Rozenberg & Co Pty Ltd. v Velin-Pharma A/S - [2017] APO 61

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Rozenberg & Co Pty Ltd. v Velin-Pharma A/S [2017] APO 61

Patent Application: 2010294197

Title:Method for the preparation of micro-RNA and its therapeutic application

Patent Applicant:  Velin-Pharma A/S
Opponent:  Rozenberg & Co Pty Ltd.
Delegate:  Dr A. Lim
Decision Date:  5 December 2017
Hearing Date:  12 September 2017, in Canberra

Catchwords: PATENTS – section 59 – opposition to the grant of a patent –allowability of amendments to the statement of grounds and particulars under subregulation 5.16 considered – lack of novelty in light of documents established – the concept of parametritis considered – the phrase “comprising a therapeutically effective amount of one or more miRNA molecule(s), said miRNA being upregulated in a blood serum preparation derived from a body fluid after activation of said body fluid” is purely descriptive and does not add a limitation to the claim – ‘grace period’ provisions of paragraph 24(1)(a), subregulations 2.2(1A) and 2.3(1A) considered require citation D13 be disregarded – lack of novelty in light of acts not established as information was not made publicly available by the doing of the acts – lack of inventive step in light of cited documents considered together with common general knowledge established – composition comprising upregulated amounts of miRNA is a manner of manufacture in light of D’Arcy v Myraid Genetics Inc [2015] HCA 35 – lack of clarity not established – lack of sufficiency not established – opposition succeeds – costs awarded against applicant – opportunity to amend

Representation: Patent attorney for the applicant: Dr Lee Miles from FB Rice. The patent applicant relied solely on written submissions
Counsel for the opponent: Mr Benjamin Fitzpatrick
Patent attorneys for the opponent: Dr Mark Wickham and Mr David Longmuir from Phillips Ormonde Fitzpatrick

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2010294197

Title:Method for the preparation of micro-RNA and its therapeutic application

Patent Applicant: Velin-Pharma A/S
Date of Decision: 5 December 2017
DECISION
The opposition is successful on the grounds of novelty and inventive step.
Each of claims 1, 2, 5, 6, and claims 9-11 and 17-20 that are dependent on claim 1 lacks novelty in light of the prior art. Each of claims 1-6 and claims 9-11 and 17-20 that are dependent on claim 1 lacks inventive step in light of the prior art considered together with CGK.
It has not been established that claim 17 is not a manner of manufacture in light of the D’Arcy v Myraid Genetics Inc [2015] HCA 35.
I allow Velin-Pharma A/S a period of two months from the date of this decision in which to propose amendments.
Costs according to Schedule 8 are awarded against Velin-Pharma A/S.
REASONS FOR DECISION

