Merial Limited v Zoetis LLC - [2013] APO 59

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Merial Limited v Zoetis LLC [2013] APO 59

Patent Application:  2003283757
Title:Veterinary Compositions for Treating Mastitis
Patent Applicant:  Zoetis LLC
Opponent:Merial Limited
Delegate:Ms Nicole Howard
Decision Date:  15 November 2013
Hearing Date:  16 May 2013 in Melbourne
Catchwords:  PATENTS – section 59 – opposition to grant of a patent – treatment of mastitis – combination claims – lack of novelty despite extant inventive step – lack of manner of manufacture – costs awarded against applicant
Representation:  Patent applicant: Patrick Flynn of Counsel, instructed by Tim Jackson Patent Attorney of Baldwins, Auckland
Opponent:Marcus Caulfield, Patent Attorney of FB Rice, Melbourne

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2003283757
Title:Veterinary Composition for Treating Mastitis

Patent Applicant: Zoetis LLC
Date of Decision: 15 November 2013
DECISION
The opposition succeeds on the grounds of novelty and manner of manufacture.
I allow Zoetis LLC two months to propose amendments to the specification.
I award costs according to Schedule 8 against Zoetis LLC.
REASONS FOR DECISION
Background

Patent application 2003283757 (‘hereafter the application’) was filed under the PCT (WO2005/051352) by Pfizer Limited on 8 December 2003. It claims priority from GB 0229642.4 filed on 20 December 2002. Following amendments the specification was advertised accepted on 18 December 2009.

A notice of opposition to grant of a patent was filed on 21 April 2010 by Merial Limited, (hereafter ‘Merial’), followed by a statement of grounds and particulars (hereafter ‘SGP’) on 21 July 2010.
Further minor amendments to the claims were proposed on 15 May 2013 (one day before the hearing). At the hearing it was agreed by all parties that opposition proceedings should be based on the specification including these proposed amendments. Any findings in this decision are equally applicable to the specification as accepted. Following the hearing the applicant has been changed to Zoetis LLC (hereafter 'Zoetis') due to an assignment. I will refer to the applicant simply as Zoetis throughout this decision.

Evidence was completed on 19 December 2011. Dr Whittem and Mr Page are the primary declarants. Both have extensive experience in the field of veterinary science and veterinary pharmacology and are considered qualified to comment on the present invention.
Grounds of Opposition
The SGP raised several grounds pursuant to section 59 of the Patents Act 1990. At the hearing Merial expressly limited their grounds of opposition to lack of novelty, lack of inventive step and failure to comply with manner of manufacture requirements.
The specification
The description
The specification describes veterinary compositions and methods of their use for the prevention and treatment of mastitis in mammals, more particularly cows. The ‘compositions’ comprise two parts either separately or in a single formulation. Generally the two parts will be administered as two separate formulations.

The first part is a teat seal formulation comprising a gel base and a nontoxic heavy metal salt in the base in an amount of at least 30% by weight of the gel base. The preferred heavy metal salt is bismuth sub-nitrate and the preferred concentration of heavy metal salts is between 40% to 80%. The preferred gel base is based on aluminium stearate.
The second part is an oil-based antibiotic formulation preferably based on a vegetable oil. Most preferred is peanut oil and/or hydrogenated peanut oil. The antibacterial agent may be a beta-lactam antibiotic and most preferred is cloxacillin.

Bacterial infections via the teats of cows are the most common cause of mastitis. Previously, treatments have included antibacterial washes for cleaning the teats and the application of film-forming compositions which can be applied to the teat to provide a barrier to the entry of bacterial agents. Other approaches involve the provision of a physical barrier within the teat canal in combination with an antibacterial formulation to form a plug and treat mastitis. Particular reference is made to prior art documents GB 2 273 441 (equivalent of D1) and GB 2 273 443 (equivalent of D2). It is explained that D1 and D2 disclose the use of an antibacterial formulation and a seal formulation for the treatment of mastitis in cows. In D1, the seal formulation comprises a gel base and a non-toxic heavy metal salt in the base whereas in D2 the seal formulation comprises a polyethylene gel and a non-toxic heavy metal salt. The seal formulation components of D1 and D2 are expressly stated as being suitable for use in the present application. According to the present specification, the antibiotic aspect of D1 and D2 is provided in an aqueous formulation.
The specification explains that the co-administration of the two parts leads to an improvement in seal effectiveness and improved compatibility with the seal in the teat canal relative to aqueous formulations, thereby improving consumer health and animal welfare outcomes. While the reason for this improved performance is not fully understood it is believed that the physical properties such as the density and viscosity of the oils are in some way connected.
The specification finishes with an assessment of the integrity of the veterinary formulations by administration into the quarters of a dry (non-lactating) cow. The cow was dosed with three different vegetable oil-based intra-mammary antibiotic formulations, each placed in a separate teat. The teats were then sealed with a 65% bismuth-based teat seal (described in formulation 2A4 of D1). The fourth teat did not receive any antibiotic formulation. The teats were assessed by X-ray analysis at days 1, 7, 14 and 21 and the radio-opacity of the heavy metal salt assessed as an indicator of seal integrity and amount of seal within the desired area of the teat canal. The results are shown in Table 1, reproduced below.
Table 1

