Orion Corporation v Actavis Pty Ltd
[2015] FCA 909
•21 August 2015
FEDERAL COURT OF AUSTRALIA
Orion Corporation v Actavis Pty Ltd
[2015] FCA 909
Citation: Orion Corporation v Actavis Pty Ltd [2015] FCA 909 Parties: ORION CORPORATION AND OTHERS AS NAMED IN THE SCHEDULE v ACTAVIS PTY LTD ACN 003 854 626 AND ANOTHER AS NAMED IN THE SCHEDULE; ACTAVIS PTY LTD ACN 003 854 626 AND ANOTHER AS NAMED IN THE SCHEDULE; ORION CORPORATION AND OTHERS AS NAMED IN THE SCHEDULE File number: NSD 2456 of 2013 Judge: RARES J Date of judgment: 21 August 2015 Catchwords: PATENTS – whether patent invalid for failure to define invention – construction of patent – whether characteristics described in complete specification defined invention or constituted preferred embodiments – infringement – addition of integers to invention did not create a new working combination of integers to take claim beyond infringement – whether claims sufficiently clear – construction of phrase “substantial portion” – elucidation of a workable standard for skilled addressee must form part of construction of claim – whether claims fairly based on matter described in specification – description of certain embodiments in specification did not exclude those embodiments from invention merely because other embodiments described as preferable – whether claims lacked utility – whether assertion of monopoly in claims limited to useful results – determination of relevant priority date – whether claims lacked novelty compared with prior art base – skilled addressee’s “background knowledge” of extrinsic matters not relevant to consideration of novelty – whether invention involved inventive step – consideration of difficulties and complications inventors faced, in determining obviousness of invention Legislation: Patents Act 1990 (Cth) Cases cited: Advanced Building Systems Pty Ltd v Ramset Fasteners (Aust) Pty Ltd (1998) 194 CLR 171
Apotex Pty Ltd v Les Laboratoires Servier [2013] FCA 1426
AstraZeneca AB v Apotex Pty Ltd (2014) 226 FCR 324
Austal Ship Sales Pty Ltd v Stena Rederi Aktiebolag (2008) 77 IPR 229
Austal Ships Pty Ltd v Stena Rederi Aktiebolag (2005) 66 IPR 420
Bitech Engineering Pty Ltd v Garth Living Pty Ltd (2010) 86 IPR 468
CCOM Pty Ltd v Jiejing Pty Ltd (1994) 51 FCR 260
Coopers Animal Health Australia Ltd v Western Stock Distributors Pty Ltd (1987) 15 FCR 382
Firebelt Pty Ltd v Brambles Australia Ltd (t/as Cleanaway) (2002) 188 ALR 28
General Tire& Rubber Co v Firestone Tyre and Rubber Co Ltd [1972] RPC 457
GlaxoSmithKline Australia Pty Ltd v Reckitt Benckiser Healthcare (UK) Ltd (2013) 305 ALR 363
ICI Chemicals & Polymers Ltd v Lubrizol Corp Inc (2000) 106 FCR 214
Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd (2001) 207 CLR 1
Lewis v Daily Telegraph Ltd [1964] AC 234
Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (2004) 217 CLR 274
Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (No 2) 235 CLR 173
Martin v Scribal Pty Ltd (1954) 92 CLR 17
Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253
Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59
Olin Corporation v Super Cartridge Co Pty Ltd (1977) 180 CLR 236
Otsuka Pharmaceutical Co Ltd v Generic Health Pty Ltd (No 4) (2015) 113 IPR 191
Pfizer Overseas Pharmaceuticals v Eli Lilly & Co (2005) 68 IPR 1
Ranbaxy Australia Pty Ltd v Warner-Lambert Co LLC (2008) 77 IPR 449
Re Stauffer Chemical Co’s Application [1977] RPC 33
Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79
Sigma Pharmaceuticals (Australia) Pty Ltd v Wyeth (No 3) [2011] FCAFC 132
Société des Usines Chimiques Rhône-Poulenc v Commissioner of Patents (1958) 100 CLR 5
Stena Rederi Aktiebolag v Austal Ships Sales Pty Ltd (2007) 73 IPR 257
Uniline Australia Ltd v SBriggs Pty Ltd (2009) 81 IPR 42
Washex Machinery Corporation v Roy Burton & Co Pty Ltd (1974) 49 ALJR 12
Welch Perrin & Co Pty Ltd v Worrel (1961) 106 CLR 588Date of hearing: 7 April 2015-17 April 2015 Place: Sydney Division: GENERAL DIVISION Category: Catchwords Number of paragraphs: 320 Counsel for the Applicants/Cross-Respondents: Mr C Dimitriadis SC with Mr C Burgess Solicitor for the Applicants/Cross-Respondents: Clayton Utz Counsel for the Respondents/Cross-Claimants: Mr SCG Burley SC with Mr JS Cooke and Mr D Larish Solicitor for the Respondents/Cross-Claimants: Ashurst
IN THE FEDERAL COURT OF AUSTRALIA
NEW SOUTH WALES DISTRICT REGISTRY
GENERAL DIVISION
NSD 2456 of 2013
BETWEEN: ORION CORPORATION AND OTHERS AS NAMED IN THE SCHEDULE
ApplicantsACTAVIS PTY LTD ACN 003 854 626 AND ANOTHER AS NAMED IN THE SCHEDULE
Cross-ClaimantsAND: ACTAVIS PTY LTD ACN 003 854 626 AND ANOTHER AS NAMED IN THE SCHEDULE
RespondentsORION CORPORATION AND OTHERS AS NAMED IN THE SCHEDULE
Cross-RespondentsJUDGE:
RARES J
DATE OF ORDER:
21 AUGUST 2015
WHERE MADE:
SYDNEY
THE COURT ORDERS THAT:
1.On or before 28 August 2015 the parties confer and prepare draft orders to give effect to these reasons and:
(a)if the form of those orders is:
(i)agreed provide them to the associate to Rares J;
(ii)not agreed provide the respective forms of orders for which each contends together with written submissions limited to one page in support;
(b)deal with the question of costs, if agreed.
2.If on or before 2 September 2015 the parties cannot agree on what order for costs is appropriate, they confer as to a timetable to file and serve any evidence and written submissions limited to five pages in chief and reply so that the question of costs be ready to be heard on a date to be fixed.
3.The proceedings stand over to 28 August 2015 at 2.15 pm for mention.
Note: Entry of orders is dealt with in Rule 39.32 of the Federal Court Rules 2011.
