Amazentis SA
[2024] APO 27
•28 June 2024
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Amazentis SA [2024] APO 27
Patent Application: 2021201143
Title:Compositions comprising an urolithin compound
Patent Applicant: Amazentis SA
Delegate:Dr Scott D. Makin
Decision Date: 28 June 2024
Hearing Date: Written submissions filed on 1 May 2023
Catchwords: PATENTS – examiner objection – novelty and inventive step – amended claims are novel – inventive step objection unable to be maintained – amended claims possess an inventive step - combination of features not obvious – consideration of common general knowledge – no motivation to combine documents – hindsight analysis – application accepted
Representation: Patent attorney for the applicant: FB Rice Pty Ltd
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2021201143
Title:Compositions comprising an urolithin compound
Patent Applicant: Amazentis SA
Date of Decision: 28 June 2024
DECISION
The remaining objections raised by the examiner are not sustainable and I find that all claims as they are currently proposed to be amended are novel and possess an inventive step over the cited prior art. I grant leave to allow the amendments in the third statement of proposed amendments and direct the application proceeds to acceptance.
REASONS FOR DECISION
Background
Patent application 2021201143 (the application or the present application) was filed by Amazentis SA (the applicant) on 22 February 2021. It is a divisional application of 2016314988 (the parent application) and has an earliest claimed priority date of 28 August 2015.
The parent application was the subject of three (3) examination reports (issued on 21 February 2020, 2 February 2021 and 19 February 2021). The parent application failed to gain acceptance within 12 months of issuing the first examination report and duly lapsed.
The present application has so far been the subject of two (2) examination reports—the first was issued on 23 December 2021 and the second on 2 December 2022. The applicant refiled an identical specification to the PCT pamphlet that formed the basis of the specification that entered national phase for the parent application. Accordingly, the first examination report of the present application was raised on identical grounds to the first examination report of the parent application. Proposed amendments and accompanying submissions were filed by the applicant on 11 November 2022. In the second examination report, the examiner maintained that some claims lacked novelty and all claims lacked an inventive step.
In response to the second examination report, a second set of proposed amendments was received on 20 December 2022 proposing to delete the claims alleged to lack novelty accompanied by further submissions as to the inventiveness of the remaining claims. Although a third examination report was not issued, conversation records on file indicate the examiner intended to maintain the inventive step objection to the remaining claims.
Subsequently, the applicant wrote to the Commissioner on 23 December 2022 and requested to be heard in relation to the outstanding objections. Written submissions were received on 1 May 2023 accompanied by a third statement of proposed amendments.
As the present application was filed on 22 February 2021, the amendment of the Patents Act 1990 (the Act) brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 applies to the present application. The standard of proof that applies to the examination of the present application is the balance of probabilities.
Pursuant to regulation 13.4(1)(g), when the Commissioner gives an applicant an opportunity to be heard in relation to an examiner’s objection and issues a written decision, the period for gaining acceptance of the application may be extended until three months from the date the decision is issued or, pursuant to regulation 13.4(3), for a period of longer than three months if the Commissioner is satisfied that acceptance should be postponed.
The complete specification
The description as filed
The present application is generally directed to nutritional and medical formulations comprising compositions of urolithin compounds, in particular urolithin A, and proteins.[1]
[1] Present application, p. 1, lines 1-2.
The background of the invention outlines the need for good muscle performance and potential drawbacks of treating muscle wastage using drugs like anabolic steroids. It also outlines that protein-containing nutritional products are available that are specifically formulated to increase muscle mass, improve muscle performance and/or reduce muscle wasting and related conditions, especially in elderly or hospitalised individuals and in improving muscle performance in athletes. It is also said, however, that regular exercise is generally required for the desired benefits of these protein formulations to be achieved.[2]
[2] Present application, Background, p. 1, lines 3-30.
The applicants have allegedly found that a composition of protein and urolithin A has a surprisingly beneficial and enhanced effect when compared to protein on its own and is thus useful in treating diseases and conditions characterised by low muscle mass or poor muscle performance, in enhancing muscle growth and/or performance and in maintaining muscle performance.[3] Further, the compositions of the alleged invention are also said to provide enhancement of muscle function in the absence of exercise or with less exercise being necessary.[4] The applicant then goes on to say that the present invention provides a composition for treating muscle-related pathological conditions and in enhancing muscle performance.[5]
[3] Present application, p. 2, lines 1-17.
[4] Present application, p. 2, lines 19-21.
[5] Present application, p. 3, lines 1-7.
The protein used in the compositions of the invention is preferably purified,[6] which the applicants define as being isolated from its food ingredient source. Preferred proteins include those isolated from pea, whey, soy, and casein.[7]
[6] Present application, p. 4, lines 3-4.
[7] Present application, p. 5, lines 5-18.
The specification goes on to say that urolithins are metabolites produced by the action of the mammalian gut microbiota on ellagitannins and ellagic acid, which are commonly found in foods such as pomegranates, nuts and berries. Urolithin A is particularly preferred and is generally micronized prior to use in a composition because this is said to allow it to be dissolved or suspended more rapidly and more effectively.[8]
[8] Present application, p. 7, line 5 to p. 6, line 9.
Additional dietary ingredients may be added to the compositions including vitamins, minerals, polyunsaturated fatty acids and functional amino acids to provide other health benefits and may be formulated as a variety of foodstuffs including powders, drinks, bars, and yoghurts.[9]
[9] Present application, p. 8, line 11 to p. 10, line. 29.
The Examples
The description provides six examples to illustrate the invention.