Patent application number 2010294197 (the opposed application) was filed on 10 September 2010 under the provisions of the Patent Cooperation Treaty. The applicants at the time of filing the opposed application were the inventors, Mr Flemming Velin and Mr Svend Lindenberg. A request by both inventors to assign their rights in the opposed application to Velin-Pharma A/S (Velin-Pharma) was filed on 29 September 2015. Copies of the deeds of assignment from Mr Flemming Velin and Mr Svend Lindenberg to Velin-Pharma were also filed. The assignment of the rights of the application to Velin-Pharma was recorded. The opposed application claims priority from the application EP09169937.1 (the priority document) which was filed on 10 September 2009.
The opposed application was examined and advertised accepted on 20 August 2015. Rozenberg & Co Pty Ltd. (Rozenberg) served a notice of opposition on 20 November 2015 and filed a statement of grounds and particulars (SGP) on 22 February 2016.
Velin-Pharma requested leave to make voluntary amendments to the claims of the opposed application on 24 August 2016. These amendments were allowed on 14 December 2016. Consequently, these amendments form part of the specification.
1 Amendment of the SGP
An application to amend Rozenberg’s SGP was filed on 30 August 2017, a day after Rozenberg filed written submissions for an oral hearing. Velin-Pharma made no submissions in regard to the amended SGP within the time period provided for comment.
A hearing was held on 12 September 2017 in Canberra to decide the opposition. Velin-Pharma represented by Dr Lee Miles did not attend the hearing and relied solely on written submissions. Rozenberg was represented by Mr Benjamin Fitzpatrick, counsel, and Dr Mark Wickham and Mr David Longmuir, patent attorneys.
At the hearing, in response to my question regarding the purpose of Rozenberg’s application to amend the SGP, Rozenberg told me that the amendments were being sought to align references to the claims in the SGP with the claims as amended on 24 August 2016. Rozenberg also noted, at the time, that it wished to review the claim numbering in its application to amend the SGP filed 30 August 2017.
After the hearing, Rozenberg filed a further application to amend the SGP on 28 September 2017. Rozenberg stated:
“The Opponent has prepared a revised Statement of Grounds and Particulars amended to clarify the particulars in relation to novelty. In particular, the amendments are to clarify that the documents relied on are relevant to all claims, including at least the specifically recited claims.”
On 12 October 2017, Velin–Pharma made submissions in regard to both sets of amendments to the SGP filed by Rozenberg.
In regard to the amendments to the SGP filed on 28 September 2017, Velin-Pharma submitted:
“The Applicant submits that the amendments are not merely for the purpose of clarification as contended by the Opponent, because nowhere in the Opponent’s original SGP, amended SGP filed 30 August 2017, evidence or written submissions has it been suggested, either explicitly or implicitly, that the prior art relied upon by the Opponent is alleged to be relevant to all claims. Rather, in each case, the Opponent has chosen to particularise claims to which the prior art documents are alleged to be relevant, and the evidence and written submissions filed reflect those particulars.”
and
“The amendment also comes as a surprise to the Applicant, as it was made after the Opponent’s full case was presented to the Applicant and Hearing Officer, and after the hearing date. Consequently, the Applicant has not had any chance to consider the implications of the amendments or to respond to the new allegations.”
and
“…..In this regard, the Applicant is unduly prejudiced by the unnecessary delays on the part of the Opponent in seeking this latest amendment.”
In regard to the amendments to the SGP filed on 30 August 2017, Velin-Pharma submitted:
“Although the timeframe set by the delegate for comment on the Opponent’s amendments to the SGP filed on 30 August 2017 has passed, we are also of the view that the Applicant is unduly prejudiced by the Opponent’s unnecessary delays in amending the SGP to add Meier [sic] et al., (2003) Inflamm. Res., 52(10):404- 407 (D20) as a prior art document to be relied upon for novelty.”
Velin-Pharma also submitted:
“If the amendments to the SGP outlined above are to be admitted then there will be a denial of natural justice to the Applicant.”
In order to address Velin-Pharma’s submissions regarding natural justice, a Delegate of the Commissioner invited Velin-Pharma to provide any further submissions, not already addressed in its written submission, on the novelty of all claims in light of the prior art documents cited in Rozenberg’s written submissions. On 27 October 2017 Velin-Pharma filed further submissions in relation to the citation authored by Meijer, H., et al, (2003) Inflamm. Res., 52(10):404- 407, in so far as the applicant considers the citation relevant to novelty of all claims. Rozenberg was also given an opportunity to respond to Velin-Pharma’s further submissions should it wish to do so. Rozenberg filed further submissions on 17 November 2017.
Subregulation 5.16 of the Patents Regulation 1991 (the Regulations) governs the amendment to the SGP in the present matter. The amendment to the SGP is subject to the Commissioner being satisfied that the amendment should be made.
The relevant factors taken into account when determining whether it is appropriate to make amendments to the SGP were considered in CSL Limited v Isconova AB et al (the CSL decision).[1] The factors include
[1] [2016] APO 82.
- the prospect of undue prejudice to a party — for example, the applicant may be unduly prejudiced by unnecessary delays in seeking amendment, or by the introduction of further particulars that change the case the applicant has to answer (as discussed in Diamond Scientific Company v CSL Limited (the Diamond decision))[2]; and
- the timing of the amendment request and the reasonableness of the explanation of the delay; and
- the public interest — noting that a correct determination of the opposition is one based on the issues properly raised in the opposition proceedings.
In regard to the consideration of undue prejudice, the Delegate in the Diamond decision stated:
“This is not to say, however, that all amendments to particulars will give rise to undue prejudice. Amendments to particulars may properly arise incidental to the preparation of the case - as distinct from efforts by the opponent to find a `better' basis for its opposition. In my view, extra particulars that arise incidental to the preparation of the case which:
i. do not result in any protraction of the preparation of the case, and
ii. are included by way of amendment of the statement of grounds and particulars at the earliest reasonable opportunity, and
iii. do not substantially change the case the applicant has to answer in the opposition
will not prima facie give rise to the applicant being unduly prejudiced by the relevant amendments.”[3]
[3] The Diamond decision at page 8.
As discussed above, the amendments to the SGP that Rozenberg seeks arise as a result of voluntary amendments to the claims. I consider the amendments that seek to align references to the claims in the SGP with the claims as amended by the voluntary amendments arise incidental to the preparation of the case. Whilst Rozenberg has chosen to particularise “at least” specific claims to which the prior art documents are alleged to be relevant, I consider it is reasonable to interpret an implicit reference that the prior art documents are relevant to all claims. I consider Rozenberg’s amendments to the SGP filed 30 August 2017 and 28 September 2017 seek to make what is implicit explicit. I note that in their written submissions Velin-Pharma appeared to have understood Rozenberg’s implicit allegation of lack of novelty to all claims.[4] I also note that Professor Hill made statements in his evidence-in-reply addressing the claims as amended by the voluntary amendments. Therefore, I consider Rozenberg’s amendments to clarify that the prior art documents relied on, for an allegation of lack of novelty, are relevant to all claims do not substantially change the case the applicant has to answer in the opposition.
[4] The written submissions of Velin-Pharma, dated 04 September 2017, at [30].
The citation authored by Meijer, H., et al, (2003) Inflamm. Res., 52(10):404- 407 is a document addressed by Professor Hill in his evidence-in-support (EIS) and provided as annexure AH-6. Velin-Pharma’s declarant, Ms Key, was aware of AH-6 when she made statements in relation to Professor Hill’s EIS. Ms Key acknowledges in her evidence-in-answer that the annexures of Professor Hill were provided to her. I also note that Velin-Pharma addressed AH-6 in their written submissions.[5] Therefore, I consider Rozenberg’s amendment of the SGP to add AH-6 as a prior art document to be relied upon for novelty does not substantially change the case the applicant has to answer in the opposition.
[5] The written submissions of Velin-Pharma, dated 04 September 2017, at [78] - [82].
I conclude that any prejudice suffered by Velin-Pharma as a result of the collective effect of the two sets of amendments to the SGP is not undue prejudice.
In regard to timeliness of the amendment requests, Rozenberg filed the first set of amendments after filing its written submissions and the second set of amendments after the hearing. Rozenberg’s requests to amend the SGP were clearly not timely. The purpose of the SGP is to give early notice of the opponent’s case, and whilst the amendments to the patent specification may require the opponent to make consequential changes, “the expectation still must be that amendments to the statement are made at the earliest reasonable opportunity.”[6] Whilst not unimportant, the delay in Rozenberg’s request to amend the SGP is not sufficient to weigh in favour of not allowing the amendments because of the nature of Rozenberg’s amendments.
[6] The CSL decision at [14] - [15].
It is in the public interest that a correct determination of the opposition is one based on the issues properly raised in the opposition proceedings.
On balance, I am satisfied that the amendments to the SGP filed on 30 August 2017 and 28 September 2017 should be allowed.
2 The opposition
The grounds of opposition pressed at the hearing were novelty, inventive step, manner of manufacture, sufficiency and clarity.
The evidence is summarised in the table below.

