Novogen Research Pty Ltd v G.J. Consultants Pty Ltd
[2008] APO 24
•16 September 2008
ABSTRACTS OF DECISIONS
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Application : No. 777324 in the name of G. J. Consultants Pty Ltd
Title: “Isoflavone Metabolites”
Action: Opposition to the grant of a patent under section 59 and a request for a determination of the Commissioner under section 32 by Novogen Research Pty Ltd
Decision: Issued 16 September 2008.
Abstract
The invention relates to isoflavonoid compounds containing vicinal diol moieties and their use in the treatment of various diseases. The present dispute has its origin in a consultancy arrangement between Novogen and the inventor Dr Joannou that commenced in 1995 and was terminated in December 1998 by execution of a Termination and Option agreement. The opponent claimed that the invention was conceived during the consultancy agreement and as a consequence they were the sole person eligible for the grant of the patent. In response the applicant submitted that the invention was made after the termination of the agreements. On that basis they claimed the opponent had no entitlement to the invention. The parties did not dispute that Dr Joannou was the sole inventor.
The evidence establishes that the key compound 5-OH-O-Dma (compound A) which comprises vicinal diol groups was conceived during the period of the consultancy arrangement. Two further isoflavone compounds having vicinal diol groups were also conceived prior to the execution of the Termination and Option agreement. Furthermore the compounds were conceived in the context of a project, and inform of a broader class of compounds having vicinal diol groups in the benzo ring of isoflavone (and their analogues and derivatives). I therefore consider that Novogen is entitled to this matter.
However, Novogen is not entitled to the invention in respect to compounds having vicinal diol groups on the 3-phenyl ring (and their analogues and derivatives). Accordingly the application has been directed to proceed jointly in the names of Novogen Research Pty Ltd and G. J. Consultants Pty Ltd. This direction will take effect once the time for seeking review before the AAT has expired and no application for review of the decision has been made.
As the opponent has been successful in its opposition, costs are awarded against the applicant, G.J. Consultants Pty Ltd.
PATENTS ACT 1990
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Re:Patent Application No. 777324 by G. J. Consultants Pty Ltd. Opposition to the grant of a patent under section 59 and a request for a determination of the Commissioner under section 32 by Novogen Research Pty Ltd
BACKGROUND
Patent application 777324 in the name of G. J. Consultants Pty Ltd (hereinafter the Applicant) was advertised accepted on 14 October 2004. A Notice of Opposition under section 59 was filed on 14 January 2005 by Novogen Research Pty Ltd (hereinafter the Opponent). A Statement of Grounds and Particulars was filed on 14 April 2005. The sole ground of opposition related to entitlement. The Opponent subsequently made a request for a determination of the Commissioner under section 32 on 18 October 2005. Pursuant to a request by the applicant, evidence in support of the section 59 opposition was directed to also constitute evidence for the purposes of the section 32 determination.
The hearing in relation to both matters was held in Sydney on 16 June 2008. Mr Christian Dimitriatis of Counsel, appeared for the applicant. Mr George Patrinos and the inventor and owner of G. J. Consultants Pty Ltd, Dr George Joannou, also attended for the applicant. Ms Katrina Howard, Senior Counsel, assisted by Dr Ross Heisey of Davies Collison Cave appeared for the opponent. Dr Joanna Jones of Davies Collison Cave, and Ms Georgia Marshall and Ms Deborah Roach of Blake Dawson also attended for the opponent.
THE EVIDENCE
Evidence in support was completed on 1 February 2006 and comprised the following declarations:
(a) Dr H. Ming Williams dated 16 September 2005 (Williams 1);
(b) Dr Chris Naughton dated 7 October 2005; and
(c) Ms Gail Sukadana dated 31 January 2006.
Evidence in answer was completed on 31 January 2007, and comprised the following declarations:
(a) Dr Anthony Reeder dated 25 January 2007; and
(b) Dr George Eustace Joannou dated 29 January 2007 (the Joannou declaration).
Evidence in reply was completed on 31 January 2008 and comprised the following declarations:
(a) Mr Benjamin Lee Miller dated 16 January 2008;
(b) Alan Scott dated 28 December 2007;
(c) Dr Williams dated 23 January 2008 (Williams 2); and
(d) Dr Andrew Heaton dated 21 January 2008.
