BioNTech RNA Pharmaceuticals GmbH v CureVac SE
[2023] APO 36
•16 June 2023
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
BioNTech RNA Pharmaceuticals GmbH v CureVac SE [2023] APO 36
Patent Application: 2016251687
Title:RNA containing composition for treatment of tumor diseases
Patent Applicant: CureVac SE
Opponent: BioNTech RNA Pharmaceuticals GmbH
Delegate: L. F. McCaffery
Decision Date: 16 June 2023
Hearing Date: 11 April 2023, by videoconference
Catchwords: PATENTS – compositions comprising mRNA – consideration of allowability of amendments under subsections 102(1) and 102(2)(b) – whether the amendments extend beyond the disclosure as filed – whether, as a result of the amendments, the claims are not clear and not supported – opposition unsuccessful – amendments are allowable – costs awarded.
Representation: Patent attorney for the applicant: Allens Patent & Trade Mark Attorneys
The Opponent did not appear or provide submissions for the hearing.
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2016251687
Title:RNA containing composition for treatment of tumor diseases
Patent Applicant: CureVac SE
Date of Decision: 16 June 2023
DECISION
The amendments are allowable. The opposition is unsuccessful.
Costs according to Schedule 8 are awarded against the Opponent, BioNTech RNA Pharmaceuticals GmbH
REASONS FOR DECISION
The present matter relates to Australian Application 2016251687 (the application) in the name of CureVac SE (the Applicant) and an opposition to an amendment under s104(4) of the Patents Act 1990 (Cth) (the Act) by BioNTech RNA Pharmaceuticals GmbH (the Opponent).
The application was filed as International Patent Application PCT/EP2016/059109 on 22 April 2016 and published as WO2016/170176 on 27 October 2016. The application entered the national phase in Australia on 3 August 2017. The application was advertised as accepted on 11 June 2020. A notice of opposition to the grant of the patent under s59 of the Act was filed on 11 September 2020 (the S59 opposition).
The Applicant filed a request to amend the specification on 20 July 2021 (the amendment). Leave to amend was granted and the application for amendment advertised for opposition on 2 September 2021. A notice of opposition to the amendment was filed by the Opponent on 1 November 2021 (the S104 opposition). The present determination relates to the S104 opposition.
A statement of grounds and particulars (SGP) was filed on 1 December 2021. Both parties filed evidence in the opposition. Evidence in Support was completed on 15 February 2022 and consisted of the following declarations:
Cornelis J. M. Melief, dated 14 February 2022, and exhibits CJMM-12 to CJMM-14 (Melief 2)[1]
Mark Edward Wickham, dated 15 February 2022, and exhibits MEW-1 to MEW-6 (Wickham)
[1] Professor Melief had filed an earlier declaration in the S59 Opposition. I have included it in the present numbering of declarations as Melief 1.
On 21 April 2022 the Applicant requested a direction by the Commissioner that the time to file their Evidence in Answer (EIA) be extended. They subsequently filed their evidence on 20 May 2022. This consisted of a declaration by Colin W. Pouton, dated 20 May 2022, together with exhibits CP-1 to CP-17 (Pouton). A delegate subsequently refused the request on 8 June 2022 and therefore the EIA was not filed in time. The Applicant requested that the evidence alternatively be considered under Regulation 5.23 and on 29 June 2022 the delegate directed that paragraphs 1 to 47 and 152 to 211 of Pouton and exhibits CP-1 to CP-17 would be evidence for the present opposition (the 5.23 evidence).
Evidence in response to the 5.23 evidence was filed by the Opponent on 29 July 2022 and consisted of a declaration by Professor Melief dated 27 July 2022 (Melief 3).
The matter was set for hearing on 11 April 2023. The Opponent did not appear, nor did they provide any written submissions. However, while the Opponent took no active part in the hearing, they advised on 1 September 2022 that they were not withdrawing the opposition.
As the Opponent did not appear or file written submissions for the hearing, I can only proceed on the assumption that they intend to pursue all of the grounds of opposition given in their SGP. The Opponent’s actions are not ideal since it has precluded any opportunity to narrow the issues under consideration. This has impacted on the resources and time of both the Applicant and the Patent Office and is detrimental to the efficient resolution of both the present matter and the substantive opposition. The Opponent is certainly not prevented under the Act from taking such an approach to their opposition, but I note it is a factor that can be taken into consideration in the award of costs in both oppositions.
