Sun Pharmaceutical Industries (Australia) Pty Ltd v Tasmanian Alkaloids Pty Ltd

[2018] APO 7

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Sun Pharmaceutical Industries (Australia) Pty Ltd v Tasmanian Alkaloids Pty Ltd

[2018] APO 7

Patent Application:                2009253741

Title:Papaver somniferum with high concentration of codeine

Patent Applicant:                   Tasmanian Alkaloids Pty Ltd

Opponent:  Sun Pharmaceutical Industries (Australia) Pty Ltd

Delegate:  Dr S. J. Smith

Decision Date:  31 January 2018

Hearing Date:  14 June 2017 in Canberra

Catchwords:  PATENTS – opposition to the grant of a patent – grounds of utility, manner of manufacture and inventive step – not established that claims do not achieve the promise of the invention – lack of utility ground unsuccessful – not established that the claims encompass naturally-occurring subject matter – manner of manufacture ground not successful – inventive step – expectation of success not established – inventive step ground not successful – costs awarded against opponent

Representation:  Counsel for the applicant: Ms Katrina Howard SC

Patent attorney for the applicant: Dr Charles Tansey of Shelston IP

Counsel for the opponent: Mr Ben Fitzpatrick

Patent attorney for the opponent: Dr Mark Wickham and Mr David Longmuir of Phillips Ormonde Fitzpatrick

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Patent Application:                2009253741

Title:Papaver somniferum with high concentration of codeine

Patent Applicant:                   Tasmanian Alkaloids Pty Ltd

Date of Decision:                   31 January 2018

DECISION

The opposition is unsuccessful.  Subject to appeal of this decision or TPI Enterprises Ltd v Tasmanian Alkaloids Pty Ltd [2018] APO 8 I direct that the application proceed to grant.

I award costs according to Schedule 8 against Sun Pharmaceutical Industries (Australia) Pty Ltd.

REASONS FOR DECISION

Background

1. Patent application 2009253741 was filed by Tasmanian Alkaloids Pty Limited (TasAlk) on 28 May 2009 under the provisions of the Patent Cooperation Treaty.  The application claims priority from US 61/056,880, US 61/160,532 and US 61/160,749, which were filed on 29 May 2008, 16 March 2009 and 17 March 2009, respectively.

2. Acceptance of the application was advertised on 11 June 2015.  Sun Pharmaceutical Industries (Australia) Pty Ltd (Sun) filed a notice of opposition under section 59 on 11 September 2015 and a hearing was held in Canberra on 14 June 2017.  TPI Enterprises Ltd also opposed grant of the application and the decision in relation to that opposition is reported as TPI Enterprises Ltd v Tasmanian Alkaloids Pty Ltd [2018] APO 8 (the TPI opposition).

3. TasAlk proposed post-acceptance amendments to the specification on 22 April 2016 which were allowed unopposed on 17 August 2016.  This decision is in relation to the specification as amended.

   The Opposition

1. The statement of grounds and particulars was filed on 11 December 2015 and identified a number of grounds of opposition but only manner of manufacture, inventive step and utility were pressed at the hearing.  An amended statement of grounds and particulars was filed on 30 June 2017 and the amendment allowed unopposed on 21 July 2017.

   Evidence

2. The evidence filed during the evidentiary periods is summarised in the table below:

Evidence	Declarant	Exhibits	Date of declaration	Reference
In Support	Christopher P. L. Grof	CG-1 to CG-8	10 March 2016	Grof
	Ian Alexander Graham	IAG-1 to IAG-19	10 March 2016	Graham 1
In Answer	Wayne Lyle Gerlach	WLG-1 to WLG-5	1 July 2016	Gerlach
	Anthony Millgate	AM-1 to AM-5	4 July 2016	Millgate
	Douglas Blackaby	-	1 July 2016	Blackaby
In Reply	Tim Bowser	TB-1 to TB-4	5 September 2016	Bowser
	Ian Alexander Graham	IAG-20 to IAG-24	6 September 2016	Graham 2

1. Mr Blackaby is the Managing Director of TasAlk and his evidence was confined to the date on which a high codeine poppy was first sold.  As this is not relevant to the grounds of opposition pressed at the hearing his evidence does not need to be considered.

