Ipsen Pharma S.a.s v Allergan, Inc

[2012] APO 21

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Ipsen Pharma S.A.S v Allergan, Inc [2012] APO 21

Patent Application:                2005200251

Title:Method for treating pain associated with a muscle disorder

Patent Applicant:                   Allergan, Inc

Opponent:  Ipsen Pharma S.A.S.

Delegate:  Dr Leslie F. McCaffery

Decision Date:  7 February 2012

Hearing Date:  21 September 2011, in Canberra

Catchwords:  PATENTS – opposition to grant – requests for further evidence by both the Applicant and the Opponent – an adequate explanation of the delay not provided by the Opponent – nature and significance of the evidence justifies further evidence – fair basis and priority date of the claims – claimed invention fairly based on earlier applications – novelty – construing citations – features disclosed by the prior art – claims lack novelty – inventive step – claims lack inventive step – section 40 ­– claims are clear and fully described – best method has been provided– utility – no evidence to show that claimed matter would not produce the desired result – new manner of manufacture – on the face of the specification the invention was not known

Representation:  Patent applicant:  Dr Gavin Recchia and Dr Nigel Lokan of Davies Collison Cave (Sydney)

Opponent:Mr Ian Horak of Counsel, instructed by Ms Amanda Jones of Watermark (Melbourne)

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Patent Application:                2005200251

Title:Method for treating pain associated with a muscle disorder

Patent Applicant:                   Allergan, Inc

Date of Decision:                   7 February 2012

DECISION

The opposition succeeds.  The subject matter of Claims 1 to 7 lacks novelty and inventive step.  Allergan is allowed 2 months from the date of this decision to file amendments to address the deficiencies.  Costs according to Schedule 8 are awarded against Allergan.

REASONS FOR DECISION

Background

1.   Patent application 2005200251 was filed on 21 January 2005 by Allergan, Inc (hereinafter the Applicant).  This application is a divisional of application 29231/02 (the parent), which is a divisional of 16361/00 (the grandparent), which is a divisional of 70105/98 (712502, the great grandparent), which in turn is a divisional of 15162/95 (688452 the great-great grandparent).  The application is also related to numerous other applications which derive from 15162/95, but these are of little relevance to the present matter and I will not discuss these in detail in this decision.

2.   A notice of opposition was served on the Applicant by Societe de Conseils de Recherches et D’Applications Scientifiques (S.C.R.A.S., hereinafter the Opponent) on 18 April 2007.  The Opponent later requested that its name be changed to Ipsen Pharma S.A.S.  on 12 March 2009, and this change was recorded on 15 April 2009.

3.   A Statement of Grounds and Particulars was on served on 17 July 2007. 

4.   Evidence in support was completed on 24 July 2009 and comprises the following declarations:

• Statutory declaration of Amanda Lee Jones dated 7 May 2009 and Exhibits ALJ-1 to 6 (Jones 1).
• Statutory declaration of Mithu Abhik Palit dated 25 May 2009 and Exhibits MAP-1 to 10 (Palit 1).
• Statutory declaration of Amanda Lee Jones dated 21 July 2009 and Exhibits ALJ-7 to 15 (Jones 2).
• Statutory declaration of Mithu Abhik Palit dated 22 July 2009 (Palit 2).

1. Evidence in Answer was completed on 24 February 2011 and consists of a declaration by Marc Andrew Russo and Exhibits MAR-1 and 2 (Russo).

2. No Evidence in Reply was filed.

3. Further evidence was requested by both parties.  These requests were considered at hearing and a direction for the evidentiary process in relation to the further evidence made following the hearing.  This is discussed in detail in the Decision section below.

4. Further evidence was requested by the Opponent on 12 September 2011.  This evidence comprises a statutory declaration by Amanda Lee Jones together with Exhibit ALJ-16 (Jones 3). 

5. On 22 September 2011 (after the hearing) the Applicant filed a request to serve further evidence together with a statutory declaration by Rebecca Dunbar and Exhibit RD-1 (Dunbar).

1. Evidence in response to the Opponent’s further evidence was filed on 31 October 2011 and comprises statutory declarations by Andrew Michael Blumenfeld and Exhibits AB-1 to 6 (Blumenfeld).

1. Evidence in response to the Applicant’s further evidence was filed on 28 October 2011 and comprises statutory declarations from: Mithu Abhik Palit and Exhibit MAP-11 (Palit 3); Amanda Lee Jones and exhibits ALJ-18 to 20 (Jones 4); and Hyam Barry Rawicki and Exhibits BR-1 to 4 (Rawicki).

1. The hearing was held in Canberra on 21 September 2011.  The Applicant was represented by Dr Gavin Recchia and Dr Nigel Lokan, patent attorneys of Davies Collison Cave, Sydney.  The Opponent was represented by Mr Ian Horak of Counsel, instructed by Ms Amanda Jones, patent attorney of Watermark, Melbourne.

   Specification

2. Botulinum toxins are a family of toxins produced by the anaerobic bacterium Clostridium botulinum.  To date seven immunologically distinct neurotoxins (designated A, B, C, D, E, F and G) have been identified.  The specification states that botulinum toxins have previously been used in the treatment of various neuromuscular disorders involving muscular spasm.  The toxins act by binding to presynaptic cholinergic nerve terminals and inhibiting the exocytosis of acetylcholine.  This decreases the frequency of acetylcholine release, resulting in local paralysis and relaxation of the spasmodic muscle.  Botulinum toxin type A is generally used in treating neuromuscular conditions, and is currently available commercially under such trade names as “DYSPORT” and “BOTOX”.

1. The specification describes the treatment of pain across a broad range of neuromuscular diseases with various botulinum toxins.  Different aspects have been claimed in the various related divisional applications originating from application 15162/95.  The present invention relates to the use of botulinum toxins for the relief of pain associated with muscle spasms, and in particular a method for the treatment of ‘post stroke spasticity pain’. 