Evidence Declarant Exhibits Date Reference

In Support Andrew Hill AH-1 to AH-9 23 May 2016 Hill #1

Dominic Wall DW-1 to DW-3 23 May 2016 Wall

Julian Willmore JW-1 to JW-3 20 May 2016 Willmore

In Answer Stine Thuren Key STK-1 to STK-5 19 August 2016 Key

In Reply Andrew Hill AH-10 to AH-11 24 October 2016 Hill #2

The request for examination of the opposed application was filed on 12 April 2013. As a consequence, the substantive amendments of the Patents Act 1990 (the Act) brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 do not apply to the present application. This includes the amendment to subsection 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. The onus of proof in this opposition rests with Rozenberg who must demonstrate that it is clear that a valid patent cannot be granted.[7]
[7] F.Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283 at [67]; 50 IPR 305, Commissioner of Patents v Sherman [2008] FCAFC 182 at [18]; 79 IPR 426.
The standard of proof of evidence leading to a conclusion of lack of novelty or lack of inventive step as stated by Besanko J. in Aspirating IP Limited v Vision Systems Limited is proof to a level of practical certainty:
“The primary facts are to be established on the balance of probabilities, but the ultimate facts – the facts leading directly to a conclusion of a lack of novelty or a conclusion of obviousness – must be proved to the level of practical certainty. In Austal Ships, Bennett J said (at 423 [12]):
‘I can accept that a lower standard may apply to proof of evidence such as whether a document has been published or, indeed, whether a prior art vessel was well-known. I do not accept that it properly applies to the factual question that itself is the test for obviousness or lack of inventive step. Where the factual question is itself the legal test, as set out in s 7(3) of the Act, it seems to me that it should be determined at the higher standard. That means that where there are two opposing expert views that are conclusive on obviousness, both presented bona fide by witnesses of accepted expertise, unless one set of views can be rejected on proper grounds, the legal burden to establish a ground of opposition is not discharged; the court cannot be practically certain that obviousness or lack of inventive step is established.’”[8]
[8] [2010] FCA 1061 at [35]; 88 IPR 52.
3 The specification
The specification relates to a method of preparing compositions and therapeutic applications of the prepared compositions. The specification has 21 claims. There are two independent claims: claim 1 and 8. Claim 21 is an omnibus claim. The full claim set is reproduced in the Annex to this decision.
3.1 Principles of construction
The principles of construction of specifications are well established:
“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.”[9]
[9] Eli Lilly and Company Limited v Apotex Pty Ltd [2013] FCA 214 at [139]; 100 IPR 451.
3.2 The background to the invention
Inflammation is described by the specification as being a key component of the immune system which functions in both physiological and pathophysiological events to maintain homeostasis of tissues, organs and individual cells.[10] The specification states:
[10] The present specification at page 1.
“Without inflammation, wounds and infections would not be able to heal and progressive destruction of the tissue would threaten the survival of the organism. Inappropriate inflammation, on the other hand, can lead to various diseases, including but not limited to indications such as hay fever, atherosclerosis, neurodegenerative diseases such as Alzheimer's, cancer and rheumatoid arthritis. For these reasons, inflammation is tightly regulated by the body.”[11]
[11] The present specification at page 2.
The specification describes a potential role of microRNAs (miRNAs) as regulators of the immune system and disease. The specification states:
“MicroRNAs (miRNAs) are short (about 21-24-nucleotides) noncoding RNAs that are thought to regulate gene expression through sequence-specific base pairing with target mRNAs. The underlying mechanism is still poorly understood, but it appears to involve the inhibition of translational initiation.
Many of the functional roles of microRNAs hint at the potential involvement of microRNAs in human disease, and as major regulators of growth and proliferation. As many microRNAs are de-regulated in primary human tumours, a role of microRNAs in human cancers has been suggested. Accordingly miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from myocardial infarction to cancers.
Potential roles of microRNAs in the development as well as the regulation of the immune system have also been suggested.”[12]
[12] The present specification at page 1.
The specification states that glucocorticoids and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) represent the most effective treatment for inflammatory conditions but have side effects that may threaten the overall health of the patient.[13]
[13] The present specification at pages 2 - 3.
3.3 The aim of the invention
The specification states:
“There remains a need to develop a safe, effective method of treating autoimmune diseases, inflammatory disorders, and cancers or other indications associated with abnormal cell growth or cell division. The present invention provides compositions and methods for treating such diseases and disorders.
…..
The invention provides compositions suitable for the treatment of autoimmune diseases, inflammatory disorders, and cancers or other indications associated with abnormal cell growth or cell division, including but not limited to infertility, decreased sperm production, abortus habitualis and colitis.”[14]
[14] The present specification at page 3.
3.4 The invention as described
The specification states that the inventors of the opposed application found that upon activation of blood fluids certain miRNAs are upregulated in the body fluids.[15]
[15] The present specification at pages 3 and 6.

