Bayer Health Care AG v Novartis AG

ABSTRACTS OF DECISIONS

DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS

Application : No. 696581 in the name of Bayer HealthCare AG

Title: Non-Systemic Control of Parasites

Action: Opposition under section 59 of the Patents Act 1990 by Novartis AG

Decision: Issued 29 July 2005.
Abstract

The invention relates to use of members of a broad class of nicotinergic acetylcholine receptor modulators for non-systemic control of parasitic lice and fleas in animals wherein the modulators are applied to the dermis of the animal.

The opposition was unsuccessful on all grounds.

Costs were awarded to the applicant.

PATENTS ACT 1990

DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS

Re:Patent Application No. 696581 by Bayer HealthCare AG and opposition under section 59 of the Patents Act 1990 by Novartis AG.

BACKGROUND

Patent application 696581 (20144/95) in the name of Bayer HealthCare AG (hereafter referred to as Bayer) was filed as a convention application on 18 May 1995 claiming priority from DE 4417752, which was filed on 25 May 1994. The application was advertised as accepted on 17 September 1998. Novartis AG (hereafter referred to as Novartis) filed a notice of opposition on 17 December 1998 and served their statement of grounds and particulars on 17 March 1999. Service of evidence in support was completed on 5 June 2000.
Evidence in answer was completed on 1 November 2001 and evidence in reply completed on 7 March 2003.
Amendments to the claims were filed on 28 May 2001 and 23 August 2001, the amendments were incorporated into the specification on 30 April 2002 and the allowance advertised on 6 June 2002.
The specification that was the subject of the hearing was the specification as accepted, including the amendments of 28 May and 23 August 2001.
The matter was heard in Sydney on Thursday 26 May 2005. Novartis was represented by Ms Katrina Howard of Counsel, assisted by Mr Paul Power and Dr John McCann of Spruson and Ferguson and Dr Hans Lesiecki and Dr Thomas Friedel. Bayer was represented by Mr Graeme Clarke of Counsel, assisted by Dr Peter Stearne and Ms Susan Tanks of Davies Collison Cave and Dr Matthias Storch and Mr Robert Cranna.

THE EVIDENCE

The evidence in support consists of:
·      Statutory Declaration of Paul Anthony Power, made 17 March 2000, together with exhibits PAP-1 to PAP-33.
·      Statutory Declaration of George Crank, made 19 April 2000.
·      Statutory Declaration of Desmond Ronald Hennessy, made 1 May 2000, together with exhibit DRH-1.
·      Statutory Declaration of Gregory John Cox, made 2 June 2000, together with annexes A to D.
The evidence in answer consists of:
·      Statutory Declaration of Terence J Hopkins, made 29 May 2001, together with exhibits TJH1 to TJH4.
·      Statutory Declaration of Richard Bruce Atwell, made 26 October 2001, together with exhibits RBA-1 to RBA-3.
·      Statutory Declaration of Dr Hubert Dorn, made 11 October 2001, together with exhibits HD1 and HD2.
·      Statutory Declaration of Dr Olaf Hansen, made 20 June 2001, together with exhibit OH1.
·      Statutory Declaration of Mr Murray Collins, made 25 May 2001.
·      Statutory Declaration of Mr Devin Reginald Boys, made 25 May 2001.
The evidence in reply consists of:
·      Statutory Declaration of George Crank, made 28 March 2002.
·      Statutory Declaration of Thomas Friedel, made 27 February 2003, together with exhibits TF-1 and TF-2.
·      Statutory Declaration of Desmond Ronal Hennessy, made 27 November 2002, together with exhibit DRH-2.

