Endorecherche Inc v Merck & Co., Inc
[1999] APO 74
•23 November 1999
OFFICIAL NOTICE
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Application : No. 665311 in the name of ENDORECHERCHE INC.
Title: Method of Treatment of Androgen-related Diseases
Action: Opposition under Section 59 by MERCK & CO., INC.
Decision: Issued
Abstract
The invention as defined by the claims is a manner of manufacture, is novel and fairly based on the description.
Independent process claims 1 to 4 do not define the invention since they are not limited to the administration of an androgen receptor antagonist in association with either a 5a-reductase, 17b- hydroxysteroid dehydrogenase (17b-HSD) or 3b- hydroxysteroid dehydrogenase (3b-HSD) inhibitor.
Claims 1, 2, 5, 6, 7, 9 (in part - when appended to claim 1 or 2), 10, 11, 15, 16 & 19-20 (in part) which relate to the use of a 5a-reductase inhibitor and an androgen receptor antagonist lack an inventive step in light of opposition exhibits JJG6 and JJG10 separately.
Claims 3, 4, 9 (when appended to either claim 3 or 4), 12-14, 17, 18 and 21-23 are non-obvious and involve an inventive step. The opponent did not establish that the use of a 17b-HSD inhibitor or a 3b-HSD inhibitor either alone or in combination with other active agents is common general knowledge in relation to the treatment of prostate cancer.
The applicant is given the opportunity to propose suitable amendments to overcome the deficiencies identified.
PATENTS ACT 1990
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Re:Patent Application No. 665311 in the name of Endorecherche Inc. and
opposition thereto by Merck & Co., Inc.
BACKGROUND
Patent application 63425/94 was filed on 30 May 1994 in the name of Endorecherche Inc. as a divisional application of patent application 58516/90. 63425/94 was advertised accepted on 21 December 1995 and assigned serial number 665311.
A notice of opposition to the grant of a patent was filed by Merck & Co., Inc. on 21 March 1996. The Statement of Grounds and Particulars was served on 21 June 1996. Evidence in support of the opposition was served on 23 December 1996.
On 20 August 1997 the applicant filed a first amendment request under section 104 in order to “limit the issues in dispute in the opposition”. This amendment was allowed on 23 March 1998 and resulted in substantial amendment to the specification and claims of the accepted application.
Evidence in answer was served by the applicant on 7 May 1998. Evidence in reply was served on 3 September 1998.
Also on 3 September 1998 the applicant filed a second amendment request to “incorporate ‘Swiss style’ claims and other claims into the specification”. This amendment was subsequently allowed on 1 March 1999.
The amendments to the accepted specification resulted in the opponent filing two amended statements of grounds and particulars. The later of these, dated 17 February 1999, sets out the issues relied upon in the opposition.
The matter was heard in Sydney on 29 and 30 March 1999. The patent applicant was represented by Ms Pamela Tate of counsel, assisted by Mr Stephen Sharp, patent attorney, of Griffith Hack. The opponent was represented by Mr Anthony Franklin of counsel, assisted by Mr Colin Bodkin, patent attorney, of Spruson & Ferguson.
GROUNDS OF OPPOSITION
The statement of grounds and particulars, dated 17 February 1999, specifies three grounds of opposition:
S.59(a) - The nominated person is not entitled to a grant for a patent for the invention;
S.59(b) - Manner of Manufacture, Novelty, Inventive Step; &
S.59(c) - Section 40 deficiencies.
EVIDENCE
Evidence in support of the opposition consists of a statutory declaration (#1) by Professor John J Grygiel, dated 23 December 1996, with exhibits JJG-1 to 81. Professor Grygiel is a Senior Staff Specialist in the Department of Medical Oncology, at St. Vincent’s Hospital and an Associate Professor in the Faculty of Medicine, University of New South Wales. He has practised Medical Oncology for the past 15 years and has been involved in genitourinary oncology research throughout this period.
Evidence in answer to the opposition consists of statutory declarations by Professor David Joshua Handelsman (with exhibits DAH-1 & 2) and Professor John Anthony Levi (with exhibits JAL-1 to 4). Professor Handelsman is the Professor of Reproductive Endocrinology & Andrology at the University of Sydney and the Director of the Andrology Unit, at Royal Prince Alfred Hospital. He has worked as an endocrinologist and andrologist since 1980. Professor Levi is the Head of the Department of Oncology at Royal North Shore Hospital and Clinical Professor of Medicine in the Department of Medicine, the University of Sydney. He has practised Medical Oncology for the past 27 years.
Evidence in reply in the opposition consists of a further declaration (#2) by Professor Grygiel, dated 2 September 1998.
During the hearing, Ms Tate in her submissions for the applicant asserted that “The opponent has not proven the publication dates of any of the documents upon which it relies” in relation to novelty. As a result of this submission counsel for the opponent made a request to adduce further evidence in relation to the publication date of opposition exhibit JJG-9. Following submissions from both parties I granted the opponents request to serve the further evidence. A further statutory declaration from Gregory John Cox, a Librarian at Spruson & Ferguson, dated 16 April 1999 with exhibit GJC-1 was served on even date.
As indicated above, the specification was amended during the evidentiary phases of the opposition. The first amendment resulted in the replacement of the term ‘antiandrogen’ with the expression ‘androgen receptor antagonist’ in the claims of the accepted specification. The expert witnesses agree that the term ‘antiandrogen’ can in differing contexts have a wide or narrow meaning. The opposition and the evidence in support of the opposition by Professor Grygiel were directed to the wide meaning of the term. The applicant’s first amendment has limited the meaning of the term to the narrower version, ie the terms ‘antiandrogen’ and ‘androgen receptor antagonist’ are used synonymously in the amended specification. The evidence in support of the opposition, in some instances, needs to be read in light of the understanding that the evidence was directed to the broader meaning of the term ‘antiandrogen’.
THE SPECIFICATION
The specification states that the invention relates to:
“ . . . a method of treatment of androgen-related diseases such as prostate cancer in warm-blooded male animals (including humans) in need of such treatment, and in particular, to a combination therapy comprising administering an antiandrogen (that is, an androgen receptor antagonist) in association with an inhibitor of sex steroid biosynthesis to such animals.”
The specification indicates that androgen-related diseases include those whose onset, maintenance or progress is, at least in part, dependent upon biological activities induced by androgens. Prostate cancer is an androgen-related disease, since activation of androgen receptors stimulates the growth of prostatic cancer cells.
Androgens are one of a group of male sex hormones that stimulate development of the testes and male secondary sexual characteristics. Testosterone and dihydrotestosterone (DHT) are both androgens. Androgens are produced principally by the testes when stimulated by luteinizing hormone.