THE SPECIFICATION
Isoflavones are a class of predominantly plant-derived phytoestrogens which possess a range of biological activities, including oestrogenic, anticarcinogenic, antifungal, antiproliferative and anti-oxidative activity. Legumes, and particularly soybeans, lentils, clover, chick peas and alfalfa, are a particularly rich source of the oestrogenic isoflavones genistein, biochanin, daidzein, glycitein and formononetin. These generally exist in glycosidic forms that undergo various metabolic processes after ingestion, including hydrolysis (to provide aglycones), hydroxylation and demethylation. Aglycones undergo microbial fermentation in the gut to produce bioactive metabolites such as equol, dehydroequol, O-desmethylangolensin, dihydrodaidzein, tetrahydrodaidzein and dihydrogenistein.
In vitro microbial fermentation of soybeans has also been widely used to obtain various isoflavone metabolites. Of particular relevance to the present case are the studies of Gyorgy et al. [Nature (1964) 203, pp. 870-872] and Klus et al. [Arch. Microbiol., 164:428-434, (1995)], which describe the formation of polyhydroxylated isoflavones during the traditional tempeh fermentation of soybeans. These include a metabolite referred to as factor 2, which contains vicinal diol groups (that is, adjacent carbon atoms in a ring are substituted by hydroxyl groups).
Factor 2The invention is said to provide novel isoflavonoid compounds for use in treating hormone dependent conditions. Specifically, the invention (as defined in Claim 1) relates to isoflavonoid compounds containing vicinal diol moieties in either or both of the benzo or 3-phenyl rings. These compounds have the following formula (the first being referred to hereinafter as the isoflavone ring form, and the second as the open-ring analogues):
or
(isoflavone ring form) (open-ring form)
in which the fused ring A is selected from one of the following moieties:
where: one of R1 and R2 is selected from H, OH and OCH3, and the other of R1 and R2 is selected from OH and OCH3;
one of R3 and R4 is selected from H, OH and OCH3, and the other of R3 and R4 is selected from OH and OCH3;
provided that at least one of the pairs R1, R2 and R3, R4 are both OH;
R5 is selected from OH and OCH3; and,
the dotted bond may be a single or double bond;
or a pharmaceutically acceptable salt or prodrug thereof, but provided that:
(a) when A is
and R3 and R4 are both OH, then R2 is other than H;(b) when A is
and R3 and R4 are both OH and R2 is OCH3, then R1 is other than H or OCH3.
I note that the present claims essentially comprise two separate, but related combinations: firstly, isoflavone derivatives comprising vicinal diol groups on the benzo ring (that is, R3 and R4 are both OH); and secondly, isoflavone derivatives which comprise vicinal diol groups on the 3-phenyl group (that is R1 and R2 are both OH).
Various compositions comprising the compounds of the invention are also described. These include typical pharmaceutical compositions with pharmaceutically acceptable carriers, adjuvants, diluents, and excipients, as well as food and drink compositions. Compositions comprising a microbial culture that is capable of producing the compounds of the invention from daidzein and/or glycitein form a further aspect of the invention.
The compounds are said to be useful in the treatment of a wide range of diseases, including: menopausal syndrome (including depression, anxiety, hot flushes, night sweats, mood swings, and headache); osteoporosis; rheumatic diseases; atherosclerosis; premenstrual syndrome (including fluid retention, cyclical mastalgia, and dysmenorrhoea); coronary artery spasm; vascular diseases (including Reynauds Syndrome); Buergers Disease; migraine headaches; hypertension; benign prostatic hypertrophy; “all forms” of cancer (including breast cancer, endometrial cancer, prostatic cancer, uterine cancer, ovarian cancer, testicular cancer, large bowel cancer); Alzheimers disease; inflammatory diseases (including Crohns disease, inflammatory bowel disease and ulcerative colitis); baldness (including male pattern baldness); psoriasis; acne; and diseases associated with oxidant stress (including myocardial infarction, sunlight induced skin damage, arthritis, or cataracts).
