beyond maternal antibody decay in Table 1 would comprise an RSV F glycoprotein. However, as previously discussed under novelty at paragraph [101], I construe Table 1 as disclosing an RSV prophylactic option for infants born at term which comprises maternal vaccination of the infant's mother during the third trimester, and optionally vaccinating the infant with a live attenuated vaccine at a point in time near the end of maternal antibody decay (i.e. at around 6 months of age). In my view, the evidence fails to establish that a PSA would be directly led as a matter of course to administer the live-attenuated vaccine disclosed in Table 1 at about 4 months old or younger. Following maternal vaccination, passively acquired maternal antibodies would afford the infant protection up to about 6 months of age. The evidence establishes that it would be suboptimal to deliver the subunit vaccine during the first six months of life in an infant born from a vaccinated mother due to maternal antibody immunosuppression and the immaturity of the infant's immune system. As a result, I am not satisfied that any of the claims lack inventive step in view of D2.
Martinez et al (1999) (D19). The disclosure of D19 was discussed above.
As previously discussed under novelty at paragraph [124], D19 fail to disclose vaccination of a female during pregnancy. The evidence fails to establish that a PSA, in light of D19 would be directly led as a matter of course to administer the vaccine disclosed in D19 to a female during pregnancy. In the absence of evidence to the contrary, as discussed at paragraph [138], the CGK fails to directly lead a PSA to administer an RSV vaccine during pregnancy. As a result, I am not satisfied that any of the claims lack inventive step in view of D19.

Siegrest, C.-A. et al., The Journal of Infectious Diseases, 1999, Vol. 179, pages 1326-1333 (designated D18) was published in June 1999. Consequently it is part of the prior art base.
D18 discloses a recombinant vaccine (BBG2Na) derived in part from the RSV subgroup A G protein which induced moderate antibody titers after 1 immunisation in 1-week-old mice but conferred complete lung protection upon RSV challenge.[208] D18 also discloses that BBG2NA-induced protective immunity was maintained even after early life immunisation in the presence of high titers of maternal antibodies.[209] Furthermore D18 theorises that this protective efficacy reflected the high capacity of the nonglycosylated G2Na immunogen to escape inhibition by RSV-A-induced maternal antibodies.[210]
[208] D18 - Abstract.
[209] D18 - Abstract.
[210] D18 - Abstract.
D18 fails to disclose a two- step regimen wherein a pregnant woman was vaccinated with an RSV F glycoprotein containing vaccine, and an infant born from that pregnancy was vaccinated with an RSV F glycoprotein containing vaccine at or about 4 months old or younger. In my view, a PSA would not be directly led as a matter of course to follow the regimen disclosed in D18, whilst replacing the RSV G protein immunisation with a RSV F glycoprotein immunisation, with a reasonable expectation of providing protective immunity to the infant. D18 teaches away from this course of action. D18 theorises that the protective efficacy conferred in the infant in the presence of maternal antibodies was by the nonglycosylated G2Na immunogen to escape inhibition by RSVA-induced maternal antibodies. That is, it was specifically the presence of the G protein in the infant vaccine that allowed protective immunity in the presence of maternal antibody. This is contrasted with the two-step regimen under opposition which vaccinates with the same RSV F glycoprotein in the pregnant mother and the infant. As a result, I am not satisfied that any of the claims lack inventive step in view of D18.

Conclusion on inventive step

This ground of opposition fails. The opponent has not shown that the claims lack inventive step in light of their evidence.

Full Description

The test for sufficiency of description under s 40(2)(a) of the Patents Act as it was at 12 April 2013, is set out by the High Court as:[211]

"will the disclosure enable the addressee of the specification to produce something within each claim without new inventions or additions or prolonged study of matters presenting initial difficulty?"
[211] Kimberly-Clark Australia Ltd v Arico Trading International Pty Ltd [2001] HCA 8; 207 CLR 1 at [25].

The opponent submits that all the claims of the opposed application are insufficient because they fail to provide sufficient instructions to allow the PSA to provide "protective immunity" in an infant.[212]

[212] Opponent's Written Submissions at [65].

