Merial, Inc. v Bayer New Zealand Limited

[2020] APO 6

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Merial, Inc. v Bayer New Zealand Limited [2020] APO 6

Patent Application:                2015261543

Title:Controlled release compositions and their methods of use

Patent Applicant:                   Bayer New Zealand Limited

Opponent:  Merial, Inc.

Delegate:  Dr S. J. Smith

Decision Date:  29 January 2020

Hearing Date:  10 April 2019, in Canberra

Catchwords:  PATENTS – opposition to the grant of a patent – controlled release intramammary compositions – grounds of clarity, novelty and inventive step – construction of controlled release – lack of clarity not established – claims not novel – claims lack inventive step – costs awarded

Representation:  Counsel for the applicant: Ian Finch of James & Wells

Solicitor for the applicant: Alexia Mayer of James & Wells

Counsel for the opponent: Christian Dimitriadis SC and Clare Cunliffe

Patent attorneys for the opponent: Marcus Caulfield, John Landells and David Herman of FB Rice

Additional representatives of the opponent: Judy Jarecki-Black and Tom Kowalski

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Patent Application:                2015261543

Title:Controlled release compositions and their methods of use

Patent Applicant:                   Bayer New Zealand Limited

Date of Decision:                   29 January 2020

DECISION

Claims 1, 2, 4, 7, 8, 10-15, 18-21 and 28 are not novel in light of D17.  Claims 1-28 lack inventive step in light of D4.

Bayer New Zealand Limited is allowed two months from the date of this decision to file amendments to overcome these deficiencies.

I award costs according to Schedule 8 against Bayer New Zealand Limited.

REASONS FOR DECISION

Background

1. Patent application 2015261543 was filed by Bayer New Zealand Limited (Bayer) on 24 November 2015 as a divisional application of application 2013201147 (the parent application).  The parent application was filed on 27 February 2013 as a Convention application claiming priority from NZ 598443, which was filed on 27 February 2012.

2. Acceptance of the application was advertised on 28 September 2017.  Merial, Inc. (Merial) filed a notice of opposition under section 59 of the Patents Act 1990 (the Act) on 22 December 2017.

3. The statement of grounds and particulars was filed on 22 March 2018 and an amendment to the statement was allowed on 14 August 2018.  The statement identifies the following grounds of opposition: entitlement, manner of manufacture, novelty, inventive step, utility, clear enough and complete enough disclosure, best method, support and clarity.  At the hearing grounds of clarity, novelty and inventive step were pressed.

   Evidence

4. The evidence filed during the evidentiary periods is summarised in the table below:

Evidence	Declarant	Exhibits	Date of declaration	Reference
In Support	David Alan John Herman	P1-P4, D1-D17	22 March 2018	Herman
	Joe R. Pippia	JRP-1 to JRP-31	22 June 2018	Pippia 1
	Joe R. Pippia	JRP-32 to JRP-40	22 June 2018	Pippia 2
	Stephen W. Page	SWP-1 to SWP-31	21 June 2018	Page 1
	Pradipto K. Bhattacharjee	PKB-1 to PKB-4	18 June 2018	Bhattacharjee 1
In Answer	Craig Bunt	CB-1 to CB-44	12 September 2018	Bunt
In Reply	Joe R. Pippia	JRP-41	19 November 2018	Pippia 3
	Stephen W. Page	SWP-32 to SWP-34	16 November 2018	Page 2
	Pradipto K. Bhattacharjee	-	15 November 2018	Bhattacharjee 2

Onus

1. The application was filed on 24 November 2015 and consequently the amendments of the Act brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 (the Raising the Bar Act) apply to the present application. This includes section 60(3A) of the Act, which provides that the Commissioner may refuse an application if satisfied on the balance of probabilities that a ground of opposition exists.  It is the opponent who carries the onus of proof.

   The specification

2. The specification is directed to an intramammary formulation for the treatment of mastitis in lactating cows.  The specification ends with 16 figures and 28 claims.

3. Before construing the specification, I note the comments of Middleton J in Eli Lilly and Company Limited v Apotex Pty Ltd:[1]

   “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.”

   [1] [2013] FCA 214; 100 IPR 451 at [139].

   The person skilled in the art

4. It is well established that many of the issues in an opposition are answered by reference to the person skilled in the art:

   “He is the person to whom the patent is addressed and who must construe it.  He is the person whose knowledge will determine whether a patent is novel.  He is the person who will judge whether a patent is obvious.”[2]

   [2] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [70].

5. The hypothetical skilled person works in the field with which the invention is connected and is a non-inventive person or team likely to have a practical interest in the subject matter of the invention.[3]  As noted above, the present specification is directed to an intramammary formulation for the treatment of mastitis in lactating cows.  Accordingly, the skilled person, or team, would be expected to have a practical interest in this field, including the development and administration of such formulations.  There is no real dispute as to the expertise of the skilled team, and I consider that it would include a number of variously skilled persons, particularly veterinarians with an interest in dairy cattle and formulation chemists.  The key declarants in this matter are Mr Pippia, Dr Page and Dr Bunt.

   [3] Ibid at [70]-[72].

6. Mr Pippia is a consultant chemist specialising in formulations for animal health, complementary health and agriculture, including work on products for livestock.[4]  He has particular experience in the development of injectable, topical and oral veterinary products.[5]

   [4] Pippia 1 at [1], [3].

   [5] Pippia 1 at [4]-[5].

7. Dr Page is a member of the Australian College of Veterinary Scientists and a consultant on the use and development of new veterinary medicines in livestock animals.[6]  He had experience with products for intramammary use, including managing clinical studies of such products in dairy cattle in New Zealand, and aspects of development of novel intramammary formulations, before the priority date.[7] 

   [6] Page 1 at [1], [3].

   [7] Page 1 at [5], [10].

8. Dr Bunt is an Associate Professor in animal science with extensive experience as a pharmaceutical formulation scientist, and had experience examining the physical properties of intramammary formulations and developing agricultural controlled release formulations before the priority date.[8]  Dr Bunt is also a member of the Controlled Release Society.[9]

   [8] Bunt at [5], [8]-[9]; Exhibit CB-2.

   [9] Bunt at [6].

9. I am satisfied that each of these declarants have backgrounds that enable them to understand the specification and provide evidence as to what a person skilled in the art knew or would have done at the relevant date.  Where there is conflicting evidence I will decide which evidence to give greater weight.

10. Merial also filed evidence from Dr Bhattacharjee with respect to measurement of samples.  Dr Bhattacharjee is the Research Director of Rheology Solutions, a company offering rheological consultancy services, and has experience in the rheology of structured complex fluids.[10]

    [10] Bhattacharjee 1 at [9], [14].

11. I note that each of these declarants has also provided evidence in a corresponding proceeding before the Intellectual Property Office of New Zealand.

    The invention as described

12. The specification indicates that the invention described:

    “relates to controlled release compositions and their method of use, and preferably, but not specifically, to low viscosity controlled release compositions for the treatment of mastitis in lactating animals.”[11]

    Background of the invention

    [11] Page 2, lines 4-6.

13. The specification indicates that to treat lactating animals with mastitis (or another microbial infection) antibiotic compositions are most often utilised, and a number of commercially available antibiotic compositions are used for this purpose.[12]  However, the specification explains that poor controlled release of the active agent over the treatment period is a major problem encountered with antibiotic treatment, and can lead to problems with maintaining the active agent concentrations above the minimum inhibitory concentration at which 90% of the microbes are killed (the MIC90).  As an example, if antibiotic is released too quickly, it can come out with the first milking after administration, leaving the concentration of the antibiotic too low for the remaining period before the next administration.  This can lead to failure to effectively treat the infection, longer treatment periods and/or increased antibiotic resistance.[13]

    [12] Page 2, lines 8-11.

    [13] Page 2, lines 12-21.

14. To counter this, existing products are often designed to have higher viscosity to slow the release profile of the active agent:

    “this is the approach taken for lactation and dry cow mastitis therapy known as long acting formulations, where the active is slowly released from a generally thick paste over an extended period of time.  For instance, if the antibiotic gets administered 48 hourly during the lactation period, the antibiotic is released slowly with concentrations above the MIC90 for about 36 hours after treatment.  Then, the concentrations of the antibiotic are too low for the remaining period before receiving the subsequent administration, often 12 hours later.  Again, this can lead to failures in effectively treating the infection.”[14]

    [14] Page 2, line 25 – page 3, line 6.

15. The specification explains that high viscosity compositions can enhance the physical stability of compositions, but can lead to other problems, including prolonged low levels of antibiotic in milk, which must then be withheld from the market, difficulty with infusion through a syringe to the udder and poorer distribution in the udder, more time consuming and costly manufacturing and difficulty re-dispersing the formulation if sedimentation occurs upon storage.[15]

    Aim of the invention

    [15] Page 2, line 7 – page 3, line 5.

16. Against this background, the specification states:

    “there is a long felt need in the industry to develop improved compositions for the treatment of conditions such as mastitis during the lactating period of an animal.  In the case of mastitis treatment, desired traits of such a composition may include:

    -     controllable release profile of the active agent;

    -     a short with-holding period (WHP) – for example, for treatment of conditions such as mastitis during the lactation period of the animal;

    -     good re-dispersability after storage, or before administration;

    -     ease of injectability or other mode of administration;

    -     good distribution of the composition into the region to be treated;

    -     the composition’s base being adaptable to use with different active agents for treating or preventing any disease or condition, yet controlled and/or sustained release of the active;

    -     the composition’s base being adaptable to account for different treatment regimes (i.e. different controlled release profiles); and/or

    -     easy to manufacture, and using pharmaceutically acceptable excipients.

    It is an object of the present invention to address the foregoing problems or at least provide the public with a useful choice.”[16]

    Nature of the invention

    [16] Page 3, lines 6-23.

17. The specification goes on to state that one aspect of the present invention is a composition including a therapeutically effective amount of an active agent or agents and a base including colloidal silica, at least one oil and at least one surfactant, wherein the viscosity of the composition is below 1000 mPas at a shear rate of 100 1/s and at a temperature of 20°C.  This composition is said to be particularly effective in mastitis treatment as it may help to provide (a) a controllable release profile of the active agent – which may be used to maintain the concentration of active agent above the MIC90 during the treatment period; (b) a low viscosity to assist with injectability, re-dispersability and/or good distribution in the udder; and/or (c) a shorter withholding period relative to other available mastitis compositions.[17]

    [17] Page 5, line 17 – page 6, line 10.

18. The specification explains:

    “it is believed that this controllable release may be due to the surfactant interacting with the colloidal silica, with the result being a change in the release profile of the active agent from the composition.

    Importantly this control of release profile of the active agent may be achieved without overly altering the viscosity of the composition, and in particular without a substantial increase in the composition’s viscosity.

    By example in Figure 2, in vitro studies showed the inventors were able to decrease drug recovery (equating to a decreased release profile in vivo) in dissolution media from approximately 50% to 5% w/w over a 180 minute time period.  This beneficial effect was obtainable while the viscosity of the composition only increased marginally from 90 mPas to 118 mPas (at a shear rate of 100 1/s and at a temperature of 20°C).  As shown in Figure 2, this recovery rate of 5% w/w was similar to that obtained by a competing product, Orbenin^TM LA.  However, Orbenin^TM LA has a viscosity of 1080 mPas, approximately 10 fold of that shown in this example of the present invention.”[18]

    [18] Page 6, lines 17 – page 7, line 9.