As background to the invention, the specification recites various studies in relation to the treatment of hormone-dependent prostate cancer. A range of examples relating to the treatment of the prostate cancer with various active substances, including the use of combination therapies, are disclosed.
In its simplest form the combination therapy of the invention involves the administration of two separate classes of compounds directed at inhibiting biological activities which lead to prostatic cancer cell growth.
The first class of compounds are androgen receptor antagonists (antiandrogens - in the narrow sense) which bind to the androgen receptors of prostatic cells to prevent them from being activated by androgens. It is important that the antiandrogen be a pure antagonist which has no agonistic activity, otherwise the compound may itself activate the receptor, which is undesirable. Antiandrogens useful in the current invention include, but are not limited to:
1) flutamide (trade name EULEXIN);
2) nilutamide (trade name ANANDRON);
3) cyproterone acetate (trade name ANDROCUR); &
4) Casodex.
In addition to the administration of an antiandrogen the process of the current invention involves administration of a second class of compounds, inhibitors of sex steroid biosynthesis. Both androgen and estrogen sex steroids are targeted, as estrogens are known to stimulate some human prostatic cancer cells. Sex steroid formation inhibitors are compounds capable of blocking the activity of various enzymes which catalyse the formation of sex steroids, for example:
a) 5a-reductase, an enzyme which irreversibly converts testosterone to the more potent androgen DHT;
b) 17b-hydroxysteroid dehydrogenase (17b-HSD), which catalyses inter alia the production of natural sex steroids such as testosterone and various estrogens;
c) 3b-hydroxysteroid dehydrogenase (3b-HSD), an enzyme which catalyses the conversion of dehydroepiandrosterone (DHEA) to androstenedione (which is the precursor of some sex steroids) as well as the conversion of the estrogen andro-5-ene-3b,17b-diol to testosterone in peripheral tissues (ie not in the adrenal glands or the testes).
An inhibitor of 5a-reductase activity is a particularly preferred sex steroid synthesis inhibitor since it selectively reduces DHT levels without reducing testosterone levels. Preferred compounds described as 5a-reductase inhibitors include, MK-906 a product of Merck Sharp & Dohme and 17b-N,N-diethylcarbamoyl-4-methyl-4-aza-5a-androstan-3-one (4MA).
Various 17b-hydroxysteroid dehydrogenase (17b-HSD) and 3b-hydroxysteroid dehydrogenase (3b-HSD) inhibitors are described in the specification. 4MA while described as a 5a-reductase inhibitor has also been found to inhibit 3b-HSD, and can be used for that purpose.
The specification further indicates that it is difficult to block all androgen receptor sites, so it is also desirable to simultaneously decrease the concentration of androgens available to activate androgen receptors. Hence, a preferred form of the invention includes additional inhibition of secretion of androgens by the testes either by surgical orchiectomy (castration) or by administration of luteinizing hormone-releasing hormone (LHRH) agonists or antagonists.
The independent claims which define the invention are as follows:
1. A method for treating prostate cancer in a human or other warm-blooded animal in need of such treatment, said method including the steps of administering a therapeutically effective amount of an inhibitor of 5a-reductase activity and administering a therapeutically effective amount of an androgen receptor antagonist.
2. A method for treating prostate cancer in a human or other warm-blooded animal in need of such treatment, said method including the steps of administering a therapeutically effective amount of an inhibitor of 5a-reductase activity and administering a therapeutically effective amount of an androgen receptor antagonist which has no agonistic activity.
3. A method for treating prostate cancer in a human or other warm-blooded animal in need of such treatment, said method including the steps of administering a therapeutically effective amount of an inhibitor of 17b-HSD and administering a therapeutically effective amount of an androgen receptor antagonist.
4. A method for treating prostate cancer in a human or other warm-blooded animal in need of such treatment, said method including the steps of administering a therapeutically effective amount of an androgen receptor antagonist and administering a therapeutically effective amount of an inhibitor of the 3b-hydroxysteroid dehydrogenase catalysed conversion of dehydroepiandrosterone to androstenedione or conversion of androst-5-ene-3b,17b-diol to testosterone in peripheral tissues.
10. Use of an inhibitor of 5a-reductase activity and an androgen receptor antagonist for the manufacture of a medicament for the treatment of prostate cancer in a human or other warm-blooded animal.
11. Use of an inhibitor of 5a-reductase activity and an androgen receptor antagonist which has no agonistic activity for the manufacture of a medicament for the treatment of prostate cancer in a human or other warm-blooded animal.
12. Use of an inhibitor of 17b-hydroxysteroid dehydrogenase and an androgen receptor antagonist for the manufacture of a medicament for the treatment of prostate cancer in a human or other warm-blooded animal.
13. Use of an androgen receptor antagonist and an inhibitor of the 3b-hydroxysteroid dehydrogenase catalysed conversion of dehydroepiandrosterone to androstenedione in peripheral tissues for the manufacture of a medicament for the treatment of prostate cancer in a human or other warm-blooded animal.
14. Use of an androgen receptor antagonist and an inhibitor of the 3b-hydroxysteroid dehydrogenase catalysed conversion of androst-5-ene-3b,17b-diol to testosterone in peripheral tissues for the manufacture of a medicament for the treatment of prostate cancer in a human or other warm-blooded animal.
15. Use of an inhibitor of 5a-reductase activity and an androgen receptor antagonist in the treatment of prostate cancer in a human or other warm-blooded animal.
16. Use of an inhibitor of 5a-reductase activity and an androgen receptor antagonist which has no agonistic activity in the treatment of prostate cancer in a human or other warm-blooded animal.
17. Use of an inhibitor of 17b-hydroxysteroid dehydrogenase and an androgen receptor antagonist in the treatment of prostate cancer in a human or other warm-blooded animal.
18. Use of an androgen receptor antagonist and an inhibitor of the 3b-hydroxysteroid dehydrogenase catalysed conversion of dehydroepiandrosterone to androstenedione or conversion of androst-5-ene-3b,17b-diol to testosterone in peripheral tissues in the treatment of prostate cancer in a human or other warm-blooded animal.
From a reading of the specification it is clear to me that these independent claims define the essential features of the invention, in its various forms.
As a matter of construction, where a claim involves a process which combines biological activity A with biological activity B, generally, this would include the possibility where both biological effects A and B are produced by a single compound, unless the contrary indication appears. Thus a claim of this form, such as claim 1 for example, would encompass within its scope the use of a single compound which is both a 5a-reductase inhibitor and an androgen receptor antagonist.
The specification at page 20 indicates that compound 4MA, an inhibitor of sex steroid biosynthesis, is both a 5a-reductase inhibitor and has also been found to inhibit 3b-HSD. Thus when 4MA is used it produces both biological effects. This supports the construction above where one compound may be used to effect more than one biological activity.