The specification goes on to describe several specific examples of the invention. Example 4 describes a compound having an isoflavone ring system, while Examples 1, 3, 5 and 6 are open-ring analogues. The compounds of Examples 3, 4 and 5 possess R1 and R2 as hydroxy while the compounds of Examples 1 and 6 have R3 and R4 as hydroxy. Example 2, which contains an isoflavone ring system, is excluded from the claims by proviso (a). Examples 7 to 11 describe various bioassays, including assays of MCF7 (estrogen-positive) and MDA-MB-468 (estrogen-negative) breast cancer cells.
BASIS OF THE DISPUTE
The present dispute has its origin in a collaborative arrangement between Novogen and Dr Joannou (the inventor) that formally commenced in 1995 and eventually terminated in December 1998.
In 1985 Dr Joannou and Dr Graeme Kelly began collaborative research on the analysis of equol (a phytoestrogen) in the urine of humans and animals. This work was expanded to the analysis of other urinary phytoestrogens and resulted in the publication of several papers, including a key paper in the present dispute: “A Urinary Profile Study of Dietary Phytoestrogens. The Identification and Mode of Metabolism of New Isoflavonoids”, J. Steroid Biochem. Molec. Biol., 54(3/4), 1995, pp. 167-184 (hereinafter “Joannou et al. 1995”). This paper described the metabolic fate of dietary isoflavones daidzein and genistein in humans. A number of metabolites were identified by gas chromatography and mass spectrometry, including 6-hydroxy-O-demethylangolensin (6-OH-O-Dma) and 2-dehydro-O-demethylangolensin (2-dehydro-O-Dma).
6-OH-O-Dma 2-dehydro-O-Dma
In September 1995 Dr Kelly approached Dr Joannou to become a consultant to Novogen (at that time named Norvet) and to be involved in further investigation of the compounds described in the Joannou et al. 1995 paper. Dr Joannou agreed, and a formal consultancy agreement commenced on 1 November 1995 (hereinafter the “1995 consultancy agreement”). Agreements relating to confidentiality and royalties were also executed by the parties.
The consultancy was initially limited to 130 hours for an initial term of one year, and required the following services of Dr Joannou:
“(1)To advise Company and the Norvet Group as required on matters of either a general or specific nature as follows:
(1) research in the areas of but not limited to steroids, phytoestrogens, their derivatives and metabolites;
(2) assist with the chemical recovery, isolation, identification and synthesis of these products as well as qualitative and quantitative analysis of biological and chemical samples; and
(3) provide 20 GCMS assays.
(2) To contribute to the Norvet Scientific Advisory Panel as and when requested.”
The collaboration resulted in the filing of a patent application by Novogen (PCT Application WO 1998/08503). This application included compounds from the Joannou et al. 1995 paper as preferred embodiments, as well as disclosing a broader Markush structure of analogues and derivatives of the metabolites. There is no question concerning the ownership of the compounds described in that patent.
As noted above, the 1995 consultancy agreement had an initial term of one year. However, the agreement provided that “[A]t the expiration of the Initial Term the Term will continue until the expiration of the period of notice, being not less that one month, of termination of the engagement given by either party to the other”. Pursuant to this clause, the consultation agreement continued until notice of termination was provided by a letter from Novogen dated 27 February 1998. The consultancy agreement was subsequently terminated on 31 March 1998. Apparently “protracted” discussions between Dr Joannou and Novogen continued after this time, but ultimately on 22 December 1998 the parties executed a Termination and Option Agreement which terminated all agreements between the parties.
At hearing the parties did not dispute that Dr Joannou was the sole inventor, and there was general agreement that Novogen had entitlement to any invention conceived prior to the execution of the Termination and Option agreement. Thus the key point of dispute concerns when the invention was conceived. In order to clarify events, I will refer to the declarations by the inventor Dr Joannou; Dr Williams, who worked under Dr Joannou’s direction between June 1996 and April 2001 at RAHC; and Dr Reeder, who worked under Dr Joannou’s direction at RPAH until April 1993 and subsequently provided mass spectrometric analysis of compounds and mixtures made in the Joannou laboratory (including the period 1998 to 2000).
I note that Dr Joannou commented in evidence about shortcomings in Dr Williams’ record keeping and her level of proficiency in the English language. He referred to a breakdown in communication between he and Dr Williams that he attributed to her dissatisfaction with providing detailed Progress Reports, and which eventually led to mediation between the two in July 1999. At hearing the applicant further highlighted what they considered were several “errors and inconsistencies” in Dr Williams’ evidence, including the absence of any reference to a key paper until after Dr Joannou’s reference to it in evidence in answer and the failure by Dr Williams to set out the difficulties she had with Dr Joannou.
