Celgene Corporation
[2011] APO 37
•3 June 2011
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Celgene Corporation [2011] APO 37
Patents:2003228508 & 2004270211
Title of 2003228508: Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of myelodysplastic syndromes
Title of 2004270211: Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
Patentee: Celgene Corporation
Delegate: Dr S.D.Barker
Decision Date: 3 June 2011
Hearing Date: 5 May 2011 in Canberra
Catchwords: PATENTS – applications for extension of term of patents – whether a composition "when used" is a process or a pharmaceutical substance per se – whether pharmaceutical substance is a specific polymorph – whether “goods” in section 70(3) includes the indication of the product in the ARTG – no evidence that the goods included in the ARTG contain the specific polymorph of the claims –date of first inclusion in the ARTG considered – applications for extension of term were not made within the time specified in section 71(2) – applications refused
Representation: Patentee: Phillips Ormonde Fitzpatrick
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patents:2003228508 & 2004270211
Title of 2003228508: Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of myelodysplastic syndromes
Title of 2004270211: Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
Patentee: Celgene Corporation
Date of Decision: 3 June 2011
DECISION
The applications for extension of term were not made within the time specified in section 71(2), and there are no prospects that this can be corrected.
I refuse the applications for extension of term.
REASONS FOR DECISION
Celgene Corporation is the patentee in respect of patents 2003228508 and 2004270211. On 27 September 2010 Celgene applied for extensions of the term of both patents. The extensions are based upon the inclusion in the Australian Register of Therapeutic Goods (ARTG) of the product REVLIMID.
The Patents Act 1990 prescribes a six month period for applying for an extension of term of a patent. For the purposes of the present patents, the starting date for the six month period is the date of first inclusion of relevant goods in the ARTG. REVLIMID was first registered on the ARTG on 20 December 2007. Consequently the Commissioner advised the patentee that the applications for extension of term were made outside the six month period set by section 71(2)(b). The patentee responded by drawing attention to the fact that the Therapeutic Goods Administration (TGA) issued amended Certificates of Registration (having the same ARTG registration numbers) on 21 May 2010.
The patentee requested a hearing on whether the applications for extension of term had been made within time. The matter was heard in Canberra on 5 May 2011. The patentee was represented by David Tadgell, patent attorney of Phillips Ormonde Fitzpatrick. Richard Girards, patent counsel for Celgene, and Yeah-Sil Moon of Jones Day, also attended.
THE ARTG REGISTRATIONS
The patentee relies upon four ARTG registrations: AUST R132510, AUST R132514, AUST R132515 and AUST R132516. All registrations commenced on 20 December 2007. The product covered by AUST R132510 is described as "REVLIMID lenalidomide 5 mg capsule blister pack". The products covered by the other registrations differ only in the amount of lenalidomide in the capsule blister pack (the amounts being 10 mg, 15 mg and 25 mg). Throughout this decision when I refer to the products on the ARTG I will only refer to AUST R 132510 (the 5mg capsule), but the same comments apply to the other products.
I am informed that on 21 May 2010 the TGA issued amended Certificates with an alteration of the Product Specific Indication. The Indication as amended states:
"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."
I am also informed that the second sentence was added in the reissued Certificate.
THE RELEVANT LAW
The present case turns on the proper construction of section 71(2). That subsection states:
An application for an extension of the term of a standard patent must be made during the term of the patent and within 6 months after the latest of the following dates:
(a) the date the patent was granted;
(b) the date of commencement of the first inclusion in the Australian Register of Therapeutic Goods of goods that contain, or consist of, any of the pharmaceutical substances referred to in subsection 70(3);
(c) the date of commencement of this section.For present purposes, it is paragraph (b) that is relevant.
Section 71 does not stand in isolation, and must be understood in the context of section 70. In order to obtain an extension of term, it is necessary that certain requirements are met:
- the specification must disclose and claim a pharmaceutical substance per se (s 70(2)(a));
- goods "containing, or consisting of" the pharmaceutical substance must be included in the ARTG (s 70(3)); and
- the application is made within 6 month of the first inclusion of the goods (s 71(2)(b)).
It is clear that two questions are of central importance: what is the pharmaceutical substance, and what is the goods.
THE PHARMACEUTICAL SUBSTANCE
The ‘508 patent relates to the substance lenalidomide, which has the systematic name 3-(4-amino-1-oxo-3H-isoindol-2-yl)piperidine-2,6-dione. The patent specification describes the use of lenalidomide for the treatment of myelodysplastic syndrome (MDS). MDS refers to a diverse range of disorders related to malfunction of the stem cells in the bone marrow. The most relevant claim for present purposes is claim 36:
"A pharmaceutical composition when used for treating a myelodysplastic syndrome including a compound selected from 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione having the formula
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, together with a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant, wherein said 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)piperidine-2,6-dione is administered in an amount of about 5 to 50 mg per day."
