Pharma Mar S.A. applied for a patent term extension (PTE) for their Australian patent 754073 on the basis of the listing on the Australian Register of Therapeutic Goods (ARTG) of the product APLIDIN. APLIDIN is indicated for the treatment of relapsed and refractory multiple myeloma. The product is a co-pack of a vial of the active ingredient plitidepsin in powder form, and an ampoule containing PEG-35 castor oil and ethanol. In use, the reconstitution solvents from the ampoule are added to the plitidepsin powder, and the resulting mixture diluted with saline or glucose solution. Plitidepsin is difficult to formulate, and the invention of AU 754073 lies in the particular combination of reconstitution solvents, which allow the preparation of a stable aqueous solution. However, the reconstituted solution is not sufficiently stable to be sold in that form, and this was a decisive factor in the application for PTE being refused.
To recap the relevant law, s 70 of the Patents Act 1990 provides that a patentee may apply for a PTE where (amongst other requirements):
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; (s 70(2)(a))
goods containing, or consisting of, the substance must be included in the Australian Register of Therapeutic Goods; (s 70(3)(a))
Pharma Mar’s PTE application was met with deficiency notices alleging that the requirements of s 70(2)(a) and s 70(3) were not satisfied, and the matter proceeded to a hearing before a Delegate of the Commissioner of Patents (full decision here).
What are the goods listed on the Australian Register of Therapeutic Goods (ARTG)?
The public summary for the ARTG listing of APLIDIN identifies the product as ‘plitidepsin 2 mg powder for infusion vial and diluent ampoule composite pack’. The Product Information for APLIDIN further indicates that it ‘must be reconstituted and further diluted prior to administration’.
The Delegate considered that it was clear that a co-pack of plitidepsin and reconstitution solvent is included in the ARTG. However, she also underlined that in determining what goods are included on the ARTG, the goods themselves must be distinguished from directions or indications for their use (following Celgene Corporation and Commissioner of Patents and Children’s Medical Center Corporation (Joined Party)  AATA 55). Reconstitution of plitidepsin with the reconstitution solvent to form a solution was found to be a direction for use of the product. Thus, the goods included on the ARTG were limited to the co-pack, and did not extend to the reconstituted solution.
What in substance falls within the scope of the claims?
In the present case, as required by s 70, the goods on the ARTG must contain a pharmaceutical substance per se, and that substance must fall within the scope of the claims. The relevant claims of AU 754073 are as follows, noting that plitidepsin is a didemnin compound:
1. A pharmaceutical composition of a didemnin compound, comprising firstly a lyophilised didemnin preparation including water-soluble material and secondly a reconstitution solution of mixed solvents.
2. A didemnin composition according to claims 1, intended for reconstitution for administration to patients as an antitumor treatment.
8. A didemnin composition according to any one of the preceding claims, which comprises a vial of lyophilised didemnin preparation including a water-soluble bulking agent, and a separate vial of a premix of non-ionic surfactant/ethanol/water.
Although it is unusual for a claim to a composition to be construed as encompassing two physically separated components, this was the construction accepted by the Delegate, who ultimately concluded that the co-pack listed on the ARTG fell within the scope of the claims.
A co-pack is not a pharmaceutical substance per se
However, the Delegate also concluded, consistent with a number of Federal Court decisions and Celgene Corporation and Commissioner of Patents and Children’s Medical Center Corporation (Joined Party)  AATA 55, that a pharmaceutical substance per se must be a single entity, and cannot be in the form of separated components, i.e. a kit or co-pack. Accordingly, the PTE application was refused.
This is no doubt a very frustrating result for the patentee. The particular combination of reconstitution solvents described by the patentee was acknowledged during examination to provide a novel and inventive solution to a real technical problem. However, the physical nature of the reconstituted solution necessitates that it be sold as a co-pack. As submitted by the patentee:
‘It would be entirely perverse if a claim to a new formulation of a known stable and soluble drug that does not require reconstitution prior to administration […] could form the basis of a term extension, but not a claim to a new formulation of a drug that has stability and/or solubility issues and which formulation overcomes difficulties arising from those issues.’ (at 43)
Unfortunately, this is the outcome of the Delegate’s decision and it is difficult to see how the patentee could have done anything to avoid it. If the claims were construed to be directed to a composition in the conventional sense, rather than encompassing separated components, the goods listed on the ARTG may not fall within the scope of the claims and thus the patent would still be ineligible for PTE. Although the Delegate was not unsympathetic to the patentee’s situation, she remained unconvinced that s 70 and the existing case law allows for a pharmaceutical substance per se to encompass the claimed ‘composition’ comprising physically separated components.
We will be watching with interest to see whether this decision is appealed and will keep you updated.