LTS Lohmann Therapie-Systeme AG and Schwarz Pharma Limted
[2009] APO 16
•21 August 2009
ABSTRACTS OF DECISIONS
DECISION OF A DEPUTY COMMISSIONER OF PATENTS
Application : No. 746856 in the name of LTS Lohmann Therapie-Systeme AG and Schwarz Pharma Limited
Title: Transdermal therapeutic system which contains a D2 agonist and which is provided for treating Parkinsonism, and method for the production thereof
Action :Request under s 70 of the Patents Act for an extension of term and objections of the Commissioner thereto
Decision :21 August 2009
Abstract
The patent relates to a transdermal therapeutic system (transdermal patch) to deliver the D2 receptor agonist rotigotine), for the purpose of treating Parkinson’s syndrome. Transdermal administration of rotigotine via a patch is known in the art, but the invention lies in the matrix formulation which allows administration of the active, free base form of rotigotine, improved release of the agonist from the patch, and ease of manufacture.
The patentee applied for an extension of term of the patent based on the inclusion of NEUPRO® on the Australian Register of Therapeutic Goods which if successful, would extend the term of the patent until 22 November 2022 rather than 18 March 2019.
It was considered whether a pharmaceutical substance per se within the meaning of the Patents Act 1990, in substance falls within the scope of a claim or claims of the specification and more particularly whether the claimed product is a “substance (including a mixture or compound of substances) for therapeutic use”.
It was found that the claimed pharmaceutical compound comprised three components - a polymer matrix containing rotigotine, an inert backing layer and a protective layer. It was further found that the claimed product as a whole, comprising a protective layer which is to be removed before use, constituted a pharmaceutical substance in combination with a separate integer, and consequently the application does not satisfy the requirements of s 70(2)(a) and the patent cannot be granted an extension of term. Boehringer Ingelheim International GmbH v Commissioner of Patents [2001] FCA 647 and Prejay Holdings Ltd v Commissioner of Patents [2003] FCAFC 77 applied.
PATENTS ACT 1990
DECISION OF A DEPUTY COMMISSIONER OF PATENTS
Re:Patent Application No. 746856 in the name of LTS Lohmann Therapie-Systeme AG and Schwarz Pharma Limited, a request under s 70 of the Patents Act for an extension of term and objections of the Commissioner thereto.
BACKGROUND
This matter concerns a request by the patentee, LTS Lohmann Therapie-Systeme AG and Schwarz Pharma Limited (hereafter LTS), for an extension of term of patent number 746856 under section 70 of the Patents Act 1990. The patent is entitled “Transdermal therapeutic system which contains a D2 agonist and which is provided for treating Parkinsonism and method for the production thereof”. The application was filed on 18 March 1999, sealed on 15 August 2002, and its 20-year term will expire on 18 March 2019. LTS have requested an extension of term which, if successful, would extend the term of the patent until 22 November 2022.
The matter was heard in Canberra on 7 July 2009. LTS were represented by Ben Katekar of Counsel assisted by Lachlan Mullane patent attorney of Hodgkinson McInnes Patents, Sydney.
THE SPECIFICATION
The patent relates to a transdermal therapeutic system (transdermal patch) to deliver the D2 receptor agonist (-)-5,6,7,8,tetrahydro-6-[propyl[2-(2-thienyl)-ethyl]amino]-1-naphthol (rotigotine), for the purpose of treating Parkinson’s syndrome. Transdermal administration of rotigotine via a patch is known in the art and is preferable since the compound has a short in vivo half life and is subject to a high first pass effect when taken orally.
The description teaches that the patch is characterised by a matrix based on an acrylate or silicone-based non-aqueous polymer adhesive, having a solubility for the rotigotine free base of greater than or equal to 5% w/w. The transdermal therapeutic system consists of a backing layer, a self-adhesive matrix containing the active substance, and a protective film to be removed before use. This system has the following advantages over the prior art:
(i)The active form of the D2 agonist (rotigotine free base) may be used directly in this patch, whereas prior art patches contain the hydrochloride salt. The release of rotigotine free base from the patch is markedly improved in comparison to the salts used in prior art patches.