Onus
The substantive amendments to the Act brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 (Cth) apply to the present case. The standard of proof in opposition proceedings, including oppositions under s104(4),[2] is the balance of probabilities. The opponent bears the onus of proof.
[2] Cytec Industries Inc. v Nalco Company [2018] APO 4 at [18].
The amendments
10. The invention relates to RNA-containing compositions for use in the treatment or prophylaxis of tumour and/or cancer diseases.[3] The specification states that conventional gene therapies based on the use of DNA to transfer the desired information into the cell can be problematic. The use of DNA risks the DNA being inserted into an intact gene of the host cell genome by, for example, recombination. The affected gene may be mutated and inactivated or may give rise to misinformation. Anti-DNA antibodies may also be induced, which can result in potentially fatal immune responses. The use of RNA as a gene therapeutic agent is said to avoid these issues. [4]
[3] Specification, page 1, lines 8-11.
[4] Specification page 1, line 29 to page 2, line 8.
11. The detailed description of the invention states that compositions according to the invention comprise at least one RNA and are preferably administered intratumorally (direct to the tumour). The RNA may be selected from a wide range of RNA types, and in specific embodiments are said to be selected from coding or non-coding RNA species.[5] The coding RNA may be mRNA, viral RNA, retroviral RNA and replicon RNA. The RNA is also said to code for different proteins (cytokines, chemokines, suicide gene products, immunogenic proteins, apoptosis inducers, angiogenesis inhibitors etc.).[6] However, the claims as accepted were limited to methods using compositions comprising mRNA encoding interleukin-12 (a cytokine).
[5] Specification at page 23, lines 1 to 20.
[6] Specification at page 2, line 23 to page 24, line 6.
12. The Applicant submitted that the present amendments were sought in order to narrow the issues in dispute in the s59 opposition.[7] The amendments replace the accepted claims, numbered 1 to 36, with new claims 1 to 42. Corresponding amendments are made to the consistory statements in the description. The Applicant provided a broad summary of the substance of the amendments as follows:
a. Amended claim 1 removes the use of the RNA composition for prophylaxis of cancer thereby specifying that the invention is to be used for treatment. Further, amended claim 1 clarifies that the at least one coding RNA is “not a replicon RNA”.
b. Amended claim 5 clarifies that the coding RNA is the “at least one further RNA” recited in claim 4.
c. Added claims 36 and 40 clarify that the at least one coding RNA is “not a viral RNA or a retroviral RNA”.
d. Added claims 37 and 41 specify that the at least one coding RNA is a “purified mRNA”.
e. Added claims 38 and 42 specify that the at least one coding RNA is complexed with one or more lipids to form liposomes, lipid nanoparticles or lipoplexes.
f. Amended claim 39 (previous claim 36) is amended similarly to claim 1.[8]
[7] Applicant submissions (AS) at [27].
[8] AS at [26].
13. The claims in dispute are given in the attached Annex. Amendments are indicated by underlining or strikethrough. Several other claims contain minor amendments. These are not in dispute and have not been included here.
The grounds of opposition
14. The SGP sets out grounds of opposition under sections 102(1) and 102(2)(b). In short, the grounds of opposition relied on by the Opponent are:
Section 102(1)
There is no basis in the specification as filed for the “negative limitations” introduced by the amendments, and as a consequence the proposed amendment results in the specification claiming and disclosing matter that extends beyond that disclosed in the specification as filed. The Opponent specifically referred to the disclaimers of claims 1 and 39 (“wherein the at least one coding RNA is not a replicon RNA”) and claims 36 to 38 and 40 to 42 (“wherein the at least one coding RNA is not a viral RNA or a retroviral RNA”, and “wherein the at least one coding RNA is a purified RNA”).
Section 102(2)(b)
The specification would not comply with subsections 40(2) or (3) as a result of the amendment. The Opponent asserted that claims 1 and 39 lack support due to the limitation “wherein the at least one coding RNA is not a replicon RNA” and claims 36 to 38 and 40 to 42 lack clarity and support due to the definitions in these claims of “at least one coding RNA” and “wherein the at least one coding RNA is not a viral RNA or a retroviral RNA”.
15. Details of the Opponent’s arguments are provided below.
The relevant legislation and legal principles
16. Subsections 102 (1) and (2) state that:
(1) An amendment of a complete specification is not allowable if, as a result of the amendment, the specification would claim or disclose matter that extends beyond that disclosed in the following documents taken together:
(a) the complete specification as filed;
(b) other prescribed documents (if any).
