Merial Ltd v Norbrook Laboratories Limited - [2014] APO 60

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Merial Ltd v Norbrook Laboratories Limited [2014] APO 60

Patent Application: 2006207326

Title:Anthelmintic composition

Patent Applicant:  Norbrook Laboratories Limited
Opponent:  Merial Ltd
Delegate:  Dr S.D. Barker
Decision Date:  19 August 2014
Hearing Date:  15 May 2014, in Melbourne
Catchwords:  PATENTS – opposition to the grant of a patent – lack of inventive step not established – lack of novelty, clarity, fair basis, manner of manufacture and utility not established – opposition fails

Representation: Patent applicant: Michael Caine and Grant Barry of Davies Collison Cave
Opponent:John Landells, Marcus Caulfield and Jess Smith of FB Rice

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2006207326

Title:Anthelmintic composition

Patent Applicant: Norbrook Laboratories Limited
Date of Decision: 19 August 2014
DECISION
The opposition fails.
Subject to appeal, I direct the application proceed to grant.
I award costs according to Schedule 8 against Merial Ltd.
REASONS FOR DECISION

Patent application number 2006207326 was filed on 19 January 2006 as an international application under the Patent Cooperation Treaty. The applicant is Norbrook Laboratories Limited (Norbrook). The application was examined and accepted by the Commissioner, and subsequently opposed by Merial Ltd (Merial). A hearing was held on 15 May 2014 in Melbourne to decide the opposition. Subsequent to the hearing I allowed the parties an opportunity to provide additional written comments (on a point that arose during the hearing). Both parties provided comments.
The opposition
The statement of grounds and particulars identified several grounds of opposition: manner of manufacture, novelty, inventive step, utility, secret use, full description, clarity and fair basis. At the hearing, the opposition was limited to the grounds of manner of manufacture, novelty, inventive step, utility, fair basis and clarity.
The parties relied upon evidence by several declarants. Evidence in support consists of two declarations by Stephen W Page (Page 1 and Page 2). Evidence in answer consists of two declarations by Craig Bunt (Bunt 1 and Bunt 2) and a declaration by Ian Stanley Pascarl. Evidence in reply consists of a further declaration by Stephen W Page (Page 3). I will refer to the relevant parts of the evidence where appropriate.
The request for examination in relation to the patent application was filed before 15 April 2013. As a consequence, substantive amendments of the Patents Act (the Act) brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 do not apply to the present patent opposition. 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 exists.
The specification
The specification relates to anthelmintic formulations. The specification ends with 14 claims. Claims 1 and 12 are the only independent claims.
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
At page 1 the specification sets out the broad field of the invention as follows:
"a composition displaying efficacy against infections of Fasciola hepatica, Ostertagia ostertagi and Cooperia oncophora in susceptible ruminants, especially cattle"
Infections by these organisms are a known problem, and treatments using an injection of ivermectin and clorsulon are known. Topical formations, however, are not known (page 1):
"Currently, there is no known topical formulation, and this is likely to be due to foreseeable difficulties in achieving adequate penetration of the skin by clorsulon."
This leads to the objective, stated on page 1 as:
"An objective of the invention is to provide a topical formulation which is effective against the aforesaid infections, preferably presented as a pour-on formulation. A further object of the invention is [sic] provide a composition comprising at least one effective agent derived from Streptomyces avermitilis, i.e. a macrocyclic lactone or chemically modified or synthetic derivative thereof together with another anthelmintic of the sulphonamide type. Another objective of the invention is to provide a composition suitable for the treatment of immature Fasciola hepatica."
Merial argued that the problem addressed by the specification is the development of a topical anthelmintic formulation for treating cattle starting from a known anthelmintic formulation of ivermectin and clorsulon. On the other hand, Norbrook said the problem is the development of a topical formulation effective against Fasciola hepatica, Ostertagia ostertagi and Cooperia oncophora, preferably as a pour-on.
Merial's formulation of the problem relies upon giving greater weight to the first quotation than the second quotation. However, I consider that it is appropriate to view the first quotation as part of the background and not the starting point of the invention. Consequently I agree with Norbrook's formulation of the problem addressed by the application.
The nature of the invention
At page 3 the specification summarises the invention in broad terms as a composition of two active agents (a macrocyclic lactone and a sulphonamide) "in a carrier that facilitates topical administration and delivery of the active agents transdermally". The carrier is then explained:
"A carrier that is useful for this purpose comprises alcoholic solvents, such as ethanol, and isopropanol, with optional excipients and formulation aids, which may comprise a polymeric species such as PVP or a poloxamer."
Later on page 3 there is a description of one aspect of the invention, in which
"the alcoholic solvents comprise at least 30% (v/v) of ethanol together with an isopropanol quantity sufficient to 100%"
A single embodiment of a formulation is provided in the text bridging pages 3 and 4. That embodiment is:
"Ivermectin 0.5% (w/v)
Clorsulon 5.0% (w/v)
Ethanol 30% v/v
PEG200 10% v/v
Crodamol Cap 20% v/v
