Alphapharm Pty Ltd v Novartis AG, Apotex Pty Ltd v Norartis AG - [2016] APO 77

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Alphapharm Pty Ltd v Novartis AG
Apotex Pty Ltd v Novartis AG
[2016] APO 77

Patent Application: 2009330176

Title:Dosage regimen for a S1P receptor agonist

Patent Applicant:                   Novartis AG
Opponent 1:  Alphapharm Pty Ltd
Opponent 2:  Apotex Pty Ltd
Delegate:  Dr S.D. Barker
Decision Date:  2 November 2016
Hearing Date:  Written submissions completed on 1 September 2016

Catchwords: PATENTS - oppositions under section 104 – allowability under section 102(2)(a) and 102(2)(b) considered – oppositions unsuccessful – amendment allowed – costs awarded against the opponents

Representation: Patent attorney for the applicant: Davies Collison Cave
Solicitor for the opponents: DibbsBarker

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2009330176

Title:Dosage regimen for a S1P receptor agonist

Patent Applicant: Novartis AG
Date of Decision: 2 November 2016
DECISION
The oppositions are unsuccessful.
Subject to appeal I allow the amendments filed on 2 April 2015 and 25 June 2015.
I award costs according to Schedule 8 against Alphapharm Pty Ltd and Apotex Pty Ltd.
REASONS FOR DECISION
Background

