Northern Rivers Pty Ltd v Janssen Oncology, Inc - [2015] APO 53

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Northern Rivers Pty Ltd v Janssen Oncology, Inc. [2015] APO 53

Patent Application: 2007287098

Title:Methods and compositions for treating cancer

Patent Applicant:                   Janssen Oncology, Inc.
Opponent:  Northern Rivers Pty Ltd
Delegate:  Dr S.D. Barker
Decision Date:  19 August 2015
Hearing Date:  24 June 2015, in Sydney
Catchwords:  PATENTS – opposition to the grant of a patent – treatment of prostate cancer by the use of abiraterone acetate and prednisone – novelty considered – the citation does not disclose use of prednisone – inventive step considered – abiraterone acetate was not common general knowledge – use of prednisone would not be a matter of routine – opposition fails on all grounds

Representation: Patent applicant: Katrina Howard SC, Katrina Crooks
Opponent:Ben Fitzpatrick, Melissa McGrath, Eliza Forsyth

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2007287098

Title:Methods and compositions for treating cancer

Patent Applicant: Janssen Oncology, Inc.
Date of Decision: 19 August 2015
DECISION
I allow the amendment to the statement of grounds and particulars.
The opposition fails on all grounds.
I award costs according to Schedule 8 against Northern Rivers Pty Ltd.
Subject to appeal, I direct that the application proceed to grant.
REASONS FOR DECISION