19. The specification indicates that “colloidal silica should be taken as meaning particles of fumed amorphous silica with a greatest diameter of a single silica particle between 1 nm and 1000 nm”.[19]  In particular, hydrophobic colloidal silica is preferred:

    “The inventors identified hydrophobic colloidal silica may be significantly more effective than hydrophilic colloidal silica at altering the release profile of the active agent, whilst keeping the viscosity relatively low and/or substantially unchanged.  This was a surprising result as formulations using hydrophobic colloidal silica have a lower viscosity than those using its hydrophilic counter-part.  Hydrophilic colloidal silica is known to be used as a thickening agent, which imparts a slower release profile as a result of the thickened composition.

    Instead, when the inventors used hydrophilic silica, inclusion of a surfactant tended to increase the viscosity of the composition more than when compared to using hydrophobic silica.  This was a particularly surprising result, as the use of hydrophobic silica instead of hydrophilic silica in the present invention tended to provide a greater control of the active agent’s release.”[20]

    [19] Page 9, lines 7-9.

    [20] Page 9, line 21 – page 10, line 9.

20. The specification provides preferred quantities of colloidal silica,[21] and indicates that the higher the concentration of colloidal silica in the base of the composition, the slower the release rate of the active agent.[22]  The specification states that a skilled person would be easily able adjust the amount of colloidal silica “to achieve the desired release rate of substantially any composition.”[23]  Aerosil R972 is identified as a preferred commercially available hydrophobic colloidal silica.[24]

    [21] Page 10, lines 12-16.

    [22] Page 11, lines 8-10.

    [23] Page 11, lines 5-7.

    [24] Page 10, lines 10-11.

21. The specification elaborates on the use of colloidal silica, noting that while it is typically used as a viscosity modifier or thickening agent, and therefore alters release of active agents by virtue of the general principle that the thicker a composition is, the slower the release of the active is, that is a different concept to the present invention.[25]  That is, according to the specification the prior art does not disclose the interaction of surfactant and  colloidal silica to effect controlled release of an active agent.[26]

    [25] Page 18, line 21 – page 19, line 4.

    [26] Page 20, lines 5-7.

22. The specification then states:

    “Fumed colloidal silica exists in particles (termed primary, secondary or tertiary particles depending on their level of aggregation and/or agglomeration).

    Under mechanical stress, the silica tertiary structure is broken down to primary or secondary aggregates, the system becomes more fluid, and the viscosity drops.  Once returning to rest, the tertiary structure of agglomerated silica particles builds up again, and the viscosity returns to its original value.”[27]

    [27] Page 20, lines 16-21.

23. I understand this to be an explanation of the observed thixotropic (i.e. decrease of viscosity at shear, e.g. when shaken, followed by a return to a more viscous state at rest) behaviour of compositions comprising colloidal silica.

24. According to the specification:

    “it was surprising to find that altering the components of the present composition substantially influences the release profile of the active agent without overly affecting the viscosity.”[28]

    [28] Page 21, lines 10-12.

25. The specification indicates that preferred surfactants to include in the composition are sorbitan esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene castor oil derivatives, polyoxyethylene stearates and polyethylene oxide monooleate, with some surfactants more effective than others at controlling a given active agent’s release rate.[29]  Further, a greater concentration of surfactant is associated with a slower release of the active agent.[30]

    [29] Page 12, lines 2-7.

    [30] Page 12, lines 12-13.

26. The oily vehicle of the composition should be comprised of a low viscosity oil, preferably between 1 and 100 mPas, and more preferably less than 40mPas at 20°C.[31]  The specification indicates that the oil is preferably selected from the group consisting of medium chain triglycerides (for example, Miglyol 812, Miglyol 840), ethyl oleate, light liquid paraffin, sesame oil and peanut oil.[32]  Notably, the use of different oils impacts the release of the active agent, although to a lesser extent than alterations in the active agent, amount or type of surfactant, or amount of colloidal silica.[33]

    [31] Page 13, lines 7-13.

    [32] Page 13, lines 14-16.

    [33] Page 13, lines 19-22.

27. The specification indicates that the viscosity of the composition may be tailored to specific requirements and may be relatively high or low.[34]  The viscosity of the compositions of the invention is less than 1000 mPas at a shear rate of 100 1/s and at a temperature of 20°C, more preferably less than 300 mPas and most preferably less than 150 mPas.  This may provide better characteristics in terms of good syringeability, re-dispersability, udder distribution and/or short withholding period compared to competing long acting, more viscous, formulations, while ensuring the release profile is suitably controlled to allow the active to maintain substantially above the MIC90 during the entire treatment period.[35]

    [34] Page 14, lines 7-10.

    [35] Page 15, lines 3-10.

28. The specification states:

    “A particularly advantageous use of the present invention may be the combination treatments of different compositions having different release profiles during the treatment period.

    To illustrate this, a mastitis treatment may encompass the initial use of a relatively slow active-releasing composition over the first part of the treatment period, yet the latter treatment(s) may use a faster active-releasing composition.”[36]

    [36] Page 17, lines 3-8.

29. However, the specification notes that the composition of the present invention may be used to treat substantially any condition or disease depending on the choice of active agent, and “[t]he underlying inventive concept should not be limited to compositions for intramammary treatment of mastitis.”[37]

    [37] Page 15, lines 19-22.

1. The specification provides a method of manufacturing the composition of the invention, including: (a) mixing the oil and surfactant to form a homogenous oil mixture (optionally a preservative may also be mixed into the oil mixture); (b) dispersing the active agent in the oil mixture; and (c) adding the colloidal silica to the oil mixture.[38] 

   [38] Page 17, lines 15-24.

2. It is noted that the use of micronised active agents helps prevent quick settling of the composition.  The inventors also postulate that release of a micronised active agent is easier to control due to more consistent particle size distribution and note that interaction with other components of the composition is likely to be enhanced due to the larger surface area.[39]

   The Examples

   [39] Page 18, lines 13-19.

3. The specification concludes with 18 examples.  Of these, 17 are compositions comprising an oily base, a surfactant, antibiotic, hydrophobic colloidal silica and optionally preservatives.  It is demonstrated that the exemplified compositions exhibit low viscosity relative to selected commercial formulations[40] and that selection of surfactant (type and concentration),[41] concentration of colloidal silica,[42] oil type[43] and selection of active agent[44] all impact on the release profile of the active.  The specification suggests that the release of the active agent may be influenced by interaction with a possible structural network formed by excipients in the composition’s base.[45]

   [40] Figure 1.

   [41] Page 29, lines 9-19; Figures 2, 3.

   [42] Page 29, line 24 – page 30, line 5; Figure 4.

   [43] Figure 6.

   [44] Page 30, lines 18-25; Figures 8, 9.

   [45] Page 30, lines 22-25.

4. Quite diverse release profiles are demonstrated by the exemplified compositions, as shown in Figure 3, reproduced below.[46]

   [46] Example 6: 9.18% cloxacillin sodium, 2.25% Aerosil R972 Pharma, 0.10% PEG12Oleate, 88.47% Miglyol 812.

5. The specification describes Figure 3 as follows:

   “Figure 3 illustrates that the recovery rate of the active agent can be affected not only by the choice of the surfactant type, but also the concentration thereof.  This is exemplified by the increase of the concentration of Span80 (HLB=4.3) from 0.05% to 1% (Examples 8 to 11).  Only a small rise in the viscosity is seen, yet a disproportionate decrease in the active recovery is provided.”[47]

   [47] Page 29, lines 15-19.

6. The examples also demonstrate that hydrophobic colloidal silica lowers the recovery rate of the active relative to hydrophilic colloidal silica, despite the composition comprising hydrophobic colloidal silica having a lower viscosity.[48]  It is also shown that certain examples demonstrate a shorter withholding period (i.e. the period before the active agent is below the maximum residue limit) than commercially available products.[49]

   [48] Page 30, lines 6-11.

   [49] Figure 15.

7. A further example formulation (Example 18), consisting of cloxacillin sodium, methyl paraben, propyl paraben, sorbitan monooleate (Span 80), hydrophobic silica (Aerosil R972 Pharma) and fractionated coconut oil (Miglyol 812N), was investigated for efficacy in the treatment of mastitis in dairy cows, and provided a bacteriological cure proportion of 69.6%.[50]  Based on formulation stability data, the specification indicates that a shelf-life of at least 18 months at 25°C is expected.[51]

   [50] Page 33, lines 11-13.

   [51] Page 34, lines 8-15.

   The invention as claimed

8. The correct approach to the construction of claims was discussed by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd:[52]

   “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.”

   [52] [2009] FCAFC 70; 81 IPR 228 at 254, [118]-[120].

9. The entire claim set is reproduced at Annex A.  Claim 1 is the only independent claim:

   A composition,

   the composition including a therapeutically effective amount of at least one active agent, and a base configured to provide a controlled release of the at least one active ingredient, the base including,
   an amount of colloidal silica wherein the colloidal silica is a hydrophobic type; at least one oil; and at least one surfactant,

   wherein the active agent is an antibiotic;

   wherein the viscosity of the composition is below 1000 mPas at a shear rate of 100 1/s and at a temperature of 20°C; and

   wherein the colloidal silica is dispersed in the oil.

10. Notably this claim is not directed to compositions specifically suitable for intramammary infusion and includes within its scope any composition having the requisite components and viscosity.

    Active agent

11. It is apparent that there may be more than one active agent present in the composition.  One of these must be an antibiotic, and there may be further antibiotic or non-antibiotic active agents.  The specification indicates that cloxacillin is a preferred antibiotic agent[53] and preferably the active agent is micronised.[54]

    Colloidal silica

    [53] Page 7, line 25.

    [54] Page 8, lines 22-24.

12. The colloidal silica included in the composition must be hydrophobic, and it must be dispersed in the oil.  While the claim does not specify the amount of colloidal silica to be used, the specification indicates that the concentration of silica is preferably between 0.1-5% w/w, more preferably 1-3% w/w and 1.75% w/w is a particularly preferred amount.  However, the amount of colloidal silica used may be governed partially by the active used, and the desired release rate.[55]

    Oil

    [55] Page 10, lines 12-25.

13. As noted above, the oil is preferably a low viscosity oil, selected from the group consisting of medium chain triglycerides (for example, Miglyol 812, Miglyol 840), ethyl oleate, light liquid paraffin, sesame oil and peanut oil, but other low viscosity oils may also be used.[56]  It is apparent that the base may include more than one oil.

    Surfactant

    [56] Page 13, lines 14-17.

14. The specification indicates that the surfactant is preferably a non-ionic surfactant, but amphoteric, anionic or cationic surfactants should also work.[57]  More than one surfactant may be present.[58]  The amount or type of surfactant may provide a means to control the release rate of the active agent.[59] 

    Base configured to provide a controlled release

    [57] Page 11, lines 20-22.

    [58] Page 12, line 18.

    [59] Page 12, lines 14-15.

15. “Controlled release” is not explicitly defined in the specification but its construction is of importance to each of Merial’s grounds of opposition.  In Merial’s submission, to the extent that it can be given a meaning, a controlled release formulation is any formulation that determines the rate of release of an active.