(ii) The patches are more easily manufactured since they overcome a difficulty in coating the prior art matrix to a backing layer.
Claims relevant to s 70 considerations are those relating to a pharmaceutical formulation. LTS has indicated at paragraph [8] of the written submissions, that they wish to prosecute the application for an extension of term based on claims 1-13 and 30 contained in amendments to the specification filed on 19 March 2009. These claims are as follows:
Claim 1:
A pharmaceutical compound for the treatment of disease adapted to be transdermally administered to a patient in need of said treatment comprising:
an effective amount of a free base (-)-5,6,7,8,tetrahydro-6-[propyl[2-(2-thienyl)-ethyl]amino]-1-naphthol and an acrylate or silicone based non-aqueous polymer adhesive compound, wherein the solubility of the (-)-5,6,7,8,tetrahydro-6-[propyl[2-(2-thienyl)-ethyl]amino]-1-naphthol base is greater than or equal to 5% (per weight); and
a backing layer, which is inert to the (-)-5,6,7,8,tetrahydro-6-[propyl[2-(2-thienyl)-ethyl]amino]-1-naphthol base and the adhesive compound, having a protective layer, which is to be removed prior to administration of the pharmaceutical compound to the patient.
Independent claim 12 is similar in scope to claim 1. Dependent claims 2-11 and 13 specify components of the matrix and polymer adhesive.
Claim 30:
A pharmaceutical compound substantially as hereinbefore described with reference to the Examples.
THE APPLICATION FOR AN EXTENSION OF TERM
LTS were granted an extension of time under s 223(2)(a) to lodge, on 5 June 2008, a request for an extension of term. This request was based on pre-TGA marketing approval by a Delegate of the Secretary at the Department of Health and Aging dated 14 November 2007, which approval took effect from the date the of registration on the Australian Register of Therapeutic Goods (ARTG). After an examiner advised that such approval did not constitute pre-TGA marketing approval, LTS filed an amended request under s 104 for an extension where there is NO pre-TGA marketing approval, the basis for which is the inclusion in the ARTG of NEUPRO® (rotigotine) on 22 November 2007 with the registration numbers AUST R 131370, 131381, 131382, 131383.
During prosecution of the extension the examiner advised LTS that the application did not satisfy the requirements of s 70(2)(a) of the Patents Act 1990, because the claimed “transdermal therapeutic system” comprising 3 layers included a separate physical integer unrelated to the mixture of chemical entities and as a result were not directed to a “pharmaceutical substance per se” within the meaning of the Act.
The examiner reported that proposed amendments filed by LTS on 20 January 2009 were contrary to ss 102(1) and 102(2)(a), since inter alia they introduced new claims in which the phrase “transdermal therapeutic system” was substituted with “pharmaceutical preparation for the treatment of disease” or “dosage form for the treatment of disease”. On 19 March 2009, LTS proposed further amendments in which the “dosage form” claims were deleted and the claims reciting a “pharmaceutical preparation” were amended to a “pharmaceutical compound”. LTS submitted at this point that the pharmaceutical compound as claimed comprised the polymer matrix and rotigotine. The backing and protective layers were separate and subsidiary physical integers that “in no way contribute to the working of the therapeutic substance of the pharmaceutical compound”. While the examiner reported that the claims as proposed to be amended were not directed to a pharmaceutical substance per se, the amendments were allowed on 14 August 2009 and will be advertised on 1 October 2009.
Despite these amendments to the specification and further submissions by LTS, on 18 May 2009 the examiner maintained in a fourth report that the subject matter of the claims does not qualify as a “pharmaceutical substance per se” under the Act, because it relates to a device having three distinct layers, rather than a pharmaceutical substance by itself.
The patentee’s submissions
10. LTS identified the critical issue as whether the patent claims a pharmaceutical substance per se, and their submissions in this regard can be summarised as follows:
Claim 1 as amended defines a pharmaceutical compound which is a new pharmaceutical substance. Properly understood, the patent claims a “new and inventive product alone”, which the Full Court confirmed is the only type of claim that is to be the subject of extension rights. (Boehringer Ingelheim International GmbH v Commissioner of Patents [2001] FCA 647 at [17])
“NEUPRO® comprises the known active ingredient (rotigotine) and an acrylate or silicone based non-aqueous polymer adhesive compound into which rotigotine free base is able to be dissolved to enable transdermal application. The combination of the stated elements comprises the new “pharmaceutical substance per se” (not being limited to the active ingredient alone: Prejay Holdings Ltd v Commissioner of Patents [2002] FCA 881 per Heerey J in which his Honour quoted the Patent Office Manual, upheld on appeal [2003] FCAFC 77; Pharmacia Italia SpA v Mayne Pharma Pty Ltd [2006] FCA 305 at [107])”.