1. Spasticity is caused by an exaggeration of the normal reflexes that occur when the central nervous system is stimulated in certain ways.  Spasticity following an injury of the central nervous system occurs as a result of the nerve cells controlling muscle activity becoming ‘disinhibited’ and continually ‘over firing’.  This leads to certain muscles receiving stimuli to contract, resulting in muscle tightness.  This may lead to muscle pain and such pain can be a driver for more muscle spasm (Palit 1 at paragraphs 20 – 21).

1. No definition is provided in the specification as to what is meant by post stroke spasticity pain.  Dr Palit considered that this was not a term ordinarily used in medicine but in the context of the application took this to mean pain that is concurrent with the spasticity and which results from the overactivity of the muscles (Palit 1 at paragraph 31).  While not disputing this definition, Dr Russo noted that pain could be central or peripheral.  Peripheral pain is caused by a primary lesion or dysfunction in the peripheral nervous system (the nerves or ganglia outside of the brain and spinal column), whereas central pain is caused by a primary lesion or dysfunction in the central nervous system (the nervous system in the brain and spinal column).  He stated that pain associated with post stroke spasticity is peripheral pain (Russo at paragraph 18).

1. The description provides twelve examples.  Example 10, entitled “The use of Botulinum toxin Types A-G in the treatment of Muscle Spasms and Control of Pain Associated with Muscle Spasms in Spasticity Conditions Secondary to Stroke, Traumatic Brain or Spinal Cord Injury”, is the only one relevant to the present invention.  The method is described in only general terms, and Dr Palit considered that it did not provide any indication of the toxin used in the treatment.  However, I note that Examples 1 to 4 separately describe treatments using the various toxin types.  While Examples 5 to 11 do not separately describe the treatments, the title refers to treatment with toxin types A-G.  I read this as describing the use of each of the named toxins in the particular treatments.  Furthermore, Dr Russo interpreted this example as disclosing a method in which relief of both muscle spasms (spasticity) and pain associated with muscle spasms.  I note that the claims include an omnibus claim that is referenced to Example 10.  I will use this interpretation in my determination of novelty and inventive step.

1. The specification ends with seven claims.  Claims 1 and 6 are as follows:

   1. A method for treating post stroke spasticity pain, the method comprising the step of intramuscular injection to a cholinergic influenced muscle of a patient a therapeutically effective amount of botulinum toxin type A, thereby reducing a post stroke spasticity pain.

   6.Use of botulinum toxin type A for the manufacture of a medicament for the treatment of post stroke spasticity pain, wherein the medicament is administered to a cholinergic influenced muscle of a patient by intra-muscular injection.

2. Claim 1 is clearly to a method of treatment. Claim 6 is in the form of a “Swiss-style claim”, which is interpreted as defining the manufacture of a medicament, wherein the medicament is intended for a specified medical treatment.  Claim 7 is an omnibus claim which defines a method for the treatment of post stroke spasticity pain with reference to the examples.  Claims 2 to 5 are dependent on Claim 1 and further characterise the invention by way of the particular muscles treated and the time by which relief is provided by the treatment. 

   THE APPLICATIONS FOR FURTHER EVIDENCE

   The Konstanzer document

3. On 12 September 2012 (9 days prior to the hearing), the opponent requested leave to serve further evidence.  In particular they sought to adduce an English language translation of Konstanzer et al., ‘Local injection treatment with botulinum toxin A in severe arm and leg spasticity’, Nervenartz.  1993 Aug; 64(8): 517-523 (hereinafter Konstanzer).  An English language abstract of this document had been included in the statement of grounds and particulars and placed in evidence as MAP-4 in the first statutory declaration of Dr Palit.

4. The Applicant sought to defer the hearing until after the request for further evidence had been determined.  However, it is often advantageous to hear a request for further evidence as part of a substantive opposition in order to make such a determination.  Further evidence can add significantly to the opposition time but ultimately be of little or no relevance to the determination.  Considering the evidence as part of the substantive hearing can make the opposition process more efficient and avoid unnecessary delay.  On that basis the request for further evidence was heard in conjunction with the substantive matter.

5. Before granting leave to serve further evidence, the Commissioner must be reasonably satisfied that the serving of further evidence is appropriate in all the circumstances.  The law relating to regulation 5.10 has been thoroughly considered in Ferocem Pty Ltd v Commissioner of Patents[1994] FCA 981; (1994) 28 IPR 243, A Goninan and Co Ltd v Commissioner of Patents and Another [1997] FCA 424; (1997) 38 IPR 213 and National Starch & Chemical Company v Commissioner of Patents [2001] FCA 33; 50 IPR 398, which set out that regulation 5.10 confers a broad discretion that cannot be reduced to imperative compliance with particular requirements. On the contrary, it is necessary to give proper, genuine and realistic consideration to all relevant aspects of the case. Relevant aspects broadly include the reasons for the delay, and the interests of the parties, including the nature and significance of the evidence. I will address each of these factors in my decision.

   Reasons for the delay

6. The onus lies with the party seeking an extension of time to justify the need for the extension with sufficient details of the circumstances and reasons for needing the extensions, but a satisfactory explanation is not a mandatory requirement (Ferocem IPR at 247).

7. The Opponent did not directly address the issue of delay in filing the further evidence.  Apparently the motivation for the request was that the Applicant had sought clarification of whether the Opponent was intending to rely on an English language translation of the full document, and if so, requested that they provide a copy of such.  As a ‘matter of caution’ they were seeking to serve further evidence.  Indeed, there was initially some dispute between the parties as to whether the document even constituted further evidence.  The Opponent noted that the English language abstract of the citation had been particularised and discussed widely during the evidentiary process.  As a consequence they considered that the existence of the document and their reliance on it in the opposition was ‘not completely unexpected’.  The inference is therefore that the Opponent did not seek further evidence sooner as they did not consider the document constituted further evidence.

8. Nevertheless the Opponent also submitted that the document provides clarification on the issues raised by the applicant in their evidence in answer as to the extent of disclosure provided by the English language summary.  I consider that if there were issues to be addressed then it would have been more appropriate to do so in evidence in reply.  However no evidence in reply was filed and no explanation has been provided as to why the evidence was not adduced sooner.