IPA (isopropanol) to 100% v/v
Brilliant Blue Dye 0.01% (w/v)
Denatonium Benzoate 0.001% (w/v)
The nominal dose rate thereof is 500 µg ivermectin and 5 mg clorsulon per kg bodyweight.
The method of countering infection by immature Fasciola hepatica is enabled using such a formulation."
The specification then describes the results obtained by use of a formulation that appears to be that described above.
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 reads as follows:
A topical anthelmintic formulation comprising as active ingredients, a therapeutically effective amount of a least one anthelmintic agent derived from Streptomyces avermitilis, with a therapeutically effective amount of at least one other anthelmintic of the sulphonamide type, in a carrier suitable for topical administration and delivery of active ingredients transdermally, wherein the carrier comprises alcoholic solvents with optional excipients and formulation aids, and wherein the alcoholic solvents comprise at least 30% (v/v) of ethanol together with an isopropanol quantity sufficient to 100%.
The claim is directed to a formulation characterised by several features:
·    the formulation contains at least one anthelmintic derived from Streptomyces avermitilis
·    the formulation contains at least one sulphonamide anthelmintic
·    formulated for transdermal administration
·    the carrier is an alcoholic solvent, being at least 30% ethanol and the remainder isopropanol
The priority date of the claims
The application claims priority from GB 0501220.8 (the priority document), which was filed on 21 January 2005. At the hearing there was a discussion of whether the claims were entitled to priority from the priority document. Due to the conclusions that I have come to in relation to novelty and inventive step, it is not necessary to come to a conclusion on this point.
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 in Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59, 212 CLR 411 approved this approach.
In the present case the problem addressed by the specification is the development of a topical formulation effective against Fasciola hepatica, Ostertagia ostertagi and Cooperia oncophora, preferably as a pour-on. Merial's attack on inventive step proceeded on several bases:
·    the invention defined by claims 1 – 14 lacks inventive in the light of the common general knowledge alone
·    the invention defined by claims 1 – 14 lacks inventive step in the light of the common general knowledge and a patent document
·    the invention defined by claims 1 – 14 lacks inventive step in the light of the common general knowledge and several documents (combined with each other)
The common general knowledge
As is normal in opposition matters, the parties were not in agreement as to what matters were common general knowledge. I will address the important matters in turn.
a) Ivermectin and clorsulon combinations for use in treating cattle
Ivermectin and clorsulon were known and widely used agents before the priority date of the claims. This is apparent from Page 1 and Bunt 2.
Merial asserted that it was common general knowledge that ivermectin and clorsulon could be used together to provide a broad spectrum anthelmintic formulation. I accept that this combination had been used, as evidenced by the product IVOMEC F. However, IVOMEC F is an injectable formulation. The broad thrust of the Page 1 evidence is that IVOMEC F was sufficiently well known to be regarded as common general knowledge. Bunt 2 does not disagree.
I am satisfied that it was common general knowledge that a combination of ivermectin and clorsulon can be used as an injectable formulation.
b) Alcohol solvents for use in topical formulations
It was agreed that the use of alcoholic solvents in topical formulations was common general knowledge. Page 1 at [77] says:
"the use of alcohols such as ethanol and isopropanol is common in the area of pour-on formulations"
It was not accepted that it was common general knowledge to use mixtures of ethanol and isopropanol. Norbrook pointed to Bunt 2 at [42]:
"Although selection of an aliphatic alcohol in a solvent system is not unusual the selection of two aliphatic alcohols as the solvent system for a pour-on formulation is atypical."
I consider that this represents a fair summary of the position at the priority date of the claims.
What is routine
There are two key matters that must be shown to be matters of routine in order for Merial to succeed. The first is whether it would have been routine to use a combination of ivermectin and clorsulon. The second is whether it would have been a matter of routine to use a solvent of at least 30% ethanol in isopropanol. I will consider each in turn.
a) Using both ivermectin and clorsulon
An important question is whether it would have been a matter of routine to use a combination of ivermectin and clorsulon as an active agent. The fact that these two active agents were probably part of the common general knowledge individually does not mean that their use in combination would have been a matter of routine.
Merial relied on the fact that a combination of ivermectin and clorsulon was common general knowledge (in the form of the injectable formulation IVOMEC F, discussed above). Even if this is true, what has not been shown is that it would have been a matter of routine to select the combination of ivermectin and clorsulon as the agent to use to solve the problem in this case (i.e. for a topical formulation against the range of organisms). I do not accept that as a matter of logic whatever is part of the common general knowledge would have been a routine starting point. I have carefully considered the evidence and I cannot find a clear statement that this would have been a matter of routine.
b) Using a solvent of at least 30% ethanol in isopropanol