IN THE FEDERAL COURT OF AUSTRALIA
NEW SOUTH WALES DISTRICT REGISTRY
GENERAL DIVISION
NSD 2456 of 2013
BETWEEN: ORION CORPORATION AND OTHERS AS NAMED IN THE SCHEDULE
ApplicantsACTAVIS PTY LTD ACN 003 854 626 AND ANOTHER AS NAMED IN THE SCHEDULE
Cross-ClaimantsAND: ACTAVIS PTY LTD ACN 003 854 626 AND ANOTHER AS NAMED IN THE SCHEDULE
RespondentsORION CORPORATION AND OTHERS AS NAMED IN THE SCHEDULE
Cross-Respondents
JUDGE:
RARES J
DATE:
21 AUGUST 2015
PLACE:
SYDNEY
REASONS FOR JUDGMENT
This case concerns, first, the validity of Orion Corporation’s Australian patent No. 765932, that makes claims for a monopoly over compositions consisting of a combination of three known active pharmaceutical ingredients (APIs) called levodopa, carbidopa and entacapone, and methods of producing that combination and tablets comprising it, secondly, whether Actavis Pty Ltd’s compositions of those three APIs infringe any of the valid claims in the patent and thirdly, whether some of the claims are invalid on various bases. The three APIs are used in the treatment of Parkinson’s disease.
Parkinson’s disease affects the ability to initiate movement voluntarily. Its principal characteristics are slowness or lack of movement, rigidity of the limbs or trunk and tremor of body parts when at rest. Sufferers of this disease often have a stooped posture, shuffling gait and an expressionless face. Typically, the onset of the disease occurs between the ages of 40 and 70, and the average age for its onset is about 60.
In the late 1950s and early 1960s scientists discovered, first, the role of dopamine as a neurotransmitter in the brain, secondly, an association between a depletion of dopamine in the brain and symptoms of Parkinson’s disease and, thirdly, that that depletion could be reversed or reduced by administering an amino acid, the abbreviated name of which was D,L-dopa. D,L-dopa can be partially converted to dopamine in the brain by the enzyme dopa decarboxylase (DDC).
Importantly, dopamine cannot be administered to a patient directly, that is, orally or by injection into peripheral tissues, because it degrades rapidly in the body before it reaches the brain. And, the administration of D,L-dopa in large doses produces serious and unwanted side effects. The next discovery, in 1969, was that L-dopa, an isomer of D,L-dopa, was effective in treating the disease and could be administered in markedly lower doses. L-dopa is called “levodopa”.
Then, in 1974, scientists discovered that two substances, carbidopa and benserazide inhibited the action of DDC in peripheral tissues, but not in the brain. That resulted in a significant reduction in the rate of degradation of a dose of levodopa in the body and bloodstream before the dose reached the brain. In other words, the DDC inhibitors protected the dose of levodopa from degrading while it traveled through the body, but, at the blood-brain barrier, the DDC inhibitors did not cross into the brain with the levodopa. The consequence was a further reduction in the size of the necessary dose of levodopa that a patient needed. From the time of this discovery, the standard therapy for Parkinson’s disease employing levodopa invariably consisted of using that API in formulations prepared together with either carbidopa or benserazide in particular fixed ratios.
Even so, only 5% to 10% of the initial dose of levodopa administered with a DDC inhibitor ultimately reached the patient’s brain to produce dopamine and its beneficial effect. That was partly because of a further degrading effect as a result of the action of another enzyme present in the body, catechol O-methyl transferase, called COMT. That enzyme naturally converted levodopa into a substance called 3-O-methyldopa.
By at least June 1999, persons skilled in this field were aware of the desirability of using a COMT inhibitor in conjunction with the administration of levodopa in order to increase the amount of levodopa that reached the brain. Early investigations into potential COMT inhibitors had encountered problems with toxicity and a lack of selectivity. However, three COMT inhibitors had been progressed to use in experiments on animals with parkinsonian symptoms, two of those, tolcapone and entacapone, had been the subject of clinical trials and had been brought to market for use in levodopa therapy.
Tolcapone was first marketed in the United Kingdom in August 1997 and in Australia in 1998. It only needed to be administered three times daily. However, experience developed in 1998 that led to the appreciation that tolcapone had a rare, but potentially fatal, side effect – it could cause major liver toxicity, that had resulted in the death of some patients. This side effect led to tolcapone being withdrawn from the market very early in 1999 in some countries, including the United Kingdom and Australia. The occurrence of this side effect was unexpected, since tolcapone had previously passed regulatory scrutiny, including toxicity assessment, for use in the treatment of Parkinson’s disease.
One consequence of the problems with tolcapone was heightened interest in entacapone. However, entacapone had to be administered more frequently, namely with each dose of levodopa, because it had a shorter half-life in the body than tolcapone.
Orion’s related companies, Novartis Pharma AG (a Swiss corporation) and Novartis Pharmaceuticals (Australia) Pty Ltd, claim to be, respectively, the exclusive licensee and sub‑licensee of the patent. Actavis and its related company, Medis Pharma Pty Ltd, dispute the effect of the inter-group licensing arrangements. That issue has been separated from those that I must decide in this stage of the proceedings.
Orion relied on the patent having the priority date of 30 June 1999 being the date, for the purposes of s 43(1) of the Patents Act 1990 (Cth), of filing in Finland of the priority document being the original patent application No. 991485. The complete specification of the patent was filed on 29 June 2000, and that is the deferred priority date for which Actavis contended in relation to whether claims 19, 20 and 21 were novel or involved an inventive step, as I will explain later in these reasons.
The above history helps set the scene for consideration of the first set of issues in these proceedings. Those issues are:
(1)is any of claims 1, 2, 12, 13, 14, 17, 18 and 21 invalid because it fails to define the invention? (the definition of the invention issue);
(2)what is the proper construction of the patent? (the construction issue);
(3)do Actavis’ products infringe any of claims 1, 2, 12, 13, 14, 17, 18, 19, 20 or 21? (the infringement issue);
(4)is any of claims 1, 2, 13, 14, 17, 18 and 21 invalid because it is not clear? (the clarity issue);
(5)is any of claims 1, 2, 12, 13, 14, 17, 18, 19, 20 and 21 fairly based on the matter described in the specification? (the fair basis issue);
(6)is any of claims 1, 2, 12, 13, 14, 17, 18, 19, 20 and 21 invalid because it lacks utility? (the utility issue);
(7)is any of claims 19, 20 and 21 invalid because when compared with the prior art base as it existed before the asserted or deferred priority date of that claim because:
(a)it was not novel? (the novelty issue);
(b)it did not involve an inventive steps? (the inventive step issue).