(2) An amendment of a complete specification is not allowable after the relevant time if, as a result of the amendment;
(a) a claim of the specification would not in substance fall within the scope of the claims of the specification before amendment; or
(b) the specification would not comply with subsection 40(2), (3) or (3A).
17. Notably the legislation requires that the failure to meet the requirements of subsections 102(1) and (2) must be the result of the amendment.[9] If any of these matters do not arise as a result of the amendments, for example if the particular issue existed prior to amendment, then it will not result in the amendment being not allowable. However, the issue may still be relevant to a substantive opposition under section 59.
[9] United States Gypsum Company v CSR Building Products Ltd [2017] FCA 595 at [34] to [36].
18. The legal principles of subsection 102(1) were considered in Commonwealth Scientific and Industrial Research Organisation v BASF Plant Science GmbH,[10] where Beach J provided a summary as follows:
“214. I see no good reason not to follow the UK authorities to the extent of applying analogous concepts to the construction of the present form of s 102(1). In summary the following may be noted.
215. First, as has been pointed out, the test is a strict one.
216. Second, subject matter will be impermissibly added unless the matter is clearly and unambiguously disclosed in the application as filed.
217. Third, the required disclosure may be express or implied, but on any view must be clearly and unambiguously so. In this regard, a patent applicant is not permitted to add by amendment matter simply because it would have been obvious to the skilled person.
218. Fourth, context is important. A patent applicant cannot extract features disclosed in one context and introduce them into a specification stripped of that context. So, the concept of intermediate generalisation as discussed in the UK authorities applies to s 102(1) in its construction and application.”
[10] [2020] FCA 328.
19. My understanding is that the concept of “intermediate generalisation” is at the heart of the present opposition. This concept and its relevance to the consideration under subsection 102(1) was explained by Beach J as follows:
“An amendment is not allowable if it takes a feature which is only disclosed in a particular context and seeks to introduce it into a claim deprived of that context. In the United Kingdom, this is described as an ‘intermediate generalisation’ and is an established aspect of ‘added matter’”.[11]
[11] Ibid at [205].
20. Beach J also summarised some of the principles set out in several UK decisions:
“211. In summary, an amendment utilising a feature may amount to added subject matter, such that it is not relevantly disclosed, even where there is a literal reference to such a feature in the specification as filed. An example of where this may occur is where by reason of the amendment, a feature that was not suggested to be significant is, for the first time, suggested to have a technical significance. Such a suggestion of technical significance might arise where a feature is taken from a specific embodiment, and introduced into a claim in a manner that is stripped from relevant context provided by that embodiment. To avoid a conclusion of added subject matter, the skilled person must have appreciated from the complete specification as filed that the selected feature was more generally applicable. This may involve asking whether the skilled person is being presented with any new information about the invention which is not directly and unambiguously apparent from the original disclosure. Further, even if a feature was suggested to be technically significant, an impermissible intermediate generalisation may take place if by the amendment the feature is used in a manner significantly different from its original context.
212 Further, what constitutes an impermissible addition of subject matter by way of an ‘intermediate generalisation’ is to be distinguished from an amendment that claims a sub-class of an inventive concept, whether or not it is presented as inventively distinct in the specification as filed. This is consistent also with established practice in relation to patent claiming, where a patent will routinely include cascading claims directed to progressively narrower characterisations of the disclosed invention. A patent applicant is not limited to a single patent claim, directed to a preferred embodiment.
213 Further, there may be an impermissible intermediate generalisation where a new combination of features is sought to be created by the proposed amendment which was not apparent in the application as filed. As has been pointed out… the question is ‘whether the features combined in the amended claim were disclosed as a combination in the application [as filed]’” (citation omitted). [12]
[12] Ibid at [211]-[215].
21. As indicated by Beach J, the approach when considering whether an amendment would result in the specification claiming or disclosing new matter is to ask whether the person skilled in the art would, on looking at the specification as proposed to be amended, learn anything about the invention which they could not learn or directly derive from the complete specification as filed.[13]
[13] Ibid at [202].