The opponent also states:

"nowhere does the specification disclose a method in which maternal antibody is transferred via placenta to an infant to provide protective immunity, and in which the infant is vaccinated to induce protective immunity, and that immunity shown to establish protection to RSV by challenge with RSV."[213]
[213] Opponent's Written Submissions at [67].

The evidence of Dr Lowenthal supports this view and states that the opposed application provides no examples of there being maternal antibody received across the placenta resulting from vaccination of the mother.[214]
[214] Lowenthal-2 at [31].
Dr Lowenthal further states:
"transplacental (maternal) antibody is functionally different from serum-derived antibody (as used in the Examples of the patent) so it is not possible to predict whether protective immunity with transplacental antibody should be seen from use of injected antibody"

and

"nowhere in the examples of the patent or otherwise does the patent show the obtainment of protective immunity in an infant (human) to RSV"[215]
[215] Lowenthal-3 at [20].

Dr Lowenthal further notes that:

"some of the earlier RSV studies in my first declaration had failed to develop a protective immunity, so clearly there are some compositions containing RSV antigens that give protective immunity and some that do not."[216]
[216] Lowenthal-2 at [29].

The opponent further submits that a PSA would not have considered working the invention because of the lack of a vaccine with regulatory approval.[217]
[217] Opponent's Written Submissions at [66].

The applicant submits that the opponent has not established that the description of the opposed application lacks sufficiency for several reasons. Firstly, the applicant submits that none of the expert witnesses give evidence that the skilled person could not make or do at least one thing within each claim without new inventions, or additions, or prolonged study of matters presenting initial difficulty.[218] Secondly, the applicant submits that the correct legal test for sufficiency is whether a PSA could perform the invention based on the description in the specification, not whether a PSA would choose to perform the invention.[219] Thirdly, the applicant submits that in order to establish sufficiency, the specification does not need to prove the conferral of protective immunity onto the infant.[220] The applicant submits that the specification teaches by reference to the animal models in Examples 3 and 4, that protective immunity is able to be achieved in human infants by (a) the passive transfer of RSV-neutralising antibodies to the infant from his or her vaccinated pregnant mother, and (b) the infant generating his or her own RSV-neutralising antibodies, despite being vaccinated at a time (4 months old or younger) when maternal RSV-neutralising antibodies remain present at protective levels.[221]
[218] Applicant's Written Submissions at [78].
[219] Applicant's Written Submissions at [81]; Warner-LambertCompany LLC v Apotex Pty Ltd (No 2) (2018) 129 IPR 205 at [132].
[220] Applicant's Written Submissions at [83].
[221] Applicant's Written Submissions at [85].
With regard to the suitability of the animal models disclosed in the examples of the opposed specification, Prof Young makes the following comments. Firstly, he states that the assays described in Example 1 "would have been considered as a reasonable means of evaluating the RSV vaccination regimen described and claimed in the opposed application."[222] Secondly, he states that Example 2 is an "acceptable model of a prime-boost scenario in humans."[223] Thirdly, he states that Example 3 "shows that passively transferred antibodies can protect a recipient from RSV challenge and that the higher neutralisation titer of serum transferred from RSV-infected donors who were also immunised provides greater protection."[224] Finally, Prof Young states:
"Example 4 is, in my view, the perfect complementary experiment to Example 3, as it goes on to test whether you can then avoid engagement/interaction of vaccine antigen and circulating passively transferred antibody when delivering the RSV F protein in the presence of passively transferred antibody."[225]
[222] Young at [38].
[223] Young at [39].
[224] Young at [40].
[225] Young at [41].
The opponent's argument that the invention is not fully described appears to be predicated on a utility question. That is, whether the described two-step vaccination method, when followed by a PSA, would provide "protective immunity" against RSV in an infant? As noted by the applicant at the hearing, the opponent did not contest the validity of the opposed application on the ground of utility. The ground of lack of full description will only be established, if the evidence establishes that the disclosure of the specification will not enable the skilled addressee to produce something within each claim without new inventions or additions or prolonged study of matters presenting initial difficulty.