The legislative scheme
Relevantly, the Act provided at 29 June 2000, being the time of filing of the complete specification, as follows:
7 Novelty and inventive step
(1)For the purposes of this Act, an invention is to be taken to be novel when compared with the prior art base unless it is not novel in the light of any one of the following kinds of information, each of which must be considered separately:
(a)prior art information (other than that mentioned in paragraph (c)) made publicly available in a single document or through doing a single act;
(b)prior art information (other than that mentioned in paragraph (c)) made publicly available in 2 or more related documents, or through doing 2 or more related acts, if the relationship between the documents or acts is such that a person skilled in the relevant art in the patent area would treat them as a single source of that information;
(c)prior art information contained in a single specification of the kind mentioned in subparagraph (b)(ii) of the definition of prior art base in Schedule 1.
(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 either of the kinds of information mentioned in subsection (3), each of which must be considered separately.
(3) For the purposes of subsection (2), the kinds of information are:
(a)prior art information made publicly available in a single document or through doing a single act; and
(b)prior art information made publicly available in 2 or more related documents, or through doing 2 or more related acts, if the relationship between the documents or acts is such that a person skilled in the relevant art in the patent area would treat them as a single source of that 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 and regarded as relevant to work in the relevant art in the patent area.
[Notes:
(1)For the meaning of document see section 25 of the Acts Interpretation Act 1901.
(2)See also the definitions of prior art base and prior art information in Schedule 1: see also paragraph 18(1)(b) and subsection 98(1).]
Division 1—Validity
18 Patentable inventions
(1)Subject to subsection (2), a patentable invention is an invention that, so far as claimed in any claim:
…
(b)when compared with the prior art base as it existed before the priority date of that claim:
(i) is novel; and
(ii) involves an inventive step; and
(c) is useful; and
(d)was not secretly used in the patent area before the priority date of that claim by, or on behalf of, or with the authority of, the patentee or nominated person or the patentee’s or nominated person’s predecessor in title to the invention.
(2)Human beings, and the biological processes for their generation, are not patentable inventions.
[Note: see also sections 7 and 9.]
40 Specifications
(1) A provisional specification must describe the invention.
(2) A complete specification must:
(a)describe the invention fully, including the best method known to the applicant of performing the invention; and
(b)where it relates to an application for a standard patent– end with a claim or claims defining the invention; and
(c)where it relates to an application for a petty patent– end with a single claim, or a single independent claim and not more than 2 dependent claims, defining the invention.
(3)The claim or claims must be clear and succinct and fairly based on the matter described in the specification.
(4) The claim or claims must relate to one invention only.
43 Priority dates
(1) Each claim of a specification must have a priority date.
(2) The priority date of a claim is:
(a) the date of filing of the specification; or
(b)where the regulations provide for the determination of a different date as the priority date – the date determined under the regulations.
(3)Where a claim defines more than one form of an invention, then, for the purposes of determining the priority date of the claim, it must be treated as if it were a separate claim for each form of the invention that is defined.
(4)The priority date of a claim of a specification may be different from the priority date of any other claim of the specification.
138 Revocation of patents in other circumstances
(1)The Minister or any other person may apply to a prescribed court for an order revoking a patent.
…
(3)After hearing the application, the court may, by order, revoke the patent, either wholly or so far as it relates to a claim, on one or more of the following grounds, but on no other ground:
…
(b) that the invention is not a patentable invention;
…(f) that the specification does not comply with subsection 40(2) or (3).
The Dictionary in Sch 1 to the Act provided:
invention means any manner of new manufacture the subject of letters patent and grant of privilege within section 6 of the Statute of Monopolies, and includes an alleged invention.
prior art base means:
(a)in relation to deciding whether an invention does or does not involve an inventive step:
(i)information in a document, being a document publicly available anywhere in the patent area; and
(ii)information made publicly available through doing an act anywhere in the patent area; and
(iii)where the invention is the subject of a standard patent or an application for a standard patent–information in a document publicly available outside the patent area; and
(b) in relation to deciding whether an invention is or is not novel:
(i) information of a kind mentioned in paragraph (a); and
(ii)information contained in a published specification filed in respect of a complete application where:
(A)if the information is, or were to be, the subject of a claim of the specification, the claim has, or would have, a priority date earlier than that of the claim under consideration; and
(B)the specification was published after the priority date of the claim under consideration; and
(C)the information was contained in the specification on its filing date and when it was published.
[Note: For the meaning of document see section 25 of the Acts Interpretation Act 1901.]
prior art information means:
(a)for the purposes of subsection 7(1) – information that is part of the prior art base in relation to deciding whether an invention is or is not novel; and
(b)for the purposes of subsection 7(3) – information that is part of the prior art base in relation to deciding whether an invention does or does not involve an inventive step.
The patent
The patent described the field of the invention as relating to, first, new pharmaceutical compositions comprising entacapone, levodopa and carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, secondly, a preparation method of the compositions, thirdly, a use of the compositions in a therapeutic method and, fourthly, the use of entacapone, levodopa and carbidopa in the manufacture of an oral solid fixed dose combination (page 1 par 1 [The patent does not have line or paragraph numbers. I will use the first full paragraph on a page to describe paragraph numbers]).
Throughout the patent, references to the three APIs are accompanied by references to their pharmaceutically acceptable salts or hydrates, but, for simplicity, I will omit referring to those alternatives because there is no issue that concerns whether the form of the API is pure, or a salt or hydrate.
The complete specification described the background of the invention by stating the chemical name of each API. It noted that entacapone had been described as a COMT inhibitor in US Patent 5,446,194 and that the US Patent had also discussed the API being administered by enteral (basically, oral) and parenteral (basically, intravenous) routes. The specification noted that Orion manufactured and marketed in Europe an oral compacted composition containing entacapone under the trademarks COMTESS® and COMTAN®. It stated that levodopa and carbidopa were the most commonly used drugs to treat Parkinson’s disease and were commercially available as combination tablets sold in Europe by Du Pont Pharma under various trademarks, including SINEMET®.
The background explained that patients needed to take parkinsonism medication several times daily to keep them without symptoms. It observed that patient compliance, especially for those with tremor and old age, could be improved by using a fixed dose combination of all three APIs rather than two separate tablets (namely, the combination levodopa/carbidopa tablet and a separate entacapone tablet) several times a day.
The patentee said that the inventors had found that the three APIs “are preferable [sic] released from the oral composition as soon as possible after ingesting it”. It said that it was very difficult to adjust the absorption of three different active agents from a single oral, solid composition and that, usually in practice, absorption of one active agent could decrease while another’s increased. It stated that numerous factors had to be considered when selecting excipients, disintegrants and other auxiliary agents for use in combination with the active agents, including the chemical and physical characteristics of those agents and the auxiliary agents, the bioavailabilities of the active agents, the stability of the composition and its method of preparation (pages 1-3).
