Novartis Vaccines and Diagnostics S.r.l.
[2015] APO 2
•2 February 2015
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Novartis Vaccines and Diagnostics S.r.l. [2015] APO 2
Patent Application: 2002330681
Title:Vaccines comprising aluminium adjuvants and histidine
Patentee: Novartis Vaccines and Diagnostics S.r.l.
Delegate: Dr B. Akhurst
Decision Date: 2 February 2015
Hearing Date: 28 November 2014
Catchwords: PATENTS – section 70 – extension of term – s 70(2)(b) –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.
Representation: Patentee: Peter Maddigan of Counsel and Paul Whenman, patent attorney of FB Rice
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2002330681
Title:Vaccines comprising aluminium adjuvants and histidine
Patentee: Novartis Vaccines and Diagnostics S.r.l.
Date of Decision: 2 February 2015
DECISION
I accept the request for an extension of term of the patent.
REASONS FOR DECISION
Background
Patent application number 2002330681 was filed on 26 July 2002 and granted on 8 September 2008. The date of the patent is 26 July 2002 and its 20 year term would expire on 26 July 2022. On 13 February 2014 the patentee, Novartis Vaccines and Diagnostics S.r.l. (Novartis), applied for an extension of term of the patent based on the inclusion of the product Bexsero® on the Australian Register of Therapeutic Goods (ARTG).
During prosecution of the extension request, Novartis accepted that the application did not satisfy s 70(2)(a) of the Patents Act 1990 (the Act) and relied instead on s 70(2)(b). However, a delegate of the Commissioner did not think the complete specification satisfied s 70(2)(b) because the processes set out in the claims did not require the involvement of recombinant DNA technology. The delegate maintained this objection despite submissions to the contrary by Novartis, who requested an oral hearing. The matter was heard in Canberra on 28 November 2014.
The relevant law
Part 3 of Chapter 6 of the Patents Act 1990 (the Act) provides the 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.”
The expression “pharmaceutical substance” is defined in Schedule 1 of the Act:
“pharmaceutical substance means 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.”
The term “therapeutic use” is also defined in Schedule 1:
“therapeutic use means use for the purpose of:
i.preventing, diagnosing, curing or alleviating a disease, ailment, defect or injury in persons; or
ii.influencing, inhibiting or modifying a physiological process in persons; or
iii.testing the susceptibility of persons to a disease or ailment.”
Subsection 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.”
Subsection 70(4) requires that the patent must not have been previously extended under Part 3.
Construction of s. 70(2)(b) “pharmaceutical substance when produced by a process that involves the use of recombinant DNA technology”
Novartis submitted that the pharmaceutical substance will be produced by a process that involves the use of recombinant DNA technology so long as the antigen, being the active agent in the pharmaceutical substance, is recombinantly-produced. In this regard, Novartis drew my attention to two judicial statements, as follows:
“… [s 70(2)(b)] does not require the disclosure of a process. Rather, it requires the disclosure of “one or more pharmaceutical substances” that are produced by a particular process.” (The Full Court in Prejay Holdings Ltd v Commissioner of Patents (Prejay) [2003] FCAFC 77 at [25])
“… s 70(2)(b) permitted one particular form of process claim involving a particular category of pharmaceutical substances …” Rares J in Spirit Pharmaceuticals Pty Ltd v Mundipharma Pty Ltd (Spirit) [2013] FCA 658 at [52]
Consistent with the above, s70(2)(b) applies to pharmaceutical substances that are the product of a process involving recombinant DNA technology. However, Prejay and Spirit were primarily concerned with the application of s 70(2)(a) and do not address the question of the degree to which recombinant DNA technology must be involved in the process. In this regard, the delegate’s rejection of the extension request was based on her construction of s 70(2)(b) as requiring a claim to be explicitly limited to a recombinantly-produced pharmaceutical substance.
More recently, the Deputy Commissioner in ImmunoGen, Inc. (ImmunoGen) [2014] APO 88 construed s 70(2)(b) more broadly than the delegate. He found at [20] that s 70(2)(b) does not require the disclosure of a new recombinant process, nor does it require that a claim is limited entirely to a product produced by recombinant DNA technology. At [21], the Deputy Commissioner concluded that:
“In simply requiring a process “that involves the use of recombinant DNA technology” the legislation appears to encompass a range of scenarios including the [scenario in that case] where the processes described includes forming a conjugate from an antibody produced by known recombinant techniques.”
I agree with the Deputy Commissioner’s broader interpretation of s 70(2)(b), which I adopt for the purposes of this decision.
