No patent term extension for drug combination

Article  \  5 Dec 2011

In its recent decision in The Children's Medical Center Corporation [2011] APO 80, the Australian Patent Office refused to extend the term of a pharmaceutical patent that claimed a combination of two active ingredients for the treatment of cancer.  This decision makes it clear that a combination of drugs as separate dosage forms is ineligible for a patent term extension.

The patent

The particular patent related to the treatment of angiogenesis.  Angiogenesis is the generation of new blood vessels in a tissue or organ.  Angiogenesis occurs only in restricted situations in healthy individuals, but occurs in an uncontrolled manner in certain diseases, such as cancers.

The drug thalidomide is an anti-anigogenic agent.  The invention related to combinations of thalidomide with anti-inflammatory compounds, in particular steroids.

Claim 1 of the patent defined the invention as follows:

An anti-cancer combination comprising a therapeutically effective amount of thalidomide and a therapeutically effective amount of a steroid.

The patent also specifically claimed thalidomide in combination with the steroid dexamethasone, and thalidomide in combination with prednisone and melphalan.

Requirements for a patent term extension

Australian law provides for the extension of the term of certain patents to compensate for delays incurred in obtaining marketing approval for pharmaceutical products.  Section 70 of the Patents Act   sets out the conditions that must be met for an extension of term to be granted.

The two conditions relevant to this case were:

70(2)(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.
70(3)(a):  goods containing, or consisting of, the pharmaceutical substance must be included in the Australian Register of Therapeutic Goods (ARTG).

The goods included in the ARTG

The patentee relied on four entries in the ARTG in support of its extension of term request.  Each entry identified the relevant goods as "THALOMID, thalidomide X mg hard capsule blister pack" (where X is 50, 100, 150 or 200 mg for each respective entry).

The entry also included a section titled "Product Specific Indications", which referred to the intended use of thalidomide in combination with a steroid:

 "Thalomid in combination with melphalan and prednisone is indicated for the treatment of patients with untreated multiple myeloma aged 65 years or over or ineligible for high dose chemotherapy.  Thalomid in combination with dexamethasone is indicated for induction therapy prior to high dose chemotherapy with autologous stem cell rescue, for the treatment of patients with untreated multiple myeloma."

The patentee identified the relevant pharmaceutical substance as a combination of thalidomide and at least one steroid, presented as separate oral dosage forms of the two drugs to allow the doctor to control the side effects of the drug combination.

However, the therapeutic goods included in the ARTG entry were thalidomide alone.  The Delegate held that the indication that the product may be used in combination with steroids to treat multiple myeloma is not an element of the therapeutic goods.  The requirements of Section 70(2)(a) were not satisfied because there were no goods containing the claimed combination in the ARTG.

Pharmaceutical substance per se

In case he was wrong in his decision that the goods included in the ARTG did not contain the combination, the Delegate went on to consider whether the requirement of Section 70(3)(a), namely that the combination of drugs identified in the request is a pharmaceutical substance per se, was met.

Schedule 1 of the Patent Act defines the term "pharmaceutical substance" as a substance (including a mixture or compound of substances) for therapeutic use...".

In its recent decision in The Children's Medical Center Corporation [2011] APO 80, the Australian Patent Office refused to extend the term of a pharmaceutical patent.

The Delegate referred to several earlier decisions of Australian Courts that had considered the meaning of the term "pharmaceutical substance per se".  He concluded that from these decisions it is clear that a "pharmaceutical substance per se" is intended to be a pharmaceutical that is presented as a single entity, and not in the form of a kit or as separate dosage forms.  The requirement of Section 70(3)(a) was therefore not met either.

What the decision means for pharmaceutical patent owners

The Australian Patent Office's decision confirms that a combination of two drugs as separate dosage forms is not a "pharmaceutical substance per se" and is therefore not eligible for a patent term extension.

On the other hand, it seems from the Delegate's comments that if the combination was produced and registered as a single unit dosage, it would qualify as a "pharmaceutical substance per se" as a "mixture of substances", and be eligible for a patent term extension.  However, it may not be practical in many cases to produce a drug combination as a single unit dosage.