9. As a consequence I consider that the Opponent has not provided an adequate explanation of the delay.

   Interests of the parties, including the nature and significance of the evidence

10. The public interest calls for a balance between the requirements that the Commissioner deal with opposition matters expeditiously and economically and that a serious opposition is dealt with on its merits.  In order to make such an assessment, the Commissioner must form a view as to the nature of the evidence and the significance of that evidence for the opposition proceedings.  In forming this view, the significance of the evidence to be adduced is assessed in the context of the opposition and a prima facie view of its relevance, rather than being an assessment of its merits (Goninan IPR at 225-226).

11. The Opponent submitted that Konstanzer was highly relevant as a novelty-destroying document, and indeed it was discussed extensively at hearing.  The Applicant did not dispute the relevance of the document.  However, a further consideration is whether the issues under discussion were in the nature of further evidence, or whether they had already been the subject of evidentiary consideration in relation to the English language summary.  In this regard a prima facie consideration suggested that a major issue that had not been previously considered during the evidentiary process was whether the document disclosed post-stroke spasticity, and particularly whether an ‘ischaemic insult with sensory and motor hemiplegia’ is synonymous with ‘stroke’.  Prima facie, this could be a significant factor in determining the novelty of the present claims. 

12. Given the relevance of the document, the interests of the Opponent clearly lie in the further evidence being allowed.  The interests of the Applicant lie in having the opposition dealt with expeditiously as well as having the opportunity to respond to further evidence.  As a consequence their interests can be considered to lie against allowing the further evidence.  However, these factors may be addressed through the ‘reasonable terms’ on which the further evidence is allowed.

13. On balance, I consider that the interests of the parties lie in this further evidence being allowed. 

    The Dunbar declaration

14. During the hearing the Applicant referred to evidence on the availability of the Konstanzer article in Australia (the Dunbar declaration) and its relevance to the assessment of inventive step.  A request for further evidence was received following the hearing.  I do not intend to provide a detailed assessment of the request for further evidence in relation to this evidence.  In short the evidence relates to the full text Konstanzer article which was not entered into evidence until the Opponent requested further evidence.  Accordingly I consider that there was no real delay in serving this evidence.  Prima facie this evidence was of significance to a correct determination in the opposition. 

15. Similarly to the determination with respect to Konstanzer above, I consider the interests of the parties lie in this further evidence being allowed.

    The Direction

16. Pursuant to my determination in relation to the further evidence, I made the following directions under Regulation 5.10(1)(a):

    • Konstanzer was allowed as further evidence subject to reasonable terms as set out below.
    • That parties provided evidence in relation to the term ‘ischaemic insult’, particularly in the context of ‘ischaemic insult with sensory and motor hemiplegia’, and how this relates to stroke.
    • That such evidence was provided concurrently by the parties within one month of the date of the direction.
    • That the parties provided written submissions in relation to Konstanzer at the same time as their evidence.  Parties then had 1 week to provide written submissions in response.
    • The Opponent had 1 month from the date of the direction to provide evidence in response to the Applicant’s further evidence (the Dunbar declaration). 

17. This process was completed on 7 November 2011.

    OPPOSITION UNDER SECTION 59

    Onus of proof

18. The onus of proof in opposition proceedings lies with the opponent, who must establish that it is clear that a valid patent cannot be granted (F.Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283 at [29], [67]; (2001) 50 IPR 305 at 311 [29], 319 [67]; Commissioner of Patents v Sherman [2008] FCAFC 182 at [18], [22]; (2009) 79 IPR 426 at 430 [18], 432 [22]).

    Grounds of opposition

19. At hearing the opponent pressed the grounds of novelty, inventive step, utility, manner of manufacture, clarity and best method of performance.

    Novelty

20. A claimed invention is deprived of novelty if it has been given to the public before the priority date, either by prior use of a product or process, or by publication of information that equates to the claimed invention (Justice Bennett in Danisco A/S v Novozymes A/S (No 2) [2011] FCA 282 at [248]; (2011) 91 IPR 209 at [248]). It is well established that the general test for anticipation is the reverse infringement test. The classic formulation of this test is that given by Aickin J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19 at [20]; (1977) 137 CLR 228 at 235:

“The basic test for anticipation or want of novelty is the same as that for infringement and generally one can properly ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement.”

1. This test is satisfied if the alleged anticipation discloses all of the essential features of the invention as claimed (Nicaro Holdings Pty Ltd v Martin Engineering Co [1990] FCA 40 at [19]; (1990) 16 IPR 545 at 549). To meet this requirement, the prior art must contain “clear and unmistakable directions” to the claimed invention (Pfizer Overseas Pharmaceuticals v Eli Lilly and Co [2005] FCAFC 224 at [314]; (2006) 68 IPR 1 at 67 [314]). However, if the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee’s claim, but would be at least as likely to be carried out in such a way that would not do so, the patentee’s claim will not be anticipated (General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd (1971) 1A IPR 121 at 138).  Where a prior publication does not explicitly disclose all of the integers of the claimed invention, it would still deprive the claimed invention of novelty if (i) the skilled reader understands the disclosures of the prior publication to include a missing integer, and (ii) if the document contains a direction to use a process that inevitably or inexorably results in something within the claim (Justice Bennett in Danisco (No 2) [2011] FCA 282 at [248]; (2011) 91 IPR 209 at [248]).

1. Information is part of the prior art base for the purposes of novelty if it was in a publicly available document or made publicly available through doing an act before the priority date (see the definition of “prior art base” in Schedule 1 of the Act).

