ImmunoGen, Inc.
[2014] APO 88
•19 December 2014
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
ImmunoGen, Inc. [2014] APO 88
Patent No.:2006283726
Title:Process for preparing maytansinoid antibody conjugates
Patentee: ImmunoGen, Inc.
Hearing Officer: P M Spann, Deputy Commissioner of Patents
Decision Date: 19 December 2014
Hearing Date: 22 October 2014, Melbourne; Written submissions completed 11 November 2014
Catchwords: PATENTS – extension of term – whether a pharmaceutical substance, when produced by a process that involves the use of recombinant DNA technology, falls within the scope of the claims – extension application accepted – whether leave to amend should be granted – leave granted.
Representation: Mr B Caine, QC
Mr J Lambert, Solicitor, Griffith Hack
Dr M Lyons, Patent Attorney, Griffith Hack
Ms A Stark, Patent Attorney, Griffith Hack
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent No.:2006283726
Title:Process for preparing maytansinoid antibody conjugates
Patentee: ImmunoGen, Inc.
Date of Decision: 19 December 2014
DECISION
I accept the application for an extension of term pursuant to section 74.
I grant leave to amend in relation to the statements of proposed amendments filed on 15 October and 11 November 2014.
REASONS FOR DECISION
Background
This matter concerns a request for an extension of the term of patent no. 2006283726 in the name of ImmunoGen, Inc. (ImmunoGen). The date of the patent is 14 August 2006 and accordingly the maximum 20-year term will expire on 14 August 2026. An application for extension of the term of the patent was filed under section 70 of the Act on 28 February 2014.
The basis for the request for an extension of term is the inclusion in the Australian Register of Therapeutic Goods (ARTG) of KADCYLA®, of which trastuzumab emtansine is the active ingredient. This product was subject to ARTG registrations commencing on 3 September 2013 (AUST R 201621 and AUST R 201622). It follows from this information and the formula set out in section 77 that, if granted, the extended term of the patent would expire on 3 September 2028.
Following the filing of the application, a delegate of the Commissioner reported that she considered that:
“None of the present claims appear to define a pharmaceutical substance per se, or a pharmaceutical substance when produced by a process that involves the use of recombinant DNA technology. While the anti-HER2 monoclonal antibody may have been humanised by recombinant DNA technology, this antibody when produced by recombinant DNA technology is not within the scope of any of the claims. The drug trastuzumab emtansine rch (the antibody- maytansinoid conjugate) is the pharmaceutical substance. The process defined in the claims for preparing this conjugate is a crosslinking process, not a process involving recombinant DNA technology.”
Following a response by the patentee the objection was repeated. The patentee then requested a hearing and provided submissions together with a declaration by Dr Malcolm Lyons. At the same time on 15 October 2014 it also filed a first statement of proposed amendments.
At the oral hearing I invited further written submissions and these were filed on 11 November 2014 together with a second statement of proposed amendments. I was informed that the amendment of the patent specification is sought whether or not I find that the extension is justified on the basis of the claims as granted.
Specification
The specification indicates that the invention relates to a process of preparing conjugates of high quality and purity “wherein the conjugates comprise a cell-binding agent coupled with a drug”. A particular application is the coupling of antibodies to cytotoxic molecules for the treatment of cancer. The process in general is reflected in claim 1 of the patent as granted.
1. A process for preparing an antibody-maytansinoid conjugate
comprising the steps of:
(a) contacting an antibody with a bifunctional crosslinking reagent to
covalently attach a linker to the antibody and thereby prepare a first mixture
comprising antibodies having linkers bound thereto,
(b) subjecting the first mixture to tangential flow filtration, selective
precipitation, adsorptive filtration, or adsorptive chromatography and thereby
prepare a purified first mixture of antibodies having linkers bound thereto,
(c) conjugating a maytansinoid to the antibodies having linkers bound
thereto in the purified first mixture by reacting the antibodies having linkers
bound thereto with a maytansinoid in a solution having a pH of about 4 to about 9
to prepare a second mixture comprising (i) antibody chemically coupled through
the linker to the maytansinoid, (ii) free maytansinoid, and (iii) reaction byproducts
produced during step (c), and
(d) subjecting the second mixture to tangential flow filtration to purify
the antibodies chemically coupled through the linkers to the maytansinoid from
the other components of the second mixture and thereby prepare a purified second
mixture of antibodies chemically coupled through the linkers to the maytansinoid.While the specification anticipates other alternatives, particularly preferred antibodies are said to be “humanized monoclonal antibodies, examples of which include huN901, huMy9-6, huB4, huC242, trastuzumab, bivatuzumab, sibrotuzumab, and rituximab.” Relevantly claim 31 of the granted patent states:
31. The process of any of claims 1-18, wherein the antibody is trastuzumab, the bifunctional crosslinking reagent is N-succinimidyl 4- (maleimidomethyl) cyclohexanecarboxylate (SMCC), and the maytansinoid is N2 - deacetyl- N2 -(3-mercapto-l-oxopropyl)-maytansine (DMI).