Patent application 2009330176 was filed by Novartis AG (Novartis) on 21 December 2009 under the provisions of the Patent Cooperation Treaty as international application PCT/US2009/068888. The application was advertised as accepted on 6 March 2014.
Notices of Opposition to the grant of the patent were filed by Alphapharm Pty Ltd (Alphapharm) and Apotex Pty Ltd (Apotex) on 6 June 2014 and Evidence in Support (for both oppositions) was completed on 8 December 2014. No Evidence in Answer was filed.
Novartis filed requests to amend the specification on 2 April 2015 and 25 June 2015. Leave to amend was advertised on 12 November 2015. Two Notices of Opposition to the allowance of the amendments were filed by Alphapharm and Apotex (collectively the Opponents) on 12 January 2016. This decision relates only to the oppositions to the allowance of the amendments.
The opposition
Statements of Grounds and Particulars were filed by Alphapharm and Apotex on 12 February 2016, each specifying grounds of opposition that the proposed amendments are not allowable because they do not comply with s 102(2)(a) or s 102(2)(b).
Evidence in Support for both opponents consists of a declaration of Professor John Owen King (King) with exhibits JK-1 and JK-2 filed on 29 April 2016. No Evidence in Answer was filed.
The matter was heard by way of written submissions, which were completed on 1 September 2016.
The specification
The specification relates to a dosage regimen for the initiation of S1P receptor modulator or agonist therapy aimed at reducing side effects associated with such therapy. S1P receptor modulators or agonists are useful for the treatment of various conditions, including transplant rejection and inflammatory and immune diseases, such as multiple sclerosis, and the specification indicates that a preferred S1P receptor agonist is FTY720 (also known as fingolimod and 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol). In the disclosed dosage regimen the S1P receptor modulator or agonist is administered at a dose lower than the standard daily dose during an initial period of treatment, after which the dose is increased to the standard daily dose. The specification indicates that this dosage regimen allows the standard daily dose of S1P receptor modulator or agonist therapy to be achieved with minimal negative chronotropic effects and/or AV block effects associated with S1P receptor modulator or agonist therapy.
At acceptance, the specification included one example describing a nine day FTY720 dose titration study wherein FTY720 was administered to healthy subjects at a dose of 0.125 mg for the initial three days, 0.25 mg for the next two days, 0.5 mg for the following two days, and 1.25 mg for the final two days. In comparison with administering a 1.25 mg dose of FTY720 for each of the nine days, the titration regimen reduced the heart rate decrease observed on the first day of administration, and provided improved minimum heart rates over the course of the study.
The legislation
Examination of the application was requested before 15 April 2013 and therefore substantive amendments to the Patents Act 1990 (the Act) brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 do not apply to the present application.
Subsection 102(2) of the Act as it applies to the present application is as follows:
(2) An amendment of a complete specification is not allowable after the relevant time if, as a result of the amendment:
(a) a claim of the specification would not in substance fall within the scope of the claims of the specification before amendment; or
(b) the specification would not comply with subsection 40(2) or (3).
The "relevant time" for the purpose of s 102(2)(a) is after the specification has been accepted (s 102(2A) of the Act). As the present specification had been accepted when the amendments were requested, the requirements of s 102(2) apply.
The applicable parts of s 40 of the Act as they apply to the present case are set out below:
(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.
(3)The claim or claims must be clear and succinct and fairly based on the matter described in the specification.
The nature of the amendments
The specification at acceptance included 26 claims. The amendments proposed on 2 April 2015 are directed to both the claims and the description, and reduce the number of claims to 21. The amendment proposed on 25 June 2015 was filed in response to an adverse examination report on the proposed amendments of 2 April 2015, and is directed to deletion of an omnibus claim (claim 21 of the claims as proposed to be amended on 2 April 2015, corresponding to claim 26 of the claims as accepted), reducing the number of claims to 20.
As proposed to be amended the claims define various uses of a dosage regimen in which an S1P receptor modulator or agonist as defined in the claims is administered at a lower than standard daily dose for an initial treatment period, after which the dose is increased to the standard daily dose of 0.5 mg, and wherein the initial daily dose is 0.125 mg or 0.25 mg. The claims as proposed to be amended include Swiss type claims directed to the preparation of a medicament for the treatment of multiple sclerosis (claims 1-6) or for ameliorating, preventing or limiting a negative chronotropic side effect associated with treatment of an autoimmune disease (claims 13-15); method of treatment claims directed to the treatment or prevention of multiple sclerosis (claims 7-12); a method claim directed to ameliorating, preventing or limiting a negative chronotropic side effect associated with treatment of an autoimmune disease (claim 16); and claims directed to a kit when used according to the dosage regimen of preceding claims (17-20).