DECISION
Counsel from both parties made extensive submissions in relation to the matters raised in the statement of grounds and particulars, as well as providing me with a written summary. I will refer to their submissions where appropriate in my decision.
At the outset, Mr Franklin for the opponent indicated that they would not be pursuing two matters listed in the statement of grounds and particulars. Firstly, the opponent would not contest the earliest priority date of 7 July 1989 and would, for the purposes of this opposition, concede that date as the priority date of the claims. Secondly, the opponent would not be pursuing the allegation that the invention was not a manner of new manufacture solely as a result of the invention being not novel or not involving an inventive step.
I will consider each of the three grounds of opposition in turn.
THE NOMINATED PERSON IS NOT ENTITLED TO A GRANT FOR A PATENT FOR THE INVENTION
In support of this ground the opponents sole allegation is that the invention defined in the claims is not novel and lacks an inventive step, as to be determined under the appropriate ground, and as a result of that the nominated person is not entitled to the grant of a patent. My decision in relation to novelty and inventive step raised under ground II) below will be my determination in relation to this ground also.
MANNER OF MANUFACTURE, NOVELTY & INVENTIVE STEP
Manner of Manufacture
Counsel for the opponent alleged that the invention is not a manner of manufacture in accordance with section 18(1) (a) of the Act. Specifically that:
The specification merely defines desirable characteristics to be exhibited by substances for use in the claimed methods of treatment of prostate cancer, which properties were, before the relevant priority date, characteristics known to be desirable in agents useful for treating prostate cancer. Thus, on its face, the specification lacks the necessary quality of inventiveness for it to define a manner of manufacture.
On the face of the specification treatment of prostate cancer by the administration of at least the following active substances was known: LHRH agonists and antagonists; Antiandrogens (androgen receptor antagonists); Inhibitors of sex steroid biosynthesis; Inhibitors of 5a-reductase. Further, that combination therapies were known.
In response to the opponents allegations Ms Tate for the applicant submitted that:
The methods of treatment of humans are no less a manner of manufacture than a method of ridding crops of weeds, Anaesthetics Supplies Pty Ltd v. Rescare (1994) 50 FCR 1 at 19.
The opponents have misrepresented the information which was known or accepted as at the priority date of the present application. Specifically, at the priority date:
- It was not the case that 5a-reductase inhibitors were known to have properties which render them suitable for use in treatment of prostate cancer. Very little was known about 5a-reductase inhibitors. Nor was it known that 17b-HSD or 3b-HSD inhibitors had properties which rendered them suitable for use in treatment of prostate cancer.
- Androgen receptor antagonists were known to have only a limited usefulness in the treatment of prostate cancer.
- Further, it was not known that it was desirable to use the particular combination of agents referred to in the present claims in the treatment of prostate cancer.
Mr Franklin made much of the disclosures of the documents referred to in the current specification. He submitted that the information from these disclosures showed that the invention lacked the threshold inventiveness required for there to be a manner of manufacture. I will confine my consideration here to those matters which the specification, on its face, reveals to be known or accepted in the art.
There are a number of documents referred to in the current specification which provide a background against which one can consider the current invention. These documents variously describe the use of different compounds or methodologies in the treatment of hormone-dependent tumours, particularly but not exclusively, prostate cancer. Many are research papers publishing results of various experiments related to cancer treatment while others are patent documents relating to the treatment of prostate cancer or benign prostatic hypertrophy. These documents clearly disclose that various methods of treating prostate cancer were being investigated before the priority date of the present application and that some of these had been shown to be successful. These documents also disclose that in certain instances combination therapies may be useful as treatments for prostate cancer.
Contrary to the opponents submission that the invention lacks inventiveness by virtue of the disclosures of prior art in the specification itself, the specification states that while previous investigators have been studying prostate cancer none have proposed the combination therapy of the current invention. It is further stated that two objects of the invention are to provide a combination therapy having increased effectiveness and having significantly reduced frequency of unwanted side effects.
There is nothing in the specification which suggests to me that the information contained in any one of the documents cited is, or would be regarded as, common general knowledge in the field of the invention. Further, the disclosures of the various treatments for prostate cancer in the documents are not of such a nature that one would immediately consider the combination therapy of the present invention as being clearly lacking in inventive merit. I do not believe that it is apparent on the face of the specification itself that the quality of inventiveness necessary for there to be a proper subject of letters patent under the Statute of Monopolies is absent. The claims define a manner of manufacture.
Under this ground, Mr Franklin for the opponent also submitted that claim 9 does not define a manner of manufacture by virtue of the fact that it merely defines a collocation of known integers.
In response, Ms Tate stated that claim 9 does not define a mere collocation of known components. A mere collocation comprises a number of known integers or process steps in such a way that no working interrelationship exists between the various constituent parts, International Paint Co. Ltd.'s Application, (1982) RPC 247. She further stated that claim 9 is a claim to a kit “when used in” the novel methods of any one of claims 1 to 7. Thus the claim is limited to the environment of the novel methods of treatment. When used in these methods there is a working or potential working interrelationship between the components of the kit.
Claim 9 is as follows:
9. A kit when used in the treatment of prostate cancer as defined or according to any one of claims 1, 2, 3, 4, 5, 6 or 7, said kit having a plurality of containers which together hold the active ingredients used in any one of said methods, wherein at least one container has contents different from at least one other container.
This claim is a claim to a kit “when used” in the treatment of prostate cancer in accordance with the method defined in any one of claims 1 to 7. The term “when used” has the effect of limiting the scope of the claim to a particular environment or time. Thus as a matter of construction, claim 9 is akin to a process claim and is not a claim to a kit per se. Support for this can be found in Wellcome v Commissioner of Patents, 30 ALR 510 at 516 (a similar opinion was expressed in Bernard Joo’s Application, (1972) AOJP 3429 at 3430):
“there is no distinction between the claim to the process and the claim to the substance when the substance claim is limited to its use in the process”
I believe it is appropriate in the present situation to consider a kit in the same manner as the “substance” referred to in the above quote. There is nothing to suggest to me that a “kit when used” claim should necessarily be treated any differently from a “compound/substance when used” claim. Hence claim 9 is not a claim to a kit per se, but a kit when used in the process of one of the claims to which it is appended.
The opponent has not made allegations similar to those against claim 9 in relation to the process claims 1 to 7 of the invention. In that claim 9 is limited to the use of the kit in the process of any one of the claims to which it is appended, the opponents allegation that claim 9 is not a manner of manufacture as it merely defines a collocation of known components is of no moment. Claim 9 is not a claim to a kit per se. Claim 9 defines a manner of manufacture since there is nothing inherently unpatentable in a claim of that type.