Further evidence

On 25 May 2005, immediately prior to the hearing, Novartis filed two further folders containing exhibits PAP-34 to PAP-48.
Bayer did not object to the filing of PAP 34-39, 41, 47 and 48. These documents simply repeat information already available in documents filed as evidence in support. However Bayer did object to PAP-40 and 42-46, which are copies of later patents granted to the applicant and an examiner’s report that have not previously been filed in this opposition. Mr Clarke submitted that as such they were not relevant to the current proceedings.
Mr Clarke directed my attention to Pfizer Inc v Commissioner of Patents [2005] FCA 137 (1 March 2005) where Bennett J held that it was inappropriate to use a subsequent patent as evidence in the construction of an earlier patent. Although these comments were made in relation to a divisional application and the question of “in substance” disclosure for the purpose of an application for an extension of time under s70(2)(a) of the Patents Act 1990, I believe that they are also relevant here. At the heart of both matters is the role of the specification, which is to describe the invention in sufficient detail for the skilled person to ascertain the nature of the invention. However, it is not appropriate to use a later patent application to colour the interpretation of an invention disclosed in an earlier document.
As such PAP 40 and 42-46 cannot be considered to be relevant to the current proceedings.
Following discussion of this matter at the hearing both parties agreed that PAP-40, 42 and 43-46 would not be considered in the opposition proceedings but that PAP-34 to PAP-48. PAP-34-39, 41, 47 and 48 could be retained as further representatives of documents already filed during the standard process of filing evidence in support.

THE SPECIFICATION

The specification relates to use of members of a broad class of agonists and antagonists of nicotinergic acetylcholine receptors for the non-systemic control of parasitic lice and fleas on animals wherein the modulators are applied to the dermis of the animal.
The introduction to the specification explains that agonists and antagonists of nicotinergic acetylcholine receptors such as the nicotinyl insecticides are well known to have outstanding activity against parasitic insects of plants. In particular they are widely known to be useful for systemic and non-systemic control of insect parasites in plants.
The specification also discloses a previous patent application, WO 93 24002, which describes use of imadicloprid, a chloronicotinyl insecticide for the systemic control of lice and fleas on animals. Systemic control involves introduction of the insecticide into the host animal’s bloodstream via oral or parenteral administration. This means of administration enables distribution of the insecticide to all parts of the animal and delivery of the insecticide in every blood meal taken from the host.
The specification explains that, in contrast to the systemic control described in WO 93 24002, the applicant’s invention relates to non-systemic delivery of compounds of formula I to the parasite from the skin, hair or fur of the host. As such, although the invention of 696581 is similar to that in WO 93 24002, in that it involves controlling parasites such as fleas and lice by treating the host on which the parasites lives, the applicant’s method exposes the parasite to the insecticide on the outer surface, or dermis of the host, rather than in a blood meal taken from the host.
The specification concludes with 19 examples, 17 of which relate to formulations comprising imidacloprid as active ingredient for dermal application. The formulations represent sprays, pour-on formulations, shampoos, powders and shaped articles to contact the dermis of the subject animal. The remaining two examples are “use” examples describing the efficacy of spray and spot-on formulations when used to treat fleas on dogs.
The specification ends with 15 claims.
Claim 1 is the only independent claim in the specification. It recites

Use of agonists and antagonists of nicotinergic acetylcholine receptors of insects for non-systemic control of parasitic insects of the orders Anoplura, Mallophaga, and Siphonaptera on animals, including humans, by dermal administration of one or more compounds of the general formula (I)

