Merial Limited v Bayer Intellectual Property GmbH

[2016] APO 16

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Merial Limited v Bayer Intellectual Property GmbH [2016] APO 16

Patent Application:                2007341647

Title:Agents for controlling parasites on animals

Patent Applicant:                   Bayer Intellectual Property GmbH

Opponent:  Merial Limited

Delegate:  Dr M-A. Fam

Decision Date:  1 April 2016

Hearing Date:  18 February 2016, in Canberra

Catchwords:  PATENTS – section 59 – opposition to the grant of a patent – grounds of novelty and inventive step considered – novelty – citation does not disclose all the features of the claims – inventive step – determining the problem requires consideration of the common general knowledge and subsection 7(3) information – problem addressed is the provision of an alternative topical ectoparasiticidal formulation – evidence does not establish that formulation of an active ingredient and three other components is a matter of routine – opposition fails

Representation:  Patent applicant: Mr Julian Cooke of counsel instructed by Dr Mathew Lucas and Dr Althea Tsang of Davies Collison Cave

Opponent: Mr Tom Cordiner of counsel instructed by Dr Marcus Caulfield and Dr Toby Thompson of FB Rice

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Patent Application:                2007341647

Title:Agents for controlling parasites on animals

Patent Applicant:                   Bayer Intellectual Property GmbH

Date of Decision:                   1 April 2016

DECISION

The opposition fails on all grounds.  Subject to appeal, I direct the application proceed to grant.  Costs according to Schedule 8 are awarded against Merial Limited.

REASONS FOR DECISION

1.        Background

1. The present application was filed by Bayer Healthcare AG on 14 December 2007.  Bayer Healthcare AG subsequently changed its name to Bayer Animal Health GmbH and the latter assigned its rights to Bayer Intellectual Property GmbH (Bayer).  Following examination, the application was advertised accepted on 3 October 2013. 

2. A notice of opposition was filed by Merial Limited (Merial) on 3 January 2014.  A hearing was held in Canberra on 18 February 2016.  Bayer was represented by Mr Julian Cooke of counsel instructed by Dr Mathew Lucas and Dr Althea Tsang of Davies Collison Cave.  Merial was represented by Mr Tom Cordiner of counsel instructed by Dr Marcus Caulfield and Dr Toby Thompson of FB Rice. 

3. The request for examination in relation to the application was filed on 22 September 2011.  Consequently, substantive amendments of the Patents Act 1990 brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 do not apply to the present application. This includes the amendment to subsection 60 (3A) that allows the Commissioner to refuse a patent application if satisfied on the balance of probabilities that a ground of opposition exists. Any subsequent references to sections of the Patents Act relate to the Patents Act 1990 prior to amendment by the Raising the Bar Act.  A similar qualification applies to references to the Patents Regulations 1991.

4. It is noted that the parties were heard in relation to the opposition to the grant of patent application 2007341648 on 19 February 2016.  The present application and 2007341648 relate to similar subject matter.  However, each case has its own evidence and the issues considered are not identical (for the decision on 2007341648 see Merial Limited v Bayer Intellectual Property GmbH [2016] APO 17).

   2.        Grounds of opposition

5. The original statement of grounds and particulars was filed on 3 April 2014.  A request to amend the statement was filed on 5 February 2015 and subsequently refused.

6. The statement of grounds and particulars specifies the following grounds of opposition:

   • novelty
   • inventive step
   • manner of manufacture
   • section 40 issues of clarity, fair basis and full description
   • utility
   • secret use
   • entitlement to the grant of a patent.

7. The grounds pressed at the hearing were limited to novelty and inventive step.

   3.        Standard of proof

8. The onus of proof in this opposition proceeding rests with the opponent, who must demonstrate that it is clear that a valid patent cannot be granted (F.Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283 at [67]; 50 IPR 305; Commissioner of Patents v Sherman [2008] FCAFC 182 at [18]; 79 IPR 426).

   4.        Evidence

9. The evidence is summarised in the table below.

Evidence	Declarant	Exhibits	Date	Reference
In Support	Leonore C. Witchey‑Lakshmanan	LCWL-1 to LCWL-20	1 September 2014	Witchey-Lakshmanan-1
In Answer	Simren Kaur Khosa	SKK-1 to SKK-5	2 December 2014	Khosa
James S. Rowe	JSR-1 to JSR-5	4 December 2014	Rowe
Leonore C. Witchey‑Lakshmanan	LCWL-21 to LCWL-34	3 February 2015	Witchey-Lakshmanan-2
In Reply	Jeffrey N. Clark	JNC-1 to JNC-14	2 February 2015	Clark
John Simon Landells	D18	5 February 2015	Landells
Joe R. Pippia	JRP-1 to JRP-4	5 February 2015	Pippia

1. Parts of the evidence filed in reply were subsequently found not to be evidence in reply and therefore do not form part of the evidence in the opposition.  In a decision issued by a Delegate of the Commissioner (Merial Limited v Bayer Intellectual Property GmbH [2015] APO 16), the Delegate found that:

   ·paragraphs [50] – [52] of the Clark declaration are not evidence in reply.

   ·the references to D18 in Witchey-Lakshmanan-2 are not evidence in reply.

   ·regulation 5.23 is not invoked in relation to D18 or paragraphs [50] – [52] of the Clark declaration.