I do not consider these matters give rise to any significant concerns over the veracity of Dr Williams’ evidence. Given the length of time that has passed since the events set out in evidence it is not unexpected that there would be some minor inconsistencies or errors in evidence. Moreover, Dr Williams’ evidence is essentially a statement of her recollection of when experiments were carried out in the Joannou laboratory. I also note that Dr Williams has no connection with the opponent and no other interest in the matter. Accordingly, I am satisfied that any difficulties between Dr Joannou and her were of little relevance to that evidence and on that basis were not included in Dr Williams’ statement. Nevertheless, where necessary I have attempted to verify the statements of both parties with supporting evidence.
RELEVANT EVENTS IN THE JOANNOU LABORATORY
Dr Williams stated that her role was to design, synthesise and characterise isoflavone compounds, including compounds described in the Joannou et al.1995 paper (Williams 1 at paragraph 2). She also stated that she supervised the work of another chemist, Peter Mitchell. Dr Joannou disputed the latter statement, asserting that Mr Mitchell reported directly to him and not to Dr Williams. However, I note that in an email to Dr Williams on 5 May 1999 (page 210 of Annex GEJ-2 in the Joannou declaration) Dr Joannou wrote “[P]lease I would appreciate it if you could sort out these samples as you were acquainted with his work.” Accordingly, I am satisfied that even if Dr Williams did not directly supervise Mr Mitchell, she is in a position to comment on the nature and direction of his work.
The Joannou et al. 1995 paper described a number of metabolites including one which was tentatively identified as 6-OH-O-Dma based primarily on its mass spectra. The Joannou laboratory began studies on this compound in late 1997 (Williams 1 at paragraph 6), and subsequent comparison with a commercial sample established that the tentative identification of the metabolite as 6-OH-O-Dma in the Joannou et al. 1995 paper was incorrect. Dr Joannou considered that the metabolite could alternatively be the isomeric compound 5-OH-O-Dma (compound A), and informed Novogen of this hypothesis during meetings on 27-28 February and 10 March 1998 (Joannou declaration at paragraph 127).
Compound A
Dr Joannou recalled that Novogen categorically rejected any further work on the phytoestrogens project as they considered that it had been completed and were no longer interested in continuing research on the metabolism of isoflavonoids. This was confirmed in a meeting of 23 March 1998 (Joannou declaration at paragraph 129). Dr Joannou stated that:
“[f]ollowing the termination of my consultancy with Novogen on 31 March 1998, I resolved to seek out new material for further publications. One avenue I thought of was to try and sort out some of the questions that remained unanswered in the 1995 Paper, being the identity and origin of the compounds mischaracterised as 5-OH-O-Dma and 2-dehydro-O-Dma in the paper. I regarded myself as being at liberty to investigate these areas in my own research, particularly given the comments made by Dr Kelly and Mr Naughton at the meetings referred to above” (Joannou declaration at paragraph 130).
Dr Williams stated that she and Mr Mitchell were asked by Dr Joannou to synthesise compound A. She claimed that the two methods described in Example 1 for the synthesis of compound A of the present specification were developed by Mr Mitchell, and recalled that the work was completed by March or April 1998 (Williams 1 at paragraph 10). Dr Joannou disputed this statement, asserting that he had instructed Mr Mitchell only, and not Dr Williams, to prepare compound A (Joannou paragraph 70). Furthermore, he had no record of Mr Mitchell’s results and had not been provided with a sample that could enable analytical or biological testing to be carried out (Joannou paragraph 73). Nevertheless he recalled that by late May to early June 1998 Mr Mitchell had carried out a synthesis which provided a number of products, one of which gave GC data that was in agreement with that published for 6-OH-O-Dma in the Joannou et al.1995 paper (Joannou declaration at paragraph 73). Dr Williams later repeated the synthesis of compound using Mr Mitchell’s method. This was completed on 21 December 1998 but Dr Joannou stated that he did not receive this sample until after execution of the Termination and Option agreement (Joannou declaration at paragraph 49).