Patent application number 2007287098 was filed as an application under the provisions of the Patent Cooperation Treaty. The applicant was identified as Cougar Biotechnology, Inc., but has recently been changed to Janssen Oncology, Inc. (the applicant). The application was examined and accepted by the Commissioner, and subsequently opposed by Northern Rivers Pty Ltd (the opponent). A hearing was held on 24 June 2015 in Sydney to decide the opposition. The applicant was represented by Katrina Howard SC of counsel. The opponent was represented by Ben Fitzpatrick of counsel.
An unusual feature of the hearing was that a person observed the hearing by telephone. At one point there was an objection to the arrangement, and an insistence by counsel for the applicant that the person identify themselves. This was resolved by agreement between the parties and the identity of the person was disclosed. However, I wish to make an observation on this situation. It is accepted that the Commissioner acting as a tribunal is "master of its own procedure" (similar to the planning inquiry of the Minister in T.A. Miller Ltd v Minister for Housing and Local Government (1968) 1 WLR 992, [1969] RPC 91). A hearing is normally in public, and persons not connected with the matter can attend and observe. However, the Commissioner has a power to exclude persons from the hearing room. A party cannot demand a person to identify themselves, but they can ask the hearing officer to make such an enquiry. Where a person refuses a reasonable request from the hearing officer, such as to identify themselves, they may be excluded from the hearing room (and in the case of a person who is present by telephone, the telephone connection can be discontinued).
1 The opposition
The statement of grounds and particulars identified several grounds of opposition: inventive step, novelty, sufficiency and clarity. At the hearing, the opposition was limited to the grounds of inventive step and novelty.
The parties relied upon evidence by several declarants. Evidence in support consists of declarations by Jacqueline Anne Warner and Helen Grimes. Evidence in answer consists of declarations by Lieven Meerpoel and Paul De Souza. Evidence in reply consists of declarations by Jacqueline Anne Warner and Gavin Marx. I will refer to the relevant parts of the evidence where appropriate.
An amendment of the statement of grounds and particulars was filed shortly before the hearing. The amendment alters some of the particulars of the ground of novelty. There was no objection to the amendment, and I will formally allow the amendment.
2 Background to the invention
The present invention relates to the treatment of prostate cancer. Before dealing with the specification, it is useful to set down some technical background that is not in dispute.
2.1 Terminology
To assist understanding, I will provide a short summary of relevant terms that are used throughout this decision.
Steroids are a family of organic compounds characterised by an arrangement of four fused rings. Steroids are found in many living organisms. A class of steroids known as steroid hormones function as signalling molecules, that is they regulate the operation of systems within an organism. The gonadal (testicular and ovarian) steroid hormones include testosterone, estrogens and progestogens. Testosterone is an androgen, a class of steroids that regulate the development and maintenance of male characteristics.
The adrenal glands are a further source of steroid hormones. They are located on top of each kidney and contain two functionally distinct zones. The inner portion of the adrenal gland is the medulla, which produces adrenaline and noradrenaline. Most relevant to this opposition, the adrenal cortex is located along the perimeter of the adrenal gland and produces the corticosteroids, including glucocorticoids, mineralocorticoids and adrenal androgens.
The glucocorticoids regulate (among other things) glucose metabolism; cortisol in particular rises in response to stress and low blood glucose concentrations to increase blood glucose. The adrenal androgens, dehydroepiandrosterone (DHEA), DHEA sulphate and androstenedione, have minimal androgenic activity compared with testosterone. However, the adrenal androgens can be converted to testosterone by aromatase enzymes, which occurs predominantly in peripheral tissues. The mineralocorticoids and in particular aldosterone, regulate salt and water balance.
There are several books and articles that I will refer to throughout this decision. They are:
Auchus, Richard J "The Genetics, Pathophysiology, and Management of Human Deficiencies of P450c17", Endocrinology and Metabolism Clinics of North America 30: 101 – 119, 2001 (the Auchus article) (Annexure JW-11 of the first Warner declaration)
Gerber, G.S., et al. "Prostate Specific Antigen for Assessing Response to Ketoconazole and Prednisone in Patients with Hormone Refractory Metastatic Prostate Cancer", Journal of Urology 144: 1177 - 1179, 1990 (the Gerber article) (Annexure JW-14 of the first Warner declaration)
"Prostate Cancer" edited by R.S. Kirby et al. (Kirby) (Annexure JW-4 of the first Warner declaration)
Lam, J.S., et al. "Secondary Hormonal Therapy for Advanced Prostate Cancer", Journal of Urology 175: 27 - 34, 2006 (the Lam article) (Annexure JW-12 of the first Warner declaration)
O'Donnell, A., et al. "Hormonal impact of the 17α-hydroxylase / C_17,20-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer", British Journal of Cancer 90: 2317 – 2325, 2004 (the O'Donnell article) (Annexure JW-9 of the first Warner declaration)
"Remington: The Science and Practice of Pharmacy" (Remington) (Annexure JW-5 of the first Warner declaration)
Tannock, I. et al. "Treatment of Metastatic Prostatic Cancer with Low-Dose Prednisone: Evaluation of Pain and Quality of Life as Pragmatic Indices of Response", Journal of Clinical Oncology 17: 590 - 597, 1989 (the Tannock article) (Annexure JW-13 of the first Warner declaration)
2.2 The prostate, and prostate cancer
The male prostate gland is about the size of a walnut. It sits below the bladder, and controls the release of urine. It also secretes "prostatic fluid" that together with sperm from the testes, fluid produced by the seminal vesicles and mucoproteins produced by the bulbourethral gland, make up the semen.
Cancer is a group of diseases involving abnormal cell growth. Cancer of the prostate is a very significant medical condition. Globally it is the second most common cause of cancer and the fifth leading cause of cancer-related death in men (Professor De Souza at paragraph 4).
Most prostate cancers are slow growing and confined to the prostate. If the cancer spreads to other tissue it is referred to as metastatic. The most common sites for metastatic prostate cancer are the bones, lymph nodes, liver and lungs. Although the cancer has spread to other tissue, it remains a prostate cancer.
2.3 The role of androgens in prostate cancer
In men, the major site for the production of the androgen testosterone is the testes, with a very small amount produced in the adrenal glands. When testosterone enters the prostate it is rapidly converted to a more active androgen dihydrotestosterone (DHT), resulting in a DHT concentration in the prostate about 10 times higher than the concentration of testosterone (Kirby at page 86).
The importance of androgens to the functioning of prostate cells, including cancerous prostate cells, has been recognised for many decades. Maintenance of prostate tissue and function requires chronic stimulation with androgens. Androgen deprivation, for example by castration, induces programmed cell death (apotosis) in the androgen-dependent prostate cells and results in rapid involution of the gland (Kirby at page 85).
Prostate cancer may also be under the tropic influence of androgens such as testosterone and DHT. Exogenous androgen administration may lead to prostate cancer growth, and worsening symptoms associated with proliferating cancer cells. Conversely, the removal of androgenic sources in a patient, either by surgical or chemical means, results in improvement in the signs and symptoms of a substantial proportion of patients (Kirby at page 916).
2.4 Treatment of organ-confined prostate cancer
Professor De Souza explains at paragraph 8 that the main treatments of organ-confined prostate cancer are:
"(i) watchful waiting for the appearance of symptoms, (ii) surgery, or (iii) radiation. Patients can live with asymptomatic prostate cancer for many years without consequence. Upon diagnosis, the disease is often curable with local therapy including, for example, prostatectomy (surgical removal of the prostate gland) and radiotherapy (using radioactive beads or external beam radiation)."
However, he goes on to note that:
"local therapy fails in up to a third of men who go on to develop incurable metastatic disease".
2.5 First stage treatment of metastasised prostate cancer
In the case of metastatic prostate cancer, treatment is more difficult. Professor De Souza states at paragraph 10:
"In 2006, the mainstay of treatment for early stage metastatic prostate cancer was androgen deprivation therapy (ADT) by surgical or medical castration. Surgical castration (also referred to as orchiectomy) is simply the removal of both testes. Medical castration is the administration of luteinizing hormone-releasing hormone (LHRH) agonists such as goserelin (known as Zoladex in Australia) and leuprorelin acetate (known as Lucrin in Australia), which stimulate the anterior pituitary gland resulting in inhibition of luteinizing hormone (LH), the global regulator of testicular steroid synthesis. Inhibition of LH suppresses androgen synthesis in the testes. In 2006, LHRH agonists were administered in most cases as a monotherapy by injection every 3 to 4 months. Administration of LHRH results in a flare of testosterone that is subsequently turned down by about 95%. LHRH agonists can also be administered concomitantly with antiandrogens, which act to prevent interaction of androgens with the androgen receptor (AR). (Antiandrogens could also be used on their own as a therapy.) Examples of antiandrogens include, but are not limited to, bicalutamide, flutamide and nilutamide. As the aim of ADT is to reduce circulating levels (and action) of androgens, it is considered to be a first-line ‘hormonal therapy’. When LHRH agonists became available, orchiectomy went out of favour.”
However, castration is seldom effective (Professor De Souza at paragraph 11):
"About 95% of men with metastatic prostate cancer initially respond rapidly to castration and have decreased PSA levels as well as reduction in bone pain. However, the duration of response is highly variable ranging from as little as 6 months to more than 10 years, the average being about 3 years. In almost all patients it is followed by the emergence of castration-resistant prostate cancer (CRPC). (CRPC is now the accepted name for this condition, whereas in 2006 it was variously referred to as CRPC, hormone-resistant prostate cancer (HRPC), hormone-refractory prostate cancer (HRPC) or androgen-independent prostate cancer (AIPC))."
Professor De Souza goes on to say at paragraph 16:
"In 2006, CRPC typically led to death within about 12 months."
The mechanism of castration-resistant prostate cancer (CRPC) development was unclear, as noted by Professor De Souza at paragraph 12:
"In 2006, the mechanism for the subsequent progression to CRPC was not fully understood and it was believed that there were many different contributing factors."
2.6 Second stage treatment of metastasised prostate cancer
Professor De Souza says that the treatment of CRPC patients was primarily palliative care. However, at paragraph 16 he says:
"Occasionally patients were offered chemotherapy, hormonal therapy or inclusion in a clinical trial."
The hormonal therapies are described at paragraph 18 of his declaration:
"These therapies included ketoconazole (only administered by a select few oncologists), aminoglutethimide (only rarely used as it did not produce good results), diethylstilbestrol (DES, used only rarely because it had side effects such as clots leading to deaths and is no longer used today), PC-SPES herbal therapy and monotherapy with low-dose corticosteroids."
At paragraph 22 Professor De Souza says:
"A number of these treatments operate on the adrenal steroid synthesis pathway to reduce the amount of testosterone produced in the adrenal cortex."
The steroid synthesis pathway leading to the production of testosterone is shown by Professor De Souza at paragraph 26 of his declaration:
At paragraph 32 Professor De Souza summarises:
"the purpose of some secondary hormone treatments is to inhibit enzymes in the steroid synthesis pathway to prevent the ultimate production of testosterone".
2.7 Prednisone
Prednisone features prominently in this invention, so before moving on to look at the specification it is worth pausing to record what was known about prednisone, and particularly its use in the treatment of prostate cancer. Prednisone is a synthetic glucocorticoid having the formula:
Professor De Souza comments variously on the properties of prednisone. At paragraph 51 he says:
"Prednisone, hydrocortisone and dexamethasone were all steroids in common clinical usage at 2006, but 95% of the time were used for reasons unrelated to prostate cancer."
At paragraph 75 he says:
"Prednisone was known to have some mild effect on symptomatic control for metastatic prostate cancer, and in particular low dose steroids were a good potential treatment for fatigue and bone pain which were often symptoms of metastatic disease."
At paragraph 81 he says:
"the primary reason for combining cytotoxic therapies with corticosteroids, such as prednisone or dexamethasone, was to exploit their anti-inflammatory and anti-nausea properties which helped to deal with the notoriously unpleasant side-effects of cytotoxic treatment."
At paragraph 89 he says:
"glucocorticoid replenishment therapy can be given to increase the levels of cortisol to an appropriate level. Glucocorticoids used for this purpose include steroids such as hydrocortisone, dexamethasone and prednisone".
The replacement of glucocorticoids is variously referred to in the evidence as "replenishment", "repletion", "replacement" and "supplements". In this decision I will use the term "replacement".
At paragraph 151 Professor De Souza says:
"while I understand that prednisone could be used as a glucocorticoid replenishment, it was not clear that cortisol production would in fact be inhibited by the use of abiraterone acetate".
The totality of Professor De Souza's evidence is that prednisone had been used for a number of purposes: as an anti-inflammatory and anti-nausea agent, to treat fatigue and bone pain, and for glucocorticoid replacement.
The treatment of pain is discussed by Professor Marx at paragraph 15 of his declaration:
"DibbsBarker asked me why prednisone is used in combination with the agents referred to in paragraph 14 above. Prednisone is used in combination with other therapeutic agents for prostate cancer for both historical and efficacy reasons. I recall that the first relevant historical use of prednisone was in a study by Ian Tannock published in the Journal of Clinical Oncology. This study established the historical gold standard dose of 5 mg b.i.d. (that is, 5 mg of prednisone administered twice daily). Later studies adopted this dose of prednisone as it was considered unethical not to administer prednisone (the gold standard) with new therapies for prostate cancer being trialled. The dosage regimen of 5 mg b.i.d. of prednisone continues to be the gold standard in combination with other agents for use in the treatment of prostate cancer."
The study by Ian Tannock that is referred to is the Tannock article, which reports the use of prednisone for pain relief in patients with advanced prostate cancer. The overall conclusion is reported on the first page of the article (at page 590):
"We conclude that (1) low-dose prednisone may cause useful relief of pain in some patients with advanced prostate cancer; (2) relief of pain was associated with suppression of adrenal androgens; and (3) measures of pain and quality of life can be used to assess possible benefits of systemic therapy in patients with metastatic prostate cancer."
The treatment regimen is stated on page 591:
"Most patients in the retrospective series, and in the early part of the prospective study, received prednisone in a dose of 5 mg in the morning and 2.5 mg in the evening; subsequently, patients received 5 mg twice daily."
The authors ultimately recommend the use of prednisone at page 596:
"In the absence of randomized trials demonstrating superiority of other drugs, a trial of low-dose prednisone can be recommended for most patients with progressive symptomatic prostate cancer who have undergone orchidectomy, or who are receiving estrogens or LHRH agonists."
The mechanism of action is far from certain. Page 596 of the Tannock article says:
"The antiinflammatory properties of prednisone might lead nonspecifically to improvement in pain and other symptoms. However, this mechanism seems unlikely to explain the magnitude of responses seen in the present study, since the low dose of prednisone used was comparable to the physiological production of corticosteroids by the adrenal gland. It seems probable that most of the benefit was mediated through hormonal effects on the adrenal gland."
Professor De Souza seems to agree that the Tannock article discloses that prednisone is effective for treatment of pain, but draws the distinction that it is not used to treat the cancer:
"this was a paper essentially about how prednisone might improve quality of life in men with pain from metastatic prostate cancer" (paragraph 76)
and
"The Tannock (1989) study provides no support to improving survival in prostate cancer patients using prednisone alone, since prednisone very much had a palliative care function of controlling symptoms." (paragraph 77)
I think that the evidence is consistent in showing that prednisone was known to be an effective pain relief agent in the treatment of metastatic prostate cancer. Professor Marx says that 5 mg twice daily was the gold standard, from which I conclude that if prednisone was used then 5 mg was the dosage that would be used. It is not apparent that Professor Marx is saying that prednisone usage had become the gold standard. The evidence does not establish that it was routine to use prednisone for pain relief as part of the treatment of metastatic prostate cancer.