2. The Opponent pressed four documents under the ground of novelty:

   (a) Konstanzer (English language translation – see further evidence section for details)

   (b) Memin et al., Treatment of spasticity with Botulinum toxin, Rev.  Neurol.  (Paris), 1992: 148(3): 212-214 (hereinafter Memin)
   (c) Sampaio et al., Botulinum toxin type A for treatment of arm and hand spasticity in stroke patients, Clin Rehabil., 1997: 11, 3-7 (hereinafter Sampaio)
   (d) Das et al., Effect of treatment with botulinum toxin on spasticity, Postgrad.  Med.  J., 1989: 65(762): 208-10 (hereinafter Das)

3. Sampaio was published after the priority date of the present application.  However the Opponent submitted that the application was not fairly based on matter disclosed in earlier members of the present divisional family.  In particular they argued that the earliest priority date that the present application could be given was 11 February 2000.  The implication of this argument was that Sampaio could be considered for novelty and inventive step purposes.  Therefore before turning to each of these citations I will determine the priority date of the present claims.

   Priority

4. Section 43(1) sets out that each claim must have a priority date.  As noted above, the present application is the latest in a string of divisional applications.  In such cases the priority date of claims is determined according to reg 3.12 which in effect provides that the claims will take the priority date of the earliest disclosure on which the matter of the claim is fairly based.  This may be the date of filing of the application, the filing date of the parent application(s), the filing date of one or more priority documents, or the date of amendments introducing the matter on which the claim is fairly based. 

5. In the present case, the Opponent argued that the only reference to the present invention in the priority document (US Serial Number 08/173996), the great-great grandparent (AU 688452) and the great grandparent (712502) is a single example (Example 9, which notably corresponds to Example 10 of the present application).  The specifications of each of the three earlier applications are much the same, so for sake of brevity I will refer only to the priority document in this analysis. 

6. The Opponent argued that there are no general statements as to the invention in these applications, and the single example provided cannot provide fair basis for the broader invention defined in the present claims.  Indeed Dr Palit questioned whether the priority document disclosed treatment of post stroke spasticity pain at all (Palit 2 at paragraphs 7 to 13, 16 and 18).  He further noted that the example did not indicate which toxin was used, the dosage, the source of the toxin (different commercial sources have different potencies), or the weight of the patient, all of which would be required to determine the dosage required (Palit 1 at paragraphs 26 to 28). 

7. The Opponent concluded that the only claims that can take the priority date of these earlier applications are those defining the specific conditions set out in the example, and in particular, dosage, muscles injected and time for efficacy.  This in effect means that only the omnibus claim would be fairly based in as much as it is dependent on the example. 

8. I do not find these submissions persuasive.  The High Court in Lockwood Security Products v Doric Products [2004] HCA 58 at [27]; (2004) 217 CLR 274 noted that fair basis is concerned “purely with the relationship between the body and claims of the one specification”. The primary test for fair basis is simply whether the claims are consistent with what the specification as a whole describes as the invention.  The High Court accepted that there were two subsidiary tests (sub-tests) for fair basis which were relevant to the consideration of fair basis: is there “a real and reasonably clear disclosure” of the invention in the specification? [from Société Des Usines Chimiques Rhône-Poulenc v Commissioner of Patents [1958] HCA 27; (1958) 100 CLR 5 and cited with approval in Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79]; and do the claims travel beyond the subject matter of the invention described in the specification? [Olin v Super Cartridge [1977] HCA 23; (1977) 180 CLR 236].

9. Lockwood v Doric provides further guidance at [69]:

   “Section 40(3) requires, in Fullagar J's words, "a real and reasonably clear disclosure." But those words, when used in connection with s 40(3), do not limit disclosures to preferred embodiments. 

   "The circumstance that something is a requirement for the best method of performing an invention does not make it necessarily a requirement for all claims; likewise, the circumstance that material is part of the description of the invention does not mean that it must be included as an integer of each claim.  Rather, the question is whether there is a real and reasonably clear disclosure in the body of the specification of what is then claimed, so that the alleged invention as claimed is broadly, that is to say in a general sense, described in the body of the specification."

   Fullagar J's phrase serves the function of compelling attention to the construction of the specification as a whole, putting aside particular parts which, although in isolation they might appear to point against the "real" disclosure, are in truth only loose or stray remarks”.

10. Thus, the key consideration is whether the claimed invention is broadly described in the earlier application as a whole rather than limiting the consideration to preferred embodiments.  Turning to the priority document, the “Field of the Invention” states that:

    “The present invention provides novel methods for treating various disorders and conditions, with Botulinum toxins.  Importantly, the present invention provides methods useful in relieving pain related to muscle activity or contracture and therefore is of advantage in the treatment of, for example, muscle spasm such as Temporomandibular Joint Disease, low back pain, myofascial pain, pain related to spasticity and dystonia, as well as sports injuries, and pain related to contractures in arthritis” [emphasis added].

11. Thus there is broad disclosure of the treatment of pain related to spasticity.  The subsequent consideration is whether the specification broadly discloses treatment of pain related to post stroke spasticity.  In this regard, Example 9 is titled “The Use of Botulinum toxin Types in the Treatment of Muscle Spasms and Control of Pain Associated with Muscle Spasms in Spasticity Conditions Secondary to Stroke, Traumatic Brain or Spinal Cord Injury”.  I note that the example does not specifically refer to “post stroke spasticity pain”, but consistent with the view of Dr Palit (Palit 1 at [31]) pain associated with muscle spasms in spasticity secondary to stroke may be read as such.  I therefore consider that the priority document discloses the treatment of post stroke spasticity pain.

12. The priority document also broadly discusses the manner in which the toxin may be administered.  In particular, the toxin may be administered directly into a local area, such as a spastic muscle, but alternative administration such as subcutaneous injection directly to the affected area may be employed.  The dosage is said to be typically between 0.01 and 1000 units, and in the case of treating pain up to about 50 units may be employed.  The exact dose is said to depend on the severity of the condition and may be determined by the practitioner.  I consider that this provides for a broader reading of the invention than that relied upon by the Opponent.  The great-great grandparent (AU 688452) and the great grandparent (712502) provide essentially the same disclosure and accordingly these similarly provide fair basis for the treatment of post stroke spasticity pain.

