Ipsen Pharma S.A.S. v the Regents of the University of Colorado, a Body Corporate - [2013] APO 23

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Ipsen Pharma S.A.S. v The Regents of the University of Colorado, a body corporate
[2013] APO 23

Patent Applications:                2005234633, 2006225233, and 2008201535
Title: (for each application)     Use of Neurotoxin Therapy for Treatment of Urologic and Related Disorders
Patent Applicant:  The Regents of the University of Colorado, a body corporate
Opponent:Ipsen Pharma S.A.S.
Delegate:Ms Nicole Howard
Decision Date:  5 March 2013 (corrected on 14 March 2013)
Hearing Date:  10 & 11 December 2012 in Canberra
Catchwords:  PATENTS - section 59 - opposition to grant of a patent – botulinum toxin for treatment of incontinence and related disorders - opposition partially succeeds on grounds of novelty and inventive step – review article that incorrectly interprets source references does not stand alone – costs awarded against applicant – 60 days to amend allowed
Representation:  Patent applicant: Christian Dimitriadis of Counsel, instructed by Gavin Recchia, Patent Attorney of Davies Collison Cave, Sydney
Opponent:Ian Horack of Counsel, instructed by Amanda Jones and Caroline Harris, Patent Attorneys of Watermark, Melbourne

CORRIGENDUM
Decision of 5 March 2013 has been corrected on 14 March 2013 as follows.

Under ‘DECISION’ on page 1, 2005232633 has been corrected to 2008201535

Paragraph 49 has been corrected to reflect that claims 1-7 of 233 are not anticipated (previously 1-11)

Paragraph 58 has been corrected to reflect that claims 1 and 3-7 of 233 are obvious (previously claims 1 and 3-12)

Paragraph 63 has been corrected to reflect that claims 1 and 3-7 of 233 lack an inventive step (previously claims 1 and 3-12 of 633)

Paragraph 70 has been corrected to reflect that claims 1 and 3-7 lack novelty and an inventive step (previously claims 1 and 3-12 of 633)

Paragraph 71 has been corrected to reflect that 60 days are allowed for amendment to 233 (previously 633)

IP AUSTRALIA,
AUSTRALIAN PATENT OFFICE
Patent Application: 2005234633, 2006225233, and 2008201535
Title:Use of Neurotoxin Therapy for Treatment of Urologic and Related Disorders (x3)

Patent Applicant: The Regents of the University of Colorado, a body corporate
Date of Decision: 5 March 2013 (corrected on 14 March 2013)
DECISION
The opposition succeeds on the grounds of novelty and inventive step in 2008201535 and 2006225233. Costs awarded against the applicant.
REASONS FOR DECISION
Background

The present applications are divisional applications filed by The Regents of the University of Colorado, a body corporate (hereafter RUC). Priority details are as follows:

·2005234633 (hereafter 633) filed on 16 November 2005 claims divisional status from Australian Patent 743085, filed on 15 July 1998, which claims priority from US 60/052,580, filed on 15 July 1997;
·2006225233 (hereafter 233) filed on 4 October 2006 claims divisional status from 2005234633;
·2008201535 (hereafter 535) filed on 4 April 2008 claims divisional status from Australian Patent 2007200509 which in turn claims divisional status from 2005234633.

It is noted that 633 and 233 were amended during the evidentiary process.

Notices of opposition were filed on 18 July 2007 (633), 7 March 2007 (233) and 26 September 2008 (535) by Ipsen Pharma S.A.S. (hereafter Ipsen). Statements of grounds and particulars (SGP) were filed on 18 October 2007 (633), 6 June 2007 (233) and 24 September 2008(535). All SGPs were subsequently amended.
Evidence
The parties rely on evidence deposed by the same declarants in each application. In these cases the skilled addressee is considered to be a specialist working in the field of urology. The Applicant’s evidence consists of declarations by Dr Jeffrey Thavaseelan, a qualified specialist in urology residing in Western Australia and Professor Philip van Kerrebroeck, residing in the Netherlands who is also a qualified specialist in urology. The Opponent’s evidence consists of declarations by Carolyn Joy Harris of the Opponent’s patent attorneys, Dr Peter Dwyer, a medical practitioner resident in Victoria who is a qualified specialist in obstetrics and gynaecology and Dr Laurence Stewart, a medical practitioner resident in the United Kingdom who is a qualified specialist in urology. While considerable submissions were made at the hearing as to the appropriate weighting of the declarations, I accept that Dwyer, Stewart, Thavaseelan and Kerrebroeck are all in a position to provide relevant evidence. Dr Dwyer and Dr Thavaseelan are the chief declarants, while Dr Kerrebroek and Dr Stewart are supporting declarants. I will only refer to the evidence of Kerrebroek and Stewart if necessary.
Grounds of Opposition
The grounds relied upon by the Opponent are:
·Lack of Novelty
·Lack of Inventive Step
·Failure to comply with s.40 (fair basis, clarity, sufficiency)
·Inutility
·Manner of Manufacture
There is considerable overlap in the grounds, evidence and submissions for all three applications. For the purposes of this decision I think it prudent to address matters globally and only refer to specific applications as required.
The specifications
The description
The specifications are titled ‘Use of neurotoxin therapy for treatment of urologic and related disorders’.