16. Mr Pippia, with whom Dr Page was in substantial agreement,[60] took a broad view of “controlled release”:

    “The term ‘controlled release’ without further qualification is a relatively broad term, and essentially requires that a formulation controls the release rate of the active agent, and encompasses a variety of release profiles, such as fast or prolonged release, especially in the context of intramammary infusion formulations.  If a specific release profile was important then it would need to be clearly defined in the specification, for example by defining the specific parameters of the release profile intended.

    …it appears that compositions demonstrating little or no release of the active agent, as seen in Example 6 of Figure 2, is considered just as much ‘controlled release’ as Example 14 at Figure 5, where essentially all of the active has released from the formulation within 30 minutes at an initial rapid rate, fast tapering off and with all release completed by about 60 minutes, which would be considered ‘rapid release’ especially when treating mastitis in lactating cows.  As such, it is unclear to me how the opposed specification would otherwise define ‘controlled release’ and in the absence of any definition and in view of the data provided.  It covers a broad range of release profiles including both rapid and prolonged release.”[61]

    [60] Page 1 at [178], [180], [181].

    [61] Pippia 1 at [206]-[207].

17. In contrast, Dr Bunt, who I accept has significant expertise in relation to controlled release formulations,[62] understood the specification to distinguish controlled release from rapid or immediate release.[63]  He stated:

    “At its heart, as a person working as a formulation chemist and/or in the field of mastitis would understand, controlled release provides a mechanism for delivering an active over an extended/sustained period of time.”[64]

    “…the specification is distinguishing the controlled release defined in the claims from release which occurs ‘too quickly’.  Clearly the specification distinguishes such ‘rapid’ or ‘immediate’ release profiles from controlled release.  At the very least the specification states that these forms are ‘poor controlled release’.”[65]

    “‘Rapid’ release does not provide controlled release as it is understood in the industry.  To all meaningful purposes, particularly in the context of intramammary formulations, rapid release is equivalent to immediate release which is not controlled release as a person working as a formulation chemist and/or in the field of mastitis would understand.”[66]

    [62] For example, Bunt at [4]-[7].

    [63] Bunt at [752]-[753].

    [64] Bunt at [626].

    [65] Bunt at [753].

    [66] Bunt at [576].

18. Dr Bunt also indicated a concern that faster-releasing formulations could not sustain an appropriate level of active in the udder over the desired treatment period,[67] which is clearly an object of the invention.  Mr Pippia, however, noted that release of the active agent out of the formulation does not eradicate presence of the active from the udder, where it may remain at an appropriate level for a desired 24 or 48 hour treatment period.[68] 

    [67] Bunt at [754].

    [68] Pippia 3 at [68].

19. While I note that Example 14 includes hydrophilic colloidal silica and so does not fall within the scope of the claims, it nevertheless provides a useful indication of how the experts characterise a given release profile.  Dr Bunt considered that Example 14 (shown in Figure 5 reproduced below) represents a controlled release formulation.[69]  He described Figure 5 as demonstrating “prolonged release of the active in a controlled manner”[70] and stated that a “consistent and common feature of controlled release is the gradual tailing-off of release.”[71]  However, Example 14 was characterised by Mr Pippia and Dr Page as an example of rapid release.[72]  

    [69] Bunt at [221].

    [70] Bunt at [656].

    [71] Bunt at [655].

    [72] Page 1 at [180], Pippia 1 at [207], Pippia 3 at [72].

20. Bayer submitted that, consistent with Dr Bunt’s evidence, controlled release should be understood as sustained/extended release, excluding rapid release.  Bayer drew my attention to passages of the specification in support of that view, such as:

    “one of the major problems encountered with antibiotic treatments is a poor controlled release of the active agent over the treatment period.”[73]

    “some surfactants appeared to work better than others at controlling a chosen active agent’s release rate.

    For example, 0.1% w/w PEG12-oleate had a greater effect at slowing the release rate of cloxacillin than 0.1% w/w Span 80”[74]

    “…beneficial features [of viscosity below 1000 mPas] may be retained whilst ensuring the release profile of the active is suitably controlled to allow the active to remain substantially above the MIC90 during the entire treatment period.”[75]

    [73] Page 2, lines 12-13.

    [74] Page 12, lines 6-9.

    [75] Page 15, lines 8-10.

21. I agree that there is a focus in the specification on the capacity to achieve a release profile like that of long acting formulations such as Orbenin LA or NitroClox LA with a lower viscosity,[76] and it is reasonably clear from the background presented that the preferred solution to what the specification identifies as the problem lies in a low viscosity formulation with a relatively slow release profile. However, as Beach J observed, “the specified objects are not controlling in terms of construing a claim: glosses cannot be drawn from the objects”,[77] and the specification refers to the base being adaptable “to use with different active agents … yet controlled and/or sustained release of the active” and “to account for different treatment regimes (i.e. different controlled release profiles)”[78] and Bayer submitted that the meaning of controlled release is determined having regard to the active and the therapeutic goal concerned.  This, and the statement in the specification that the invention may be used to treat “substantially any condition or disease”[79] seems consistent with the diversity of exemplified release profiles in the specification.

    [76] For example, page 7, lines 1-9, page 11, lines 8-13, page 31, line 10 – page 32, line 5, Figures 13-16.

    [77] GlaxoSmithKline Consumer Healthcare Investments (Ireland) (No. 2) Limited v Apotex Pty Ltd [2016] FCA 608 at [272].

    [78] Page 4, lines 16-20.

    [79] Page 15, lines 19-20.

22. Bayer also submitted that there is a presumption against redundant drafting and all the words in the claim should have meaning,[80] and construing controlled release to mean effectively any release profile would make these words redundant. I agree that all the words in a claim will have a meaning, which will be informed by the context of the specification and the expert evidence.

    [80] Referring to Technip France SA’s Patent [2004] RPC 46.

23. At the hearing I asked about the scope of “sustained/extended” release and whether certain examples in the specification fall within the scope of the claims according to Bayer’s construction.  I understand Bayer’s submission to be that Examples 8 and 9, which demonstrate particularly rapid release in the in vitro test (shown in Figure 3, reproduced above), may or may not, and in vivo testing results would be required to establish whether or not they do.  It is concerning that although the specification states that “[r]ecovery rates in dissolution media (shown in Figures 2-6) are considered by the inventors to be indicative of in vivo release rates”[81] it seems that on Bayer’s construction of the claims that it is not apparent from the data in the specification whether the exemplified compositions fall within the scope of the claims. 

    [81] Page 29, lines 1-2.

24. However, despite the apparent conflict between the declarants in the passages set out above, there seems to be a level of agreement between the declarants that diffusion control is a form of controlled release.[82]  In this regard Dr Bunt stated:

    “Typically oil or water suspensions are more suitable for the controlled release of the active (antibiotic) whereas solutions (in water and to a lesser extent oil) tend to be more suitable for rapid release of the active.

    …

    Oil based formulations are normally employed to achieve a slow and prolonged delivery of active.  The aim of this slow delivery is opposite to any intention to achieve a rapid commencement of treatment. 

    The release of the active agent is typically under diffusion control – that is, the formulation dictates the rate at which the active agent releases and can have an effect on the infectious agent.

    Where the active agent is solubilised in a low viscosity formulation, particularly an aqueous formulation, the diffusion/drug release is rapid with very little, if any, control over the release of the active agent. …

    In other cases, greater control over the diffusion of the active agent is required.  The most commonly used technique for slowing the rate of diffusion from the formulation is to provide the active agent in solid form in a suspension formulation.  This is particularly well suited for those active agents that are sparingly water soluble, so that they must first slowly dissolve into the intramammary aqueous environment before they can contact the infectious agent or be absorbed into the internal tissue within the udder.”[83]

    [82] Pippia 3 at [143], Bunt at [205], Page 2 at [64].

    [83] Bunt at [55]-[61].

25. Dr Bunt also indicated that a controllable release profile of an active agent would be “addressed by controlling the dissolution of the active by suspending particles of the drug in a non-solvent”.[84]  I do note, however, that Dr Bunt went on to identify many compositions comprising active agents suspended in an oily base as not being controlled release,[85] despite the fact that I understand from the preceding passages that their release would be under diffusion control.

    [84] Bunt at [205].

    [85] For example, Bunt at [302], [482].

26. Given the evidence, and a consideration of the specification itself, I think that it is reasonable to conclude that a person reading the specification would understand the examples to be presented as examples of the invention.  While Bayer submitted that the purpose of the Figures was to demonstrate the effect of varying particular parameters on the resulting formulation, the description of the figures follows a heading “Exemplification of controlled release rate of active agent”.  With the exception of the obvious comparator example (using hydrophilic colloidal silica) there is no suggestion that any examples should not be considered to form part of the invention.[86]  Nor is it clear which examples would form part of the invention if Bayer’s proposed construction were adopted.  This leads me to a view that controlled release in the context of the specification includes diffusion control.  It follows from this construction that where there is a dispersion of a solid active in an oily base such that the release of the active agent is under diffusion control, I consider that such a composition will inevitably exhibit “controlled release” within the meaning of the present claims.  That release may be more or less retarded – sustained or under “poor” control – but not immediate.

    Viscosity

    [86] For example, Pippia 1 at [207].

27. The viscosity of the composition is of some importance to the grounds of opposition.  It is clear that compositions of the claim must have a viscosity of below 1000 mPas at a shear rate of 100 1/s and a temperature of 20°C.  This is a high shear viscosity measurement.[87]  However, notwithstanding that the specification refers to the compositions of the invention as “low viscosity” I cannot see any basis to import any further requirement regarding the viscosity of the composition (i.e. at rest) into the claim.

    [87] Bhattacharjee 1 at [27], Pippia 1 at [285].

28. I note that Orbenin LA has a viscosity of 1080 mPas at the conditions described in the claim and is described in the specification as a “thick paste”.[88]  Mr Pippia suggested the difference between 1080 mPas for Orbenin LA and 1000 mPas in the present claims cannot be considered a significant difference,[89]  but it is unnecessary to determine that point.  It is quite clear that formulations which are “extremely thick” at rest may nevertheless have a low viscosity at the shear conditions defined in the claim.[90]

    Appended claims

    [88] Page 2, line 22 – page 3, line 1.

    [89] Pippia 1 at [155].

    [90] Bunt at [132]. See also WO 00/10528 A1 (D6), Example 6 (composition has a zero shear viscosity of 55,400 Pas and a viscosity at 100/s of 282 mPas); Bhattacharjee 2 at [26]-[31].

29. Claims 2-23 define narrower embodiments of the composition of claim 1.  Claims 10-13 define various properties of “the surfactant”.  While the composition may contain more than one surfactant, I understand these claims to require that at least one of the surfactants present in the composition has the defined property.

30. Claim 24 is directed to a method of manufacturing a composition according to the claims:

    A method of manufacturing a composition as claimed in any one of claims 1 to 23 including the steps of:

    a) mixing the oil and surfactant in a container to form a homogenous oil mixture;

    b) dispersing the active agent in the oil mixture; and

    c) subsequently adding the colloidal silica to the oil mixture.

1. It is apparent that these steps must be carried out in the defined sequence.  Any additional components may be added at any point.