Example 1 is an animal model trial where elderly mice were fed with either a high protein diet alone or a high protein diet containing Urolithin A.[10] Both diets also contained other essential nutrients for optimal muscle function. The results found that mice being fed the diet containing Urolithin performed better on a treadmill test indicating increased muscle function. The applicants anticipate similar improvements would be observed with urolithin A in elderly humans in comparison to the current standard of care where only an optimal protein diet is recommended. Neither group of mice were subjected to exercise regimens prior to the endurance tests which is said to indicate that the diet containing urolithin may help improve muscle function with less or no exercise.
[10] Present application, p. 21, line 8 to p. 23, line 9.
Examples 2-5 disclose various high protein compositions comprising urolithin A which include a powder formula, an enteral nutrition liquid composition, a cereal bar and a yoghurt having varying doses of proteins, urolithin A and other nutritional ingredients.[11]
[11] Present application, p. 23, line 11 to p. 25.
Example 6 examines the effect of particle size on urolithin A bioavailability where the applicants conclude from their data that urolithin A shows an increased bioavailability when particle size is reduced below a D90 of 50µm and that preparations having a urolithin A particle size of D90 less than 20µm are especially advantageous because they enable much higher peak urolithin A blood levels.[12]
[12] Present application, p. 26-28.
The Claims
Along with their submissions of 1 May 2023, the applicant provided a third statement of amendments under S104 proposing further amendments to the claims. This was in addition to the proposed claim set filed by the applicant on 20 December 2022 in response to the second examination report. I consider that the amendments filed on 1 May 2023 are allowable, so the matter before me proceeds on the proposed claims filed on 1 May 2023. The specification as it is currently proposed to be amended ends with twenty (20) claims and these claims are set out in Annex A for reference.
Claim 1 is an independent clam that reads:
1. A composition comprising:
a)a source of protein and
b)urolithin A;
wherein the source of protein is in a range of 20 to 90 g and the urolithin A is in a range of 20mg to 2500mg.
This claim is directed to a composition “comprising” the specified components. The applicant has not defined the term “comprising” so the meaning of this term, whether it should be construed exhaustively or non-exhaustively, needs to be determined in accordance with the context of the specification. Given the nature of the examples and the general background of the invention indicates optionally having additional elements in the bendamustine compositions, the term “comprising” must be construed as being non-exhaustive. That is to say, the composition must have components (a) and (b) but may also include further additional components. This is made evidently clear throughout the specification, including the examples, where additional nutritionally required ingredients are added to the compositions. I will note here that the amount of the source of protein has been proposed to be amended to 20 to 90g (from 10 to 30g) compared to the proposed claims last considered by the examiner and does not change the substantive issues being considered.
Claims 2-10 are dependent on earlier claims and define further embodiments of the compositions, including particle size range of urolithin A, weight percentage of protein, ratio of protein to urolithin A, the source from which the protein is derived, and the form of the composition (yoghurt, powder etc.).
Claims 11 is a “when used” type claim and reads:
11.A composition as claimed in any one of claims 1 to 10 when used as a medicament, dietary supplement, functional food, functional beverage or medical food.
Consistent with normal Australian construction, the phrase “when used” has the effect of limiting the composition to the particular application, environment or timing claimed. These types of claims are generally considered to be equivalent to method claims and there is no good reason to depart from that construction.
Claims 12-17 are dependent claims and define further embodiments relating to the intended use, types of conditions and sub-populations of subjects requiring treatment in which the compositions comprising the protein source and urolithin A are to be used.
Claim 18 as proposed to be amended reads:
18.A kit comprising:
a)urolithin A in a range 20mg to 2500mg; and
b)a source of protein in a range 20 to 90g;
when used in the composition according to claim 1.
Claim 18 also is a “when used” type claim limiting the kit to the particular application or timing. The wording of this claim as it is currently proposed to be amended is slightly unusual as the environment in which the kit is used would normally be drafted as a method of treating a condition or the intended functional use of the components of the kit. Here, the kit is used “in the composition according to claim 1.” Nevertheless, a construction can be put on the claim and, as currently drafted, I consider this claim is directed to the use of a kit that has urolithin A and a protein source in the specified ranges to make a composition within the scope of claim 1.
Claim 19 is another “when used” claim and is directed to a composition of a source of protein and urolithin A when used for improving muscle growth, strength, endurance and function with no or less exercise. The amount of protein and urolithin A are limited to the ranges, particle sizes, ingredient ratios and other features are per claims 1 to 11.
Claim 20 is dependent on claim 19 and limits the uses of improving muscle growth, strength, endurance and function with no or less exercise to being in sedentary individuals and the elderly.
The remaining objections
The examiner’s objections at items 6 and 7 of the second examination report issued on 2 December 2022, can be summarised as follows:
6.Claims 19 and 20 [as were proposed to be amended at that time] are not novel over WO 2012/088519 (hereinafter referred to as D7) and claims 1-18 and 21-22 do not involve an inventive step over D7 when read in view of the common general knowledge in the art. Documents D8 and D9 were put forward as evidence of the common general knowledge[13] to substantiate the objection on the grounds of inventive step over D7.
7.Claims 19 and 20 [as were proposed to be amended at that time] are not novel over WO 2014/004902 (hereinafter referred to as D5), and claims 1-18 and 21-22 do not involve an inventive step over D5 when read in view of the common general knowledge in the art. Patent document AU 2013101214 (hereinafter referred to as D4) and non-patent literature documents D8 and D9 were presented as evidence of the common general knowledge to substantiate the objection on the grounds of inventive step over D5.