The patentee stated that none of the earlier patents cited in the background section, or any other patent or publication of which it was aware, described an oral solid composition comprising the three APIs. It also said that the purpose of the discussion in the background section was to explain the context of the invention, but was not an admission that any of the material it referred to had been published, or was known or part of the common general knowledge in Australia as at the priority date of each claim (page 3).
Under the heading “Summary of the invention”, the specification stated (page 3 pars 3-4):
Applicants have discovered that entacapone, levodopa and carbidopa … can be combined into one oral solid composition with particularly interesting properties.
The invention thus provides an oral solid fixed dose composition comprising pharmacologically effective amounts of entacapone, levodopa, and carbidopa …, and comprising at least one pharmaceutically acceptable excipient (hereinafter referred to as a composition according to the invention), which has i.a. [scil: inter alia] preferable stability and bioavailability characteristics and which is easy to swallow. (emphasis added)
The patentee then asserted that the invention particularly provided an oral solid composition comprising pharmacologically effective amounts of the three APIs and, first, at least one pharmaceutically acceptable excipient being a sugar alcohol, starch or both (and preferably the former was mannitol and the latter maize starch), and secondly, one excipient other than microcrystalline cellulose (MCC) (pages 3-4).
Next, the background continued (page 4 pars 2-3):
Applicants have found that a particularly interesting way to increase the bioavailability of carbidopa from an oral solid composition comprising entacapone, levodopa, and carbidopa is to add carbidopa separately, for instance by granulating first levodopa and entacapone together and then adding carbidopa to these granules separately.
Accordingly, the invention further provides an oral solid composition comprising pharmacologically effective amounts of entacapone, levodopa, and carbidopa … and a pharmaceutically acceptable excipient, wherein a substantial portion of carbidopa is separated from entacapone and/or levodopa. (emphasis added)
The specification then discussed different techniques to accomplish the separation of carbidopa from the other two APIs, that included granulating and mixing levodopa and entacapone together and adding carbidopa separately, “as such” or in granule form. The specification recorded that, therefore, the invention also provided a method for producing an oral solid pharmaceutical composition comprising the three APIs and a pharmaceutically acceptable excipient, that involved first mixing levodopa and entacapone separately and then adding carbidopa separately (pages 4-5). It stated that the oral solid composition according to the invention included “a tablet [being the preferable form], a capsule and the like” (page 5 par 1). The specification also said that the invention provided a method for treating Parkinson’s disease (but this aspect is not in issue in these proceedings).
The background then stated that the invention provided a use of the three APIs in the manufacture of an oral solid composition for treating Parkinson’s disease in its different stages. The section concluded by saying that the description it contained, and that which followed in the specification, were “exemplary and explanatory only and [did] not restrict the invention, as claimed” (page 5 par 5).
Next, the specification gave a brief description of the drawings at the end of the document. The drawings were, in fact, six graphs that depicted two separate sets of blood plasma concentrations of each of the three APIs achieved after a single oral dose of, in each set, a reference dosage being a 200 mg COMTESS® tablet (i.e. entacapone) together with a SINEMET® PLUS 100/25 tablet (i.e. 100 mg of levodopa and 25 mg of carbidopa) and, in one set, formulations 1 and 2 as later described in the complete specification and in the second set, formulations 3 and 4 also later described there.
Figures 1 and 4 recorded the concentrations for entacapone, Figures 2 and 5 those for levodopa and Figures 3 and 6 those for carbidopa respectively for the three recorded dose forms, being the reference and two relevant formulations (p 6, Figures 1-6). The two reference doses produced different graphical results for each comparator API, as compared to those in the other set. The four described formulations also produced different graphical results for each API.
The next heading in the specification was “Detailed description of the invention” and it was followed immediately by the statements (page 7 pars 1-2):
Applicants have surprisingly discovered that an oral solid composition enabling sufficient absorption of active agents can be achieved by combining entacapone, levodopa and carbidopa … in a single formulation. This has been achieved, inter alia, by improving the bioavailability and the stability of the composition, and improving the method for preparing the composition.
Applicants have found that absorptions of levodopa, carbidopa and entacapone from the digestive tract are highly variable. The bioavailabilities of levodopa and carbidopa vary both intra- and interindividually. The bioavailability of entacapone has also been extensively studied by the Applicant to arrive at the present invention. (emphasis added)
The patentee then stated that it was very challenging to harmonise the absorptions of the three APIs from the one oral solid composition. It said that it had found that the method for preparing the composition had a significant effect on the bioavailability of carbidopa, and continued:
For example, the bioavailability of carbidopa from Formulation 1 (see Example 1, Table 1), wherein all the active agents are wet granulated together, is too low compared to the reference product, SINEMET® PLUS 100/25 mg tablet. On the other hand, the bioavailability of carbidopa from Formulation 2 (see Example 1, Table 1), wherein all the active agents are dry granulated together (compaction granulated) is acceptable. However, polyethylene glycol used in Formulation 2 as a compression aid found [sic] to cause stability problems as indicated below. The absorption data from the bioavailability studies of Formulations 1 and 2 are shown in Figures 1-3. (pages 7-8) (emphasis added)
The patentee stated that the inventors had found that a preferred way to increase the bioavailability of carbidopa from a oral solid composition comprising the three APIs was to mix, for example to granulate, levodopa and entacapone together and then to add carbidopa to that mixture, for example in granules, separately.
The specification then set out its first consistory clause, corresponding to claim 1, as:
The invention therefore provides an oral solid composition of entacapone, levodopa, and carbidopa … and a pharmaceutically acceptable excipient, wherein a substantial portion of carbidopa is separated from entacapone and levodopa. (emphasis added)
The specification then identified a preferred way of obtaining a composition of the invention “wherein a substantial portion of carbidopa is separated from entacapone and levodopa”, was to mix (e.g. granulate) entacapone and levodopa particles separately and then to add carbidopa particles separately, “as such or in the form of granules”, optionally adding one or more excipients and formulating the mixture “thus formed to an oral solid composition, e.g. tablet, of the invention” (emphasis added) (page 8 par 3).
The specification then stated the following consistory clause, reflecting what would be included as claims 12 and 13 (page 8 par 4):
Accordingly, a preparation process for an oral solid composition of the invention is also provided, wherein carbidopa… is added separately to the composition, e.g. entacapone and levodopa, together with (an) excipient(s), are first mixed separately, carbidopa is added separately to the mixture obtained and the mixture is formulated, optionally together with (an) excipient(s), to a plurality of dosage forms.