2. TasAlk questioned an inconsistency in Dr Graham’s evidence – there is a reference to the specification at [74] of Graham 1, in the section of the declaration asserted to be given before reviewing the specification. At the hearing Sun submitted that the sentences referring to the specification were inadvertently included in [74], but were intended to be included in [174]. I accept this submission and I am satisfied that with this exception Dr Graham’s evidence in the relevant section of his declaration was given prior to reviewing the specification. I note that Sun provided an additional declaration to this effect at the hearing for consideration under regulation 5.23, but in light of Sun’s submission I have not had regard to that declaration.

Onus

1. The request for examination of this application was filed on 11 April 2013 and consequently substantive amendments of the Patents Act 1990 (the Act) brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 do not apply to the present application.  This includes the amendment to subsection 60(3A) that allows the Commissioner to refuse a patent application if satisfied on the balance of probabilities that a ground of opposition exists.  The onus of proof in this opposition proceeding therefore rests with the opponent, who must demonstrate that it is clear or practically certain that the patent is invalid.[1]

   [1] F.Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283; 50 IPR 305 at 319, [67]; Commissioner of Patents v Sherman [2008] FCAFC 182; 79 IPR 426 at [18].

   The specification

2. The opposed specification relates to Papaver somniferum poppy plants improved to produce codeine in high concentration.  The specification ends with 4 figures and 46 claims.  Claims 1-9, 20, 26, 27, 30, 39 and 41 are independent claims. 

3. Before construing the specification, I note the comments of Middleton J in Eli Lilly and Company Limited v Apotex Pty Ltd:

   “It is well settled that the Court should, from the outset, approach the task of patent construction with a generous measure of common sense. The Court must place itself in the position of a person skilled in the relevant art, being the subject matter of the patent. From this perspective, the patent is to be read as a whole, in the context of the specification and in light of the prevailing common general knowledge and state of the relevant art at the priority date.”[2]

   [2] [2013] FCA 214; 100 IPR 451 at [139].

   The person skilled in the art

4. It is well established that many of the issues in an opposition are answered by reference to the person skilled in the art:

   “He is the person to whom the patent is addressed and who must construe it.  He is the person whose knowledge will determine whether a patent is novel.  He is the person who will judge whether a patent is obvious.”[3]

   [3] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [70].

5. The hypothetical skilled person works in the field with which the invention is connected, and is a non-inventive person or team likely to have a practical interest in the subject matter of the invention.[4]  Relevantly:

   “The identification of the relevant field will, in its turn, determine the characteristics of the notional worker skilled in the art who must provide the answer to the question whether the invention was obvious. Such characteristics will include the qualifications of the notional worker, the setting in which and resources with which he or she operates and the practices and techniques that he or she will regard as commonplace and known.”[5]

   [4] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [70]-[72].

   [5] Aktiebolaget Hässle v Alphapharm Pty Ltd [2002] HCA 59; (2002) 212 CLR 411 at 465, [153].

6. The present specification is directed to the development of improved Papaver somniferum plants, and therefore the person skilled in the art would have experience or a practical interest in this field.

7. Professor Grof is a Professor of Plant Science at the University of Newcastle.  At the priority date he had experience in plant molecular biology research, but he does not have experience working with poppies.[6]

   [6] Grof at [3]-[6], [41].

8. Professor Graham is Head of the Department of Biology at the University of York.  His background is in plant biology, including forward genetic approaches to identify plants with interesting phenotypes and using molecular tools to develop improved poppies.[7]

   [7] Graham 1 at [5]-[17].

9. Mr Bowser is Head of Research and Development, Controlled Substance Division at Sun.  At the priority date Mr Bowser had experience overseeing research programs directed at the development of poppy varieties with high alkaloid yields and in the commercialisation of technical projects.[8]

   [8] Bowser at [2]-[3], [10].

