Celgene Denied Term Extension on REVLIMID Patent

Celgene Corporation [2011] APO 37 (3 June 2011)

Pharmaceutical extensions of term – whether patent for a subsequent medical use of a known compound can be extended – whether registered product contains a compound within the scope of patent claims – whether date of amendment of ARTG registration can be used as the basis for extension application

In a decision by Hearing Officer Dr Steven Barker, the Australian Patent Office has refused to grant to Celgene Corporation extensions of the term of two patents relating to the pharmaceutical product marketed as REVLIMID.

The active ingredient in REVLIMID is lenalidomide, a drug which is a close relative to the infamous thalidomide.  Lenalidomide was originally developed as a treatment for multiple myeloma (a rare cancer of the blood), and has more recently been shown to be effective in treating the class of genetic blood disorders disorders known as myelodysplastic syndromes (MDS).

Celgene’s application to extend the term of its patents was based specifically on the use of REVLIMID in the treatment of MDS.  This particular indication was first added to the Australian Register of Therapeutic Goods (ARTG) in May 2010, although the product itself had been registered since 2007.

The Hearing Officer found not only that the applications for extension of term were filed out-of-time, but also that neither of the two patents is eligible for an extension of term based on the registration of REVLIMID.  In particular, this decision indicates that:

1. patents for subsequent medical uses of drugs (e.g. having claims of the form ‘compound X when used for the treatment of condition Y…’) cannot be extended on the basis of a registration of a product containing the compound;
2. for a patent directed to specific novel forms of a compound to receive an extension of term, evidence must be provided showing that the registered product actually contains the compound in the specific form claimed; and
3. an application for an extension of patent term must be based upon the original registration of a product, and not upon a subsequent registration or amendment by which an additional indication is included on the ARTG.

BACKGROUND

Australian patent no. 2003228508 (the ’508 patent) covers the use of lenalidomide for the treatment of MDS, while patent no. 2004270211 (the ’211 patent) has claims directed to specific crystalline forms of lenalidomide.  It is not disputed that lenalidomide was a known compound before the priority dates of the patents – the ’508 patent is for a subsequent medical use, while the ’211 patent is for novel forms of the compound.

REVLIMID was registered on the ARTG on 20 December 2007.  On 21 May 2010 amended Certificates of Registration were issued, including updated Product Specific Indications, as follows:

Revlimid in combination with dexamethasone is indicated for the treatment of multiple myeloma patients whose disease has progressed after one therapy. Revlimid is indicated for treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1 risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

REVLIMID had not previously been registered with an indication for use in the treatment of MDS.

‘SUBSEQUENT MEDICAL USE’ PATENT NOT EXTENDIBLE

The ’508 patent relevantly claims (with the chemistry elided):

A pharmaceutical composition when used for treating a myelodysplastic syndrome including a compound selected from [lenalidomide], or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, together with a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant, wherein said [lenalidomide] is administered in an amount of about 5 to 50 mg per day.

Section 70(2)(a) of the Patents Act 1990 provides that an extension of the term of a patent may be granted on the condition that:

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.

Celgene argued that its claim ‘should be considered a claim to a pharmaceutical composition per se, wherein the composition is limited to "when used" in the specified treatment’ (at [10]).

The Hearing Officer disagreed, referring to obiter dicta of the High Court in Wellcome Foundation Ltd v Commissioner of Patents [1980] HCA 21, in which it was stated that ‘there is no distinction between the claim to the process and the claim to the substance when the substance claim is limited to its use in the process.’  Furthermore, it was clearly established in Prejay Holdings Ltd v Commissioner of Patents [2003] FCAFC 77 that a claim to a process is not a claim to a substance per se.

From this it follows that the above claim of the Celgene patent – and, by direct implication, any such claim directed to a second or subsequent medical use of a known compound – cannot form the basis for an extension of the term of the patent.

By way of further emphasis, the Hearing Officer cited (at [13]) the Explanatory Memorandum accompanying the Intellectual Property Laws Amendment Bill 1997 (which brought in the present extension of term scheme):

Claims which limit the use of a known substance to a particular environment, for example claims to pharmaceutical substances when used in a new and inventive method of treatment, are not considered to be claims to pharmaceutical substances per se.

REGISTERED PRODUCT MUST CONTAIN CLAIMED COMPOUND

A further condition for the grant of an extension of term is that (section 70(3)(a)):

goods containing, or consisting of, the substance must be included in the Australian Register of Therapeutic Goods.

Claim 1 of the ’211 patent recites:

Crystalline [lenalidomide] having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5 and 16 degrees 2θ.

This claim essentially defines a specific crystalline form of lenalidomide.

Celgene attempted to argue that the pharmaceutical substance covered by this claim could (somehow) be seen as lenalidomide, without reference to the specific crystalline form).  The Hearing Officer was unpersuaded (at [17]):

In order to determine the pharmaceutical substance, I have to ask what is the substance that is the subject of the claims of the patent ….  It is an essential feature of claim 1 that the lenalidomide has the specified X-ray diffraction pattern.  This feature is missing if the lenalidomide has a different crystal form.  Consequently, lenalidomide lacking the specific crystal form would not fall within the scope of claim 1, and thus cannot be the pharmaceutical substance.

The reason for Celgene’s somewhat optimistic argument appears to be that it had no evidence that the REVLIMID product actually contains the form of lenalidomide defined by the claims of the ’508 patent.  As the Hearing Officer found (at [25]-[27]):

In the absence of clear evidence, it is not safe to conclude that the new polymorphs would inevitably have been included in a routine sample of lenalidomide.
…
I cannot identify any goods that contain, or consist of, the polymorphs covered by the '211 patent.

EXTENSION MUST BE BASED ON ORIGINAL REGISTRATION

Additionally, the Hearing Officer found that the applications for extension of term of the patents had been made out-of-time.  As we recently explained (see Extension of Time Granted to Correct Extension of Term Error) the time limit is the later of:

1. six months of the date of first inclusion of a product containing the patented compound on the ARTG;
2. six months of the date of grant of the patent; and
3. 26 July 1999 (six months after commencement of the extension of term provisions).

The question in this case was whether the date of ‘first inclusion’ was the original date of registration (20 December 2007), or the later date upon which the indication for treatment of MDS was added (21 May 2010).

The authorities establish that the date of ‘first inclusion’ is the earliest relevant date (e.g. Pfizer Corp v Commissioner of Patents [2006] FCAFC 190 at [57]: ‘As a matter of ordinary English, “first inclusion in” the Therapeutic Register means the first time when goods are included in the Therapeutic Register pursuant to Division 2 of Part 3-2, irrespective of the part of the Therapeutic Register in which they are included’).

Thus the earlier date applies, and Celgene’s application was made out-of-time.

COMMENT

Some general conclusions can be drawn from this decision:

1. ‘first inclusion of a product containing the patented compound…’ means exactly what it says – the very earliest inclusion of any product, for any purpose, which includes a compound covered by one or more patent claims;
2. a patent claiming a second or subsequent medical use of a known compound, in the form of a ‘method of treatment’ type claim, will never be extendible under the Australian provisions; and
3. before granting an extension of term, a decision-maker will need to be satisfied that the registered product actually contains a compound falling within the scope of the patent claims, i.e. that the product would infringe the patent if sold without authority of the patentee.

Tags: Australia, Extension of patent term, Pharmaceuticals