2. Claims 25 and 26 define methods of treatment including the step of administering the composition of the preceding claims by intramammary infusion:

   25. A method of treating a non-human animal in need thereof with a composition as claimed in any one of claims 1 to 23 wherein the method includes the step of administering the composition to the animal by intramammary infusion.

   26. The method as claimed in claim 25 including a dosage regime of between 1 - 6 doses of 5 g formulation composition over a period of 0 to 120 hours administered 3 x 24 hours or 6 x 24 hours.

3. These claims do not specifically define the condition to be treated, but the treatment is by intra-mammary infusion of an antibiotic containing agent, and it is apparent that an animal in need of such treatment would be suffering from, or at risk of, mastitis.  Claim 27 defines that the method is for the treatment or prevention of mastitis during the lactation period of a non-human animal.

4. At the hearing I queried the construction of claim 28, which reads:

   A use in the manufacture of a composition as claimed in any of claims 1 to 23 for the treatment or prevention of a pre-clinical or clinical mastitis in an animal in need thereof.

5. While on a cursory reading this resembles a Swiss type claim (i.e. use of [substance] in the manufacture of a medicament for the treatment or prevention of [medical condition]), it does not properly adopt that structure. Despite an apparent intention for the claim to be in the Swiss form, a Swiss type claim is given a particular construction on the basis of its structure (that is, these claims are construed as method or process claims that derive novelty from the defined therapeutic use),[91] and I do not consider that such a construction is appropriate in the present circumstances.

   [91] See, e.g., Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4) [2015] FCA 634; 113 IPR 191 at [119]-[120] (not disturbed on appeal), John Wyeth & Brother Ltd’s Application; Schering AG’s Application [1985] RPC 545.

6. I will adopt what I consider to be the most reasonable construction of the claim as it is drafted, and so I take the claim to be directed to a process of manufacturing a composition of any one of claims 1-23, which is suitable for the treatment or prevention of pre-clinical or clinical mastitis.

   Clarity

7. It is a requirement of subsection 40(3) of the Act that the claims be clear.  This requirement is satisfied if a person could ascertain “whether or not what he proposes to do falls within the ambit of the claim”.[92]  However, the terms used in claims need not be precise and absolute, as set out in Flexible Steel Lacing Company v Beltreco Ltd:

“Lack of precise definition in claims is not fatal to their validity, so long as they provide a workable standard suitable to the intended use. The consideration is whether, on any reasonable view, the claim has meaning. In determining this, the expressions in question must be understood in a practical, commonsense manner. Absurd constructions should be avoided and mere technicalities should not defeat the grant of protection.” [93]

[92] Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59 at 60.

[93] [2000] FCA 890; (2001) 49 IPR 331 at [81] (cited with approval in Austal Ships Sales Pty Ltd v Stena Rederi Aktiebolag [2008] FCAFC 121; (2008) 77 IPR 229) (citations omitted).

1. Merial submitted that “controlled release” as used in the specification is unclear, referring to the absence of a definition of the term in the specification and the disagreement between the experts.[94]  In the alternative, Merial submitted that any meaning ascribed to controlled release should be broad and encompass at least the exemplified formulations.  I have construed the claims above and considered the submissions of the parties and the evidence in doing so.  I agree with Bayer that a dispute between experts does not inevitably lead to a lack of clarity[95] and does not in this case. 

   [94] Merial’s written submissions at [90].

   [95] Novozymes A/S v Danisco A/S [2013] FCAFC 6; 99 IPR 417 at [95].

2. Merial has not made out this ground of opposition.

   Novelty

3. 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) provides that an invention is taken to be novel unless it is not novel in light of the prior art base.  Prior art information made publicly available in a document or through the doing of an act forms part of the prior art base for the purpose of novelty if it was published before the priority date of a claim.

4. It is well established that the general test for lack of novelty is the reverse infringement test, as set out by Aickin J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd:[96]

   “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”.

   [96] [1977] HCA 19; 137 CLR 228 at 235, [20].

5. This test is satisfied if the alleged anticipation discloses all the essential features of the invention as claimed.[97]The level of disclosure required is set out in General Tire & Rubber Co v Firestone Tyre and Rubber Co Ltd:

   “If the prior inventor’s publication contains a clear description of, or clear instructions to do or make, something that would infringe the patentee’s claim if carried out after the grant of the patentee’s patent, the patentee’s claim will have been shown to lack the necessary novelty, that is to say, it will have been anticipated.  The prior inventor, however, and the patentee may have approached the same device from different starting points and may for this reason, or it may be for other reasons, have so described their devices that it cannot be immediately discerned from a reading of the language which they have respectively used that they have discovered in truth the same device; but if carrying out the directions contained in the prior inventor’s publication will inevitably result in something being made or done which, if the patentee’s patent were valid, would constitute an infringement of the patentee’s claim, this circumstance demonstrates that the patentee’s claim has in fact been anticipated.

   If, on the other hand, the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee’s claim, but would be at least as likely to be carried out in a way which would not do so, the patentee’s claim will not have been anticipated, although it may fail on the ground of obviousness.  To anticipate the patentee’s claim the prior publication must contain clear and unmistakable directions to do what the patentee claims to have invented.  A signpost, however clear, upon the road to the patentee’s invention will not suffice.  The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee.”[98]

   [97] See Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513 at 517.

   [98] General Tire & Rubber Co v Firestone Tyre and Rubber Co Ltd [1972] RPC 457 at 485-486 (citations omitted).

6. It was clarified in Novozymes A/S v Danisco A/S[99] (Novozymes) that where a publication provides a direction which, if followed, would inevitably result in something that falls within the scope of the claims, that is sufficient.  It is not necessary for the skilled person to understand the presence of the inevitable result of the disclosure.[100]

   [99] [2013] FCAFC 6; 99 IPR 417.

   [100] Novozymes at [166].

7. The specificity of a disclosure is important when determining anticipation, as highlighted by the majority in AstraZeneca AB v Apotex Pty Ltd:[101]

   “The metaphor of planting the flag has been taken up in this Court.  For example, in ICI Chemicals, the Full Court at [51], after noting the metaphor, remarked that, in that case, the appellant’s argument involved the skilled addressee rummaging through a ‘flag locker’ to find a flag which the prior art document possessed and could have planted.  In Apotex Pty Ltd and Another v Sanofi-Aventis and Another [2008] FCA 1194; (2008) 78 IPR 485 (‘Sanofi-Aventis (2008)’), Gyles J at [91] adopted a different metaphor, remarking that ‘anticipation is deadly but requires the accuracy of a sniper, not the firing of a 12 gauge shotgun’. Each metaphor underlines the importance of the specificity required in order for a prior art document to anticipate an invention as claimed.”

   [101] [2014] FCAFC 99; 107 IPR 177 at [294].

8. Merial asserted that the claims lack novelty in light of each of US 4,079,920 (D4) and US 2010/0261688 A1 (D17).

   D4  

9. D4 discloses a veterinary composition for intramammary administration to animals comprising a suspension of a semi-synthetic penicillin in an oily vehicle comprising triglycerides or propylene glycol diesters of 8-10 carbon fatty acids, that has a short milk out time and good stability and shelf-life.  D4 states that:

   “Additives may also be present in the oily vehicle in minor proportions.  Examples of such additives include conventional thickening agents such as 12-hydroxy stearin, aluminium stearate and colloidal silica, and conventional surfactants such as those sold under the Trade Marks ‘SPAN’ and ‘TWEEN’. …  When the compositions contain additives they are normally present as up to 10% by weight of the composition.”[102]

   [102] D4 at column 2, lines 1-11.

10. The examples of D4 include 12-hydroxystearin at 1% by weight, and in particular, the composition of Example 3 of D4 consists of 6.7% sodium cloxacillin, 1.0% 12-hydroxystearin, 3.0% surfactant (58:42 Tween 80:Span 80) in Miglyol 812.  Merial submitted that the disclosure of colloidal silica in D4 encompasses both hydrophobic and hydrophilic colloidal silica, but that in implementing the disclosure the skilled person would understand that a hydrophobic colloidal silica would be preferred when using an oily base.[103]  As such, Merial submitted that a composition comprising hydrophobic colloidal silica is within the disclosure of D4 and provided evidence directed to the properties of a composition prepared with hydrophobic colloidal silica.  However, there are no examples in D4 in which colloidal silica is used as the thickening agent – this is work that has not yet been done.[104] 

    [103] Merial’s written submissions at [112].

    [104] See, e.g. Pippia 1 at [286]-[287] which indicates that there is work to be done to arrive at a composition of the present claims.

11. While of course an example is not essential for a document to be anticipatory and it is the content of the information in a disclosure that is critical,[105] it is clear that what is needed is a clear description of, or instructions to do, what is claimed.  In this regard, D4 is not explicit as to the nature of the colloidal silica to be employed – hydrophobic or hydrophilic,[106] or the quantity to be used, which would be expected to impact on the viscosity of the resulting formulation.  On balance, while I consider that D4 provides a signpost along the way, I am not persuaded that it “plants the flag” at the claimed compositions.

    [105] See, e.g., Novozymes at [177].

    [106] On the basis of the evidence discussed below I consider that both hydrophobic and hydrophilic colloidal silicas were known to be useful in thickening non-polar liquids.

12. Accordingly, I find that D4 does not anticipate the present claims.

    D17

13. D17 discloses the use of amphiphilic substances to stabilise fluid oil-based suspensions comprising a hydrophobic silica, and in particular discloses medicaments comprising in an oily base 1) an active ingredient, 2) a hydrophobic silica and 3) a polyoxyethylated compound.  The suspensions of D17 may range from low-viscosity suspensions to pastes, but preferably flow under their own weight.[107]  D17 indicates the disclosed medicaments are “suitable in principle for all possible modes of administration”, and refers particularly to treatment of the auditory canal, noting that for this purpose “[t]hixotropic formulations are particularly advantageous”.[108]  D17 does not refer to intramammary use.

    [107] D17 at [0014]-[0020].

    [108] D17 at [0116]-[0117].

14. The examples of D17 include a fungicide and an anti-inflammatory suspended in an oil, and an antibiotic that is either suspended in the oil or dissolved in benzyl alcohol before being mixed with the oil.  Merial drew my attention particularly to Example 8:

    “0.1% enrofloxacin
    1.0% clotrimazole
    0.05% dexamethasone acetate
    0.1% sorbic acid
    0.05% polyoxyethylene 20 sorbitan monooleate
    3.2% colloidal hydrophobic silica

    ad 100% medium-chain triglycerides

    0.1 g of sorbic acid is heated in 95 g of MCT to 60° C. and dissolved.  At about 22°, 0.1 g of enrofloxacin, 1.0 g of clotrimazole, 0.05 g of dexamethasone acetate, 0.05 g of polyoxyethylene 20 sorbitan monooleate and 3.2 g of colloidal hydrophobic silica are dispersed.  The suspension is then homogenized for about 10 min with a homogenizer.”

15. I note that Example 6 is the same as Example 8, but for the inclusion of 0.14% pradofloxacin trihydrate and 1.0% bifonazole instead of the fungicide and antibiotic included in Example 8.  Similarly, Example 10 differs only in the replacement of clotrimazole with bifonazole.

