N. v Organon

[2009] APO 8

ABSTRACTS OF DECISIONS

DECISION OF A DEPUTY COMMISSIONER OF PATENTS

Application  :          Patent No. 726934 in the name of N. V. Organon.

Title:          Drug delivery system for two or more active substances

Action  :Request under s 70 of the Patents Act for an extension of term and objections of the Commissioner thereto

Decision:          Issued    28 May 2009

Abstract

The patent relates to a drug delivery system adapted to the slow release of particular steroidal mixtures such as for the purpose of contraception or hormone replacement therapy. A key aspect of the invention is that the steroidal mixture is contained in a thermoplastic polymer core over which is laid a permeable thermoplastic skin.

The patentee applied for an extension of term of the patent based on the inclusion of NUVARING^® on the Australian Register of Therapeutic Goods. If allowed and, subject to any opposition that might be filed, granted, the effect of the extension would be that the maximum term of the patent would expire on 27 June 2021 rather than 8 April 2018.

Considered whether the product NUVARING as claimed in the patent was a pharmaceutical substance within the meaning of the Act and more particularly whether it was a substance (including a mixture or compound of substances) for therapeutic use as provided in the definition given in Schedule 1.

Found that the definition of a pharmaceutical substance encompasses a compound with a controlled spatial configuration if, as a whole, it can still be considered a “pharmaceutical substance”, but the combination of such a substance with what would reasonably be considered a separate physical device, layer or structure is excluded. It may be difficult to determine whether a particular feature of a product is correctly considered part of a “substance” rather than a separate physical integer but in the present case the steroidal components are mixed with and necessarily diffuse through the thermoplastic materials in the core and skin regions and as such the product as a whole exhibits a level of integration or interaction between the component parts that was considered more characteristic of a pharmaceutical substance in itself rather than a substance combined with another element or thing.

Consequently the application to extend the term of the patent was allowed.

PATENTS ACT 1990

DECISION OF A DEPUTY COMMISSIONER OF PATENTS

Re:Patent No. 726934 in the name of N. V. Organon, a request under s 70 of the Patents Act for an extension of term and objections of the Commissioner thereto.

BACKGROUND

1. This matter concerns a request for an extension of the term of patent no. 726934 in the name of N. V. Organon (Organon).  The patent relates to a "Drug delivery system for two or more active substances ".  The date of the patent is 8 April 1998 and accordingly the maximum 20-year term will expire on 8 April 2018.  An application for extension of the term of the patent was filed on 21 December 2006, and if an extension of the term of the patent is granted, the maximum term would be extended to 27 June 2021.

1. The basis for the request for an extension of term is the inclusion in the Australian Register of Therapeutic Goods (ARTG) of NUVARING^®, a “etonogestrel 11.7 mg and ethinyloestradiol 2.7mg vaginal drug delivery system” which was subject to an ARTG registration commencing on 27 June 2006 (AUST R 96229).  Following the filing of the application, a delegate of the Commissioner reported that he considered that the “ ‘system’ for which a Certificate of Medicine Registration has been issued, and which is the subject of both the Application for an Extension of Term, and the claims of patent 726934, is not a ‘pharmaceutical substance’ ”. Organon provided a number of submissions disputing this finding but the examiner’s objections were maintained. 

1. The patentee requested a hearing and the matter was subsequently heard in Canberra on 27 November 2008.  Ms Shahnaz Irani, patent attorney of Spruson & Ferguson represented the patentee and provided a number of submissions both at the hearing and subsequently in response to matters on which I requested further clarification. I have also been provided a declaration by the patentee’s expert Dr Wouter de Graaff concerning the nature of the Nuvaring product and have taken this and Ms Irani’s submissions into account in reaching my decision.

THE SPECIFICATION

1. The patent relates to a drug delivery system adapted to the slow release of particular steroidal mixtures such as for the purpose of contraception or hormone replacement therapy. A key aspect of the invention is that the steroidal mixture is contained in a thermoplastic polymer core over which is laid a permeable thermoplastic skin. By carefully selecting and treating these components it is said that, surprisingly, a reliable release ratio is achieved over a prolonged period of time. Preferably both the core and skin are formed from ethylene-vinyl acetate copolymers and are formed into a vaginal ring containing etonogestrel as the progestogenic compound of the steroidal mixture and ethinylestradiol as the estrogenic compound. The examples reveal that the core is prepared by mixing the steroidal compounds with Evatane^® 28-25 and co-extruding the mixture with Evatane^® 1020 VN3.