10. Dr Gerlach has a background in molecular biology and has worked at CSIRO and Johnson & Johnson Research Pty Limited.  Dr Gerlach was involved with scientists from TasAlk in the project giving rise to the top1 mutant poppy, which is discussed below.  While following the development of the top1 poppy Dr Gerlach’s career took a different path, he indicated that he has kept generally up to date with research on Papaver somniferum.[9]

    [9] Gerlach at [4]-[6], [47].

11. Dr Millgate undertook a PhD in plant molecular biology involving a study of morphinan biosynthesis in Papaver somniferum which was completed in 2004.  Prior to this, Dr Millgate had experience in plant tissue culture maintenance, the development of new transformation systems for plant species and transforming an insect RNA virus into tobacco and cotton plants.  While Dr Millgate has held various roles in the Australian public service subsequent to completion of his PhD, he kept abreast of developments in the field of morphinan biosynthesis for a number of years following conferral of his PhD.[10]

    [10] Millgate at [5]-[7].

12. Both parties accept that each of the declarants is skilled in the relevant art, but each suggest that various factors should affect the weight given to the evidence.  Specifically, TasAlk pointed to Professor Grof’s lack of experience in working with opium poppies, noting that secondary metabolites in poppies is a specialised field.  TasAlk also submitted that Mr Bowser is employed by Sun and was employed by its predecessor company and Professor Graham has an ongoing relationship with Sun, and accordingly in TasAlk’s submission their evidence must be treated with caution.  Sun noted in response to TasAlk’s comments that Dr Millgate and Dr Gerlach each have an association with the applicant.

13. I am satisfied that the declarants all have backgrounds that enable them to understand the specification and provide evidence in relation to what a person skilled in the art knew or would have done at or before the priority date.  Where there is conflicting evidence, I will decide which evidence should be given greater weight.

    The invention as described

    Background of the invention

14. According to the specification, there are two commercial methods by which alkaloids are extracted from the poppy capsules of Papaver somniferum.  In one method, the immature capsule is cut and the latex collected from the wound; the resulting air-dried latex is opium.  In an alternative method the mature poppy capsules and poppy capsule stems are collected and threshed to remove the seeds and form a straw, which, when necessary is dried to a water content below 16%.[11] 

    [11] Page 4, lines 3-10.

15. The following table is extracted from the specification and provides the alkaloid content of opium, and of straw, on a dry basis, for varieties of Papaver somniferum normally grown:[12]

    [12] Page 4, Table 1.

opium	straw
morphine, %	10-16	1-3
codeine, %	0.8-2.5	0.05-0.3
oripavine, %	0-0.1	0-0.05
thebaine, %	0.5-2	0.15-0.65

1. The postulated bifurcated morphine biosynthetic pathway which depicts these alkaloids is set out in Scheme 1 of the specification at page 22 and reproduced below:

2. It is apparent that poppies typically produce a mixture of alkaloids and accordingly the yield of codeine from poppies is confounded with that of other alkaloids.

3. The specification states that codeine is the most widely used opiate in the world, and is used for its analgesic, antitussive and antidiarrheal properties.  As codeine typically constitutes only a minor fraction of the total alkaloids derived from Papaver somniferum, most codeine currently manufactured is obtained through O-methylation of morphine.[13]  The specification sets out various problems associated with the manufacture of codeine from morphine, including the generation of the toxic byproduct N,N-dimethylaniline and associated waste disposal, OHS and environmental concerns, and yield losses from undermethylation, overmethylation and processing requirements.[14]

   The aim of the invention

   [13] Page 1, lines 18-24.

   [14] Pages 2-3.

4. Against this backdrop, the specification states that:

   “A poppy producing predominantly codeine, e.g., as 55% or more of the total alkaloids, would enable a simpler extraction/purification process, resulting in higher yields, better quality and throughput and lower costs.”[15]

   Nature of the invention

   [15] Page 4, lines 16-18.

5. The specification describes the production of high codeine poppies via mutagenesis of poppy seeds and screening of the progeny of plants grown from the mutagenised seed, and provides an explanation of mutagenesis techniques and the approach to be taken in screening plants grown from mutagenised seed.