16. In the introduction to the Examples of D17 it is stated that:

    “Medium-chain triglycerides to be used are the triglycerides of caprylic/capric esters, for example Miglyol® 812 from Sasol/Witten (e.g. used in Examples 3 and 6).  The methylated silica Aerosil® R972 from Degussa is used as colloidal hydrophobic silicas.”[109]

    [109] D17 at [0123].

17. Evidently the compositions of D17 comprise the components defined in present claim 1 – hydrophobic colloidal silica dispersed in an oil, a surfactant and an antibiotic.  However, D17 does not explicitly disclose the release profile or the viscosity of the disclosed compositions and Merial has filed no experimental evidence establishing these properties.  Before considering the evidence and submissions of the parties regarding D17 further, I will address this point.

18. It is uncontroversial that the onus is on Merial to make out its grounds of opposition.  In this regard, Bayer referred to the comments of Yates J in Novozymes that “one is accustomed to seeing the tender of experimental proof to make good the existence of the ‘inevitable result’.”[110] Bayer submitted that in the absence of experimental evidence the onus was not discharged, and further submitted, noting that Merial adduced experimental evidence in relation to D4, that it would be appropriate to draw an adverse inference on the basis of the absence of experimental data in relation to D17.  In response to this Merial noted that pre-grant opposition proceedings are intended to be a relatively streamlined and cost effective means of testing validity, and testing evidence is not essential.  Merial also submitted that while it had provided evidence in relation to D4, a more ready inference could be drawn as to the properties of the compositions of D17. 

    [110] Novozymes at [228].

19. I agree that opposition proceedings are intended to be relatively quick and cost effective, although I note that this does not diminish the onus on an opponent to establish its grounds of opposition.  I will add that in Novozymes Yates J went on to state that the appellants did not tender experimental proof (they relied on admissions by the respondents),[111] but the asserted lack of novelty was made out in that case.  In the present case I draw no inference from the absence of experimental evidence relating to D17.  Although experimental evidence would, of course, have been of assistance, it is incumbent on me to consider the evidence that is before me and determine whether a sufficiently strong inference as to the properties of the composition(s) of D17 can be drawn to support a conclusion that, on the balance of probabilities, the claims are anticipated. 

[111] Ibid at [229].

1. Dr Bunt does not consider D17 to provide a disclosure of the presently claimed compositions with respect to controlled release and low viscosity,[112] and he commented that:

“the examples in D17 all use the same very small amount of surfactant and a relatively large amount of hydrophobic colloidal silica.  In each case a very specific ratio of surfactant to colloidal silica is used – 64:1.  Given that the colloidal silica is used to thicken the composition in D17, and the presence of a surfactant has a very noticeable effect on reducing sedimentation in D17, I can only assume that this ratio is important for the invention in D17 to work.”[113] 

[112] Bunt at [477].

[113] Bunt at [493].

1. Dr Bunt contrasted this with the finding in the present application that increasing the amount of surfactant decreases the rate of release of the active agent.[114]  However, the importance or otherwise of this ratio is not to the point of the properties of the exemplified compositions.  Dr Bunt also noted when the antibiotic of D17 is dissolved in benzyl alcohol it would provide a rapid effect of the antibiotic.[115]

   [114] Bunt at [494].

   [115] Bunt at [483].

2. Mr Pippia indicated a view that the formulations of D17 would have a low viscosity at the shear rate defined in the claims, noting the explicit statement in D17 that the formulations can be thixotropic, and the similar quantity of hydrophobic colloidal silica in the examples of D17 and the present application (which have viscosities below 1000 mPas at the defined shear rate).[116]  While Dr Bunt noted that D17 is silent as to the viscosity of the disclosed compositions, and is not concerned with ensuring a viscosity within the scope of the claims, he did not provide any reasoned explanation for why they would not fall within the parameter defined in the claim.[117]

   [116] Pippia 1 at [314], Pippia 3 at [141].

   [117] For example, Bunt at [492], [778].

3. The evidence indicates that some intramammary suspensions are shear thickening and some are shear thinning.[118]  D17 states:

   “In a preferred embodiment, the formulation of the invention can be adjusted so that it has thixotropic properties, meaning that it becomes less viscous on shaking, and the viscosity increases again at rest. … Thixotropic formulations are produced by adding an appropriate additive to the formulation base (fluid, oily base) if the fluid base is not itself thixotropic.  Such an additive is normally a suspension stabilizer or thickener such as, for example, colloidal silicon dioxides.”[119]

   [118] Exhibit CB-4.

   [119] D17 at [0097].

4. This seems to me to constitute a statement that colloidal silicon dioxides are thixotropic additives in the formulations of D17.  This is consistent with the statement in the present specification regarding the effect of mechanical stress on silica particles I referred to earlier.[120]  Given these statements and in the absence of any contradictory information, I am satisfied on the balance of probabilities that the compositions of D17 would be thixotropic.

   [120] See also Handbook of Pharmaceutical Excipients, 5^th edition, edited by R.C. Rowe et al. London: Pharmaceutical Press, 2004 (Exhibit SWP-7) at page 188.

5. At the hearing Merial provided a table comparing the constituents of Example 8 of D17 with examples of the present application which I found helpful, and a modified and expanded version of that table is shown below:

D17 Example 8	Example 7	Example 8	Example 17	Example 16
Active agent	1.15% Enrofloxacin, clotrimazole, dexamethasone acetate	9.18% Micronised cloxacillin sodium	9.18% Micronised cloxacillin sodium	8.74% Micronised cloxacillin sodium	4.5% Micronised cloxacillin sodium, tylosin base
Hydrophobic colloidal silica	3.2%	2.25%	2.25%	3.0%	4.0%
Surfactant	0.05% Tween 80 HLB = 15[121]	0.05% PEG12Oleate HLB = 13.7	0.05% Span 80 HLB = 4.3	2.0% Span 80 HLB = 4.3	2.0% Span 80 HLB = 4.3
Preservatives	0.1% Sorbic acid	-	-	0.012% Methyl paraben, propyl paraben	0.006% Methyl paraben, propyl paraben
Medium chain triglycerides	95.5%	88.52% Miglyol 812	88.52% Miglyol 812	86.25% Miglyol 812	89.49% Miglyol 812
Viscosity at 100 1/s and 20°C	-	118 mPas	62 mPas	104 mPas	-

[121] Tadros, T.F. Applied Surfactants. Weinheim: Wiley-VCH, 2005 (Exhibit SWP-8) at page 439.

1. Example 8 of D17 is evidently quite similar to examples of the present application, particularly with regard to content of hydrophobic colloidal silica and surfactant.  Bayer drew attention to the significant difference between the loading of active in the formulations, and the expectation that changing any parameter will have an effect on the formulation.[122]  I appreciate this, and I note that the present specification exemplifies the effects of varying various parameters, but given that the loading of suspended active agent contributes to the thickness of a formulation,[123] it seems reasonable to expect that the decreased proportion of active agent would lead to a decrease in viscosity.  Further, while the specification refers to a difference in rate of release associated with the nature of the active,[124] I have not located and Bayer did not point to anything in the evidence to suggest that the viscosity would be markedly impacted by the nature of the active.  I think it is a reasonable inference that, at rest, this formulation would have a viscosity similar to the compositions exemplified in the present application. 

   [122] See, e.g. Bunt at [544], [669].

   [123] Bunt at [63]-[64].

   [124] Page 8, lines 15-17.

2. Further, given that the thixotropic agent, colloidal silica, is present in similar proportions in the formulations of D17 and the present application, I think it is a safe inference that the formulations of D17 would behave similarly at high shear.  I am satisfied on the balance of probabilities that the compositions of D17 satisfy the viscosity requirement of claim 1.

3. I have decided above that release of a solid active from an oily base under diffusion control is a form of controlled release.  Example 8 of D17 refers to suspension of the (solid) active agents in the oily base.  Accordingly, I consider that the release of the active would be diffusion controlled and satisfy the requirement of controlled release in the present claims.

4. It follows that I am satisfied that D17 anticipates claim 1. 

5. D17 also discloses the features (relating to the oil,[125] surfactant and active) defined in claims 2, 4, 7, 8, 10-15 and 18-21 and therefore these claims are also not novel.  Given the construction I have adopted for claim 28 it is also not novel in light of D17 which discloses a process of manufacturing a composition of any one of claims 1-23, which, noting the wide range of compositions which are so suitable (i.e. from <50 mPas to >2500 mPas),[126] is prima facie suitable for the treatment or prevention of pre-clinical or clinical mastitis.

   [125] Miglyol 812 has a viscosity of 28-32 mPas at 20°C – Exhibit SWP-7 at page 455.

   [126] Klink, P.R. et al. Formulation of veterinary dosage forms. In: Development and Formulation of Veterinary Dosage Forms, 2^nd edition, edited by G.E. Hardee and J. D. Baggot. New York: Marcel Dekker, 1998 (Exhibit JRP-5, Exhibit SWP-5) at page 200.

6. Merial submitted that claims 9 and 22-24 are also anticipated by D17.

7. Claim 9 defines the composition of the preceding claims wherein the concentration of colloidal silica is between 1-3% w/w.  D17 indicates that the colloidal silica is preferably present at 1.5-4.0% by weight.  The examples relied on by Merial each contain 3.2% hydrophobic colloidal silica.  While 3% is included within the range disclosed by D17, I am not satisfied that there is a sufficiently specific teaching of this concentration to be considered clear and unmistakable directions and therefore claim 9 is not anticipated.

8. Claims 22 and 23 define that the viscosity at 100 1/s and 20°C is less than 300 mPas and 150 mPas, respectively.  I am satisfied that a strong inference can be drawn that the composition of D17 satisfies the viscosity parameter in claim 1 given the large difference between the claimed viscosity parameter and that of the exemplified compositions, but there is a point at which inferences regarding the viscosity of the compositions of D17 become weaker.  While the compositions of D17 may well have a viscosity as defined in claims 22 and 23, there is no experimental evidence on this point and I am not satisfied that the inference that they do is sufficiently strong.  I am not persuaded that Merial has established that these claims are not novel.

9. Claim 24 defines the manufacture of a composition as defined in the preceding claims including the steps of a) mixing the oil and surfactant to form a homogenous oil mixture, b) dispersing the active agent in the oil mixture and c) subsequently adding the colloidal silica to the oil mixture.  D17 indicates that the formulations are produced by dispersing the active ingredients/excipients that are to be suspended in the base, with a homogeniser employed where appropriate and that the sequence of addition of the ingredients may be varied according to the formulation.  It is not evident to me that D17 explicitly discloses the order of addition defined in claim 24.  While Mr Pippia indicated that the claimed order of addition is standard and routine, he does not suggest that it is disclosed in the document.[127]  Merial has not established that claim 24 is not novel.

   Conclusion

   [127] Pippia 1 at [360]-[362].

10. Claims 1, 2, 4, 7, 8, 10-15, 18-21 and 28 are not novel in light of D17.

    Inventive step

11. 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 light of the common general knowledge as it existed (whether in or out of the patent area) before the priority date of the relevant claim when considered alone or together with the information mentioned in subsection 7(3). 

1. Subsection 7(3) defines the relevant information as:

The information for the purposes of subsection (2) is:

(a) any single piece of prior art information; or

(b) a combination of any 2 or more pieces of prior art information that the skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have combined.