1. The specification ends with 14 claims, of which claims 1 and 6 are independent. They read as follows:

1. A drug delivery system comprising at least one compartment which comprises a thermoplastic polymer core and a thermoplastic polymer skin covering the core, said core comprising a mixture of a steroidal progestogenic compound and a steroidal estrogenic compound in a ratio by weight that allows a direct release from the said polymer of both the said progestogenic compound and the said estrogenic compound in physiologically required amounts, said progestogenic compound being initially dissolved in the said polymer core material in a relatively low degree of supersaturation, said estrogenic compound being dissolved in the said polymer core material in a concentration lower than that of the said progestogenic compound, and said thermoplastic skin being permeable for the said progestogenic and estrogenic compounds.

6. A drug delivery system in a substantially ring-shaped form and suitable for vaginal administration comprising at least one compartment which comprises a thermoplastic polymer core and a thermoplastic polymer skin covering said core, said core comprising a mixture of a progestogenic steroidal compound and an estrogenic steroidal compound in a ratio by weight of 10 parts of the progestogenic compound to 1.5 - 5 parts of the estrogenic compound, said progestogenic compound being initially dissolved in the said polymer core in a relatively low degree of supersaturation, and said polymer skin being permeable for both the progestogenic and the estrogenic compounds.

THE RELEVANT LAW

1. Part 3 of Chapter 6 of the Patents Act provides a 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."

1. The expression "pharmaceutical substance" is defined in Schedule 1 of the Act. It is:

"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."

1. 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."

1. 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."

1. Section 70(4) requires that the patent must not have been previously extended under Part 3.

1. There appears to be no question that NUVARING is included in the ARTG, is disclosed in the patent specification and in substance falls within the scope of the claims. Similarly the other requirements set out in ss 70(3) and (4) appear to be met. S 70(2)(b) clearly does not apply, so consequently the sole issue to be determined in the present matter is whether the requirement of s 70(2)(a) is satisfied and more particularly whether NUVARING is a pharmaceutical substance per se.

DECISION

1. 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, the Full Court referred with approval, at [34] and [37], to the submission of the respondent 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).

1. 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. It is not sufficient for a substance to appear in a claim only in combination with other integers or as part only of the description of a method or process that is the subject of a claim. The Court noted at [24] that extensions of the patent term are confined to patents that claim invention of the substance itself.

1. Where what is involved is substances comprising a number of components it is not necessary that all chemical entities within that combination be therapeutically active. Rather it appears that it is the substance as a whole that must meet the requirements for therapeutic action or interaction within the definition of a pharmaceutical substance. This matter was considered by Justice Weinberg in Pharmacia where he concluded in light of Justice Heerey’s decision at first instance in Boehringer:

“[107] His Honour’s approval of the Manual, and its analysis of the concept of a pharmaceutical substance which was generally accepted as correct by the Full Court, cannot be reconciled with Dr Elliott’s view that the introduction of any non-active ingredient into a product prevents it from being a pharmaceutical substance. For one thing, her approach would effectively mean that s 70 had almost no function to perform. Almost every pharmaceutical product will consist of a combination of individual substances, some of which may be intrinsically therapeutic (active ingredients), while others serve different, albeit essential, roles. To restrict the capacity to extend a patent to those unlikely cases where every component of the compound is itself therapeutically useful would be to deprive the section of any real utility, and largely defeat the purpose of its enactment.”

1. It will be apparent that factual circumstances so far considered by the Court have focussed attention on the per se limitation of s 70(2). Specifically the claims in Boehringer involved a container including a spray composition and a nozzle for nasal administration, Prejay related to a method for hormonal treatment including a particular dosage regime and Pharmacia, a anthracycline glycoside solution defined in some respects by reference to process steps. Here, as I have indicated, it appears that the pharmaceutical goods NUVARING falls with in the scope of the claims. Therefore if NUVARING is, by itself, a pharmaceutical substance within the definition of Schedule 1 the requirements of s 70(2) will be met. I accept in this regard that it is for therapeutic use, most relevantly in “influencing, inhibiting or modifying a physiological process in persons …” and that it involves a chemical interaction, or physico-chemical interaction, with a human physiological system. Accordingly the fundamental question is whether NUVARING is “a substance (including a mixture or compound of substances)”?