22. These are the principles that I will apply in the present determination.
Considerations under Section 102(1)
“Wherein the at least one coding RNA is not a replicon RNA” (Pages 3 and 3a, Claims 1 and 39)
23. The gist of the Opponent’s opposition as set out in their SGP was that the amendment to further characterise the coding RNA to exclude replicon RNA amounted to the addition of new matter. They referred to passages in the specification that indicate that the coding RNA can be selected from the group of mRNA, viral RNA, retroviral RNA and replicon RNA,[14] which they said makes it clear that the coding RNA of the claims can be replicon RNA.[15]
[14] SGP at (vii) and (viii), referring to the specification at page 23 lines 22 to 26, page 21 lines 11 to 17, page 23 lines 14 to 18 and page 23 lines 22 to 26.
[15] SGP at (ix).
24. The opponent went on to state that there is no basis in the application for the “negative limitations” in the proposed amendments. For example, there is no disclosure in the specification as originally filed that with regard to the coding RNA referred to in the claims, a replicon RNA is to be avoided. Professor Melief stated that in the context of the specification, there does not appear to be any reason or rationale for limiting the coding RNA to exclude replicon RNA, and that the specification specifically indicates that a replicon RNA can be used in the invention.[16] He considered that the specification taught that the different coding RNA are interchangeable, and therefore it made no sense to him to exclude replicon RNA from the claimed composition. He stated that:
“…excluding replicon RNA from the coding RNAs changes the nature of, or recharacterizes, the claimed invention. That is, limiting the coding RNA to require that it not be a replicon RNA suggests to me that the purpose of the coding RNA in the claimed composition is something other than the ensuring that the RNA can be translated to produce IL-12 protein in circumstances where it is clear that a replicon RNA could perform that function and was considered interchangeable by the authors. For example, the proposed claims appear to suggest that selecting non-replicon RNA is preferred relative to other coding RNA, and has advantages over other coding RNA. Relevantly, there is no evidence, from my reading of the application, to prefer non-replicon RNA, or to suggest that the use of a coding RNA that is not a replicon RNA has any advantage, for example, over replicon RNA.”[17]
[16] Melief 2 at [12] to [13].
[17] Melief 2 at [22]
25. The Opponent stated that as a result of the amendment, a feature that was not suggested to be significant is for the first time suggested to have a technical significance. In particular:
a.The skilled person could not have appreciated from the complete specification as filed that the feature of an mRNA that is not a replicon RNA was more generally applicable; and/or
b.The original context of the disclosure in respect of replicon RNA in the complete specification as filed is contradictory to that proposed by the amendments[18] (presumably as the specification as filed indicates the coding RNA can be replicon RNA).
[18] SGP at (xiv).
26. The Opponent concluded that the proposed amendment to claims 1 and 36 (and corresponding changes to the description) is therefore not allowable under subsection 102(1) because it results in the specification claiming and disclosing matter that extends beyond that disclosed in the specification as filed.[19]
[19] SGP at (xv).
27. The Applicant acknowledged that the specification as filed made it clear that the coding RNA can be replicon RNA, but it does not state that the coding RNA should or must be a replicon RNA. They referred to the evidence of Professor Pouton who stated that the amendments do not provide a different or new invention, but instead aligns the invention more closely with what is exemplified in the specification, namely the use of non-viral and non-replicon RNA such as mRNA. Thus, the amendment aims to clarify the scope of the invention. Rather than being the first time a defined feature is suggested to have a technical significance, a feature that has always had technical significance is being defined more narrowly.
28. The Applicant also noted that in most cases, and while not an automatic rule, amendments reducing the scope of a claim will usually satisfy the statutory requirements because they will not travel beyond the matter disclosed in the specification.[20] They referred me to Boehringer Ingelheim Animal Health USA Inc v Elanco New Zealand,[21] where an amendment was made to a claim defining a class of antiseptics to include a proviso “wherein the antiseptic is not an acridine”. The amendment was found to be allowable because the specification did not indicate a preference for acridine antiseptics. As there was no positive recommendation to use acridines, there was no fundamental inconsistency between the body of the specification and the amended claims. The Applicant submitted that the present case was like Boehringer since there is no positive recommendation in the present specification to use a replicon RNA or a viral RNA or retroviral RNA. They also noted that it is not unusual for a patent to disclose various possibilities but claim only certain features.[22]
Determination
[20] AS at [55].
[21] [2021] FCA 1457 at [112].
[22] AS at [57].