I agree with the applicant's submission that the test for sufficiency is not whether a PSA would perform the invention based on the description in the specification, but rather whether a PSA could perform the invention. This renders moot, the opponent's argument that a PSA would not have worked the invention because of the lack of a regulatory approved vaccine.

The only remaining question therefore, is whether the disclosure of the specification would enable a PSA to perform the claimed method, such that "protective immunity" is provided to the infant? Prof Young's evidence provides that Example 3 describes an appropriate animal model for demonstrating protective immunity in an infant from passively transferred antibodies, and Example 4 describes a "perfectly complementary" experiment to Example 3 which describes an appropriate animal model for demonstrating protective immunity in an infant in the presence of passively transferred antibodies. Dr Lowenthal's evidence is that the description of the opposed patent application does not show the obtainment of protective immunity to RSV in a human infant, as the description fails to provide examples of protective immunity in an infant in the presence of maternal antibody received across the placenta.
In my view, the evidence provides competing scientific opinion on whether the method of the invention would, as a matter of fact, provide protective immunity in an infant. It is arguable that the data provided in the specification cannot prove the conferral of protective immunity on an infant. On the other hand, there is insufficient evidence to establish that the method as described would not result in protective immunity in an infant. The onus is on the opponent to establish that a PSA could not produce something within each claim (i.e. the conferral of protective immunity in an infant), and the evidence provided by the opponent has failed to discharge this onus. It follows that it has not been shown that any of the claims are not fully described.

Best Method of Performance

The specification, in addition to fully describing the invention, must include the best method of performing the invention. In American Cyanamid Company v Ethicon Limited [1979] RPC 215 at page 269, it was stated:

"The Act is intending to protect the public against a patentee who deliberately keeps to himself something novel and not previously published which he knows of or has found out gives the best results, with a view to getting the benefit of a monopoly without giving to the public the corresponding consideration of knowledge of the best method of performing the invention."

The specification will fail for want of best method if it can be shown that the best method known to the applicant at the date of filing is not included.[226]
[226] Pfizer Overseas Pharmaceuticals v Eli Lilly [2005] FCAFC 224 at [366]-[379].
The opponent argues that the applicant has failed to disclose the best method of performing the invention, as there is no teaching which indicates the composition of a suitable vaccine where the regimen would be safe and efficacious.[227]
[227] Opponent's Written Submissions at [69].
Contrary to the opponent's submissions, the legal test for best method of performance does not require the disclosure of a suitable vaccine where the regimen would be safe and efficacious. What is required is for the opponent to establish that the applicant knew a better way of performing the invention and did not disclose that method in the complete specification. The opponent has provided no evidence to establish this. As a consequence, the opponent has not discharged their onus that there is no best method of performance.

Manner of Manufacture

Section 18(1)(a) of the Act requires that the invention, so far as claimed in any claim, must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies. The High Court in National Research Development Corporation v Commissioner of Patents (NRDC)[228] laid out the proper question for determination when considering manner of manufacture as:
“Is this a proper subject according to the principles which have developed for the application of s. 6 of the Statute of Monopolies?”[229]
[228] [1959] HCA 67; 102 CLR 252.
[229] NRDC at [269].

With this at the fore of their considerations in respect of a claim to a process for eradicating weed from a stretch of land, the High Court in NRDC described subject matter that would be considered patentable:
“The point is that a process, to fall within the limits of patentability which the context of the Statute of Monopolies has supplied, must be one that offers some advantage which is material, in the sense that the process belongs to a useful art as distinct from a fine art ... that its value to the country is in the field of economic endeavour.”[230]
[230] NRDC at [275].

More recently, it has been made clear that the assessment of whether a claimed invention is a manner of manufacture is one of substance rather than form:
“Whatever words have been used, the matter must be looked at as one of substance and effect must be given to the true nature of the claim.”[231]
[231] D'Arcy v Myriad Genetics Inc [2015] HCA 35; 258 CLR 334 at [144].