The term ‘activation’ is stated in the specification to refer the following:
“the treatment of a body fluid or element thereof in vitro or in vivo, for a period of time in a container comprising a surface, such as a surface that is able to trigger an immunological response in the leukocytes, such as monocytes or dendritic cells of a blood preparation. In some embodiment whole blood is activated by exposure to an enhancing agent, or by stimulation to express an enhancing agent.”[16]
[16] The present specification at pages 11 - 12.
The specification also states that the inventors:
“found that such activated body fluid may be used in the treatment of a wide range of indications, such as diseases or disorders associated with inflammation, a disease of the immune system, such as undesirable activation of the immune system, cancer or other indications associated with abnormal cell growth or cell division.
Accordingly the present inventors have realised that compositions may be prepared to contain therapeutically effective miRNA molecules or functional variants thereof.”[17]
[17] The present specification at page 6.
Under the heading “Summary of the invention” the specification sets out the invention in various aspects. These aspects include (1) methods for the preparation of a composition comprising a therapeutically effective amount of one or more miRNA molecule, the miRNA being upregulated in a body fluid upon activation of the body fluid; (2) compositions prepared by such methods for the preparation of a medicament; and (3) methods of treatment or alleviating symptoms of a disease or disorder associated with inflammation, a disease of the immune system such as undesirable activation of the immune system and/or cancer or other indications associated with abnormal cell growth or cell division, the method comprising administering the compositions comprising a therapeutically effective amount of one or more miRNA molecule.[18] I note that these three mentioned aspects are described in the examples of the specification.
[18] The present specification at pages 3 - 6.
The Examples
Example 1 describes the preparation of activated serum from blood. Example 1 reads:
“Blood is collected from either an animal or human being or alternatively a population of animals or human beings, preferably without any infection or fewer. The blood is taken by a venous transcutane puncture and collected in a container. Hereafter whole blood or alternatively buffy coat with or without plasma is transferred to a container with a surface, or containing an activating substances such as glass beats [sic] etc, preferably a 60 ml container suitable for centrifugation comprising two rubber ports for injection and a small hole for pressure equalization, the container being with or without 2 -25 gram of glass beads, 1-8 mm, such as 4mm.
In some embodiments a buffy coat preparation with or without a plasma fraction is incubated together with a growth medium. This may be either prior to or during the procedure exposing the body fluid to the activating surfaces.
The sample is regurgitating or in any other procedure exposing the blood cells to the activating surfaces for 1, 2, 4, 10, 24, 48, 72, 96, 120, or 150 hours in 37 degrees celcius [sic].
Hereafter the incubation is terminated by lowering the temperature to room temperature and separating the serum from the clotted blood by filtration or centrifugation. In some embodiments of the invention the whole blood is incubated using anticoagulants and after the incubation time the serum is collected by centrifugation or filtration.
The prepared serum, plasma or buffy coat preparation is then stored either at room temperature, frozen at -5-18 degrees celcius [sic] or otherwise prepared for freezing storage to optimized [sic] the preservation of more complex structures as membrane like vesicles etc.”[19]
[19] The present specification at pages 35 - 36.
In Example 1, the serum is prepared from blood of an animal or human being. The blood is collected in a container that is suitable for centrifugation and incubated in the container for various periods of time at 37 degrees Celsius. The container can include glass beads to increase the surface area that the blood is exposed to. However, I note that Example 1 includes within the method described incubating the collected blood in contact with the surface of the container itself. After the incubation period, the serum is collected by centrifugation or filtration.
Example 2 describes the preparation of activated serum from blood by an alternative procedure that includes the exposure of blood to glass beads during an incubation period and centrifugation to separate the serum from blood cells. Example 2 reads:
“Blood is incubated in sterile 60 ml containers over a time period of 2-72, 96, 120, or 150 hrs, which container contain glass beads (SiliBeads-Borosilicate, Sigmund Linder, Germany). Glass beads are 2-5 mm, such as 2-4 mm in diameter, and are of medical grade. The container are packed with 5-25, such as 18 grams of beads and may be sterilized either by autoclaving or gamma- irradiation.
Blood culture techniques: In all experiments, containers (e.g. 60 ml container) packed with beads are filled with freshly drawn human whole blood from healthy, male or female donors, between 20 and 70 years old, without anti-coagulants unless mentioned otherwise. Whole blood cultures are established under sterile, laminar flow conditions. Incubation is carried out aseptically at 37°C, 5% C02 for 2-72 hrs intervals. After incubation, serum is retrieved and centrifuged (4200 rpm, 10 min). Alternatively after incubation the serum is separated from the blood cells by centrifugation at 5000 g for 10 min.”[20]
[20] The present specification at page 36.
Examples 3-5 describe the administration of the activated serum prepared in Examples 1 or 2 for the treatment of various conditions in human subjects.[21] Example 3 describes administration of the activated serum to treat inflammation and the associated pain. Example 4 describes administration of the activated serum to alleviate symptoms associated with endometriosis. Example 5 describes administration of the activated serum to two patients during In Vitro Fertilisation (IVF). The specification suggests improvement in the conditions of Examples 3 and 4, and conception of one patient in Example 5, to be due to the administration of the activated serum.
[21] The present specification at pages 36 - 37.
Examples 8 describes in vitro assays — miRCURY^TMLNA Array microRNA profiling service performed by Exiqon (Denmark) — were done on the activated serum prepared in Examples 1 and 2.[22] Table 1 of the specification show the results of the in vitro assays and report a 1.01 to 2.40 fold change in the concentration levels of different miRNA species.[23]
[22] The present specification at page 38.
[23] The present specification at pages 39 - 40.
Example 13 describes an in vitro assay done on activated serum prepared in Examples 1 and 2 where there was an incubation period of 150h.[24] The specification describes the amount of miRNA in the activated serum was assessed by quantitative PCR and compared to control samples. The specification states a range of different miRNA species upregulated 1.5 to 680 times.
[24] The present specification at pages 42 - 43.
Example 9 describes reduction of cell proliferation of tumour cells in vitro by application of the activated serum prepared in Examples 1 and 2.[25] Examples 10 and 11 describe the treatment of tumours in horses by the administration of activated serum prepared in Examples 1 and 2.[26] The specification suggests the reduction in tumours in the horses to be due to the administration of the activated serum.
[25] The present specification at pages 40 - 41.
[26] The present specification at page 41.
3.5 The field of the invention and the problem addressed
The specification states:
“FIELD OF THE INVENTION
The present invention relates to compositions comprising a therapeutically effective amount of miRNAs, their use for the treatment of medical conditions benefiting from being treated with these compositions. Also encompassed by the present invention are methods for the preparation of a composition comprising miRNAs.”[27]
[27] The present specification at page 1.
Rozenberg submitted:
“The field of the invention is compositions comprising therapeutically effective miRNAs and methods for their preparation. The problem faced by the skilled addressee is how to develop such compositions.”[28]
[28] The written submissions of Rozenberg, dated 29 August 2017, at [135] which references the opposed specification, page 1, lines 3-6 and Hill #1 at [23].
Velin-Pharma submitted:
“It is also noted that in the Opponent's submissions dated 29 August 2017, the ‘problem to be solved’ at paragraph [135] has been impermissibly formulated to include the solution. It was not previously known that miRNAs could or would be upregulated in a blood composition following activation in accordance with the present invention. Inclusion of the claimed invention within the ‘problem to be solved’ is an entirely inappropriate use of the problem-solution approach.”[29]
[29] The written submissions of Velin-Pharma, dated 04 September 2017, at [120].
At the oral hearing I asked Rozenberg how it formulated the problem to be solved by the opposed application and the relevance of the prior art citations it relies on since most of these citations, as will be discussed below, do not mention miRNA.
Rozenberg submitted that the field of the invention is to be understood in the context of statements in the specification regarding the background of the invention. Rozenberg referred me to the following paragraphs in the specification — which I have considered above to be the aim of the invention — and acknowledged that the field of the invention is blood serum compositions:
“There remains a need to develop a safe, effective method of treating autoimmune diseases, inflammatory disorders, and cancers or other indications associated with abnormal cell growth or cell division. The present invention provides compositions and methods for treating such diseases and disorders.
…..
The invention provides compositions suitable for the treatment of autoimmune diseases, inflammatory disorders, and cancers or other indications associated with abnormal cell growth or cell division, including but not limited to infertility, decreased sperm production, abortus habitualis and colitis.”[30]
[30] The present specification at page 3.
Rozenberg submitted that the prior art citations it relies on are relevant since these citations are in regard to blood serum compositions.
From the written submissions quoted below, I consider that Velin-Pharma characterises the field of the invention as “immunostimulatory compositions from blood” and “conditioned blood preparations”:
“The Opponent's SG&P fails to identify who the PSA would be in the present matter. However, we submit that the PSA can be considered to be someone having a practical interest in formulating immunostimulatory compositions from blood for administration for the treatment of one or more medical conditions.”[31]
[31] The written submissions of Velin-Pharma, dated 04 September 2017, at [102].
and
“In the Opponent's submissions dated 29 August 2017, we note that when addressing the issue of inventive step, the Opponent has defined the PSA at paragraph [33] as:
‘ .... a person, or more likely a group of persons, involved in research and development into the relevance of miRNA and exosomes to disease’
In this regard, we submit that the Opponent has impermissibly framed the PSA with the benefit of hindsight based on the teaching in the opposed application, as it was not previously known that miRNAs could be upregulated in a blood composition which has undergone activation in accordance with the present invention, much less that such upregulated miRNAs would be therapeutically effective for treating disease. At best, the PSA may be considered a person or persons involved in research and development into the relevance of protein factors in conditioned blood preparations to disease, as is reflected by the prior art submitted by the Opponent.”[32]
[32] The written submissions of Velin-Pharma, dated 04 September 2017, at [119].
I am satisfied that the field of the invention and the problem to be solved by the opposed invention is to be understood in the context of the whole specification including the background to the invention. As I have discussed above, the specification describes preparation of activated serum compositions from blood — these compositions are also referred to as conditioned serum preparations from blood[33]. Therefore, I conclude the field of the invention is in regard to conditioned serum preparations from blood, and the problem addressed by the opposed application is the development of improved conditioned serum compositions from blood and methods for their preparation.
[33] The present specification at page 11, lines 30 - 32; Hill#1 at [132] - [133], [255], [275] - [276].
3.6 The person skilled in the art
It is well established that many of the issues in an opposition are answered by reference to the person skilled in the art:
“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.”[34]
[34] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [70]; 177 ALR 231.
However, the person skilled in the art is an artificial construct that is used as a tool of analysis, and there is a danger in trying to identify them as an actual person or persons:
“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.”[35]
[35] AstraZeneca AB v Apotex Pty Ltd [2015] HCA 30 at [23]; 89 ALJR 798.
An understanding of the person skilled in the art is based on evidence from persons with knowledge of the art as to the things that they know and do, and what they understand to be commonly known and done. In this opposition there are declarations by a number of people. They are Professor Hill, Dr Wall, Mr Willmore and Ms Key. Professor Hill has many years of research experience working at different universities and research institutes. Professor Hill states in his declaration that by 2009 his laboratory had a well-established research programme which included work in exosomes, including their role and association with disease, and exosomes derived from body fluids.[36] Professor Hill also states that by 2009, he was working on miRNA and investigating the role they play in the transfer of transmissible prion proteins between cells.[37] Dr Wall has many years’ experience working at the Centre for Blood Cell Therapies and Department of Pathology, Peter MacCallum Cancer Center. [38] Mr Willmore is a veterinary surgeon with many years’ experience working on equine medicine and surgery.[39] Ms Key is a developmental scientist and she states in her declaration that she graduated with a Bachelor of Science in Biology from Copenhagen University with specialized studies in the detection of miRNA in serum.[40]
[36] Hill #1 at [8]; Annexure AH-1.
[37] Hill #1 at [8].
[38] Wall at [1] - [11]; Annexure DW-1.
[39] Willmore at [1] - [14]; Annexure JW-1.
[40] Key at [2] - [3]; Annexure STK-1.
Rozenberg submitted:
“As at the Priority Date the deponent for the Applicant (Ms Key), had recently completed her Bachelor of Science degree and only just commenced a Master of Science and Engineering degree the month before.¹³ She has not listed any scientific publications in her CV,¹⁴ nor were any scientific publications, or any publications in the field of miRNAs, able to be found, either before or after the Priority Date.¹⁵ It is unlikely that Ms Key had the necessary qualifications or experience to be considered a person skilled in the art as at the Priority Date and her evidence in relation to what would have been known or understood by a PSA at the Priority Date should be treated with caution.”[41]
[41] The written submissions of Rozenberg, dated 29 August 2017, at [34] which references Annexure STK-1 and Hill#2 at [27].
I consider that all of the declarants mentioned above are in a position to provide evidence as to what the person skilled in the art knew and would have done. The weighing and evaluating of the evidence to decide the characteristics of the person skilled in the art is part of the normal work of a delegate of the Commissioner.
3.7 The invention as claimed
The correct approach to the construction of claims was discussed by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd.:
“the words in a claim should be read through the eyes of the skilled addressee in the context in which they appear … while the claims define the monopoly claimed in the words of the patentee's choosing, the specification should be read as a whole … it is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification … terms in the claim which are unclear may be defined or clarified by reference to the body of the specification”[42]
[42] [2009] FCAFC 70 at [118] – [120]; 81 IPR 228.
Claim 1
Claim 1 is the first independent claim of the present application. It reads:
“A method for the preparation of a composition comprising a therapeutically effective amount of one or more miRNA molecule(s), said miRNA being upregulated in a blood serum preparation derived from a body fluid after activation of said body fluid, the method comprising the steps of
a)Collecting said body fluid from a mammal;
b)Incubating the collected body fluid in contact with an increased surface area for more than 24 hours;
c)Collecting said body fluid produced after step b) and preparing the serum preparation comprising the upregulated miRNA therefrom.”
What does the method of claim 1 define?
Claim 1 recites a method that includes the following three steps:
(1) a collection step where a body fluid from a mammal is collected (step a),
(2) an incubation step of more than 24 hours where the collected body fluid is placed in contact with an increased surface area (step b); and
(3) a serum preparation step where after incubation the body fluid is collected and serum is prepared from the incubated body fluid (step c).
I will now consider the meaning of several terms in claim 1.
“body fluid”
The specification provides the following definition for a body fluid:
“The term ‘body fluid or element thereof’ refers to any fluid or elements derived thereof that may be obtained from the body of a mammal. Included within this definition are cerebrospinal fluids, blood, such as blood from the circulatory system or from the umbilical cord, serum, lymph fluid, plasma, pleura exudates, peritoneal exudates, bone marrow exudates, extracellular fluids, fluids from the joints, amniotic fluids. Included within this definition are also cells, such hematopoietic stem cells or in vitro cell cultures, such as a monocyte cell cultures, as well as exosomes or other substructures that may be derived from a body fluid.”[43]
[43] The present specification at page 11.
Since claim 1 recites the miRNA as being upregulated in a blood serum preparation derived from a body fluid, the person skilled in the art would understand the method as being in the context of preparing a serum preparation from blood — that is, the body fluid is blood.
“more than 24 hours”
Step b of claim 1 defines an incubation step of “more than 24 hours”. Adopting a plain meaning of the words, the terms mean incubating the collected blood for any time period that is more than 24 hours.
“upregulated”