13. I therefore consider that there is a real and reasonable disclosure of the invention as presently claimed in the earlier applications and that the invention as presently claimed may be afforded the priority date of 28 December 1993.  A consequence of this conclusion is that Sampaio is not relevant for the purposes of novelty and inventive step.  The following determinations of novelty and inventive step are therefore limited to Konstanzer, Memin and Das.

    Konstanzer

14. Before turning to the details of the Konstanzer document, I will deal with some peripheral issues concerning the evidence.  In particular, I sought evidence from the parties on the term ‘ischaemic insult with sensory and motor hemiplegia’.  The Applicant advised that Dr Russo, who had provided evidence in answer for the Applicant, was not available to provide evidence due to lecture commitments and an overseas business trip.  The Opponent submitted that I should draw the inference that Dr Russo’s evidence would have been adverse to the Applicant (Jones v Dunkel [1959] HCA 8; 101 CLR 298 at 321). However, contrary to this submission I consider that the reasons provided by the Applicant are prima facie valid, particularly in view of the time frames required by my direction under Reg 5.10(1)(a).  I therefore do not consider an adverse inference is appropriate.

15. The Applicant instead provided evidence from Dr Blumenfeld.  Dr Blumenfeld is a specialist neurologist.  He has experience treating stroke patients and has treated patients suffering from pain using botulinum toxin.  The Opponent provided evidence from Dr Palit and Dr Rawicki.  Dr Palit is a specialist physician in rehabilitation medicine with interests in the rehabilitation of patients following brain injury.  He has experience in the use of botulinum toxin for the treatment of spasticity.  Dr Rawicki is a specialist physician in rehabilitation medicine.  He has extensive experience in the rehabilitation of patients with neurological conditions, spinal cord injury and stroke.  He was one of the first medical practitioners in Australia to use botulinum toxin for the treatment of spasticity.  I consider each of the experts to be skilled in the present art and therefore in a position to provide skilled opinion on the Konstanzer document. 

16. However, the Opponent noted that Dr Blumenfeld did not appear to have been provided with any expert witness guidelines and that he is a consultant for the Applicant, including being listed as the inventor on three patents owned by the Applicant.  On the other hand, the Applicant submitted that Dr Rawicki’s evidence was not consistent with the expert witness guidelines in that it lacked factual or opinion based evidence, or any reasoning to support the statements made.  In this regard I note that the Commissioner is not bound by the rules of evidence, but these types of issues may be relevant considerations when determining the extent to which evidence may be relied upon.  In the present case I do not consider that the issues identified by the parties significantly impacted on the evidence and the weight it could be given in my determination.

17. The Opponent submitted that Konstanzer anticipates all of the present claims since the treatment of spasticity inherently resulted in the reduction of pain associated with spasticity.  Konstanzer describes an investigation of BOTOX as an alternative to the systemic use of antispastic drugs.  The original Konstanzer article is in German, but includes an English language summary which was exhibited early in the opposition.  A complete translation of the document was exhibited in further evidence.  The Opponent referred me to the English language summary, which states that 11 patients (mean age 48 years) with severe focal spasticity of the flexor muscles of the hand and arms, the adductor muscles of the legs or the plantar flexors of the foot due to multiple sclerosis, cervical myelopathy or stroke related hemi-paresis were treated using BOTOX.  Efficacy was assessed according to scales of spasticity, pain and hygiene, and improvements in each of these were recorded by 10 of the patients.  Effects could be observed after 4 – 7 days.  The Opponent also referred to Table 1, which included details of three patients (numbered 1, 5 and 7) who had suffered “ischaemic insult with sensory and motor hemiplegia”.

18. Notably the English summary is the only place where the term “stroke” is used.  The body of the document instead uses the term “ischaemic insult” and “ischaemic insult with sensory and motor hemiplegia”.  The parties differed as to whether or not these terms are synonymous with “stroke”.   This is clearly central to the consideration of novelty, and it is therefore necessary for me to first construe the meaning of these terms in order to determine whether Konstanzer provides a disclosure of the treatment of post stroke related pain.  I note that the primary facts are to be established on the balance of probabilities, but the ultimate facts – the facts leading directly to a conclusion of lack of novelty or a conclusion of obviousness – must be proved to the level of practical certainty (Aspirating IP Ltd v Vision Systems Ltd [2010] FCA 1061 at [35]; (2010) 88 IPR 52 at 63 [35). It is incumbent on the Opponent to establish their case.

19. The same rules of construction used for patent specifications apply to citations.  A useful summary of these principles was recently provided in the Full Federal Court in Kimberly-Clark Australia Pty Limited v Multigate Medical Products Pty Limited [2011] FCAFC 86 at [38]. Relevantly, a document is not to be read in the abstract but is to be construed in the light of the common general knowledge and the art before the priority date (Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd [2001] HCA 8 at [24]; (2001) 207 CLR at [24]). Furthermore at [13], Emmett J noted that:

    “The author of a document such as a patent specification uses language to make a communication for a practical purpose.  A rule of construction that gives that language a meaning differing from how that language would have been understood by the persons to whom it is addressed is liable to defeat the author’s intentions.  Thus, a patent specification should be given a purposive construction rather than a purely literal one derived from applying to it a meticulous verbal analysis.  Construction of a patent is not subjectively concerned with what the author meant to say.  Rather, it is objective, in the sense that it is concerned with what a reasonable person to whom the patent is addressed would have understood the author to be using the words to mean (see Kirin-Amgen Inc v Hoechst Marion Roussel Limited [2004] UKPC 6; (2004) 64 IPR 444 at [30] – [32])”.

20. At first blush it could be argued that the reference to stroke in the English language summary would lead the skilled person to read the document as disclosing the treatment of stroke.  However, Dr Blumenfeld noted that the English summary is not a translation of the German language summary.  He considered it likely that it had been prepared by the journal’s editorial staff rather than by the authors.  It is therefore possible that they may have interpreted the term “ischaemic insult with sensory and motor hemiplegia” to mean “stroke related hemi-paresis”, possibly in order to reduce the length of the summary (Blumenfeld at paragraph 11).  He also highlighted that the summary used the term hemi-paresis rather than hemiplegia.  These terms are not synonymous: hemi-paresis is a weakness on one side of the body, whereas hemiplegia is the complete paralysis of one side of the body.  Given the inconsistency in the language he considered the “scientifically appropriate” approach would be to rely on the body of the article rather than the summary in order to draw conclusions on the article.  Indeed he stated as a general point that he saw the purpose of an abstract as merely being a guide to the content of the article and therefore he did not draw conclusions from the abstract alone.  He considered others working in this field would view scientific articles in a similar manner. 