The specification said that preferably, entacapone and levodopa should be first granulated, either separately or together, and that carbidopa be separated from them by adding it to the mixture either as separate granules, or “extragranularly as such (in powder form)”. The latter alternative was reflected in claims 2 and 14. The patentee noted that both wet and dry granulation could be used. However, it stated that wet granulation was preferable, as later reflected in claim 18, and that suitable granulation methods were known in the art (page 9 par 1).
The specification described examples of “these kinds of formulations according to the invention” in Example 2. The specification stated that the absorption of the three APIs, from formulations 3 and 4 (being those in Example 2) had been studied and that the results in Figures 4-6 showed that the respective absorption from those formulations was comparable to commercial reference formulations (page 9 par 2).
The specification stated that the inventors had found that the three APIs “are as such compatible with each other” (page 9 par 3). But, it then noted that the inventors had found that many commonly used excipients were “not suitable to be used in oral solid compositions” containing the three APIs. It continued (page 9 par 4-page 10):
Most of the levodopa-carbidopa formulations available in the market contain microcrystalline cellulose as a carrier. Also, the entacapone formulations COMTESS® and COMTAN®, which recently became available in Europe, contain considerable amounts of microcrystalline cellulose. In the prior art microcrystalline cellulose appears to be an acceptable excipient. For compositions of the invention, applicants unexpectedly found that microcrystalline cellulose destabilizes the formulations on long term storage, when all three active agents are combined together. (emphasis added)
The specification continued with a consistory clause foreshadowing claim 11, that the invention provided an oral solid pharmaceutical composition comprising pharmacologically effective amounts of the three APIs “and at least one pharmaceutically acceptable excipient other than [MCC]” (page 10 par 1).
Next, the specification stated that the inventors had found that tablets containing polyethylene glycol (being the product Macrogol 6000) as an excipient were unstable in a standard stability test, as in formulation 2. The inventors said that they believed that a reason for the stability problems was that the surface activity of polyethylene glycol might have enhanced the degradation of the active substance,s and that they had found that other surface active substances such as polysorbate and sodium lauryl sulphate were also “incompatible with the fixed dose combination e.g. as indicated by standard stability tests”. The stability tests had also revealed “incompatibilities of the drug combination with colloidal silicon oxide, copolyvidone and previously mentioned substances with surface active properties” (page 10 par 2). The specification said that a preferred embodiment of “a stable oral solid pharmaceutical composition” would be comprised of pharmacologically effective amounts of the three APIs and “at least one pharmaceutically acceptable excipient other than [MCC] and/or surface active agents and/or silica” (page 10–page 11)). It continued (page 11 par 1):
Despite the several incompatibilities found, the oral solid composition according to the invention can still surprisingly be prepared by using few compatible excipients alone or two or more together. Compatible excipients include, e.g., sugar alcohols, preferably mannitol, and starch, preferably maize starch as well as other appropriate excipients mentioned herein.
The specification then proceeded to recite a consistory clause for claim 4 based on the above identification of “compatible excipients” and to discuss preferable proportions of those and other excipients (page 11 par 2 – page 12).
The patentee then said that the amount of each API in the oral composition “is dependent on numerous factors known to one skilled in the art, such as, the severity of the condition of the patient, the desired duration of use, etc” and that “[t]he solid oral composition of the invention may also contain one or more other pharmacologically active agents”. The specification then stated that in the formulation according to the invention, the amounts of each API were, preferably, 25 to 400 mg of entacapone, 25 to 300 mg of levodopa and 5 to 75 mg of carbidopa, with especial ranges within each of the wider ones (page 12 par 3 – page 13). It said that the inventors had discovered that “the following embodiment is particularly preferred, e.g. for a wide variety of patient populations, including early and late stage Parkinson patients” namely doses of 200 mg of entacapone with 100 mg of levodopa and 25 mg of carbidopa, and then gave four other preferred embodiments, with 200 mg of entacapone in each and dosages of levodopa/carbidopa of: 50/12.5 mg, 150/37.5 mg, 100/10 mg and 250/25 mg, reflecting ratios of either 4:1 or 10:1 (page 13 par 1).
The specification then recited a consistory clause for claim 21 (page 13 par 2):
As a further aspect the invention provides an oral solid fixed dose composition comprising pharmacologically effective amounts of entacapone, levodopa, and carbidopa … and comprising at least one pharmaceutically acceptable excipient, whereby the therapeutic effect achieved with the said composition in the treatment of Parkinson's disease is comparable, e.g. similar, to that achieved with the known separate formulations of entacapone, levodopa and carbidopa, e.g. entacapone tablets and levodopa-carbidopa tablets referred to herein, which are administered concomitantly, at the same doses of the active agents as the combination formulation of the invention.
(the italicised portions above were not later included in claim 21; the word “therapeutic” appeared in claim 21 as “therapeutical” but it was common ground that the latter word meant therapeutic; and the final phase appeared in claim 21 as the “present combination formulation”)Next, the patentee stated that one embodiment of “the said composition of the invention” was “pharmacokinetically comparable” to the known reference formulations, and another embodiment was “substantially bioequivalent with” those reference formulations (page 13 par 3 – page 14):
e.g. the bioavailability achieved with the composition of the invention is at levels comparable to that achieved with the concomitant administration of the same doses of the known separate formulations of entacapone, levodopa and carbidopa, e.g. the entacapone and levodopa-carbidopa formulations used herein as a reference. (See also Examples). (emphasis added)
Importantly, the specification then set out five preferred embodiments using the same dosage combinations as in [40] above, the first of which was (page 14 par ):
In preferred embodiments,
a}the therapeutic effect, such as pharmacokinetics, e.g. bioavailability, achieved with a combination composition of the invention of the dose of 200 mg entacapone/100 mg levodopa/25 mg carbidopa is comparable to that of the known formulation of entacapone and the known formulation of levodopa-carbidopa administered concomitantly at the same doses of active agents as the present combination composition;
The specification stated that COMTESS and COMTAN were made using compaction granulation for which “large amounts of excipients are needed to obtain compressible granules and tablets having the desired, fast, dissolution behaviour of an immediate release formulation”. The patentee said that the compactability of entacapone was sufficient to allow a tablet with a 200 mg dose that was relatively easy to swallow. The patentee then explained that the compactability of the fixed dose combination tablets was “surprisingly worse than that of entacapone alone”. It said that using polyethylene glycol improved compactability but produced tablets “indicated to be unstable in storage”. The specification stated that the size of a 3-in-one composition prepared by compaction granulation could become too large “especially for parkinsonism patients who have difficulties in swallowing” (page 16).