A mere idea is not patentable subject matter. In Hickton's Patent Syndicate v Patents and Machine Improvements Co. Ltd.[232], it was stated:
"No doubt you cannot patent an idea, which you have simply conceived, and have suggested no way of carrying it out, but the invention consists in the thinking or conceiving something and suggesting a way of doing it … I think you can have a Patent for an idea, which is new and original and very meritorious, if you suggest a way of carrying it out. If you do not so suggest, you cannot no doubt have a patent …"
[232] (1909) 26 RPC 339 at 348.
Consistent with these authorities, the approach I will take here is to determine what is the substance of the claims, and whether or not the substance is patentable subject matter. I note that the substance of the claim is not necessarily the subject matter of the claim as defined by the words of the claim.

What is the subject matter of the claims?

All claims are limited to providing protective immunity against RSV in an infant, comprising (a) administering a first anti-RSV immune response inducing composition comprising an RSV F glycoprotein to a pregnant female, and (b) administering a second anti-RSV immune response inducing composition comprising an RSV F glycoprotein to an infant that is born from the pregnancy at about 4 months old or younger.

What is the substance of the claims?

The opponent submits that the substance of the present invention is the assertion that a largely unspecified vaccine having a particular effect can be administered first, to the pregnant mother, and then to the baby born from that mother, and it is nothing more than an idea (and a known one at that) without technical application.[233] The opponent argues that while any technical application might rest in the creation of a suitable vaccine and, in appropriate circumstances, a unique administration regimen for that vaccine, the opposed application does not disclose the creation of any vaccine.[234]
[233] Opponent's Written Submissions at [126].
[234] Opponent's Written Submissions at [126].
The applicant submits that the opponent's argument that the claimed invention is not a manner of manufacture because it is nothing more than an idea without technical application, disregards both the claims and the description in the opposed application.[235] The applicant submits that the opposed application claims a specific therapeutic method that involves, inter alia, the administration of a suitable anti-RSV immune response inducing composition that provides an RSV-F glycoprotein antigen, and this is plainly a manner of manufacture within the meaning of s 18(1)(a) of the Patents Act.[236]
[235] Applicant's Written Submissions at [223].
[236] Applicant's Written Submissions at [223].
I consider the applicant's submission is correct. The substance of the claims aligns with the subject matter of the claims and is a therapeutic method involving a two-step vaccination regimen comprising administration of an RSV F glycoprotein antigen. The substance of the claims is not an idea without technical application, as the technical application is the particular two-step regimen of administering RSV F glycoprotein in order to provide protective immunity against RSV in an infant. The fact that the invention does not lie in the creation of an RSV vaccine per se is immaterial, as the invention lies in the particular administration regimen which is carried out using an RSV F glycoprotein antigen. If follows that I am satisfied that the invention as claimed in all claims is for a manner of manufacture.

Conclusion

The opposition fails on all grounds.

Costs

It is normal in matters before the Commissioner that costs should follow the event. I see no reason to depart from that approach in the present case. I will award costs according to Schedule 8 against the opponent.

D. S. Triffett
Delegate of the Commissioner of Patents

ANNEX

1. A method for providing protective immunity against respiratory syncytial virus (RSV) in an infant, comprising:

(a)administering a first anti-RSV immune response inducing composition which provides one or more RSV antigens to a female during pregnancy; and
(b)administering a second anti-RSV immune response inducing composition which provides one or more RSV antigens to the infant that is born from the pregnancy, at about 4 months old or younger;

wherein the one of more RSV antigens comprises an RSV F glycoprotein.

2. Use of an anti-respiratory syncytial virus (RSV) immune response inducing composition which provides one or more antigens in the preparation of a medicament for inducing an anti-RSV immune response in an infant, wherein inducing the anti-RSV immune response in the infant comprises:

(a)administering a first anti-RSV immune response inducing composition which provides one or more RSV antigens to a female during pregnancy; and
(b)administering a second anti-RSV immune response inducing composition which provides one or more RSV antigens to the infant that is born from the pregnancy, at about 4 months old or younger;

wherein the one of more RSV antigens comprises an RSV F glycoprotein, and at least one of (a) and (b) comprises administering the medicament to administer the anti-RSV immune response inducing composition.