The request for an extension of term
The extension request was made in the form required and within the time set by section 71 of the Act. The request identifies two Bexsero® products which differ only in the presence or absence of a needle for the syringe container. Both products are identified in their ARTG certificates as a “multi-component Meningococcal B vaccine (recombinant, adsorbed) suspension for injection”.
The information provided by Novartis[1] establishes that Bexsero® contains four active (antigenic) ingredients derived from N. meningitides serogroup B, in addition to aluminium hydroxide, histidine, sodium chloride, sucrose and water. The antigens are as follows:
1)Neisseria Heparin Binding Protein (NHBA) fusion protein (designated DG287-953) is a product of the primary antigen NHBA (protein 287) and accessory protein 953 to enhance immunogenicity;
2)Factor H Binding Protein (fHBP) fusion protein (designated 936-741) is a product of antigen fHBA (protein 741) and accessory protein 936;
3)A fragment of Neisseria adhesion A protein (NadA, the fragment is protein 961c); and
4)An outer membrane vesicle (OMV) preparation, the antigens being membrane-associated proteins and lipopolysaccharides.
[1] ARTG Certificates 190718 and 190719 for Bexsero®, the Australian Public Assessment Report for Multi-Component Meningococcal B vaccine (Bexsero®) October 2013 and additional information provided at and after the hearing.
The three protein antigens are produced using recombinant DNA technology. The OMV preparation is an extract prepared from the N. meningitides bacterial cells.
The pharmaceutical substance
Novartis submitted that the pharmaceutical substance relevant to section 70 is the antigen that has the therapeutic effect without the aluminium salt and histidine. However, that substance is not the subject of any of the claims, so it could not satisfy the requirements of s 70(2).
In my view the pharmaceutical substance is the mixture of NHBA and fHBP fusion proteins (DG287-953 and 936-741, respectively), NadA fragment protein 961c, OMVs, aluminium hydroxide and histidine. This substance is consistent with the patent which discloses and claims a composition comprising a mixture of one or more antigen(s), an aluminium salt and histidine. A mixture of substances is explicitly included within the definition of “pharmaceutical substance” provided in Schedule 1 of the Act. The substance is for therapeutic use as a vaccine, and in generating an immune response in the recipient, its application involves a physico-chemical interaction with a human physiological system, which ultimately acts on an infectious agent in a human body. The substance is not solely for in vitro diagnostic use or in vitro testing.
I conclude that the pharmaceutical substance is the mixture of protein antigens DG287-953, 936-741 and 961c, OMVs, aluminium hydroxide and histidine. It is this pharmaceutical substance, when produced by a process that involves the use of recombinant DNA technology, that 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.
Compliance with s 70(2)(b)
Is the pharmaceutical substance when produced by a process that involves the use of recombinant DNA technology in substance disclosed in the complete specification?
The requirement for an “in substance disclosure” will be met where the complete specification contains a “real and reasonably clear disclosure” of the relevant pharmaceutical substance when produced by a process that involves the use of recombinant DNA technology (consistent with Bennett J in Pfizer Inc v Commissioner of Patents [2005] FCA 137 at [75] in the context of s 70(2)(a)).
The specification relates to the use of the amino acid histidine to improve the stability of vaccine compositions containing aluminium salt as adjuvant (page 1A). The specification describes a process involving admixture of antigen, aluminium salt and histidine; in a preferred embodiment the histidine is present when the antigen and aluminium salt are mixed (page 9, lines 8-9). Preferred antigens are from N. meningitides serogroup B (page 2A, lines 10-18). Particularly preferred are protein 287 and its truncated derivative DG287 missing the N-terminal amino acids up to and including its hexaglycine region (page 2A lines 14-16 and page 10, lines 31-33). Other preferred antigens from N. meningitides serogroup B include protein 961c (a truncated version of NadA protein lacking the C-terminal anchor domain), and an OMV preparation (page 12, lines 18-21 and page 2A lines 17-18, respectively). Examples 1, 3-6 demonstrate the adsorption of one or more N. meningitides protein(s) and/or OMV antigens onto the aluminium oxohydroxide salt in the presence of histidine buffer. Most relevantly, Example 6 describes adsorption of the hybrid (i.e. fusion) proteins DG287-953 and 936-741, protein 961c and OMVs in combination. In this disclosure, the specification provides a real and reasonably clear disclosure of a substance comprising a relevant mixture of antigens, aluminium hydroxide and histidine. The question remains whether the complete specification discloses the substance when produced by a process that involves the use of recombinant DNA technology?