Relevantly, the specification then set out consistory clauses for claims 16 and 17, the latter dealing with a four step process for preparing an oral solid composition “according to the invention”. That process consisted of, first, mixing pharmacologically effective amounts of entacapone and levodopa with at least one pharmaceutically acceptable excipient and, optionally, a disintegrant to obtain a first mixture, secondly, granulation of that mixture to obtain a plurality of granules, thirdly, adding a pharmacologically effective amount of carbidopa and optionally both a lubricant and one or more pharmaceutically acceptable excipients to the granules to obtain a second mixture and, last, formulating the second mixture into a plurality of dosage forms (page 17 par 1). The specification discussed different mixing techniques, including wet granulation and coating for the tablets (page 17 par 2) and then stated (page 17 par 3 – page 18):
By using the process of the invention tablet compositions of the invention may be made which are particularly small for the dosages contained therein and are convenient to administer. These may be any of a wide variety of shapes, although an oval form is preferred. The small size is particularly surprising in view of the size of the presently commercialized COMTAN®/COMTESS® entacapone tablet and in view of the fact that entacapone is difficult to compress and still give an acceptable release especially in the presence of levodopa and carbidopa. Furthermore, we have found that the composition of the invention surprisingly have [sic] especially good flowability properties. (emphasis added)
Next, the specification set out consistory clauses for claims 19 and 20 that said that another aspect of the invention provided “an oral pharmaceutical tablet” comprising the preferred ranges of dosages of the three APIs and preferable weights, volume and dimension ranges for the tablets (page 18 pars 1 and 2).
The patentee stated that “[i]nsofar as the details of the pharmaceutical excipients are not specifically described herein”, they were described in handbooks known in the art (page 18 par 5). The specification then set out details of Examples 1 and 2 that recorded the absorptions of the three APIs when tested using Formulations 1 and 2 and Formulations 3 and 4 respectively, against two sets of reference products from the known formulations. Thus, the patentee described Example 1 as follows (pages 19 par 3 – page 20 par 2):
EXAMPLE 1
The absorptions of entacapone, levodopa, and carbidopa from entacapone/levodopa/carbidopa 200/100/25 mg tablet formulations containing different excipients and prepared by different methods were tested after a single oral dose in 15 healthy volunteers. The tablets were prepared by wet granulating all the active agents at the same time (Formulation 1) and by compaction granulating all the active agents at the same time (Formulation 2). The formulations were as described in Table 1.
The absorption study was designed to assess the absorption of the active substances between two fixed dose combination tablets and an entacapone 200 mg tablet administered together with a levodopa/carbidopa 100/25 mg tablet, i.e., SINEMET PLUS® distributed in Europe by DuPont Pharmaceuticals Ltd. The study was performed according to an open randomized cross-over design. The plasma entacapone, levodopa, and carbidopa concentrations were determined by two separate reversed-phase HPLC methods, i.e., the entacapone concentrations were measured by one method and the levodopa and carbidopa concentrations by another method.
The results are shown in Figures 1-3. (emphasis added)
Table 1 set out three columns identifying the ingredients and, for each of formulations 1 and 2, the quantity of any ingredient added. The table culminated in giving, first, the total theoretical weights of the coated tablets as 619.5 mg and 660 mg respectively and, secondly, the methods of manufacture being, high shear granulation of all active substances together for Formulation 1 and compaction granulation of the three APIs together with Formulation 2 (pages 20-21).
The specification then proceeded to explain Example 2, which had adopted a similar process of recording test results using 15 healthy volunteers, a control dose and then doses of Formulations 3 and 4. The specification described these as “[e]xamples of suitable entacapone/levodopa/carbidopa 200/100/25 mg tablet formulations”. The inventors said that they added carbidopa separately as granules in Formulation 3 and in powder form in Formulation 4. They stated that otherwise they prepared both formulations 3 and 4 by, first, wet granulating entacapone and levodopa together with maize starch, mannitol, croscarmellose sodium and povidone in a conventional high shear mixer, secondly, wet granulating the respective form of carbidopa separately with the same excipients in a high shear mixer, thirdly, mixing the dry entacapone/levodopa granulates and the dry carbidopa granules with croscarmellose sodium, mannitol and magnesium stearate and then compressing the mass so obtained into tablets with an oval shape that were coated with a coloured HPMC coating (page 21 par 1 – page 22). Example 2 concluded (page 22 par 1):
According to the results shown in Figures 4-6 the absorptions of the tested two formulations are comparable to the commercial reference formulations. The dissolved amounts of entacapone, levodopa and carbidopa are at least 50 % in 30 minutes when measured with USP dissolution equipment. (emphasis added)
Table 2 was as follows (page 23):
Formulation 3 (mg) Formulation 4 (mg) Entacapone 200.0 200.0 Levodopa 100.0 100.0 Carbidopa monohydrate 27.0 27.0 Maize Starch 85.0 75..0 Mannitol 86.1 44..0 Croscarmellose sodium 23.7 20..0 Povidone 39.7 36.0 Magnesium stearate 8.5 8.0 Theoretical weight of the core tablet 570.0 510.0 HPMC-coating containing colour pigments 17.0 15.0 Theoretical weight of the coated tablet 587.0 525.0 Manufacturing of Granules Entacapone/ Levodopa Granules and Carbidopa Granules were Manufactured Separately i[n]a high shear mixer Entacapone/ Levodopa granules were Manufactured in a high shear mixer. Carbidopa was added as such to the granules together with tabletting excipients.
excipients
The oval tablets compressed from the tablet mixtures had the following dimensions: Formulation 3 (length of 16.4 mm; width of 7.7 mm and height of 5.7 mm) and Formulation 4 (length of 16.4 mm; width of 7.7 mm and height of 5.1 mm)
Next, Example 3 used different dosages of levodopa and carbidopa in Formulation 5 (150/37.5 mg) and Formulation 6 (100/10 mg) that Table 3 recorded as having a core weight of 694 mg and 444 mg respectively, before a weight gain of about 2-3% from a coloured HPMC coating (page 24 par 1).
The specification stated that those skilled in the art would recognise that other embodidments were possible “without departing from the spirit and scope of the invention” and that the specification and examples be considered as exemplary only “with a true scope and spirit of the invention being indicated by the following claims” (page 24 par 3 – page 25). The specification next stated:
Throughout the description and claims of the specification the word “comprise” and variations of the word, such as “comprising” and “comprises”, is not intended to exclude other additives, components, integers or steps.
After setting out the 21 claims, the specification concluded with 6 sheets, being Figures 1-6.