The amendments to the claims have the effect of limiting accepted claims 1 and 9 (corresponding to amended claims 1 and 7) such that the autoimmune disease or disorder being treated by the S1P modulator or agonist is multiple sclerosis, defining the standard daily dose in accepted claims 1, 9, 17, 21 and 22 (corresponding to amended claims 1, 7, 13, 16 and 17, respectively) as 0.5 mg, and defining the initial daily dose in accepted claims 1, 9, 17 and 21 (corresponding to amended claims 1, 7, 13 and 16, respectively) as 0.125 mg or 0.25 mg. Accepted claims 23 and 24 (corresponding to amended claims 18 and 19, respectively) have been amended to delete references to doses corresponding to less than 0.125 mg. Claim 1 has also been amended such that it refers only to treatment of the relevant disease or disorder, rather than treatment or prevention.
To more clearly illustrate the nature of the amendments, a marked up version of claim 1 is reproduced below:
1. Use of an S1P receptor modulator or agonist in the preparation of a medicament for the treatment ~~or prevention~~ of an autoimmune disease or disorder in a person in need thereof, wherein the S1P receptor modulator or agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form, or the phosphate thereof of formula Ila,
wherein R_2a is H, R_3a is OH, X_a is O, R_1a and R_1b are OH, and
wherein said S1P receptor modulator or agonist is administered at a lower dose than the standard daily dosage of said S1P receptor modulator or agonist during an initial treatment period, and following the initial treatment period the dosage is increased to the standard daily dosage of said S1P receptor modulator or agonist,
wherein the standard daily dose is 0.5 mg and the initial daily dose is 0.125mg or 0.25mg and
~~2. Use according to claim 1,~~ wherein the autoimmune disease or disorder is multiple sclerosis.
The amendments of 2 April 2015 also introduce a second example to the description. This example reports a titration regimen of fingolimod (i.e. 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol as recited in the claims), wherein fingolimod is administered to healthy subjects at a dose of 0.125 mg on days 1-14, 0.25 mg on days 15-28 and 0.5 mg on days 29-30. This regimen is stated to attenuate the negative chronotropic effect seen on day 1 of fingolimod treatment initiation without initial dose titration.
Subsection 102(2)(b)
Failure to define the invention, lack of clarity
The Opponents submit that the claims as proposed to be amended do not comply with ss 40(2) and 40(3) because they lack clarity and the skilled reader is unable to ascertain the precise extent of the monopoly claimed.
It is a requirement of s 40(3) of the Act that the claims be clear. This requirement is satisfied if a person could ascertain "whether or not what he proposes to do falls within the ambit of the claim".[1] However, the terms used in claims need not be precise and absolute, as set out in Flexible Steel Lacing Company v Beltreco Ltd[2] at [81] (references omitted):
"Lack of precise definition in claims is not fatal to their validity, so long as they provide a workable standard suitable to the intended use. The consideration is whether, on any reasonable view, the claim has meaning. In determining this, the expressions in question must be understood in a practical, commonsense manner. Absurd constructions should be avoided and mere technicalities should not defeat the grant of protection."
[1] Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59 at 60.
[2] [2000] FCA 890; (2001) 49 IPR 331 (cited with approval in Austal Ships Sales Pty Ltd v Stena Rederi Aktiebolag [2008] FCAFC 121; (2008) 77 IPR 229).
The requirement of s 40(2)(b) that the specification "end with a claim or claims defining the invention" is related to the requirement of clarity, and has been considered in PhotoCure ASA v Queen's University at Kingston[3] at [117] (references omitted):
"if sufficient ambiguity attends a claim it may be invalid for failing to define the invention. However, invalidity will only arise if the claim is 'incapable of resolution by a skilled addressee by the application of common sense and common knowledge'."
[3] [2005] FCA 344; (2005) 215 ALR 41.
The Opponents submit that the phrase "initial treatment period" is unclear, and is made more unclear by the introduction of Example 2.
Pre-existing defects in the specification are not relevant to consideration of the allowability of amendments under s 102, as noted by Bennett J in Apotex Pty Ltd v Les Laboratoires Servier (No 2):[4]
"There may be deficiencies in the (existing) complete specification or lack of compliance with s 40 which do not fall for consideration at this time. The question is whether, as a result of the introduction of the proposed new claims, the amendments are not allowable because of the requirements of s 102."
[4] [2009] FCA 1019; (2009) 83 IPR 42 at 48, [28].
References to the "initial treatment period" have not been amended in the claims, and there has been no suggestion, and nor do I consider, that the amendments to the claims have any effect on the meaning of this phrase. Therefore the question to be considered is whether the amendment to add Example 2 to the description has resulted in a lack of clarity such that the specification does not comply with ss 40(2) and 40(3).