The inventions provide methods for treating neuronally-mediated urologic and related disorders, for example incontinence, urge type dysfunction and urgency and frequency symptoms of overactive bladder. This is accomplished by administering the neurotoxin, botulinum toxin.
The description explains that many medical conditions in urology are rooted in spastic dysfunction of the sacral reflex arcs. Examples of such conditions include pelvic pain, urinary incontinence (e.g. unstable bladder, unstable sphincter), prostate disorders, urinary retention and neurogenic bladder dysfunction. While much of the descriptions are devoted to the treatment of prostate disorders they also refer to the treatment of either urge type dysfunction (535), incontinence (633) or symptoms of overactive bladder (233). Botulinum toxin A is taught to be the preferred neurotoxin. Six examples are provided, with example 3 disclosing the successful treatment of two patients for incontinence and, in the case of the second patient, urge type dysfunction. The botulinum toxin is injected into the bladder.

The claims

The key claims of the application are recited as follows.
633
1.The use of a botulinum toxin in the preparation of a pharmaceutical composition for treating urinary incontinence.
2.   The use of claim 1, wherein the urinary incontinence is unstable bladder.
3.   The use of claim 1, wherein the urinary incontinence is urge incontinence.
233
1.   The use of a botulinum toxin in the preparation of a pharmaceutical composition for treating at least one symptom of overactive bladder.
2.   The use of claim 1, wherein the symptom of overactive bladder is urinary incontinence.
4.The use of claim 1 or 2, wherein the composition is provided in a form that is suitable for administration to the bladder of a patient.
535
1.A method for treating an urge type dysfunction in a patient, comprising administering a therapeutically effective amount of botulinum toxin to the patient, whereby the urge type dysfunction is treated.
2.   The method of claim 1, wherein administration is to the urinary tract of the patient.

3. The method of claim 1, wherein administration is to the bladder of the patient.
28.A therapeutic agent comprising a botulinum toxin type A for treating at least one of the urgency and the frequency symptoms of overactive bladder in a patient with overactive bladder by administering said therapeutic agent to the bladder wall of the patient.

Other claims will be referred to as necessary.

The urinary tract

Both parties agree that the Dwyer declaration correctly describes the basic anatomy and functioning of the urinary tract (paragraphs 13-19). Ipsen have summarised this part of the Dwyer declaration in their submissions. I think it useful to reproduce this summary as background.
‘The urinary tract consists of the kidneys, the ureters, the bladder and the urethra. A diagram of the urinary tract is … shown below.
The two kidneys and ureters are referred to as the upper urinary tract and the bladder and the urethra as the lower urinary tract. The kidneys are an abdominal organ which is the waste disposal unit of the body. The two kidneys produce urine which passes down the ureters which are muscular tubes which travel through the body and empty into the bladder.
The bladder is a hollow organ which holds urine. It consists of three layers, an inner membrane, an intermediate thick middle layer (the detrusor muscle) and an outer layer. The detrusor muscle consists of interlacing smooth muscle cells which run in bundles and when stimulated by the bladder nerves contracts in all dimensions to efficiently expel urine. The nerve supply to the bladder consists of parasympathetic and sympathetic neural fibres. The parasympathetic nerve fibres stimulate the bladder muscle to relax while stimulating the urethral sphincter muscle to contract. The urethra is a fibro muscular tube that leads from the bladder to the body’s exterior. During urination the urethral muscles relax and the urethra opens. Urination occurs as a result of coordinated synchronous act of urethral relaxation and detrusor muscle contraction.’
The Thavaseelan declaration adds some further background as follows:

‘Broadly speaking, the bladder stores urine and releases this into the urethra (voiding) upon contraction of bladder smooth muscle, co-ordinated with the relaxation of the bladder neck (internal sphincter) and the external urethral sphincter which consist predominantly of striated muscle. The smooth muscle of the bladder and the striated muscle of the sphincter are fundamentally different, in terms of their structure, the nature of their contraction and the regulation of this contraction.’