in which
R     represents hydrogen or optionally substituted radicals from the series of acyl, alkyl, aryl, aralkyl, heteroaryl, and heteroaryl-alkyl;
wherein said acyl radicals are formyl, alkylcarbonyl, arylcarbonyl, alkylsulphonyl, arylsulphonyl, or (alkyl-)-(aryl-)-phosphoryl;
said alkyl is C₁₄-alkyl;
said aryl is phenyl;
said aralkyl is phenylmethyl, or phenethyl;
said heteroaryl radicals are thienyl, furyl, thiazolyl, imidazolyl, pyridl, or benzothiazolyl;
said heteroarylalkyl is heteroarylmethyl, or heteroarylethyl;
said optional substituents being from the series:
alkyl with 1 to 4 carbon atoms; alkoxy with 1 to 4 carbon atoms; alkylthio with 1 to 4 carbon atoms; halogenoalkyl with 1 to 4 carbon atoms and 1 to 5 halogen atoms, said halogen atoms being identical or different from the series fluorine, chlorine, or bromine; hydrozyl; halogen; cyano; nitro; amino; monoalkyl- and dialkylamino with 1 to 4 carbon atoms per alky group; carboxy; carbalkoxy with 2 to 4 carbon atoms; sulpho (-SO₃H); alkyl-sulphonyl with 1 or 2 carbon atoms; phenylsulphonyl, and heteroarylamino and heteroarylalkylamino;
A     represents hydrogen or optionally substituted radicals from the series of acyl, alky, or aryl, which have the abovementioned meanings for R; or as a bifunctional group which is linked to the radical Z, an optionally substituted aklylene with 1-4 C atoms, said optional substituents being the optional substituents abovementioned for R, and said alkylene groups optionally being interrupted by heteroatoms from the series N, O, S;
A and Z may, together with the atoms to which they are bonded, form a saturated or unsaturated 5- or 6-membered heterocyclic ring, optionally containing 1 or 2 identical or different heteroatoms and/or hetero groups wherein said heteroatoms are from the series O, S or N, and said hetero groups are represented by N-alkyl, wherein alkyl of the N-alkyl group contains 1 or 2 carbon atoms;
E     represents NO₂ or CN;
X     represents –CH= or –N=, wherein the radical –CH= can be linked in place of the H atom to the radical Z;
Z     represents optionally substituted radicals alkyl, -OR, -SR, -NRR, where R and the optional substituents have the abovementioned meaning;
Z     may, apart from the abovementioned ring, form together with the atom to which it is bonded in the case where X represents the radical

a saturated or unsaturated hetercyclic 5- or 6-membered ring optionally containing a further 1 or 2 identical or different heteroatoms and/or hetero groups wherein said heteroatoms are from the series O, S or N and said hetero groups are N-alkyl, wherein the alkyl of the N-alkyl group contains 1 or 2 carbon atoms.
Claim 2-9 define specific alternatives for the compounds disclosed in claim 1.
Claims 10 defines use of the method to treat fleas in cats and dogs and claim 11 defines use of the method to treat lice in humans.
Claims 12, 14 and 15 define specific methods of dermal administration and claims 13 and 16 define the use of adjuvants and/or carriers in association with the active compound.

CONSTRUCTION

Novartis submitted that the invention relates to controlling fleas and lice by a non-systemic method of application of the compounds of formula I to the dermis of the host animal. If this construction is correct the compounds can either remain on the skin, hair or fur of the host animal and kill by surface contact with the parasite, or they can cross the dermis into the host bloodstream and kill via ingestion with a blood meal taken from the host.
However, I believe that this construction ignores the description of systemic control in the specification. The specification describes systemic control as delivery of the active compound to the bloodstream of the animal from where “the fleas then take up the active compound when they suck the blood”. When systemic control is defined in this way it is clear that systemic control is not simply the way in which the compound is administered to the host but also the way in which the compound is delivered to the parasite. This makes it clear that systemic control includes any method of delivering an active compound to a parasite via the host bloodstream, including methods where the active compound is applied to the dermis in such a way that it travels across the dermis and into the host bloodstream.
Thus, where the specification contrasts prior art systemic control and the applicant’s non-systemic control it is distinguishing between systemic control methods where the active compound is transported from the dermis to the host bloodstream and non-systemic control methods where the active compound remains on the dermis of the host.
This distinction is also consistent with the general description of methods of application and the examples provided in the application, all of which relate to the preparation of powders, shampoos and articles for controlling the parasite by contact with the active compound on the skin, hair or fur of the host.
It is also clear from the general description and examples that dermal administration is an important feature of the invention. This feature draws a distinction between methods where the compound is applied to the skin of the host animal and methods where the compounds are applied directly to the parasite or to the environment in which host animal lives.
As such, there are two important features to the method of controlling parasites that is described in the specification and defined in the claims, the first is that the active compounds are applied to the dermis of the host animal and the second is that the compounds kill by surface contact with the parasites on the skin of the host.
In part Novartis’ construction of the invention appears to arise from the belief that the results reported by Bayer cannot arise from non-systemic delivery alone and that there must be transdermal movement of the compounds of formula I into the bloodstream of the host where they are then taken up by the parasite in a blood meal. In his second declaration Novartis’ expert Dr Hennessey states:
“I cannot believe that the control is achieved by non-systemic means alone.”
However, there is no evidence to suggest that the effect seen by Bayer is the result of systemic rather than non-systemic delivery of the compound.
Although Ms Howard and Dr McCann suggested that the presence of additives such as dimethyl sulphoxide and benzyl alcohol in the exemplified formulations was consistent with transdermal formulations, Dr Stearne pointed out that these chemicals are also routinely used as evaporants to deposit a powdered residue of the active compound that remains on the skin of the host. As such there is no evidence that the formulations and methods disclosed in 696581 are directed at anything other than non-systemic delivery of the compounds of formula I to the parasite.
At the hearing Ms Howard also submitted that the invention should be construed as a method suitable for non-systemic control rather than a method specifically directed at non-systemic control. Ms Howard argued that statements such as those at pages 1a and 8, which describe the compounds of formula I as “particularly suitable for the non-systemic control of parasitic insects” and “suitable for the control of parasitic insects” teach toward a method that is merely suitable for control of parasites.
Bayer did not accept this and submitted that the claims should be construed as limited to the method of non-systemic control as recited in the claims. Much of Bayer’s argument at the hearing was in relation to Swiss-type claims and as such was not directly relevant to the claims of 696581. However as with Swiss-type claims, claims that are written in the form of “use of” a compound for a specific purpose are generally properly construed as being restricted to that purpose, unless the specification expressly teaches that the broader construction should be applied.
In the current situation there is if anything a clear teaching to support the normal construction. The specification draws a clear distinction between the systemic use of WO 93 24002 and the non-systemic use of the invention and all of the examples relate to methods and formulation that appear to be directed to non-systemic delivery of the compounds to the parasite. As such I am satisfied that the claims should be construed as relating to method expressly undertaken for the purpose of non-systemic control of fleas and lice.