Turning to glucocorticoid replacement, Remington at page 1366 discusses this form of therapy:
"MODALITIES AND REGIMENS OF CORTICOSTEROID THERAPY - Replacememt Therapy - Treatment of primary and secondary adrenal insufficiency requires replacement of both glucocorticoids and mineralocorticoids in sufficient doses to relieve the signs and symptoms of insufficiency. However, when the patient experiences an additional stress, supplements of glucocorticoids may be required. The dose and dose-interval vary from patient to patient, but the doses are small, and complications are infrequent and minimal; the most difficult challenge is in the adjustment of dosage in response to changes in stress."
It seems to be well understood that glucocorticoid replacement can be used. Remington records prednisone as a glucocorticoid (for instance, page 1364, 1369). Further, at page 1369 it is stated that it has higher glucocorticoid activity than hydrocortisone, but "it cannot be used alone for replacement therapy in adrenal insufficiency". This seems to be because it has low mineralocorticoid activity. For present purposes it is interesting to note that at page 1369 it is said that prednisone "is the glucocorticoid predominantly used in cancer chemotherapy, always in combination with other drugs." Given the context of this statement, it seems more likely that it is referring to use as a glucocorticoid replacement, rather than use as a direct treatment of cancer. The teaching is away from the use of prednisone alone.
Looking at the other evidence available in the opposition provides scant assistance. The Gerber article (discussed in detail below) establishes that it was known (at least as early as 1990) that prednisone could be used as a glucocorticoid replacement. There is no suggestion that this was widely known or a matter of routine in the treatment of prostate cancer.
The Auchus article at pages 114 – 115 discusses treatment of CYP450c17 deficiency (a deficiency that is analogous to the inhibition of androgen production by a 17-hydroxylase / C_17,20‑lyase inhibitor: see the first Warner declaration at paragraph 58) by glucocorticoid replacement, usually with dexamethasone or prednisone.
The Lam article (discussed in detail later) provides a summary of steroid use in second stage treatment of prostate cancer in Table 1 (at page 28). Four steroids are listed as monotherapy: prednisone, hydrocortisone, dexamethasone and liarozole (Professor De Souza says at paragraph 51 that he was not familiar with the fourth steroid, so it is reasonable to conclude it was not a commonly used steroid). It is clear from what is said on page 29 of the Lam article that glucocorticoids "have modest anticancer activity", and at page 30 that "corticosteroids should be considered active hormonal agents for prostate cancer". It is then noted that "these effects may also be short in duration". The Lam article provides evidence that prednisone has been used as a direct anticancer agent, but it is not apparent that it is an effective treatment. The Lam article also does not address the question of which glucocorticoids should be preferred for glucocorticoid replacement.
In summary, the evidence shows that:
·prednisone had been used to treat symptoms associated with prostate cancer;
·prednisone had been used, but not routinely used, to achieve pain relief in metastatic prostate cancer;
·prednisone had been used, but not routinely used, as a glucocorticoid replacement in the treatment of prostate cancer;
·when used as a glucocorticoid replacement in cancer therapy, prednisone is used in combination with other drugs;
·prednisone had been used as an anti-inflammatory;
·prednisone had been used as an anti-nausea agent; and
·prednisone has been used to treat prostate cancer, but it is not clear that the treatment is effective.
3 The invention as described
Before commencing to construe the specification, I note what Middleton J said in Eli Lilly and Company Limited v Apotex Pty Ltd [2013] FCA 214, 100 IPR 451 at [139]:
"It is well settled that the Court should, from the outset, approach the task of patent construction with a generous measure of common sense. The Court must place itself in the position of a person skilled in the relevant art, being the subject matter of the patent. From this perspective, the patent is to be read as a whole, in the context of the specification and in light of the prevailing common general knowledge and state of the relevant art at the priority date."
3.1 Background to the invention
The specification states that at the date of the application, the main treatment of organ-confined prostate cancer was prostatectomy (the surgical removal of all or part of the prostate) or radiotherapy (the use of radiation to kill cancer cells).
3.2 The aim of the invention
The specification sets out its aim on page 2:
"There remains a need for more effective ways to treat cancer such as, but not limited to, prostate cancer and breast cancer. Additionally, there is a need for effective anti-cancer treatment options for patients who are not responding to current anti-cancer treatments. Also, there is a need for effective anti-cancer treatment options for patients whose cancer has recurred."
3.3 The nature of the invention
While the aim of the invention is stated to be directed to cancer generally, the nature of the invention is focussed on prostate cancer. The specification sets out the invention in seven aspects. The first aspect is stated on page 2:
"Accordingly, in one aspect the present invention provides a use of a therapeutically effective amount of abiraterone acetate or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of a prostate cancer in a human, wherein the medicament is administered in addition to a therapeutically effective amount of prednisone."
Abiraterone acetate is a synthetic steroid having the structure:
Abiraterone acetate is an inhibitor of the enzyme 17α-hydroxylase / C_{17, 20}-lyase (page 4):
"a therapeutically effective amount of a 17α-hydroxylase / _17,20-lyase [sic] inhibitor, such as abiraterone acetate (i.e. 3-acetoxy-17-(3-pyridyl)androsta-5,16-diene), is administered to a patient".
The specification describes a large number of additional additives, having a range of roles. Prednisone is referred to on page 14:
"The 17α-hydroxylase / C_{17, 20}-lyase inhibitors may also be administered or combined with steroids, such as corticosteroids or glucocorticoids. The 17α hydroxylase / C_17,20-lyase inhibitors and the steroid may be administered in the same or in different compositions. Non-limiting examples of suitable steroids include hydrocortisone, prednisone, or dexamethasone. The amount of the steroid administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a 17α‑hydroxylase / C _17,20-lyase inhibitor."
The prednisone is administered in an amount "sufficient to treat the cancer whether administered alone or in combination". This is somewhat surprising, as there is no suggestion in the specification that prednisone is used to treat the cancer directly. There is evidence (see the discussion of prednisone later in this decision) that prednisone has been used to treat prostate cancer directly (in the Lam article), but normally prednisone has been used as part of combination treatments, apparently to treat pain and inflammation associated with the cancer. In the absence of a clear indication that prednisone is being administered to directly treat the cancer, I think it is more likely that the specification is suggesting that prednisone should be used in an amount sufficient to treat symptoms associated with the cancer, and I believe this is the way that the specification would have been understood.
Other aspects of the invention are described, such as:
·the formulation is for the treatment of refractory prostate cancer, and
·the amount of abiraterone acetate administered is 50 – 2000 mg/day, and the amount of prednisone administered is 10 – 250 mg/day.
Numerous other aspects of the invention are described, but these aspects are not explicitly mentioned in the claims. Consequently I will not dwell on these aspects.
3.4 How does the invention work
The specification explains at page 4 that 17α-hydroxylase / C_17,20-lyase inhibitors have been shown to be useful in the treatment of hormone-dependent disorders such as prostate cancer, and reference is made to US patent 5,604,213 (the Barrie patent). Abiraterone acetate is example 11 of the Barrie patent. The 17α-hydroxylase / C_17,20-lyase enzyme is known to be essential for the biosynthesis of androgens (the Barrie patent at column 1).
I have been unable to otherwise find any reference in the specification to an explanation of how the invention works. It would appear that the specification assumes that it is self-evident how the invention works, or that it is unknown.
A single enzyme catalyses the 17α-hydroxylase and C_17,20-lyase activities which operate at two points in the pathway reproduced from Professor De Souza's evidence (at one occurrence it is identified as 17α-hydroxylase, and in the other it is identified as C_17,20-lyase), and the effect of inhibiting this enzyme is to reduce the production of adrenal androgens, and ultimately of testosterone. It is apparent from the pathway that this may also inhibit the production of cortisol.
The hearing proceeded on the understanding that the use of prednisone provided a replacement for cortisol (both being glucocorticoids). While the specification does not suggest this, it is consistent with the suggestion in the O'Donnell article (discussed below) that abiraterone acetate therapy may require glucocorticoid replacement. For the purposes of understanding this decision it is sufficient to assume that this is the role of the prednisone, but it should not be assumed that this has been demonstrated in the evidence.
3.5 Examples
At page 19 of the specification there is a heading "Compositions Containing a 17α-hydroxylase / C_17,20-lyase Inhibitor and an Additional Therapeutic Agent". What follows is more a recitation of preferred embodiments than examples. There is a reference to an example in paragraph [0089]:
"One example of a composition comprising a 17α-hydroxylase / C_17,20-lyase inhibitor and an additional therapeutic agent is an oral composition or composition suitable for oral administration comprising abiraterone acetate in combination with a steroid. For example, the oral composition can be a solid dosage form such as a pill, a tablet or a capsule. The oral composition can comprise about 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1000 mg of abiraterone acetate. The oral composition can comprise about 0.25 mg, 0.5 mg, 0. 75 mg, 1.0 mg, 1.25 mg, 1.5 mg, 1.75 mg, 2.0 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3.0 mg, 3.25 mg, 3.5 mg, 3.75 mg, 4.0 mg, 4.25 mg, 4.5 mg, 4.75 mg, 5.0 mg, 7.5 mg, 10 mg, 20 mg, 30 mg, 40 mg or 50 mg of a steroid, such as a glucocorticoid."
In the following paragraph there is a specific mention of prednisone:
"In one embodiment, the oral composition can comprise about 50 mg to about 500 mg of abiraterone acetate and an amount of about 0.25 mg to about 3 5 mg of the steroid, such as hydrocortisone, prednisone or dexdamethasone [sic]. In other instances, the composition can comprise about 50 mg to about 300 mg of abiraterone acetate and an amount of about 1.0 mg to about 2.5 mg of the steroid, such as hydrocortisone, prednisone or dexamethasone. In another embodiment the composition can comprise about 50 mg to about 300 mg of abiraterone acetate and about 0.5 mg to about 3.0 mg of a steroid. For example, the oral composition can be a tablet containing 250 mg of abiraterone acetate; 1.25 mg or 2.0 mg of a steroid, such as hydrocortisone, prednisone or dexamethasone; and one or more carriers, excipients, diluents or additional ingredients. Additionally, the oral composition can be a capsule containing 250 mg of abiraterone acetate; 1.25 mg or 2.0 mg of a steroid, such as hydrocortisone, prednisone or dexamethasone; and one or more carriers, excipients, diluents or additional ingredients."
There is no disclosure of the actual therapeutic use of any composition, or demonstration that it has the desired activity.
4 The invention as claimed
The correct approach to the construction of claims was discussed by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70, 81 IPR 228 at [118] – [120]:
"the words in a claim should be read through the eyes of the skilled addressee in the context in which they appear … while the claims define the monopoly claimed in the words of the patentee's choosing, the specification should be read as a whole … it is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification … terms in the claim which are unclear may be defined or clarified by reference to the body of the specification".
4.1 Claim 1
Claim 1 is an independent claim. It reads
A use of a therapeutically effective amount of abiraterone acetate or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of a prostate cancer in a human, wherein the medicament is administered in addition to a therapeutically effective amount of prednisone.
This claim has an unusual structure. The claim begins with wording that resembles a Swiss style claim, but then has a final portion that defines the way in which the medicament is administered with prednisone. Yates J recently considered a Swiss style claim in Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4) [2015] FCA 634 and came to the conclusion that it should be construed in the same way as in Europe. However, as claim 1 of the present application is not a Swiss type claim, the approach to construing this claim is the same as for any claim – start by reading the words through the eyes of a skilled addressee.
The claim is directed to a "use", in other words it is prima facie a method. Methods are characterised by the steps of the method. The method involves the use of abiraterone acetate "in the preparation of a medicament". There are no specific details of how the medicament is prepared, so this step of the method can be done in any way that produces a medicament containing abiraterone acetate. The medicament is qualified in that it is "for the treatment of a prostate cancer", which implies a suitability for use in this treatment.
The claim next recites "wherein the medicament is administered". This could be seen as either a description of the intended use of the medicament, or as a further step of the process. However, the claim says that the compound "is" administered. The use of the present tense, rather than the future tense or the present future tense (i.e. "will be" or "is to be") implies that the administration is a part of the claim, rather than a future step. Consequently, I consider that the process includes the step in which the compound "is administered", and logically that administration is for the treatment of prostate cancer.
The claim further defines the administration as "in addition to a therapeutically effective amount of prednisone". This raises three questions, addressed below.
Does the medicament contain prednisone, or is the prednisone administered separately?
The words used in the claim place no limitation that the medicament must also contain prednisone. I see no reason to read such a requirement into the claim. This is consistent with paragraph [0057] of the specification: "the additional therapeutic agent can be in separate compositions prior to administration" or "the additional therapeutic agent can be combined into a single composition".
It is not essential that the medicament contains prednisone.
Is the prednisone administered at the same time as the abiraterone acetate?
The claim says that the medicament is administered "in addition to" the prednisone. The plain meaning of this expression is that the prednisone is administered before, at the same time as, or after the administration of the abiraterone acetate. This is consistent with paragraph [0058] of the specification: "the additional therapeutic agent can be administered sequentially or simultaneously".
Is it possible for the abiraterone acetate treatment to take place subsequent to the completion of a prednisone treatment? In other words, many months (if not years) before the abiraterone acetate treatment. The answer to this question lies in what the person skilled in the art would understand to be the meaning of the claim.
On the whole the declarants do not construe any of the claims, so there is no direct evidence of how they understand this expression. Professor De Souza merely repeats the words of the claim at paragraph 128 of his declaration:
"the pharmaceutical is administered in addition to a therapeutically effective amount of prednisone".
However, when considering the prior art at paragraph 147 he says that no document "discloses that particular combination", and at paragraph 151 talks about whether he would have been motivated "to combine abiraterone acetate and prednisone". It seems clear that Professor De Souza regards the invention as a combination treatment, and consequently the prednisone is administered as part of the same treatment regimen, and not as part of a separate treatment.
While the simplest means of operating the invention would be to administer the abiraterone acetate and prednisone as a single formulation, the claim does not require this. I will proceed on the basis that a single formulation is not required, as stated previously in paragraph 72.
What is the amount of prednisone?
The claim specifies the use of a "therapeutically effective" amount of prednisone. As already mentioned, prednisone is known to be useful for control of the symptoms of prostate cancer, and has also been used to directly treat prostate cancer. The evidence is that treatment of symptoms is the normal use of prednisone, which leads me to believe that this is the therapy that is envisaged by the claim. The amount of prednisone used is the amount necessary for the control of symptoms.
Overall
Claim 1 defines a process having two steps: prepare a medicament containing abiraterone acetate, then administer the medicament and prednisone as part of the course of treatment (in an amount effective for the treatment of symptoms)
4.2 Claim 2
Claim 2 has a different form:
A compound for use in the treatment of a prostate cancer in a human, wherein the compound is a therapeutically effective amount of abiraterone acetate or a pharmaceutically acceptable salt thereof, and wherein the compound is administered in addition to a therapeutically effective amount of prednisone.
The opponent put forward a construction that claim 2 is merely directed to abiraterone acetate per se, based on the use of the term "for use", which is traditionally viewed as merely requiring a suitability for the prescribed use. I agree that the compound as defined in claim 2 has to be suitable for use in the treatment of prostate cancer. However, the final part of the claim recites:
"and wherein the compound is administered in addition to a therapeutically effective amount of prednisone"
Similarly to claim 1, the use of the present tense – "is" administered – implies that the administration is a part of the claim. In other words, the claim is directed to a method of treatment using abiraterone acetate. The prednisone is part of the course of treatment. This claim differs from claim 1 in that it is not specified that a medicament is prepared as the first step of the process.
4.3 The other claims