[13] D8: Paddon-Jones, D., et al., Current Opinion in Clinical Nutrition and Metabolic Care, 2009, vol. 12, pp. 86-90; D9: Deutz, N.E.P., et al., Clinical Nutrition, 2014, vol. 33, pp. 929-936.
Novelty
At the time of issuing the second examination report, proposed claim 19 was an independent claim directed to a method of treating muscle-related pathological condition using “an effective amount of urolithin A” and “an effective amount of a protein source” which could be administered at the same or different times and claim 20 was directed to a kit comprising the effective amounts of urolithin A and the protein source when used in the method of claim 19. In response to items 6 and 7 of the second examination report, the applicant submits that because previous claim 19 was proposed to be deleted and that because previous claim 20 (currently proposed claim 18) is limited to the composition as defined in claim 1, then claim 18 as is currently proposed to be amended is also novel over D7 and D5.[14]
[14] Applicant’s submissions; p. 3 and p. 8,
A detailed analysis is not required. Claim 1 as was proposed to be amended at the time the second examination report was issued had already been acknowledged as being novel over the previously cited prior art—the currently proposed amendments changing the amounts in the ranges of protein source in the composition do not alter that. It follows that if currently proposed claim 1 is novel, proposed amendments to later claims that introduce the same feature(s) that render claim 1 novel, will necessarily render those later claims novel. In conclusion, claims 1-20 as currently proposed to be amended are novel over the cited prior art.
Inventive step
The remaining issue to consider, then, is that of inventive step raised at items 6 and 7 of the second examination report. Although a third examination report was not issued, records on file indicate the examiner intended to maintain the inventive step objection in view of the proposed amendments and the accompanying submissions filed in response to the second report.
The basis of the applicant’s submissions filed on 1 May 2023 was:
1. Documents D4, D8 and D9 cited by the examiner are not authoritative of common general knowledge in the art, and the examiner has erred in their assessment by relying upon these documents to substantiate the outstanding inventive step objections over D7 and D5,
2. Regardless as to whether D4, D8 and D9 are considered authoritative of common general knowledge, the invention as claimed clearly possesses an inventive step compared to D7 and D5, and
3. The person skilled in the art could not be reasonably expected to combine D7 with D8 or D9 or be expected to combine D5 with D4 or additionally D8 or D9 to arrive at the claimed invention.
The issue of inventive step has been maintained consistently by the examiner and, as I noted above, three examination reports were issued on the parent application reaching a similar impasse with a similar set of clams. In the parent application, the amount of protein source and urolithin A were slightly different to that of the currently proposed claims but the general outstanding issue was the same and documents D8 and D9 were also used at that time as assertions of common general knowledge in the art.
According to the examiner at objection item 6 of the second examination report, D7 outlines the application of urolithin A in combination with a controlled diet which it is said would inevitably contain protein and it is thus concluded that “D7 differs from the present independent claims by failing to explicitly teach the ranges of protein.” The second examination report then goes on to say, “Claim 1 is not considered to be inventive based on the obvious combination of urolithin A and established dietary standards for protein intakes in elderly individuals.” The examiner uses D8 and D9 as evidence of the established protein intake for elderly individuals, stating that D8 teaches “25-30g of protein with each meal or as a supplement 3 times a day” and D9, which the examiner points out is referenced in the present application, teaches protein intake in the order of 1.0-1.2 g/kg/day in older individuals and 1.2-1.5 g/kg/day in situations with illness. The examiner then considers that none of the remaining claims involve an inventive step because the additional features in those claims are disclosed in D7 or relate to matters of common general knowledge.
My reading of objection item 6 of the second examination report is that the examiner indicates that if the claims were limited to the extent that the compositions were to be used on elderly individuals to aid muscle growth, an inventive step could be acknowledged. I note that the applicant also makes that conclusion, referring to this in their submissions and stating that the applicant’s inventive contribution is broader than just the use and that “claim 1 and its dependent claims are equally patentable”. I agree with the applicant that there should be no need to limit the claims only to a method of using the compositions and I will come back to this point shortly. However, at the time the second examination report was issued, none of the method claims were limited solely to the use of the compositions in elderly patients, so the inventive step objection was maintained.
Objection item 7 in the second report is similar. According to the examiner, D5 discloses urolithin A within the range of the present claims in a high fat diet, which it is said would inevitably contain protein, and provides animal modelling experiments on muscle function and muscular strength. It is concluded from this that “the only thing missing is motivation to provide protein in the amounts as defined in the present claims.” D8, D9 and D4 are then given as examples of common general knowledge of the levels of protein in the presently claimed compositions and, as a result, claim 1 is said to lack an inventive step. Again, the examiner considers none of the remaining claims possess an inventive step because the additional features in those claims are disclosed in D5 or are matters of common general knowledge.
My understanding of the prosecution to this point is that the examiner’s position on whether the present claims involve an inventive step seems to hinge on what is common general knowledge in the art. The applicant clearly disagrees with the examiner’s stance and, for completeness, has submitted that regardless of common general knowledge, the present claims have an inventive step over D7 and D5 and, further, that the person skilled in the art would not reasonably be led to combine D7 or D5 with any of the documents submitted to be relevant common general knowledge in the respective objections.
Applicable law for inventive step
The statutory basis for inventive step is set out at subsections 7(2) and 7(3) of the Act, and is reproduced below:
(2) For the purposes of this Act, an invention is to be taken to involve an inventive step when compared with the prior art base unless the invention would have been obvious to a person skilled in the relevant art in the light of the common general knowledge as it existed (whether in or out of the patent area) before the priority date of the relevant claim, whether that knowledge is considered separately or together with the information mentioned in subsection (3).