If it is assumed that a person wished to prepare topical formulations, would it have been a matter of routine to use a solvent system of at least 30% ethanol in isopropanol?
Dr Bunt in Annexure CB-4 to his first declaration discussed in general terms the requirements of a formulation:
"A solvent or solvents to dissolve triclabendazole, a surfactant to enhance penetration, with the likely added benefit of aiding dissolving triclabendazole; and a viscosity modifier to increase viscosity to aid retention at the site of application."
I accept that it would have been routine to include such components in any formulation. Looking at the solvent system, Page 1 says at [77]:
"the use of alcohols such as ethanol and isopropanol is common in the area of pour-on formulations. Alcohols such as these are employed for their use as simple carriers and also as penetration enhancers."
and at [78]:
"The selection of this mixture appears to be arbitrary in the absence of comparative data with formulations comprising other ratios of ethanol and isopropanol or alternatives to this specific alcoholic mixture. As such, I consider that 30% (v/v) ethanol together with isopropanol to 100% is a trivial selection of a solvent mixture that a skilled person would arrive at through routine experimentation."
Dr Bunt disagrees in Bunt 2 at [42]:
"Page also says in paragraph 78 of his 10 August 2012 declaration that the combination of 30% ethanol together with isopropanol to 100% is a trivial selection of a solvent mixture that a skilled person would derive through routine experimentation. I disagree with this comment. Although selection of an aliphatic alcohol in a solvent system is not unusual the selection of two aliphatic alcohols as the solvent system for a pour-on formulation is atypical."
It seems to be accepted that there is a wide range of solvents that can be used, and ethanol and isopropanol are part of that wide range. It is not agreed by the declarants whether it would have been a matter of routine for a formulator to try every combination of every solvent within that wide range.
I have looked at the compositions that are referred to in the evidence on file, and it is not apparent that ethanol in isopropanol was a common solvent system. Based on this observation, I prefer the evidence of Dr Bunt that at least 30% ethanol in isopropanol would not have been arrived at as a matter of routine.
Obviousness in the light of the common general knowledge alone
I already found that it would not have been a matter of routine to use a solvent of at least 30% ethanol in isopropanol. Consequently the invention defined in the claims would not have been obvious in the light of the common general knowledge alone.
Obviousness in the light of the prior art WO 02/09764
WO 02/09764 (the Razzak patent) was published on 7 February 2002. Consequently it is part of the prior art base.
The threshold question is whether the Razzak patent would have been ascertained, understood and regarded as relevant. In Page 1 at [39] it is stated:
"When developing a new product, it was my practice, and I believe the practice of others skilled in the art before the priority date, to search the existing literature (which included patent databases and published journal article databases) and develop a dossier of literature regarding the proposed active combination."
It seems to me that Mr Page would have consulted databases containing patent literature. Mr Page considered that the Razzak patent was a document that he would have ascertained in a search of those databases (see Page 2 at [25]):
"[Razzak] was publicly available at the priority date of the opposed patent and as such I would have identified this document in a search for literature relating to anthelmintic formulations and particularly for formulations which comprise ivermectin alone or in combination with other anthelmintics"
I will accept that the Razzak patent could have been ascertained. The Razzak patent relates to veterinary compositions. There is no specific discussion of treating Fasciola hepatica, Ostertagia ostertagi or Cooperia oncophora. However, it is apparent that the active agents are anthelmintics, including avermectins and clorsulon. I consider that the Razzak patent could have been regarded as relevant to work on anthelmintics.
Looking in detail at the Razzak patent, it discloses veterinary compositions having a combination of hydrophilic and lipophilic active agents. Norbrook pointed out that the Razzak patent does not disclose topical formulations. At page 3 the Razzak patent says:
"preferably, the compositions of the present invention can be easily adapted to be suitable for oral, nasal, ophthalmic and topical administration in addition to
subcutaneous and intra muscular administration"
Topical formulations are clearly envisaged. Preferably the lipophilic active agent can be a macrocylic lactone, "including avermectins". Ivermectin is specifically used in Example 5. Preferably the hydrophilic active agent is selected from a group including clorsulon. The solvent is selected from organic solvents, which can be "alcohol including isopropyl" (page 3). It seems to be a safe conclusion that the Razzak patent indicates a range of active agents that can be combined, and this range includes ivermectin and clorsulon. This is confirmed by Example 5, which is a composition containing 1% ivermectin and 10% clorsulon. The solvent system in Example 5 does not utilise either ethanol or isopropanol.
The critical issue is whether it would have been a matter of routine to alter the composition of Example 5 to use a solvent of ethanol and isopropanol. In my discussion above I concluded that the evidence does not establish that it would have been a matter of routine to use a solvent of at least 30% ethanol in isopropanol. It follows that it has not been established that the claims lack inventive step in the light of Razzak.
Obviousness in the light of a combination of documents