It is important to note that the above describes a healthy urinary tract.
Construction

The principles of construction are well settled. In considering the definition of terms used in claims in Sachtler GmbH & Co KG v RE Miller Pty Ltd [2005] FCA 788, Bennett J restated the following points:

·Terms in the claim which are unclear may be defined or clarified by reference to the body of the specification
·It is legitimate to refer to the rest of the specification to explain the background to the claims, to ascertain the meaning of technical terms and to resolve ambiguities in the construction of the claims. Where the language of the claim is obscure or doubtful the doubt is sometimes resolved by referring to words in the body of the document to explain it.
·A patent should be given a purposive construction. However, that does not involve extending or going beyond the definition of the technical matter for which the patentee seeks protection in the claims. The question is always what the person skilled in the art would have understood the patentee to be using the language of the claim to mean. For this purpose, the language chosen is usually of critical importance.

Central to the outcome of the present oppositions is the construction of the claims.

Claim 1 of 633 is directed to ‘The use of a botulinum toxin in the preparation of a pharmaceutical composition for treating urinary incontinence.’ It is clear from both Dwyer and Thavaseelan that urinary incontinence is the complaint of any involuntary leakage.
Claim 1 of 233 is directed to ‘The use of botulinum toxin in the preparation of a pharmaceutical composition for treating at least one symptom of overactive bladder’ [emphasis added]. Dwyer provides that the symptoms of overactive bladder include urgency, frequency, nocturia and incontinence. He further explains that ‘The cause of this functional abnormality is classified as idiopathic detrusor overactivity where no defined cause is found or neurogenic detrusor overactivity where the overactivity is due to a neurological condition.’ Thavaseelan does not contravert these points. There is however, vigourous disagreement as to the terms synonymous with overactive bladder. Dwyer argues that overactive bladder is one and the same with ‘spastic bladder/neurogenic bladder’. While Thavaseelan agrees that spastic bladder and neurogenic bladder are equivalent he strongly argues that overactive bladder is not spastic/neurogenic bladder. Rather, he argues that spastic bladder/neurogenic bladder is an alternative term for detrusor sphincter dyssynergia (DSD). DSD is condition characterised by a spastic urethral sphincter which ‘prevents or at least reduces the removal of urine from the bladder, by virtue of the sphincter contracting at the same time as the bladder and therefore restricting the flow or urine out of the bladder.’ …The neurogenic bladder may include bladder overactivity (sometimes referred to as unstable bladder)…It is the bladder overactivity component of neurogenic bladder that causes urinary incontinence…In other words, spastic urethral sphincter or DSD is characterised by urinary retention and is not a cause of urinary incontinence.’
The differences in opinion of the declarants can be easily resolved by reference to the specification. Page 6, lines 8-9 clearly contemplate the symptoms of overactive bladder to be selected from urinary incontinence and urinary retention. It follows that the term ‘overactive bladder’ in claim 1 includes DSD/spastic bladder or other conditions characterized by urinary retention.
Claim 2 is clearly limited to the incontinence aspect of overactive bladder and excludes retention. Claim 4 recites the use of claim 1 or 2, wherein the composition is provided in a form that is suitable for administration to the bladder of a patient.’ I construe the composition of claim 4 as being only limited by a suitability. The claim is not limited to actual administration to the bladder.
Claim 1 of 535 is directed to ‘A method for treating an urge type dysfunction in a patient, comprising administering a therapeutically effective amount of botulinum toxin to the patient, whereby the urge type dysfunction is treated.’ Thavaseelan provides ‘I understand the term “urge-type dysfunction” to be a bladder dysfunction precipitated or characterised by abnormal urge symptoms and thus resulting in urgency.’ … ‘I therefore understand that an urge type dysfunction as used in the Patent Application equates to urgency.’ Dwyer describes “urgency” as a strong desire to void. Referring to the specification, Example 3 (patient 2) explains that following botulinum toxin injections into the lateral bladder wall, the patient ‘no longer had annoying constant urge type dysfunction’. I am satisified that urge type dysfunction is simply a strong desire to void.
Claim 2 is directed to the same method wherein the toxin is injected into ‘the urinary tract’. On the face of it this claim may seem broader than claim 1. However, claim 1 militates that urge type dysfunction actually be treated. Injection into parts of the urinary tract other than the bladder (in particular the external sphincter) will not treat the dysfunction. It follows that claim 2 does not add anything to the scope of the claim.