TEAT 1 TEAT 2 TEAT 3 TEAT 4

ANTIBIOTIC FORMULATION None Formulation A Formulation B Formulation C

AVERAGED AREA OF OPACITY 1.0 1.1 1.7 1.6

Formulation A contained peanut oil and hydrogenated peanut oil. Formulations B and C contained peanut oil. The specification points out that co-administration of the vegetable oil-based antibiotic formulation in conjunction with the seal formulation led to an increase in the amount of seal present at the base of the teat canal, and that despite an expectation that this might disperse the oil-based seal, an improvement over the prior art was observed.
The claims as proposed to be amended
The accepted specification including the proposed amendments ends with 12 claims recited as follows:
1. A veterinary composition for intra-mammary use in non-human animals comprising an oil-based antibacterial formulation and a separate oil-based seal formulation, wherein the seal formulation comprises a gel base and a non-toxic heavy salt in the base in an amount of at least 30% by weight of the gel base.
2. A veterinary composition comprising an oil-based antibacterial formulation and an oil- based seal formulation formulated as a single formulation which may be administered to the teat canal of a non-human animal directly in one step, wherein the seal formulation comprises a gel base and a non-toxic heavy metal salt in the base in an amount of at least 30% by weight of the gel base.
3. A composition as claimed in claim 1 or 2, wherein the heavy metal is bismuth.
4. A composition as claimed in claim 3, wherein the heavy metal salt is bismuth sub-nitrate.
5. A composition as claimed in any one of claims 1 to 4, wherein the heavy metal salt is present in an amount of from 40% to 80% by weight of the gel base.
6. A composition as claimed in any one of claims 1 to 5, wherein the co-administered oil-based antibiotic formulation is based on a vegetable oil.
7. A composition as claimed in any one of claims 1 to 6, wherein the gel base is based on aluminium stearate.
8. A composition as claimed in claim 6, wherein the vegetable oil is peanut oil and/or hydrogenated peanut oil.
9.A composition as claimed in any one of claims 1 to 8, wherein the antibacterial agent is a beta-lactam antibiotic.
10. A composition as claimed in claim 9, wherein the antibacterial agent is cloxacillin.
11. Use of a veterinary composition comprising an oil-based antibacterial formulation and an oil-based seal formulation either separately or in single formulation as defined in any one of claims 1 to 10 in the manufacture of a medicament for the treatment or prophylaxis of mammary disorders in non-humans.
12. A method for the treatment or prophylaxis of mammary disorders in non-human animals the method comprising administering to one or more teat(s) of the non-human mammal a veterinary composition comprising an oil-based antibacterial formulation and an oil-based seal formulation either separately or in a single formulation as defined in any one of claims 1 to 10.
Claim Construction
At first blush claim 1 is directed to a ‘composition’, which taken in its ordinary use would mean the various components would be in admixture or in some kind of integrated structural arrangement and that the combined effect of the components in use would be assured. However, this is not the case here. The claim clearly contemplates an antibacterial agent and a separate seal formulation. Consequently, the composition is made up of two separate formulations.
The ‘composition’ is for intra-mammary use, so it may be argued that this foreshadows some kind of intention to use, or prospective use of the formulations in combination, I do not see this as providing any limitation on the claim except that the formulations must be suitable for intra-mammary use. The claim is not directed to the actual use of the formulations or limited to the formulations when combined as a composition in situ.
I construe claim 1 as defining two separate formulations per se that may be used together as a composition wherein the formulations are suitable for intra-mammary use. I also note that claim 1 is not limited by any particular outcomes in use.

Claim 2 is also directed to a ‘composition’, however the two formulations are combined as a single formulation. The composition may be administered to the teat canal of a non-human animal directly in one step. I construe claim 2 as defining a single formulation that is merely suitable to be administered to the teat canal of a non-human animal in one step. Since the specification does not provide guidance on what is contemplated by a ‘single formulation’, the formulation is construed as a mixture or some kind of structural arrangement suitable for single step administration such as a syringe containing an oil-based antibiotic in the front portion and a seal formulation in the back formulation (the latter being typical). Again, I note the absence of any limitations on particular results in use.
Claim 11 is drafted in ‘Swiss style’. Australian practice in the construction of these claims is recited in the Manual of Practice and Procedure as follows:
The typical form of a Swiss claim is:
“The use of (substance X) for the manufacture of a medicament for the therapeutic and/or prophylactic treatment of (medical condition Y).”
Swiss claims are construed as defining the manufacture of a medicament, wherein the medicament is intended for a specified medical treatment. The novelty and inventiveness of Swiss claims is considered to derive from the new medical use and not from the manufacture of the medicament. Therefore, a prior art disclosure of a method of making the medicament will not in itself anticipate a Swiss claim. In order to anticipate a Swiss claim, a citation must disclose both a method of preparing the medicament and the specific treatment claimed. (This approach is consistent with that followed in British (John Wyeth & Brother Ltd's Application [1985] RPC 545, Bristol-Myers Squibb Co. v Baker Norton Pharmaceuticals Inc. [1999] RPC 253) and New Zealand decisions (Pharmaceutical Management Agency Ltd. V Commissioner of Patents (Pharmac) (2000) NZCA 330)).
Consistent with this practice, I construe claim 11 as defining the manufacture of a medicament intended for use in the treatment or prophylaxis of mammary disorders in non-humans.