It was argued that a combination of the Razzak patent and one or more of WO 2005/007241 (Blakely) and the products IVOMEC F and IVOMEC Pour-on, renders the invention obvious.
Section 7(3) permits an opponent to rely on a combination of any two or more pieces of prior art information if the skilled person could, before the priority date, "be reasonably expected to have … combined" the pieces of information.
The feature that is missing from the Razzak patent is the solvent. Consequently it is this feature that must be found in the other documents in order for them to advance the cause of Merial.
IVOMEC Pour-on contains ivermectin, triethanloamine and isopropanol. IVOMEC F contains ivermectin, clorsulon, propylene glycol and glycerol formal. Neither product contains ethanol and isopropanol. Even if these disclosures were combined with the Razzak patent they do not assist with respect to the solvent.
Blakely was published on 27 January 2005, which is after the filing date of the priority document. As stated earlier, I have not decided whether the application is entitled to priority from the priority document. This is because the combination of Blakely and Razzak does not render the invention obvious, so the priority date is immaterial. My reasons for that conclusion are as follows.
Blakely discloses anthelmintic compositions. For the purposes of this discussion I have assumed that it would have been ascertained, understood and regarded as relevant (for similar reasons to those discussed for the Razzak patent). Formulation 1 in Blakely is as follows:
Ivermectin                   0.25% w/v
Closantel  5.0% w/v
Ethanol            30% v/v
Isopropyl Alcohol to     100% v/v
Clearly there is a disclosure of the solvent system that is missing from the Razzak patent. Would it have been "reasonably expected" that a person could combine the relevant pieces of information in the two documents? Page 2 at [151] says:
"I consider that a skilled person would combine the disclosures of the Razzak and Blakely papers and in doing so, I consider that a skilled person would consequently be led to formulations comprising ivermectin and clorsulon, in an alcoholic solvent comprising at least 30% ethanol v/v with isopropanol to 100% v/v together with optional excipients and formulation aids, i.e., the formulation claimed in the opposed patent."
Bunt 2 says at [92]:
"there is nothing in patent documents 02/09764 [Razzak], WO 2005/007241 [Blakely] …that would have caused me to combine any one of them."
The evidence on whether or not a person would consider it obvious to combine the teachings of Razzak and Blakely is the statements made by the declarants. The declarants provide contrary opinions without a rationale for their views. I consider that the motivation to combine the information in the Razzak and Blakely documents is that it gives all the integers of the present composition. However, without the benefit of hindsight it is not apparent on the face of the documents that it would have been reasonably expected that a person could combine the information. Given that the onus rests on Merial in this opposition, I am not satisfied that they have made a case for combining the teachings.
Conclusion
It has not been established that any of the claims lack inventive step in the light of either the common general alone, or any of the documents cited.
Novelty
It is a requirement of subsection 18(1) of the Act that the invention, so far as claimed in any claim, is novel. Subsection 7(1) states that an invention is taken to be novel unless it is not novel in the light of the prior art. A citation is part of the prior art base for the purposes of novelty if it was published before the priority date of the claim.
It is well established that the general test for lack of novelty is the reverse infringement test. The classic formulation of this test is that given by Aickin J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19 at [20], 137 CLR 228 at 235:
"The basic test for anticipation or want of novelty is the same as that for infringement and generally one can properly ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement"
The disclosure necessary to support the ground of lack of novelty has variously been described as "clear and unmistakeable directions" (The General Tire & Rubber Company v The Firestone Tyre and Rubber Company Limited [1972] RPC 457 at 486), "the accuracy of a sniper, not the firing of a 12 gauge shotgun" (Apotex Pty Ltd v Sanofi-Aventis [2008] FCA 1194, 78 IPR 485 at [91]) or "what a prior art document teaches" as distinct from "what might be 'included' or 'encompassed in' a prior art document" (Sanofi-Aventis Australia Pty Ltd v Apotex Pty Ltd (No 3) [2011] FCA 846, 92 IPR 320 at [180]). There is a degree of specificity that is required.