LTS conceded at [19] of the written submissions, that a key difficulty is the inclusion in the claims of backing and protective layers. However, at [20] “Despite the fact that the backing layer is a another physical integer, it is submitted that this does not render the claims made in the patent as extending to a method or process, of which the NEUPRO® drug is a part (cf Boehringer at [17]).” The presence of the backing and protective layers “is no different in substance to any claim for a pharmaceutical product which is in a tablet or capsule form and which, of its nature, is intended to be administered orally.”
LTS contended that if an extension is not granted in the present instance on the basis of the reasoning in Euro-Celtique, S.A. [2007] APO 13, the outcome would be anomalous and inconsistent with the intention of the legislation. LTS noted that the delegate of the Commissioner in Euro-Celtique considered that “all other factors being equal, there is no difference between a pharmaceutical being delivered orally from one delivered dermally”. LTS distinguished their product from that refused an extension in Euro-Celtique, because it was not a “transdermal delivery system” and “when claim 1 is read in the context of the specification and claims as a whole, the backing layer and the protective layer are conceptually no different to the binding features of a tablet, or a capsule which contains a new drug”.
In the hearing, Counsel for the patentee also compared the present formulation to that in Pharmacia Italia SpA v Mayne Pharma Pty Ltd [2006] FCA 305 which granted an extension to a patent claiming a ready-to-use injectable solution comprising the active ingredient dissolved in a solvent, in combination with an acid. Counsel noted that the injectable product must have been in a container, but this did not prevent an extension of term being given in that case. LTS’s claimed product is in the same area, only distinguished by the fact that the container (i.e. the backing and protective layers) is identified in the present invention.
DECISION
11. The requirements of s 70(2)(a) are not met, because the specification does not include any claim where a pharmaceutical substance per se in substance falls within the scope of the claim. I therefore refuse the request to extend the term of patent 746856.
STATEMENT OF REASONS
The relevant law
12. Part 3 of Chapter 6 of the Patents Act 1990 provides the statutory framework for the extension of the term of standard patents relating to pharmaceutical substances. Section 70 relevantly provides:
“(1)The patentee of a standard patent may apply to the Commissioner for an extension of the term of the patent if the requirements set out in subsections (2), (3) and (4) are satisfied.
(2) Either or both of the following conditions must be satisfied:
(a) one or more pharmaceutical substances per se must in substance be disclosed in the complete specification of the patent and in substance fall within the scope of the claim or claims of that specification;
(b) one or more pharmaceutical substances when produced by a process that involves the use of recombinant DNA technology, must in substance be disclosed in the complete specification of the patent and in substance fall within the scope of the claim or claims of that specification.”
The expression “pharmaceutical substance” is defined in Schedule 1 of the Act to mean:
“a substance (including a mixture or compound of substances) for therapeutic use whose application (or one of whose applications) involves:
(a) a chemical interaction, or physico-chemical interaction, with a human physiological system; or
(b) action on an infectious agent, or on a toxin or other poison, in a human body;
but does not include a substance that is solely for use in in vitro diagnosis or in vitro testing.”
The term “therapeutic use” is also defined in Schedule 1. It means:
“use for the purpose of:
(a)preventing, diagnosing, curing or alleviating a disease, ailment, defect or injury in persons; or
(b)influencing, inhibiting or modifying a physiological process in persons; or
(c)testing the susceptibility of persons to a disease or ailment.”
Section 70(3) provides that the following conditions must be satisfied in relation to at least one of the pharmaceutical substances referred to in s 70(2):
“(a)goods containing, or consisting of, the substance must be included in the Australian Register of Therapeutic Goods;
(b)the period beginning on the date of the patent and ending on the first regulatory approval date for the substance must be at least 5 years.”