Claim 28 is construed as a therapeutic agent comprising botulinum toxin type A that is merely suitable for use in the treatment of at least one of the urgency and frequency symptoms of overactive bladder and as such will be anticipated by any formulation of botulinum toxin type A suitable for administration to the bladder wall of a patient. At the hearing this was conceded by the applicant.
Swiss style claims
The claims of 633 and 233 are drafted in Swiss style. Australian practice in the construction of these claims is recited in the Manual of Practice and Procedure as follows:
The typical form of a Swiss claim is:
“The use of (substance X) for the manufacture of a medicament for the therapeutic and/or prophylactic treatment of (medical condition Y).”
Swiss claims are construed as defining the manufacture of a medicament, wherein the medicament is intended for a specified medical treatment. The novelty and inventiveness of Swiss claims is considered to derive from the new medical use and not from the manufacture of the medicament. Therefore, a prior art disclosure of a method of making the medicament will not in itself anticipate a Swiss claim. In order to anticipate a Swiss claim, a citation must disclose both a method of preparing the medicament and the specific treatment claimed. (This approach is consistent with that followed in British (John Wyeth & Brother Ltd's Application [1985] RPC 545, Bristol-Myers Squibb Co. v Baker Norton Pharmaceuticals Inc. [1999] RPC 253) and New Zealand decisions (Pharmaceutical Management Agency Ltd. V Commissioner of Patents (Pharmac) (2000) NZCA 330)).
Current Australian practice has been applied in this decision.
Onus of proof
In proceedings such as these before the Commissioner, the onus rests with the opponent to clearly establish its case in reaching a conclusion on any issue. In F. Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283, Emmett J of the Federal Court found that in opposition proceedings, the Court (and by implication the Commissioner of Patents in her role as a tribunal) should be "clearly satisfied that the patent, if granted, would not be valid". Where questions of fact such as obviousness and existence of invention are involved "the grant should not be refused unless it has been clearly shown that the grounds of opposition have been clearly made out" (Montecatini v Eastman Kodak (1971) 45 ALJR 593).
Priority
Ipsen contend that the claims of the applications should not be afforded the earliest priority date of 15 July 1997 because the claims are not fairly based on the priority documents.
The general test for fair basis set out in Lockwood Security Products Pty Ltd v Doric Products Pty Ltd [2004] HCA 58 at [69]; (2004) 217 CLR 274 at 300 [69] requires that there be 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.’
On inspection of the entire patent family including the original US priority document it is abundantly clear that the treatment of incontinence, urge type dysfunction and a symptom of overactive bladder using botulinum toxin have a real and reasonably clear disclosure in each and every document. The documents are all broadly directed to the treatment of urologic and related disorders. The background of the invention in each case specifically lists urinary incontinence and urinary retention as medical conditions in urology. The detailed description of the preferred embodiment also lists urinary incontinence and urinary retention as urological-neurological conditions or disorders. Patients 1 and 2 of Example 3 are clearly treated for incontinence and, in the case of patient 2, it is specifically stated that their urge type dysfunction is treated.

The 633 case is directed to the treatment of incontinence and is self evident. Considering the 233 case, while overactive bladder is not explicitly disclosed, the major symptoms of overactive bladder have been identified as incontinence and retention above and are clearly contemplated by the priority documents (noting again that claim 1 defines the treatment of symptoms). The 535 case, being directed to treatment of an urge type dysfunction takes basis from patient 2 of Example 3.
I am satisfied that the priority date is 15 July 1997.
Novelty
The law of novelty
The basic test for novelty is the “reverse infringement” test as stated in General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd (1972) RPC 457 at pages 485, 486:

“If carrying out the directions contained in the prior inventor's publication will inevitably result in something being made or done which, if the patentee's patent were valid, would constitute an infringement of the patentee's claim”.