The claims
The specification included the following claims that are in issue in these proceedings.
CLAIMS:
1.An oral solid composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, and a pharmaceutically acceptable excipient, wherein a substantial portion of carbidopa is separated from entacapone and levodopa.
2.The composition according to claim 1, wherein entacapone and levodopa are in the form of granules and carbidopa is in powder form.
…
12.A method for preparing an oral solid composition comprising entacapone, levodopa, and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, which comprises adding carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, separately to the remainder of the composition.
13.A method for preparing an oral solid composition comprising entacapone, levodopa, and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, which comprises mixing first entacapone and levodopa separately, adding carbidopa separately and formulating the mixture into a plurality of dosage forms.
14.A method according to claim 12 or 13, wherein carbidopa is added in powder form extragranually to granules of entacapone and levodopa.
…
17.A method for preparing an oral solid composition comprising entacapone, levodopa, and carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, wherein the method comprises
a)mixing pharmacologically effective amounts of entacapone and levodopa, or a pharmaceutically acceptable salt or hydrate thereof, with at least one pharmaceutically acceptable excipient and a disintegrant to obtain a first mixture;
b) granulating the first mixture to obtain a granule batch;
c)adding a pharmacologically effective amount of carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, optionally a lubricant, and optionally one or more pharmaceutically acceptable excipients to the granule batch to obtain a second mixture;
d) formulating the second mixture into a plurality of dosage forms.
18.The method according to claim 16 or 17, wherein the granulation method is wet granulation.
19.An oral pharmaceutical tablet comprising 200 mg entacapone, 50-150 mg levodopa, and 10-37.5 mg carbidopa and having substantially the following characteristics:
weight 400-750 mg; and volume dimensions for tablet from 200 to 1000 mm3.
20.An oral pharmaceutical tablet comprising 200 mg entacapone, 50-150 mg levodopa, and 10-37.5 mg carbidopa and having substantially the following characteristics:
weight 400-750 mg; and volume dimensions for tablet: length 13‑18 mm; width 6-9 mm; and height 4-7 mm.
21.An oral solid fixed dose composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, and comprising at least one pharmaceutically acceptable excipient, whereby the therapeutical effect achieved with the said composition in the treatment of Parkinson's disease is comparable to that achieved with the known separate formulations of entacapone and levodopa and carbidopa which are administered concomitantly at the same doses of the active agents as the present combination formulation. (emphasis added)
The skilled addressee
The objective person through whose experience and knowledge the construction of a patent and issues about it must be approached is a person skilled in the relevant art who is aware of, or able to access, the common general knowledge as it existed at a relevant priority date. This person is a skilled addressee. Very often, in pharmaceutical or other technical patent cases, the issues arising in relation to an invention are not confined simply to one field, discipline, or art. Thus, the skilled addressee will be a legal construct whose appreciation must draw upon expertise in more than one field, discipline or art. That will reflect the likely reality that the claimed invention will have involved an inter-disciplinary team of various skilled persons, as Sachs LJ explained giving the reasons of the Court of Appeal of England and Wales in General Tire& Rubber Co v Firestone Tyre and Rubber Co Ltd [1972] RPC 457 at 485. The legal standard for the degree of expertise that the skilled addressee will bring to the problem at hand, in light of the common general knowledge, is, again, an objective one of a non-inventive skilled worker in the field: Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253 at 293 per Aickin J with whom Barwick CJ, Stephen, Mason and Wilson JJ agreed.
The purpose of this legal construct, like that of the reasonable person in the law of negligence, or the ordinary reasonable reader, viewer or listener in the law of defamation, is to provide an objective standard that can be applied to the resolution of the issue at hand. Here, it was common ground that the skilled addressee of the patent consists of persons skilled in the arts of clinical medicine, pharmacology, pharmacy and formulation of medicines in the treatment of Parkinson’s disease.
The expert witnesses
The diversity of callings of the members of the skilled composite or team to whom the patent was addressed was reflected in the expert witnesses. Orion relied on four experts, Professor Martyn Davies, Professor Peter Jenner, Dr Angelo Morella and Dr John O’Neill.
Professor Davies had been Professor of Biomedical Surface Chemistry in the School of Pharmacy at the University of Nottingham since 1996. He had extensive academic and practical experience in pharmaceutical technology, formulation of oral compositions, advanced drug delivery systems and consulting for pharmaceutical companies. This had included supervising detailed analysis of various combination products for medical treatments, including determining their structure and the compatibility of various APIs with one another as well as with formulation excipients. Although, as at June 1999, he was familiar with the use of levodopa and carbidopa and the SINEMET product in the treatment of Parkinson’s disease, he did not recall then (or at June 2000) being aware of entacapone. Prof Davies gave evidence principally on matters concerning the issue of the construction of the patent.
Professor Jenner had been Emeritus Professor of Pharmacology, Kings College, London, since 2008. Until recently he had been Director of the Neurodegenerative Diseases Research Centre at King’s College and Director of the National Parkinson Foundation Centre of Excellence. He had worked in the area of pharmacology of Parkinson’s disease for over 40 years. He had been, among other distinctions, a Fellow of the Royal Pharmaceutical Society of Great Britain since 1994, a Fellow of the British Pharmacological Society since 2005 and a Fellow of the Royal Society of Medicine since 2011. He is one of the most cited authors in Neuroscience having authored or co-authored over 700 papers, review articles and book chapters, written or edited numerous monographs and, before June 1999, over 200 of his then 319 publications related to Parkinson’s disease. He had undertaken research into Parkinson’s disease continuously from the early 1970s, during much of which time he worked in a clinical department of neurology. He had worked, written and spoken extensively in relation to clinical practice of treating Parkinson’s disease at the clinician-patient level, and on the use of drugs and treatment strategies of neurologists treating patients with the disease.
Prof Jenner had contributed chapters to the multi-volume book series Handbook of Clinical Neurology that Dr Richard Peppard, a clinician called by Actavis, described as being in the nature of an encyclopaedia of clinical neurology focused primarily on the pathological features, clinical manifestations and diagnoses of neurological disorders. Dr Peppard referred to that text as at June 1999 and subsequently in relation to, among others, Parkinson’s disease in the course of his clinical practice, teaching and research. Prof Jenner had also consulted extensively for pharmaceutical companies, principally in relation to the discovery and development of new therapeutic drugs for treatment of neurological disorders, including Parkinson’s disease. He gave evidence relating to pharmacological and formulatory issues, although he had not worked on drug formulation in the way a formulator would. He also had extensive experience of working with clinicians in the treatment of Parkinson’s disease.