   5.        Regulation 5.23

2. Two of the prior art documents relied on by Merial, AU 2004237454 (D3) and AU 2002338201 (D11), are in evidence as the B level publications which were published after the earliest priority date of the present claims (27 December 2006).  During the hearing I invoked regulation 5.23 in relation to the corresponding A level publications of these documents.  A comparison of the A and B level publications indicates that the differences between the documents are only minor in nature.

   6.        The subject matter of the specification

   6.1      Background of the invention

3. The specification relates to compositions for controlling parasites on animals.  N-Phenylpyrazoles are known for their insecticidal and acaricidal activity.  In particular, the compound 1-[2, 6-dichloro-4-(trifluoromethyl)phenyl]-3-cyano-4-[(trifluoromethyl)sulphinyl]-5-aminopyrazole (fipronil) is regarded as being particularly effective for controlling most parasites (page 1).

4. When formulations containing N-phenylpyrazoles are applied topically, the compounds accumulate in the sebaceous glands and are gradually released over a period of time.  The specification states that in the case of customary formulations, penetration of the N‑phenylpyrazoles into the circulation is also likely, and thus the availability of the active compound on the animal is limited both with respect to duration and concentration (pages 1 – 2).

   6.2      Aim of the invention

5. The specification states (page 2, lines 11 – 12):

   “This disadvantage of the formulation of the prior art was to be reduced by modifying the basic properties of the formulation without losing the positive efficacy properties.”

   6.3      Nature of the invention

6. The specification indicates that certain additives can improve the efficacy of the N‑phenylpyrazoles.  Thus, in one aspect, the invention provides compositions comprising:

   ·an N-phenylpyrazole;

   ·an aliphatic cyclic carbonate;

   ·an aliphatic cyclic or acyclic polyether; and

   ·one or more esters of a dihydric or trihydric alcohol having up to three carbon atoms with organic fatty acids having 6 to 18 carbon atoms (fatty acid ester).

7. In a further aspect, the compositions may be used to control parasites on animals and in particular ectoparasites such as fleas and ticks.

   6.4      The claims of the specification

8. The claims as accepted consist of composition claims 1 – 6, “Swiss” claim 7 and method claims 8 and 9.

   7.        The person skilled in the art

9. The person skilled in the art was considered at the hearing.  As stated in Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [70] – [71]; 49 IPR 225:

   “He is the person to whom the patent is addressed and who must construe it.  He is the person whose knowledge will determine whether a patent is novel.  He is the person who will judge whether a patent is obvious.  ….

   In Catnic Lord Diplock said (at 242) that skilled addressees are ‘those likely to have a practical interest in the subject matter of [the] invention’.  A variety of people may have that interest.  There are those who might wish to make or construct the invention, those who may wish to compound the invention and those who may wish to use the invention.  The skilled addressee seems to me to be a relative expression which does not identify any specific person.”

10. Dr Witchey-Lakshmanan has experience in the formulation and process development of pharmaceutical veterinary products, including topical and spot on formulations.  Dr Rowe has experience in the formulation and testing of a range of veterinary products such as topical pour on formulations.  Dr Clark has experience in animal health products with a focus on parasite control.  Mr Pippia has experience in the development of spot on insecticidal formulations for animals.  I consider that Dr Witchey-Lakshmanan, Dr Rowe, Dr Clark and Mr Pippia would all have a practical interest in the invention.

11. Merial submitted that there were inconsistencies in Dr Rowe’s evidence and made reference to such a finding by the Full Federal Court in Generic Health Pty Ltd v Bayer Pharma Aktiengesellschaft [2014] FCAFC 73. I note that this case relates to formulations for oral contraceptives and is not considered relevant to the present matter.

12. I will give regard to all of the evidence provided by the four declarants.  Where there is conflicting evidence, I will use the normal practice of evaluating and weighing the evidence in order to resolve any conflict.

    8.        Claims construction

13. The approach to claims construction was considered by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70 at [118]-[120]; 81 IPR 228:

    “… the end point is that 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 …  However, terms in the claim which are unclear may be defined or clarified by reference to the body of the specification …”

    8.1      Construction of claim 1

14. Claim 1 is the only independent claim and is as follows:

    A composition for controlling parasites on animals, comprising:

    an N-phenylpyrazole;

    an aliphatic cyclic carbonate;

    an aliphatic cyclic or acyclic polyether; and

    one or more esters of a dihydric or trihydric alcohol having up to three carbon atoms with organic fatty acids having 6 to 18 carbon atoms.

    (a)Composition for

15. The claim is directed to “A composition for controlling parasites on animals”.  The term “for” is construed as merely indicating that the composition must be suitable for the intended purpose, but does not limit the composition only to that environment (Faberwerke Hoescht Aktiengesellschaft vormals Meister Lucius & Bruning’s Application (1964) AOJP 1483).  Thus, the claim is considered to define a composition per se, wherein the composition is such that it is suitable for controlling parasites on animals.

    (b)N-Phenylpyrazole

16. Adopting the plain meaning, an N-phenylpyrazole is understood to be a compound wherein a phenyl group is attached to one of the nitrogen atoms of the pyrazole ring.  The parties confirmed that this is the intended meaning in the claims, notwithstanding the broader definition given in the specification on pages 2a and 3, which allows for both phenyl and pyridyl rings to be attached to the pyrazole. 

    8.2      Construction of claim 7

17. Claim 7 reads as follows:

    Use of a composition according to any one of claims 1 to 6 for preparing a medicament for controlling parasites on animals.