In applying this test regard must be given to the level of disclosure in the prior publication. As stated in Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR at 517:

“It is well accepted that the prior art must disclose all features of the invention embodied in the patent in suit and must do so in clear, unequivocal and unmistakeable terms. The prior art must enable the notionally skilled addressee at once to perceive and understand and be able practically to apply the discovery without the necessity of making further experiments. Whatever is essential to the invention must be read out of or gleaned from the prior publication.”

In Nicaro Holdings, Gummow J also referred to the speech of Lord Reid in C. Van Der Lely N.V. v Bamfords Limited (1963) RPC 61 and 71-72 where Lord Reid reaffirmed the principle set down by Lord Westbury in Hills v Evans [1862] 4 De G, F & J 288; 45 ER 1195 in relation to the level of disclosure necessary to anticipate a claimed invention:

"a person of ordinary knowledge of the subject would at once perceive and understand and be able practically to apply the discovery without the necessity of making further experiments".

The Opponent presses the following documents under the ground of novelty.
US 4 932 936 (Dykstra)
Dykstra D, Sidi A A, ScottA B, Pagel J M and Goldfish G D, Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients, Journal of Urology 1988: 139:919-922
B Schurch J et al, Botulinum A toxin as treatment of detrusor-sphincter dyssynergia: a prospective study in 24 spinal cord injury patients”, Journal of Urology 155, p 1023-1029
Dykstra D D, Sidi A A Treatment of detrusor-sphincter dyssynergia with Botulinum A toxin: a double blind study, Arch Phys Med Rehabil 1990; 71:24-26

These four documents disclose the treatment of DSD using botulinum toxin A. The toxin is injected into ‘spastic urethral sphincters’ which results in voiding of the bladder. That is, relief of the sphincter spasticity treats the urinary retention aspect of DSD. The compositions are in a liquid injectable form inherently suitable for administration into the bladder. It follows that claims 1 and 3-7 of 233 are not novel. Claim 28 of 535 is also not novel in light of the botulinum toxin A disclosures.

No treatment of incontinence or urge type dysfunction is mentioned whatsoever. All claims of 633, claims 1-27 of 535 and claim 2 of 233 are not anticipated by these documents.
Review of Jankovic J J and Brin M
F, Therapeutic uses of botulinum toxin, the New England Journal of Medicine 1991, 324: 1186-1194
This review broadly describes the therapeutic uses of botulinum toxin. Under the heading ‘Other Potential Indications’ is found the solitary statement ‘Injections of botulinum toxin into the detrusor and sphincter muscles have been found to improve bladder function in patients with spinal cord injury.’ No other support for the treatment of bladder function is provided.

The Opponent argues that injection into the detrusor muscle will treat incontinence. Indeed, according to the evidence this is likely to be the case. However, the statement is referenced from two publications that in fact do not disclose injection of toxin into the detrusor muscle of the bladder. I am aided by the Patent Examiner’s Manual of Practice and Procedure. 2.4.5.2. recites
Where there is an error in the citation, that error is not to be given a literal interpretation. In particular:
·if the skilled addressee would have recognized the error but knew how to correct it, the corrected version is disclosed but the original version is not
·if the skilled addressee would have recognized the error but not known how to rectify it, the matters relating to that error and its correction have not been disclosed, and
·if the skilled addressee would not have recognized the error, again the matters relating to that error have not been disclosed.
Dykstra D, Sidi A A, ScottA B, Pagel J M and Goldfish G D, Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients, Journal of Urology 1988: 139:919-922 and DykstraD D, Sidi A A, Treatment of detrusor-sphincter dyssynergia with Botulinum A toxin: a double blind study, Arch Phys Med Rehabil 1990; 71:24-26 are both collectively discussed above. It is clear from these documents that only the treatment of DSD (urinary retention) is disclosed. Accordingly this review document is considered to only disclose injection of botulinum toxin into the sphincter muscle and not the detrusor muscle.
It follows that for the reasons discussed above, claims 1 and 3-7 of 233 are not novel. Claim 28 of 535 is also not novel in light of the botulinum toxin A disclosure.
All claims of 633, claims 1-27 of 535 and claim 2 of 233 are not anticipated by these documents.
US 5 183 462 (Borodic)
This document relates to a method for controlled administration of chemodenervating agents such as botulinum toxin A, useful in attenuating neural stimulation and spasmodic activity of muscle. Under ‘Background to the Invention’, in reference to the above US patent it recites ‘Dykstra et al have proposed in U.S. Pat. No. 4932936 that botulinum toxin can be used in the treatment of spasmodic sphincter muscle which leads to urinary incontinence (‘neurogenic bladder’) characteristic of some forms of cancer.’ However, the ‘936 patent does not disclose the treatment of incontinence; rather it only discloses the treatment of urinary retention. The reference to incontinence is clearly incorrect.