Section 40

Novartis submitted that the term “non-systemic control” was unclear because the term could either relate to the way in which compounds of formula I were administered to the host or the mode of action of the compounds in the parasite. However as discussed above, neither of these constructions is consistent with the invention as described in the specification where “non-systemic control” defines the way in which the compounds are delivered to the parasite by the host.
Both parties’ declarants also appear to be in general agreement that this term relates to the way in which the compounds are brought into contact with the target parasite. Novartis’ expert declarants Dr Hennessey states in his first declaration at paragraph 12.
“Central to a consideration of the opposed application, it is my opinion, and I believe would be the opinion of those skilled in this art, that it is the understanding of what would be reasonably interpreted by someone with physiological, parasitological, pharmacological or biochemical knowledge, as “non-systemic” control. With many years of experience in physiological, parasitological and pharmacological veterinary research, I understand the term “non-systemic control” to mean that the presentation of a drug to a target parasite reaches that parasite via a non-systemic route.”
As such, I believe that the scope and meaning of the term “non-systemic control” would be clear to the skilled worker.
Novartis also submitted that the claims lacked fair basis if “non-systemic control” relates to the mode of action of the compounds of formula I in the parasite. However, as discussed in the previous section this construction is not correct and the invention is correctly construed as relating to the mode of delivery of the drug to the parasite. Given this, and given that the specification provides a real and reasonably clear disclosure of delivery of the drug by a non-systemic route, the claims are fairly based.
A further clarity issue was raised with respect to the meaning of “agonists and antagonists of nicotinergic acetylcholine receptors”. Novartis submitted that it was unclear whether this phrase meant the compound must have the action of both an antagonist and agonist or only one of them. However, I am satisfied that the skilled person would readily appreciate that a class of compounds that bind a specific receptor may include both antagonists and agonists and that the claimed compounds may be either antagonists or agonists. I am also satisfied that the skilled person could readily apply standard tests and assays to identify whether a compound in question represented an antagonist or an agonist. As such I am satisfied that the term and its usage do not lack clarity.
Novartis also submitted that the claims lacked fair basis and that the specification did not full describe the invention because the specification only exemplifies a single member of a very broad class of compounds and only establishes efficacy of these compounds against fleas.
However, Novartis did not provide any evidence to suggest that the basic structure provided in formula I was insufficient to confer insecticidal activity or the ability to modulate nicotinergic acetylcholine receptors of insects. Furthermore, given the large range of compounds of formula I that are described in each of the 27 documents cited by Novartis as prior art, there is substantial evidence to support the ability of a range of compounds of formula I to modulate receptor activity and act as insecticides. Similarly, given that these documents also disclose a very broad spectrum of insect pests that are susceptible to the compounds of formula I, it is reasonable to expect that the compounds act similarly when used against both fleas and lice.