18. Claim 7 is a “Swiss” type claim, the construction of which was considered by Yates J in Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4) [2015] FCA 634; 113 IPR 191. It was held that a Swiss claim defines a method or process for making a medicament, wherein the intended therapeutic use of the medicament qualifies the scope of the claim.

19. Claim 7 is construed to define a method for making a medicament containing the composition of any one of claims 1 to 6, wherein the intended use of the medicament is to control parasites on animals.  

    9.        Novelty

20. Under subsection 7(1), an invention is taken to be novel unless it is not novel in the light of the prior art base.  Information in a document forms part of the prior art base for the purposes of novelty if it was published before the priority date of a claim.

21. It is well established that the general test for anticipation is the reverse infringement test.  The classic formulation of this test is that given by Aicken J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19 at [20]; 137 CLR 228:

    “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”.

22. This test is satisfied if the alleged anticipation discloses all the essential features of the invention claimed (Nicaro Holdings Pty Limited v Martin Engineering Company [1990] FCA 40 at [19]; 16 IPR 545). In order to meet this requirement, the prior art “must contain clear and unmistakeable directions to do what the patentee claims to have invented” (The General Tire & Rubber Company v The Firestone Tyre and Rubber Company Limited [1972] RPC 457 at 486) (General Tire).

23. Merial submitted that claims 1 – 9 are not novel in view of AU 2004237454 (D3).

    9.1      AU 2004237454 (D3)

24. D3 (A level publication) was published on 18 November 2004 and therefore forms part of the prior art base.  D3 describes compositions comprising a pyrethrin or pyrethroid and the synergist MGK 264 and their use in controlling parasites on animals.  D3 indicates that in a further embodiment other active ingredients may be included in the composition, of which N‑phenylpyrazoles are one of a range of possibilities (page 4, lines 27 – 33; pages 15 – 16).

25. The compositions may contain other components, including cyclic carbonates (such as propylene carbonate), aliphatic cyclic or acyclic ethers [such as diethylene glycol monoethyl ether (DGME)] and triglycerides based on caprylic acid and caprinic acid (fatty acid ester) (page 23, lines 15 ‑ 26). 

26. The 17 preparative examples describe various formulations.  Each formulation contains the pyrethroid flumethrin in combination with another active ingredient belonging to the neonicotinoid class of insecticides, i.e. no N-phenylpyrazoles are exemplified.  In relation to the other components of the formulation, 10 examples contain propylene carbonate, 3 examples contain Miglyol 812® (a mixture of caprylic/capric triglyceride fatty acid ester) and 1 example contains both propylene carbonate and Miglyol 812®.  However, none of the examples contain the combination of an aliphatic cyclic carbonate, an aliphatic cyclic or acyclic polyether and an ester of a dihydric or trihydric alcohol (fatty acid ester). 

27. D3 does not provide clear and unmistakeable directions to prepare a composition comprising an N-phenylpyrazole, an aliphatic cyclic carbonate, an aliphatic cyclic or acyclic polyether and a fatty acid ester. 

28. Merial further submitted that the claims do not represent a valid selection over the disclosure of D3.  Thus, the claimed formulations are not associated with any particular advantage and arbitrarily singling out one combination of suitable carriers over others does not constitute a valid selection.

29. It is only necessary to consider the issue of a selection where a citation contains clear and unmistakeable directions and prima facie the claims lack novelty.  As I have found that the claimed invention is novel according to the principles outlined in General Tire, the issue of a selection does not require further consideration.

30. It has not been demonstrated that the claims lack novelty.

    10.      Inventive step

31. Under subsections 7(2) and 7(3), an invention is taken to involve an inventive step unless it would have been obvious to the person skilled in the art in the light of the common general knowledge, either considered alone or together with the prior art.  The prior art is information that the skilled person could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood and regarded as relevant.

32. The test for whether an invention is obvious is whether it would have been a matter of routine to proceed to the claimed invention.

    “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.” (Wellcome Foundation Ltd v VR Laboratories (Aust) Pty Ltd [1981] HCA 12 at [45]; 148 CLR 262)

33. In Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59 at [53]; 212 CLR 411 (Alphapharm), the High Court accepted the approach taken in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd [1970] RPC 157 at [187] where Graham J posed the reformulated Cripp’s 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 combination] in the expectation that it might well produce a [useful or better result]?” (emphasis in original)

34. Where the invention is a combination of integers (as in the present case), obviousness is to be determined by reference to the combination as a whole and not each integer individually.  As stated in Alphapharm at [41]:

    “The claim is for a combination, the interaction between the integers of which is the essential requirement for the presence of an inventive step.  It is the selection of the integers out of ‘perhaps many possibilities’ which must be shown by Alphapharm to be obvious, bearing in mind that the selection of the integers in which the invention lies can be expected to be a process necessarily involving rejection of other possible integers.”

35. In AstraZeneca AB v Apotex Pty Ltd [2014] FCAFC 99; 107 IPR 177 (AstraZeneca), the court held that in formulating the problem it is not permissible to incorporate information that is not available to the person skilled in the art either as common general knowledge or information available under subsection 7(3).

    10.1     Determining the problem

36. Bayer submitted that the specification addresses the problem of existing formulations containing N-phenylpyrazoles penetrating into the circulation and therefore the availability of the active compound on the animal is limited both with respect to duration and concentration.  Merial stated that the problem addressed by the specification is the provision of an alternative topical ectoparasiticidal formulation.