For the purpose of this decision I accept that the humanized monoclonal antibody trastuzumab can at this point in time only be produced by recombinant DNA techniques. This is supported by the declaration made by Dr Lyons. The techniques for producing trastuzumab and other humanized monoclonal antibodies are well known and are referred to directly and by cross-reference in the description.
Proposed amendments
The effect of the first and second statements of proposed amendments is to add the following claims:
“32.A process for preparing trastuzumab-MCC-DM l comprising the steps of:
(a) humanizing a mouse monoclonal antibody comprising grafting complementarity determining regions (CDR) of the mouse monoclonal antibody onto a framework of a human antibody molecule to produce trastuzumab,
(b) contacting trastuzumab with SMCC to covalently attach SMCC to trastuzumab and thereby prepare a first mixture comprising trastuzumab having SMCC bound thereto,
(c) subjecting the first mixture to tangential flow filtration, selective precipitation, adsorptive filtration, or adsorptive chromatography and thereby prepare a purified first mixture of trastuzumab having SMCC bound thereto,
(d) conjugating DM l to trastuzumab having SMCC bound thereto in the purified first mixture by reacting trastuzumab having SMCC bound thereto with DMl in a solution having a pH of about 4 to about 9 to prepare a second mixture comprising (i) trastuzumab chemically coupled through SMCC to DM l, (ii) free DM l, and (iii) reaction byproducts produced during step (c),
and
(e) subjecting the second mixture to tangential flow filtration to purify trastuzumab chemically coupled through SMCC to DM l from the other components of the second mixture and thereby prepare a purified second mixture of trastuzumab-MCC-DM l.
33.Trastuzumab-MCC-DM l when prepared by the process of any one of claims 1 to 32.
34.An antibody-maytansinoid conjugate when prepared by the process of any one of claims 1 to 30.”
Law
Part 3 of Chapter 6 of the Patents Act provides a statutory framework for the extension of the term of standard patents relating to pharmaceutical substances. Section 70 relevantly provides:
“(1) The patentee of a standard patent may apply to the Commissioner for an extension of the term of the patent if the requirements set out in subsections (2), (3) and (4) are satisfied.
(2) Either or both of the following conditions must be satisfied:
(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;
(b) one or more pharmaceutical substances when produced by a process that involves the use of recombinant DNA technology, 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.”
10. The expression "pharmaceutical substance" is defined in Schedule 1 of the Act. It is:
"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 physico-chemical 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."
11. The term "therapeutic use" is also defined in Schedule 1. It means:
"use for the purpose of:
(a) preventing, diagnosing, curing or alleviating a disease, ailment, defect or injury in persons; or
(b) influencing, inhibiting or modifying a physiological process in persons; or
(c) testing the susceptibility of persons to a disease or ailment."
12. Section 70(3) provides that the following conditions must be satisfied in relation to at least one of the pharmaceutical substances referred to in s 70(2):
"(a) goods containing, or consisting of, the substance must be included in the Australian Register of Therapeutic Goods;
(b) the period beginning on the date of the patent and ending on the first regulatory approval date for the substance must be at least 5 years."
13. Section 70(4) requires that the patent must not have been previously extended under Part 3.
14. In relation to the proposed amendment of the patent specification it is to be noted that the request for examination in relation to the patent application was filed before 15 April 2013. As a consequence, substantive amendments of the Patents Act brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 do not apply to the present application.
15. Instead, the relevant sections of the Patents Act in the current case are sections 102(1) and (2) as they existed prior to the introduction of the Raising the Bar Act. These are set out below:
“102(1) An amendment of a complete specification is not allowable if, as a result of the amendment, the specification would claim matter not in substance disclosed in the specification as filed.