In order to determine when compound A was first prepared, the opponent referred to a data sheet for compound A with the annotation “PM#2-011” (this being a reference to Peter Mitchell’s laboratory notes) which referred to a GC trace numbered “#1645”. Cross reference to a second GC trace numbered 1840 and dated 17 March 1998 indicated that Mr Mitchell had completed the synthesis of compound A prior to that date. Apparently GC traces are sequentially numbered and up to 10 may be performed daily, which would suggest that the trace numbered #1645 was run by at least late February 1998 (Williams 2 at paragraph 22). This suggests that Mr Mitchell first prepared compound A around that time.
In July 1998, Dr Williams also attempted to prepare two further compounds containing vicinal diol groups via a “multi-product procedure”: 2-dehydro-5-OH-ODma (Example VIII of the present application) and dihydrofactor-2 (Example III of the present application). Compound A was apparently also obtained by the reaction (Williams 2 at paragraph 27).
2-Dehydro-5-OH-ODma Dihydrofactor-2
Dr Joannou stated that the sample of dihydrofactor-2 obtained by Dr Williams from the multi-product procedure used in 1998 was in fact a brominated derivative. This was identified with the assistance of Dr Reeder in 1999. Reaction conditions were subsequently modified in September 1999 to obtain the desired isoflavonoid derivatives, including dihydrofactor-2. Example 6 of the present application describes the multi-product procedure. Dr Joannou also claimed that samples of compounds A and 2-dehydro-5-OH-ODma obtained by Dr Williams in July and September 1998 showed no activity in biological testing, while later tests on different samples showed a high level of activity. He attributed the lack of activity to the samples being the wrong compounds or the presence of impurities that interfered with the biological assay (Joannou declaration at paragraphs 83 to 86).
Following the execution of the Termination and Option Agreement on 22 December 1998, Dr Joannou holidayed in New Zealand before returning to Australia in the first week of January 1999. He set about conducting literature searches in order to develop a new direction for his research, and focussed on microbial transformation of isoflavonoids. It was as a result of this line of research that he first became aware of the Klus et al. paper, which described the formation of metabolites comprising vicinal diol groups via microbial transformation of isoflavonoids (including the isoflavone “Factor 2”). The Klus et al. paper suggested that the vicinal diol groups imparted a pronounced antioxidant activity on the metabolites (Joannou declaration paragraphs 30 to 37).
Dr Joannou stated that it was as a result of reading the Klus et al. paper that he recognised that isoflavonoids containing vicinal diol groups could provide a valuable new avenue of investigation. He claimed to have realised that the microbial strains described in the Klus et al. paper had the potential for use in probiotics to enhance isoflavone metabolism in order to combat hormonal disorders and to transform metabolically unwanted dietary isoflavones into other compounds that may be beneficial. He also considered the vicinal diol groups would enhance pharmacokinetics and could provide a site for derivatives and complexes that would assist targeted drug delivery.
On 12 January 1999 Dr Joannou retained Spruson & Ferguson to conduct searches to determine whether any patents had been filed by the authors of the Klus et al. paper. This search was completed on 14 January 1999. He subsequently set about gathering data for a patent application by synthesising a number of isoflavonoids containing vicinal diol groups and testing them for biological activity. A provisional application was filed on 30 April 1999 which described biological activity for two compounds having vicinal diol groups: Compound A and factor-2. The present application was filed on 1 May 2000.
At hearing the opponent questioned the veracity of Dr Joannou’s version of events concerning the conception of the invention. They particularly questioned whether conception of the invention, reduction to practice and filing of the provisional patent application could occur in a period of about 10 weeks, particularly in view of Dr Joannou’s statements concerning the difficulties in obtaining suitable samples for testing prior to December 1998. However, the applicant stated that the synthetic methods were based on known methods which were not in themselves inventive, and the information provided by Klus apparently enabled the invention to be reduced to practice in that timeframe. I note that Klus does not appear to provide any synthetic methods for the preparation of factor 2 (or indeed any other isoflavones such as the hydrogenated analogues of the present invention), but the applicant submitted that once the structure of Factor-2 was known it was routine chemistry to obtain the compounds of the invention.