37. In determining the problem it is necessary to have regard to the specification, and consider the common general knowledge and subsection 7(3) information as per AstraZeneca.  Prima facie all of the documents in evidence (identified in the statement of grounds and particulars or presented as exhibits) relate to aspects of ectoparasiticidal formulations and are considered potential subsection 7(3) information.

    10.1.1  What does the specification say?

38. The specification states at page 1 that existing formulations of N-phenylpyrazoles (fipronil) have a high content of DEE (Transcutol) (DGME), which facilitates penetration into the sebaceous glands and epithelium.  Reference is made to an article by Cochet et al., European Journal of Drug Metabolism and Pharmacokinetics, 1997, 22(3), 211 – 216 (Cochet), which demonstrates that fipronil accumulates in the sebaceous glands and epithelial layers.  Cochet further confirms “the low percutaneous passage of fipronil” (Summary). 

1. The specification indicates on page 2 that penetration of N-phenylpyrazoles into the circulation is also likely, “since each hair follicle [which is associated with one or more sebaceous glands] is supplied by a blood vessel and the follicles are thus separated from the circulation by only a very thin area.”  In this context reference is made to an article by Meidan et al., International Journal of Pharmaceutics, 2005, 306, 1 – 14 (Meidan).  Meidan discusses exploiting the follicles as transport shunts for systemic drug delivery (Abstract).

   10.1.2  What was the common general knowledge and subsection 7(3) information?

2. I will now consider the common general knowledge and subsection 7(3) information insofar as they are relevant to determination of the problem.  A more detailed discussion of the common general knowledge is provided in part 10.2.

   (a)Fipronil

3. The evidence indicates that it is commonly known that N-phenylpyrazoles, and in particular fipronil, are broad spectrum ectoparasiticides.[1]  Fipronil is the active ingredient in the Frontline® range of commercial products.[2]  Dr Witchey-Lakshmanan and Dr Clark state that when fipronil is applied topically, it accumulates in the sebaceous glands and is then gradually released over a period of time.[3]

   [1] Witchey-Lakshmanan-1 [34] – [35]; LCWL-5; Rowe [17]; Clark [40].

   [2] Witchey-Lakshmanan-1 [31], [38]; Clark [44]; Pippia [27].

   [3] Witchey-Lakshmanan-1 [36]; Clark [42].

   (b)Penetration of fipronil into the circulation

4. Dr Witchey-Lakshmanan indicates that fipronil is not thought to be systemically active, i.e. it is not effectively absorbed into the bloodstream.[4]  With reference to Brayden, Irish Veterinary Journal, 2003, 56(6), 310 – 316 (LCWL-21) (Brayden), she states that the loss of fipronil to systemic delivery is no more than 5%.  Therefore, even if a formulation could prevent the entire 5% from being delivered systemically, then any increase in duration of delivery would amount to at most 5%.[5]  The loss of fipronil to systemic absorption is insignificant and does not impact on the effectiveness of fipronil.[6]  Thus, Frontline® products are demonstrated to have a long duration of efficacy.[7]  Dr Witchey-Lakshmanan considers the problem posed by Bayer as insignificant.[8]

   [4] Witchey-Lakshmanan-1 [187] with reference to Cochet. 

   [5] Witchey-Lakshmanan-2 [10], [95].

   [6] Witchey-Lakshmanan-2 [85].

   [7] Witchey-Lakshmanan-1 [193]; Witchey-Lakshmanan-2 [13] – [14]; LCWL-19; LCWL-23; LCWL-24. 

   [8] Witchey-Lakshmanan-2 [18] – [19], [86].

5. Dr Clark states that the Cochet study demonstrates that no fipronil passes into the bloodstream.  Furthermore, it is very unlikely that there is significant accumulation of fipronil in the blood upon topical administration, as oral consumption of fipronil at or near the therapeutic dose for flea efficacy can lead to vomition in dogs.[9]  Dr Clark agrees that fipronil has demonstrated long activity.[10]  He considers that the problem stated by Bayer “simply does not exist as the current formulation of Frontline® Top Spot does not lead to any significant fipronil blood levels.”[11]

   [9] Clark [42]; JNC-5. 

   [10] Clark [43]; JNC-6.

   [11] Clark [56] – [59].

6. Bayer made reference to several exhibits (SKK-5) to demonstrate that fipronil (contained in various Frontline® products) is absorbed into the bloodstream.  These are summarised in the table below.

Frontline® Product	Amount of Systemic Absorption of Fipronil	Document Date (1. Date of the First Authorisation/Renewal of the Authorisation 2. Date of Revision of the Text)
Combo Spot-on Cat	18% (additional potential oral exposure from licking)	1. 26 September 2008 2. October 2012
Combo Spot-on Dog L	11%	1. 26 September 2008 2. October 2012
Combo Spot-on Dog M	11%	1. 26 September 2008 2. October 2012
Combo Spot-on Dog S	11%	1. 26 September 2008 2. October 2012
Combo Spot-on Dog XL	11%	1. 26 September 2008 2. October 2012

1. These documents are all dated after the earliest priority date (27 December 2006) and there is no evidence that establishes when this information was first publicly available.  It therefore follows that the SKK-5 exhibits are not part of the common general knowledge or subsection 7(3) information.  Consequently, the information in the exhibits relating to the systemic absorption of fipronil cannot be used when formulating the problem that the specification seeks to address.