3. The method of claim 1 or the use of claim 2, wherein administering in (a) is a prime or
a boost.

4. The method or use of claim 3, wherein the administering in (a) boosts a neutralizing antibody response in said female.

5. The method or use of claim 4, wherein the neutralizing antibody response in the female is characterized by a 2-fold or greater increase in neutralizing titer.

6. The method or use of claim 4 or 5, wherein the neutralizing antibodies are complement independent.

7. The method according to any one of claims 1 or 3 to 6 or the use according to any one of claim 2 to 6, wherein administering in (a) is during the second or third trimester of pregnancy.

8. The method according to any one of claims 1or 3 to 7 or the use according to any one of claims 2 to 7, wherein the first anti-RSV immune response inducing composition and the second anti-RSV immune response inducing composition are the same.

9. The method according to any one of claims 1 or 3 to 8 or the use according to any one of claims 2 to 8, wherein the first and second anti-RSV immune response inducing compositions each comprise an RSV subunit composition, a nucleic acid, a viral replicon particle (VRP), a live attenuated virus, an inactivated virus particle, a recombinant viral vector, or a virus-like particle.

10. The method according to any one of claims 1 or 3 to 7 or the use according to any one of claims 2 to 7, wherein the first anti-RSV immune response inducing composition is not the same as the second anti-RSV immune response inducing composition.

11. The method or use of claim 10, wherein the first anti-RSV immune response inducing composition comprises an RSV subunit composition, a nucleic acid, a recombinant viral vector, or a viral replicon particle (VLP); and the second anti-RSV immune response inducing composition comprises an RSV subunit composition, a nucleic acid, a recombinant viral vector, or a viral replication particle; with the proviso that the first and second anti-RSV immune response inducing compositions are not both an RSV subunit composition, a nucleic acid, a recombinant viral vector or a viral replicon particle.

12. The method according to any one of claims 1 or 3 to 11 or the use according to any one of claims 2 to 11, wherein the second anti-RSV immune response inducing composition comprises an RSV subunit composition, a nucleic acid, a recombinant viral vector, or viral replicon particle (VLP).

13. The method according to any one of claims 1or3 to 12 or the use according to any one of claims 2 to 12, wherein the second anti-RSV immune response inducing composition comprises a nucleic acid.

14. The method according to any one of claims 1or3 to 12 or the use according to any one of claims 2 to 12, wherein the first anti-RSV immune response inducing composition comprises an RSV subunit composition.

15. The method according to any one of claims 1or3 to 12 or the use according to any one of claims 2 to 12, wherein the second anti-RSV immune response inducing composition comprises a viral replicon particle (VLP).

16. A method for providing protective immunity against respiratory syncytial virus (RSV) in an infant, comprising administering to an infant at about 4 months old or younger an anti-RSV immune response inducing composition which provides one or more RSV antigens, wherein said infant was born to a female to whom an anti-RSV immune response inducing composition which provides one or more RSV antigens was administered during the time when said female was pregnant with said infant, wherein the one or more RSV antigens comprises an RSV F glycoprotein.

17. Use of an anti-respiratory syncytial virus (RSV) immune response inducing composition which provides one or more respiratory syncytial virus (RSV) antigens in the preparation of a medicament for inducing an anti-RSV immune response in an in infant, wherein inducing the anti-RSV immune response in the infant comprises administering to the infant at about 4 months old or younger the medicament, wherein said infant was born to a female to whom an anti-RSV immune response inducing composition which provides one or more RSV antigens was administered during the time when said female was pregnant with said infant, wherein the one or more RSV antigens comprises an RSV F glycoprotein.

18. The method of claim 16 or the use of claim 17, wherein the anti-RSV immune response inducing composition administered to said female boosted a neutralizing antibody response in said female.