DECISION
Relevant Law
The relevant law is set out by Sections 59 and 32 as follows:
59Opposition to grant of standard patent
The Minister or any other person may, in accordance with the regulations, oppose the grant of a standard patent on one or more of the following grounds, but on no other ground:
(a)that the nominated person is either:
(i) not entitled to a grant of a patent for the invention; or
(ii) entitled to a grant of a patent for the invention but only in conjunction with some other person…
32Disputes between applicants etc.
If a dispute arises between any 2 or more interested parties in relation to a patent application whether, or in what manner, the application should proceed, the Commissioner may, on a request made in accordance with the regulations by any of those parties, make any determinations the Commissioner thinks fit for enabling the application to proceed in the name of one or more of the parties alone, or for regulating the manner in which it is to proceed, or both, as the case requires.
In oppositions under section 59 the onus is on the opponent to establish that the patent, if granted, would be clearly invalid [F. Hoffmann-La Roche AG v New England Biolabs, Inc. (2000) 99 FCR 56]. Ultimately, Novogen bears the onus of proof in establishing that they have entitlement. However, in making a determination under section 32 I am entitled to act on any material which is “logically probative” and the standard of proof required is the civil standard of proof on the balance of probabilities [Dunlop Holdings Ltd's Application, (1979) RPC 523].
I also note that oppositions under section 59 may be made by the “Minister or any other person” while under section 32 a direction may only be requested by an “interested party”. At hearing the applicant submitted that the parties to the Termination and Option Agreement were the inventor, Dr George Joannou, and Novogen Ltd (the parent company of the opponent). They argued that the present opponent (Novogen Research Pty Ltd) was not a party to the agreement, and therefore was not an “interested” party who could request a direction pursuant to section 32. However Schedule 1 of the Patents Act defines an “interested party” to be the applicant or a joint applicant, or a person who claims to be entitled to the grant of a patent on the application, either alone or jointly with another person. Accordingly, as the opponent claims to be entitled to the grant of the patent, I am satisfied that they are an interested party according to the Act.
Entitlement and inventorship have been the considered in a number of decisions, but two timely Federal Court decisions have provided some valuable guidance for considerations such as this: University of Western Australia v Gray [2008] FCA 498 and Polwood Pty Ltd v Foxworth Pty Ltd [2008] FCAFC 9. Furthermore, a recent Patent Office decision (The Commonwealth of Australia v John Murray Charlesworth [2008] APO 16) involved an entitlement dispute where, like the present case, inventorship was not in dispute but rather whether the invention was conceived during a period covered by an agreement between the parties. Following the guidance provided by UWA v Gray, the delegate applied the following principles:
(i)Identify the "inventive concept" of each relevant invention as defined by the claims.
(ii)Determine inventorship including the person responsible for the inventive concept and the time of conception as distinct from its verification and reduction into practice.
(iii)Determine if contractual or fiduciary relationships between the parties at the time of the inventorship give rise to the proprietary rights claimed by the opponent.
As noted by French J in UWA v Gray (at 1426), the inventive concept marks the boundary between invention and verification. Thus, inventorship ends at the time of conception and is distinct from verification and reduction to practice. He referred to the following principles as established by US appellate courts:
- “Conception is the touchstone of inventorship, the completion of the mental part of inventions.
- Conception is the “formation in the mind of the inventor of a definite and permanent idea of the complete and operative invention as it is hereafter to be applied in practice”. It is complete only when the idea is so clearly defined in the inventor’s mind that only ordinary skill would be necessary to reduce the invention to practice without extensive research or experimentation.
- An inventor need not know that the invention will work for conception to be complete. The inventor need only show that he or she had the idea. The discovery that an invention actually works is part of its reduction to practice.
- It is not the law that the inventor’s definite and permanent idea must include a reasonable expectation that the invention will work for its intended purpose even when it deals with uncertain or experimental disciplines where the inventor cannot reasonably believe that an idea will be operable until some result supports that conclusion.”
Furthermore, in Polwood v Foxworth (at 41) the court noted that in determining inventorship ‘what one is normally looking for is “the heart” of the invention. There may be more than one “heart” but each claim is not to be considered as a separate “heart” on its own’ (per Jacob LJ in Markem Corp.v Zipher Ltd [2005] All ER 377). The opponent noted that Delegates of the Commissioner have previously taken such an approach to determining inventorship by focussing on the “key inventive concept” or “heart” of the invention disclosed in the application (see for example Iluka Midwest Ltd v Wimmera Industrial Minerals Pty Ltd (2001) 55 IPR 140).