The term “upregulated” is a technical term that the skilled person would understand in the context of the concentration level of miRNA in the blood serum preparation. The specification describes the miRNA to be in a concentration which is expressed as a percentage that is higher than the concentration level of miRNA in a composition that has not been activated by step b.[44] The specification also describes the concentration of miRNA as a fold increase “such as 0.00001 to 1000 fold increase in the measurable amount during activation”.
[44] The present specification at page 26 describes embodiments where the one or more miRNA is upregulated to a concentration level at least about 50% to 800% as compared to the concentration level of miRNA that has not been activated under step b.
“activation”
As discussed above, the term “activation” is defined in the specification.[45] In the context of claim 1, the skilled person would understand “activation of said body fluid” to mean a biological mechanism that is triggered in response to incubating the collected blood in contact with an increase surface area for more than 24 hours. The mechanism that is triggered results in an increase in the concentration level of miRNA.
[45] The present specification at pages 11 - 12.
“increased surface area”
As discussed above Example 1 describes a method of incubating the collected blood in a container that is suitable for centrifugation with or without glass beads. Whilst the specification describes glass beads to be a means for increasing the surface area that the collected blood is exposed to,[46] I consider that the skilled person would understand from Example 1 that incubating the collected blood in a container with a surface to fall within the scope of “incubating the collected body fluid in contact with an increased surface area” as recited in claim 1. My conclusion is consistent with the following description in the specification which states that the wall of the chamber of prior art devices as having a surface structure which stimulates the production of miRNA:
[46] The present specification at page 6.
“In still other alternatives peripheral blood, a preparation of bone marrow, or other preparation containing blood components is removed from an individual or obtained in other ways, transferred to a device as described herein or potentially in any one of EP0740964, EP1638691, W02008097230, EP1093390, or EP1549552, the device being prefilled in the chamber for collection of supernatant with beads to stimulate the production of miRNA, or the wall of the chamber for collection of supernatant having a surface structure, including a clean surface, which stimulates the production of miRNA according to methods of the present invention.”[47]
[47] The present specification at page 18.
“preparing the serum preparation comprising the upregulated miRNA therefrom”
Example 1 discussed above describes techniques for separating serum from clotted blood or blood that was treated with anticoagulants— these techniques being centrifugation and filtration. Example 2 discussed above also describes centrifugation at different speeds to separate serum from blood cells.
Professor Hill states:
“The method of claim 1 now also includes the step of preparing the blood serum preparation from the body fluid (assumed to be blood) in step c). Blood serum is the fluid without the red or white blood cells. As discussed in my First Declaration, the serum will contain all proteins not used in clotting and numerous other molecules. No details as to the blood serum preparation are specified in claim 1 although blood serum is routinely prepared by collecting whole blood, incubating the blood to allow it to clot then pelleting the clot by centrifugation. The resulting supernatant is the blood serum.”[48]
[48] Hill #2 at [12].
Reading step c of claim 1 in the context of the specification and in light of routine methods known to the skilled person, the skilled person would understand step c of claim 1 to include techniques that are performed for the purpose of separating the serum that comprises the upregulated miRNA from the clotting proteins of blood. The techniques include centrifugation and filtration.
I note that apart from centrifugation or filtration, there are no steps described in the in Examples 1 and 2 to further purify the miRNA contained in the activated blood serum. As discussed above, Example 8 and Table 1 of the specification describe an increase in the concentration levels of various different miRNA species. Read in the context of the specification, the person skilled in the art would understand the blood serum prepared by the method of claim 1 to comprise a mixture of different miRNA species of which at least one miRNA species is present in an increased concentration level.
“a therapeutically effective amount of one or more miRNA molecule(s), said miRNA being upregulated in a blood serum preparation derived from a body fluid after activation of said body fluid”
I will now consider what “a therapeutically effective amount of one or more miRNA molecule(s)” means. Under the hearing “Detailed disclosure of the invention” the specification states:
“The present inventors have found that upon activation, such as stimulation on a surface of body fluids containing monocytes certain miRNAs are upregulated. The present inventors have also found that such activated body fluid may be used in the treatment of a wide range of indications, such as diseases or disorders associated with inflammation, a disease of the immune system, such as undesirable activation of the immune system, cancer or other indications associated with abnormal cell growth or cell division.
Accordingly the present inventors have realised that compositions may be prepared to contain therapeutically effective miRNA molecules or functional variants thereof.”[49]
[49] The present specification at page 6.
Examples 1 and 2 describe a method of preparing a blood serum preparation comprising an increased concentration level of different miRNA species. As discussed above, the prepared blood serum was administered to human subjects or horses to treat various conditions and the specification reports improvement of the conditions as a result of the administered blood serum.
Reading the phrase “a therapeutically effective amount of one or more miRNA molecule(s)” in the context of the subsequent phrase in claim 1, and the specification as a whole, the skilled person would understand that “a therapeutically effective amount” to be a definition by reference to the result achieved by performing the steps of claim 1. When the steps of claim 1 are performed, the result is an increased concentration level (upregulation) of at least one miRNA species. I consider the skilled person would understand that any increased concentration level of miRNA as a result of performing the steps of claim 1 would be “a therapeutically effective amount of one or more miRNA molecule(s)”. My interpretation is consistent with the specification which describes a therapeutic effect was observed in each example described.
In summary, I interpret claim 1 to define a method that includes the three steps (steps a, b and c) mentioned above. The result of performing the three steps is the preparation of a composition comprising an increased concentration (upregulated) level of at least one miRNA species. This increased concentration level of at least one miRNA species is a therapeutically effective amount of one or more miRNA molecule(s).
Rozenberg made submissions with respect to clarity of the terms “therapeutically effective” and “therapeutically effective amount” in claim 1. These submissions are discussed below where I consider the ground of clarity.
Claim 8
Claim 8 reads:
“A method for the preparation of a composition comprising a therapeutically effective amount of one or more miRNA molecules(s), said miRNA being upregulated in a blood serum preparation derived from a body fluid after activation of said body fluid, the method comprising the steps of:
a)   Collecting said body fluid from a mammal;
b)   Incubating the collected body fluid in contact with an increased surface area for more than 24 hours;
c)   Identifying one or more miRNA upregulated in said body fluid;
d)   Providing said one or more miRNA molecule identified in step c) in isolated form and adding them to said composition”
What does the method of claim 8 define?
Claim 8 recites a method that includes the four steps, the first two steps mentioned above being the same as that defined in claim 1. I will now consider what steps c and d of claim 8 mean.
Step c: “Identifying one or more miRNA upregulated in said body fluid”
The specification provides the following definition and characterisation of miRNA:
“As used herein, the term ‘miRNA’ or ‘miR’ or ‘microRNA’ means a non-coding RNA between 17 and 25 nucleobases in length which hybridizes to and regulates the expression of a coding RNA. A 17-25 nucleotide miRNA molecule can be obtained from a miR precursor through natural processing routes (e.g., using intact cells or cell lysates) or by synthetic processing routes (e.g., using isolated processing enzymes, such as isolated Dicer, Argonaut, or RNAase III). It is understood that the 17-25 nucleotide RNA molecule can also be produced directly by biological or chemical syntheses, without having been processed from a miR precursor.
As used herein the term ‘miRNA molecule’ refers to any nucleic acid molecule representing a miRNA. Included within this definition is natural miRNA molecules, pre-miRNA, pri-miRNA, miRNA molecules identical in nucleic acid sequence to the natural forms as well as nucleic acid sequences, wherein one or more nucleic acids has been replaced or is represented by one or more DNA nucleotide and/or nucleic acid analogue. miRNA molecules is in the present specification occasionally refered [sic] to as a nucleic acid molecule encoding a miRNA or simply nucleic acid molecule.”[50]
[50] The present specification at pages 10 - 11.