1. It is unfortunate that this latter phrase, which Justice Burchett in passing thought an “unusual expression, in a scientific context”[1], has not yet been the subject of substantive judicial consideration. However some guidance in its interpretation may be obtained from the small number of Patent Office decisions that have some similarity with the present case including LTS Lohmann Therapie-Systeme GmbH & Co KG [2002] APO 12 which was relied on by the delegate in his report. It related to a transdermal patch which delivered a known drug, 17-[beta]-estradiol. Claim1 was defined in the following terms:

“Transdermal therapeutic system containing the active substance 17-[beta]-estradiol and optionally further active substances, with a laminated structure comprising a backing layer which is substantially impermeable to moisture and impermeable to active substance, one or more matrix layers and, where non-adhesive matrix layers are present, an adhesive layer, characterised in that the concentration of the dissolved estradiol in all matrix layers and, where an adhesive layer is present, in the adhesive layer, lies between its saturation concentration in dry condition and its saturation concentration in moist condition, whereby the term "dry condition" is understood to mean that the base material is in equilibrium with a gas phase with less than 10% relative humidity, and the term "moist condition" is understood to mean that the base material is in equilibrium with a gas phase with more than 90% relative humidity.”

[1] Virbac (Australia) Pty Limited and Ancare Distributors Limited v Merck Patent Gmbh [1994] FCA 1255

1. Deputy Commissioner Herald concluded that the qualification “including a mixture or compound of substances” to the definition of “a substance” in Schedule 1 makes clear that “substance” is not limited to single chemical entities, but extends to mixtures and compounds of chemical entities.  He went on to state at [16] that the definition of “pharmaceutical substance” is necessarily limited to chemical entities per se, compounds of chemical entities, and mixtures of chemical entities - noting that mixtures entail an uncontrolled spatial configuration of the entities in the mixture.  It was concluded at [17] that “....if a claim to an alleged pharmaceutical substance includes features specifying spatial configuration of the entities in the substance, it is not a claim to a pharmaceutical substance per se but a claim to an arrangement of substances characterised by that spatial configuration.”

1. The more recent case in Sanofi-Aventis [2007] APO 35 also dealt with similar considerations. There the invention claimed was:

1. A pharmaceutical composition comprising zolpidem or a salt thereof wherein said composition consists of a controlled-release dosage form adapted to release zolpidem or a salt thereof over a predetermined time period, according to a biphasic in vitro profile of dissolution when measured in a type II dissolution apparatus according to U.S. Pharmacopoeia in 0.01 M hydrochloric acid buffer at 37°C, where the first phase is an immediate release phase having a maximum duration of 30 minutes and the second phase is a prolonged release phase, and wherein 40 to 70% of the total amount of zolpidem is released during the immediate release phase and the time for release of 90% of the total amount of zolpidem is between 2 and 6 hours.

1. It had been argued by the examiner on the basis of Lohmann that the spatial configuration of the bi-layered tablet STILNOX CR^® falling within the scope of this claim resulted in it not being a mixture or compound of substances. However Deputy Commissioner Jenkins’ in her decision found that the word “compound” must be understood in the sense used within the pharmaceutical industry rather than the narrow meaning in pure chemistry. Otherwise it would be redundant. She further indicated in relation to the meaning of “compound” that:

“36. These definitions qualify a compound as being a true mixture (in the Lohmann sense), but also contemplate a compound that is formed by combining elements or parts, or creating a union of parts. In this sense a compound is not necessarily limited to any particular spatial arrangement of components. It would seem reasonable to infer that a tablet formed by the combination or union of two layers falls within the meaning of compound”.

1. A further relevant case is Euro-Celtique, S.A. [2007] APO 13 where what was claimed was “A pharmaceutical formulation for treating pain in a human patient comprising a pharmaceutically effective amount of buprenorphine in a transdermal delivery system containing…” The delegate concluded that a spatial arrangement was not claimed and hence Lohmann was distinguished. He however 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 hence what was claimed was not “a substance (including a mixture or compound of substances)”.