As such, I am satisfied that the invention is sufficiently described in the specification and that the extent of this description is consistent with the invention as defined in the claims.
In summary, I am satisfied that the claims are clear and fairly based and that the invention is fully described.

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”.
However, in applying this test regard must be given to whether the prior art publication has provided clear and unmistakable directions to do what patentee has claimed, as also stated in General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd at page 486:
"To anticipate the patentees 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."
At the hearing Novartis elected to focus on only 12 of the 27 documents cited against the novelty of 696581. Mr Clarke explained that this was not because the other 14 documents were less relevant than the 12 discussed at the hearing rather it was because there was substantial overlap between all of the documents such that the 12 documents could be regarded as representative of all 27. Mr Clarke also suggested that the sheer number of documents covering similar subject matter was a very good illustration of the amount of work that had already been conducted on use of the compounds of formula I as insecticides at the priority date of 696581.
I agree with Mr Clarke’s assessment of the strong overlap between the documents and as a consequence have restricted my detailed discussion to the 12 documents selected by Novartis.
These documents are WO 93 24002, US 4742060, EP 302833, US 5063236, US 5303605, EP 163855, DE 4207604, EP 375907, EP 296453, EP 259738, EP 254859 and EP 285985.
11 of the 12 documents are all very similar in structure and subject matter. Each document begins with a general description of the chemistry of compounds of formula I, an extensive list of insects that are susceptible to the compounds, a list of the various methods of application that are generally used with plant and animal insecticides and a list of possible formulations suitable for use in the various applications. The documents then continue with a number of examples of specific formulations and methods of testing the efficacy of the compounds against insect parasites.
Although all of the documents disclose parasites of the orders Siphonaptera, Mallophaga and/or Anoplura (fleas and lice), dermal application of compounds of formula I to animals and non-systemic control of parasites, in every case each of these features is disclosed independently and buried within a long list of either parasites, methods of administration or means of control. None of these documents is specifically directed at methods of controlling parasites on animals let alone non-systemic control of parasites on animals.
Where any of the documents do focus on a specific type of parasite the focus is on plant parasites and the control of insects such as leaf hoppers, aphids and other plant insect parasites. In 9 of the 11 documents all of the examples relate to control of plant parasites. In the remaining two documents, one has 4 plant examples and 1 example of systemic control of the blowfly Lucillia cuprina by feeding blowfly larvae on horse meat (EP 285985) and the other has 14 plant examples and 1 example of flea control by application of a compounds of formula I directly to flea eggs in a test chamber (US 5303605).
With respect to the example in which a compound of formula I is applied directly to flea eggs, this example is distinguished from the methods of the claims because the example relates to applying the compound directly to flea eggs in a test chamber. This is in contrast to the claimed invention where the compound is applied to the host animal, not directly to fleas or lice. As pointed out by Bayer’s expert declarants, there are considerable differences between a method of testing a compound for insecticidal activity by direct application to a parasite and a method of controlling a parasite by application of the compound to the dermis of a host animal. Methods of dermal application require that the compound is formulated in a manner that produces effective dispersal of the compound over the skin and hair of the animal, that is acceptable and safe and easy to use for to pet owners and that does not lead to parasites escaping through moving away from an advancing chemical front.
Given this, it cannot be said that a method of topical application directly to fleas can be regarded as a clear and unmistakeable directions for a method of dermal application of the compounds of formula I to a host animal for non-systemic control of fleas.
As such, none of the 11 citations explicitly teaches to combine use of compounds of formula I, non-systemic control of fleas and lice and dermal application to animals.
Given this, I believe that Novartis has conducted a “cherry picking” exercise in which they have excised the independent features of the method from each of the 11 citations without taking into account the context of these features as they appear in the citation. As pointed out by Mr Clarke, although all of the independent features of the claims may be found in each citation the correct question to ask is “what does each citation teach when read as a whole?” and the answer to this is that none of the 11 citations provide clear and unmistakeable directions to the invention.
The twelfth document, WO 93 24002 is the prior art document discussed at page 1a of the specification. This document is the only document that specifically focuses on the use of a compound of formula I to control fleas on an animal. However, in direct contrast to 696581, WO 93 24002 teaches a method of systemic application.
Novartis submitted that WO 93 24002 discloses methods for the non-systemic application of compounds of formula I in the following statement:
“Since those compounds exhibit all of their outstanding anti-flea activity also when they are administered systemically”. (emphasis added)
They argued that this sentence describes a comparison between the systemic method that is the subject of WO 93 24002 and previous non-systemic methods of treating fleas on animals.
However, this statement does nothing more than suggest that at the priority date of WO 93 24002 it was known that the compounds of formula I had anti-flea activity. As discussed in relation to US 5303605, demonstrated anti-flea activity is generally associated with direct application of insecticidal compounds to fleas under laboratory test conditions, and is quite different to a method of applying a compound to a host animal for the control of fleas. Furthermore, any further discussions of non-systemic control of fleas in WO 93 24002 are simply general discussions referring to the disadvantages of known methods of flea control using any unspecified insecticide. Given this, I do not believe that WO 93 24002 clearly discloses preparation or testing of non-systemic control using the compounds of formula I on animals.
The other 15 documents that were cited by Novartis against novelty but were not discussed in any detail at the hearing are similar in content to the 11 documents I have discussed above. All disclose compounds of formula I and detail their insecticidal activity, most focus on control of plant parasites and none teach toward the use of the compounds to control parasites on animals by dermal application.
In conclusion, I do not believe that any one of the citations provides a disclosure sufficient to deprive the claims of novelty.