1. Having identified the common general knowledge and any relevant information as defined in 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, as set out by Aickin J:

“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.”[128]

[128] Wellcome Foundation Ltd v V.R. Laboratories (Aust.) Pty Ltd [1981] HCA 12; (1981) 148 CLR 262 at 286.

1. The High Court in Aktiebolaget Hässle v Alphapharm Pty Ltd[129] (Alphapharm) approved this approach, noting that matters of routine are to be distinguished from other courses of action:

   “The tracing of a course of action which was complex and detailed, as well as laborious, with a good deal of trial and error, with dead ends and the retracing of steps is not the taking of routine steps to which the hypothetical formulator was taken as a matter of course.”[130]

   [129] [2002] HCA 59; 212 CLR 411 at 432-433, [50]-[52].

   [130] Alphapharm at 436, [58].

2. The High Court in Alphapharm also approved the approach taken in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd[131] of asking whether the person skilled in the art would be directly led as a matter of course to try what was claimed in the expectation that it might well produce a useful or desired result.[132]

   [131] [1970] RPC 157 at 187.

   [132] Alphapharm at 433, [53].

3. In both approaches a person skilled in the art must have a reasonable expectation of success.  This is explicit in the expectation that an approach “might well” succeed, and implicit in the characterisation of steps as those to be taken as a matter of routine,[133] but this expectation does not require that success is guaranteed.  It is possible that the person skilled in the art might be directly led to try more than one alternative expecting that each may well produce a useful or desired result.[134]

   [133] Generic Health Pty Ltd v Bayer Pharma Aktiengesellschaft [2014] FCAFC 73; 314 ALR 91 at [71].

   [134] Mylan Health Pty Ltd (formerly BGP Products Pty Ltd) v Sun Pharma ANZ Pty Ltd (formerly Ranbaxy Australia Pty Ltd [2019] FCA 28 at [192]. Also Nichia Corporation v Arrow Electronics Australia Pty Ltd [2019] FCAFC 2 at [91]-[93].

4. Principles identified by the High Court in Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (No 2) as of “continuing relevance” in relation to inventive step include:

   “…obviousness and inventiveness are antitheses and the question is always ‘is the step taken over the prior art an “obvious step” or “an inventive step”’?  An inventive step is often an issue ‘borne out by the evidence of the experts’.  There is no distinction between obviousness and lack of inventive step.  A ‘scintilla of invention’ remains sufficient in Australian law to support the validity of a patent.  In R D Werner Lockhart J stated that there must be ‘some difficulty overcome, some barrier crossed’.  This is consonant with older authorities in the United Kingdom which recognised that some inventiveness was required to distinguish patentable advances over the prior art from advances which ‘any fool’ could devise.  It also accords with the requirement in the United States that for an invention to be ‘non-obvious’ it must be ‘beyond the skill of the calling’.”[135]

[135] [2007] HCA 21; 72 IPR 447 at [52] (citations omitted).

1. However, I note the guidance of the majority of the High Court in Alphapharm, who referred with approval[136] to the observations of Judge Rich in In re O’Farrell in rejecting an “obvious to try” approach to inventive step:

“The admonition that ‘obvious to try’ is not the standard under §103 has been directed mainly at two kinds of error.  In some cases, what would have been ‘obvious to try’ would have been to vary all parameters or try each of numerous possible choices until one possibly arrived at a successful result, where the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful. … In others, what was ‘obvious to try’ was to explore a new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it.”[137]

[136] Alphapharm at 442-443, [76].

[137] (1988) 853 F 2d 894 at 903.

1. Where a claim is directed to a combination of known integers obviousness is not established merely by identifying each of those features in the prior art or the common general knowledge – the question is whether the combination of those features is obvious,[138] and the danger of misusing hindsight is particularly acute when considering such claims.[139]  In this regard, the High Court’s observation is apposite:

   “It is the selection of the integers out of ‘perhaps many possibilities’ which must be shown 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.”[140]

Common general knowledge

[138] Minnesota Mining and Manufacturing Co v Beiersdorf (Aust) Ltd [1980] HCA 9; 1A IPR 231 at 256; Alphapharm at 429, [41].

[139] Alphapharm at 423-424, [21].

[140] Ibid at 429, [41].

1. Common general knowledge is the background knowledge and experience available to all those working in the relevant art:

   “The notion of common general knowledge itself involves the use of that which is known or used by those in the relevant trade.  It forms the background knowledge and experience which is available to all in the trade in considering the making of new products, or the making of improvements in old, and it must be treated as being used by an individual as a general body of knowledge.”[141]

   [141] Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd [1980] HCA 9; 1A IPR 231 at 255-256.

2. However, it is not enough that information is recorded in a document, even if that document is widely circulated – it is only part of the common general knowledge when it is generally known and accepted:

   “information does not constitute common general knowledge merely because it might be found, for example, in a journal, even if widely read by persons in the art … Reference in this regard is made to the words of Luxmoore J in British Acoustic Films (1936) 53 RPC 221 at 250, cited by Lehane J in Aktiebolaget Hässle v Alphapharm Pty Ltd (1999) 44 IPR 593; [1999] FCA 628 at 605 [39]:

   In my judgment it is not sufficient to prove common general knowledge that a particular disclosure is made in an article, or series of articles, in a scientific journal, no matter how wide the circulation of that journal may be, in the absence of any evidence that the disclosure is accepted generally by those who are engaged in the art to which the disclosure relates. A piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated. Such a piece of knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in the particular art; in other words, when it becomes part of their common stock of knowledge relating to the art.”[142]

   [142] Ranbaxy Laboratories Limited v AstraZeneca AB [2013] FCA 368; 101 IPR 11 at [217].

3. The evidence establishes that the common general knowledge at the priority date included the knowledge that:

   ·      Intramammary infusions are a common treatment for mastitis infections in cows and can be administered either while the cow is lactating (lactating cow therapy, LC) or when the cow is dried off (dry cow therapy, DC).

   ·      Formulations for lactating cow therapy are generally designed to provide fast and effective release of an active agent to maintain effective concentrations of active agent throughout the mammary gland during the treatment period, while minimising the withholding period after the final administration of the formulation.[143]  These formulations should be of a viscosity that facilitates effective dispersion of the active into the milky fluid, but viscous enough not to drip out during administration.[144] 

   ·      Formulations for dry cow therapy are typically slow release preparations, and either a poorly soluble salt of an antimicrobial agent is used, or the formulation is such that the release of the antimicrobial is relatively constant.[145]

   ·      Intramammary mastitis formulations can be formulated as oil formulations.  Most oil formulations consist of a suspended finely milled active agent and thickening or suspending agents, such as hydrogenated castor oil, aluminium mono- or distearate, colloidal silica and waxes.[146]  Such formulations may also include emulsifying agents (i.e. surfactants) or stabilising agents.[147]  Suitable oils include: vegetable oils such as peanut oil, paraffin oils and medium chain triglycerides.[148]

   ·      A formulation dictates the rate at which active agent is released, with a more viscous formulation associated with slower release.[149]

   ·      Cloxacillin sodium is a particularly well known antibacterial for use in intramammary formulations.  Combinations of actives may also be used.[150]

   [143] Exhibit SWP-5 at page 200, Exhibit JRP-6 at page 247, Pippia 1 at [143], Page 1 at [53], Exhibit JRP-3 at page 1957.

   [144] Pippia 1 at [46], Page 1 at [361], Bunt at [44].

   [145] Exhibit JRP-6 at page 248, Exhibit JRP-3 at page 1957.

   [146] Exhibit SWP-5 at page 201, Page 1 at [69].

   [147] European Pharmacopoeia, 7^th edition, Strasbourg: European Directorate for the Quality of Medicines and Healthcare , 2010 (Exhibit JRP-7) at page 714, Page 1 at [69].

   [148] Exhibit JRP-5 at page 201, Pippia 1 at [53], Page 1 at [69].

   [149] Specification, page 21, lines 7-9; Pippia 1 at [61]; Bunt at [63].

   [150] Exhibit JRP-6 at page 247-248; Gruet, P. et al. (2001) ‘Bovine mastitis and intramammary drug delivery: review and perspectives’, Advanced Drug Delivery Reviews, vol. 50, pages 245-259 (Exhibit SWP-3) at page 252-254; Page 1 at [61].

4. A broad range of viscosities are known in commercially available intra-mammary mastitis infusion products – from low viscosity formulations to viscous pastes.[151]  However, as previously noted, a formulation which is thick at rest may exhibit low viscosity at high shear.

   [151] Exhibit JRP-5 at page 200.

5. The use of colloidal silica, particularly hydrophobic colloidal silica, in intramammary formulations was a subject of disagreement between the parties.  It is a fact that colloidal silica may be hydrophobic or hydrophilic.  Unmodified colloidal silica is hydrophilic[152] and hydrophobic colloidal silica may be obtained by surface treatments.[153]  The contemporaneous documents referring to colloidal silica in the main refer to it generically, and not to whether it is hydrophilic or hydrophobic.  The experts in this proceeding referred only to generic colloidal silica prior to reviewing documents.  This raises a question of how the generic term is understood and used – that is, as any form of colloidal silica, or as the “native” unmodified hydrophilic colloidal silica.

   [152] Bunt at [220].

   [153] Exhibit SWP-7 at page 190.

6. Mr Pippia (with whom Dr Page agreed[154]) indicated that colloidal silica, particularly hydrophobic colloidal silica, was a typical thickening agent for oily formulations, although his evidence in this regard was given following review of the present specification:

   “It is well known that various types of colloidal silica are available and can be used to provide differences in release rates and viscosities.  Hydrophobic colloidal silica is also well-known for use as a viscosity modifying agent for oily based formulations.”[155]

   “I consider hydrophobic colloidal silica was a well-known type of colloidal silica routinely used in veterinary formulation development and is often used in commercial products.  Hydrophobic colloidal silica has been successfully used to modify the viscosity of oily suspensions, including intramammary products for treating mastitis… Orbenin LA contains hydrophobic colloidal silica. … I am also familiar with hydrophobic colloidal silica, and it is a standard agent I keep in stock in the laboratory, and was so before 2012.  I consider it is one of the routine viscosity modifying agents.”[156]

   [154] For example, Page 1 at [170], [177], [191].

   [155] Pippia 1 at [158].

   [156] Pippia 1 at [201].

7. I think it is fair to understand Mr Pippia’s evidence as meaning he understands generic references to colloidal silica to mean any form of colloidal silica, including hydrophobic colloidal silica,[157] despite the elaboration on this meaning being given after review of the present specification.

   [157] For example, Pippia 1 at [271], [280].

8. Dr Bunt’s evidence suggests that he understood generic references to colloidal silica to refer to hydrophilic colloidal silica, and that this was the most commonly used form.[158]  Dr Bunt disagreed that colloidal silica is commonly used in intramammary compositions:

   “In my experience, colloidal silica would not be commonly used in mastitis formulations.  Where it was used, it would be used as a thickening agent.  In my mind its use would be inconsistent with the invention of developing a low viscosity formulation.”[159]

   “Mr Page believes that hydrophobic colloidal silica is commonly used as a thickener.  It is not.  Only two examples in the evidence actually use it.  …Mr Page seems to suggest that I have intentionally omitted reference to colloidal silica as a thickener …  I have omitted it not because I am unaware of its use, but because in my work formulating veterinary compositions I do not like to use it.  It certainly isn’t commonly used as Mr Page states, otherwise I can only assume that he would have identified a greater number of commercial examples where it is used for that purpose.”[160]

   [158] For example, Bunt at [266], [280], [580], [581]

   [159] Bunt at [69].