To address this question, it is necessary to construe "initial treatment period". The principles to be applied in construing claims are well established, and were summarised by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd: [5]
"the words in a claim should be read through the eyes of the skilled addressee in the context in which they appear ... While the claims define the monopoly claimed in the words of the patentee's choosing, the specification should be read as a whole ... It is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification ... terms in the claim which are unclear may be defined or clarified by reference to the body of the specification."
[5] [2009] FCAFC 70; (2009) 81 IPR 228 at 254, [118]-[120].
Construction of the specification is a question of law, and while expert evidence may assist in this process, it is a matter for the Court to decide on their construction.[6]
[6] Jupiters Ltd v Neurizon Pty Ltd [2005] FCAFC 90; (2005) 222 ALR 155 at 168-169, [67].
"Initial period of treatment" appears to be used interchangeably with "initial treatment period" in the specification and I am satisfied that it has the same meaning. The specification at pages 8-9 includes the following passage:
"According to the invention, the 'initial period of treatment' refers to the period during which the S1P receptor modulator or agonist is administered at a dosage lower than the standard daily dosage."
Although Novartis submit that no definition of "initial treatment period" is required or provided in the specification,[7] I am satisfied that this passage establishes a definition for "initial period of treatment" and that the meaning of "initial treatment period" is the same. This definition has not been altered by the proposed amendments. The specification subsequently describes embodiments of the initial period of treatment comprising four to fourteen days. There is no indication in the specification that these should be understood as limiting the meaning of "initial period of treatment".
[7] Novartis' Submissions at [64].
The Opponents rely on the evidence of Professor King, who is a Consultant Neurologist and treats patients with multiple sclerosis. Since 2000 around a quarter of his patients are multiple sclerosis patients.[8] Professor King is therefore a person who would have a practical interest in using the invention and can provide useful evidence of the understanding of the hypothetical skilled addressee.[9] Professor King states that:
"the term 'initial treatment period' is ambiguous because it is unbounded: the claim does not tell me the length of that period, when it starts or when it stops. I cannot meaningfully understand what the term is intended to encompass without knowing this boundary. Claim 1 does not give me enough information and I therefore find the term 'initial treatment period' ambiguous."[10]
[8] JK-1 at [1]-[13].
[9] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980; (2000) 49 IPR 225 at 241-242, [71]-[72].
[10] King at [10].
Professor King further states that the phrase in the claims as proposed to be amended "remains ambiguous".[11] Consideration of the dependent claims, the specification, and Example 1 of the description lead to Professor King's observation that "none of the potential periods exceed the potential boundary of 14 days".[12] Considering Example 2, Professor King infers that "the 'initial period of treatment' is 28 days since this is the period of time that the Titration Group is given a lower dose than the Active Control Group."[13] This "creates even greater uncertainty as to what the term 'initial treatment period' is supposed to mean"[14] and "introduces for the first time the concept of 28 days for an initial treatment period which is outside the bounds of anything disclosed in the Patent Application, or elsewhere in the Amended Application."[15]
[11] King at [14].
[12] King at [17].
[13] King at [21].
[14] King at [22].
[15] King at [25].
Novartis submit that there is no basis in the description for limiting the duration of the initial treatment period, [16] and that "at no point does Professor King indicate that he does not know what the phrases 'initial treatment period' and 'initial period of treatment' mean, or that he believes the phrases themselves are unclear."[17]
[16] Novartis' Submissions at [67].
[17] Novartis' Submissions at [78].
Professor King’s observation that the initial treatment period is ambiguous is because it is unbounded, and he therefore has recourse to the description to ascribe a duration to the period. The introduction of Example 2 changes the scope of that duration. However, I consider Professor King's comments regarding the ambiguity of the initial treatment period to reflect a search for a degree of precision and specificity in the claims which is not required, and despite Professor King's statement regarding the ambiguity of the phrase "initial treatment period", he is able to identify that the initial treatment period in Example 2 is 28 days. That is, he is able to identify what falls within the scope of the phrase.
Having considered the evidence and the text of the specification, it is apparent that the initial treatment period is that period in the claimed regimen during which a lower than standard daily dosage is administered, prior to the standard daily dosage being commenced. While the duration of this period is not specifically identified, it can be understood and identified in the context of the claimed methods, and in the absence of ambiguity in the phrase there is no necessity to limit the meaning of the initial treatment period by reference to preferred embodiments in the specification.[18] This has not changed as a result of the amendment.
[18] Kinabalu Investments Pty Ltd v Barron & Rawson Pty Ltd [2008] FCAFC 178 at [44].
Given that I do not consider the meaning of "initial treatment period" to have changed due to the amendments, it follows that the amendments have not resulted in a lack of clarity in the claims or a failure of the claims to define the invention.
Further, while not raised by either party, I note that claim 17 as amended refers to "the dosage regimen defined in any one of claims 1 to 1" (the corresponding claim 22 prior to amendment referred to the regimen defined in "any one of claims 1 to 11"). While it appears that the reference to "claims 1 to 1" is an error, it does not give rise to a lack of clarity, as the reference to "any one of claims 1 to 1" can be understood as a reference to claim 1.
I also note that the Statements of Grounds and Particulars refer to s 40(2)(a) in the context of the assertion that the claims do not define the invention. It is s 40(2)(b) which requires that the claims define the invention. In context, I consider that it is sufficiently clear that the particulars relate to clarity and failure to define the invention, and that the reference to s 40(2)(a) is in error. Novartis made submissions in relation to s 40(2)(a) rather than s 40(2)(b), which may have been responsive to this error in the particulars. However, Novartis' submissions in relation to clarity are also applicable to s 40(2)(b), and therefore Novartis have had an opportunity to respond to the case put by the Opponents.
Fair basis