Section 70(4) requires that the patent must not have been previously extended under Part 3.
13. There is no argument that the pharmaceutical good NEUPRO® is included in the ARTG. The elapsed period between the date of the patent and 1st regulatory approval is more than 8 years, and the patent has not been previously extended under Part 3 of the Act. I am therefore satisfied that the patent meets the requirements of ss 70(3) and (4). The patent under consideration in this case does not involve recombinant DNA technology, and hence s 70(2)(b) has no relevance. Consequently, what must be determined is whether the application fulfils the requirements of s 70(2)(a), that a pharmaceutical substance per se is in substance disclosed in the complete specification and in substance falls within the scope of a claim or claims of the specification.
14. The meaning of the expression “pharmaceutical substance per se” in s 70(2)(a) has been considered by the Federal Court in Boehringer Ingelheim International GmbH v Commissioner of Patents [2001] FCA 647, Prejay Holdings Ltd v Commissioner of Patents [2003] FCAFC 77 and in Pharmacia Italia SpA v Mayne Pharma Pty Ltd [2006] FCA 305. In Boehringer at [37], the Full Court referred with approval to the submission at [34] that the introduction of the words “per se” by the 1998 amendments to the Patents Act indicated a clear intention to limit the operation of s 70 to patents disclosing and claiming a pharmaceutical substance “by or in itself, intrinsically, essentially” (New Shorter Oxford English Dictionary), or “taken alone; essentially; without reference to anything else” (Butterworth’s Australian Legal Dictionary).
15. This approach was approved in Prejay, in which the Full Court held that the qualification per se requires that the pharmaceutical substance is itself the subject of a claim. The Court noted at [24],
“As is apparent from the context of these words, especially the Full Court's references to the legislative history of s 70, the Full Court was saying that, for a substance to fall within s 70(2)(a) it must itself be the subject of a claim in the relevant patent. It is not enough that the substance appears in a claim in combination with other integers or as part of the description of a method (or process) that is the subject of a claim. The policy adopted in s 70 was to confine extensions to patents that claim invention of the substance itself.” (Emphasis in original.)
16. In Pharmacia at [107], Justice Weinberg found that where a pharmaceutical substance comprises a number of components, it is not necessary that all chemical entities within that combination be therapeutically active. Rather it is the substance as a whole that must meet the requirements for therapeutic action or interaction within the definition of a pharmaceutical substance.
17. In the present case it is not entirely clear what constitutes the pharmaceutical substance upon which the applicant wishes to base their application for an extension of term. Three alternatives are presented, as follows:
a.The extension request identifies rotigotine, which is contained in the ARTG-listed good NEUPRO®,
b.In their written submissions at [1], LTS states that the subject matter of new claim 1 is the pharmaceutical substance per se, which prima facie encompasses the good NEUPRO® as a whole.
c.LTS further submits at paras [1]-[2], [17] and [35] that “properly understood” claim 1 defines a new drug, this being the polymer adhesive matrix with the rotigotine free base dissolved within it, and that this matrix-rotigotine combination is the pharmaceutical substance per se. In this scenario, claim 1 merely refers to backing and protective layers.
18. I accept that the application satisfies s 70(2)(a) insofar as each of these three possible substances are in substance disclosed in the complete specification of the patent. But does one or more of these substances as a whole, by itself, in substance fall within the scope of a claim or claims of the specification? To answer this question it is necessary to construe the claims in order to determine their scope.
19. The principles for the construction of a patent specification were summarised by Sheppard J in Decor Corporation Pty Ltd v Dart Industries Inc (1988) 13 IPR 385 at 400. Briefly and most relevantly, a claim must be construed in its plain meaning unless this is displaced by a dictionary definition in the body of the specification or by the technical knowledge of a person skilled in the art. The claims must be construed in the context of the specification as a whole, and be given a purposive construction.
20. Claim 1, as amended, is clear and in its plain meaning defines a pharmaceutical compound comprising three components:
a.a matrix layer comprising an effective amount of rotigotine free base and a non-aqueous acrylate or silicone-based adhesive polymer, said matrix layer having a solubility for the rotigotine free base of greater than or equal to 5% (per weight);
b.a backing layer which is inert to the ingredients of the matrix; and
c.a protective layer which is to be removed before application.