The construction of the remaining claims is readily apparent and does not require further elaboration here.
Onus of proof
In proceedings such as these before the Commissioner, the onus rests with the opponent to clearly establish its case in reaching a conclusion on any issue. In F. Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283, Emmett J of the Federal Court found that in opposition proceedings, the Court (and by implication the Commissioner of Patents in her role as a tribunal) should be "clearly satisfied that the patent, if granted, would not be valid". Where questions of fact such as obviousness and existence of invention are involved "the grant should not be refused unless it has been clearly shown that the grounds of opposition have been clearly made out" (Montecatini v Eastman Kodak (1971) 45 ALJR 593).
Novelty
All documents pressed under the ground of novelty are clearly published well before the requisite priority date. They are:
·NZ 258 199 (Bimeda Research and Development Limited) ‘Aqueous antibiotic composition for veterinary use’ (and GB equivalent GB 2 273 441) published 29 January 1997 (D1)
·GB 2 273 443 (Bimeda Research and Development Limited) ‘Veterinary composition for treating mastitis’ published 22 June 1994 (D2)
·Moorepark 25^th Anniversary Publication, Part II,: Animal Health and Machine Milking published 1986 (D5)
·Meaney, W J, ‘Dry Period Teat Seal’ The Veterinary Record 99:30, published 1976 (D6)
·Meaney, W J ‘Effect of a dry period teat seal on bovine udder infection’, Irish Journal of Agricultural Research 16(3) 293-299 published 1977 (D7)
·NZ 336 153 (Bimeda Research and Development Limited) ‘Anti-infective free intramammary veterinary composition (and US equivalent 6254881) published 25 June 1998 (D13)
The law on novelty
The basic test for novelty is the “reverse infringement” test as stated in General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd [1972] RPC 457 at pages 485, 486:
'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'.
In applying this test regard must be given to the level of disclosure in the prior publication. As stated in Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR at 517:
'It is well accepted that the prior art must disclose all features of the invention embodied in the patent in suit and must do so in clear, unequivocal and unmistakeable terms. The prior art must enable the notionally skilled addressee at once to perceive and understand and be able practically to apply the discovery without the necessity of making further experiments. Whatever is essential to the invention must be read out of or gleaned from the prior publication.'
In Nicaro Holdings, Gummow J also referred to the speech of Lord Reid in C. Van Der Lely N.V. v Bamfords Limited [1963] RPC 61 and 71-72 where Lord Reid reaffirmed the principle set down by Lord Westbury in Hills v Evans [1862] 4 De G, F & J 288; 45 ER 1195 in relation to the level of disclosure necessary to anticipate a claimed invention:
'a person of ordinary knowledge of the subject would at once perceive and understand and be able practically to apply the discovery without the necessity of making further experiments'
Accordingly the alleged anticipation must not only disclose all of the integers of the claim, it must also provide sufficient detail to enable the skilled addressee to combine those integers to produce the invention without the need for further experimentation. This is particularly relevant to applications such as the present which include combinations and methods comprising a combination of steps.
NZ 258 199 (Bimeda Research and Development Limited) ‘Aqueous antibiotic composition for veterinary use’ (and GB equivalent GB 2 273 441) published 29 January 1997 (D1)

Merial submit that this document anticipates (at least) claims 1-5, 7 and 9-12. The invention disclosed is a veterinary composition and its use in the prevention and treatment of mammary disorders in cows. The composition is in two parts. First, there is an antibiotic formulation of 600mg of cloxacillin (as benzathine) per unit dose having an average dimension of less than 25 microns in an aqueous suspension including a suspension aid, a buffer and a surfactant. Second, there is a gel base seal formulation most preferably containing bismuth subnitrate at 65% by weight of the gel base. The two formulations are infused into the udder of a drying out cow.
D1 is silent on antibiotic formulations containing vegetable oils, peanut or otherwise. D1 also does not clearly disclose a single formulation of the gel base seal and the oil-based cloxacillin antibiotic.

D1 clearly teaches the seal formulation of the opposed claims (and has been explicitly incorporated into the description of the opposed case). The inventive concept of D1 however, is squarely directed to the use of aqueous antibiotic formulations in combination with the seal, and not the oil-based antibiotic formulations in the opposed application. In this regard, Zoetis and Merial are not in dispute.

The opponent’s lack of novelty argument is directed to the comparative example called "INJECTOR TYPE 2A – Study 3". This example provides a comparison of treatment using an aqueous antibiotic formulation in combination with a seal, and an oily antibiotic formulation in combination with a seal. The formulations are listed as 2A6 and 2A6'. 2A6 is a combination of a seal formulation with the composition 3.1% aluminium stearate, 31.8% liquid paraffin, 0.1% acriflavin and 65% bismuth subnitrate, and an antibiotic formulation simply described as "Oily". 2A6' has the same seal formulation, but the antibiotic formulation is "Aq.".
Reading D1 as a whole I have no doubt that the aqueous antibiotic formulation is that listed at page 4 of that specification: a suspension of cloxacillin in water with various additives. D1 gives no such exemplification of an oily antibiotic formulation. However, I am left with no doubt that it is a suspension of cloxacillin in an oily medium.
The comparison of 2A6 to 2A6’ is based on measuring the Effective Seal Duration (ESD), amount of seal material recovered, amount of bismuth subnitrate recovered and amount of bismuth subnitrate recovered from mammary fluids at parturition. D1 concludes that 2A6' is superior to 2A6 based on better ESD and reduced bismuth subnitrate (BSN) loss:
‘A combination of a seal and an aqueous based antibiotic offers a superior combination to a seal and an oily based antibiotic. This can be deduced from the fact that the ESD’s for the seal/aqueous combinations were significantly better than those for oily combinations. This is further evidenced by the high BSN recoveries (>75%) for the aqueous products, indicating retention of seal in situ. In contrast, the amount of bismuth found in the fluid portion at parturition was far lower for the aqueous than oily combination. This shows there was a larger degree of dispersal of the seal into the udder with the oily combinations.’
I am satisfied that D1 discloses the combination of oily antibiotic/ seal formulations as defined in claims 1, 3-5, 7 and 9-12 of the opposed application. I am also satisfied that D1 teaches the aqueous antibiotic/seal combination to be superior to the oily antibiotic/seal combinations of the opposed application.

Zoetis argue that because D1 teaches the reader that oily antibiotic/ seal formulations are inferior, it does not deprive the claims of novelty. They cite Bristol-Myers Squibb Company v FH Faulding & CoLtd (2000) 46 IPR 533 as authority. This case relates to two petty patents claiming methods for administrating the anti-cancer drug taxol, in reduced amounts and over a shorter period of time. In this way the highly toxic effects of the drug are reduced.
The Full Court noted the limitations of the reverse infringement test when considering paper citations at [62]:

‘In the case of a paper anticipation the reverse infringement test cannot be applied literally.’