While it identifies suitable antigens, the complete specification provides details of the antigens and their preparation by reference to other documents, the contents of which are explicitly incorporated into the specification on pages 18-20. The referenced documents confirm that relevant protein antigens are produced by recombinant DNA technology. For example WO 01/64922 (reference 90) discloses the production of protein 961c and the DG287-953 fusion using recombinant DNA technology. Similarly, WO 01/64920 (reference 92) discloses the recombinant production of DG287-953. Furthermore, for practical purposes the DG287-953 and 936-741 fusion proteins, at least, are not naturally occurring and cannot be extracted from a natural source. Therefore, given the extended disclosure of the specification and the nature of the fusion proteins, it is reasonable to conclude that the complete specification discloses the three protein antigens in the pharmaceutical substance as the products of recombinant DNA technology.
I am satisfied that the complete specification provides a real and reasonably clear disclosure and, it follows, an in substance disclosure of the relevant pharmaceutical substance when produced by a process that involves the use of recombinant DNA technology.
Does the pharmaceutical substance when produced by a process that involves the use of recombinant DNA technology in substance fall within the scope of the claims?
In Boehringer Ingelheim International GmbH v Commissioner (Boehringer) [2001] FCA 647 at [42]; (2001) 52 IPR 529 at [42], the Full Court stated:
“… in the context of s 70(2)(a) we think that falling within the scope of a claim in a patent specification means included amongst the things claimed.”
I agree with and adopt the Deputy Commissioner’s application of that principle to s 70(2)(b) in ImmunoGen at [26], where he said:
“… I do not consider it necessary for the claim to explicitly recite recombinant process steps. It is enough for a product made by a process including such steps be “included amongst the things claimed”.”
Claim 1 is the only independent claim and provides the process for making the product, as follows:
“1. A process for producing a composition comprising an antigen, an aluminium salt and histidine, the process comprising the steps of:
(i)admixing the aluminium salt and histidine to give a histidine/aluminium salt mixture; and
(ii)admixing the histidine/aluminium salt admixture and the antigen.”
Novartis relied on claim 20 to as the basis for its request to extend the patent term:
“20.A composition comprising an antigen, an aluminium salt and histidine obtained by a process according to any one of claims 1 to 19, wherein the antigen is a bacterial antigen selected from the group consisting of:
- a protein antigen from N. meningitidis;
- an outer-membrane vesicle (OMV) preparation from N. meningitidis;
- a saccharide antigen from N. meningitidis.”
None of claims 2-19 explicitly refers to, or necessarily requires, the involvement of recombinant DNA technology. Therefore, for the purposes of this decision I will consider claim 20 in its broadest form, as dependent on claim 1.
Appended to claim 1, claim 20 encompasses a composition which is a mixture of an aluminium salt, histidine and one or more N. meningitidis bacterial antigen(s) selected from protein antigen(s), OMV preparation and/or saccharide antigen(s). Where the antigen is recombinantly-produced, the composition of claim 20 necessarily includes “amongst the things claimed” a substance when produced by a process that involves the use of recombinant DNA technology.
The pharmaceutical substance I have identified above is a mixture of an aluminium salt (aluminium hydroxide), histidine and four N. meningitidis bacterial antigens. The antigens are three recombinantly-produced protein antigens (fusion proteins DG287-953 and 936-741, and protein 961c) and OMVs. This pharmaceutical substance is included within the scope of claim 20. It follows that the pharmaceutical substance when produced by a process that involves the use of recombinant DNA technology in substance falls within the scope of this claim.
For completeness, consistent with the Deputy Commissioner in ImmunoGen, Inc. (ImmunoGen) [2014] APO 88 at [24], Novartis could equally have relied on ‘process’ claim 1 as the basis for its extension request because it includes within its scope the product of the process.
Subsections 70(3) and 70(4)
Two Bexsero® products were listed on the ARTG on 14 August 2013. The constituents of Bexsero® are identified at [13] above and I am satisfied that these goods contain the relevant pharmaceutical substance. The period beginning on the date of the patent to first regulatory approval date is more than 5 years and the patent has not been previously extended.
Conclusion
Since all of the requirements of sections 70 and 71 have been met, pursuant to subsection 74(1), I accept the application for an extension of term based on the ARTG registration of Bexsero®.
Subsection 74(2) requires the Commissioner to notify the applicant in writing of the acceptance. This decision represents that notification. The notice of acceptance will be published in due course.
Barbara Akhurst
Delegate of the Commissioner of Patents
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