The opponent submitted in this regard that the “heart” of the present invention lay in the identification and synthesis of compound A, which they claimed was conceived during the period of the consultancy. They referred to the principles laid out in Kimberly-Clark Australia Pty v Arico Trading Pty Ltd [2001] 207 CLR 1 (at 21) wherein it was stated that “the invention” is the “embodiment around which the claims are drawn”. They argued that compound A could be considered the “heart” of the invention and as a consequence the point at which this compound was conceived was the point at which the underlying inventive concept of the invention came into existence.
The applicant submitted that the inventive concept did not lie only in the structure of the compounds (and particularly the structural feature of vicinal diol groups), but also in the identification of the link between the vicinal diol groups and biological activity. This link was not formed until after the discovery of the Klus et al. paper by Dr Joannou, which they considered represented the earliest possible identification of the inventive concept. They argued that a single compound alone cannot inform of a class of compounds. Thus the “heart” of the present invention did not lie in the identification of a single compound having vicinal diol groups (compound A), but in identifying the structural features of the class that gave the “whole” of the invention. The applicant further argued that the improved activity profile of the compounds should be viewed as being relevant to the invention since mere speculation of an activity from a proposed structure was not sufficient.
In determining the present matter, I particularly note the statements of French J in UWA v Gray at [1440] (discussing Polwood v Foxworth):
“Their Honours referred to the discussion of inventive concept in Gunter v Stream 573 F 2d 77 (1978), where the “conception” of the invention was described as the complete performance of the mental part of the inventive act. That is to say the invention is the formation in the mind of the inventor of a definite and permanent idea of the complete and operative invention as it is thereafter to be applied in practice: see also Burroughs Wellcome (1994) 40 F 3d 1223 cited above. What remains belongs in the department of construction. A concept can be complete although experimentation may continue. It is complete when a person of ordinary skill in the art could construct the apparatus without unduly extensive research of experimentation.”
I consider that there are several key principles that underpin conception of an invention in chemistry. Firstly, a “complete and operative” invention in the chemistry field requires a fully defined compound (or compounds) to have been formulated, even if only in an abstract form, by the inventor. In this regard, the mere identification of a structural element in isolation (such as vicinal diol groups) is not sufficient to constitute the conception of a chemical invention.
Secondly an operative means of preparing the compounds must be envisaged, but not necessarily actually carried out (this would constitute a reduction to practice). Thirdly, a chemical compound without a use is a mere discovery or curiosity and does not constitute patentable subject matter, but will represent an invention when a practical or commercial use has been identified. However, it is not necessary for biological activity to actually be demonstrated in order for the invention to be conceived provided there is that “definite and permanent idea” that the compound will have the particular activity. As noted in UWA v Gray (supra), an inventor need not know that the invention will work for conception to be complete. The subsequent confirmation that an invention actually works (or in this case, actually possesses the predicted activity) is part of its reduction to practice.
In the present case, the evidence shows that compound A was “hypothesised” by Dr Joannou by at least 10 March 1998 (when Dr Joannou informed Novogen of his hypothesis), and furthermore evidence in relation to the GC traces indicates that an operative means of preparation existed and the compound was made (even if only in an impure form) prior to 17 March 1998. The applicant submitted that the development and synthesis of compound A was in the nature of a different problem, namely the mischaracterisation of a compound in the 1995 Joannou et al. paper, and this was in the nature of an academic exercise for the purpose of publishing papers, rather than for the purposes of identifying therapeutically useful compounds. However, I note that compound A was conceived under the consultancy agreement, and particularly in the context of the Novogen phytoestrogen project. That project was specifically intended to identify useful biological activities for isoflavone metabolites from the 1995 Joannou et al. paper, including the activities described in the present application, and was not in the nature of an academic investigation of isoflavone metabolites. Accordingly I consider that compound A, its preparation, and its biological activity was conceived prior to execution of the Termination and Option agreement.