29. For simplicity, I have provided the following shortened form of the invention to highlight the issue in dispute. The proposed amendment seeks to incorporate the underlined portion:
An RNA containing composition when used in the treatment of tumor and/or cancer… comprising at least one coding RNA encoding interleukin-12 (IL-12)…
wherein the at least one coding RNA is an mRNA,
and wherein the at least one coding RNA is not a replicon RNA…
30. The scope of the claim, as accepted, is limited to compositions comprising an mRNA encoding IL-12.[23] The amendment characterises the at least one coding RNA as being an mRNA and not replicon RNA. The key issue in the Opponent’s SGP is that there is no disclosure in the specification as originally filed that, with regard to the coding RNA, a replicon RNA is to be avoided.
[23] The compositions can also include further coding and non-coding RNA components – see, for example, Claim 4.
31. I do not agree with this characterisation of the amendment as resulting in the coding RNA as excluding replicon RNA. I agree that the specification makes it clear that coding RNA used in the compositions includes replicon RNA. But it is the at least one coding RNA of the composition (that is, the “first” coding RNA in the composition) that must be mRNA and not a replicon RNA. Put in another way, the compositions of the invention must include at least one mRNA encoding an IL-12. This does not change the broader definition of coding RNA as set out in the specification.
32. I also note that the open-ended language of the claim allows for the inclusion of other components in the composition, including further coding or non-coding RNA components. In addition to being implicit in claim 1, this is explicitly defined in claims 4 and 5. Contrary to the statements in the SGP, the amendment does not result in the specification generally requiring that the coding RNA cannot be replicon RNA, or even that the compositions claimed cannot include replicon RNA.
33. As a further point, an alternative interpretation of the proviso is that it is intended to exclude replicon RNA as a type of mRNA. At first blush this would seem unnecessary since replicon RNA is not ordinarily considered to be an mRNA. For example, Professor Pouton stated that:
“In contrast to mRNA, the other coding RNA disclosed in the application are much larger pieces of RNA i.e. they are fragments of viruses either joined together or are entirely viral RNA. I would consider viral RNA, retroviral RNA and replicon RNA to encompass viral genomes or at least several viral genes and/or the respective regulatory sequences. The viral RNA, retroviral RNA and replicon RNA will contain coding RNA, but they are much more complex pieces of RNA compared to an mRNA (messenger RNA). Normally what we regard as 'mRNA' is just something that expresses a protein. In other words, mRNA would not be understood as a whole host of genes you would find in a virus. Therefore, in my opinion, the other terms mentioned under coding RNA are actually big complex molecules which I do not believe is the essence of the invention disclosed in AU'687. As I said above, I understand the invention is really about mRNA which necessarily encodes IL-12.”
34. Notwithstanding the accepted meanings in the art of these terms, evidence in the substantive opposition included comments in relation to a prior art document, D1.[24] The same document was raised in an opposition on the corresponding European application, which the Opponent entered into evidence in the present opposition.[25] D1 discloses intratumoral injection of a replication deficient Semliki Forest Virus (SFV) virion encoding IL-12 (SFV-IL12) in combination with an anti-PD-1 or anti-PD-L1 monoclonal antibody. While D1 does not refer to it as such, Professor Melief stated that the SFV-IL12 RNA virus genome encodes IL-12 and he therefore considered it a messenger RNA.[26] That being the case, the amendment could constitute a ‘belt and braces” approach such that if replicon RNA is interpreted as being mRNA, the amendment puts it beyond doubt that the at least one coding RNA, which is mRNA, cannot be replicon RNA.
[24] Quetglas J. et al., 2015, Virotherapy with a Semliki Forest Virus-Based Vector Encoding IL 12 Synergizes with PD- 1/PD-L1 Blockade, Cancer Immunology Research 3:449-454.
[25] Wickham at page 308.
[26] Melief 1 at [267].
35. In any case, I do not consider that the present amendment represents an impermissible intermediate generalisation. The SGP referred to CSIRO, where the invention was directed to a delta-6 desaturase characterised by substrate specificity and conversion preference. The specification disclosed these features together, but not individually. An amendment to define the enzyme only by its substrate specificity was considered an impermissible intermediate generalisation since in the context of the specification as filed the two properties were always together.