Inventive Step

An appropriate test for inventive step is that given in Olin Mathieson v Biorex (1970) RPC 157 at page 187, and approved by the High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59 (12 December 2002):
"Would the notional research group at the relevant date in all the circumstances ... directly be led as a matter of course to try the invention claimed in the expectation that it might well produce a useful desired result.",
In respect of inventions relating to a specific combination of integers or features guidance is also provided in Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd (1979-80) 144 CLR 253 at page 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 of itself make an alleged invention obvious. It is the selection of the integers out of, perhaps many possibilities, which must be shown to be obvious."
Broadly stated the problem that the current invention seeks to solve is the problem of control of parasitic insects, primarily fleas and lice, on animals, including humans.
At the hearing Novartis focused their arguments on a lack of inventive step in light of either common general knowledge in the art alone, or in combination with any one of EP 285985, WO 93 24002 or US 4742060. Novartis did not go into the remaining 24 documents in any detail. As he did for novelty Mr Clarke explained that this was not because these citations were necessarily significantly different or closer to the invention than the other 24 citations, it was simply because these citations could be used to summarise the information also found in the other citations.
In my following discussions I have taken a similar, although less restricted approach and confined my discussions to two groups of citations. Group 1 contains the 11 citations discussed in detail in paragraphs 45 to 47 of the novelty section, including EP 285985 and US 4742060. Group 2 is restricted to WO 93 24002. Collectively these citations represent the closest art.
I have also relied on both parties’ declarants to varying extents. Although Mr Clarke made submissions at the hearing about the unsuitability of Novartis’ expert declarants and the inappropriate application of hindsight, I am satisfied that both parties’ declarants are suitability qualified and are able to assist me in areas where I may need further elaboration of the state of common general at the priority date of the application, or technical matters relating to the workings of the invention.