The Opponents submit that the proposed amendments would result in the claims not being fairly based on the subject matter described in the specification as required by s 40(3) of the Act.
The High Court in Lockwood Security Products Pty Ltd v Doric Products Pty Ltd[19] approved the approach to fair basis set out by Gummow J in Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd:[20]
"the question is whether there is a real and reasonably clear disclosure in the body of the specification of what is then claimed, so that the alleged invention as claimed is broadly, that is to say in a general sense, described in the body of the specification."
[19] [2004] HCA 58; (2004) 217 CLR 274.
[20] (1988) 81 ALR 79 at 95.
It is the Opponents' submission that even as amended by the addition of Example 2, the specification only discloses an initial treatment period of between 4 and 28 days. As only claims 4, 10 and 14 as proposed to be amended limit the initial treatment period to a specific duration, the Opponents submit that the remaining claims, which define an unbounded initial treatment period, lack fair basis.
Novartis submit that any alleged deficiency would exist irrespective of the proposed amendments, as since there is no suggestion that "initial treatment period" should be construed as limited to the preferred embodiments of the invention, the introduction of new Example 2 does not alter the meaning of the phrase.[21]
[21] Novartis' Submissions at [71]-[72].
As noted previously, s 102(2)(b) relates only to deficiencies arising as a result of the amendment. As indicated above, I do not consider that the meaning of "initial treatment period" should be limited by reference to preferred embodiments in the specification. The claims as accepted define the same unbounded initial treatment period as the claims as proposed to be amended and I am therefore not satisfied that any lack of fair basis has arisen as a result of the amendment. It is not necessary to consider for the purpose of this decision whether the unbounded initial treatment period defined in the claims gives rise to a lack of fair basis in itself.
Subsection 102(2)(a)
The Opponents submit that as a result of the amendments the claims would not fall within the scope of the claims before amendment and therefore the amendments do not satisfy s 102(2)(a). The requirement of s 102(2)(a) is understood as equivalent to asking whether the amendment would have the effect of making something an infringement that would not have been an infringement before the amendment. [22]
[22] Bristol-Myers Squibb Company v Apotex Pty Ltd [2010] FCA 814; (2010) 87 IPR 516 at 523, [40].
The Opponents submit that if the term "initial treatment period" is considered to be clear, it can only be given meaning by reference to the description, which prior to amendment refers to initial treatment periods of between 4 and 14 days, and after the amendment introducing Example 2 discloses for the first time an initial treatment period of 28 days. The Opponents argue that "this new disclosure gives different content to the claims and means they are of different scope to the prior to amendment claims"[23] and "a claim construed to permit an initial treatment period of up to 28 days would not fall within the scope of pre-amendment claims construed to permit an initial treatment period of up to 14 days."[24]
[23] Opponents' Submissions at [35].
[24] Opponents' Submissions at [36].
In contrast, Novartis submit that the specific time periods referenced in the specification are identified as "embodiments" and not intended to limit the duration of the initial treatment period. Novartis pointed to similar circumstances in SyngentaCrop Protection AG v Bayer Intellectual Property GmbH, [25] where, in the absence of any indication in the specification that the Examples should be seen as limiting on the claims, the addition of new examples did not change the scope of the claims and was not proscribed by s 102(2)(a).[26]
[25] [2015] APO 65 at [32].
[26] Novartis' Submissions at [53]-[54].
I have discussed the construction of the phrase "initial treatment period" above and I do not consider it necessary to limit the meaning by reference to preferred embodiments in the specification. There is no suggestion in the specification that it should be understood with reference to the preferred embodiments or examples. Consequently, the introduction of new Example 2 does not alter the scope of the claims and does not make anything an infringement which would not have been an infringement before the amendment. The amendment therefore does not offend s 102(2)(a).
Conclusion
The opposition fails. The proposed amendments are allowable.
Costs
Ordinarily in proceedings such as these, costs follow the event. I see no reason to depart from this approach. I will award costs in accordance with Schedule 8 against the Opponents.
Dr S.D. Barker
Delegate of the Commissioner of Patents