Mr Tadgell argued that claim 36 should be considered a claim to a pharmaceutical composition per se, wherein the composition is limited to "when used" in the specified treatment. The leading authority on the construction of "when used" claims is the decision of the High Court in Wellcome Foundation Ltd v Commissioner of Patents [1980] HCA 21, (1980) 145 CLR 520. The Court stated at 529:
"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"
While this statement may be obiter, it is not a comment that is lightly disregarded. A "when used" claim clearly differs in form from the equivalent process claim, but is there any substantial difference between the claims? In a "when used" claim of the present type the focus is on the composition, but only when it is part of the process of treatment. The effect of this temporal limitation is that an act would only fall within the scope of the "when used" claim if it includes (i) the specific composition and (ii) the process of treatment. The equivalent process claim would require the same integers. The acts that fall within the scope of a claim to lenalidomide when used to treat MDS are the same as the acts that fall within a claim to a process of treating MDS by using lenalidomide. As the High Court noted, there is "no distinction" between these claims – because claim construction is a matter of substance, and not a matter of form. I consider that claim 36 is in substance a process claim.
It is well established that a process claim is not a claim to a pharmaceutical substance per se. In Prejay Holdings Ltd v Commissioner of Patents [2003] FCAFC 77 at [24], 57 IPR 424 at 429 Wilcox and Cooper JJ stated:
"for a substance to fall within s 70(2)(a) it must itself be the subject of a claim in the relevant patent. It is not enough that the substance appears in a claim in combination with other integers or as part of the description of a method (or process) that is the subject of a claim."
Claim 36 of the '508 patent is not directed to a pharmaceutical substance per se, and consequently I cannot identify a pharmaceutical substance for the purposes of section 70. If there were any doubt about the correctness of this conclusion, I note that the Explanatory Memorandum, Intellectual Property Laws Amendment Bill 1997 (being the Bill that introduced the present extension of term scheme) states at page 18:
"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."
The consequence of this finding that there is no pharmaceutical substance is that there is also no relevant goods. In the absence of relevant goods, the time period set by section 71(2) has not yet started - so the requirements of section 71(2) have not been met. However, even if I am wrong in this conclusion – and lenalidomide can be regarded as the pharmaceutical substance - the application for extension of term was not made in time for reasons that I will explain when considering the date of first inclusion.
The '211 patent relates to polymorphic forms (i.e. different crystal forms) of the compound lenalidomide. The specification states that it also relates to “their use for the treatment of diseases and conditions including, but not limited to, inflammatory diseases, autoimmune diseases, and cancer” (page 1). Claim 1 of the '211 patent reads as follows:
"Crystalline 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5 and 16 degrees 2θ."
Other polymorphs, defined in other ways, are the subject of other claims. There are no significant differences for present purposes between claim 1 and the other claims.
The patentee suggested that the pharmaceutical substance could be seen as lenalidomide (without reference to the polymorph form). 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 (see Prejay Holdings v Commissioner at [24]). 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. I am satisfied that the pharmaceutical substance in relation to the '211 patent is the specific polymorph of lenalidomide, not lenalidomide.
THE GOODS INCLUDED IN THE ARTG
In the present case there are different ways to interpret the goods included in the ARTG. The Patents Act does not define the term "goods", but uses it in connection with the ARTG. The ARTG Certificate issued by the TGA does not contain an entry called either "goods" or "therapeutic goods". It does contain two pieces of relevant information. First, the Certificate states at the top:
"ARTG Certificate
issued to
Celgene Pty Limited
for approval to supply
REVLIMID lenalidomide 5 mg capsule blister pack"Second, the Certificate contains a statement called "Products covered by this Entry" which states:
"Products covered by this Entry
1. REVLIMID lenalidomide 5 mg capsule blister pack
Container Type
Container Material Container Condition Container Closure Shelf Life Time Shelf Life Temperature Shelf Life Conditions Blister Pack PVC/PCTFE (Alcar)/A1 Not recorded Not recorded 3 Years Store below 25 degrees Celcius Store in Original Container"
This information demonstrates that the product included in the ARTG is REVLIMID. There is also information in the Certificate under the following headings: Product Specific Conditions, Product Standard Indications, Product Specific Indications, Warnings, Dosage Form, Route of Administration, Visual Identification, Additional Product Information, Product Formulation(s). The relevant part for the present matter is the Product Specific Indications which states:
"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."
The product REVLIMID is clearly indicated for treatment of MDS. Is REVLIMID per se the "goods", or is REVLIMID indicated for treatment of MDS the "goods"?
The goods that are included in the ARTG are limited to therapeutic goods (section 9A of the Therapeutic Goods Act 1989), which are goods intended for therapeutic use (section 3 of the Therapeutic Goods Act). Goods included in the ARTG have an indication, which is defined as the therapeutic use of the goods (section 3 of the Therapeutic Goods Act). The Therapeutic Goods Act draws a clear distinction between the goods and their indications. This distinction is evident in H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70 at [239], 81 IPR 228 at 276, where Bennett J stated:
"The level of the inquiry required by s 70(3) does not look to the therapeutic effect of the pharmaceutical substance. Rather, it is a simple comparison of the pharmaceutical substance with the 'ingredients' of the goods on the ARTG."