In addition, the compounds dihydrofactor-2 and 2-dehydro-5-OH-ODma are two further analogues which were also specifically made prior to execution of the Termination and Option agreement. While dihydrofactor-2 may not have initially been obtained by the reaction and was not actually obtained until the reaction conditions were changed, Dr Joannou stated (paragraph 49 of the Joannou declaration) that the synthetic methods for the preparation of the compounds of the invention are based on literature techniques which “are not in themselves claimed to be inventive”. It follows that the difficulties encountered during the “multi-product procedure” and other difficulties associated with obtaining sufficiently pure samples were not in the nature of invention, but rather of routine experimentation to determine optimal reaction conditions. Thus identification of the compounds themselves and an operative means of preparing them could be considered sufficient for conception.
Furthermore, isoflavone metabolites are known to possess estrogenic activity and the conception of compound A identified a new substitution pattern within that class of compounds. The “heart” of the invention, or key inventive concept, lay in this new substitution pattern in estrogenic isoflavone metabolites. The identification of similarly substituted derivatives (dihydrofactor-2 and 2-dehydro-5-OH-ODma) provided a range of compounds across, and informs of, a broad class as defined in the present claims. I note that this class closely correlates with the broad class of isoflavones determined as part of the phytoestrogen project and given in the Markush structure shown in the Novogen patent application (absent the vicinal diol groups). It may be that Dr Joannou subsequently considered on reading the Klus et al. paper that vicinal diol groups might impart some particularly advantageous properties on isoflavones, but there was no evidence provided of any such advantage and in any case the underlying biological activities were already known from the phytoestrogen project.
As a consequence, I consider that the key inventive concept relating to isoflavones having vicinal diol groups in the benzo ring (that is, those defined by the present claim in which R3 and R4 are hydroxy) was conceived prior to the execution of the Termination and Option agreement. However, I note that no submissions were made in respect of compounds having vicinal diol groups in the 3-phenyl ring (that is, where R1 and R2 are both hydroxy), and I do not consider this matter to be in dispute. In any case there is no evidence to suggest that the inventive concept relating to this matter was conceived during the consultancy agreement, and these were not compounds that were described in the 1995 Joannou et al. paper. Prima facie this constitutes a separate inventive concept for which Novogen can claim no entitlement.
Contractual relationships between the parties
The applicant’s submissions were predicated on conception of the invention occurring after execution of the Termination and Option agreement on 22 December 1998. As noted above I consider that the inventive concept was conceived prior to that date. However the applicant argued that the wording of the Termination and Option agreement was such that Novogen had no rights in the invention. In particular, they argued that the agreement required that there must at least have been a patent, a right in respect of a patent application, a patentable invention or a right to apply for registration of a patent as at the relevant date of 22 December 1998 for Novogen to be entitled. They claimed that this was not the case.
I do not find the applicant’s submissions persuasive in this regard as a patentable invention, which could indeed be as simple as a single compound but as noted above included a broader class of compounds, was created prior to 22 December 1998. Accordingly, I consider a patentable invention was created prior to the execution of the Termination and Option agreement and the applicant’s submissions in this regard fail.
CONCLUSION
I have found above that the inventive concept relating to isoflavones having vicinal diol groups in the benzo ring (where R3 and R4 are both hydroxy) was conceived prior to 22 December 1998, and that Novogen has entitlement to this matter. The opponent is therefore successful in their opposition to the grant of the patent.
However, Novogen is not entitled to the invention in respect to compounds having vicinal diol groups on the 3-phenyl ring (where R1 and R2 are both hydroxy). Accordingly under section 32 I direct that the application proceed jointly in the names of Novogen Research Pty Ltd and G. J. Consultants Pty Ltd. Once this direction takes effect the grounds of refusal pursuant to the opposition under section 59 will also be overcome.
Decisions under section 32 are reviewable by the Administrative Appeals Tribunal (AAT). Accordingly, I state that the direction will not come into effect until the time for seeking review before the AAT has expired and no application for review of the decision has been made.
COSTS
Both parties submitted that costs should follow the event. The power to award costs is based on section 210 and regulation 22.8. As the opponent has been successful in their opposition I award costs in accordance with Schedule 8 against the applicant G. J. Consultants Pty Ltd.
Leslie F. McCaffery
Delegate of the Commissioner of Patents
16 September 2008
Patent attorneys for the applicant : None
Patent attorneys for the opponent : Davies Collison Cave, Sydney
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