Merial Limited v Bayer New Zealand Limited
[2014] APO 86
•17 December 2014
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Merial Limited v Bayer New Zealand Limited [2014] APO 86
Patent Application: 2007221747
Title:Medicament
Patent Applicant: Bayer New Zealand Limited
Opponent: Merial Limited
Delegate: Dr S.D. Barker
Decision Date: 17 December 2014
Hearing Date: 12 November 2014, in Canberra
Catchwords: PATENTS – opposition to the grant of a patent – inventive step considered – would not be a matter of routine to use greater than 20% suspended solids – opposition fails
Representation: Patent applicant: Ian Finch and Peter Brown of James & Wells
Opponent:Marcus Caulfield and Marianne Seter of FB Rice
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2007221747
Title:Medicament
Patent Applicant: Bayer New Zealand Limited
Date of Decision: 17 December 2014
DECISION
I allow the amendment of the statement of grounds and particulars. I allow the further evidence.
The opposition is unsuccessful.
Subject to appeal, I direct the application to proceed to grant.
I award costs according to Schedule 8 against Merial Limited.
REASONS FOR DECISION
Patent application number 2007221747 was filed on 1 October 2007. The applicant is Bayer New Zealand Limited (Bayer). The application was examined and accepted by the Commissioner, and subsequently opposed by Merial Limited (Merial). A hearing was held on 12 November 2014 in Canberra to decide the opposition. Bayer was represented by Ian Finch and Peter Brown of James & Wells. Merial was represented by Marcus Caulfield and Marianne Seter of FB Rice.
The opposition
A request to amend the statement of grounds and particulars was filed on 3 November 2014. There was no objection, and I will allow the amendment. The statement of grounds and particulars identifies multiple grounds of opposition. However, at the hearing, the opposition was limited to the grounds of lack of inventive step and clarity.
The parties relied upon evidence by several declarants. Evidence in support consists of declarations by Gottfried Lichti (Lichti 1) and Marcus Caulfield. Evidence in answer consists of declarations by Fadil Al Alawi and Raid Ghassan Marhoon Alany. Evidence in reply consists of declarations by Gottried Lichti (Lichti 2) and Marcus Julian Caulfield. Further evidence was filed by Merial in the form of declarations by Sean Daly and Julie Buston. There was no objection to the further evidence, so I will allow the further evidence. I will refer to the relevant parts of the evidence where appropriate.
The specification
The specification relates to anthelmintic formulations. The specification ends with 20 claims. Claim 1 is the only independent claim.
What is the invention as described
Before commencing to construe the specification, I note what Middleton J said in Eli Lilly and Company Limited v Apotex Pty Ltd [2013] FCA 214, 100 IPR 451 at [139]:
"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."
The background to the invention
The specification begins by stating that anthelmintics are well known:
"Anthelmintics are widely used in aqueous formulations for the control of parasitic helminths, namely round worms (nematodes), tapeworms (cestodes), or flukes (trematodes).
Anthelmintics have been used in a variety of animal species including sheep, cattle, goats, deer, horses, cats, dogs, llama, buffalo and poultry."
At page 2 the specification talks about the treatment of horses:
"Worming horses can be a difficult exercise, despite the large number of worming products currently available and attempts to increase the palatability of products.
For the treatment of horses, drenches pour-on products, granular products put in to feed, and pastes have been used with varying success."
Difficulties associated with known modes of administration are described on pages 2 to 3.
The aim of the invention
This leads to the objective, stated on page 4 as:
"It is therefore an object of the present invention to provide a product which is easily administered to horses or other equine species, and overcomes the above mentioned problems."
At the hearing there was broad agreement between the parties that the problem addressed by the specification is the provision of a broad spectrum worming treatment for horses that overcomes the known problems of solid formulations and liquid formulations. Effectively, the area of interest is in paste formulations, and specifically pastes that are not readily "spat out" by the horse.
The nature of the invention
At page 5 the specification summarises the invention in broad terms as:
"According to one aspect of the present invention there is provided a medicament for oral administration to a subject, which includes
at least one compound which is selected for its activity against strongyles, and
at least one macrocylic lactone (or pharmaceutical acceptable salts), and
praziquantel (or pharmaceutical acceptable salts),
if required, at least one thickening agent to provide the required viscosity,
characterised in that
the medicament is formulated to within a viscosity range of 20,000 to 150,000 cp at 20°C when measured on a rotating spindle at 6.0 rpm which ensures that once administered orally the medicament spreads readily into the mouth of the subject."