I conclude that in identifying the goods that are included in the ARTG I should not import elements of the indication of the goods. The "goods" for the purposes of the Patents Act is equivalent to the product that appears in the ARTG Certificate, and does not extend to the indications.
It is clear that the patentee has approval to supply the product REVLIMID, which is indicated for a specified use. Based on the distinction between goods and their indication, I must conclude that the goods that is included in the ARTG is the product called REVLIMID. The Certificate does not identify the crystal form (or forms) of the lenalidomide as it exists in REVLIMID, and there is no other evidence as to the crystal form (or forms).
DO THE GOODS CONTAIN THE PHARMACEUTICAL SUBSTANCE
There is no evidence that the goods called REVLIMID contain the specific polymorphs that are the subject of the '211 patent. The patentee said that REVLIMID could include the specific polymorphs of the '211 patent. The '211 patent acknowledges that lenalidomide was a known substance, and the invention resides in the new polymorphs. 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.
The patentee submitted that the goods called REVLIMID contain lenalidomide, and this is enough. This would be correct if the pharmaceutical substance was lenalidomide, rather than the specific polymorphs of lenalidomide.
I cannot identify any goods that contain, or consist of, the polymorphs covered by the '211 patent. In the absence of relevant goods, the application for extension of term cannot proceed. However, even if I am wrong in this conclusion – and REVLIMID can be regarded as the goods - the application for extension of term was not made in time for reasons that I will explain when considering the date of first inclusion.
THE DATE OF FIRST INCLUSION
In Pfizer Corp v Commissioner of Patents (No 2) [2006] FCA 1176, 69 IPR 525 Bennett J considered the expression "the date of commencement of the first inclusion in the Australian Register of Therapeutic Goods of goods that contain, or consist of, the substance" as it occurs in section 70(5)(a). The fact situation in that case was that goods had been first entered on the ARTG as "listed goods" for export only, and subsequently entered as "registered goods" for marketing in Australia. Her Honour concluded at [32] that section 70(5)(a) should be given its plain meaning, and the relevant date was the date of "the entry, first in time, in a part of the ARTG". On appeal (Pfizer Corp v Commissioner of Patents [2006] FCAFC 190, 238 ALR 519), the Full Court came to the same view, stating 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."
The same construction seems equally applicable when considering the same words as they appear in section 71(2). Where there are two relevant entries in the ARTG, the "first inclusion" is that which is first in time.
I reached the same conclusion in G.D.Searle LLC [2008] APO 31 when considering section 71(2) for a different purpose. The facts of that case were that two substances within the scope of the patent had been included in the ARTG at different times. I concluded at [18]:
"Based on the structure of the Act, I conclude that the intention of the Act is that an application for extension of term is to be made within 6 months of the earliest first inclusion in the ARTG. Consistent with this intention, when subsection 71(2) refers to the date of first inclusion of any pharmaceutical substance, it must be construed as reference to the earliest first inclusion date."
It follows that the only relevant goods in the present cases are the various REVLIMID products (without reference to their indications), and that the date of their first inclusion was the earlier date, i.e. 20 December 2007.
The applications for extension of term were not made within six months of the date of first inclusion of the REVLIMID products. Consequently, the applications would fail to satisfy section 71(2).
OTHER CONSIDERATIONS
The patentee submitted that the product could not be used in the treatment of MDS until it had been registered for that use. In this regard, the patentee drew attention to the Explanatory Memorandum, Intellectual Property Laws Amendment Bill 1997 (being the Bill that introduced the present extension of term scheme). At page 4 the Memorandum states:
"The objective of this proposal is to provide an 'effective patent life' – or period after marketing approval is obtained, during which companies are earning a return on their investment – more in line with that available to inventions in other fields of technology. It is also intended to provide a patent system which is competitive with other developed nations."
While the intention was clearly to provide for an extension of term for pharmaceutical inventions, the intention was not an extension without limits. This is made clear at page 18 of the Memorandum:
"The extension of term provisions will be available for patents that include claims to pharmaceutical substances per se (provided that the other criteria are met). These claims to pharmaceutical substances per se would usually be restricted to new and inventive substances. Patents that claim pharmaceutical substances when produced by a particular process (product by process claims) will not be eligible unless that process involves the use of a recombinant DNA technology. 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."
Section 70 prescribes limitations on the patents that can be extended. It seems to me that the present patents are examples of patents outside the scope of the extension of term scheme.
CONCLUSION
The applications for extension of term were not made within the time specified in section 71(2). Given the nature of the defect, this cannot be remedied by an extension of time under section 223.
Section 74(3) says that the Commissioner must refuse to accept an application for extension of term if the requirements of section 71 are not satisfied. In the present case, those requirements are not satisfied and there are no prospects that the defect can be remedied. I have no choice – the application must be refused.
Dr S.D.Barker
Delegate of the Commissioner of Patents
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