The ‘462 document clearly directs the skilled reader to inject toxin into striated muscle and does not contemplate any administration to smooth muscle such as the detrusor muscle in the bladder wall. The evidence has established that treatment of incontinence or urge type dysfunction cannot be achieved by the injection of toxin into the striated muscle of the urinary sphincter. It follows that the claims defining such treatments cannot be anticipated. Claims 1-12 of 633, 1-27 of 535 and claim 2 of 233 are novel when compared to this document.

For the reasons outlined in the ‘462 document above claims 1 and 3-7 of 233 and claim 28 of 535 are anticipated by this document.
Jankovic J, Botulinum toxin in movement disorders, Current Opinion in Neurology 1994; 7:358-366
The Jankovic document is a review primarily relating to the use of botulinum toxin in movement disorders. Botulinum toxin A is disclosed. No mention is made of the treatment of incontinence or urge type incontinence. It follows that claims 1-12 of 633 and 1-27 of 535 cannot be anticipated by this document. Under the heading ‘Other Applications’ DSD is included in a list of a number of potential therapies being explored. No further information is provided and the mere inclusion of DSD in such a list does not fulfil the requirement of a clear and unmistakable direction. Claims 1-7 of 233 are also novel in light of this document.

Claim 28 of 535 is anticipated by the disclosure of botulium toxin A.
US 5 437 291 (Pasricha)
This patent is directed to methods for treating gastrointestinal disorders and other smooth muscle dysfunction. Spastic bladder is included in a list as one of a number of smooth muscle disorders that are amenable to local treatment with botulinum toxin. The specification is otherwise silent on the treatment of bladder disorders, let alone the incontinence, urge type dysfunction or symptoms of overactive bladder. No enabling disclosure is provided. All claims of 633 and 233 and claims 1-27 of 535 are novel when compared to this patent.

Claim 28 of 535 is anticipated by the disclosure of botulinum toxin A.
Steinhardt G F, Naseer S and Cruz O A, Botulinum toxin: novel treatment for dramatic urethral dilatation associated with dysfunctional voiding, Journal of Urology 1997; 158; 190-191
This document discloses a novel treatment using a single urethral sphincter injection (4 quadrants) of botulinum toxin A on a patient with DSD. The patient is a seven year old girl with fetal alcohol syndrome and a history of lower urinary tract infections and daytime wetting. The patient had a thickened bladder wall and marked dilatation of the urethra indicative of the bladder contracting against the contracted urethra. The degree of deformity in the urethra was dramatic. The figure shows a bulge in the urethra that reduced following treatment. After 18 months of follow-up the patient had no daytime wetting.

While superficially it may be argued that the treatment of incontinence or urge type dysfunction is disclosed, the document explains that botulinum toxin only lasts for 2-4 months. The resolution of daytime wetting after 18 months is clearly outside of this time frame. As Thavaseelan attests, ‘the report does not indicate when the improvements began and thus it is difficult to conclusively attribute the improvements observed to the botulinum toxin injection.’ The treatment of a patient who has incontinence does not necessarily equate to the treatment of the incontinence. In my view this document does not disclose the treatment of incontinence or urge type dysfunction. In any event, it does not provide clear and unmistakable directions to the skilled reader especially considering the unusual nature of the case. All claims of 633, claims 1-27 of 535 and claim 2 of 233 are not anticipated by these documents.

The document does however disclose the treatment of DSD (urinary retention). It follows that claims 1 and 3-7 of 233 are not novel.

Claim 28 of 535 is anticipated by the disclosure of botulinum toxin A.
Ewing et al, ‘Subtrigonal phenol injection for urge incontinence secondary to detrusor instability in females’, British Journal of Urology 1982; 54:689-692
This document does not disclose the use of botulinum toxin and is not considered relevant for the purposes of novelty.
Carpenter F. G., ‘Motor responses of the urinary bladder and skeletal muscle in botulinum intoxicated rats’, Journal of Physiology; 1967, 188:1-11
This document discusses the effect of botulinum toxin on motor responses in rats. There is no discussion in the document of the treatment of urinary incontinence, urge type dysfunction or overactive bladder (including DSD) and the document therefore does not anticipate any claims of 633, claims 1-27 of 535 and claims 1-7 of 233. Claim 28 of 535 is anticipated by the disclosure of botulinum toxin A.
In summary