There are several other independent claims, which all relate to the use of abiraterone acetate to form a medicament, or the use of abiraterone acetate and prednisone for the treatment of prostate cancer. The various appended claims generally refer to specific amounts of abiraterone acetate and prednisone.
5 Novelty
The opponent alleged that there is a lack of novelty in the light of abiraterone acetate per se. This argument arises from its view that claims 1 and 2 should be construed as directed to the substance per se rather than a method. However, I have construed these claims as directed to methods, so this argument must fail. The opponent also alleged lack of novelty in the light of several documents. I will consider this argument in detail.
5.1 The law
It is a requirement of subsection 18(1) of the Patents Act 1990 (the Act) that the invention, so far as claimed in any claim, is novel. Subsection 7(1) states that an invention is taken to be novel unless it is not novel in the light of the prior art. A citation is part of the prior art base for the purposes of novelty if it was published before the priority date of the claim.
It is well established that the general test for lack of novelty 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], 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".
In Apotex Pty Ltd v Sanofi-Aventis [2009] FCAFC 134, 82 IPR 416 the Full Court of the Federal Court recognised that sometimes a prior publication may be lacking in details. There may still be a lack of novelty if the reader would supply the omissions (at [104]):
"There is anticipation if the skilled addressee would add missing information to what is disclosed in the prior art as a matter of course and without the application of inventive ingenuity or undue experimentation".
Alternatively, it was noted in Bristol-Myers Squibb Co v FH Faulding & Co Ltd [2000] FCA 316, 46 IPR 553 at [67]:
"a prior publication, if it is to destroy novelty, must give a direction or make a recommendation or suggestion which will result, if the skilled reader follows it, in the claimed invention".
5.2 The O'Donnell article
The O'Donnell article was published on 18 May 2004 (paragraph 5 of the Grimes declaration). Consequently it is part of the prior art base.
The O'Donnell article says that the beneficial effect of androgen ablation (suppression) on metastatic prostate cancer was realised in the 1940s. The first-line treatment of prostate cancer by androgen ablation was achieved by medical or surgical testicular castration (because testosterone is produced in the testes). However, testosterone is also produced as a result of androgen production by the adrenal glands even after castration. Hence the article investigates the potential of a second-line chemical inhibition of extratesticular androgens.
The O'Donnell article acknowledges that ketoconazole and aminoglutethimide have been evaluated previously as second-line agents for prostate cancer treatment. The article reports phase one trials on the substance abiraterone acetate, a "novel 17α-hydroxylase / C_17,20-lyase inhibitor". Specifically, the article reports determination of the dose of abiraterone acetate that will result in maximum suppression of testosterone.
The conclusions of the O'Donnell article on page 2324 are:
"These studies demonstrate for the first time the potential utility of specific inhibition of 17α-hydroxylase / C_17,20-lyase in causing reductions in testosterone levels in both castrate and noncastrate males with prostate cancer. The data indicate that reliably maintaining castrate testosterone levels in intact males in the face of increased levels of LH may require higher doses of abiraterone acetate. The present data, however, do support the potential utility of this drug in the second-line treatment of patients who have become refractory to gonadotrophin‑releasing hormone agonists."
This is a clear disclosure of the use of abiraterone acetate to reduce testosterone, with the potential for use in second-line treatment of prostate cancer. However, at page 2323 the article says:
"In the clinical use of both aminoglutethimide and ketoconazole, it is common practice to administer supplementary hydrocortisone and this may prove necessary with 17α-hydroxylase and C_17,20-lyase inhibitors such as abiraterone acetate. However, the omission of glucocorticoid replacement has been shown to be safe and effective (Eichenberger and Trachtenberg, 1988; Dowsett et al, 1988; Harnett et al, 1987; Rostom et al, 1982). In the light of this clinical evidence, further studies with abiraterone acetate will be required on a continuous basis, at times of physiological stress, if patients become symptomatic or indeed at all."
The opponent relies on this as an instruction to additionally use a hydrocortisone. It is not in dispute that hydrocortisone is a corticosteroid, and prednisone is a glucocorticoid of the hydrocortisone type with three to five times the activity of hydrocortisone (Remington at page 1369, Annexure JW-5), but it is in dispute that a person reading O'Donnell would have considered that they were given a direction, recommendation or suggestion to use hydrocortisone.
The language of the O'Donnell article is not a clear and unmistakable direction, recommendation or suggestion to use supplementary hydrocortisone, or prednisone particularly. It cautions that it may be necessary to use supplementary glucocorticoid, but that further investigation is required to determine whether glucocorticoid therapy is necessary, and if so, whether it should be administered continuously or at times of stress. It cannot be said that there is a lack of novelty in the light of the O'Donnell article.
5.3 The Lam article
The Lam article was published on 6 January 2006 (paragraph 5 of the Grimes declaration). Consequently it is part of the prior art base.
The Lam article is a review of peer-reviewed literature on secondary hormonal therapies. For present purposes it is relevant to note that Lam contains a summary of the O'Donnell article. The Lam article does not indicate that the O'Donnell article discloses the use of supplementary hydrocortisone, or prednisone specifically.
After discussion of abiraterone acetate, there is a new section that reads as follows:
"CORTICOSTEROIDS
Glucocorticoid repletion is a standard supportive therapy in patients treated with agents that inhibit adrenal function."