(3) The information for the purposes of subsection (2) is:
a) any single piece of prior art information; or
b) a combination of any 2 or more pieces of prior art information that the skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have combined.
Where claims define a combination of features, such as is the case in the present application, the key issue is whether it is the combination of features that is obvious, not whether those integers in isolation might themselves be individually known or considered to be obvious. This was considered in Minnesota Mining & Manufacturing Co. v Beiersdorf (Australia) Ltd. (3M),[15] where Aickin J said:
“In the case of a combination patent the invention will lie in the selection of integers, a process which will necessarily involve rejection of other possible integers. The prior existence of publications revealing those integers, as separate items, and other possible integers does not of itself make an alleged invention obvious. It is the selection of the integers out of, perhaps many possibilities, which must be shown to be obvious.
“It is in relation to this process that the misuse of hindsight is most common. When once an idea or an object or a process or a combination, admittedly novel, has been published, it is very easy to say after perhaps months of search and study…that the integers to which the patent might be dissected could be found scattered amongst the prior documents by a person who already knew the solution to the problem and therefore knew what to look for and what to discard. But that process does not demonstrate lack of an inventive step. The opening of a safe is easy when the combination has already provided.”
[15] [1980] HCA 9 at [116]; (1980) 144 CLR 253 at 293
This was prefaced earlier in 3M also at [293] where Aickin J said:
“The question is, is the invention itself obvious, not whether a diligent searcher might find pieces from which there might have been selected the elements which make up the patent. If this were not so, there could never be a valid patent for a new combination of old integers.”
The outstanding inventive step objections seem to suggest that both D5 and D7 disclose all the features of claim 1 (as was proposed to be amended at the time of the second report) except the claimed protein range and, that when these documents are read in light of the common general knowledge, the person skilled in the art would be directly led to the invention as presently claimed. While I agree with the examiner’s summary in the second examination report of what D5 and D7 disclose and its relevance to the claims that were deemed to be not novel at that time, I come to a different conclusion on the features of claim 1 that are disclosed in these documents that may be relevant to claim 1. I am of the view there are additional differences between present claim 1 (and by implication claim 1 at the time the second report was issued) over and above the amount of protein source in that neither D5 nor D7 specifically disclose the claimed range of the urolithin A.
As I see it, the claimed invention effectively distils to a combination of features already present or suggested (individually) in the prior art and I have set out above the caution of Aickin J regarding hindsight when mosaicking features said to be in documents and combining those disclosures to arrive at the claimed invention. I think similar issues of hindsight can exist when suggesting that a difference between a claimed invention and the prior art is common general knowledge, then searching to find that missing feature in another prior art document as confirmation of common general knowledge. To all intents and purposes, it is the same process and lays itself open to falling into the same trap of impermissible hindsight.
Inventive step considerations
The so-called problem-solution approach is the preferred methodology to consider whether an invention possesses an inventive step because it reduces the risk of an ex post facto analysis and helps to identify all relevant issues. This approach has been endorsed by the Australians courts. In Wellcome Foundation Ltd. V VR Laboratories (Aust) Pty. Ltd. [1981] HCA 12 at [45]; (1981) 148 CLR 262 at 286 (Wellcome), Aickin J posed it as:
“The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not.”
In Aktiebolaget Hässle v Alphapharm Pty Ltd [2002] HCA 59 at [53]; 212 CLR 411 at [51]-[53] (Alphapharm), the High Court endorsed the use of the reformulated Cripps question:
“Would the notional research group at the relevant date in all the circumstances directly be led as a matter of course to try [the claimed invention] in the expectation that it might well produce a useful alternative…?”
The first step of the problem-solution approach is to determine the problem that the claimed invention is seeking to address. Identifying the problem provides the context for identifying the person skilled in the art and the relevant common general knowledge that person would have at their disposal.
There has been no discussion to this point during the examination process nor the applicant’s submissions regarding who person skilled in the art may be. I imagine this is because it is not contentious, and nothing will turn on it anyway. Given the nature of the invention disclosed, I consider the hypothetical skilled addressee to be a team including a food technologist with knowledge and skills in the formulation of dietary compositions and the machinery used in their production and a dietician or nutritionist.
At various points in their submissions (as well as in the response to the first examination report), the applicant indicates that the problem being solved is to achieve improvements in muscle function in elderly patients without the need for exercise. The applicants use a composition high in protein in combination with urolithin A to achieve that effect.
The examiner’s determination of the problem differs to the applicant’s and then seemingly changes during prosecution. I note that in the first examination report, the problem was formulated by the examiner as “improving the effectiveness of a urolithin compound in the treatment of a muscle-related pathological condition or in the enhancement of muscle performance.” The applicant submitted in response to the first examination report, at least in relation to the inventive step objection over D5, that the problem had been set incorrectly by the examiner. However, the examiner found that submission irrelevant because “D5 and the present invention are aiming to address or reduce the effects of muscle loss in aging individuals” and that “[t]he present claims are not directed to the treatment of individuals in the absence of exercise”. I take this last statement, as does the applicant, as an indication the examiner would have acknowledged an inventive step the claims were limited to a method of using the compositions in treating muscle conditions in the absence of exercise—in other words limiting the claims to the problem that the applicant perceived as being addressed.