Merial relied on the Razzak patent to allege lack of novelty. As noted above, the Razzak patent is part of the prior art base. Norbrook pointed out that the Razzak patent does not explicitly disclose topical formulations. At page 3 it says:
"preferably, the compositions of the present invention can be easily adapted to be suitable for oral, nasal, ophthalmic and topical administration in addition to subcutaneous and intra muscular administration"
The Razzak patent also refers to solvents in very broad terms. At page 3 it says:
"alcohol including isopropyl"
Example 5 of the Razzak patent is the most relevant for the present opposition. It describes a composition containing ivermectin and clorsulon. The solvent does not contain either ethanol or isopropanol.
While it is clear that the Razzak patent can be seen to disclose subject matter that broadly overlaps with the territory of the claims of the present specification, it does not disclose that subject matter in clear and unmistakeable terms. It has not been established that the claimed invention lacks novelty in the light of the Razzak patent.
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).
Merial argued that claim 10 lacks clarity. Claim 10 says:
A topical anthelmintic formulation according to Claim 1, which in use provides at least 2 µg of a benzenesulphonamide per ml of blood plasma.
Merial said that typically such a blood plasma concentration would be accompanied by a time or time range at which this concentration occurs. The claim says that a dosing of 2 µg per ml must be obtained at ANY time after administration. Is see no reason to consider that a person would not be able to tell whether a formulation fell within the scope of this requirement. I am not satisfied that claim 10 lacks clarity.
Fair basis
It is a requirement of subsection 40(3) of the Act that the claims must be fairly based on the matter described in the specification. The High Court in Lockwood Security Products Pty Ltd v Doric Products Pty Ltd [2004] HCA 58 at [69], 217 CLR 274 at 300 approved the words of Gummow J in Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79 at 95:
"the question is whether there is a real and reasonably clear disclosure in the body of the specification of what is then claimed, so that the alleged invention as claimed is broadly, that is to say in a general sense, described in the body of the specification"
Merial asserts that it is essential that the compositions contain Crodamol Cap, and consequently there is a lack of fair basis whenever the claims omit this feature. The question is whether there is a real and reasonably clear disclosure of compositions that do not contain Crodamol Cap.
The single example includes Crodamol Cap, which is used as a spreading agent. However, the broader statements of the invention do not suggest that the invention is limited the use of Crodamol Cap. There can be no doubt that there is a real and reasonable disclosure of compositions that do not contain Crodamol Cap.
Manner of manufacture
It is a requirement of subsection 18(1) of the Act that the invention, so far as claimed in any claim, must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies. The statement of grounds and particulars asserts that the necessary quality of invention is not present on the face of the specification. It follows from my consideration of inventive step in the light of the common general knowledge and the prior art that this ground cannot be made out.
Utility
It is a requirement of subsection 18(1) of the Act that the invention, so far as claimed in any claim, must be useful. The issue of utility was considered by the Full Court of the Federal Court in H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70, 81 IPR 228. Emmett J at 247 [81] stated:
"A claim is bad if it covers means that will not produce the desired result, even if a skilled person would know which means to avoid. That is to say, everything that is within the scope of a claim must be useful, otherwise the claim will fail for inutility"
Merial allege that there is a lack of utility because not all sulphonamides are soluble in alcohol. The solubility data for ivermectin and clorsulon presented earlier shows that solubility is a matter of degree. In the absence of evidence that an effective formulation would not be possible, it seems more likely that solutions of sulphonamides could be prepared, which would be effective to some degree.
Conclusion
I have found that all grounds of opposition fail.
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