The specification states the following about nucleic acid sequences of miRNA:
“Nucleobase sequences miRNAs and their corresponding stem-loop sequences described herein may be found in miRBase, an online searchable database of miRNA sequences and annotation, found at Entries in the miRBase Sequence database represent a predicted hairpin portion of a miRNA transcript (the stem-loop), with information on the location and sequence of the mature miRNA sequence. The miRNA stem-loop sequences in the database are not strictly precursor miRNAs (pre-miRNAs), and may in some instances include the pre-miRNA and some flanking sequence from the presumed primary transcript. The miRNA nucleobase sequences described herein encompass any version of the miRNA, including the sequences described in Release 10.0 of the miRBase sequence database and sequences described in any earlier Release of the miRBase sequence database. A sequence database release may result in the re-naming of certain miRNAs. A sequence database release may result in a variation of a mature miRNA sequence.”[51]
[51] The present specification at page 13.
Reading the phrase “Identifying one or more miRNA upregulated in said body fluid” in context of the specification, the skilled person would understand step c of claim 8 to mean characterising the species of miRNA based on the nucleic acid sequence of the miRNA, for example using known databases to identify the miRNA contained in the body fluid.
Step d: “Providing said one or more miRNA molecule identified in step c) in isolated form and adding them to said composition”
The specification states:
“In some embodiments the nucleic acid molecule used in the compositions of the invention is prepared by synthetic means.”[52]
[52] The present specification at page 24.
As described above, the nucleic acid molecule encoding a miRNA can be produced by using isolated enzymes, such as Dicer, Argonaut or RNAaseIII, or by chemical synthesis. The specification also states that the miRNA prepared by synthetic means “may be crude or purified”.[53] Reading the phrase “Providing said one or more miRNA molecule identified in step c) in isolated form” in context of the specification, the skilled person would understand step d of claim 8 to mean supplying an identified species of miRNA that was prepared by using isolated enzymes or by chemical synthesis.
[53] The present specification at page 14.
What is “said composition”?
Reading the phrase in the context of the other words in claim 8, I consider “said composition” to mean “a composition comprising a therapeutically effective amount of one or more miRNA molecules(s), said miRNA being upregulated in a blood serum preparation derived from a body fluid after activation of said body fluid”. Therefore, I interpret step d of claim 8 to be a step of adding identified miRNA, prepared by using isolated enzymes or by chemical synthesis, to the body fluid that was collected from a mammal and that had been incubated for more than 24 hours as recited in step b of claim 8
For the same reasons as discussed for claim 1, the person skilled in the art would understand the body fluid of claim 8 to be blood.
In summary, I interpret claim 8 to define a method that includes four steps (steps a, b, c and d) mentioned above.
Claim 17
Claim 17 reads:
“A composition comprising a therapeutically effective amount of one or more miRNA molecule(s), said miRNA being upregulated in a blood serum preparation derived from a body fluid after activation of said body fluid obtained by a method according to any one of claims 1 to 16; for use as a medicament.”
What does the composition of claim 17 define?
Claim 17 defines a composition obtained by a method recited in any one of claims 1 to 16. Therefore, I consider the composition of claim 17 to be limited to a composition that is prepared by the methods of claims 1 to 16.
Rozenberg submitted:
“The requirement in claim 17 that the composition is ‘for use as medicament’ only limits the scope of the claim to the extent that the composition must be suitable for that purpose. The inclusion of the words ‘for use as medicament’ does not therefore alter the fact that claim 17 is to a composition per se.”[54]
[54] The written submissions of Rozenberg, dated 04 September 2017, at [3] which references the Manual of Practice and Procedure at 2.11.2.3.3.
I agree with Rozenberg that the composition of claim 17 is a composition per se to the extent that the composition per se is limited to those compositions prepared by the methods defined in claims 1 to 16. The composition per se must be suitable for use as a medicament.
The definition of miRNA quoted above from the specification makes it clear that the scope of claim 17 includes a composition comprising “natural miRNA molecules, pre-miRNA, pri-miRNA, miRNA molecules identical in nucleic acid sequence to the natural forms as well as nucleic acid sequences, wherein one or more nucleic acids has been replaced or is represented by one or more DNA nucleotide and/or nucleic acid analogue.”
4 Lack of compliance with subsection 40(2): sufficiency
It is the requirement of paragraph 40(2)(a) that a complete specification must describe the invention fully, including the best method known to the applicant of performing the invention.
The question for the purposes of paragraph 40(2)(a) was stated in Kimberly Clark Australia Pty Ltd. v Arico Trading International Pty Ltd. (Kimberly Clark) as follows:
“The question is, 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?”[55]
[55] [2001] HCA 8 at [25]; 207 CLR 1.
The court in Lockwood Security v Doric Products affirmed this legal question and further stated that it is not necessary for the inventor to disclose all alternative means of performing the invention:
“For the purposes of s40(2)(a), it is not necessary for the inventor to disclose all the alternative means; it is enough that there is disclosure in the sense of enabling the addressee of the specification to produce something within each claim without new inventions or additions or prolonged study of matters presenting additional difficulty..’^[56]
[56] [2004] HCA 58 at [60]; 217 CLR 274.
Rozenberg submitted:
“the specification does not enable a single embodiment relating to a therapeutically effective amount of one or more microRNA.”[57]
[57] The written submissions of Rozenberg, dated 29 August 2017, at [181].
and
“While the Examples include methods of making a composition including a number of microRNAs, in the absence of any link between one or more microRNAs and a therapeutic effect in the treatment of a relevant disorder, a skilled addressee would not, without undertaking further experiments, be able to determine how to perform the invention so as to upregulate one or more microRNAs in order to treat a relevant condition. Indeed it is apparent from the evidence that a skilled address would not be in a position to draw any meaningful conclusions about the data presented in the Opposed Application. As such the specification has not described the invention fully as required by the Act.”[58]
[58] The written submissions of Rozenberg, dated 29 August 2017, at [184].
Professor Hill states the following in relation to the examples in the opposed application:
“While the Examples include methods of making a composition including a number of microRNAs, I consider there is nothing in the examples that demonstrate any supposed therapeutic effect is attributable to microRNAs in the compositions, let alone to one or more ‘upregulated’ microRNAs, rather than the other components of the compositions, such as proteins, which have been characterised previously in compositions made according to the same method steps.”[59]
[59] Hill #1 at [106].
“Overall, I consider there is no data in the application linking one or more microRNA to a therapeutic effect, let alone one or more microRNAs that are upregulated upon activation, with a therapeutic effect.”[60]
[60] Hill #1 at [117].
Professor Hill also states the following in relation to the activated serum prepared by the method of the opposed application:
“For example, any therapeutic effect observed may be attributed to other components of the serum used in the examples, such as the molecules shown in the prior art to be increased using the same physical treatment. The experiments of the examples do not allow the effect or role of any microRNA, or upregulated microRNA, to be determined.
For example it has previously been shown in at least D1, D2 and Meier et al.[sic] that Autologous Conditioned Serum (ACS), which is generated by incubating body fluids such as blood with an increased surface area provided by glass beads, can be used to treat a range of conditions such as osteoarthritis and other inflammatory conditions. Furthermore, these documents discuss an upregulation in cytokines such as IL-1Ra and to a lesser extent IL-4 and IL-10 in the ACS. These documents postulate that it is these cytokines which provide anti-inflammatory effects.
Given that the method steps in Examples 1 and 2 are identical as those for preparing ACS, I believe that the activated serum used in the Opposed Application would have elevated cytokine levels, including IL-1Ra. As such, I believe that it cannot be concluded, based on the Examples and disclosures of the Opposed Application, that the microRNA component of the activated serum is providing the therapeutic benefit.
In my opinion, a researcher or physician would need to carry out experiments to determine whether one or more microRNAs in the compositions of the Opposed Application are responsible for any stated therapeutic effect.
I consider that significant experimentation would be required to show this.
Moreover, I note that nowhere in the specification is the miRNA isolated and administered in a purified form, and there is no disclosure of administrating a purified form of miRNA to treat a disease or disorder.
I also have a serious question as to whether the microRNA in the compositions of the Opposed Application could be therapeutically effective.” [61]
[61] Hill #1 at [131] - [137].