   [160] Bunt at [833].

1. For completeness, I note that Mr Pippia observed a release profile for the hydrophobic colloidal silica sample similar to that shown in Figure 5 of the present application.[206]  While Bayer criticised the conditions of Mr Pippia’s measurement,[207] it appears to be not dissimilar to the approach taken by inventors of the present application to test similar compositions.[208]  In any event, it seems uncontroversial that release from compositions produced according to D4 would be under diffusion control.

   [206] Pippia 2 at [13]-[16].

   [207] Bayer’s written submission at [166.18]-[166.20].

   [208] Pippia 3 at [176]-[177].

2. Given the oil, surfactant and active of Example 3, and the viscosity of the composition prepared by replacement of 12-hydroxystearin with hydrophobic colloidal silica, it follows that claims 1-3 and 7-23 lack inventive step in light of D4.

3. D4 states that “the most useful penicillins are normally ampicillin, cloxacillin, and penicillin mixtures such as ampicillin/-cloxacillin, amoxycillin/cloxacillin; and sodium and potassium salts thereof.”[209]  Noting that combinations of actives in intramammary formulations were well known, I think it is reasonable to conclude that a skilled person would routinely use these actives and combinations when preparing formulations according to D4 and thereby arrive at the subject matter of claim 4.

   [209] D4 at column 3, lines 7-10.

4. Claim 5 defines a number of specific active agent combinations: amoxicillin and clavulanic acid, penicillin active and aminoglycoside, cloxacillin and tylosin, and an antibiotic and a non-steroidal anti-inflammatory drug.  While D4 does not disclose or suggest these combinations itself, after describing suitable antibiotic active agents known for use in treating mastitis, Dr Page, before reviewing the present specification, stated:

   “The compositions can include other active agents such as anti-inflammatory agents (e.g. prednisolone), which are used to subdue the inflammatory response, or other such combinations to prevent enzymatic degradation of the antibiotic such as clavulanic acid, which is commonly used with amoxicillin to inhibit enzymes (beta lactamases) breaking down the β-lactam ring that is essential to the activity of this antibiotic.”[210]

   [210] Page 1 at [67].

5. Dr Bunt also identified active ingredients typically used in mastitis treatment as including clavulanic acid and prednisolone.[211]  Mr Pippia said that “the combination of an antibiotic active agent with a non-antibiotic active agents is standard and routine in the development of veterinary formulations, including intramammary mastitis infusion compositions.”[212]  I consider that the evidence supports a conclusion that a skilled person would, as a matter of routine, arrive at a combination of amoxicillin and clavulanic acid as defined in claim 5.  

   [211] Bunt at [48].

   [212] Pippia 1 at [327].

6. D4 refers to the actives being “finely milled”,[213] and Mr Pippia indicated that he would “typically choose a micronised form of the active agent.”[214]  I consider that claim 6, which requires that the active agent is micronised, lacks an inventive step. 

   [213] D4 at column 4, lines 1-5.

   [214] Pippia 1 at [45]. Dr Bunt noted that D4 does not disclose or suggest the use of micronised active agents, but did not disagree with Mr Pippia’s comment.

7. Claim 24 defines a specific protocol for the manufacture of the claimed composition: mixing of the oil and surfactant, dispersion of the active, and then addition of the colloidal silica.  Mr Pippia indicated that this was a “standard and routine approach for preparing veterinary formulations”, as did Dr Page.[215]  D4 indicates that the preparation of the disclosed compositions will be “in the usual manner for suspending penicillins in oily vehicles”, and “in a preferred process, the oily vehicle is first sterilised and then a thickening agent added to it with appropriate heating and mixing.”  The chosen semi-synthetic penicillin is then added with appropriate mixing and milling to give the desired suspension.[216]  In the examples of D4 the active is added after the thickening agent.  This is also the case in D10, which also relates to penicillins in oily vehicles.  However, US 5122377 A (D12) discloses preparation of a penicillin suspension wherein Miglyol and a surfactant are combined, amoxicillin is added, and colloidal silica (hydrophilic) is then added with mixing.[217]  On balance, I am satisfied that the evidence establishes that the process of claim 24 is a standard process for the suspension of penicillins in oily vehicles, and would be adopted as a matter of routine.

   [215] Pippia 1 at [361], Page 1 at [228].

   [216] D4 at column 3, lines 17-24.

   [217] D12 at Example 2, column 4.

8. The compositions of D4 are intended for the treatment of mastitis in lactating cows, and the document indicates that a single dose of the composition “will normally contain 1 to 10 gm., preferably 3 to 8 gm., of the suspension”[218] and “it is usual practice to repeat the dose at least once (preferably three doses are given), each dosing taking place after milking.”[219]  Mr Pippia indicated that the dosage regimes defined in claim 26 are “routine when treating mastitis in lactating cows”.[220]  I am satisfied that a skilled person would arrive as a matter of routine at the methods of treatment defined in claims 25-27 and use of claim 28 in light of D4.

   D9

   [218] D4 at column 3, lines 36-37.

   [219] D4 at column 3, lines 48-50.

   [220] Pippia 1 at [367].

9. D9 relates to fluorinated cephalosporin antibiotics and their use in preventing or treating mastitis.  D9 indicates that disclosed compounds may be used in both lactating cow and dry cow therapy[221] and states: 

   “When the compound is to be used in a veterinary formulation for preventing or treating mastitis, the formulation is preferably one that can be administered by intramammary infusion.  For this type of infusion, the compound may be formulated in an oily base, e.g., a vegetable oil such as peanut oil or a non-vegetable oil such as mineral oil.  The formulation may include a thickening agent and optionally also a surfactant.”[222]

   [221] D9 at column 2, lines 35-44.

   [222] D9 at column 3, lines 15-22.

10. D9 exemplifies formulation of the disclosed compounds in peanut oil with no further additives indicated.  Merial submitted that the claimed invention is obvious in light of D9 because colloidal silica is a conventional thickening agent previously used in intramammary infusions and the viscosity of a formulation made in accordance with D9 would be less than 1000 mPas at a shear rate of 100 1/s and a temperature of 20°C.[223]

    [223] Merial’s written submissions at [157].

11. The question to be considered is what a person skilled in the art would do as a matter of routine given this document and the common general knowledge.  In this regard, I do not understand the teaching of D9 in relation to the formulation to extend beyond what was common general knowledge in the art.  Accordingly, for the same reasons as it has not been established that the claims lack inventive step in light of the common general knowledge, lack of inventive step in light of D9 is not made out on the evidence.  I am not satisfied the evidence establishes that a person would, as a matter of routine arrive at a formulation falling within the scope of the present claims when following the teaching of D9.

    D10

12. D10 relates to the treatment of mastitis with a combination of rifampicin and an isoxazolyl penicillin.  The document indicates that for intramammary administration, “the ingredients may be suspended in an oily vehicle, with an appropriate thickening agent.”[224]  D10 exemplifies a lactating cow composition, comprising 13.4% active (sodium cloxacillin and rifampicin), 0.75% 12-hydroxystearin, 0.125% polysorbate 80, 0.125% sorbitan monooleate and 0.02% butylated hydroxyanisole in fractionated coconut oil, and a dry cow composition, comprising 33.4% active (benzathine cloxacillin, rifampicin), 4.0% 12-hydroxystearin, 1.0% colloidal silica, and 0.02% butylated hydroxyanisole in arachis oil.[225]

    [224] D10 at page 3, lines 21-23.

    [225] D10 at pages 6-7.

13. Merial submitted that it would be obvious to substitute hydrophobic colloidal silica for the 12-hydroxystearin in the lactating cow composition since both were known to be suitable thickening agents, with colloidal silica in fact being used in the dry cow composition, and that the resulting composition would have a viscosity within the claimed parameters.[226]

    [226] Merial’s written submissions at [163].

14. Mr Pippia indicated that he considered the claimed invention obvious in light of D10 “as the combination of components claimed in claim 1 are standard and routine for the development of a number of typical pharmaceutical or veterinary formulations.”[227]  Mr Page made similar comments, and noted that 12-hydroxystearin in Example 1 “can be readily replaced with colloidal silica”.[228]  While I accept that the thickener in D10 could be replaced with another thickener, I am not satisfied that the evidence establishes that a skilled person would be directly led to modify Example 1 by substitution of 12-hydroxystearin with another thickener, such as hydrophobic colloidal silica, and arrive at the subject matter of the present claims.  I am not satisfied that Merial has established that the claims lack inventive step in light of D10.

    D17

    [227] Pippia 1 at [303].

    [228] Page 1 at [275].

15. I have discussed the disclosure of D17 above and found that certain of the claims lack novelty in light of its disclosure.  As I have already said, D17 does not refer to intramammary formulations.  While there is, post-Raising the Bar, no express requirement in section 7 for inventive step documents to be ascertained or regarded as relevant, the question remains whether a skilled person faced with the same problem would have taken routine steps to arrive at the claimed invention.[229]  Accordingly, if the skilled person would not consider D17 applicable to the development of intramammary formulations, they would not be expected to take routine steps from this document in order to develop such formulations.  This is notwithstanding the conclusion above regarding novelty.

    [229] The Explanatory Memorandum, Intellectual Property Laws Amendment (Raising the Bar) Bill 2011 at page 43.

16. Merial submitted that the skilled addressee would appreciate D17 as relevant to the development of intramammary mastitis formulations “since it is directed to stabilising active agents in oily suspensions to reduce sedimentation and facilitate application as a single dose.”[230]  Specifically, Merial submitted that:

    “it would be obvious to the skilled addressee that the composition in D17 could be used to make an oily formulation for intramammary infusion using an oily vehicle (such as a medium chain triglyceride), an antibiotic, hydrophobic colloidal silica, and surfactants (using, for example, Example 8 as a base formulation but using cloxacillin).  This formulation would inherently have a controlled release, and a viscosity falling within the claim.”[231]

    [230] Merial’s written submissions at [164].

    [231] Merial’s written submissions at [167].

17. D17 on its face indicates broad suitability of the compositions for administration:

    “The medicaments described herein are suitable in principle for all possible modes of administration such as, for example, dermal, oral, rectal, vaginal or nasal administration.  They are particularly suitable for local administration into the auditory canals.”[232]

    [232] D17 at [0116].