After a review of the authorities, the court concluded at [67] – [68]:
'What all those authorities contemplate, in our view, is that a prior publication, if it is to destroy novelty, must give a direction or make a recommendation or suggestion which will result, if the skilled reader follows it, in the claimed invention. A direction, recommendation or suggestion may often, of course, be implicit in what is described and commonly the only question may be whether the publication describes with sufficient clarity the claimed invention or, in the case of a combination, each integer of it. …
Senior counsel for the respondent acknowledged that not every prior published description of a method falling within the claims would amount to an anticipation. He accepted that a mere speculation as to whether the method subsequently claimed would work would not, of itself, destroy novelty. With somewhat greater hesitation, he accepted that a mere proposal for a trial of the method claimed might not be an anticipation. … The question is still, what does the prior publication teach? Each of the reports taught, no doubt, some useful things relating to the administration of taxol. But none of them taught the method of the claims.'

In my view, D1 clearly teaches the 2A6 oily antibiotic/seal formulation and its use. The results indicate an effective seal duration of around 47 days. Admittedly, there is evidence of seal disintegration over the trial period, however the results section of D1 does not indicate a gross failure of 2A6. The fact that the aqueous antibiotic/seal formulation is superior does not erase the fact that the oily antibiotic/seal formulation is suitable for use in the prevention and treatment of mammary disorders in cows. It follows that claims 1, 3-5, 7 and 9-12 are anticipated.
Turning to claim 2, I note that D1 does not disclose a single formulation containing both cloxicillin and the seal. However, the seal formulation of 2A6 contains acriflavin, which is itself an antibacterial agent, albeit in a small amount. Because 2A6 is in fact oil based, it discloses all the essential features of claim 2. Consequently claim 2 is not novel.
D1 does not disclose the use of vegetable oil, peanut oil and/or hydrogenated peanut oil and therefore does not anticipate claims 6 or 8.
In summary claims 1-5, 7 and 9-12 are not novel when compared to D1.
GB 2 273 443 (Bimeda Research and Development Limited) ‘Veterinary composition for treating mastitis’ published 22 June 1994 (D2)
D2 is almost identical to D1 but for the use of a different gel. Comparative example 2B8 discloses a gel based seal containing polyethylene, liquid paraffin, acriflavin and bismuth subnitrate (at 65% by weight of the gel base). The seal is tested in combination with oil based cloxacillin. Claims 1-5 and 9-12 are not novel for the same reasons as those discussed under D1 above.

The seal does not contain aluminium stearate and the document does not disclose vegetable oil based antibiotics or seals containing aluminium stearate and therefore does not deprive claims 6-8 of novelty.
In summary claims 1-5 and 9-12 are not novel in light of D2.
Moorepark 25th Anniversary Publication, Part II,: Animal Health and Machine Milking published 1986 (D5)

This document relates to studies on the effect of a teat seal in combination with antibiotics on bovine udder infections during the dry period. Various experiments were performed using teat seals and antibiotics both individually and in combination. Variables included slow release antibiotics/quick release antibiotics and administration of the teat sealant at drying off/28 days after drying off. It is important to keep in mind that to anticipate the claims, an oil-based antibacterial formulation must be shown to be used in combination with an oil-based seal formulation comprising a gel base and a non-toxic heavy metal salt in an amount of at least 30% by weight of the gel base. It is useful to address the experiments individually.

What has caused come difficulty in this opposition is determining the exact composition of the various antibacterial and sealant formulations. The term ‘teatseal’ is apparently commonly used in the art both generally and as a tradename. To further complicate matters, different compositions (including those made by the same company) often use the same names. I have attempted to resolve this by drawing from across the evidence and explicitly list my sources as necessary.
Experiment 1
Experiment 1 compares the effect of a test sealer with that of an antibiotic in the treatment of bovine mammary infections during the dry period. The test sealant is known as ‘Osmonds Teat Seal’ (Osmonds Ltd., Broomhill Road, Tallaght, Co. Dublin) and is said to be a heavy inorganic salt in a paraffin/wax base with no antibiotic. Page declares:

‘one of the first commercially available internal teat sealants has been manufactured and sold in Ireland initially under the tradename ‘Osmonds Teat Seal’ since at least 1977 and comprises a non-toxic heavy metal salt, bismuth subnitrate 25% (w/w) and the antiseptic acriflavine 0.075% (w/w)’ [43].
‘A reformulation of this product has been sold in many countries, including New Zealand, by Pfizer New Zealand under the trade name ‘Teatseal’ since at least the late 1990s and comprises bismuth subnitrate 65% (w/w) in a paraffin oil base. I note that this product has been registered for sale in New Zealand under registration number A007294 since January 1997’ [44].
‘This product has also been registered for sale in Australia under Product No 51357 in the name of Pfizer Animal Health since at least 2001 under the trade name "Teatseal"’ [45].

The antibiotic is known as ‘Orbenin D.C.’ (Beecham) and is stated to contain benzathine cloxacillin. Page [34] provides a data sheet reciting that Orbenin D.C. is formulated in a long acting mineral oil base and is therefore clearly an oil-based antibacterial formulation as defined in claim 1 of the opposed application.

I have no reason to believe that the seal disclosed in D5 Experiment 1 is anything other than the original ‘Osmonds Teat Seal’. It does not contain the requisite amount of heavy metal salt and is silent on the presence of a gel and therefore is not the same as the seal defined in claim 1.
More importantly, Experiment 1 does not disclose the use of a teat seal combined with an antibiotic and so cannot be novelty destroying for any of the claims.
Experiment 2
Experiment 2 evaluates the use a teat seal in combination with an antibiotic. The antibiotic used is ‘Osmonds D.C.’ and contains procaine penicillin, penethemate hydrodide and neomycin sulphate. The discussion section of D5 informs that the antibiotic of Experiment 2 is in an oil base. Also, in his second declaration [9] Page declares Osmonds D.C. to be an oil-based, (paraffin) antibacterial formulation.