100. I accept that the Lam article is disclosing that glucocorticoid replacement is standard in the literature that has been reviewed. However, the Lam article does not suggest that it was standard to administer glucocorticoid replacement in conjunction with abiraterone acetate. Such a conclusion could only reached by mosaicing parts of the Lam article, and there is no reason to do so. It cannot be said that there is a lack of novelty in the light of the Lam article.
5.4 The combination of the O'Donnell and Lam articles
101. The situations in which it is permissible to mosaic the information in two different documents for the purposes of establishing a lack of novelty are uncommon. In Nicaro Holdings Pty Ltd v Martin Engineering Co [1990] FCA 40, 16 IPR 545, Gummow J stated at 570:
"It is difficult to see how mere identification of prior patents as related or prior art would bring them sufficiently closely together for the purpose under consideration here."

102. At page 571 this is contrasted with the situation where "the publications themselves formed what Astbury J called 'one consistent whole' ".
103. It was submitted that the O'Donnell and Lam articles could be mosaiced, and treated as a single source of information, since the Lam article makes reference to the O'Donnell article. However, the Lam article makes reference to the O'Donnell article because it contains a short summary of the O'Donnell article. The reader of the Lam article is not directed to go off and read the O'Donnell article, and the summary provided in the Lam article is sufficient to gain a broad understanding of the O'Donnell article. I do not consider that the O'Donnell and Lam articles can be read as a single source of information.
104. However, even if it were possible to treat the O'Donnell and Lam articles as a single source of information, nothing is gained over the Lam article on its own. There is no disclosure of glucocorticoid replacement in conjunction with abiraterone acetate. Such a conclusion is a mosaicing of different parts of the Lam article, and there is no reason to do so.
5.5 Conclusion on novelty
105. It has not been established that any of the claims lack novelty.
6 Inventive step
106. The opponent summarised their case in two ways. First, the invention is the use of a combination of two compounds each performing their known functions. Second, abiraterone acetate has the beneficial effect of reducing testosterone production, but this comes at the cost of cortisol depletion. This problem can be addressed by co-administration of a glucocorticoid – referred to as glucocorticoid replacement. Prednisone is a known glucocorticoid.
6.1 The law
107. It is a requirement of subsection 18(1) of the Act that the invention, so far as claimed in any claim, involves an inventive step. Subsection 7(2) states that an invention is taken to involve an inventive step unless it would have been obvious to a person skilled in the art in the light of the common general knowledge, considered alone or together with the prior art. A document is prior art for this purpose if "a skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood, regarded [the document] as relevant" (subsection 7(3)).
108. The test for whether an invention is obvious is to ask whether it would have been a matter of routine to proceed to the claimed invention. In Wellcome Foundation Ltd v V.R. Laboratories (Aust.) Pty Ltd [1981] HCA 12 at [45], 148 CLR 262 at 286 Aickin J stated:
"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."