The additional independent claims also recite a product with the same components.
21. The inclusion of the backing and protective layers in claim 1 provides a clear limitation on the claimed product that it include these layers. This is consistent with the invention described in the body of the specification, and with the fact that both layers are present in NEUPRO®, as evidenced by the extension request at para [2]. Moreover, LTS have conceded at para [35], that the layers “are necessary to protect and package the product”, and at the hearing Counsel indicated that the backing layer is necessary to facilitate successful and effective administration of the drug.
22. Conversely, Counsel also asserted that the backing and protective layers are not essential to the claimed invention. However, even if one or both of these layers is not in fact essential to the working of the invention, the applicant, by the terms of the claims as properly construed, has clearly limited the claimed product to having those features. (Catnic Components Limited v Hill & Smith Limited [1982] RPC 183 at 228)
23. Therefore, I can only conclude that the scope of claim 1 clearly extends to the pharmaceutical compound comprising the matrix-rotigotine combination, the backing layer and the protective layer, with each of these features being essential to the claimed product. This claimed product is embodied in the pharmaceutical good NEUPRO®. The specification contains no claim to rotigotine by itself, or any claim to the matrix-rotigotine combination by itself. It follows that of the three possible substances, only NEUPRO® could form the basis for an extension request insofar as only NEUPRO® as a whole, by itself, in substance falls within the scope of the amended claims of the specification as required by s 70(2)(a).
24. As noted above, LTS contended that their product should not be distinguished from the injectable solution considered in Pharmacia, for which an extension of time was granted. LTS asserted that the claimed anthracycline glycoside solution must have been in a container although this was not indicated in the claim. However, the pharmaceutical substance in Pharmacia was the solution defined by the claims. This solution was held to be a pharmaceutical substance per se as required by s 70(2)(a). The solution was contained in the pharmaceutical good, as required by s 70(3). I can find no indication that the Court construed the claims as limited to the solution in a container. In the present case, LTS have claimed the matrix-rotigotine combination in its “container”, and thus their claimed product is distinguished from that considered in Pharmacia.
25. I accept the patentee’s submissions that the reference in claim 1 to backing and protective layers does not extend the claimed subject matter to a method or process, and that the polymer matrix is in effect, an excipient acting as a diluent and carrier for rotigotine. Therefore, the critical question is whether NEUPRO® can be shown to be, by itself, a “pharmaceutical substance” within the definition of Schedule 1. In this regard it is clear that NEUPRO® is for therapeutic use, most relevantly in “influencing, inhibiting or modifying a physiological process in persons …”, it involves a chemical or physico-chemical interaction with a human physiological system, and is not for in vitro use. Consequently, the last remaining question is whether NEUPRO® constitutes “a substance (including a mixture or compound of substances)”?
26. The phrase “a substance (including a mixture or compound of substances)” has not yet been the subject of substantive judicial consideration. However some guidance in its interpretation may be obtained from a number of Patent Office decisions that have some similarity with the present case.
27. LTS Lohmann Therapie-Systeme GmbH & Co KG [2002] APO 12 related to a patent for a transdermal patch to deliver a known drug, which overcame the problems of the prior art by using a specific arrangement of structural features, these being a laminated structure comprising a backing layer, one or more matrix layers and optionally, an adhesive layer. Deputy Commissioner Herald found that the word “substance” in Schedule 1 refers to “a species of definite chemical composition” and at [12] that “a pharmaceutical substance” under the Act is “a chemical entity (including a mixture or compound of chemical entities)” and further at [15] that the term “mixture” involved, at least macroscopically, an uncontrolled spatial configuration of the entities in the mixture.
28. Clearly, the layered structure of NEUPRO® prevents it falling within the definition of a “mixture of substances” in Schedule 1, however is it a “compound of substances”?
29. The meaning of a “compound” of pharmaceutical substances was considered in Sanofi-Aventis [2007] APO 35. The Deputy Commissioner found at [36] that a “compound” may qualify as being a true mixture in the Lohmann sense, but also contemplated a compound that is formed by combining elements or parts, or creating a union of parts. Furthermore, “[i]n this sense a compound is not necessarily limited to any particular spatial arrangement of components”.