36. In contrast to the situation in CSIRO, there is no disclosure or suggestion that the at least one coding RNA must encompass a replicon RNA, or indeed any other alternative RNA referred to in the specification. The specification as filed includes different forms of the invention incorporating various coding RNA.[27] Moreover, the examples disclose specific compositions comprising mRNA encoding IL-12 and no other coding or non-coding RNA. The Opponent’s concerns appear to be a result of there being no literal disclosure in the specification corresponding to the wording of the proposed amendment. However, the limitation in the accepted claims that the composition comprises at least one mRNA encoding IL-12, in effect, excludes compositions where that RNA is viral RNA, retroviral RNA or replicon RNA and not mRNA. From a practical point of view, I am unable to envisage a situation where the proviso would result in the disclosure of something new.
[27] Specification at page 23.
37. In summary, the claim as proposed to be amended does not teach anything that the skilled person would not have gleaned from the specification as filed. Therefore, the Opponent has not made out this ground of opposition.
“Wherein the at least one coding RNA is not a viral RNA or retroviral RNA” (Pages 3 and 3a, Claims 36, 37 and 40)
38. The particulars on this point were essentially the same as made in relation to the proviso that the coding RNA is not replicon RNA. For similar reasons I do not consider the Opponent has made out this ground of opposition.
“Purified mRNA” (Claims 37 and 41)
39. The gist of the particulars on this point is that the amendment of claims 37 and 41 to include the feature “the at least one coding RNA is a purified mRNA” adds matter, and that as a result of the amendment a feature that was not suggested to be significant is, for the first time, suggested to have a technical significance.[28]
[28] SGP at [xxvii].
40. The Opponent noted that when making the amendment the Applicant stated that “[d]ependent claims 37 and 41 are added to specify that the ‘at least one coding RNA’ encoding IL-12 is ‘a purified mRNA’ (i.e. unformulated mRNA).” They also noted that Applicant’s statement that the basis for the amendment can be found at page 256, which states that the “RNA was purified using PureMessenger® (CureVac, Tübingen, Germany; WO2008/077592A1).” To that end, Professor Melief stated that
“The new proposed claims may make sense if there was a reasonable explanation for the use of purified (unformulated) RNA. However, from my review of the application there is no evidence provided in the application to prefer a purified (unformulated) RNA or that the use of a purified (unformulated) RNA has an advantage, for example, an advantage over the RNAs of the Examples which are formulated with RNAdjuvant.”
41. The Opponent stated in the SGP that the examples make it clear that the coding RNA is not unformulated, but instead is formulated with RNAdjuvant. There is no basis for the at least one coding RNA being a purified mRNA (i.e. unformulated mRNA). They also stated that the purified mRNA is stripped of its context in relation to the m7GpppG analog used to prepare the purified mRNA.
42. The Applicant cautioned that, in approaching the task of claim construction, the specification must be read as a whole, and too technical or narrow a construction of the claims must be avoided.[29] They argued that the Opponent’s reliance on CSIRO did not assist them since the inclusion of the feature that the mRNA is a purified mRNA does not suggest a new technical significance. The feature is implied in the claims since a purified mRNA encoding IL-12 is used and exemplified in the specification as originally filed.[30]
Determination
[29] Pfizer Overseas Pharmaceuticals v Eli Lilly [2005] FCAFC 224 at [249] to [250].
[30] AS at [61].
43. I do not consider the Opponent’s case as set out in the SGP to be persuasive.
44. Professor Melief does not appear to dispute that “unformulated” mRNA is taught by the specification. His concern appears to be that there is no “reasonable” explanation, or evidence in the specification, for it being “preferred”. Moreover, the reference to the term “unformulated” in his evidence is clearly based on the submissions made by the Applicant at the time they made the amendment rather than the meaning that the skilled person would give the terms used in the specification and claims. I therefore find his evidence of little assistance on this point.
45. I prefer the evidence of Professor Pouton who stated that:
“From my reading of the application and the amended claims, the meaning of purified mRNA is that the mRNA is made synthetically, and it is a defined mRNA separated from surplus reaction components (for example using purification methods), not that it is necessarily unformulated.”[31]
[31] Pouton at [210]
46. Thus Claim 1 defines a method of treatment using an mRNA-containing composition. One of the components in the composition is an mRNA that includes IL-12. The mRNA may be formulated with other excipients to provide mRNA-containing compositions. Claim 1 does not specify, for example, the source or purity of the mRNA component, and essentially covers the use of all forms in the composition. Proposed claim 37 and 41 limit the mRNA to a form that is purified – that is, one which is separated from other components such as reaction or cellular materials.[32] This is consistent with the established practice of drafting referred to by Beach J in CSIRO, where claims are directed to progressively narrower characterisations of the invention.