109. The High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59, 212 CLR 411 approved this approach, and also endorsed the well known Cripps 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 invention claimed] … in the expectation that it might well produce a useful [product or process]?

110. The Cripps question does not require the person skilled in the art to have known, before the event, that the method (or the medicament) to be investigated will in fact prove to be useful. As Jessup J emphasised in AstraZeneca 226 FCR 324 at [542], the requirement is that it “might well” be useful.
111. The argument on inventive step is put in several ways:
-lack of inventive step in the light of the common general knowledge alone,
-lack of inventive step in the light of O’Donnell, Gerber or Lam individually, and
-lack of inventive step in the light of Gerber combined with O’Donnell.

6.2 The problem
112. In the present case the problem addressed by the specification is the treatment of cancer. However, the claims are clearly limited to the treatment of prostate cancer. More particularly, the specification is only concerned with metastatic prostate cancer, and even then it is second stage treatment following an initial course of treatment.
113. This leads me to formulate the Cripps question for the present case as:
Would the notional research group at the relevant date, in all the circumstances directly be led as a matter of course to try abiraterone acetate and prednisone in the expectation that it might well produce a useful second stage treatment of metastatic prostate cancer?

6.3 The common general knowledge
114. The opponent alleged a number of matters that it asserted were common general knowledge.The most significant matter is abiraterone acetate itself. I consider that the evidence does not establish that abiraterone acetate was common general knowledge, and consequently the invention as claimed is not obvious in the light of the common general knowledge alone. I will explain why abiraterone acetate was not common general knowledge.
115. Common general knowledge is "the background knowledge and experience which is available to all in that field in considering the making of new products or making of improvements in old products" (ICI Chemicals & Polymers Ltd v Lubrizol Corporation Inc [1999] FCA 345, 45 IPR 577 at [111]), or "part of their common stock of knowledge relating to the art" (British Acoustic Films Ltd v Nettlefold Productions (1936) 53 RPC 221, cited with approval in Aktiebolaget Hässle v Alphapharm Pty Ltd [1999] FCA 628, 44 IPR 593 at [39]).
116. How is common general knowledge established? In Dynamite Games Pty Limited v Aruze Gaming Australia Pty Limited [2013] FCA 163 Emmett J said at [104]:
"It is necessary to establish common general knowledge by appropriate evidence."

117. The preparation of abiraterone acetate was reported in the Barrie patent (filed in 1994). The phase one trials on abiraterone acetate were reported in the O’Donnell article in 2004. The O'Donnell article was published in a respected journal. This establishes that abiraterone acetate was known, but not that it was generally known. There is no declaratory evidence presented by the opponent on whether the O'Donnell article or any other information about abiraterone acetate had become part of the common stock of knowledge in the art. In the absence of evidence I can see no basis on which to infer that abiraterone acetate was part of the common general knowledge.
6.4 The O'Donnell article
118. The O'Donnell article is the opponent’s best case for lack of inventive step. The main difference between this article and the invention as claimed is the use of prednisone. Thus the key issue is whether the use of prednisone would have been a matter of routine.
119. As already stated under the heading of novelty, the O'Donnell article is part of the prior art base. The threshold question is whether the O'Donnell article would have been ascertained, understood and regarded as relevant. I believe the best evidence is in Professor De Souza's evidence at paragraph 106:
"I do not generally search patent databases for information on new therapies … A patent will need to be published in peer-reviewed scientific literature before it is considered as a possible therapy."