312. The specification describes administration of the upregulated amounts of one or more miRNA molecule(s) to result in the therapeutic effect of the conditioned serum preparations. Therefore, I consider that the invention of claim 17 works by providing upregulated amounts of one or more miRNA molecule(s) — these amounts being therapeutically effective amounts — in the conditioned serum preparations.
What is the nature of the contribution to the art?
313. The next question I need to ask in determining the substance of the claim is what the nature of the contribution to the art is.
314. The upregulated amounts of miRNA in the conditioned serum preparations are produced by activating blood by the methods defined in the claim. The contribution to the art is therefore the method of upregulating the one or more miRNA molecule(s) in blood by activating blood using the methods defined in the claim. This contribution does not rely upon the genetic information in the miRNA.
The substance of claim 17
315. In order to determine the substance of the claim, I have considered how the claimed invention works and the nature of the contribution to the art. I consider that the substance of claim 17 to be conditioned serum preparation comprising upregulated amounts of miRNA. Whilst a miRNA molecule by its nature embodies and conveys genetic information, the specification does not describe the genetic information to have importance towards the utility of the claimed invention. Therefore, I consider the informational aspect of the miRNA molecule does not outweigh its form as a chemical compound such that the genetic information embodied and conveyed by miRNA warrants priority consideration. My approach is consistent with the approach of the Delegate in Arrowhead Research Corporation.[162]
[162] [2016] APO 70.
Is the substance of claim 17 “made”?
316. The conditioned serum preparation of claim 17 is prepared by activating blood using the methods defined in the claim. The conditioned serum preparation is therefore an artificially made composition for treatment.
8.1 Conclusion of manner of manufacture in light of the Myriad case
317. Consequently, I conclude it has not been established that the invention claimed in claim 17 is not for a manner of manufacture in light of the Myriad case.
9 Lack of invention on the face of the specification
318. Rozenberg submitted:
“…none of the claims of the Opposed Application claim an invention that is a ‘manner of manufacture’, according to the principles enunciated in Microcell because, on the face of the specification, all that is claimed is the use of standard techniques in a manner which the known properties of those techniques make them suitable.”[163]