The seal is designated ‘Osmonds Modified Teat Seal’ and is stated to contain bismuth subnitrate, acriflavine and heavy liquid paraffin. In the absence of any controverting evidence, again I think it reasonable to conclude that this is a version of the original ‘Osmonds Teat Seal’. While it is not entirely clear what the ‘modification’ is, I have no evidence to suggest that it includes a gel or a non-toxic heavy metal salt in the base in an amount of least 30% by weight of the base.
While I am satisfied that an oil-based antibiotic is found in combination with a teat seal, it has not been established that the seal contains a gel or a non-toxic heavy metal at the requisite amount. Experiment 2 does not anticipate any of the claims.
Experiment 3

Experiment 3 compares the effects of inserting a teat sealer at drying off or at 28 days after drying off. Both a teat sealer and an antibiotic/teat sealer combination were evaluated. The formulations were the same as those of Experiment 2 and do not deprive the claims of novelty for the reasons espoused above.

Experiment 4

Experiment 4(a) evaluates the effects of a teat seal formulation for the control of new dry period infections in uninfected cows. It does not suggest or direct the use of an antibiotic in any way and therefore cannot anticipate the claims. Experiment 4(b) evaluates the effects of a quick release antibiotic incorporated into a teat sealer, while experiment 4(c) evaluates the use of an antibiotic/seal formulation in eliminating infections at drying off. There is no evidence to support that the antibiotics are oil-based or that the teat sealers comprise a gel base with a heavy metal salt in an amount of at 30% or above in either 4(b) or 4(c). Experiment 4 does not anticipate any of the claims.
Experiment 5
Experiment 5 compares the efficacy of three formulations for use during the dry period (i) slow release antibiotic; (ii) slow release antibiotic plus teat sealer and (iii) quick release antibiotic plus teat sealer. The slow release antibiotic used in (i) is Osmonds D.C. as described in Experiment 2 above. In (ii) Osmonds D.C. is used in combination with Osmonds Modified Teat Seal, also described in Experiment 2. (i) does not describe an antibiotic in combination with a sealant. (ii) uses a suitable oil based antibiotic in combination with a sealant, but (as established above) it has not been demonstrated that Osmonds Modified Teat Seal contains a gel and heavy metal salt in the requisite amount.
(iii) describes the intramammary infusion of the antibiotic formulation ‘Osmonds Teat Seal 1’ followed by the teat sealant ‘Osmonds Teat Seal 2’. Osmonds Teat Seal 1 is stated as containing procaine penicillin and dihydrostreptomycin sulphate in a quick release base. D5 does not describe the composition of Osmonds Teat Seal 2. Page declares at [47]

‘A combination product has been sold under the tradename of ‘Osmonds Teat Seal’ in Ireland since at least the late 1970’s. This product comprises twin single dose intramammary syringes, the first labelled Teat Seal 1 (cloxacillin benzathine formulation) and the second labelled Teat Seal 2 (teat sealer consisting of bismuth subnitrate in a liquid paraffin base). This product is sold with instructions to administer the antibacterial formulation first followed by the teat sealant.’