30. A further relevant case is Euro-Celtique, S.A. [2007] APO 13 where the claims were directed to a pharmaceutical formulation comprising an active ingredient in a transdermal delivery system. A spatial arrangement was not claimed and hence Lohmann was distinguished. However, at [26] the delegate found that the reference to a “transdermal delivery system” implied the presence of a backing layer or patch on which a mixture of chemical entities is applied. This constituted a separate physical integer unrelated to the mixture of chemical entities and therefore what was claimed did not constitute “a substance (including a mixture or compound of substances)”. It followed that the claims were not directed to a pharmaceutical substance per se.
31. At the hearing LTS sought to distinguish their product from that of Euro-Celtique making the case that the backing and protective layers are conceptually no different to the binding features of a tablet, or a capsule which contains a new drug.
32. In this regard, guidance can be taken from the most recent case, N. V. Organon [2009] APO 8, which related to a drug delivery system in which a mixture of two active ingredients is dissolved in a thermoplastic core material over which is laid a permeable thermoplastic skin. Counsel noted that Deputy Commissioner Spann had allowed an extension in that case because the “product as a whole exhibits a level of integration or interaction between the component parts that … is more characteristic of a pharmaceutical substance in itself rather than a substance combined with another element or thing”. In coming to this conclusion, the Deputy Commissioner at [23] observed that where it is difficult to determine whether a particular feature of a product can correctly be considered part of a “substance” rather than a separate physical integer, it is convenient to consider whether the characteristics of what is claimed more predominately lie with it being a substance, rather than a substance in combination with a separate integer. In considering the point, he noted that it is more important to consider the actual features of the product claimed, rather than the term used to characterise the product.
33. In the present case the claimed product is variously described as a transdermal therapeutical system, a pharmaceutical compound…adapted to be transdermally administered or a pharmaceutical compound for transdermal administration. However, irrespective of these characterising terms, the features of the claimed product are consistent. As does claim 1, the construction of which is discussed above, all of the claims explicitly define a product comprising a polymer matrix containing rotigotine, an inert backing layer, and a protective layer to be removed before use.
34. Prima facie, the presence in NEUPRO® of an inert backing layer and a protective layer which is removed before use, would exclude it from being a “compound of substances” for the purposes of s 70. However, following the reasoning in Organon, these layers would not be fatal to an extension if the patentee could demonstrate that the product as a whole shows a level of integration or interaction between the component parts such that it would fall within the definition of a pharmaceutical substance under the Act. However, LTS’s submissions during prosecution of the extension have been that the backing and protective layers constitute separate and subsidiary physical integers, that “in no way contribute to the working of the therapeutic substance”. This position is wholly inconsistent with NEUPRO® as a whole, being considered “a substance (including a mixture or compound of substances)” within the definition of Schedule 1.
35. At the hearing Counsel also submitted that, like the thermoplastic materials in the Organon product, the inert backing layer in NEUPRO® has a “physical purpose to position, contain and provide for the controlled release” of the active ingredient. Ultimately however, the nature of the backing layer is not critical to this decision. The protective layer, since it is removed before use, cannot be considered to integrate or interact in any way with the other component parts of NEUPRO®. Therefore, the presence in NEUPRO® of this layer at least, renders the claimed product as a substance in combination with a separate integer. It follows that no pharmaceutical substance per se in substance falls within the scope of the claims of the specification.
Conclusion
36. The product that in substance falls within the scope of the claims of patent 726943, embodied by the pharmaceutical good NEUPRO® as a whole, is not a pharmaceutical substance per se within the meaning of the Patents Act 1990. As a result, the application does not satisfy the requirements of s 70(2)(a) and cannot be granted an extension of term. Boehringer Ingelheim International GmbH v Commissioner of Patents [2001] FCA 647 and Prejay Holdings Ltd v Commissioner of Patents [2003] FCAFC 77 applied.
Dr Gillian Jenkins
Deputy Commissioner of Patents
21 August 2009
Patent attorneys for the patentee: Hodgkinson McInnes Patents, Sydney
0
9
0