120. This suggests that it would be normal to search databases of peer-reviewed literature when investigating possible therapies. The O'Donnell article was published in the British Journal of Cancer. Dr Warner stated (at paragraph 43 of her first declaration) that:
"[t]he British Journal of Cancer was ranked in the top ten journals by total document numbers in the field of medicine and sub-field of oncology in 2006"

121. I am satisfied on balance that a person would have searched peer-reviewed literature, and ascertained the O'Donnell article.
122. It is clear from the content of the O'Donnell article that it would have been regarded as relevant. The disclosure of the O'Donnell article has been discussed previously. It discloses the successful trials of abiraterone acetate, and highlights the potential need for glucocorticoid replacement. It says at page 2323:
"In the light of this clinical evidence, further studies with abiraterone acetate will be required to ascertain if concomitant therapy with glucocorticoids is required on a continuous basis, at times of physiological stress, if patients become symptomatic or indeed at all."

123. This is an indication on the face of the citation that a person looking to take this work to the next stage should investigate whether glucocorticoid replacement is necessary (on either a continuous or intermittent basis). Professor De Souza analysed the O'Donnell article, and came to the view that "the balance of glucocorticoids and mineralocorticoids in the adrenal pathway was maintained", from which I conclude that he believes that a person would not look to glucocorticoid replacement, at least on a continuous basis. While I understand the reasons presented by Professor De Souza, there is a risk that evidence given with the benefit of hindsight may not fully reflect the views at the time. Consequently I will consider the evidence of the contemporaneous interpretation of the O'Donnell article.
124. Contemporaneous summaries of the O'Donnell article provide conflicting interpretations of the article. In Kirby at page 920 it is stated:
"Adrenocortical suppression may necessitate concomitant treatment with replacement glucocorticoid"

and a reference is made to the O'Donnell article. Clearly glucocorticoid replacement is mentioned.
125. In the Lam article there is a summary of the O'Donnell article, without mention of glucocorticoid replacement. The article merely notes that:
"Abiraterone acetate appears to be well tolerated and to our knowledge no serious side effects have been reported."

126. It seems plausible that this difference is nothing more than different authors summarising the O'Donnell article in different ways, rather than the Lam article omitting the glucocorticoid replacement because it is considered not to be an issue.
127. I see no reason to depart from what the O'Donnell article says on its face - a person following the teaching of the O'Donnell article should investigate the possible need for glucocorticoid replacement. The obviousness question, expressed in terms of the Cripps question, is:
Would the notional research group at the relevant date, knowing that abiraterone acetate is a possible solution and that glucocorticoid replacement should be considered, directly be led as a matter of course to try abiraterone acetate and prednisone in the expectation that it might well produce a useful second stage treatment of metastatic prostate cancer?

128. Put simply, would a person wishing to address the possible need for glucocorticoid replacement be led as a matter of course to try prednisone? The O'Donnell article says that there are three possibilities: replacement on a continuous basis, at times of physiological stress, or not at all. It is a reasonable assumption for present purposes that a person would inevitably have determined that replacement on a continuous basis was needed. However, based on what I said above it would not have been a matter of routine to use prednisone as a glucocorticoid replacement in the treatment of prostate cancer. Also, it was not standard to use prednisone in combination with second stage treatment of metastasized prostate cancer (in order to achieve pain relief).
129. Consequently, it has not been established that claim 1 lacks inventive step. In this circumstance I do not need to consider any of the other claims.
6.5 The Lam article
130. The Lam article stands in no better position than the O'Donnell article.
131. The Lam article is part of the prior art base (as stated previously). There is no direct evidence that the Lam article would have been ascertained. However, for similar reasons to those mentioned for the O'Donnell article I will treat the Lam article as if it would have been ascertained. The Lam article contains a summary of the O'Donnell article with no reference to glucocorticoid replacement, and in the following section there is the statement that:

"Glucocorticoid repletion is a standard supportive therapy in patients treated with agents that inhibit adrenal function."

132. While it is accepted that this teaches that glucocorticoid replacement is standard in the literature that Lam reviewed, it is hard to see how this could be seen as a suggestion that glucocorticoid replacement should be considered when implementing the O'Donnell article. Of course, even if it could be said that glucocorticoid replacement would have been considered, it has not been established that prednisone would have been selected as a matter of course. It follows that it has not been established that there is a lack of inventive step in the light of the Lam article.
6.6 The Gerber article
133. The Gerber article was published on 20 December 1991 (Grimes declaration at paragraph 5), so it is part of the prior art base. There is no direct evidence that the Gerber article would have been ascertained. However, for similar reasons to those mentioned for the O'Donnell article I will treat the Gerber article as if it would have been ascertained.
134. The Gerber article teaches at page 1179 that it is known that "there may be a small subset of patients with hormone refractory disease who will benefit from ketoconazole treatment". That treatment involved "the combination of ketoconazole and physiological glucocorticoid replacement therapy". The point of the Gerber article is that "it is important to identify these patients as objectively as possible". The authors investigated whether prostate specific antigen (PSA) levels are useful to identify patients who may benefit from ketoconazole treatment. They conclude that serial PSA levels may be a useful indicator. The specific drug combination used was ketoconazole and prednisone, but there is nothing in the article to suggest that the authors considered that the prednisone was an inventive choice. Rather, the article reads as if the combination of ketoconazole and prednisone was already known.
135. It is clear from the Gerber article that prednisone has been used as a glucocorticoid replacement, and specifically as a glucocorticoid replacement during prostate cancer treatment of hormone refractory patients.
136. In order to establish a lack of inventive step, it would have to be shown that a person would have altered the treatment in the Gerber article by replacing ketoconazole with abiraterone acetate. At the hearing I summarised this argument as swapping out ketoconazole for "the new kid on the block" – abiraterone acetate.
137. The difficulty for the opponent is that it has not been established that abiraterone acetate was part of the common general knowledge. Consequently, the person skilled in the art would not have had the necessary knowledge in order to consider replacing ketoconazole with abiraterone acetate. The opponent has not established that the invention lacks inventive step in the light of the Gerber article.
6.7 The combination of the O'Donnell and Gerber articles
138. It was argued that it would be possible to mosaic the O'Donnell and Gerber articles. However, I cannot agree. The only reason for combining the teaching of these articles is that it gives all of the components of the invention as claimed. There is no evidence from any person that they would have combined the documents, and I can see no reason on the face of the documents to do so. I am not satisfied that the opponent has established that the invention lacks inventive step in the light of a combination of the O'Donnell and Gerber articles.
6.8 Conclusion on inventive step
139. I conclude that it has not been shown that there is a lack of inventive step.
7 Conclusion
140. The opposition fails on all grounds.
8 Costs
141. The parties submitted that costs should follow the event. I see no reason to depart from that result. Costs should be awarded against the opponent.
Dr S.D. Barker
Delegate of the Commissioner of Patents