and
“The method steps described, including the collecting a bodily fluid, incubation of a bodily fluid with glass beads for more than 24 hours, and collecting the bodily fluid following incubation, are all standard techniques well known and used in the field.”[164]
[163] The written submissions of Rozenberg, dated 29 August 2017, at [36].
[164] The written submissions of Rozenberg, dated 29 August 2017, at [40].

319. On a reading of the specification, there is no indication that incubation of blood for more than 24 hours is a standard technique known and used for the preparation of blood serum compositions. As previously discussed, the evidence does not establish that incubation of blood for more than 24 h when using the Orthokine® system was information that was publicly available at the priority date of the opposed application. It has not been established that there is a lack of invention on the face of the specification.
9.1 Conclusion of manner of manufacture on the face of the specification
320. It has not been established that the invention claimed in claims 1-21 is not for a manner of manufacture on the face of the specification.
10 Conclusion
321. Each of claims 1, 2, 5, 6, and claims 9-11 and 17-20 that are dependent on claim 1 lacks novelty in light of the prior art. Each of claims 1-6 and claims 9-11 and 17-20 that are dependent on claim 1 lacks inventive step in light of the prior art considered together with CGK.
322. It has not been established that claim 17 is not for a manner of manufacture in light of the Myriad case.
323. These deficiencies can be overcome by amendment, so I will allow Velin-Pharma a period of two months from the date of this decision in which to propose amendments.
11 Costs
324. The opposition is successful. It is normal that cost should follow the event. I see no reason to depart from that result. Cost should be awarded against Velin-Pharma.
Dr A. Lim
Delegate of the Commissioner of Patents
Annex: The claims
1. A method for the preparation of a composition comprising a therapeutically effective amount of one or more miRNA molecule(s), said miRNA being upregulated in a blood serum preparation derived from a body fluid after activation of said body fluid, the method comprising the steps of
a) Collecting said body fluid from a mammal;
b) Incubating the collected body fluid in contact with an increased surface area for more than 24 hours;
c) Collecting said body fluid produced after step b) and preparing the serum preparation comprising the upregulated miRNA therefrom.

2. The method according to claim 2, wherein preparing the serum preparation comprises centrifugation.
3. The method according to claim 1 or claim 2, wherein preparing the serum preparation comprises ultracentrifugation.
4. The method according to claim 3, wherein ultracentrifugation is performed at 100,000g.
5. The method according to any one of claims 1-4, wherein said body fluid is blood.
6. The method according to claim 5, wherein said blood is peripheral blood.
7. The method according to any one of claims 1 to 6, wherein the body fluid is incubated under step b) for more than 48 hours, or more than 72 hours, or up to 150 hours.
8. A method for the preparation of a composition comprising a therapeutically effective amount of one or more miRNA molecule(s), said miRNA being upregulated in a blood serum preparation derived from a body fluid after activation of said body fluid, the method comprising the steps of
a) Collecting said body fluid from a mammal;
b) Incubating the collected body fluid in contact with an increased surface area for more than 24 hours;
c) Identifying one or more miRNA upregulated in said body fluid;
d) Providing said one or more miRNA molecule identified in step c) in isolated form and adding them to said composition.

9. The method according to any one of claims 1 to 8, wherein the mammal is a human.
10. The method according to any one of claims 1 to 8, wherein the mammal is a domestic animal.
11. The method according to any one of claims 1 to 10, wherein said body fluid is collected from a combination of healthy and disease individual(s).
12. The method according to any one of claims 1 to 11, wherein said one or more miRNA(s) is upregulated to a concentration level by at least about 50%, as compared to the concentration level of said miRNA in a composition that has not been activated under step b).
13. The method according to any one of claims 1 to 12, wherein said one or more miRNA(s) is upregulated to a concentration level by at least about 100%, or by at least about 200%, or by at least about 300%, or by at least about 400%, or by at least about 500%, or by at least about 600%, or by at least about 700%, or by at least about 800%, as compared to the concentration level of said miRNA in a composition that has not been activated under step b).
14. The method according to any one of claims 1 to 13, which method further comprises a step of incubating the collected body fluid in contact with an increased surface area in the presence of synthetic miRNA.
15. The method according to any one of claims 1 to 14, wherein said composition further comprises a preparation of magnetic nanoparticles.
16. The method according to claim 15, wherein the magnetic nanoparticles are polyethyleneimine (PEI) coated iron magnetic nanoparticles.
17. A composition comprising a therapeutically effective amount of one or more miRNA molecule(s), said miRNA being upregulated in a blood serum preparation derived from a body fluid after activation of said body fluid obtained by a method according to any one of claims 1 to 16; for use as a medicament.
18. A method for the treatment or for alleviating the symptoms of a disease or disorder associated with inflammation, a disease of the immune system and/or cancer or other indications associated with abnormal cell growth or cell division, the method comprising administration of a composition comprising a therapeutically effective amount of one or more miRNA molecule according to claim 17, to a subject in need of said treatment.
19. The method according to claim 18, wherein the disease of the immune system is undesirable activation of the immune system.
20. The method according to any one of claims 18 or 19, wherein said composition is autologous to the subject in need of said treatment.
21. The method according to any one of claims 1 to 16, or 18 to 20, or the composition according to claim 17 substantially as hereinbefore described with reference to the accompanying examples.

Evidence	Declarant	Exhibits	Date	Reference
In Support	Andrew Hill	AH-1 to AH-9	23 May 2016	Hill #1
	Dominic Wall	DW-1 to DW-3	23 May 2016	Wall
	Julian Willmore	JW-1 to JW-3	20 May 2016	Willmore
In Answer	Stine Thuren Key	STK-1 to STK-5	19 August 2016	Key
In Reply	Andrew Hill	AH-10 to AH-11	24 October 2016	Hill #2