Construction of claim 1
The correct approach to the construction of claims was discussed by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70, 81 IPR 228 at [118] – [120]:
"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"
Claim 1 is the independent claim. It reads
A medicament for oral administration to a subject, which includes active ingredients including
at least one compound which is selected for its activity against strongyles, and
at least one macrocyclic lactone (or pharmaceutical acceptable salts), and
praziquantel (or pharmaceutical acceptable salts), andif required, at least one thickening agent to provide the required viscosity, characterised in that
the medicament includes over 20% w/w of suspended active ingredients; and
the medicament is formulated to within a viscosity range of:a) 100,000 to 800,000 cp at 20°C when measured on a Helipath spindle T‑F at 0.6 rpm, and;
b) 20,000 to 150,000 cp at 20°C when measured on a Helipath spindle T‑F at 6.0 rpm,
which ensures that once administered orally the medicament spreads readily into the mouth of the subject.
The composition is characterised by the active agents, and a viscosity range for the composition. Some matters of construction need to be considered.
(i)How many active agents must be included in the composition?
It is well known that macrocyclic lactones have activity against strongyles. Consequently, a macrocyclic lactone could "double up" as both the first and second active agent. However, the structure of the sentence seems to suggest that three active agents are employed. In order to resolve the ambiguity it is permissible to resort to the body of the specification to define or clarify the meaning of words used in the claims (Interlego AG v Toltoys Pty Ltd [1973] HCA 1; (1973) 130 CLR 461 at 479). I think it is readily apparent from the body of the description that application relates to the use of three different active agents, and there is no discussion of the use of two agents only. I consider that the proper construction of claim 1 is that there must be (at least) three active agents.
(ii)Are the words "which ensures that once administered orally the medicament spreads readily into the mouth of the subject" a limiting feature?
The final statement in the claim is "which ensures that once administered orally the medicament spreads readily into the mouth of the subject". This could be seen as either a further limitation on the nature of the composition (i.e. the claim is only directed to those compositions that spread readily), or as a descriptive statement of the effect achieved by the previous features (particularly the viscosity). The words appear in the context of "the medicament is formulated within a viscosity range of … which ensures that …". It seems to me that the natural meaning of the words, in the context in which they are used, is that it is a consequence of the viscosity specified that the composition will spread readily within the mouth of the horse. I am satisfied that this is the proper construction of the claim.
(iii)Parameteritis
It was argued that the viscosity parameters should be seen as merely parameteritis. I discussed this concept in Euroceltique S.A. v Sandoz Pty Ltd [2009] APO 21, and said at [112] that the critical question was whether the parameters in a claim "have been chosen to achieve a technical effect, or whether they are an arbitrary convenience". In the present case, the viscosity of the paste is related to whether or not it will be "spat out" by the horse, which is a key issue. It cannot be said that viscosity does not have a technical effect.
It may be that the viscosity is what is already known or used in pastes, but that goes to whether or not there is an inventive step, not to whether the feature has a technical effect.
Inventive step
It is a requirement of subsection 18(1) of the Act that the invention, so far as claimed in any claim, involves an inventive step. Subsection 7(2) states that an invention is taken to involve an inventive step unless it would have been obvious to a person skilled in the art in the light of the common general knowledge, considered alone or together with the prior art. A document is prior art for this purpose if "a skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood, regarded [the document] as relevant" (subsection 7(3)).
The test for whether an invention is obvious is to ask whether it would have been a matter of routine to proceed to the claimed invention. In Wellcome Foundation Ltd v V.R. Laboratories (Aust.) Pty Ltd [1981] HCA 12 at [45], 148 CLR 262 at 286 Aickin J stated:
"The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not."
The High Court approved this approach in Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59, 212 CLR 411.
In the present case the problem addressed by the specification is the provision of a broad spectrum worming treatment for horses in the form of a paste that is not readily "spat out" by the horse. The allegation of lack of inventive step is based on a consideration of the common general knowledge alone, and the common general knowledge considered together with 5 pieces of prior art information. The prior art information is:
- NZ 515772 (referred to by the parties as D3)
- The label of the product Equitak Excel (referred to by the parties as D13)
- information made publicly available through the sale of the products Equimax Oral, Equimax LV, Iverquantel and Promectin Plus
The threshold question is whether this information would have been ascertained, understood and regarded as relevant.