50.While I note that the applicant did not press the accuracy of the problem any further in response to the second report, in Nichia Corporation v Arrow Electronics Australia Pty Ltd [2019] FCAFC 2, the Full Court emphasised the importance of correctly construing the problem to be solved and said that considering the issue of obviousness by reference to the outcome to be sought (problem to be solved) is an orthodox approach.[16] The Full Court also did not accept the proposition that the qualitative aspects of the problem needed to be integers in the claims[17] and cited with approval Middleton J in Eli Lilly and Co Ltd v Apotex Pty Ltd[18] where his Honour said, “It is impermissible to divorce olanzapine from its context and subject it to an obviousness test that completely disregards its utility as an antipsychotic drug.” There are parallels here in the present application regarding the product claims and their subsequent claimed uses. As I touched upon above at [36], this means there is no requirement here for the applicant to qualify the problem to be solved in the claims by limiting their scope only to a method of using the compositions.
[16] Nichia at [81]
[17] Nichia at [68]
[18] [2013] FCA 214 at 533
While the specification does not explicitly state what the problem to be solved is, I think it can be inferred without much issue. After the specification states that there are protein-containing nutritional products available that are formulated to increase muscle mass, improve muscle performance and reduce muscle wasting, it goes on to say that it is generally necessary for regular exercise so desired improvements can be achieved.[19] This statement is repeated on the next page after the summary of the invention before the specification says “[t]here is evidence that the compositions of the invention are effective in enhancement of muscle function in the absence of exercise, or with less exercise being necessary”.[20] I think this points to the requirement for exercise with previous high-protein compositions being a problem and I agree with the applicant’s view that improving muscle function with less or without exercise is a part of the problem to be solved.
[19] Present application, p. 1, lines 27-30.
[20] Present application, p. 2, line 18-21.
I will add, though, that I do not think the problem needs to be restricted to achieving muscle function improvements in elderly patients as the applicants have indicated in their submission. It is also a problem that exists in individuals who may be suffering from conditions that affect muscle function or require muscle enhancement and those individuals may not necessarily be elderly—the specification makes this clear at several points.[21] The problem to be solved is providing formulations to achieve improvements in muscle function without the need for exercise or with less exercise.
Common General Knowledge and Consideration of Prior Art
[21] Present application, p. 16, line 13 to p. 20, line 7.
Having established the problem to be solved and the person skilled in the art, this allows what may or may not be considered common general knowledge in the art to be determined. The common general knowledge is the technical background knowledge and experience which is known or used by those in the relevant art. It is available to all in that art when developing new products or improving existing products. The common general knowledge is not limited to material that may be memorised and retained at the front of the skilled worker’s mind but also includes material which they know exists and would refer to as a matter of course. This may include, for example, textbooks, dictionaries, and publications specific to the field of the relevant art.[22] The concept of common general knowledge must not be conflated with “public knowledge”, which is the entire body of publicly available information. An important point to make here is that merely because a document is publicly available, this does not make it common general knowledge.[23] The applicant points to accepted law on what constitutes common general knowledge.[24] It is accepted that a piece of knowledge only becomes common general knowledge when it is generally known and accepted by the bulk of those who are engaged in the particular art.
[22] ICI Chemicals & Polymers Ltd v Lubrizol Corporation Inc [1999] FCA 345; 45 IPR 577 at [112].
[23] General Tire & Rubber Co. v Firestone Tyre (1972) RPC 457
[24] British Acoustic Films Ld v Nettlefold Productions (1936) 53 RPC 221, affirmed in General Tire & Rubber Company v Firestone Tyre and Rubber Company Ltd (1972) RPC 457
D4, D8 and D9 have been put forward as evidence of the common general knowledge in the art to substantiate the inventive step objections made in light of D5 and D7. The applicant continues to contend these documents are not authoritative of the common general knowledge. The continuing back and forth on the point of common general knowledge and whether these documents are representative of that somewhat misses the point, I think. The applicant states quite unambiguously in the description that “[c]onventional protein compositions are generally taken at a level of 5 to 30g per serving, and a subject generally takes one, two or three servings per day” and this would mean a daily dose of protein from a composition in the range of 5 to 90g.[25] I take this as a clear statement of common general knowledge regarding the level of protein in protein-containing compositions.
[25] Present application, p. 12, lines 22-26.
The applicant does refer explicitly to D9 in the present specification[26] and the examiner has pointed to this in previous examination reports, presumably to add substance to the argument of this citation being common general knowledge. While acknowledged prior art can carry some weight in determining the common general knowledge,[27] it is common in drafting of patent specifications for applicants to provide reference to the theory that underpins the invention and I think that is the case here with reference to protein requirements in elderly patients. Whether the person skilled in the art would immediately be able to refer to any of these documents as common general knowledge is debatable, and I am not necessarily convinced they would. However, I also think it is a moot point considering what I have said to be commonly known about the level of protein in protein-containing formulations.
[26] Present application, p. 12, line 27 to p. 13, line 2.
[27] Bristol-Myers Squibb Co. v F H Faulding and Co. Ltd 46 IPR 553
However, this does not necessarily render the presently claimed compositions and their subsequent claimed use as being obvious. The consideration that the law requires to be made is whether the claimed combination of features is obvious, not whether each feature in the claimed composition has been individually disclosed or is obvious over the prior art or common general knowledge. I have little doubt that it would be a straightforward task for a “diligent searcher” when looking backwards from the proposed solution to find multiple disclosures of protein as a recommended serve within the range claimed in the present claims. As outlined above, the courts have strongly warned against this impermissible use of hindsight and D4, D8 and D9 happen to be three documents that disclose or suggest protein levels within the claimed range of protein source. The question that needs to be answered is, when faced with the same problem that the present application is attempting to solve, would the person skilled in the art be directly led as a matter of course to the claimed invention of compositions comprising urolithin A in the claimed range in combination with a protein source in the claimed range?