Novelty - The law
The test for determining whether an invention lacks novelty is the "reverse infringement test" as stated by Aiken J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd, (1977) 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.”
Infringement of a claim occurs where “each and every one of the essential integers” of that claim have been taken, Rodi and Wienenberger AG v Henry Showell Ltd, (1969) RPC 367 at 391.
A more recent statement in relation to novelty is in Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513 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 unmistakable 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. What ever is essential to the invention must be read out of or gleaned from the prior publications”
In assessing the teaching or disclosure of the prior art, one has to consider what the skilled addressee is being taught and what they would have done on reading the citation, General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd, (1972) RPC 457 at 485, 486:
“To anticipate the patentees claim, the prior publication must contain clear and unmistakable directions to do what the patentee claims to have invented ... A signpost, however clear, upon the road to the patentee's invention will not suffice.”
Similarly, a prior disclosure will only invalidate a claim if, after having read it, the skilled addressee would rather than could have produced all the essential integers of the claim:
“Any information as to the alleged invention given by any prior publication must be for the purpose of practical utility, equal to the given by the subsequent patent. The latter invention must be described in the earlier publication that is held to anticipate it, in order to sustain the defences of anticipation. Where the question is solely one of prior publication, it is not enough to prove that an apparatus described in an earlier specification could have been used to produce this or that result. It must also be shown that the specifications contain clear and unmistakable directions so to use it. It must be shown that the public have been so presented with the invention that it is out of the power of any subsequent person to claim the invention as his own.”
Canadian General Electric Co., Ltd v Fada Radio Ltd, (1930) 47 RPC 69 at 90
Novelty - Consideration of cited documents
Counsel for the opponent only made submissions in relation to four of the documents cited in the statement of grounds and particulars in relation to the novelty of the present claims. He stated that the other six documents which were originally raised under this heading would not be relied upon as they were published after the earliest priority date of 7 July 1989.
Ms Tate, for the applicant, asserted that the opponent had not proved the publication dates of any of the documents upon which it relies for the purposes of the objection of novelty, including the four cited as prior publications.
The four documents currently relied upon by the opponent are exhibits (JJG6, JJG8, JJG9 and JJG10) to the first declaration by Professor Grygiel. As I have mentioned earlier, this matter was resolved in relation to exhibit JJG9 by the opponent adducing further evidence to establish that the document was published in April 1985, which is before the earliest priority date of the current application.
The other three documents, exhibits JJG6, JJG8 and JJG10, are all technical articles published in learned journals relating to the field of cancer or prostate research. Each of these articles has a “date”, the journal name, volume number, etc as an integral part of the published document. In most publications of this type this information is used to indicate when the article was published and for the purpose of citing or referencing the article. In my opinion, these dates which appear on the documents are prima facie proof that the articles were published, i.e. were disclosed to the public, on the respective dates. In the absence of any evidence, or more persuasive argument, to the contrary it is reasonable and appropriate to take the dates which appear as part of these articles as their date of publication for the purpose of determining the novelty, or for that matter inventive step, of the present application. All three exhibits were, prima facie, published before 7 July 1989.
Mr Franklin’s only submission in relation to exhibit JJG 8 was that the amendment to replace the term ‘antiandrogen’ in the claims of the accepted specification with the expression ‘androgen receptor antagonist’ rendered this document of no significance for novelty. The document was only pertinent to the accepted, and unamended, specification where the term ‘antiandrogen’ (which was capable of a broad meaning) was used in the claims. I will not consider this document any further.
The other three documents alleged to anticipate the claims of the current application all relate to the use of 5a-reductase inhibitors in the treatment of prostatic cancer and are considered below:
JJG10Petrow V.: “The Dihydrotestosterone (DHT) Hypothesis of Prostate Cancer and Its Therapeutic Implications”, The Prostate 9:343-361 (1986)
The abstract of this article is as follows:
“Data are presented showing that human prostatic adenocarcinoma depends on dihydrotestosterone (DHT) and not testosterone (T) for growth. It follows that androgen ablative therapy should be directed toward elimination of DHT with retention of circulating T. This can be achieved by using a 5a-reductase inhibitor such as 6-methyleneprogesterone (6-MP) (VII). Arguments are presented showing that 6-MP (VII) is expected 1) to function as a prophylactic agent against prostate cancer, 2) to represent an attractive therapeutic modality for palliative treatment of hormone-responsive disease, and 3) to be compatible with other therapeutic modalities when very low prostatic levels of DHT should be within reach.”
Expert witnesses agree that this document does not disclose, in a practical sense, the administration of a 5a-reductase inhibitor with an androgen receptor antagonist. The document does, however, postulate on theoretical grounds the use of a 5a-reductase inhibitor with other therapeutic modalities. Such therapeutic modalities include “antiandrogens”, which are described in the document itself as compounds which compete with testosterone/DHT for the androgen receptor.
The statements in relation to novelty from General Tire & Rubber Co and Nicaro Holdings Pty Ltd (supra) are clearly relevant here. This document does not contain clear and unmistakable directions to use a 5a-reductase inhibitor in association with an ‘androgen receptor antagonist’. Nor does the document, disclose all of the essential features of the presently claimed invention in clear, unequivocal and unmistakable terms. The skilled addressee would not immediately read the essential features of the present invention out of this document.
As stated in Canadian General Electric Co (supra) any information as to the alleged invention given by any prior publication must be for the purpose of practical utility, equal to the given by the subsequent patent. This is not the case in respect of this document since it only postulates the use of a 5a-reductase inhibitor with other known modalities
The claims of the specification are novel when compared to this document, however, I will consider this document further under the heading of inventive step.
JJG9Andriole et al.: “Treatment of androgen-responsive human genitourinary tumours with 4MA, a potent inhibitor of 5-alpha reductase”, Journal of Urology, Volume 133 (April 1985), No.4, Part 2, page 123A, Abstract No. 38
This exhibit is an abstract which reports the experimental findings of a study performed to evaluate the effect of 4MA (a steroidal inhibitor of 5a-reductase) on hormone-responsive human (HRH) genitourinary tumours grown in athymic nude mice (ANM). The abstract ends with the sentence:
“These results indicate that 4MA is effective in inhibiting the growth of HRH genitourinary tumors in ANM and that 4MA may achieve equivalent tumor inhibition as orchiectomy”
The abstract does not disclose the use of a separate androgen receptor antagonist. Mr Franklin for the opponent submitted that 4MA is not only a 5a-reductase inhibitor as referred to in the abstract, but, it is also an androgen receptor antagonist. Thus, the opponent asserts that the use of 4MA alone constitutes the use of a 5a-reductase inhibitor and an androgen receptor antagonist.