NZ 515772 (D3)
D3 relates to pesticidal compositions, particularly liquid formulations that contain multiple active ingredients. In general terms, the document seems to relate to the kind of problem addressed by the present application. I will accept that D3 would have been ascertained, understood and regarded as relevant.
The most important disclosure, for the purposes of this opposition, is on page 40. A composition referred to as LB99/72A has the following composition:
Soybean Oil 15.00% Teric 380 5.00% Ivermectin @ 100% 0.10% Benzyl alcohol 1.50% Levamisole HCl @ 100% 3.75% Colloidal Silicon Dioxide 8.00% Praziquantel 1.88% NaOH (to pH 3.5) 0.37% Citric acid 1.00% Water to volume To weight Appearance Homogenous white gel pH 3.5 Viscosity % >100,000 cps
At the bottom of page 40 it says:
"Formulation LB99/72A formed a white thick pourable gel which was considered to have application for example orally in horses, dogs and cats."
Dr Lichti considered this document and stated (at Lichti 1 at [119] and [120]):
"The document tells me that it was possible to formulate gel compositions which comprised a macrocyclic lactone (a compound with activity against strongyles), levamisole HCl (a compound with activity against strongyles) and praziquantel. Furthermore, the viscosity of such compositions can be adjusted with use of a colloidal silicon dioxide (thickening agent).
I would be confident that I could adjust, if needed, the quantity of colloidal silicon dioxide to develop a formulation with the viscosity range as specified in the opposed specification. That is because this document describes formulations that comprise the three claimed active agents and provides clear guidance on how to adjust the viscosity of the gel to a specific value within a wide range by the inclusion of colloidal silicon dioxide."
Equitak Excel label (D13)
D13 is the label of the product Equitak Excel. D13 was published on the Agricultural Compound and Veterinary Medicines (ACVM) database on 30 August 2006. It is my understanding that this is a New Zealand database that is accessible using the internet. The label states that the product is a three in one combination wormer for horses. The active ingredients are listed as abamectin (4 mg/g), praziquantel (50 mg/g) and oxfendazole (200 mg/g). It is apparent that the product is a paste, but the viscosity not identified.
It is not in dispute that the product Equitak Excel was not sold or publicly available before the priority date. Consequently, D13 is prior art for the purposes of this opposition if it would have been ascertained, understood and regarded as relevant from the ACVM database.
Dr Lichti says (at Lichti 1 [62] – [63]):
"I will set out the approach that I would have adopted, and still do adopt, with any project that required me to formulate an active agent for veterinary use. From my experience, a similar approach would have been adopted by most other formulators. In the initial exploratory stage of the project, I would have gone to the literature. This might involve finding a textbook and tracking its references backwards and/or arranging for a search to be carried out of the [sic] a database that included patents and Chemical Abstracts. Internet searching of available patent data bases would be a routine activity in the initial exploratory phase. One database with which I was familiar was the Derwent database. I know from personal experience that the Derwent database was available from the late 1980's. The results of the search would provide me with literature detailing the chemical and physical properties of the active agent and the manner in which it had been formulated previously including ways to address any possible instability of active ingredients.
I would also have accessed regulatory information prepared by a regulatory body or reputable vendor in relation to the active ingredient. This would include, for example, Chemical Fact Sheets and Health and Safety Guides issued in relation to the product by governmental bodies such as the Environmental Protection Authority (EPA) and the World Health Organisation (WHO). Another source of information regarding the characteristics of prior art products is their Material Safety Data Sheets (MSDS). As discussed above, I would have also examined the APVMA register for information regarding products registered in Australia and the corresponding register for products registered in New Zealand."
I conclude that a person would have consulted the ACVM database. It is not so clear that they would have ascertained this entry in the database. I understand that the ACVM database contains information about veterinary products, and the information is based on the active ingredients. Dr Lichti implies it is a means to learn about commercial products that contain an active ingredient of interest. He does not say that he would have found the information on Equitak Excel in the ACVM datatabase if he was searching for a solution to the more general problem in the present case. It seems to me that the Equitak Excel information in D13 would have been ascertained if you knew what you were looking for. I am not satisfied that it has been established that D13 would have been otherwise ascertained. It follows that the evidence does not establish that D13 would have been ascertained.
The sale of Equimax Oral, Equimax LV, Iverquantel and Promectin Plus
These products differ from D13 in that they were in use. While the evidence that these products would have been ascertained and regarded as relevant is very thin, the discussion of them by all declarants seems to suggest that they all regarded these products as well understood and clearly relevant for the purposes of the present application. In the circumstances I will proceed on the assumption that they would have been ascertained, understood and regarded as relevant.