(2) An amendment of a complete specification is not allowable after the relevant time if, as a result of the amendment:
(a) a claim of the specification would not in substance fall within the scope of the claims of the specification before amendment; or
(b) the specification would not comply with subsection 40(2) or (3).
(2A) For the purpose of subsection (2), relevant time means:
(a) in relation to an amendment proposed to a complete specification relating to a standard patent - after the specification has been accepted; or
(b) …..
(3) This section does not apply to an amendment for the purpose of correcting a clerical error or an obvious mistake made in, or in relation to, a complete specification.”
Consideration
16. For the purpose of section 70 a key issue is whether, in substance, the specification discloses and claims a pharmaceutical substance “when produced by a process that involves the use of recombinant DNA technology”. The examiner did not think this the case finding that the process of the invention involved “a crosslinking process, not a process involving recombinant DNA technology”.
17. In answer to this criticism it is said that the humanized monoclonal antibody trastuzumab is produced by recombinant DNA technology and that the use of that antibody in the process is both described and claimed. It is said that it does not matter that trastuzumab was known and that the “involvement” DNA technology is to be understood broadly given the purpose of the extension of term scheme.
18. In this regard the Explanatory Memorandum to the Intellectual Property Laws Amendment Bill 1997 states ([9]):
“The extension of term provisions will be available for patents that include claims to pharmaceutical substances per se (provided 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 the process involves the use of 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 the pharmaceutical substance per se.”
19. I was also referred to the decision of Justice Heerey at first instance in Boehringer lngelheim International v Commissioner of Patents [2000] FCA 1918 (Boehringer 1), where his honour considered the legislative history, saying at [12] to [15]
“[12] By the Patents (World Trade Organization Amendments) Act 1994 (Cth) Div 2 of Pt 3 of Ch 6 of the 1990 Act, containing the extension provisions in ss 70 to 79, was repealed. Section 70 and related sections in their present form were introduced by the Intellectual Property Laws Amendment Act 1998 (Cth). For the first time, provision was made for the extension of not just of a “pharmaceutical patent”, but a “pharmaceutical patent per se”.
[13] The 1990 Act in its present form manifests a policy which draws a distinction between, on the one hand, a pharmaceutical substance that is the subject of a patent claim and, on the other hand, a pharmaceutical substance that forms part of a method or process claim. The specific exception to the latter (an exception which proves the rule) is the provision for recombinant DNA technology in s 70(2)(b).
[14] Broadly speaking, a claim in relation to a pharmaceutical substance can be made in three ways
(i) a new and inventive product alone;
(ii) an old or known product prepared by a new and inventive process;
(iii) an old or known product used in a new and inventive mode of treatment.[15] What is clear in s 70 is that only the first type of claim to a pharmaceutical product is to be subject to extension rights. So far as a new process is concerned, it is only when the new process answers the particular description in s 70(2)(b) (recombinant DNA process) that it can be the subject of an extension. As counsel for the Commissioner submitted, the policy to be deduced in the light of the legislative history is that Parliament has decided that what is intended to be fostered is primary research and development in inventive substances, not the way they are made or the way they are used, with the sole (and important) exception of recombinant DNA techniques, this being an area particularly worthy of assistance for research and development.”
20. I have difficulty in characterising these statements as supporting a broad and inclusive interpretation of s 70(2)(b). Rather processes involving recombinant DNA technology are the exception to a general rule requiring the claiming only of a pharmaceutical substance per se. This tends to favour a narrow construction. On the other hand, while it would seem somewhat likely that the intent of the exclusion was to support the development of improved recombinant techniques, the Act itself and extrinsic materials relevant for the purpose of section 15AB of the Acts Interpretation Act 1901, fall short in my view of qualifying the term “involves” in subsection 70(2)(b) to require a product to be made by new recombinant DNA technology or that the process be limited entirely to a recombinant process.