I find that claims 1 and 3-7 of 233 and claim 28 of 535 are not novel.
Inventive step
The law of inventive step
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)
More recently, the High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59 at [53]; 212 CLR 411 at [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?”
Is the invention obvious?
The Opponent contends that the claims of the present application are devoid of an inventive step in the light of common general knowledge alone or when considered together with a number of documents particularised in the Statement of Grounds and Particulars. It is however noted that only one document (Ewing et al, ‘Subtrigonal phenol injection for urge incontinence secondary to detrusor instability in females’, British Journal of Urology 1982; 54:689-692) has actually been discussed in the evidence. I will limit my decision to this document.

The problems addressed by the present applications relate to the treatment of incontinence, the treatment of a symptom of overactive bladder and the treatment of urge type dysfunction. The problems are derived from the specifications. This is not a point of contention between the parties.

The evidenced pertaining to common general knowledge adduced by the parties is not extensive.
Dwyer seems to have three planks to his opinion on the common general knowledge. They are summarised as follows (collectively for all cases):
·In July 1997 it was well established clinical practice to treat neurogenic bladder disorders such as DSD with botulinum toxin. Prior to July 1997 the administration of botulinum toxin had been discussed as a possible treatment for overactive bladder/unstable bladder, symptoms of which are (a) urinary incontinence and (b) frequency and urgency and therefore urge type dysfunction. He would have considered injection of botulinum toxin a possible treatment because the scientific views he had read suggested overactive bladder and symptoms of overactive bladder and urge type dysfunction could be treated with botulinum toxin.
·In July 1997 it was known that botulinum toxin was administered as an intramuscular injection and was administered to other parts of the body in this way. It would therefore be logical to treat bladder dysfunction by administration of toxin to the sphincter or bladder muscle depending on where the problem was.
·Injection into the bladder wall had been used prior to 1997 to treat detrusor activity caused by neurological conditions and in idiopathic detrusor activity. Injections of phenol into the bladder wall had been used to denervate the bladder wall and improve symptoms of bladder overactivity. It would therefore be logical to treat bladder dysfunction by administration of toxin to the sphincter or bladder muscle depending on where the problem was.
Thavaseelan does not agree. He explains:

‘I currently practice neurourology and even at the present time (2010) treating neurogenic bladder disorders such as DSD with botulinum toxin is still not internationally accepted as common practice for a variety of reasons, including it lacks full regulatory approval for use in this condition, there is only Level III evidence supporting it’s usage (that is, evidence that lacks direct scientific support and instead is based on the opinions of authorities, descriptive studies or committee reports), and due to the high cost of repeated injections over the patient’s lifetime to maintain the effect.’
‘First, as I discuss below, the effect of the injection in these cases was an improvement in voiding or increase in leakage of urine from the bladder so as to promote bladder emptying. This is contrary to the teaching of the Patent Application in which the injection of botulinum is designed to reduce leakage in order to treat urinary incontinence and therefore improve bladder storage. Second, I do not believe that any sound prediction can be made, based on the injection of botulinum toxin into the striated muscle of the sphincter, of the possible effect of injecting botulinum toxin into the smooth muscle of the bladder. These are different muscle types that are anatomically and functionally distinct.’
‘In my years working in the urology and neurourology field, and working with botulinum toxin, I have no knowledge that botulinum toxin had been discussed for the treatment of unstable/overactive bladder, symptoms of frequency or urgency, or an urge type dysfunction prior to July 1997 and have not sighted any documentation that would suggest this to be the case.’
‘Reference is made by Dwyer to a paper by Ewing et al. [discussed above]. I do not believe this is of any relevance to the invention described and claimed in the Patent Application. Phenol is structurally a very different compound to botulinum toxin and I do not accept that a urologist seeking to treat an urge type dysfunction/incontinence would look to the experience of administering phenol and, on the basis of this, consider that botulinum toxin, would be effective. I also note from [the document] that injection of the phenol was into the trigone of the bladder. Phenol is injected into the trigone due to the high density of nerves in this region. Phenol toxicity precludes using it for multiple injections throughout the bladder. Thus, using phenol in any other location would not be contemplated, let alone replacingphenol for injection elsewhere with a structurally and functionally unrelated molecule such as botulinum toxin.’