There is evidence that the four products were sold before the priority date. It is convenient to summarise the composition of these products in a table:
Equimax Oral Equimax LV Iverquantel Promectin Plus Compound with strongyle activity - - - - Macrocyclic lactone 0.4% Abamectin 1.87% Ivermectin 0.4% Ivermectin 0.37% Abamectin Praziquantel 5.0% 14.3% 5.0% 4.62% Amount of suspended active agents * 5.0% 14.3% 5.0% 4.62% Viscosity 131,726 at 6 rpm
334,238 at 0.6 rpm138,124 at 6 rpm
478,366 at 0.6 rpm66,460 at 6 rpm
184,805 at 0.6 rpm66,986 at 6 rpm
194,785 at 0.6 rpm* The macrocyclic lactone is not a suspended active agent: Alawi declaration at [59], [75] and [76]
It is clear that each of these compositions lack a third active agent, and do not have greater than 20% total suspended active agents.
Common general knowledge
It is contended that the following are common general knowledge: benzimidazole anthelmintics, levamisole, macrocylcic lactones anthelmintics, praziquantel, and combination anthelmintic treatments. I accept that these are all well known in the art.
What must be shown to establish lack of inventive step?
The opponent submitted that there is a lack of inventive step because of four elements:
(1)It would have been a matter of routine to prepare a paste
(2)The selection of the three active agents would have been a matter of routine
(3)The selection of the total amount of actives of greater than 20% would have been a matter of routine
(4)The selection of the specific viscosity would have been a matter of routine
The applicant asserted that there was an inventive step because:
(5)The combination of elements (3) and (4) would not have been a matter of routine
I will consider each of these elements in turn, noting that they are interconnected.
Element 1: Would a person have prepared a paste as a matter of routine?
Yes. Pastes were a well understood formulation (Lichti 1 at [59] – [61]). The specification itself refers to the advantages of pastes over drenches, but notes the problem of spitting out. Dr Alany notes that pastes are "more palatable than liquid dosage forms for some target species (equine in particular) as they are better retained in the mouth and less likely to be spitted out" (at [40]). However, there are viscosity considerations that are discussed below.
Element 2: Would a person have selected a combination of three active agents to produce a worming composition?
The evidence shows that the three active agents in the claims were known before the priority date, and were known to have anthelmintic properties (Lichti 1 at [26] to [37]). Dr Lichti states it was common general knowledge that combining active agents could broaden the sprectrum of activity (Lichti 1 at [43]):
"it was common general knowledge that combining two or more active agents into a single product could broaden the spectrum of activity of the composite product"
Dr Alawi agrees with this statement (Alawi at [51]).
The evidence also shows that combinations of the three types had been used in commercial products, including the use of all three in a single formulation (Lichti 1 at [38] to [47], and [126] to [168]). I am satisfied it would have been a matter of routine to select a combination of three active ingredients.
Element 3: Would a person have selected a total amount of suspended actives greater than 20%?
It must be assumed that a person knew how much of each active agent would be necessary in order to achieve effective treatment, and would utilise the required amount as a starting point. This leads to the question of what is the normal usage of the three active agents?
Macrocyclic lactones are normally used in low amounts. Abamectin is used in 0.4% in the products Equitak Excel, Equimax Oral and Promectin Plus. The highest usage I have noted is 1.87% ivermectin in Equimax LV.
Praziquantel is normally used in about 5%. It is used in 4.62 – 5.0% in the products Equitak Excel, Equimax Oral, Iverquantel and Promectin Plus. However, praziquantel is used in 14.3% in Equimax LV.
Benzimidazoles are normally used in 10 to 50 times the amount of macrocylic lactones (Lichti 1 at [87]). They are used in amounts ranging from 2.0 – 21.3% in the products Triton Tape (2.0% albendazole), Matrix Tape (2.2% oxfendazole) and Canimax (21.3% oxibendazole).
It is clear that if a person used the upper amount of each active, the total amount of solid material would be greater than 20%. However, a person could just as easily select a different combination that would lead to less than 20%. In this situation it cannot be said to be a matter of routine to use greater than 20% suspended active agents.
Element 4: Would a person have prepared a paste of the specific viscosity?
Dr Lichti's first declaration refers to how he would have determined the viscosity needed in a paste at [170]:
"If I wanted to make a new medicament that also spread in the mouth, it would have been an obvious starting point to use the same or similar characteristics, e.g. flavour, viscosity parameters, etc as medicaments already on the market and known to be effective and practical for that application."