Common general knowledge

There was general agreement between both parties that topical or dermal administration of insecticides to animals was part of common general knowledge in the art at the priority date of 696581. For example when commenting on the feature of topical administration of insecticides to animals, Dr Atwell, one of Bayer’s expert declarants agreed that Novartis’ expert declarants Dr Hennessey:
“is correct in stating that generally speaking topical administration and systemic administration of insecticidal compounds to an animal were known prior to 20 May 1994”.
There was also general agreement that the compounds of formula I were known as broad spectrum insecticides.
Where the two parties differ substantially is in whether it would have been obvious for the skilled person to combine the compounds of formula I with a method of dermal administration to achieve non-systemic control of fleas and lice parasites on animals.
The main thrust of Novartis’ argument was that once it was appreciated that compounds of formula I had activity when topically applied to a broad range of insect pest, including fleas and lice, and that the compounds had low toxicity in warm-blooded animals, then it was an obvious next step to test the compounds for non-systemic control of insects on animals by dermal administration. In their submissions at the hearing Novartis stated:
“It was therefore obvious to try non-systemic use first, as this was the simplest test, involving applying the insecticidal compound to the insect”.
However as pointed out by Bayer, there is still a gap between testing a compound for insecticidal activity by contacting the compound with the parasite in question and testing the compound for non-systemic control of the same parasite by dermal application to animals. For the skilled person to take this next step they would need to believe that non-systemic control and dermal application would be likely to work and would be superior to other available means of using the insecticide in question to control fleas and lice on animals.
Bayer’s expert Dr Atwell submitted that it is not sufficient that the skilled worker understand that the compounds are active against the target pest when applied topically and that they have low toxicity in the target host, the skilled worker must also consider other issues such as effective dispersal of the compound on the host, owners’ acceptance of different modes of application and effectiveness of the compound against all stages of the parasite. Dr Atwell explained that:
“while topical application methods may have been widely used in the field prior to 20 May 1994, they had been associated with a number of problems, including: stress to the animal; inadequate coverage of the animal’s coat; owner non-compliance due to the time-consuming nature of application and themes which is often involved in attempting to treat the animal; and, non-effectiveness in insect control.”
In particular Dr Atwell highlighted problems with dispersal of active compounds across the skin and hair of animals such as dogs and cats. He explained that many insecticidal compounds do not disperse effectively and either cause local irritation at the point of contact or allow the parasite to escape killing as a result of poor coverage of the animal by the insecticide. A surprising advantage of the compounds of formula I is that it was not appreciated before the priority date of 696581 that they had the ability to disperse effectively.
In a similar vein, Bayer’s declarant Dr Hopkins likened the problem of eradication of insect parasites to a jigsaw where a matrix of factors must be put together to arrive at a method that provides effective control of all life stages of the parasite in question and that is acceptable to owners in terms of ease and frequency of application and low toxicity to the animals and the environment. Dr Hopkins explained that at the priority date there was a marked prejudice against non-systemic modes of control for the treatment of fleas because insecticides often have little residual activity or are not effective against all life stages of fleas, leading to the need to repeat the disinfestation process frequently and to treat both the animal and its environment. In addition, it is often difficult to effect complete coverage of the animal in the way provided for by systemic application.
Some of these issues are also raised in three of the general review articles exhibited by Novartis as examples of common general knowledge in the art; PAP29, PAP31 and PAP32. These documents discuss a wide range of broad spectrum insecticides and the challenges of formulating and administering these compounds in ways that use the compounds to best affect without adversely affecting the host or the environment.
Novartis did not provide evidence to suggest that these concerns and prejudices against non-systemic control were irrelevant, or that the skilled worker was unaware of such prejudices at the priority date of the application. In fact Novartis’ expert Dr Hennessey appears to support these prejudices. In his first declaration, when discussing the way in which non-systemic control works, Dr Hennessey states:
“Contact with the parasite occurs as the parasite roams over the host and crosses into a drug contaminated environment or when the drug diffuses into the parasite habitat. In reality the efficiency of this diffusion is generally poor and is exacerbated by the target insect moving away from the advancing chemical front.”
Nor did Novartis provide any evidence to suggest that there were any greater, or more pressing concerns about the disadvantages of systemic control that would have outweighed concerns about non-systemic control.
In particular, Novartis did not provide any evidence to suggest that the skilled person would have understood that these general concerns about methods of non-systemic control did not apply to compounds of formula I.
As such, based on the evidence that I have before me, although I accept that there was a general understanding that the compounds of formula I were active against insects such as fleas and lice, and there was an understanding that the compounds of formula were of low toxicity to warm-blooded animals, I believe that there was a prejudice against testing compounds for non-systemic control by dermal application to animals at the priority date of 696581. I also believe that there was an understanding that systemic delivery of insecticidal compounds reduced many of the problems associated with dispersal of non-systemic insecticides to cover the skin of a treated animal.
Therefore, I am satisfied that at the priority date of 696581 the skilled worker would have chosen to test a method of systemic control using the compounds of formula I over a method of non-systemic control.