   10.1.3  Conclusion on the problem

2. None of the subsection 7(3) information available refers to N-phenylpyrazoles penetrating into the circulation and thereby affecting the availability of the active compound with respect to concentration and duration.  Dr Witchey-Lakshmanan and Dr Clark are both of the view that systemic absorption of fipronil is not at levels significant enough to impact the efficacy of fipronil, or be considered a problem that needs to be addressed.  I therefore conclude that the problem to be addressed cannot be as stated by Bayer.  Formulation of Bayer’s problem requires incorporation of information that is not available to the person skilled in the art either as part of the common general knowledge or subsection 7(3) information.

3. I will now turn to Merial’s problem, namely to provide an alternative topical ectoparasiticidal formulation.  As discussed previously, those skilled in the art are aware of topical ectoparasiticidal formulations as part of their common general knowledge.  Such formulations commonly contain N-phenylpyrazoles.  Furthermore, on reading the present specification as a whole, the emphasis is clearly on N-phenylpyrazoles as there is no discussion of any other type of active compound.  It therefore seems reasonable to conclude that the problem to be addressed is the provision of an alternative topical ectoparasiticidal formulation comprising an N‑phenylpyrazole.

   10.2     Common general knowledge

4. The common general knowledge was considered by Emmett J in ICI Chemicals & Polymers Ltd v Lubrizol Corporation Inc [1999] FCA 345; 45 IPR 577 at [112]:

   “The common general knowledge is the technical background to the hypothetical skilled worker in the relevant art.  It is not limited to material which might be memorised and retained at the front of the skilled workers mind but also includes material in the field in which he is working which he knows exists and to which he would refer as a matter of course.  It might, for example, include:

   ·standard texts and handbooks;

   ·standard English dictionaries;

   ·technical dictionaries relevant to the field;

   ·magazines and other publications specific to the field.”

   10.2.1  Sources of common general knowledge

5. Merial submitted that sources of information that would be part of the common general knowledge include:

   ·Material Safety Data Sheets (MSDS) which inform about hazardous components of commercial products.

   ·Regulatory Databases.  Authorities such as the Australian Pesticides and Veterinary Medicines Authority (APVMA) and the Health Products Regulatory Authority (HPRA, formerly the Irish Medicines Board) have databases that provide details about authorised veterinary products.

   ·Summary of Product Characteristics (SPC) which include a summary of the active substances and a list of excipients for a veterinary product.

   ·Patent publications directed to commercial formulations.

6. Dr Witchey-Lakshmanan, Dr Clark and Mr Pippia indicate that they would consult the patent literature as a source of information.[12]  However, there is no evidence that the contents of any particular patent documents form part of the common general knowledge and I do not regard these documents as such.

   [12] Witchey-Lakshmanan-1 [23]; Clark [20]; Pippia [24].

7. In relation to the regulatory databases, SPC and MSDS, Dr Witchey-Lakshmanan, Dr Clark and Mr Pippia state that they would consult these sources to locate information about a particular product.[13]  Dr Rowe states that it is his understanding that regulatory bodies usually only publish details of the actives of veterinary products.  He does not consider such databases as an informative source as to the formulation ingredients included in any given product, nor consider that the contents of such databases would be commonly known in the field.[14]

   [13] Witchey-Lakshmanan-1 [23], [28] – [30]; Witchey-Lakshmanan-2 [7], [31] – [32]; Clark [20], [38], [57], [61]; Pippia [24], [25], [29].

   [14] Rowe [26], [31].

8. Based on the evidence, I consider it more likely than not that the skilled addressee would routinely consult regulatory databases, SPC and MSDS.  In terms of whether the contents of such information sources are part of the common general knowledge, it seems reasonable that where a particular product is common general knowledge, e.g. Frontline® as discussed above, then the information contained in the databases, MSDS and SPC as it relates to the product ingredients forms part of the common general knowledge.  Such information falls into the category of that not necessarily memorised by the skilled worker, but which is known to exist and would be referred to as a matter of course.

   10.2.2  Common general knowledge – individual ingredients

   (a)Fipronil

9. As discussed previously, it is commonly known that fipronil is the active ingredient in the Frontline® range of products. 

   (b)Aliphatic cyclic or acyclic polyether – DGME

10. DGME (also known as Transcutol) is commonly used in topical formulations as a solvent, spreading agent and/or penetration enhancer.[15]  The MSDS for Frontline® Top Spot lists DGME as an ingredient in the product[16] and this is considered to be part of the common general knowledge.

    [15] Witchey-Lakshmanan-1 [48]; Witchey-Lakshmanan-2 [25]; Rowe [23], [32].

    [16] Witchey-Lakshmanan-2 [26], [31]; JSR-3; Clark [61]; JNC-14; Pippia [27]; JRP-3.

    (c)Aliphatic cyclic carbonate – propylene carbonate

11. Propylene carbonate is a common solvent[17].  In relation to its use in topical formulations, Dr Rowe states that at the priority date he was not aware of many specific topical formulations which would have used propylene carbonate[18] (emphasis added), which suggests that he was aware of at least some.  However, he does not consider the substance to be a “favourite excipient”.[19] 

    [17] Witchey-Lakshmanan-1 [93]; Rowe [53].

    [18] Rowe [53].

    [19] Rowe [91].