21. In simply requiring a process “that involves the use of recombinant DNA technology” the legislation appears to encompass a range of scenarios including the present one where the processes described includes forming a conjugate from an antibody produced by known recombinant techniques. Consequently I am satisfied that the first leg of subregulation 70(2)(b) has been met, that is, that “one or more pharmaceutical substances when produced by a process that involves the use of recombinant DNA technology, must in substance be disclosed in the complete specification of the patent”
22. The second question is whether such a substance falls “within the scope of the claim or claims of that specification”. The patent in at least claim 31 claims a method for producing a trastuzumab-maytansinoid conjugate. It however does not include a claim specifically formulated as a product by process type referred to in the EM or of the second type mentioned in paragraph 14 of Boehringer 1. A submission made to address this fact is that what falls within the scope of a claim can be determined on what constitutes an infringement (AMP Incorporated v Commissioner of Patents (1974) AOJP 3224) and that, within the definition of the rights of a patentee to exploit an invention that is a method or process, is the right to exploit the product resulting from the use of the product or process (section 13 and Schedule 1 ‘exploit’).
23. I have doubts that there is a basis or authority to extend the test espoused by the High Court in AMP to the range of provisions of the Act that set out statutory extensions or limitations of the right to sue for infringement. An immediate difficulty with that argument is that by extension a pharmaceutical substance per se could be argued to fall within the scope of a method claim and such a submission based on section 117 of the Act was rejected by Justice Heerey in Prejay Holdings Ltd v Commissioner of Patents [2002] FCA 881 (and upheld by the Full Court on appeal in Prejay Holdings Ltd v Commissioner of Patents [2003] FCAFC 77). Rather, what I understand the Court in AMP to be doing is to apply the test in the context of an analysis of the words used in the claim to define its scope and well established common law principles of infringement. This in my view sits comfortably with the statement of the Full Court in Boehringer Ingelheim International GmbH v Commissioner (2001) 52 IPR 529 at [42] that:
“we think that falling within the scope of a claim in a patent specification means included amongst the things claimed”
24. I do not however think this fatal to the patentee’s prospects in this case due to the understanding of the scope of product by process claims that applies in Australia (but no longer in the UK). That provides, in effect, that a claim to a product made by a particular process is substantially indistinguishable in scope from a claim to the particular process used to make the product. Both are limited by the features of the process (Kirin-Amgen Inc v Transkaryotic Therapies Inc (No.1) [2002] R.P.C. 1) and an infringement of one type of claim is necessarily an infringment of the other.
25. The position is somewhat analogous to that considered by the High Court in Wellcome Foundation Ltd. v. Commissioner of Patents [1980] HCA 21 where the Court at [21] stated:
“A further answer to the appellant's submission is 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. So much appears from the judgment of Parker J. in Adhesive Dry Mounting Company Ltd. v. Trapp & Co. (1910) 27 RPC 341, at p 353, upon which the appellant, mistakenly in our view, placed reliance. There, the first claim in the patent specification was a process claim. The second claim was either a claim to a pellicle or to the use of the pellicle in the process described in the first claim. Parker J. observed that, if the second claim was a claim to the use of the pellicle in the process, it added nothing to the first claim for it was already included in that claim.”
26. On this basis I am prepared to accept that trastuzumab emtansine, when produced by a process that involves the use of recombinant DNA technology, in substance falls within the scope of a claim to a process for preparing an antibody-maytansinoid conjugate where the antibody is trastuzumab. It follows further that I do not consider it necessary for the claim to specifically recite recombinant process steps. It is enough for a product made by a process including such steps be “included amongst the things claimed”. To the extent that the claims include within their scope other things, they do not give rise to patent rights within the extended term as provided by section 78.
27. Since it is apparent that all other requirements of section 70 and 71 have been met it follows that under section 74 the application for an extension of term must be accepted.
28. As a consequence the proposed amendments are not necessary in order for the application to comply with section 70. Nevertheless the patentee requests those proposed amendments to be considered and in this regard I am satisfied that the claimed method of preparing trastuzumab-MCC-DMl and trastuzumab-MCC-DMl made by that method is in substance disclosed in the specification as filed and therefore the requirement of subsection 102(1) as it applies to this case has been met.
29. The requirement of subsection 102(2)(a) is that, as a result of the amendment, the claims must in substance fall within the scope of the claims of the specification before amendment. This mirrors the second leg of the requirement of subsection 70(2)(b) and consistent with my finding above I conclude that claims to conjugates made by the claimed processes are within the scope of the present process claims. Furthermore I do not find that as a result of the proposed amendments the claims would not comply with section 40. Therefore I consider that the proposed amendments are allowable and that leave to amend should be granted.
30. Publication of a notice of acceptance of the extension application and of leave to amend will occur in due course. Both give rise to the right of third parties to oppose under sections 75 and 104 respectively.
P M Spann
Deputy Commissioner of Patents
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