I am further aided by the document in evidence (referred to as D15):
Woolford, M W et al., ‘The prophylactic effect of a teat sealer on bovine mastitis during the dry period and the following lactation’, NZ Vet. J. vol. 46, 1, pp12-19, 1998
D15 examines the prophylactic efficacy of a teat sealer in reducing new intramammary infections at the drying off period. It discloses infusion with an antibiotic and a teat sealer. Teat Seal 1 is clearly described as cloxacillin benzathine in an aqueous base. Perhaps counterintuitively, Teat Seal 2 is not used in combination with Teat Seal 1 in this document. The document does not disclose Teat Seal 2 at all, rather it combines the antibiotic in situ with another seal known as ‘Teatseal’ (Bimeda NZ Ltd.) which does in fact comprise bismuth subnitrate (65% w/w) blended with a gel and paraffin. (The document is not pressed as a citation in this matter presumably because the antibiotic is clearly not oil-based.) I am left to conclude that Teat Seal 2 contains bismuth subnitrate in a liquid paraffin base but that in the absence of supporting evidence, does not contain a gel or bismuth subnitrate in an amount greater than 30% by weight of the gel. Nothing in Experiment 5 deprives the claims of novelty.
In conclusion, all claims are novel when compared to D5.
Meaney, W J, ‘Dry Period Teat Seal’ The Veterinary Record 99:30, published 1976 (D6)
This brief document describes experiments in cattle using a combination of teat sealers and antibiotics in a quick release base (possibly related to D7 below). The document does not disclose the composition of the teat sealers nor whether the quick release base is an oil. Claims 1-12 are clearly novel when compared to this document.
Meaney, W J ‘Effect of a dry period teat seal on bovine udder infection’, Irish Journal of Agricultural Research 16(3) 293-299 published 1977 (D7)
Experiments evaluating the effects of a dry period teat seal in bovine udders are disclosed in this document. The seal is stated to consist of a heavy inorganic salt in a paraffin/wax base and to further contain bismuth subnitrate 25% (w/w) and acriflavin 0.075% (made by Osmonds & Sons Ltd). In Experiment 2 a quick release antibiotic was incorporated into the seal. The antibiotic contained a mixture of procaine penicillin G and dihydrostreptomycin sulphate. The document is silent on the use of a gel and further (as agreed by Page at [106]) does not specifically mention the entire composition of the antibiotic preparation used nor a teat sealant formulation with greater than 25% by weight bismuth subnitrate as required by the present claims. Claims 1-12 are clearly novel in light of this document.
NZ 336 153 (Bimeda Research and Development Limited) ‘Antiinfective free intramammary veterinary composition (and US equivalent 6254881) published 25 June 1998 (D13)
This document clearly describes the preparation of oil-based teat seal formulations having approximately 65% by weight of a metal salt (e.g. bismuth subnitrate) in a gel base (e.g. aluminium stearate) as defined in the presently opposed claims. The invention is stated to reside in the surprising result that the provision of teat sealants to cattle without the additional use of antibiotics reduces the incidence of mammary disorders. The examples do however contemplate combining the seals with antibiotics for the purposes of comparison. Example 5, treatment 3 describes infusion of cloxacillin benzathine at drying off followed immediately by an infusion of the seal. The result was equivalent to that of the seal alone. No information is provided as to whether cloxacillin is formulated in an oil-base or otherwise. Page states ‘…based on my direct experience in the area, it is expected that it would be an oil based formulation. In my opinion, either vegetable or mineral oils could be used with the seal formulation described’ [124]. Wittem attests that the common long acting base at the priority date was aluminium stearate [110]. Examination of the various commercially available cloxacillin formulations provided by Page does reveal that they are often oil based. However, many of the formulations do not specify an oil base, rather they broadly state the cloxacillin to be in suspension or a ‘long-acting base’ sometimes with aluminium stearate. Indeed, as submitted by Pfizer, D1 above discloses an aqueous formulation of micronized cloxacillin benzathine. In my view it cannot be said with any certainty that Example 5 inherently or otherwise discloses the use of an oil-based antibiotic. Lack of novelty has not been established for claims 1-12.
Inventive Step
The Law of Inventive Step
The Opponent contends the claims of the opposed application to be devoid of an inventive step when considered under s7(2), s7(3)(a) and s7(3)(b).
Section 7 of the Patents Act (1990) provides
(2) For the purposes of this Act, an invention is to be taken to involve an inventive step when compared with the prior art base unless the invention would have been obvious to a person skilled in the relevant art in the light of the common general knowledge as it existed in the patent area before the priority date of the relevant claim, whether that knowledge is considered separately or together with the information mentioned in subsection (3).
(3) The information for the purposes of subsection (2) is:
(a) any single piece of prior art information; or
(b) a combination of any 2 or more pieces of prior art information;
being information that the skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood, regarded as relevant and, in the case of information mentioned in paragraph (b), combined as mentioned in that paragraph.
The test for obviousness is whether it would have been a matter of routine to proceed to the claimed invention.
‘The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not.'
(Aicken J in Wellcome Foundation Ltd v VR Laboratories (Aust) Pty Ltd [1981] HCA 12 at [45]; (1981) 148 CLR 262 at 286)
More recently, the High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59; 212 CLR 411 at [53] approved the approach taken in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd [1970] RPC 157 at 187 in which Graham J had posed the question:
‘Would the notional research group at the relevant date in all the circumstances directly be led as a matter of course to try [the claimed invention] in the expectation that it might well produce a useful, desired result’
In relation to combinations, the general test to be applied in determining obviousness is whether the invention would have been obvious to a non-inventive worker in the trade equipped with the common general knowledge (CGK) in the trade as at the priority date (Wellcome Foundation Ltd. v VR Laboratories (Aust) Pty Ltd [1981] HCA 12 at [45]; 148 CLR 262 at 286). The High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59; 56 IPR 129 also noted with approval the test set out by Aickin J in Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Limited [19080] HCA 9; 144 CLR 253 at 293
‘In the case of a combination patent the invention will lie in the selection of integers, a process which will necessarily involve rejection of other possible integers. The prior existence of publications revealing those integers, as separate items, and other possible integers does not itself make an alleged invention obvious. It is the selection of integers out of, perhaps many possibilities, which must be shown to be obvious.
It is in relation to this process that the misuse of hindsight is most common. When once an idea or an object or a process or a combination, admittedly novel, has been published,, it is very easy to say after perhaps months of search and study in the Patent Office and the public libraries that the integers into which the patent might be dissected could be found scattered amongst the prior documents by a person who already knew the solution to the problem and therefore knew what to look for and what to discard. But that process does not demonstrate lack of an inventive step. The opening of a safe is easy when the combination has been already provided.’
The Evidence of Page and Whittem
Pfizer summarize the CGK in the art in Australia at the priority date as follows: ‘oil-based antibiotics are commonly used for the treatment of mastitis in the absence of a teat seal. The most commonly used oil is a mineral oil. However, aqueous based antibiotic formulations and not oil-based antibiotic formulations should be used with oil/gel-based teat seal formulations.’
The evidence of Whittem relevantly provides the following as forming the CGK at the priority date:
·Available dry cow therapy products included antibiotics or bismuth subnitrate based teat seals [58]
·One product containing bismuth subnitrate which was available in New Zealand was Teatseal (Pfizer animal health) [60]
·Cloxacillin containing antibiotics were available in slow release formulations [62]
·D1, D2, D5 and D7 all form part of the CGK (disclosing combination therapies and discussed above) [80] These documents say that oil based antibiotic formulations increase seal disintegration compared to water based antibiotics, and therefore tell the reader not to use oil-based antibiotics [88].
·It was CGK at the priority date that gel bases for teat seals could be used and that oil bases for antimicrobial infusions could be mineral, paraffin or vegetable oil, and also that antibiotics could be used for mastitis treatment. There was no CGK on which oil bases for antimicrobial infusions might be preferred to another [84.10]
·It was an established view that teat-seal breakup occurred with coincident administration of oil-based antibiotic formulations [84.10]
·At the priority date the common view was that the use of oil based antibiotics teat seals containing heavy metals (eg) bismuth subnitrate in an oil gel base should be avoided as the seal would disintegrate or break up. This would result in the seal not having the required efficacy but also leaving particles of the seal in the udder. Aqueous formulations in contrast did not do this [112]