18. Mr Pippia considered the disclosure of D17 to be applicable to the development of compositions for intramammary infusion:

    “The compositions of D17 are versatile and can be administered via various routes to a variety of different animals. … to me D17 teaches the preparation of an oily suspension comprising an active agent and oily base which is stabilised by the inclusion of hydrophobic colloidal silica and a surfactant. …

    …I consider D17 is a highly relevant document to consider when developing intramammary infusion formulations. … D17 is directed to stabilising active agents in oily suspensions with the aim of reducing sedimentation.  Sedimentation is also undesirable for intramammary products which are often administered via single use syringes. …as D17 teaches that the oily suspensions are suitable for all modes of administration, including rectal and vaginal, I consider persons skilled in the field, would consider the oily suspensions of D17 would also be inherently suitable for intramammary infusion…

    …D17 also teaches a variety of antibiotics can be stabilised by the oily suspension, and lists a variety of examples including penicillins and cephalosporins, which are classes of actives also used to treat mastitis in lactating cows (see Exhibit JRP-8).  D17 also teaches that the components of the oily suspension can be present in varied amounts, including that the active agent can be present in the oily suspensions in an amount up to 6% by weight (see paragraph [0079]) which provides dosage relevant to current commercial intramammary mastitis infusion compositions… As such, it would be routine to develop an oil-based intramammary mastitis infusion formulation based on the teaching in D17, which is of low-viscosity and certainly likely to be below the relatively high threshold required by claim 1.”[233]

    [233] Pippia 1 at [376]-[378].

19. Dr Page had a similar view to Mr Pippia,[234] noting that “it would be a simple case of following D17 and selecting the amount of active and excipients to achieve an oily suspension suitable for intramammary infusion.”[235]  He also noted that:

    “One of the main issues routinely addressed by persons skilled in the field of developing intramammary infusion formulations is the preventing or reducing of sedimentation.  In view that this is a problem addressed by D17, I would have also considered D17 together with any one or more of D1 to D16 … when developing controlled release formulations such as intramammary infusion formulations.”[236]

    [234] Page 1 at [161], [163], [306], Page 2 at [114].

    [235] Page 1 at [163].

    [236] Page 1 at [362].

20. I think on a fair reading of Dr Bunt’s evidence, he did not consider D17 relevant to the development of an intramammary formulation:

    “In my view, D17 teaches how to provide a formulation for treating conditions of the ear in cats and dogs.  The composition must be sufficiently viscous that it does not shake out of the ear of the animal when shaken.  The composition must be sufficiently viscous that sedimentation is largely prevented.”[237]

    “The release profile in the ear of a cat or dog is entirely different to the controlled release profile intended by the opposed application, which is directed to the intramammary environment.”[238]

    [237] Bunt at [556].

    [238] Bunt at [605].

21. Dr Bunt also commented on nature of the examples in D17:

    “The maximum quantity of combined active ingredients used in the examples of D17 is around 1.2% w/w.  I believe that the use of larger amounts of active would interfere with the stability of the suspension.”[239]

    “D17 uses a very precise ratio of colloidal silica to surfactant of 64:1 in each of the examples to achieve the desired stability, and a very low amount of surfactant.  A person reading D17 would believe that these parameters are critical to obtain the benefits in D17.”[240]

    [239] Bunt at [484].

    [240] Bunt at [694].

22. However, Dr Bunt did not provide any particular reason for considering that the stability would be impaired by the use of a larger amount of active, or why a belief that a precise ratio of colloidal silica to surfactant was required would discourage a skilled worker following the teaching of D17. 

23. I am mindful of the fact that each of the declarants was somewhat familiar with the invention (owing to their provision of evidence in relation to the corresponding proceeding in New Zealand) prior to giving evidence in relation to D17.[241] This necessarily effects the weight that can be afforded to their evidence,[242] and seems to me particularly problematic in the present circumstances, as a finding of lack of inventive step relies heavily on the evidence of the declarants given that the document on its face does not relate to intramammary infusions. That is, D17 states:

    “The anti-infective is typically employed in the proportion of 0.001-6% by weight, preferably 0.01-1.0% by weight, particularly preferably 0.1-0.8% by weight, based on the finished medicament.”[243]

    Accordingly, it seems to me that there is a clear teaching in D17 on its face towards a relatively low level of anti-infective agent, below the level generally considered to be of relevance to intramammary infusions.[244]

    [241] Bunt at [76]-[77], Exhibit CB-30, Exhibit CB-34.

    [242] See, e.g. Metso Sweden AB v Outotec Pty Ltd [2019] APO 25.

    [243] D17 at [0079].

    [244] Bunt at [63].

24. I appreciate that D17 addresses a problem which is common to oily suspensions, and it may well be that a skilled person would arrive at the claimed invention as a matter of routine in light of this document, but particularly in the absence of any reference to intramammary administration in D17 (despite the references to other administration routes) the hindsight character of the evidence as to whether a skilled person would take routine steps from D17 in addressing the problem of providing controlled release formulations suitable for use as a mastitis treatment for a lactating cow is troubling, and in these circumstances I am unable to be satisfied that the claims lack inventive step in light of D17.

    Conclusion

25. Claim 1-28 lack inventive step in light of D4.

    Conclusion

26. Claims 1, 2, 4, 7, 8, 10-15, 18-21 and 28 are not novel in light of D17.  Claims 1-28 lack inventive step in light of D4. 

27. I will provide Bayer a period of time within which to file amendments to overcome the identified deficiencies.

    Costs

28. It is usual in matters before the Commissioner that costs follow the event.  Bayer submitted that in considering the question of costs, I should have regard to Merial’s late abandonment of multiple grounds of opposition and particulars (i.e. many of the documents and grounds in relation to which evidence was prepared were not pressed).  Merial submitted that it should not be penalised for streamlining its case for hearing and that costs should follow the event.

29. It is true that both parties provided evidence in relation to matters ultimately not pressed by Merial at the hearing.  However, it is not unreasonable, and is indeed preferable, for an opponent to focus its case prior to the hearing.  It is of course also preferable for an opponent to amend its statement of grounds and particulars accordingly at an early opportunity.

30. In the present circumstances, while I acknowledge that Bayer undertook preparation for the hearing and prepared evidence in relation to grounds and particulars ultimately not pursued by Merial, I am not convinced that Merial’s behaviour is such that it is appropriate to depart from the usual approach, and so I will award costs in line with the event.

    Dr S. J. Smith
    Delegate of the Commissioner of Patents

    Annex A

    1. A composition,
    the composition including a therapeutically effective amount of at least one active agent, and a base configured to provide a controlled release of the at least one active ingredient, the base including,
    an amount of colloidal silica wherein the colloidal silica is a hydrophobic type; at least one oil; and at least one surfactant,
    wherein the active agent is an antibiotic;
    wherein the viscosity of the composition is below 1000 mPas at a shear rate of 100 1/s and at a temperature of 20°C; and

    wherein the colloidal silica is dispersed in the oil.

    2. The composition as claimed in claim 1 wherein the antibiotic is selected from the group consisting of a beta-lactam, penicillin, cephalosporin, aminoglycoside, quinolones, sulphonamides, tetracyclines and macrolide antibiotic.

    3. The composition as claimed in claim 1 wherein the antibiotic is selected from the group consisting of cloxacillin or a functional derivative thereof, tylosin or a functional derivative thereof, cephapirin or a functional derivative thereof, and combinations thereof.

    4. The composition as claimed in claim 1 wherein the composition includes at least two active agents, wherein the active agents are antibiotics or at least one antibiotic and at least one non-antibiotic active agent.

    5. The composition in claim 4 wherein the active agent combination is:
    - amoxicillin and clavulanic acid;
    - penicillin active agent and aminoglycoside;
    - cloxacillin and tylosin;

    - an antibiotic and a non-steroidal anti-inflammatory drug.

    6. The composition as claimed in any one of claims 1 to 5 wherein the active agent is micronised.

    7. The composition as claimed in any one of claims 1 to 6 wherein the colloidal silica is fumed colloidal silicon dioxide.

    8. The composition as claimed in any one of claims 1 to 7 wherein the concentration of colloidal silica is between 0.1-5% w/w.

    9. The composition as claimed in any one of claims 1 to 8 wherein the concentration of colloidal silica is between 1-3% w/w.

    10. The composition as claimed in any one of claims 1 to 9 wherein the surfactant has an HLB between 0.5 and 30.

    11. The composition as claimed in any one of claims 1 to 10 wherein the surfactant has an HLB between 4 and 16.

    12. The composition as claimed in any one of claims 1 to 13 wherein the surfactant is an anionic, cationic, amphoteric or non-ionic surfactant.

    13. The composition as claimed in any one of claims 1 to 12 wherein the surfactant is a non-ionic surfactant and is selected from the group consisting of sorbitan esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene castor oil derivatives, polyoxyethylene stearates, polyethylene oxide monooleate and combinations thereof.

    14. The composition as claimed in any one of claims 1 to 13 wherein the concentration of surfactant is between 0.01 to 10 % w/w.

    15. The composition as claimed in any one of claims 1 to 14 wherein the ratio of colloidal silica to surfactant in the base is between 1:100 and 500:1.

    16. The composition as claimed in any one of claims 1 to 15 wherein the ratio of colloidal silica to surfactant in the base is between 1:5 and 6:1.

    17. The composition as claimed in any one of claims 1 to 16 wherein the base includes more than one surfactant.

    18. The composition as claimed in any one of claims 1 to 17 wherein the viscosity of the oil is between 1 to 100 mPas at 20°C.

    19. The composition as claimed in any one of claims 1 to 18 wherein the viscosity of the oil is less than 40 mPas at 20°C.

    20. The composition as claimed in any one of claims 1 to 19 wherein the oil is selected from the group consisting of medium chain triglycerides, light liquid paraffin, ethyl oleate and sesame oil.

    21. The composition as claimed in any one of claims 1 to 20 wherein the density of the oil is between 0.80 and 0.99 g/cm3.

    22. The composition as claimed in any one of claims 1 to 21 wherein the composition has a viscosity below 300 mPas at a shear rate of 100 1/s and temperature of 20°C.

    23. The composition as claimed in any one of claims 1 to 22 wherein the composition has a viscosity below 150 mPas at a shear rate of 100 1/s and temperature of 20°C.

    24. A method of manufacturing a composition as claimed in any one of claims 1 to 23 including the steps of:
    a) mixing the oil and surfactant in a container to form a homogenous oil mixture;
    b) dispersing the active agent in the oil mixture; and
    c) subsequently adding the colloidal silica to the oil mixture.

    25. A method of treating a non-human animal in need thereof with a composition as claimed in any one of claims 1 to 23 wherein the method includes the step of administering the composition to the animal by intramammary infusion.

    26. The method as claimed in claim 25 including a dosage regime of between 1 - 6 doses of 5 g formulation composition over a period of 0 to 120 hours administered 3 x 24 hours or 6 x 24 hours.

    27. The method as claimed in either of claims 25 or 26 for the treatment or prevention of mastitis during the lactation period of a non-human animal.

    28. A use in the manufacture of a composition as claimed in any of claims 1 to 23 for the treatment or prevention of a pre-clinical or clinical mastitis in an animal in need thereof.

    
    

Example 7: 9.18% cloxacillin sodium, 2.25% Aerosil R972 Pharma, 0.05% PEG12Oleate, 88.52% Miglyol 812.
Example 8: 9.18% cloxacillin sodium, 2.25% Aerosil R972 Pharma, 0.05% Span 80, 88.52% Miglyol 812.
Example 9: 9.18% cloxacillin sodium, 2.25% Aerosil R972 Pharma, 0.10% Span 80, 88.47% Miglyol 812.
Example 10: 9.18% cloxacillin sodium, 2.25% Aerosil R972 Pharma, 0.50% Span 80, 88.07% Miglyol 812.
Example 11: 9.18% cloxacillin sodium, 2.25% Aerosil R972 Pharma, 1.00% Span 80, 87.57% Miglyol 812.