12. Dr Witchey-Lakshmanan indicates that propylene carbonate is used in the Advantage® range of commercial topical formulations (which contain the neonicotinoid imidacloprid), which have been on the market for almost 10 years before the priority date.[20]  In support of this, reference is made to the SPC (D16) which lists propylene carbonate as an excipient in Advantage 40 Spot-on solution for Cats.[21]  However, the Date of the First Authorisation/Renewal of the Authorisation of this document is 7 August 2007 which is after the earliest priority date (27 December 2006).  I also note that the Date of the Revision of the Text is 23 March 2011, however the nature of the revision is not stated.

    [20] Witchey-Lakshmanan-1 [93], [181], [186]; Witchey-Lakshmanan-2 [51], [83].

    [21] Witchey-Lakshmanan-1 [162] – [164].

13. Dr Witchey-Lakshmanan also makes reference to the MSDS for Advantage® which is dated 6 November 2004.[22]  It states that Advantage® contains a carbonate derivative, the specific chemical identity of which “is withheld as a trade secret.” 

    [22] Witchey-Lakshmanan-2 [51] – [52]; LCWL-29.

14. Thus, the evidence indicates that in 2004 the product Advantage® contained a carbonate.  At the earliest priority date, Dr Rowe and Dr Witchey-Lakshmanan state that they were aware of formulations containing propylene carbonate, with Dr Witchey-Lakshmanan referring specifically to Advantage®.  In August 2007 (shortly after the earliest priority date), the carbonate was identified in D16 as propylene carbonate.  This is based on the assumption that this section of text was not subject to revision in March 2011.  However, given the evidence of Dr Rowe and Dr Witchey-Lakshmanan, on balance it seems more likely than not that propylene carbonate was listed as an ingredient in D16 in August 2007. 

15. Although the period between the earliest priority date and the date of D16 is less than 8 months, the evidence does not conclusively establish that the Advantage® formulation did not change during this short timeframe.  However, for reasons subsequently explained, it is not necessary for me to decide this matter.  Consequently, for the purposes of this decision, I will assume it more likely than not that Advantage® contained propylene carbonate and that this was common general knowledge at the earliest priority date.

    (d)Fatty acid esters – Miglyol® products

16. It is standard to use triglyceride fatty acid esters, such as Miglyol 812®, in formulations.[23]  The esters are known for their function as solvents, spreading agents, penetration enhancers and emollients.[24]

    [23] Witchey-Lakshmanan-1 [177].

    [24] Witchey-Lakshmanan-1 [94]; Rowe 53.

    10.3     Lack of inventive step in the light of the common general knowledge

17. Merial submitted that claims 1 – 9 lack an inventive step in the light of the common general knowledge alone.  In particular, in looking to provide an alternative formulation, the skilled addressee would have tried to make a composition containing an N-phenylpyrazole (e.g. fipronil), an aliphatic acyclic polyether (e.g. DGME), a fatty acid ester (e.g. Miglyol 812®) and an aliphatic cyclic carbonate (e.g. propylene carbonate), since in the light of the common general knowledge it would be expected that those ingredients would be suitable to combine into such a formulation.

18. As the claimed invention is a composition comprising a combination of ingredients, Merial must demonstrate that it would be a matter of routine to combine the ingredients in order to solve the problem.

    10.3.1  Matter of routine – individual ingredients

19. The common general knowledge indicates that the selection of N-phenylpyrazoles (e.g. fipronil), polyethers (e.g. DGME), cyclic carbonates (e.g. propylene carbonate) or fatty acid esters (e.g. Miglyol 812®) as individual ingredients in a topical formulation is a matter of routine.  However, preparing an ectoparasiticidal composition necessarily involves combining those individual ingredients into a suitable formulation.  This requirement must also be a matter of routine and is discussed below.

    10.3.2  Matter of routine – combining individual ingredients into a formulation

20. Dr Witchey-Lakshmanan states:

    “Thus, in formulating simply an alternative fipronil product, my choice of excipients would have certainly included those classes of excipients known to be effective in the fipronil marketed product.  This is because the long term stability and the in vivo effectiveness would have been known and established.  In addition, my choice of excipients would also include those known to be used in other similar products.  This is because those excipients have been known to cross the regulatory hurdles for the same type of product.”[25]

    [25] Witchey-Lakshmanan-2 [41].

21. Dr Rowe submits:

    “In the art it is quite often the case that when faced with a formulation problem one will utilise known compounds, for instance, particular solvents, surface active agents, carriers, etc.  ….  While in some instances it may be quite straight forward to solve a formulating problem by exchanging, for instance, one solvent for another, it is invariably the case that, especially when dealing with different active ingredients, one cannot predict whether a variation in the formulation would solve any given problem from the outset.  In relation to the opposed specification, which teaches a combination of three specific classes of formulation components (with a particular active) this does not represent a straight forward or routine formulation task (i.e., to choose the particular combination that would solve the problem at hand).”[26]

    [26] Rowe [46].

22. I note that Dr Rowe’s comment is made in the context of solving Bayer’s problem (reducing penetration of N-phenylpyrazoles into the circulation) rather than the problem of providing an alternative formulation.  However, his statement nevertheless indicates the issues that arise when combining ingredients into a formulation.