21. I consider this a reasonable representation of the way in which the skilled person would consider Konstanzer.  Accordingly, when construing the document I will concentrate on the disclosure in the body of the document and the way in which the person skilled in the art would construe the term “ischaemic insult with motor and sensory hemiplegia” in that context.

22. In addition to the reference to ischaemic insult with sensory and motor hemiplegia in the footnote to Table 1, there are several other references to ischaemic insult in Konstanzer:

    • Page 2, column 2: “With 3 patients an ischaemic insult and with 1 patient an operation to remove a brain tumour was the cause of a sensory and motor hemiplegia”.
    • Page 5 column 1: “In the case of 3 patients a degradation of the basic illness (… No.  5: renewed ischaemic insult of the CNS with internal complications and lacking of transportability) prevented further treatments”.
    • Page 6: “Das and Park described 8 patients with hemiparesis after cerebral ischaemic insult and flexor spasticity of the arms”

23. Both Dr Rawicki and Dr Palit stated that ischaemic insult with hemiplegia is synonymous with stroke.  Dr Rawicki stated that from his clinical knowledge and experience that he believed the diagnosis for the three patients was stroke (Rawicki at paragraph 13).  Dr Palit noted that the term “ischaemic insult” indicates that the patients have suffered tissue/cellular damage caused by anoxia (a lack of oxygen).  This can typically occur where there is an occlusion of blood vessels supplying the brain, leading to poor oxygen supply and damage to the cerebral tissue.  He considered that the reference to “ischaemic insult” in the context of “hemiplegia” confirms that the insult is stroke (Palit 3).  Dr Palit also stated that stroke may alternatively be referred to as a cerebral insult or cerebral ischaemic insult.

24. Dr Blumenfeld’s understanding of “ischaemic insult” was consistent with that given by Dr Palit.  However he stressed that ischaemic insult can result from a number of conditions, including: heart failure, haemorrhage, severe anaemia, stroke, respiratory failure, carbon monoxide poisoning, drowning and strangulation.  He noted that Konstanzer referred to the three patients having suffered “an ischaemic insult” and consequently he would not automatically infer that the patients had suffered a stroke.  Dr Blumenfeld also noted that patient 1 possessed a deformity of the foot known as pes equinus.  He considered this was more consistent with a dystonia than a stroke, thereby indicating the possibility of a more diffuse injury to the brain.  Without qualification of the organ or part of the body affected by the ischaemic insult, he considered that the type of ischaemic insult could not be conclusively determined.

25. Whilst these submissions do provide an indication of how the skilled person would construe the term “ischaemic insult”, I do not consider that they address the issue of whether an ischaemic insult with motor and sensory hemiplegia would be regarded as a stroke.  The evidence provided indicates that hemiplegia occurs as a result of the cell death associated with the ischaemic insult in particular regions of the brain (Palit 1 at paragraphs 17 and 18).  The inference is that ischaemic insult where it results in hemiplegia or associated with hemiplegia involves brain tissue.  The evidence provided by Dr Blumenfeld does not otherwise establish that ischaemic insults in other regions of the body can result in hemiplegia without there being an associated or secondary stroke. 

26. I am therefore satisfied in view of the evidence before me that the skilled person would interpret ischaemic insult with sensory and motor hemiplegia as being synonymous with stroke. 

1. As an aside, Dr Blumenfeld stated that the prevalence of stroke increases with age and is extremely rare in individuals aged 18 to 44 years and noted that the ages of the patients when they first suffered the ischaemic insult were 25, 41 and 40.  He found it statistically unlikely that three such unusual patients could be in one study, and moreover that no comment was made in this regard.  He considered this alone would lead the person skilled in the art to conclude the ischaemic insult was not stroke.  In support of this statement he referred to studies published in 2010, 2007 and 1998.  Notwithstanding any concerns I have with the nature of these studies and particularly the patient groups reported, I note that these were published well after the publication date of Konstanzer.  No other evidence was provided to indicate that this was common general knowledge at the relevant time and that the skilled person would indeed consider the patient group in this manner.  Accordingly I can give this particular submission little weight. 

2. The next question is whether Konstanzer discloses, either explicitly or inherently, the treatment of post stroke spasticity pain.  The opponent submitted that the English language summary disclosed that 10 of the patients showed an improvement in pain and concluded that focal spasticity and pain can be successfully reduced using botulinum toxin.  In support of these statements they referred to the following:

   • Page 1, column 2: “The object was to ameliorate the pain due to the spasticity, to improve hygienic situation and to alleviate care…”
   • Page 3, column 1; “Pain in connection with spasticity represented a substantial impairment with all 11 patients”.
   • Page 2, caption to photograph of patient 5: “After injection a limited loosening of the muscular fixed contraction was observed, pain was reduced and hygienic measures facilitated”.
   • Page 2, Table 1: “Indications” for patients 1 and 5 includes pain.
   • Page 6, Table 4: patients 1, 5 and 7 report a reduction on the pain scale from 1 down to 0.
   • Last page, column 2: “The experience gained in this study shows that Botox is suitable, through simple and safe handling, to produce a positive effect with selected patients on the local painful and inhibiting consequences of severe spasticity and also to obtain a functional improvement in the case of a patient sub-group with residual voluntary activity”.

3. In response the applicant argued that there was no associative link between spasticity and pain given in Konstanzer.  In particular, Dr Russo stated that Konstanzer does not mention whether the reduction in pain was a reduction in peripheral pain or in central pain and therefore it cannot be concluded that the treatment resulted in a reduction of post stroke spasticity pain (Russo at paragraph 18).