The concern I have with these documents is that even if the person skilled in the art were to read any of these documents, or to consider that they provide common general knowledge about desirable protein intake levels in a general sense, I do not think they would recognise these documents as addressing the same problem as the present application, which ultimately leads me to conclude the examiner’s stance on inventive step cannot be maintained. If these documents do not solve the problem the present application is addressing, the person skilled in the art would be unlikely to be guided by their disclosure.
D8 is a review article proposing a recommendation on dietary protein levels to preserve skeletal muscle mass in ageing. This document proposes that 25-30g of high quality protein per meal should be consumed three times per day rather than uneven protein intakes per meal as it is said this will maximise muscle protein synthesis while being cognisant of energy intake.[28] Supplementation of meals with additional amino acids, especially leucine, is posited as having some potential benefit in elders but there is nothing of note in D8 that might hint at or provide motivation to investigate other types of supplementation to accompany the proposed protein intake.[29] From my reading of D8, it also seems to generally recommend weight bearing exercise is required to maintain muscle function with the recommended level of protein intake and also indicates that where exercise is undertaken in an elderly population, there is a general improvement in all measured outcomes irrespective of whether the patients were on lower or higher protein diets.[30] The person skilled in the art would learn from this document that exercise would still be required to improve muscle function with the level of protein disclosed in this document. As a result, I cannot conclude that this document discloses common general knowledge that is directly relevant to the problem being solved by the present application.
[28] D8: Abstract, Introduction, Conclusion, Figure 1.
[29] D8: pp. 2-3.
[30] D8: p. 4, final para bridging to p. 5
Similar reasoning applies to D9, which is also a review article. It proposes a level of 1.0 to 1.2 g of protein/kg of bodyweight/day for healthy elders and 1.2 to 1.5 g/kg of bodyweight per day for older people who are malnourished or ill. D9 also alludes to supplementation with amino acids rich in leucine but teaches that long-term leucine supplementations alone do not increase muscle mass or strength, although it does disclose that its metabolite beta-hydroxy beta-methyl butyrate (HMB) might help attenuate muscle loss (which I take to mean does not necessarily maintain or improve) in patients who are critically ill and presumably are unable to exercise.[31] D9 also says the effect of supplementation with essential amino acids is unclear, referring to one study indicating increased muscle mass without exercise and other studies indicating that supplementation alone did not increase muscle mass. There is certainly nothing in D9 to suggest that protein should be supplemented with anything other than additional amino acids or some of their metabolites. The overarching teaching from D9 is that it clearly recommends daily physical activity or exercise should be undertaken in parallel with the recommended protein levels.[32] This leads me to the same conclusion as for D8 that this document, and any common general knowledge it discloses, is not directly relevant to the problem the applicant is attempting to address and that the person skilled in the art would take away from this document that exercise would still be required to maintain or improve muscle function with the level of protein recommended in D9.
[31] D9: p. 6, “Specific amino acids and metabolites”.
[32] D9: Abstract, Conclusions.
I also note the applicant’s submission on D8 and D9 arguing that they both point to a lack of consensus on dietary protein requirements, which they say means these documents would not be considered representative of the common general knowledge.[33] I think this carries some weight as to why the person skilled in the art would not necessarily rely on these documents for guidance because it might cast some doubt on optimum levels of protein required. D8 refers to the “renewed debate on recommended dietary allowance for protein” and states that “there is no consensus on the degree with which protein needs change with advancing age.”[34] Similarly, D9 also refers to the continuing discussion about a per-meal threshold amount of protein intake needed to stimulate protein synthesis in older adults.[35] In any case, as I have said above, I think these documents more strongly teach to the ordinarily skilled person that the proposed levels of protein therein would only help with muscle function combined with recommended levels of exercise and there is no motivation to supplement protein consumption with anything other than branched chain amino acids or some of their metabolites—even then, the effect of supplementation is not entirely clear.
[33] Applicant’s submissions, pages 3 – 6 and pages 8-9.
[34] D8: p. 2, last paragraph, continuing to p. 3.
[35] D9: p. 5, “Amount of protein”.
Regarding D4, I do not think this document is particularly relevant either. D4 is directed to using denatured whey protein compositions to increase blood serum concentration of free leucine. Although D4 says increasing free leucine is recognised as having a role in stimulating muscle protein synthesis, I see no evidence in this document that the increases in leucine observed in administering denatured whey protein, although said to be similar to that observed in native whey protein, result in increased muscle function.[36] I am struck, in particular, by Example 2 which is directed to the efficacy of the compositions of D4 in how it appears to be a statement of future work rather than evidence of any effect on muscle function and there are no data presented from which to draw any conclusions.[37] In any case, the main outcomes of the trial in example 2 are still intended to measure plasma concentrations of leucine and other amino acids as well as some gastrointestinal effects, not specifically for measuring any improvement in muscle function, let alone in the absence of exercise. While I note that D4 suggests supplementation with amino acid sources, precursors to and metabolites thereof, and other nutritional elements like certain vitamins and minerals[38] it is completely silent on the effect of exercise and provides no motivation to supplement protein with other compounds. The ordinarily skilled person learns nothing about the effect of protein on muscle function from this document, let alone in the absence of or even in the presence of exercise. Again, I conclude that this document, and any common general knowledge it discloses, is not directly relevant to the problem the applicant is attempting to address.
[36] D4, example 1, paras. [0110]-[0117].