Submissions from both Ms Tate and subsequently from Mr Sharp for the applicant assert that 4MA was not, and is not, an androgen receptor antagonist, nor has the opponent adduced evidence to show that that is the case. Mr Sharp further submitted that the evidence of Professors Levi and Handelsman clearly establishes that 4MA is not an androgen receptor antagonist.
Using the reverse infringement test, the disclosure of this abstract will only deprive the current claims of novelty if it is established that 4MA is in fact an androgen receptor antagonist. Evidence advanced by the opponent to support this contention is at paragraph 15 of the declaration #2 (in reply) by Professor Grygiel where he states:
“. . . Furthermore, I note that 4-MA is an androgen receptor antagonist in addition to being a 5a-reductase inhibitor. . . .”
There is little else in the statements by Professor Grygiel, either in support or in reply, which is supportive of the assertion that 4-MA is an androgen receptor antagonist. In his first declaration (in support) Professor Grygiel provides numerous statements and references which establish that 4MA is well known as a 5a-reductase inhibitor, but, nowhere in his statements is there any support for the proposition that 4MA is an androgen receptor antagonist.
Professor Handelsman, in evidence in answer, indicates at paragraph 8 of his declaration that:
“. . . In general, 5a-reductase inhibitors do not bind the androgen receptor. Accordingly, in my opinion, 5a-reductase inhibitors are not ‘androgen receptor antagonists’ as that expression is used in claims 1, 2, 3 and 4 of the amended specification. . . .”
Further on, at paragraph 62.10, Professor Handelsman also states:
“It was known to me before 7 July 1989 that there are some 5a-reductase inhibitors that have weak antiandrogenic effects. For example 4MA has a very weak affinity for the androgen receptor. . . . In my opinion, 5a-reductase inhibitors and androgen receptor antagonists are two distinct classes of compounds.”
Professor Levi, for the applicant, at paragraph 7 of his declaration states:
“. . . Some in vitro (tissue culture) experiments have indicated that certain 5a-reductase inhibitors bind weakly to androgen receptors. However, in my opinion, this weak affinity for androgen receptors does not have clinical significance in the treatment of prostate cancer. I would not classify the 5a-reductase inhibitors which have weak affinity for androgen receptors as ‘androgen receptor antagonists’ as that term is used in claims 1, 2, 3 and 4 of the Amended Specification. . . .”
Statements that 4MA has some affinity for the androgen receptor are supported by a reference in the specification itself. The article by Chan et al. referred to at page 20 of the specification discloses, inter alia, that:
“… 4-MA has been shown to have a moderate affinity for the androgen receptors (1, 15), …”
Reference 15 in the above quote is an article by Liang et al. entitled “Inhibition of 5a-reductase, Receptor Binding, and Nuclear Uptake of Androgens in the Prostate by 4-Methyl-4-aza-steroid” and provided as opponent’s exhibit JJG66. The document discloses that the compound 17b-N,N-diethylcarbamoyl-4-methyl-4-aza-5a-androstan-3-one, presently referred to as 4MA:
“… has moderate affinity for the prostate cytosol androgen receptor. … This affinity to the androgen receptor is 1,000-, 500-, 120- and 40-fold lower than that of 5a-dihydrotestosterone, testosterone, spironolactone, and cyproterone acetate, respectively …”
Firstly, it has been stated and in various cases shown that 4MA has weak to moderate (at best) affinity for the androgen receptor. Secondly, the Liang article indicates that 4MA is 1000- and 500-fold lower in terms of its affinity for the androgen receptor as compared to androgens DHT and testosterone respectively. Thirdly, 4MA has a 40-fold lower affinity for the receptor compared to cyproterone acetate which is listed in the current specification as an androgen receptor antagonist. Finally, and notwithstanding references to 4MA having some affinity for the androgen receptor, in the various documents which have referred to its use as a 5a-reductase inhibitor not one has mentioned, nor alluded to the fact, that 4MA is, or might be regarded as, an androgen receptor antagonist.
The relatively low level of affinity for the androgen receptor indicates to me that 4MA does not function as an “antagonist” to the androgen receptor in the technical sense of that word. The degree of affinity for the androgen receptor of 4MA is not of such a magnitude that one could reasonably predict that it would exclude the binding of androgens to a sufficient extent which would be regarded as antagonistic. Having weighed the evidence before me, I consider that it is more likely than not that 4MA would not act as an androgen receptor antagonist.
Hence, on the balance, I am not satisfied that 4MA is an androgen receptor antagonist as that term is used in the current specification. I find that the administration of 4MA alone does not constitute the use of a 5a-reductase inhibitor and an androgen receptor antagonist as defined in the claims. The claims of the specification are novel when compared to the disclosure of this abstract.
JJG6Sanberg A. A. & Kadohama N.: “Enzymatic and receptor systems as targets for therapy of prostatic cancer”, Progress in Cancer Research and Therapy, Vol. 31, 1984 pp 477-489
This document is a “review” type article relating to some aspects of hormonally dependent prostatic systems whose possible manipulation may have applicability in the treatment of cancer of the prostate. The document brings together many facts and findings in the context of research into treatment of prostatic cancer.
As indicated by the title, this article relates to enzymatic and receptor systems as targets for treating prostatic cancer. More particularly, at page 478 it is stated:
“We shall address ourselves primarily to the two intracellular hormonally associated systems, i.e., the 5a-reductase system responsible for conversion of testosterone (T) to dihydrotestosterone (DHT) and the androgen receptor for DHT which apparently plays a crucial role in translating the effects of androgenic hormones in the prostate.”
The document postulates, on theoretical grounds, a possible “best approach” in the treatment of prostate cancer at page 487:
“It would appear that the best approach in the treatment of prostate cancer, once the importance of the reductive and oxidative steroid pathways have been clearly established, is to use both types of agents, concomitantly, i.e. 5a-reductase inhibitors and substances with high affinity for the receptor, thus making sure that two hormonally associated systems of crucial importance to prostatic cell survival can be affected, while at the same time chemotherapy or radiation is given. There remains doubt that the use of these hormonally affecting agents per se will be the ultimate approach to the treatment of prostatic cancer; we suggest they be given in concert with several chemotherapeutic agents and/or ionizing radiation.”