19. The method or use of claim 18, wherein the boost in neutralizing antibody response is characterized by a 2-fold or greater increase in neutralizing titer.

20. The method or use of claim 18 or 19, wherein the neutralizing antibodies are complement independent.

21. The method according to any one of claims 16 or 18 to 20 or the use according to any one of claims 17 to 20, wherein the anti-RSV immune response inducing composition administered to said infant is a prime or a boost.

22. The method according to any one of claims 16 or 18 to 21 or the use according to any one of claims 17 to 21, wherein the anti-RSV immune response inducing composition administered to said female was administered during the second or third trimester of pregnancy.

23. The method according to any one of claims 16 or 18 to 22 or the use according to any one of claims 17 to 22, wherein the anti-RSV immune response inducing composition administered to the female and the anti-RSV immune response inducing composition administered to the infant are the same.

24. The method according to any one of claims 16 or 18 to 23 or the use according to any one of claims 17 to 23, wherein the anti-RSV immune response inducing compositions each comprise an RSV subunit composition, a nucleic acid, a recombinant viral vector, or a viral replication particle (VRP).

25. The method according to any one of claims 16 or 18 to 22 or the use according to any one of claims 17 to 22, wherein the anti-RSV immune response inducing composition administered to the female and the anti-RSV immune response inducing composition administered to the infant are not the same.

26. The method of claim 25, wherein the anti-RSV immune response inducing composition administered to the female comprises an RSV subunit composition, a nucleic acid, a recombinant viral vector or a viral replicon particle (VRP); and the anti-RSV immune response inducing composition administered to the infant comprises an RSV subunit composition, a nucleic acid, a recombinant viral vector or a viral replicon particle (VRP); with the proviso that the anti-RSV immune response inducing compositions administered to the female and infant do not both comprise an RSV subunit composition, a nucleic acid, a recombinant viral vector or a viral replicon particle (VRP).

27. The method according to any one of claims 16 or 18 to 26 or the use according to any one of claims 17 to 26, wherein the anti-RSV immune response inducing composition administered to the infant comprises an RSV subunit composition, a nucleic acid, a recombinant viral vector, or viral replicon particle (VLP).

28. The method according to any one of claims 16 or 18 to 27 or the use according to any one of claims 17 to 27, wherein the anti-RSV immune response inducing composition administered to the infant comprises a nucleic acid.

29. The method according to claim 28, further comprising administering a boost of RSV subunit composition to the infant.

30. The method according to any one of claims 16 or 18 to 29 or the use according to any one of claims 17 to 29, wherein the anti-RSV immune response inducing composition administered to the female comprises an RSV subunit composition.

31. The method according to any one of claims 16 or 18 to 27 or the use according to any one of claims 17 to 27, wherein the anti-RSV immune response inducing composition administered to the infant comprises a viral replicon particle (VLP).

32. The method or use according to any one of claims 9, 11, 12, 14, 24, 26, 27, 29 or 30, wherein the RSV subunit composition comprises: (a) one or more mutations that prevent cleavage at one or both of the furin cleavage sites of an RSV F protein; and/or (b) one or more mutations in the fusion peptide region of an RSV protein.

33. The method or use according to any one of claims 9, 11, 12, 14, 24, 26, 27, 29 or 30, wherein the RSV subunit composition: (a) comprises one or more mutations that prevent cleavage at one or both of the furin cleavage sites of an RSV F protein; (b) comprises one or more mutations in the fusion peptide region of an RSV protein; (c) lacks the transmembrane region and cytoplasmic tail of an RSV protein; and (d) comprises one or more oligomerisation sequences.

34. The method or use according to any one of claims 9, 11, 12, 13, 24 or 26 to 28, wherein the nucleic acid comprises: (a) DNA; or (b) RNA.

35. The method or use according to claim 34 wherein the RNA is self-replicating RNA.

36. The method or use according to any one of claims 9, 11, 12, 15, 24, 26, 27 or 31, wherein the VRP comprises an alphavirus VRP.

486.