23. As stated by Dr Witchey-Lakshmanan:

    “Moreover, if improperly formulated, fipronil may crystallize out of solution, resulting in white residue on the skin or coat of the animal that may rub or flake off into the environment.  This loss of drug is not desirable for efficacy nor for the safety of the environment.”[27]

    [27] Witchey-Lakshmanan-1 [53].

24. The evidence does not establish that it would have been a matter of routine to formulate the combination of an N-phenylpyrazole (e.g. fipronil), a polyether (e.g. DGME), a cyclic carbonate (e.g. propylene carbonate) and a fatty acid ester (e.g. Miglyol 812®).  In particular, the improper choice of formulation ingredients may result in crystallisation of fipronil and consequential loss of efficacy.  It has not been established that the claimed invention lacks an inventive step in the light of the common general knowledge alone. 

    10.4     Lack of inventive step in light of the prior art

25. Merial submitted that claims 1 – 9 are not inventive in the light of any one of AU 2004237454 (D3), US 6010710 (D8), AU 2002338201 (D11) and D8 when combined with D11, when considered together with the common general knowledge. 

26. The first question to consider is whether these documents would have been ascertained, understood and regarded as relevant.  Dr Witchey-Lakshmanan, Dr Clark and Mr Pippia indicate that they consult the patent literature.[28]  Dr Rowe states that he would search using SciFinder[29], which covers patent documents.  Therefore D3, D8 and D11 would have been ascertained. 

    [28] Witchey-Lakshmanan-1 [23]; Clark [38]; Pippia [24].

    [29] Rowe [17].

27. As discussed previously, D3 describes compositions comprising a pyrethrin or pyrethroid and the synergist MGK 264 and their use in controlling parasites on animals.  In a further embodiment other active ingredients may be included in the composition, such as N-phenylpyrazoles.  D3 would therefore be regarded as relevant.

28. D8 was published on 4 January 2000 and therefore forms part of the prior art base.  It discloses compositions for treating parasites such as ticks on cattle and sheep.  The formula depicted in the abstract and column 2 is an N-phenylpyrrole rather than an N-phenylpyrazole.  However, on reviewing the document it is apparent that there is an error in the formula and that the compound depicted should be an N-phenylpyrazole.  Thus, pyrazoles are discussed at column 1 (lines 36 ‑ 37 and 53) and fipronil is specifically mentioned at column 4 (lines 34 – 36), in the Examples and the claims.  I consider that the skilled addressee would recognise the error in the formula and understand that D8 relates to N-phenylpyrazoles.  This document is therefore regarded as relevant.

29. D11 (A level publication) was published on 6 May 2003 and thus forms part of the prior art base.  The document describes macrocyclic lactones (milbemycins) that are used together with another active ingredient, such as fipronil, to treat parasites.  D11 would therefore be regarded as relevant. 

30. I will consider each document in turn.

    10.4.1  AU 2004237454 (D3)

31. Merial submitted that the skilled addressee, in looking to provide a further topical ectoparasiticidal composition, would have been motivated to produce a formulation containing an N‑phenylpyrazole (fipronil), an aliphatic acyclic polyether (DGME), a fatty acid ester (Miglyol 812®) and an aliphatic cyclic carbonate (propylene carbonate), since having considered D3 in light of the common general knowledge, there would have been a reasonable expectation that such a composition would be effective.

32. The disclosure of D3 is discussed above.  Thus, D3 describes compositions comprising a pyrethroid or pyrethrin, the synergist MGK 264 and another active ingredient, such as N‑phenylpyrazoles.  The compositions may also contain other components.  These are listed on page 23 and include DGME, propylene carbonate and fatty acid esters.

1. Turning to the examples, Example 3 is a topical formulation that most closely represents that defined by the present claim 1.  This formulation comprises the active ingredients flumethrin (pyrethroid) and imidacloprid (neonicotinoid), propylene carbonate and Miglyol 812®.  The differences between D3 and the claimed invention are that the prior art formulation does not contain an N-phenylpyrazole (fipronil) and a polyether (DGME), although these are possible ingredients (page 15 and page 23 respectively).

2. I have previously determined that it is a matter of routine to select fipronil and DGME as individual ingredients in a topical formulation.  Therefore the skilled addressee would consider adding these components to the prior art formulation.  However, as stated above, the incorporation of fipronil into a formulation is not a matter of routine, as improper formulation may result in the active crystallising out of solution.  It has not been demonstrated that the claims lack an inventive step in the light of D3.

   10.4.2 US 6010710 (D8)

3. Merial similarly submitted that the claimed invention lacks an inventive step in view of D8 and the common general knowledge.

4. As noted previously, D8 relates to N-phenylpyrazoles and not N-phenylpyrroles as erroneously depicted in the document.  D8 discloses the use of fipronil in antiparasitic formulations (column 4, lines 33 – 38).  Other possible components include polyethers such as DGME (column 4, line 60 to column 5, line 4) and medium chain (C8 to C12) triglycerides (column 5, lines 11 – 12).  There is no disclosure of the use of cyclic carbonates.

5. The sole formulation example contains fipronil (Compound A), polyoxypropylene 15 stearyl ether (polyether), acetyl tributyl citrate and soybean oil.  The fipronil is dissolved in the acetyl tributyl citrate and then mixed with the other ingredients.