Dr Morella was a consultant in the area of drug delivery and pharmaceuticals. He had about 27 years’ experience as a pharmaceutical formulator in the industry, including extensive experience in developing oral formulations, granulation techniques and pharmacology. The latter experience included using and interpreting pharmacokinetic data (i.e. data relating to drug absorption, distribution, metabolism and excretion by the human body) and pharmacodynamic data (i.e. data relating to the biochemical and physiological effect of a drug on the body). He gave evidence relating to pharmacology and formulation.
Dr O’Neill was a consultant neurologist at St Vincent’s General and Private Hospitals and Mater Misericordiae Private Hospital in Sydney and in private practice in Wollongong who had specialised in this field since he became a Fellow of the Royal Australasian College of Physicians in 1985. He attained a Doctorate of Medicine from the University of New South Wales in 1987 and since 2002 he has been a conjoint senior lecturer at that University. From 1981 to mid-2000 Dr O’Neill had treated many hundreds of patients with Parkinson’s disease, and that class of patients had comprised a significant proportion of his neurology practice during his career. He gave evidence as to the clinical treatment of Parkinson’s disease.
Actavis relied on three experts, Dr Peppard, Dr Phillip Reece and Professor Peter Stewart.
Dr Peppard was a senior consultant neurologist at St Vincent’s Hospital, Melbourne and the senior movement disorders specialist at Wantirna Health, a rehabilitation and palliative care hospital in Victoria at which over 80% of his patients have suffered from Parkinson’s disease. He has conducted clinics in other parts of Victoria and in Hobart and Launceston. He also practised privately, specialising in diagnosis and management of movement disorders. About 70% of patients referred to him in his private practice have suffered from Parkinson’s disease. He became a Fellow of the Royal Australian College of Physicians in 1986 after completing advanced training in neurology. He was a post-doctoral research fellow at the University of British Columbia between 1986 and 1988, researching neurodegenerative disorders, including Parkinson’s disease and providing clinical care to patients suffering Parkinson’s disease and other neurodegenerative diseases. He has continued his research interest in his career. He teaches at the St Vincent’s Clinical School, that is part of the Faculty of Medicine at the University of Melbourne. In 1993 he was awarded the degree of Doctor of Medicine by that University. Dr Peppard gave evidence as to the clinical treatment of Parkinson’s disease.
Dr Reece was a clinical pharmacologist with over 30 years’ experience involving extensive research and practical work on pharmacokinetic and pharmacological studies of pharmaceuticals. Early in his career he worked as a hospital scientist. Between 1986 and 1987, in addition to his work as a scientist, he worked part-time as an evaluator of pharmacokinetic properties of about six products for the Therapeutic Goods Administration (TGA). Later, he worked for a number of pharmaceutical companies in developing new pharmaceutical products, including the conduct of clinical trials, before becoming an independent consultant in pharmaceutical and biotechnology matters in 2003. Also, in late 2003 he was appointed an Honorary Senior Fellow in the Department of Pharmacology in the University of Melbourne, and has lectured there since then. He gave evidence relating to pharmacology.
Professor Stewart was Emeritus Professor in the Faculty of Pharmacy and Pharmaceutical Sciences at Monash University. He was awarded a Doctor of Philosophy in Pharmacy by the University of Queensland in 1976, having attained his Bachelor of Pharmacy degree there in 1966. He worked in the Department of Pharmacy there from 1967 in various academic positions and was appointed Head of that Department in 1987, which he remained until 1991. In 1992 he moved to become Dean of the School of Pharmaceutics at the then Victorian College of Pharmacy, which subsequently became the Faculty of Pharmacy and Pharmaceutical Sciences at Monash University. Over the course of his career he undertook work relating to the design and manufacture of solid oral dosage forms, including work for pharmaceutical companies relating to the evaluation of both the dissolution of drugs from solid oral dosage forms and the chemical and physical stability of drugs and dosage forms, investigating mixing techniques for pharmaceutical ingredients in powder form and investigating the development of formulations for new drugs. He was made a Fellow of the Pharmaceutical Society of Australia in 1990, and between 1990 and 1995, was a member of the Pharmaceutical Sub‑Committee of the Australian Drug Evaluation Committee. He has also held a number of other positions. Prof Stewart gave evidence relating to formulation.
(1) The definition of the invention issue – Actavis’ argument
Actavis argued that the patentee had defined the invention in the whole passage that I have quoted (page 3 pars 3-4) of the complete specification at [21] above. The words on which Actavis relied were “which has i.a. preferable stability and bioavailability characteristics and which is easy to swallow”. That is, it contended that the words appearing after the words in brackets “hereinafter referred to as a composition according to the invention” defined essential characteristics of every such composition.
There was nothing in the suggestion of a possible combination in the Rinne article that a skilled addressee “could be expected to have regarded as relevant to solving” the problem of how to formulate such a 3-in-one combination or how to do so in respect of any aspect the subject of any of claims 19, 20 and 21: Lockwood (No 2) 235 CLR at 222-223 [152].
For these reasons, I would not have found that the invention would have been obvious to a skilled addressee who considered the Nomecomt report and the Rinne article, in light of the common general knowledge as at 29 June 2000.
Conclusion
I have found that the patent and challenged claims are valid and that all of Actavis’ products infringe claims 17, 18 and 21 and five of them infringe claims 19 and 20. I have rejected all of Actavis’ challenges to validity of the patent and claims.
The parties should bring in draft orders to give effect to these reasons and address the issue of costs. Each side has had a measure of substantive success and failure which may be relevant to the award of costs.
I certify that the preceding three hundred and twenty (320) numbered paragraphs are a true copy of the Reasons for Judgment herein of the Honourable Justice Rares. Associate:
Dated: 21 August 2015
SCHEDULE
NSD 2456 of 2013
BETWEEN:
ORION CORPORATION
First ApplicantNOVARTIS PHARMA AG
Second ApplicantNOVARTIS PHARMACEUTICALS (AUSTRALIA) PTY LTD ACN 004 244 160
Third ApplicantACTAVIS PTY LTD ACN 003 854 626
First Cross-ClaimantMEDIS PHARMA PTY LTD ACN 109 225 747
Second Cross-ClaimantAND:
ACTAVIS PTY LTD ACN 003 854 626
First RespondentMEDIS PHARMA PTY LTD ACN 109 225 747
Second RespondentORION CORPORATION
First Cross-RespondentNOVARTIS PHARMA AG
Second Cross-RespondentNOVARTIS PHARMACEUTICALS (AUSTRALIA) PTY LTD ACN 004 244 160
Third Cross-Respondent
6
1
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