Group 1

As discussed in the section on novelty, none of the citations in group 1 focuses on controlling fleas or lice on animals and none teaches to focus on non-systemic control or dermal application. Furthermore, when this absence of direction is also considered in the light of the prejudices against non-systemic control that existed in the art at the priority date of the application, there is clearly no incentive to lead the skilled person to explore the use of compounds of formula I for non-systemic control of fleas and lice in the manner defined in the claims.
Given this, none of the citations listed in group 1 either alone or in combination with the prior art deprives the claims of an inventive step.

WO 93 24002

As discussed in the section on novelty, although WO 93 24002 specifically focuses on the treatment of fleas or lice on host animals, it explicitly describes the disadvantages of non-systemic application in terms of ease of use, owner acceptance and efficacy and teaches toward systemic control as the more effective alternative.
As such, WO 93 24002 actually teaches away from the invention as claimed.
In summary, based on the evidence before me I do not believe that any of the claims lack an inventive step. I can find no teachings in the common general knowledge as a whole, or in any one of the prior art publications either when considered alone, or in combination with common general knowledge in the art that would directly lead the skilled worker to use the compounds of formula I for non-systemic control of parasites on animals.

Manner of Manufacture

Novartis submitted that the claimed invention was not a manner of manufacture because it was nothing more than:
“the use of a known material (compounds of the general formula I) in a known method (non-systemic application, in particular dermal administration, of insecticides to animals) for the purpose of which (to control parasitic insects) its known properties (insecticidal activity) made it suitable.”
In particular Novartis referred to the statement in the Commissioner of Patents v Microcell Ltd (1959) 102 CLR 232, that:
“a claim for the use of known of a known material in the manufacture of known articles for the purpose of which its known properties make that material suitable…..cannot be subject matter for a patent.”

However, as suggested in the discussion on inventive step, when considering the current invention it is not sufficient to restrict considerations on “suitability” to only insecticidal activity and toxicity, other matters such as dispersal, efficacy against a range of life stages and owner acceptance also contribute to suitability. Given this, in the current circumstance I do not believe that it correct to say that at the priority date of 696581 the known properties of compounds of formula I necessarily made these compounds suitable for non-systemic control of parasites on animals, or for dermal application.
The compounds of formula I would only fulfil this requirement if it could also be said that it was known that they did not suffer from the same disadvantages known for other insecticidal compounds that had been used for non-systemic control at the priority date of 696581. However, I have nothing before me from either party to suggest that there was any appreciation in the art at the priority date that the compounds of formula I had any advantageous characteristics with respect to dispersal or that they did not suffer from the standard problems associated with methods of non-systemic control and dermal application of insecticides on animals.
Given this I do not believe that it is correct to say that the invention is nothing more than a new use of an old substance in a manner that simply exploits a known property of that substance because the properties that make compounds of formula I effective in non-systemic methods were not known at the priority date of the application.
Therefore, I do not agree that the claimed invention fails to meet the requirements of manner of manufacture.

CONCLUSION

The opposition was unsuccessful on all grounds.
None of the claims lacked novelty or an inventive step in light of any one of the documents, or in the case of inventive step, in light of common general knowledge in the art alone, or in combination with any one of the documents. In addition, all of the claims were clear and fairly based and the invention was fully described.

COSTS

Both parties submitted that costs should follow the event. Given this I see no reason to depart from the principle that costs should follow the event and I therefore award costs against Novartis.

Delegate of the Commissioner of Patents

Terry Moore

29 July 2005

Patent attorneys for the applicant : Spruson & Ferguson, Sydney
Patent attorneys for the opponent : Davies, Collison, Cave, Sydney

[2005] APO 35

27 July 2005