He then considers the viscosity of various known pastes at [174]:
"The viscosity range specified in claim 1 of the opposed application is 20,000 – 150,000 cP, and the above line graph shows that at least 5 medicaments which were designed for oral administration to animals and which were commercially available on 29 Sept 2006 fall in this viscosity range. I would thus consider that the viscosity range teaching in the opposed application was not novel, and could have been inferred merely by measuring readily available anthelmintic pastes."
Noting that claim 1 was amended after this declaration was completed (changing the viscosity aspect of the claim), this evidence clearly asserts that a person wishing to make a paste would have adopted a viscosity similar to that used in commercially available pastes. This is an inherently logical assertion. Further, the viscosity range as claimed encompasses five commercial pastes. The logical conclusion, although not expressed this way by Dr Lichti, is that a person wishing to prepare a paste to administer an anthelmintic composition to a horse, would have made use of viscosities already known to be useful for worming horses, and this would have had a viscosity falling within the scope of the claim.
Element 5: Would it have been a matter of routine to combine both element 3 and element 4?
This question arises because it is well established that the stability of a suspension of particles in a fluid depends on a number of factors, including the viscosity of the fluid and the size and number of particles. This is given mathematical form in Stokes law. It is unnecessary to quote Stokes law, just to understand that as the amount of suspended particles increases, it is necessary to increase the viscosity of the liquid in order to produce a stable suspension. This much is uncontroversial, and is not in dispute.
However, the present case relates to pastes rather than suspensions, and the evidence does not clearly establish whether Stokes law applies when considering the behaviour of pastes, and more importantly, whether a person skilled in the art would have expected Stokes law to apply to the behaviour of pastes.
Dr Alany notes the difference between pastes and suspensions at [33]:
"Pastes are semi-solid dosage forms in which the active ingredient(s) are dispersed in a continuous phase. Less drastic formulation changes may need to be implemented to ensure chemical stability of the active ingredients and physical stability of the formulation if a paste rather than a conventional liquid suspension is produced."
At [34] he goes on to say:
"The rheological / flow properties of pastes are very different from those of conventional liquid suspensions. In most cases a paste would show shear-thickening rather than a shear-thinning flow and as such would not be pourable. They tend to actually resist flow until a particular amount of stress is applied (yield value)."
Dr Lichti addresses these issues in his evidence in reply. At Lichti 2 [82] he says:
"I agree that Stokes law can be used as a guiding principle for understanding some aspects of stability behaviour in formulations containing suspended particles."
However, Dr Lichti draws different conclusions from Stokes law (Lichti 2 at [89]):
"I note that one strategy is to increase viscosity. However, it would have been clearly obvious, especially in view of the Stokes law, that an equally valid formulating strategy would be to address the size of secondary agglomerates in the suspension."
The evidence leaves it unclear whether a person skilled in the art would have thought that Stokes law would apply to pastes, and consequently whether they would have sought to increase viscosity in response to increasing the amount of suspended material in a paste. In the absence of evidence that a person would have increased the viscosity of the paste, it seems an overwhelmingly reasonable conclusion that a person would have investigated the use of a viscosity that was already established to be suitable for use in worming horses.
Conclusion on inventive step
I am satisfied that the evidence shows that a person would have added additional active agents and have been led to prepare a paste of the viscosity claimed. However, the evidence does not establish that it would have been routine to produce a product with 20% or more active agents.
In the light of this conclusion, it would not have been a matter of routine to prepare a composition falling within the scope of the claims, starting from D3 or any of the four products that had been sold containing only two active agents, or the common general knowledge alone.
I am not satisfied that the ACVM information about the product Equitak Excel would have been ascertained, so it is not necessary to consider what a person would have done with that information as a matter of routine.
I conclude that it has not been established that there is a lack of inventive step.
Clarity
It is a requirement of subsection 40(3) of the Act that the claims must be clear. This requirement is understood to be satisfied if a person could ascertain "whether or not what he proposes to do falls within the ambit of the claim" (Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59).
I discussed the construction of claim 1 previously, and found that I was readily able to construe claim 1. It follows that there is no lack of clarity.
Conclusion
The opposition is unsuccessful. Subject to appeal, the application should proceed to grant.
Costs
The parties submitted that costs should follow the event. I see no reason to depart from that result. Costs should be awarded against the opponent.
Dr S.D. Barker
Delegate of the Commissioner of Patents
0
7
0