In the first point of Dwyer’s comments on the common general knowledge he refers to neurogenic bladder disorders such as DSD and overactive/unstable bladder. He attests that because incontinence/frequency and urgency is a symptom of overactive bladder/urge type incontinence, and administration of botulinum toxin had been discussed as a possible treatment for overactive bladder/urge type incontinence, he would have considered injection of botulinum toxin as a possible treatment. However, it has been established by the evidence that DSD and in this case overactive bladder is characterised by urinary retention and that botulinum toxin was used to promote voiding. Further, Dwyer makes no mention of where he would administer the toxin for both incontinence and urge type dysfunction. The claims relating to incontinence and urge type dysfunction (633 and 535) clearly require the injection of toxin into the bladder. To do so elsewhere will not result in effective treatment. He has not established that given the problems he would arrive at the solution of these claims. The 233 case is directed to treating a symptom of overactive bladder and includes the symptom of retention. The evidence has established that injection into the sphincter will treat urinary retention and his comments in this regard are consistent. Claims 1 and 3-7 are therefore obvious. (Claim 2 is directed to injection into the bladder and is therefore inventive.)

In the second point of Dwyer’s comments, he attests that botulinum toxin was known to be administered as an intramuscular injection. He broadly claims that it would be logical to treat bladder dysfunction by administering toxin to the sphincter or bladder muscle depending on the problem. He does not explain what kind of bladder dysfunction he would anticipate treating (let alone incontinence or urge type dysfunction), and even given a particular problem (such as those of the inventions) how he would be led to an appropriate solution. It therefore cannot be said that it would be a matter of routine to arrive at the claimed inventions of 633, 535 or claim 2 of 233.
In his third point, in reference to the Ewing document, Dwyer argues that because injections of phenol were known to improve symptoms of bladder over activity, and that botulinum toxin was known to treat detrusor activity it would be logical to treat bladder dysfunction by the administration of toxin. For this argument to succeed it must be clearly established that given the problem, the skilled artisan could reasonably be expected to have ascertained, understood and regarded the document as relevant. This is not the case here. Dwyer has made no claim whatsoever that he would have ascertained the document and it is therefore not available under s7(3).
Claim 28 of 535 was known at the priority date for the reasons discussed under novelty above and therefore is also not considered inventive.
In this case I do not need to elaborate on the evidence of Thavaseelan.

I find that claims 1 and 3-7 of 233 and claim 28 of 535 lacks an inventive step.
Manner of Manufacture

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).

In their SGP the opponent argued that botulinum toxins and their uses failed the threshold test for patentability because it was apparent on the face of the specification that they were known and therefore not a manner of manufacture. This reasoning simply restates the opponent’s novelty and inventive step arguments which have already been fully considered under those grounds. I do not propose to revisit the same issues under a different ground.
Fair basis

The external fair basis of the claims has been fully considered under ‘Priority’ above. I find that all claims are internally fairly based for the same reasons.
Clarity
The opponent contends that the claims of the applications are not clear. In particular, they point to the terms overactive bladder and urge type dysfunction. The meaning of these terms has been resolved under construction and does not require elaboration.
Sufficiency
Patients 1 and 2 of Example 3 of the specification clearly provide support for all claims. Patient 1 is treated for incontinence and patient 2 is treated for incontinence with urge type dysfunction.
Utility
The Opponent has not adduced any evidence that supports an allegation of inutility. I also note that Example 3 provides (as explained by Thavaseelan) treatment of neurogenic bladder by injection of botulinum toxin A into the bladder. I agree with the Applicant in that the ground of inutility has not been made out.
CONCLUSION
The opposition succeeds on the grounds of novelty and inventive step. Claims 1 and 3-7 of 233 and claim 28 of 535 are not novel and lack an inventive step.
These are matters that may be overcome by amendment. As there is clearly patentable subject matter within the specification of 233 and 535 I allow the applicant 60 days from the date of this decision in which to file proposed amendments overcoming the problems noted above.
COSTS
It is usual practice for costs to follow the event. In this case I see no reason to deviate from this approach. Accordingly I award costs against the applicant, The Regents of the University of Colorado, a body corporate, according to Schedule 8 of the Patent Regulations 1991.

Nicole Howard
Delegate of the Commissioner of Patents

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Citations

Ipsen Pharma S.A.S. v the Regents of the University of Colorado, a Body Corporate [2013] APO 23

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