The evidence of Page [41-47] includes the following:
·Antibiotics were used for the treatment and prevention of mastitis during the dry period of dairy cattle
·The dry period for dairy cattle varies from as little as 4 weeks (28 days) to 8 weeks (56 days)
·B-lactam antibiotics were found to be particularly effective against mastitis causing pathogens
·Dry cow anitbiotics were formulated in a long acting base, and generally contain an oil as part of the intramammary antibiotic composition
·Commonly used oils were either mineral or vegetable oils and were used as part of the long acting base of the intramammary antibiotic composition
·The long acting base also commonly includes a gelling agent, such as aluminium stearate as part of the formulation
·The semi-synthetic derivative of penicillin, cloxacillin, had been and continues to be, one of the most widely used dry cow antibiotics because of its stability, resistance to B-lactamase and excellent anti-staphylococcal activity
·Internal sealant infusions comprising a gel base and a non-toxic heavy metal salt in the base (generally bismuth subnitrate) in concentrations greater than 30% (e.g. Pfizer’s Teatseal product which contains 65% bismuth subnitrate in a paraffin oil base and has registered for sale since 1997)
·Combination therapy using antibiotic therapy infusion and a teat sealant was known based on early publication by Meaney (1977) (D7) and the combination therapies disclosed in D1, D2, D5, D13 and D15 (all discussed earlier)
·Products combining two strategies (antibiotic with a seal) have been on sale since the late 1970s i.e. Osmonds Teat Seal comprising Teat Seal 1 (an aqueous antibiotic formulation) and Teat Seal 2 (as described earlier)
·It was common general knowledge that gel bases for teat seals could be used and that oil bases for antimicrobial infusions could be mineral, paraffin or vegetable oil [declaration 2 [22]
·The consensus view that would have been familiar to those skilled in the area is … that mineral oil type bases were not preferred as they dispersed readily [declaration 2, 23]
·Veterinary compositions comprising an oil-based antibacterial formulation and an oil-based seal formulation either separately or in a single formulation were well known in 2002 having been described in D1, D2 and D7 [50].
Are the Claims Obvious in Light of the Common General Knowledge Alone?
It is abundantly clear (and not disputed by the parties) that separately, both oil based antibacterials (including vegetable oil based) and the oil/gel based seals of the present invention were CGK at the priority date of the claims. It is also well established that therapies using antibiotic formulations in combination with teat seals were CGK. This is apparent from the declarations of both Page and Whittem and further supported by the teachings of at least D1, D2, D5 and D7 which both declarants agree constitute CGK.

What must be established is whether the skilled artisan would consider it obvious to combine an oil based antibacterial (antibiotic) formulation with an oil based seal formulation comprising a gel base and a non-toxic heavy metal salt in the base in an amount of at least 30% by weight of the gel base as demanded by at least claim 1. Not only must the selection of each and every integer of the two formulations be shown to be obvious, but the act of combining them together for the purposes of the invention must be shown to be obvious.

Page and Whittem agree that D1 and D2 teach both the seal formulation and the antibiotic formulation of claim 1. It is also agreed that the comparative examples disclose the two formulations in combination. Whittem consistently and repeatedly states throughout his declaration that D1 and D2 teach away from using oil-based antibiotics due to seal disintegration within the teat. He also strongly argues that at the priority date, it was generally thought that oil-based antibiotics should not be used with the seals of the invention.

Page attests that not using oil based antibiotic formulations and oil/gel seals is not a reasonable interpretation of D1 and D2. This view appears to be predicated on the results of the comparative examples that demonstrate an effective seal duration of approximately 48 days. He further declares that it would have been obvious to use either a mineral or vegetable oil in combination with the seal. He does not explain why, but merely relies on the fact that oil based antibiotics were very common at the time.

On reading D1 and D2 I am inclined to prefer the view of Whittem. While the oily antibiotic formulation is disclosed, it is clear that aqueous antibiotic formulations are superior and are to be preferred. In my view, D1 and D2 teach away from the use of oil-based antibiotics with the gel/oil seals.

It is also agreed that D5 and D7 constitute CGK. D5 teaches oil-based antibiotics, aqueous antibiotics and oil-based teat seals and evaluated the effects of different combinations in the prevention and treatment of bovine udder infection. The seals do not contain a gel, and are not clearly taught to contain at least 30% heavy metal salt. None of the experiments where the oil-based antibiotics were combined with the oily seals resulted in effective treatment or prevention of mastitis. In Experiment 2 the oily antibiotic/oily teat seal combination performed better than the antibiotic alone however it was reported that the seal was breaking into small particles when mixed with the oil base of the antibiotic. Experiment 3 demonstrated that using a teat seal in combination with an oily antibiotic produced more new infections than oily antibiotic alone. Experiment 5(ii) compared quick release and oil-based antibiotics in combination with teat seals and showed the overall cure with the formulations was poor, and in fact inferior to the use of teat seal alone. Based on these results I cannot conclude that based on D5, it was obvious to combine an oil-based antibiotic with any oil-based seal let alone the oil/gel seals of the invention. In fact, D5 demonstrates it was well known that such a combination would be ineffective. This is consistent with the Whittem declaration.

D7 evaluates the effects of a dry period oil-based teat seal in bovine udders. The seal consists of a paraffin/wax base and 25% by weight bismuth subnitrate. It does not appear to contain a gel. In experiment 2 a quick release antibiotic was incorporated into the seal. The results conclude that elimination of infection from quarters treated with antibiotic/seal mixture was similar to that obtained from oil-based antibiotics (alone).

The nature of the antibiotic base (if any) is not disclosed. Page concedes this, but states that at the time it was common to use mineral or vegetable oils [106]. Whittem declares that D7 would not tell a person to use an oil based antibiotic formulation [104]. In my view there is insufficient evidence to determine the composition of the antibiotic in D7. It cannot be said that the information contained in D7 demonstrates that combining oil-based antibiotics with an oil-based teat seal is obvious. In any case the results do not demonstrate an improvement, rather they are stated as being similar to use of oily-antibiotics alone. Moreover, it certainly cannot be said that it is merely CGK to use oil-based antibiotics with the seals of the invention.