[32] AS at [63].
47. The specification teaches various general methods of chemical, in vitro and in vivo methods for preparing RNA,[33] as well as specific examples using mRNA, including mRNA encoding IL-12, which are prepared by transcription. Furthermore, while the mRNA in the examples is purified using PureMessenger®, there is nothing in the specification to suggest that the mRNA used in the compositions of the invention must be purified using this specific reagent.
[33] For example, specification at pages 19 to 21.
48. I therefore consider that the preparation and use of purified mRNA in the compositions of the invention are disclosed in the specification, including in a manner that would suggest that they are preferred. It follows that the amendment does not result in the feature that the mRNA is purified being, for the first time, suggested to have a technical significance.
49. In summary, this ground of opposition is unsuccessful.
Considerations under Subsection 102(2)(b)
50. The SGP states that, as a result of the amendments, proposed claims 1 and 36 to 41 are not allowable as the claims are unclear and are not supported by matter disclosed in the specification.
Clarity
51. The Opponent provided the following particulars in support of this ground. These essentially relate to the same issue of construction, and I have therefore considered them together.
Each of claims 36 to 38 and 40 to 42 refer to the at least one coding RNA. It is unclear if the at least one coding RNA refers only to the further coding RNA of at least claims 4 and 5, in addition to the at least one coding RNA that encodes IL-12 and is an mRNA wherein the at least one coding RNA is not a replicon RNA.
It is unclear if the at least one coding RNA of claims 36 to 38 refers to the further coding RNA of at least claims 4 and 5, in addition to the at least one coding RNA that encodes IL-12 and is an mRNA wherein the at least one coding RNA is not a replicon RNA of the claims.
Claims 36 and 40 refer to earlier claims (e.g. claim 5) which refer to the at least one coding RNA being viral RNA or retroviral RNA. It is unclear that when appended to at least claim 5, how the coding RNA can be both a viral RNA and not a viral RNA, or both a retroviral RNA and not a retroviral RNA.
Determination
52. A claim will lack clarity if a third party would be unable to ascertain whether an act would fall within the scope of the claim.[34]
[34] Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59.
53. Claim 1 defines compositions containing at least one coding RNA wherein “the at least one coding RNA is an mRNA”. Claim 4 defines that the that the RNA composition of claims 1 to 3 comprises “at least one further RNA”. That is, in addition to the first coding RNA which is mRNA as defined by Claim 1, the composition may contain a second coding or non-coding RNA.
54. Claim 5 is dependent on claim 4 and defines “the at least one further RNA is a coding RNA comprising…” The reference to the at least one further RNA in Claim 5 clearly relates to the second RNA. In contrast Claims 36 to 38 and 40 to 42 refer to “the at least one coding RNA”. This is clearly a reference to the first coding RNA component in the composition.
55. In short, I do not consider that the amendment results in a lack of clarity in the way suggested by the Opponent.
Support
56. The particulars provided on support in the SGP were much the same as those made under the ground of subsection 102(1). The Opponent is essentially arguing the same issue under the different grounds, namely that the matter introduced by the amendment was not taught by the specification as originally filed.
57. In particular, the Opponent provided the following material in support of this ground:
a)Proposed claims 1 and 39 seek to disclaim replicon RNA by indicating that the at least one coding RNA that is an mRNA is not a replicon RNA. However, the proposed amendments are not supported by matter disclosed in the specification.[35]
b)Claim 36 and claim 40 seek to disclaim viral RNA or retroviral RNA from the coding RNA that is an mRNA. For example, the proposed amendments indicate that the at least one coding RNA that is an mRNA and is not a replicon RNA, is also not a viral RNA or retroviral RNA. However, the proposed amendments are inconsistent with, and not supported by, the matter disclosed in the specification. [36]
[35] SGP, ground 2, particular (i).
[36] SGP, ground 2, particular (iv).
58. The Applicant noted that the Opponent has not articulated the technical contribution, and as a consequence their case under this ground is fatally flawed. They submitted that the invention disclosed does not relate to replicon RNA, or a viral RNA or retroviral RNA encoding IL-12, but rather to mRNA which necessarily encodes IL-12.[37] They submitted that the technical contribution to the art is premised on using an IL-12 mRNA to treat cancer.[38] The disclosure in the specification therefore provides support for the amendment to limit the RNA encoding IL-12 to an mRNA which is not a replicon RNA, or a viral RNA or retroviral RNA.