[37] D4, example 2, paras. [0118]-[0121]
[38] D4, paras. [0036], [00102]-[00103]
While D4, D8 and D9 were put forward as being representative of the common general knowledge, and much of the discussion so far has related to these documents, the inventive step objections consistently maintained through the prosecution of this application were made in relation to the “main” documents D5 and D7. The applicant contends that regardless of the state of the common general knowledge, that the presently claimed invention possesses an inventive step in view of D5 and D7. Further to this, the applicant also submitted it would not be reasonable to combine D5 with any of D4, D8 or D9 nor would it be reasonable to combine D7 with either D8 or D9. I will now turn to consider D5 and D7.
I will start with D7 because it is the earlier of the publications of the main prior art documents. D7 is generally directed to providing compositions and methods for improving mitochondrial function and treating neurodegenerative and cognitive disorders. This document generally discloses that various fruits and berries used to promote health are abundant in compounds called ellagitannins. These compounds are monomeric, oligomeric and polymeric polyphenols and have been identified as having various health benefits, acting as being antioxidants, anti-atherogenics, anti-thrombotics, anti-inflammatories and anti-angiogenics. However, according to D7, ellagitannins are poorly absorbed by the human gut but will undergo gradual metabolisation to produce urolithins A, B, C and D, which are more easily absorbed and further metabolised.[39] It is envisaged in D7 that compositions comprising urolithins may be useful in improving physical endurance and muscle performance and that such compositions will be effective in treating muscle-related pathological conditions.[40] D7 provides various examples, with examples 2 to 6 demonstrating the ability of these compounds to promote various biological functions. Example 8 specifically discloses urolithin A being fed to mice being dosed on to either a high fat diet or onto a standard chow diet. Both groups of mice displayed an increase in muscle mass as a proportion of total body mass.[41] Example 21 discloses urolithin A and its ability to improve muscle performance in 8-week-old mice using the treadmill endurance test.[42] Mice fed a standard chow diet laced with urolithin A for 6 weeks performed better on the treadmill test than a control group fed only the standard chow diet, which is said to indicate improved muscle performance. When fed to test subjects, urolithin A seems to be dosed at 55 mg per kg of bodyweight per day (mg/kg/day).
[39] D7, p. 1, line 33 to p. 2, line 7.
[40] D7, p. 57, line 11 to p. 58, line 7.
[41] D7, example 8, p. 79
[42] D7, example 21, p. 101 to 102.
The teaching of D7 in general leads me to conclude that the person skilled in the art would learn from this document that only ellagitannin metabolites such as urolithin A may have an ability to increase muscle performance. Whilst I agree with the examiner that the standard chow and high fat diets given to the test subjects would inevitably contain some level of protein, this point only seems relevant to the claims before the currently proposed amendments. The chow diets in D7 seem to be used merely as a vehicle to administer urolithin A to measure its effect versus various controls and there is no appreciable difference in effect between standard and high fat chows, which generally contain the same level of protein in their formulation. Thus, D7 does not teach the effect of protein and does not provide any motivation study the effect of urolithin with higher levels of protein sources.
Furthermore, from my reading of D7, this document also does not specifically disclose the milligram amounts in the range of urolithin A as is claimed. I note the applicant reached a similar conclusion in their submission. D7 discloses an amount of urolithin A in mg/kg of bodyweight as fed to mice for those examples relating to muscle function/mass. While there might be some general statements in D7 alluding to broad ranges of between 0.2 to 150 mg of urolithin compound per kg of bodyweight that might be administered to achieve an effect,[43] taking into account what is disclosed in the examples that relate to muscle function, there is no clear reason for the person skilled in the art to select the presently claimed range of urolithin A and then combine that with a range of protein that might be disclosed in the prior art or be considered common general knowledge in a different context. D7 seems to suggest using a level of 55 mg/kg in the examples relating to muscle function, which, for an average human adult, would generally lead to an amount of urolithin A above the top of the limit of the range claimed. As a result, I conclude that D7 would not directly lead the person skilled in the art to the presently claimed invention with any reasonable expectation of success.
[43] D7, p. 65, lines 16-25.
D5 is similar in disclosure to D7. D5 is generally directed to enhancing autophagy or increasing longevity by administering urolithin compounds or precursors thereof. This document seems to countenance a wider range of urolithin compounds,[44] however, the general disclosure in the examples seems to concentrate upon the biological activity of urolithin A where an increase in autophagy and longevity in C. elegans is allegedly displayed. Urolithins B, C and D are also studied. Example 18 specifically examines improvements in muscle strength by way of assessing the effect of urolithin A in elderly mice, where they were fed either a straight high fat diet or a high fat diet laced with urolithin A to provide a dose of 50 mg/kg/day. Other examples feeding urolithin A to mice do so at either 50 or 55 mg/kg/day. Again, and like D7, there is nothing in the teaching of D5 about the effect of protein and I see no reason why this would lead the person skilled in the art to combine urolthin A in the claimed range with high levels of protein. While I note D5 also has some general statements alluding to broad ranges of between 0.2 to 2000 mg of urolithin compound per kg of bodyweight that might be administered to achieve an effect,[45] I think the situation is the same as for D7 and there is no obvious reason for the person skilled in the art to depart from 50 or 55 mg/kg as disclosed in those example relating to muscle function. I am led to conclude that the person skilled in the art learns nothing about protein effects in D5, only that urolithin compounds may have an effect on muscle performance.
[44] D8, p. 2, line 25 to p. 4, line 20.
[45] D7, p. 65, lines 16-25.