In my view, it is clear that the information contained in D1, D2 and D5 demonstrates it was well known at the priority date that oil-based antibiotics should not be used in combination with oil-based teat seals (D7 being inconclusive). The documents also demonstrate that loss of seal integrity was a known associated issue. This is entirely consistent with the evidence of Whittem.

The evidence of Page establishes that oil-based antibiotics and the teat seals of the opposed application were CKG and also that combination treatments were well known. (This is consistent with Whittem and D1, D2 and D5.) However, in my view the evidence of Page when read in the context of D1, D2 and D5 does not establish that it was obvious to use oily antibiotics in combination with oil-based teat seals. In his second declaration at [6] he says
‘In my view, the skilled person providing recommendations for the treatment of mastitis during the dry period must first be aware of the range of products that are available for use, it is then one of the responsibilities of the skilled worker to decide which one, if any, or combination of products are indicated in each individual situation. While in some cases an internal teat seal alone may be recommended, in other cases, an antibacterial intramammary preparation may be recommended. In yet further situations, dependant on the specific circumstances of the case, it may be recommended that initial use of an antibacterial preparation may be followed by use of the teat seal. Amongst the antibacterial preparations that are used initially in this combination approach, there would likely be preparations based on a mineral oil and there would be preparations based on a vegetable oil. There being no precautions against the use of specific intramammary antibacterial products at the time, the skilled person would be free to choose whichever antibacterial preparation they thought was most appropriate.’
Page appears to be saying that when treating mastitis, the skilled artisan would contemplate the use of any available antibiotic agents and teat seals, alone or in any combination. He does not say that he would choose any particular formulation or combination, let alone that he would choose the combination as presently claimed. It is the selection of the specific antibiotic and seal formulations of the claims and their specific combination that must be shown to be obvious. In my view this requirement has not been satisfied. I further note that Page asserts there to be no precaution against the use of specific antibacterials. I do not agree. D1, D2 and D5 clearly teach away from the use of the combinations of the opposed claims.

It has not been established that it would have been obvious to combine an oil-based antibiotic with the seal formulations of the claims 1-12.
Are the claims obvious when considered in light of the citations (s7(3))?
For the purposes of s7(3) the relevant documents pressed are listed as follows:
·NZ 258 199 (Bimeda Research and Development Limited) ‘Aqueous antibiotic composition for veterinary use’ (and GB equivalent GB 2 273 441) published 29 January 1997 (D1)
·GB 2 273 443 (Bimeda Research and Development Limited) ‘Veterinary composition for treating mastitis’ published 22 June 1994 (D2)
·Moorepark 25^th Anniversary Publication, Part II,: Animal Health and Machine Milking published 1986 (D5)
·Meaney, W J ‘Effect of a dry period teat seal on bovine udder infection’, Irish Journal of Agricultural Research 16(3) 293-299 published 1977 (D7)
·NZ 336 153 (Bimeda Research and Development Limited) ‘Anti-infective free intramammary veterinary composition (and US equivalent 6254881) published 25 June 1998 (D13)
D1, D2, D5 and D7 have been established as CKG and are discussed extensively above. I need travel no further here. The only additional document is D13.
NZ 336 153 (Bimeda Research and Development Limited) ‘Anti-infective free intramammary veterinary composition (and US equivalent 6254881) published 25 June 1998 (D13)
I am satisfied that D13 would have been ascertained, understood and regarded as relevant by the person skilled in the art. It discloses an oil based teat seal formulation having approximately 65% by weight of bismuth subnitrate in an aluminium stearate gel base as defined in the opposed claims. In one comparative example, the seal is used in combination with the antibiotic cloxacillin benzathine in an unspecified base. The result was found to be no better than the seal alone. Page declares at [124] that the antibiotic base is likely to be an oil and that either vegetable or mineral oils could be used. He does not state that he would use such an oil and I therefore do not think the claims to be obvious. In any event, the CGK at the priority date discussed above clearly directs the person skilled in the art to avoid combining oil-based antibiotics with the gel/oil based seals of the opposed claims. Claims 1-12 are not obvious when compared to D13.
In conclusion none of claims 1-12 lack an inventive step.
Manner of Manufacture
Section 18(1)(a) requires that an invention must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies. Manner of manufacture is assessed by asking whether the claimed invention lacks the necessary quality of inventiveness on the face of the specification (NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd [1995] HCA 15 at [9]; (1995) 183 CLR 655 at 655).

The opponent argues that the compositions of the invention and their uses failed the threshold test for patentability because it was apparent on the face of the specification that they were known and therefore not a manner of manufacture. This reasoning simply restates the opponent’s novelty and inventive step arguments which have already been fully considered under those grounds. I do not propose to revisit the same issues under a different ground.
However, as stated earlier, claims 1 and 3-10 include within their scope two separate formulations, each of which is already well known. The claims do not assure their combination in normal use. In my view these claims define a mere collocation of known integers and are therefore not for a manner of new manufacture.
Conclusion
Claims 1-5, 7 and 9-12 not novel and claims 1 and 3-10 are not for a manner of new manufacture.
These are matters that may be overcome by amendment. I will allow the applicant two (2) months from the date of this decision in which to file amendments to overcome these deficiencies.
Costs
The opposition has succeeded on the grounds of novelty and manner of manufacture. It is usual practice for costs to follow the event. I see no reason to deviate from this approach. Accordingly I award costs against the applicant, Zoetis LLC according to Schedule 8 of the Patent Regulations 1991.

Nicole Howard
Delegate of the Commissioner of Patents

TEAT 1	TEAT 2	TEAT 3	TEAT 4
ANTIBIOTIC FORMULATION	None	Formulation A	Formulation B	Formulation C
AVERAGED AREA OF OPACITY	1.0	1.1	1.7	1.6