Determination
[37] Pouton at [160].
[38] AS at [89].
59. Support essentially requires that the extent of the patent monopoly, as defined by the claims, should correspond to the technical contribution to the art.[39] In CSR Building Products Limited v United States Gypsum Company, the delegate took the following approach to determine whether the claimed matter is supported by the matter disclosed in the specification:
(a) Construe the claims to determine the scope of the invention claimed.
(b) Construe the description and the technical contribution to the art, that is how far the concept has carried forward the state of the art.
(c) Decide whether the claims are supported by the technical contribution to the art. [40]
[39] Generics (UK) Ltd v H Lundbeck A/S [2008] EWHC 1903; [2008] RPC 29 at [241].
[40] [2015] APO 72 at [115].
60. The Federal Court has approved of this approach.[41]
[41] Cytec Industries Inc v Nalco Company (2021) 162 IPR 202.
61. Because subsection 102(2)(b) requires that the lack of support must be the result of the amendment, the consideration of whether the present amendments result in a lack of support is made based on the subject matter of the claims once the additional limitations are applied. In the present case, the claims prior to amendment define a method of treating tumors or cancer using a composition that comprises at least one coding RNA wherein the at least one coding RNA is an mRNA encoding IL-12. The proposed amendments further characterise the at least one coding RNA, which is defined to be an mRNA, as not being a replicon RNA, or a viral RNA or retroviral RNA. As discussed previously, this further characterisation of the first RNA is arguably unnecessary, in which case the scope of the claims before and after amendment is the same. But in any case, it seems to me that the nature of the amendment can only serve to further narrow, and not to expand, the scope of the claims.
62. It follows that the additional limitations incorporated by the amendments do not result in the claims lacking in support. The opposition fails on this ground.
Conclusion
63. The opposition is unsuccessful. The claims as proposed to be amended meet the requirements of subsections 102(1) and 102(2)(b).
Costs
64. Costs generally follow the event. I see no reason to depart from that approach. I therefore award costs according to schedule 8 against the Opponent, BioNTech RNA Pharmaceuticals GmbH.
Dr Leslie F. McCaffery
Delegate of the Commissioner of Patents
Annex
An RNA containing composition when used in the treatment
or prophylaxisof tumor and/or cancer diseases in a patient, wherein the RNA containing composition comprises at least one coding RNA comprising at least one coding region encoding at least one cytokine, or a fragment or variant thereof,wherein the cytokine is interleukin-12 (IL-12),
wherein the fragment or variant has the same biological function or specific activity compared to the full-length native protein,
wherein the at least one coding RNA is an mRNA, and wherein the at least one coding RNA is not a replicon RNA,
wherein the RNA containing composition is applied intratumorally, and
wherein the patient received or receives a checkpoint modulator selected from CTLA4 inhibitor and a PD-1 pathway inhibitor.
The RNA containing composition of claim 4, wherein the at least one further RNA is a coding RNA comprising
esat least one coding region encoding at least one peptide or protein selected from the group consisting of mRNA, viral RNA, retroviral RNA, and replicon RNA.
36. The RNA containing composition of any one of claims 1 to 35, wherein the at least one coding RNA is not a viral RNA or retroviral RNA.
37. The RNA containing composition of any one of claims 1 to 36, wherein the at least one coding RNA is a purified mRNA.
38. The RNA containing composition of any one of claims 1 to 37, wherein the at least one coding RNA is complexed with one or more lipids and thereby forming liposomes, lipid nanoparticles and/or lipoplexes.
3936. Use of an RNA containing composition for the manufacture of a medicament for the treatment or prophylaxis of tumor and/or cancer diseases in a patient, wherein the RNA containing composition comprises at least one coding RNA comprising at least one coding region encoding at least one cytokine, or a fragment or variant thereof,
wherein the cytokine is interleukin-12 (IL-12),
wherein the fragment or variant has the same biological function or specific activity
compared to the full-length native protein,
wherein the at least one coding RNA is an mRNA, wherein the at least one coding RNA is not a replicon RNA,
wherein the medicament is formulated to be applied intratumorally, and
wherein the medicament is formulated for useis for usewhen the patient received or receives a checkpoint modulator selected from CTLA4 inhibitor and a PD-1 pathway inhibitor.
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