[Emphasis added]
Ms Tate for the applicant submitted, inter alia, that JJG6 does not anticipate the current invention for the following reasons:
the information given by the citation is not equal to that given by the specification;
the citation does not provide sufficient information for a person of ordinary skill in the art to practically apply the discovery without making further experiments, it does not describe how the method is implemented, the compounds or the quantity to be used, or administration;
the citation expressly envisages that further experimentation is required;
the methods disclosed are merely hypotheses and mere speculation;
it is not envisaged in the citation itself that the methods of hormonal manipulation are to be undertaken alone, rather they are to be undertaken with chemotherapy or radiation;
it is uncertain whether 5a-reductase is inhibited or promoted, see p. 479
“manipulation of the systems, either by suppression or activation of the 5 a-reductase system and intracellular replacement of the active androgen (DHT) on the receptor by inactive androgens or inert substances, may be useful.”
while “substances with high affinity for the receptor” disclosed in the citation may include androgen receptor antagonists they may also include androgen receptor agonists.
Assessing this document in relation to the novelty of the present claims is not a straight-forward task. On the one hand, the document clearly refers to the use of 5a-reductase inhibitors in association with substances with high affinity for the androgen receptor, specifically including androgen receptor antagonists. On the other hand, as Ms Tate for the applicant has rightly pointed out, the document does not itself teach or show, in a practical sense, a method using both of the active substances in combination. What the document does do is to bring together information relating to 5a-reductase inhibitors and substances with high affinity for the androgen receptor, which had been arrived at separately, and to use this information to postulate a combined method of treatment. The document does not give any indication that the postulated method has been attempted.
It is clear that this document is of an intellectual nature. From the information gathered and analysed by the authors of the article they have postulated a combination therapy involving the use of 5a-reductase inhibitors and substances with a high affinity for the androgen receptor. The document itself contains various cautions in relation to the postulated treatment, for example, “once the importance of the reductive and oxidative steroid pathways have been clearly established” in the quote from p. 487 above.
It is clear that JJG6 discloses the use of 5a-reductase inhibitors and postulates their use in association with androgen receptor antagonists, but on the other hand, it also refers to the activation of the 5a-reductase system in connection with intracellular replacement of the active androgen, page 479.
I am mindful of the principle in General Tire & Rubber Co (supra) that the prior publication must contain clear and unmistakable directions to do what the patentee claims to have invented. A signpost upon the road to the patentee's invention will not suffice. The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee.
On a fair reading, I believe this document does not provide directions in the practical sense of that word, but, provides an indication or suggestion as to what would be a method of treatment worth trying. While this document provides a sign post to the invention I do not think it can be said that it has “planted the flag”.
The principle in Nicaro Holdings Pty Ltd (supra) is also apposite. 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.
Having carefully considered this document, I do not believe that the notionally skilled addressee would be able to practically apply the teachings of this document without the necessity of making further experiments. The authors of the article clearly and appropriately provide words of caution or doubt in the article which are sufficient for me to consider that this disclosure is not one which deprives the current invention of novelty.
The claims of the present application are novel when compared to the disclosure of JJG6. I will consider this document further under the heading of inventive step.
Novelty - Conclusion
No document cited by the opponent contains an anticipatory disclosure of a method of treating prostate cancer using a 5a-reductase inhibitor in association with an androgen receptor antagonist. Claims 1, 2, 10, 11, 15, & 16 and dependent claims are novel in light of the disclosures of opponent exhibits JJG6, JJG8, JJG9 & JJG10.
No documents were raised by the opponent which disclosed the use of an androgen receptor antagonist in association with either a 17b-HSD inhibitor or a 3b-HSD inhibitor. Hence, claims 3, 4, 12, 13, 14, 17 & 18 and dependent claims are novel.
Inventive Step - The law
The assessment of whether an invention lacks an inventive step, ie whether it is obvious, can be made against the common general knowledge alone or common general knowledge considered together with a document or act, provided the document or act could reasonably be expected to have been ascertained, understood and regarded as relevant to work in the relevant area by a person skilled in the art.
The general test to be applied in determining obviousness is stated in The Wellcome Foundation Limited v V. R. Laboratories (Aust) Pty Ltd (1980-1981) 148 CLR 262, specifically at 286:
“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.”
The likelihood of success necessary to render a routine investigation obvious was considered in Beecham Group Ltd's (Amoxycillin) Application (1980) RPC 261 at 290:
“It is clearly established that, for a particular step or process to be obvious .... it is not necessary to establish that its success is clearly predictable: Johns-Manville Corporation's Patent [1967] RPC 479 at 494.
It will suffice if it is shown that it would appear to anyone skilled in the art but lacking in inventive capacity that to try the step or process would be worthwhile: Technograph Printed Circuits Ltd v. Mills & Rockley ( Electronics) Ltd [1972] RPC 346 per Lord Reid at 355 and 356; Johns- Manville, supra, per Lord Diplock LJ at 493 and 494; Tetra Molelectric Ltd v. Japan Imports Ltd [1976] RPC 541 at 581, 583-4.”
Courts have used the problem solution/approach to assist in making determinations under the heading of obviousness/inventive step in order to avoid the criticism of ex post facto analysis. I will use that approach here. The problem may be formulated from a reading of the specification in light of the surrounding facts.
The specification states at the top of page 2:
“While various investigators have been studying hormone-dependent prostate cancer, none have proposed the combination therapy of this invention.”
To include the feature of a ‘combination’ therapy would in my opinion be too specific and be subject to attack on the grounds that an ex post facto analysis has been used in the formulation of the problem itself. From the above statement and a consideration of the prior art referred to in the specification I consider the problem that the present seeks to overcome is:
“To provide an effective therapy for hormone-dependent prostate cancer.”
Inventive Step - Exhibits JJG6 & JJG10
I will consider the two documents, exhibits JJG6 and JJG10, under the heading of inventive step.
Ms Tate for the applicant submitted at a general level that the opponent has not established that the documents upon which it relies would have been ascertained or regarded as relevant to the current invention before the priority date.
I cannot agree with Ms Tate in relation to opposition exhibits JJG6 and JJG10. Professor Grygiel in declaration #2, paragraph 9, states:
“I maintained awareness of developments in my field of specialisation by reading journals such as The Prostate, Journal of Steroid Biochemistry and Journal of Pharmacy and Pharmacology . . .”(emphasis added)
Relevantly the article of JJG10 is published in The Prostate.
Similarly Levi for the applicant, at paragraph 2 of his declaration states:
“I regularly review journal articles relating to the treatment of prostate cancer and regularly attend conferences at which developments in the treatment of prostate cancer are discussed. I am, therefore, aware of the methods of treating prostate cancer used by medicinal chemists and clinicians in Australia and throughout the world, as well as the published research relating to methods of treatment of prostate cancer being carried out throughout the world . . .”(emphasis added)
Given the nature and content of JJG6 and JJG10 and their publication in learned journals relating to cancer and its treatment, I believe these documents would have been ascertained, understood and regarded as relevant, as at the priority date, by the person skilled in the field of the invention.
