Definition of “pharmaceutical substance” clarified for the purpose of patent term extensions
Sanofi-Aventis  APO 35 (2 October 2007)
A delegate of the Commissioner of Patents (“the Delegate”) has allowed a request under s70 of The Patents Act 1990 to extend the term of a Sanofi-Aventis patent relating to a controlled-release formulation of Zolpidem tartrate with a bi-phasic dissolution profile. A bilayered tablet marketed as STILNOX CR™ containing an immediate release layer and a prolonged release layer was used as the basis for extending the term of the patent.
In contrast to two previous Patent Office decisions, which suggested that a formulation must have an “uncontrolled spatial configuration of entities” to be considered a “pharmaceutical substance”, the Delegate found that the bi-layered tablet was a “compound of substances” which satisfied the definition of “pharmaceutical substance” as used in s70.
On 13 December 2006 Sanofi-Aventis filed an application to extend the term of Australian Patent No. 771902 on the basis of a registration in the Australian Register of Therapeutic Goods (ARTG) of STILNOX CR™, a bi-layered tablet comprising Zolpidem tartrate. The request was rejected on the basis that the patent did not include any claim to pharmaceutical substance per se, and that the bi-layered tablets listed in the ARTG did not represent a pharmaceutical substance. Sanofi-Aventis appealed this rejection.
The patent included a single independent claim as follows:
- 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 37ºC, 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.
The specification also included, as example 6, a description of the preparation of bi-layer tablets comprising an immediate release layer and a prolonged release layer.
In order to be eligible for a patent term extension, the patent must claim and in substance disclose a pharmaceutical substance per se, and a product which is included in the ARTG must contain or consist of that pharmaceutical substance per se.
The request was initially rejected because the Examiner did not consider the bi-layered tablet to represent a pharmaceutical substance. The term “pharmaceutical substance” is defined in Schedule 1 of The Patents Act 1990 to mean:
“pharmaceutical substance” means 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 physicochemical 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.
In referring to an earlier decision of the Deputy Commissioner of Patents in LTS Lohmann Therapie-Systeme GmbH & Co. KG  APO 12 (11 April 2002), the Examiner formed the view that for a formulation to be considered a “pharmaceutical substance” there must be an uncontrolled spatial configuration of the entities of the formulation.
In the Lohmann decision the patent related to a transdermal patch to deliver a particular drug. The claim defined the arrangement of chemical entities making up the patch, but was not considered to define a mixture or compound of substances of the type referred to in the definition of pharmaceutical substance. In considering whether the transdermal patch represented a mixture of substances, the Deputy Commissioner explained that the term “mixture” involved a concept of an uncontrolled spatial configuration of the entities in the mixture. As an example, he explained that pouring salt onto the top of a bowl of sugar did not produce a mixture of salt and sugar. According to the Deputy Commissioner, it would not become a mixture of salt and sugar until the bowl was shaken. The Deputy Commissioner also took the view that for a substance to constitute a “compound” it must involve “some form of chemical association governed by the laws of chemistry”, and accordingly did not give any consideration to the possibility that the transdermal patch might represent a “compound of substances”. The Deputy Commissioner of Patents appears to have considered the term “compound” as used in the pharmaceutical arts to be equivalent to the meaning of the term as it is used in the chemistry arts.
In Euro-Celtique, S.A.  APO 13 (26 March 2007), the Delegate considered the eligibility for a patent term extension of a patent relating to a pharmaceutical formulation comprising an active agent in a transdermal delivery system. Although the claims did not refer to the presence of a backing sheet or other components of a transdermal patch, the Delegate considered that reference to a “transdermal delivery system” suggested the presence of a backing layer or patch. Although the Delegate was satisfied that claims could be distinguished from the situation in the Lohmann case above, in that they did not characterise the formulation by features of spatial configuration, he took the view that the implied presence of a backing sheet or patch meant that the claims were not directed to a pharmaceutical substance per se. The claims also made reference to the presence of instructions for use, and this further supported the Delegate’s view that the claims were not directed to a pharmaceutical substance per se.
In the present case, the patentee argued that the bi-layered tablet did not represent a mixture of substances, but a compound of substances. The patentee further argued that the Deputy Commissioner of Patents in the Lohmann case did not give due consideration to the question of what constituted a “compound of substances”.
The Delegate distinguished the Lohmann decision on the basis that it was predominantly concerned with the concept of a mixture of pharmaceutical substances. In view of the defined spatial arrangement of the layers of the bi-layered tablet, the Delegate took the view that it did not qualify as a mixture in the Lohmann sense. The Delegate then considered in some detail the meaning of the expression “compound of substances”.
In support of the applicant’s view that the term compound of substances should be interpreted in the pharmaceutical sense, rather than in a strict chemistry sense, a number of publications were provided to the Delegate referring to medicinal compounds and compound elixirs. The Delegate was also referred to the internet encyclopaedia “Wikipedia” and the description there of Lydia Pinkham’s “vegetable compound” consisting of various botanical ingredients combined with alcohol.
The Delegate was convinced to interpret the term compound in the pharmaceutical sense, and accept that the term includes true mixtures (in the Lohmann sense) but also a “compound” formed by “combining elements or parts, or creating a union of parts”. A tablet formed by the combination or union of two layers was considered to fall within the meaning of the term “compound”.
In light of this decision, it now appears more likely that patent term extensions will be granted for formulation patents which are defined with reference to a controlled spatial configuration or arrangement, such as enteric coated tablets, capsules and the like.
NB: The author represented the applicant in this matter.