6. This formulation differs from the claimed invention in that there is no fatty acid ester and no cyclic carbonate (propylene carbonate) present.  D8 lists triglycerides (fatty acid ester) as a possible ingredient and therefore the skilled addressee would consider adding this component to the formulation.  As discussed previously, propylene carbonate is known as an individual ingredient in topical formulations.  Therefore, the question to consider is whether it would be a matter of routine for the person skilled in the art to prepare an alternative formulation by combining a fatty acid ester and propylene carbonate with the formulation of D8.

7. In relation to D8, Dr Witchey-Lakshmanan states:

   “From a reading of this document, the choice of materials in the opposed specification is not an unexpected combination for a topical product containing fipronil.”[30]

   [30] Witchey-Lakshmanan-2 [63].

8. In discussing the present specification, she further states:

   “As I have noted the purported problem of the opposed specification did not exist, as evidenced by the literature available at the time of the opposed specification.  Since there was no problem to solve, the combination of ingredients need not be specific to any given situation, except to be able to deliver efficacious amounts of fipronil as a spot on, in an alternative formulation.  Because the excipients were known, and known to be used to deliver efficacious amounts of fipronil in a spot on product, it appears to me that the proposed formulations in the opposed specification are not an unexpected combination for the delivery of fipronil.”[31]

   [31] Witchey-Lakshmanan-2 [80].

9. However, Dr Witchey-Lakshmanan does not comment on whether it would be a matter of routine for the skilled addressee to formulate a fatty acid ester and propylene carbonate with an existing formulation containing fipronil and a polyether.  Although it may be possible to combine these ingredients, the assertion that the skilled addressee would do so as a matter of routine appears to be made with the benefit of hindsight.

10. I am not satisfied that the evidence demonstrates it would be a matter of routine to prepare an alternative formulation by formulating a fatty acid ester and propylene carbonate with an existing formulation comprising fipronil and a polyether.

11. It has not been demonstrated that there is a lack of inventive step in the light of D8.

    10.4.3  AU 2002338201 (D11)

12. Merial further submitted that the claimed invention is not inventive in view of D11 taken together with the common general knowledge.

13. D11 discloses compositions comprising milbemycin derivatives and another active ingredient, which may be an N-phenylpyrazole such as fipronil (page 1 and pages 6 – 7).  The compositions may further comprise a solvent such as propylene carbonate (page 17, lines 5 – 15).  There is no disclosure of the use of a polyether or a fatty acid ester.

14. Test Example 2 describes a spot on formulation comprising fipronil, benzyl alcohol and propylene carbonate, either with or without a milbemycin derivative.  This formulation differs from the claimed invention in that there is no fatty acid ester and no polyether (DGME) present.  As discussed previously, fatty acid esters (e.g. Miglyol 812 ®) and polyethers (DGME) are known individually for their use in topical formulations.  Therefore, the question to consider is whether it would be a matter of routine for the person skilled in the art to prepare an alternative formulation by combining a fatty acid ester and a polyether (DGME) with the formulation of D11.

15. In relation to the use of benzyl alcohol, Dr Witchey-Lakshmanan states:

    “Therefore, though it is a known excipient in known commercial products, a formulator could certainly have motivation to replace the benzyl alcohol with an alternative solvent, and be led directly to a solvent such as the glycol ether DGME, for example, given the excellent history of the drug [fipronil] in this vehicle.  DGME would have been my first choice to replace the benzyl alcohol.”[32]

    [32] Witchey-Lakshmanan-2 [72].

16. Dr Witchey-Lakshmanan does not comment on the addition of a fatty acid ester.  However, more importantly she does not state whether, in preparing an alternative formulation, it would be a matter of routine for the skilled addressee to formulate a fatty acid ester and DGME with an existing formulation containing fipronil and propylene carbonate.  Although it may be possible to combine these ingredients, the assertion that the skilled addressee would do so as a matter of routine appears to be made with the benefit of hindsight.

17. I am not satisfied that the evidence demonstrates it would be a matter of routine to prepare an alternative formulation by formulating a fatty acid ester and DGME with an existing formulation comprising fipronil and propylene carbonate.

18. It has not been shown that there is a lack of inventive step in the light of D11.

    10.4.4  Combination of D8 and D11

19. Merial further submitted that the claimed invention is not inventive over the combination of D8 and D11 in view of the common general knowledge.  Merial stated that D8 provides confirmation that polyethers (DGME) and medium chain triglycerides (fatty acid esters) are suitable for use in topical formulations containing N-phenylpyrazoles, whilst D11 demonstrates that propylene carbonate is a suitable solvent for the topical formulation of fipronil.  It was submitted that the skilled addressee would combine the teachings in D8 and D11 and would have been motivated to produce a composition containing an N-phenylpyrazole, a polyether, a fatty acid ester and a cyclic carbonate, since there would be a reasonable expectation that it would be an effective topical ectoparasiticide.

20. In considering whether there is any motivation to combine D8 and D11, I note that neither document makes reference to the other.  Furthermore, there is no evidence from any of the declarants that, faced with the problem of providing an alternative topical formulation, they would have a basis or motivation to combine these pieces of prior art.

21. I am not satisfied that the skilled addressee would combine D8 and D11 in order to solve the problem.  Consequently, it has not been shown that there is a lack of inventive step in the light of D8 when combined with D11.

    11.      Conclusion

22. The opposition fails on all grounds.

    12.      Costs

23. Both parties submitted that costs should follow the event.  I award costs in accordance with Schedule 8 against Merial Limited. 

    Dr M-A. Fam
    Delegate of the Commissioner of Patents