JJG6
Under the heading of novelty, I decided that this document does not anticipate the claims of the present invention which involve the use of a 5a-reductase inhibitor and an androgen receptor antagonist because the document only postulated such a treatment on theoretical grounds. Hence this document is clearly relevant to a consideration of obviousness.
In support of the applicant’s case that the present invention is not obvious in light of this document, Ms Tate made submissions in relation to the disclosure of this document on similar lines to those she made in relation to novelty. I have summarised them as dot points above and those comments apply equally here. She also indicated that no experimental data is provided. Further, she stated that the skilled addressee would not, at the priority date, have viewed the information in exhibit JJG6 as sufficient to consider treating prostate cancer by administering a 5a-reductase inhibitor and an androgen receptor antagonist.
I can not agree with Ms Tate. This document clearly points to a solution to the problem I have indicated above that the current invention seeks to overcome. Applying the test set down in Wellcome (supra) the hypothetical addressee would have taken as a matter of routine what ever steps led from this document to the current invention.
Also the statement from Beecham (supra) “It will suffice if it is shown that it would appear to anyone skilled in the art but lacking inventive capacity that to try the step or process would be worthwhile”. I believe that it would appear to a person skilled in the art to try the postulated method of this document in the treatment of prostate cancer. The situation is clearly one where it would be “obvious to try” the method disclosed in the document, W.R. Grace & Co v Asahi Kasei Kogyo Kabushiki Kaisha (1993) 25 IPR 481.
Hence I believe that independent claims 1, 2, 10, 11, 15, & 16 are obvious and lack an inventive step in light of the disclosure in exhibit JJG6. Claim 9, when appended to claims 1 or 2 is similarly obvious.
Dependent claims 5and 6 include the features of additionally inhibiting testicular hormonal secretion by surgical castration or administering a LHRH agonist or antagonist. Levi, at paragraph 21, states:
“The standard methods of treatment for advanced prostatic cancer used in clinical practice in Australia before 7 July 1989 were bilateral orchiectomy (surgical castration) or the administration of estrogens or the administration of LHRH agonists or antagonists. These methods of treatment remain the standard methods of treatment for advanced prostatic cancer used in clinical practice in Australia today.”
Similarly Grygiel #1 at paragraph 11 (point 12) indicates that orchiectomy is effective in increasing the survival rate and causing tumour regression in persons suffering from prostate cancer and Handelsman, at 62.13, indicates that before the priority date it was known to him that prostate cancer could be treated by surgical castration.
Thus I believe that, as at the priority date, orchiectomy (surgical castration) or using LHRH analogues was both known and practiced in treatments for prostate cancer. I consider both of these features were common general knowledge in the field of the invention at the priority date. Claims 5 and 6 are obvious since it would have been a matter of routine to incorporate the additional features of these claims. Similarly, claim 7 is also obvious apart from the instances where it is limited by the use of a 17b-HSD inhibitor or a 3b-HSD inhibitor.
Claims 19 & 20 which are dependent on claims 15 and 16 are obvious for the same reasons as claims 5 and 6.
JJG10
Expert witnesses agreed that this document does not describe, in a practical sense, the administration of a 5a-reductase inhibitor with an ‘androgen receptor antagonist’. Rather, the document discloses the use of a 5a-reductase inhibitor with an LHRH superagonist. The document does, however, postulate the use of a 5a-reductase inhibitor in conjunction with “current therapeutic modalities”. One of the modalities it refers to in the treatment of prostate cancer is the administration of “antiandrogens”. “Antiandrogens” are described in the document as compounds which compete with testosterone/DHT for the androgen receptor and should thus be able to antagonize both testicular and adrenal androgens.
At page 352 under the heading of ‘Methods of treatment’ this document discloses:
“Antiandrogens are recommended as an adjuvant therapy to orchiectomy in order to counteract adrenal androgen secretion in prostate cancer. They are also used with LH-RH therapy (below) when, inter alia, they counteract the temporary androgen surge induced by LH-RH administration.”
From this it can be seen that this document points to the use of androgen receptor antagonists in combination with LH-RH therapy which itself is disclosed in association with the administration of a 5a-reductase inhibitor. I consider that the disclosure of this document is clearly one where it would be “obvious to try” a method involving a 5a-reductase inhibitor in combination with LH-RH therapy and an antiandrogen, when faced with the problem I have stated above, W.R. Grace & Co (supra). Also I believe that it would appear to anyone skilled in the art but lacking inventive capacity that the process referred to would be worthwhile trying, Beecham (supra).
This document renders the claims to the use of a 5a-reductase inhibitor in association with an androgen receptor antagonists lacking an inventive step.
Claims 1, 2, 9 (in part -when appended to claims 1 and 2) 10, 11, 15, & 16 are obvious and lack an inventive step in light of the disclosure in exhibit JJG10. For the reasons stated in relation to JJG6 dependent claims 5, 6, 7 & 19-20 are also obvious, as the additional features of these claims are common general knowledge.
17b-HSD or 3b-HSD inhibitors
I have decided above that claims relating to the use of a 5a-reductase inhibitor in association with androgen receptor antagonists are obvious and lack an inventive step. What remains is to make a determination in relation to those claims which involve the use of either a 17b-HSD inhibitor or a 3b-HSD inhibitor in conjunction with an androgen receptor antagonist.
The opponent has not provided any probitive evidence to establish that the use of a 17b-HSD or 3b-HSD inhibitors alone or in combination with other active agents was known, or that it was common general knowledge, in relation to the treatment of prostate cancer as at the priority date. Hence claims to the use of these two specific inhibitors in association with an androgen receptor antagonist are not obvious.
Claims 3, 4, 9 (when appended to either claim 3 or 4), 12-14, 17, 18 and 21-23 are non-obvious and involve an inventive step.
SECTION 40 DEFICIENCIES
Section 40(2) (a)
Mr Franklin submitted that the amended specification does not fully describe the invention, nor provide the best method of performing the invention, in relation to “Swiss-style” claims 10 and 11. Specifically, he pointed to various sections of the specification to show that the it did not provide a sufficient description of a method of manufacturing a medicament using both a 5a-reductase inhibitor and an androgen receptor antagonist. He stated that there is a clear indication that 5a-reductase inhibitors can be administered separately to the androgen receptor antagonist, specifically where frequency of administration is different. He further stated that there is an omission of 5a-reductase inhibitors from the compositions described, and where 5a-reductase inhibitors are described there is no mention of androgen receptor antagonists.
Ms Tate submitted that the specification describes the compounds to be used, preferred methods of administration, the dosages to be administered over particular time periods, preferred ratio of compounds, sequence of administration and in some cases exact dosages in relation to the methods of the invention. She further stated that the above constitutes a sufficient description of the invention and the best method of performing it.