I also note the applicant’s submission that D5 teaches away from the present invention of combining urolithin A with a high protein diet,[46] where it said that “[a] low protein diet has been shown in mice to lead to a prolonged induction of autophagy. In mice with DMD fed a low protein diet, an induction of autophagy leads to an improvement and management in the disease progression.” D5 links increased autophagy with improved muscle function and I agree this would suggest to the person skilled in the art that a diet lower in protein would be beneficial when seeking to improve certain muscle-related disorders. Again, in relation to D5, I conclude that the person skilled in the art would not be directly led from this document to the presently claimed invention with any reasonable expectation of success.
[46] D5, p. 22, line 32 to p. 23, line 5.
There is little need to consider in detail whether the skilled person would combine D5 with D4, D8 or D9 or combine D7 with D8 or D9. I said earlier that I think none of the documents D4, D8 or D9 are specifically directed to solving the same problem that the present application is attempting to address because none of these documents would suggest the level of protein therein would achieve improved muscle function without the need for or with reduced amounts of exercise. In fact, D8 and D9 clearly recommend continuation of exercise in maintaining muscle function and D4 is completely silent on the effect of exercise. The person skilled in the art from reading these documents would not expect the effect of being able to maintain muscle function in the absence of exercise with protein at the levels disclosed therein. Further to this, while D5 and D7 disclose the potential of urolithin A to improve muscle function, I have already said that I do not think the person skilled in the art would be led from either D5 or D7 to the level of protein presently claimed because these documents are teaching the effectiveness of compounds like urolithin A in improving muscle function. It follows that there is no motivation to combine the disclosures of D5 or D7 with any of the documents that were put forward as representing common general knowledge. To do so would amount to hindsight.
Claims 1-20 as they are currently proposed to be amended possess an inventive step.
Conclusion
The remaining objections over the cited prior art cannot be maintained. I find that all claims as they are currently proposed to be amended (as per Annex A below) are novel and possess an inventive step. There being nothing else to consider, I grant leave to allow the amendments up to and including those in the third statement of proposed amendments and direct the application proceeds to acceptance.
Dr Scott D. Makin
Delegate of the Commissioner of Patents
Annex A
CLAIMS (as proposed to be amended by the third statement of proposed amendments filed 1 May 2023)
A composition comprising:
a)a source of protein and
b)urolithin A;
wherein the source of protein is in a range of 20 to 90g and the urolithin A is in a range of 20mg to 2500mg.
A composition as claimed in claim 1 wherein the urolithin A has a D50 size in a range of 0.5 to 50 μm and a D90 size in a range of 5 to 100 μm.
A composition as claimed in claim 1 or 2 wherein the protein makes up 20-99% w/w of the composition.
A composition as claimed in claim 3 wherein the protein makes up 30-80% w/w of the composition.
A composition as claimed in any one of claims 1 to 4 wherein the weight ratio between the protein component and the urolithin is in a range of 5:1 to 1200:1.
A composition as claimed in any one of claims 1 to 5 wherein the protein is hydrolyzed, partially hydrolyzed or non-hydrolyzed protein.
A composition as claimed in claim 6 wherein the protein is derived from a source selected from the group consisting of: milk including casein and whey; animal including meat, fish; cereal including rice and corn; and vegetable including soy and pea sources.
A composition as claimed in claim 7 wherein the protein is selected from the group consisting of: intact pea protein, intact pea protein isolates, intact pea protein concentrates, milk protein isolates, milk protein concentrates, casein protein isolates, casein protein concentrates, whey protein concentrates, whey protein isolates, sodium or calcium caseinates, whole cow's milk, partially or completely defatted milk, soy protein isolates and soy protein concentrates, and combinations thereof.
A composition as claimed in any one of claims 1 to 8, wherein the composition is in the form of a yoghurt.
A composition as claimed in any one of claims 1 to 8 wherein the composition is in the form of a solid including a tablet or a bar, a semi-solid including a softgel, a capsule including a hard capsule, a dragee, a powder or a liquid including emulsions.
A composition as claimed in any one of claims 1 to 10 when used as a medicament, dietary supplement, functional food, functional beverage or medical food.
A composition as claimed in claim 11 when used as a medicament.
A composition as claimed in any one of claims 1 to 12 when used in the treatment of a muscle-related pathological condition.
A composition as claimed in claim 13, wherein the muscle-related pathological condition is selected from musculoskeletal diseases or disorders; muscle wasting; myopathies; neuromuscular diseases, including Duchenne muscular dystrophy and other dystrophies sarcopenia including acute sarcopenia; and muscle atrophy and/or cachexia, including muscle atrophy and/or cachexia associated with burns, bed rest, limb immobilization, or major thoracic, abdominal, and/or orthopedic surgery.
A composition as claimed in any one of claims 1 to 11 when used for enhancing muscle performance.
A composition as claimed in claim 15, wherein the subject suffers age-related decline in muscle function, age-related sarcopenia, age-related muscle wasting, physical fatigue, muscle fatigue, and/or is frail or pre-frail.
A composition as claimed in claim 16, wherein the subject is frail or pre-frail.
A kit comprising:
a)a source of protein and
b)Uriolithin A;
when used in the composition according to claim 1.
A composition comprising:
a)a source of protein and
b)Urolithin
when used in enhancing muscle growth, muscle strength, muscle endurance and muscle function in the absence of exercise, or with less exercise being necessary; wherein the composition is as defined in any one of claims 1 to 11.
A composition as claimed in claim 19, wherein use is in sedentary individuals and the elderly.
0
5
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