1. In considering these decisions it appears to me that the Deputy Commissioner in Sanofi was correct in her understanding of the term “compound” in the definition of pharmaceutical substance and that as a result the reasoning in Lohmann ceases to be persuasive in these matters. If a mixture implies an uncontrolled spatial configuration it is in any event only one example of a compound of substances of which in Sanofi it was said contemplates “a compound that is formed by combining elements or parts, or creating a union of parts”. It also appears that I should be cautious in interpreting “substance” in a way that would unnecessarily exclude innovations in the pharmaceutical sector for which the extension of term scheme appears to be intended. Hence to draw a distinction between homogeneous mixtures on one hand and compounds formed with layers or structures on the other containing the same chemical entities would seem to lead to a rather arbitrary outcome. The novelty and utility of a particular pharmaceutical substance may well arise from the synergy between spatially discrete components within it, whether they are all chemically active or not. Such a product is still subject to the same regulatory processes as a simple mixture of the components and hence the conclusion that one is excluded from the benefits of the pharmaceutical extension of term scheme and the other is not would appear to lead to an unreasonable result that is not consistent with the purpose of the legislation.

1. Nevertheless while “compound”, even within a pharmaceutical context, can be given broad meaning it is apparent from the Explanatory Memorandum that the scheme established under the legislation was focussed on new and inventive substances (other than the explicit provision for processes involving recombinant DNA) and was not intended to assist the developers of other therapeutic products or processes including medical apparatus used with therapeutic substances, no matter how innovative and despite also being subject to regulatory approval processes. In this light it appears to me that a pharmaceutical substance (including a mixture or compound of substances) can include a compound with a controlled spatial configuration if, as a whole, it can still be considered a pharmaceutical “substance” but the combination of such a substance with what would reasonably be considered a separate physical device, layer or structure or, from Sanofi, “any purely physical integers” is excluded and indeed would not be a “pharmaceutical substance per se”. In this regard I understand the bracketed text in Schedule 1 to clarify the inclusive nature of the term “substance” but not to define it. Hence a “compound of substances” while encompassing more than a mixture, appears not to extend the definition beyond a pharmaceutical substance “formed by combining elements or parts, or creating a union of parts”.

1. It may be that, beyond the clear cases, it is difficult to determine whether a particular feature of a product is correctly considered part of a “substance” rather than a separate physical integer. However this difficultly can be addressed, as in this case, by asking whether the characteristics of what is claimed more predominately lies with it being a substance rather than a substance in combination with a separate integer.  Here the product claimed is couched as a “drug delivery system”. This might be somewhat indicative of the character of what is claimed but I do not think substantively so. Many pharmaceutical substances involving mixtures of active and other additives can be characterised as a delivery system. What is more important is the actual features of the product claimed. In this case it can be said that the thermoplastic materials in NUVARING have a physical purpose to position, contain and provide for the controlled release of the steroidal components for interaction with the human body. There are also two distinct and adjacent physical layers or regions that differ in composition, that is, the core and skin. I note that the bi-layered tablet considered in Sanofi could be said to have similar characteristics although, in that case, the excipients or additives dissolve in the body and do not retain their structure after the active is delivered. The latter could well suggest that the thermoplastic core and skin are more in the nature of separate physical integers. However, from Dr de Graff’s evidence, the steroidal components in NUVARING are mixed with and necessarily diffuse through the thermoplastic materials in the core and skin regions and as such the product as a whole exhibits a level of integration or interaction between the component parts that, in my view, is more characteristic of a pharmaceutical substance in itself rather than a substance combined with another element or thing.

CONCLUSION

1. I therefore consider that NUVARING is a pharmaceutical substance within the meaning of the Act. As it appears to be goods included on the ARTG, disclosed in the patent specification and which in substance fall within the scope of the claims I believe the requirements of ss70 and 71 have been met. Consequently I allow the application to extend the term of patent 726943.

P M Spann
Deputy Commissioner of Patents

28 May 2009

Patent attorneys for the patentee:   Spruson & Ferguson, Sydney