4. On balance of probabilities I am satisfied that Konstanzer discloses the features of the present claims.  The extracts from Konstanzer provided above clearly link the pain to the spasticity and are consistent with the undisputed definition of post stroke spasticity pain as being pain that is concurrent with the spasticity (see for example Palit 1 at paragraph 31).  Accordingly I consider that Konstanzer discloses a treatment that results in a reduction of pain resulting from post stroke spasticity.  Konstanzer further discloses that the injections are made at the place of strongest spastic hyperactivity (see “Injection technique and dosage” section, page 3, column 2), including muscles in the arms and legs (see Table 2, patients 1, 5 and 7).  This anticipates the matter of claims 1 to 4 and 6.  An effect began to be indicated by patients after 4 – 7 days with the maximum effect occurring at about 21 days, and an average period of effectiveness for pain reduction and reduced spasticity of 10 weeks (page 5, column 1).  I consider this discloses the features of Claim 5 in that pain is relieved in 7 to 21 days after intramuscular injection.  The matter of the omnibus claim 7 is disclosed in as much as the method is intended to provide relief of the pain and spasticity.

5. In conclusion I find that Claims 1 to 7 lack novelty in view of Konstanzer.

   Memin

6. Memin is a French language document, but an English language summary is provided by the journal.  The Opponent’s submissions were all based on that summary.  The document discloses a study of 8 patients (7 stroke and 1 head injury) with severe spasticity.  Six patients suffered pain and 4 had cutaneous lesions, especially maceration of the palm of the hand.  Spasticity was improved in all patients and 5 reported significant pain relief. 

7. The applicant submitted that, like Konstanzer, Memin did not provide an associative link between the pain and the spasticity and particularly whether the pain was peripheral or central.  The opponent submitted that the document teaches a concurrent reduction in both pain and spasticity and on that basis the document should be read as providing a reduction in post stroke spasticity pain.  They argued that Dr Russo stated in relation to present Example 10 that there can be relief of symptoms of spasticity which has the effect of relieving pain (Russo at paragraph 14).

8. The patients are said to suffer severe spasticity.  Moreover, the summary links the severe spasticity suffered by the patient group to difficulty with hygiene which has resulted in lesions in patients’ hands.  The summary also states that “Five patients reported significant pain relief on a visual analogical scale.  Most of them reported a benefit in their limb tone and referred to subjective improvements in the activity of daily life and nursing”.  I take this to mean that at least some of the group also experienced difficulties with nursing as a result of the severity of their spasticity (this is further suggested at page 213, second paragraph, wherein that one patient is said to require 2 attendants for nursing).  In this regard I note the statement of Dr Russo submitted in relation to Example 10 of the present application:

   “… I note that the patient of Example 10 had “… severe closing of hand and curling of wrist and forearm or the muscles involved in the closing of the legs such that the patient and attendant have difficulty with hygiene.”.  It is my understanding based on my clinical experience in the treatment of such patients that it would be highly unusual for spasticity of a degree that causes inability of both the patient and an attendant to for example, wash the groin area not to be painful” (Russo at paragraph 14).

9. The patient group disclosed in Memin suffer difficulty with hygiene and with nursing.  Consistent with the statement by Dr Russo, I consider on balance that the pain experienced by these patients would be associated with the spasticity.  Memin therefore discloses treatment that results in the reduction of pain associated with post stroke spasticity pain wherein botulinum toxin A is administered by intramuscular injection. 

10. Memin further discloses the features of Claims 2 to 4 since the summary discloses intramuscular injection of both arm and leg muscles.  The matter of Claim 5 is disclosed in that the average time to onset of effect was 1 to 15 days (page 213 second paragraph).  The “Methode” section discloses the preparation of formulations for use in the treatment and accordingly the matter of Claim 6 is disclosed.  The relief of spasticity and pain associated with spasticity is disclosed, thereby anticipating the matter of Claim 7.

11. In conclusion I consider that Claims 1 to 7 lack novelty in view of Memin.

    Das

12. Das discloses the treatment of 6 patients with severe spasticity resulting from stroke related hemiplegia.  Treatment involved intramuscular injection of botulinum A toxin to affected arm muscles.  Range of movement, functional ability and spasticity were assessed over a period of 4 months.  Patients were also asked to assess pain relief and discomfort.  Spasticity was relieved, but patients reported only slight relief in discomfort in the treated arms.

13. The Opponent considered that the assessment by patients of pain relief and discomfort indicates that pain relief was an intended outcome of the study.  Dr Palit interpreted the relief of discomfort as suggesting that there was a reduction in pain, albeit slight (Palit at paragraph 80). 

14. However Dr Russo considered that discomfort is not the same as pain.  He considers that discomfort is an unpleasant sensation not primarily recognised or regarded as pain.  The Applicant argued that as a consequence Das is silent as to the treatment of pain.  I agree.  The document clearly differentiates between pain and discomfort.  No reduction in pain is reported by the patients, and indeed there is nothing in Das that clearly establishes any patients were suffering any spasticity pain prior to treatment.

15. In conclusion I consider the claims are novel in view of Das.

    Inventive Step

16. The test for obviousness is whether it would have been a matter of routine to proceed to the claimed invention.

    “The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not.” (Aicken J in Wellcome Foundation Ltd v VR Laboratories (Aust) Pty Ltd [1981] HCA 12 at [45]; (1981) 148 CLR 262 at 286)

17. More recently, the High Court in Aktiebolaget Hässle v Alphapharm Pty Ltd [2002] HCA 59 at [51] - [53]; 212 CLR 411 at [51] - [53] approved the approach taken in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd [1970] RPC 157 at 187 in which Graham J had posed the question:

    “Would the notional research group at the relevant date in all the circumstances directly be led as a matter of course to try [the claimed invention] in the expectation that it might well produce a useful [desired result]?”