I am in agreement with Ms Tate. It is clear from the description that various active ingredients can physically be administered separately, and in this context it is not at all problematic that there is no one single composition that contains both a 5a-reductase inhibitors and an androgen receptor antagonist.
The specification full describes the invention of claims 10 and 11 including the best method of performance.
Section 40(2) (b)
Mr Franklin submitted that the body of the specification states that the invention is a combination therapy comprising administering an antiandrogen in association with an inhibitor of sex steroid biosynthesis. He then stated that there “are a large number of independent claims purporting to define different inventions, and not all relating to the combination therapy which is stated to be the invention.”
I believe Mr Franklin’s point is that the claims do not state that the process is a combination therapy comprising administering the two active ingredients in association with one another. The methods defined in the independent claims do not use the word “combination” nor do they refer to administering the two active ingredients “in association”.
The independent claims define methods of treating prostate cancer by administering an androgen receptor antagonist and either a 5a-reductase, 17b-HSD or 3b-HSD inhibitor. The word “and” does not directly equate with administration “in association”. The word “and” can be construed to mean that the two components are administered in series, whereas, the term “in association” has a more explicit indication that the two components are administered in parallel. For example, “and” would include, administering a first active component, ceasing to administer the first component, then administering the second active component.
The term “in association” gives a clear indication of the pairing or coalition of the two active substance where they would need to be administered in sufficiently close proximity that their two biological effects are present contemporaneously. This is clearly supported by a reading of the specification as a whole.
A reading of the claims as they presently stand does not indicate that the word “and” is used in any way other than its plain English meaning. There is no explicit dictionary meaning for the word “and” in the specification and the consistory clauses of the description are identical to the claims to which they relate which does not provide much assistance in relation to this matter.
I am cognisant of the fact that I must read the specification as a whole. That in some cases the meaning of a word may be qualified by what is said in the body of the specification and that a purposive construction should be applied where possible. However, in this case I believe that it is not legitimate to confine the scope of the claims, particularly the meaning of the word “and”, by reference to limitations which from the body of the specification that are not expressly or by proper inference reproduced in the claims themselves. In the present instance, I do not believe it is appropriate to alter the plain meaning of the word “and” in the present claims based on anything contained in the description.
It is clear from a reading of the description that the present invention is a therapy involving the use of (at least) two active substances whose biological effects must both be present during the treatment period. That is, the substances are administered “in association”. This should not be taken to mean physical association of the two active components when they are administered, although that is clearly acceptable, but, relates to the combining of the biological effects of the active substances. The independent claims, in that they use the word “and”, are not expressly nor by proper inference limited to this situation. They include the possibility of serial administration of the active components, without any limitation to the association of action, which is not an aspect of the present invention.
Independent process claims 1 to 4 do not define the invention since they are not limited to the administration of an androgen receptor antagonist in association with either a 5a-reductase, 17b-HSD or 3b-HSD inhibitor.
Section 40 (3)
Mr Franklin submitted that claims 10-14 are not fairly based on the specification since:
a method of manufacturing the particular medicaments of claims 10 and 11 is not broadly described;
there are statements in the specification which are inconsistent with a method of manufacturing a medicament using a 5a-reductase inhibitor and an androgen receptor antagonist;
the specification is silent as to the use of an androgen receptor antagonist and a 5a-reductase inhibitor in the manufacture of a medicament.
Ms Tate, for the applicant, submitted that:
the claims are fairly based on the description;
the specification does contain a proper disclosure of the best method of performing the invention, eg page 8 last paragraph;
it was not necessary for the applicant to describe all possible variations on an integer of an invention claimed;
all of the essential features of the claims have been described and the opponent appears to be covertly making an objection based on lack of utility which it is not entitled to do under section 59.
The lack of fair basis allegation rests strongly on the assertion that the specification does not specifically contain a sufficient description of manufacturing medicaments containing both a 5a-reductase inhibitor and an androgen receptor antagonist and that these two active substances can be administered separately. I have to agree with the statements of Ms Tate for the applicant that there appears to some extent to be an assertion of inutility against the current invention, which is not a ground of opposition. The specification is not silent in relation to 5a-reductase inhibitors nor in relation to androgen receptor antagonists. The opponent’s point rests on the fact that no combined medicament of these two active substances is specifically described as such.
The manufacture of medicaments containing 5a-reductase inhibitors and/or androgen receptor antagonists is, from my reading of the specification and evidence, a relatively straightforward matter. The specification contains specific data in relation to the compounds to be used, dosage rates, administration protocols etc which would be sufficient for the skilled worker to perform the invention. I believe this constitutes a broad description of the invention of claims 10-11.
To say that the description is inconsistent with, or silent in relation to, medicaments containing both a 5a-reductase inhibitor and an androgen receptor antagonist is, I believe, to read the specification with studied criticality. I do not believe it is of significance, in the present case, that different active constituents might be physically administered separately to other active constituents. Medicaments using various active substances may well be formulated for separate administration of the active substances depending upon optimum dosage frequency for the constituent parts. The specification clearly indicates 5a-reductase inhibitors can be administered on a different frequency of administration to the other components. As I have referred to above, the crucial point is that there be an association of the biological action of the active substances.
I believe the specification contains a real and reasonably clear disclosure of the invention of claims 10-14. “Swiss-style” claims 10-14 are fairly based.
CONCLUSION
The invention as defined by the claims is a manner of manufacture, is novel and fairly based on the description.
The claims do not define the invention since they are not limited to the administration of an androgen receptor antagonist in association with either a 5a-reductase, 17b-HSD or 3b-HSD inhibitor.
Claims 1, 2, 5, 6, 7, 9 (in part), 10, 11, 15, 16 & 19-20 (in part) which relate to the use of a 5a-reductase inhibitor and an androgen receptor antagonist lack an inventive step in light of opposition exhibits JJG6 and JJG10 separately.
Claims 3, 4, 9 (when appended to either claim 3 or 4), 12-14, 17, 18 and 21-23 are non-obvious and involve an inventive step.
There is patentable subject matter in the opposed specification. I allow the applicant 60 days from the date of this decision to propose suitable amendments.
COSTS
In actions before the Commissioner, costs normally follow the event. Significant amendments to the accepted specification, either as a direct or indirect result of the present opposition, have been proposed by the applicant. The opponent has been successful in relation to the ground of obviousness in this decision. Consequently, I award costs in accordance with Schedule 8 against the applicant Endorecherche Inc.
V. J. Portelli
Delegate of the Commissioner of Patents
Patent attorneys for the applicant : Griffith Hack, Sydney
Patent attorneys for the opponent : Spruson & Ferguson, Sydney
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