18. On the face of the specification the problem to be solved is the reduction of post stroke spasticity pain (Apotex Pty Ltd v Sanofi-Aventis [2009] FCAFC 134; (2009) 82 IPR 416 at [152] – [154]). The Opponent pressed inventive step under both Section 7(2), obviousness in view of the common general knowledge, and Section 7(3): obviousness in view of a prior art document. This is largely a moot point in view of my finding in relation to the novelty of the claims, so I do not intend to further detail the submissions here. In short I consider that pursuant to the lack of novelty, the claims also lack inventive step in view of Konstanzer and Memin. These documents describe the treatment of post stroke spasticity by intramuscular injection of botulinum toxin, and the treatment provides relief of post stroke spasticity pain. It follows from my determination that the claims also lack inventive step since the skilled person would need only to follow the instructions in those documents in order to arrive at the invention as claimed.

19. The question then arises as to whether the application contains patentable subject matter.  In this regard, the specification states that:

    “The dosages used in human therapeutic applications are roughly proportional to the mass of muscle being injected.  Typically, the dose administered to the patient may be up from about 0.01 to about 1,000 units; for example, up to about 500 units, and preferably in the range from about 80 to about 460 units per patient per treatment., although smaller of [sic] larger doses may be administered in appropriate circumstances such as up to about 50 units for the relief of pain and in controlling cholinergic secretions”. 

20. The gist of the Opponent’s argument is essentially that it would be obvious to relieve post stroke spasticity pain by treating the spasticity.  In contrast, the above passage suggests that there may be a different dosage amount for the relief of pain only.  If this is indeed the case, there is nothing in evidence to establish that the person skilled in the art would ascertain, understand and consider the documents relevant and would be led to administer botulinum toxin in order to relieve post-stroke spasticity pain without relieving the muscle spasticity.  However the claims are not limited in such a way and I have no submissions before me that would establish that such matter could validly be incorporated in the claims.  Accordingly I am unable to make any conclusions in this regard, and provide these comments as an observation only.

21. In summary, Claims 1 to 7 lack inventive step.

    Utility

22. Lack of utility is established when a claim includes subject matter that will not produce the desired result (H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70 at [81]; (2009) 81 IPR 228 at 247 [81]; Ranbaxy Australia Pty Ltd v Warner-Lambert LLC [2008] FCAFC 82 at [141]; (2008) 77 IPR 449 at 479 [141]).

23. The opponent submitted that the desired result is a reduction in post stroke spasticity pain.  Whilst the claims defined that treatment involved injection into a cholinergic influenced muscle and the skilled person may be able to identify the preferred muscle for injection, the claims were not limited to such muscles.  Dr Palit suggested that in view of the large number of cholinergic influenced muscles in the body a clinician could inject them into one which is not related to the spasticity (Palit 1 at paragraph 42).

24. The Applicant considered this a “quite purposeful adoption” of Claim 1 so as to suggest inutility (Washex Machinery Corporation v Roy Burton & Co Pty Ltd [1974] 49 ALJR 12 at [19]). They referred to SNF (Australia) Pty Ltd v Ciba Specialty Chemicals Water Treatments Limited [2011] FCA 452 at [293]; (2011) 92 IPR 46 at 212 [293], wherein Kenny J stated:

    “In construing the claims for the purposes of utility, the claims must, moreover, be construed from the perspective of a skilled addressee in a commonsense way, and not in such a way that any such addressee would appreciate would lead to an unworkable result.

25. I consider that the skilled person would read the claim to give it meaning and in doing so would understand that the spastic muscle is the cholinergic influenced muscle to be treated.  The Opponent has provided no evidence to show that any embodiment claimed does not produce the desired result and accordingly the lack of utility has not been made out.

    Manner of Manufacture

26. Section 18(1)(a) requires that an invention must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies.  Manner of manufacture is assessed by asking whether the claimed invention lacks the necessary quality of inventiveness on the face of the specification (NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd [1995] HCA 15 at [9]; (1995) 183 CLR 655 at 655).

27. The Opponent argued that it was known at the earliest priority date that botulinum toxin A was used to relieve muscle spasticity and this has the inevitable result of relieving post stroke spasticity pain.  However on the face of the specification it is not apparent that the use of botulinum A toxin for the treatment of post stroke spasticity pain was known.  Accordingly I consider that the invention is a manner of manufacture.

    Clarity

28. A claim is lacking in clarity if a third party could not ascertain whether an act would fall within the scope of the claim (Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59 at 60). The Opponent submitted that Claim 7 lacks clarity because it defines a method for treating post stroke spasticity pain with reference to the examples, but only one example refers to such treatment. I do not consider that this renders the scope of the claim unclear as an addressee would readily ascertain the scope of the claim.

    Best Method/ Full Description

29. The Opponent submitted that the specification does not disclose the best method of performing the invention.  I note that the specification provides an example, and prima facie the requirement of a best method has been met.

30. Furthermore, Dr Palit stated that the example did not provide sufficient information for the skilled person to determine the dosage given to the patient (Palit 1 at paragraph 28).  Dr Russo considered the example provides sufficient information for a skilled person to achieve the claimed result (Russo at paragraph 13 to 14).  A claim is fully described if the disclosure enables the addressee to produce something within the scope of each claim without new inventions or additions or prolonged study of matters presenting initial difficulty (Kimberley Clark Australia Pty Ltd v Arico Trading International Pty Ltd [2001] HCA 8 at [25]; (2001) 207 CLR 1 at 17 [25]). No evidence has been provided that establishes that the skilled person could not achieve the claimed result without the need for invention. I consider that a full description has also been met.

    CONCLUSION

31. Claims 1 to 7 lack novelty and inventive step.   The opposition therefore succeeds. 

32. A prima facie consideration of the specification suggests that there may be patentable subject matter.  Accordingly I allow the Applicant 2 months from the date of this decision to propose amendments to overcome the deficiencies.

    COSTS

33. Costs generally follow the event.  I see no reason to depart from that practice.  The opposition has been successful on the grounds of novelty and inventive step.  I therefore award costs according to Schedule 8 against the applicant, Allergan, Inc.

    L. F. McCaffery
    Delegate of the Commissioner of Patents