6. The specification indicates that the invention is directed to a Papaver somniferum plant which upon harvesting of its poppy capsules will yield a poppy straw with codeine constituting about 40% by weight or more of an alkaloid combination, or which upon collection and drying of latex from immature poppy capsules will yield an opium having codeine constituting about 40% by weight or more of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine.[16]  The specification provides various embodiments directed to increased codeine content both absolutely and relative to other alkaloids.  In a preferred embodiment, there is substantially no morphine in the alkaloid combination.[17]

   [16] Page 5, lines 20-30.

   [17] Page 6, lines 9-11.

7. In an embodiment of the invention the poppy plant is “stably reproducing”.[18]  This is defined in the specification as follows:

   “A “stably reproducing” Papaver somniferum poppy plant as described herein refers to a poppy plant that is stably reproducing as required to plant and harvest seed poppy crop over multiple generations where each generation would be suitable, without seed selection, for commercial planting of a field crop or stand of plants exhibiting the desired alkaloid characteristics.  A stably reproducing poppy plant contains the desired alkaloid characteristics as described herein, and when self pollinated, or cross pollinated by a plant with the same genes controlling alkaloid content, produces a subsequent generation of plants which substantially all have the same desired alkaloid characteristics as the parent plant.”[19]

   [18] Page 6, lines 13-14.

   [19] Page 18, lines 20-29.

8. The specification exemplifies poppies yielding codeine as the predominant alkaloid and only small amounts of other alkaloids.  In the preferred method of the specification, these poppies are arrived at by crossing mutagenised poppies having high levels of thebaine and substantially no oripavine, morphine or codeine with morphine-containing poppy strains. 

9. The specification teaches that high thebaine poppies are achieved by mutagenesis and screening of poppies having the top1 mutation.[20]  The top1 mutation affects both arms of the bifurcated morphine biosynthetic pathway, preventing conversion of thebaine to neopinone and conversion of oripavine to morphinone.  That is, the top1 mutation appears to block demethylation of the enol ether in both thebaine and oripavine.[21]  Poppies containing this mutation therefore accumulate thebaine and oripavine, but are substantially free of morphine and codeine.  The specification states that using these poppies as a starting point is preferred as there are fewer alkaloid peaks to be separated in the chromatographic analysis[22] and discloses a rapid and efficient screening method, allowing for over 1000 samples to be analysed daily.[23] 

   [20] Example 1.

   [21] Page 20-21, bridging paragraph.

   [22] Page 17.

   [23] Page 16, lines 31 – page 17, line 8.

10. When the high thebaine poppies identified from the screening process were crossed with morphine-containing poppy strains, poppies of the F2 generation were identified as accumulating high levels of codeine.  The specification explains that outcome as follows:

    “Whilst we cannot be certain of the reason that the new plants accumulate codeine, reference to the metabolic pathway suggests that the step between codeine and morphine has been substantially blocked. This suggests that the gene controlling the step between thebaine and oripavine that appears to have been blocked in the high thebaine poppy described above, is also responsible for the conversion of codeine to morphine. Therefore, when the gene responsible for producing thebaine-only poppies in conjunction with the TOP1 or Norman mutation is introduced into plants lacking that mutation, a codeine phenotype is produced.” [24]

    [24] Page 22.

11. The specification indicates that mutagenesis and screening of a morphine-containing poppy line could also be used to arrive at high codeine poppies:

    “A more direct method of mutagenizing a morphine-containing poppy line and then using an efficient screening method as described above (except that the screen would select morphine free plants containing high proportions of  codeine) could alternatively be used to produce the same outcome.”[25]

    The Examples

    [25] Page 17, lines 24-27.

12. The specification ends with 13 examples. 

13. Example 1 describes the production of a high thebaine poppy.  Production of this poppy involved fast neutron mutagenesis of poppy seeds containing the top1 mutation.  Plants were grown from the mutagenised seed (the M1 generation) and subsequently M2 plants were grown and the alkaloid profile screened.  34,358 M2 plants (from 4,176 M1 lines) were tested in the project.  An M3 generation of two of the highest thebaine lines was grown and evaluated, and poppy straw from these plants contained very high levels of thebaine and very low levels of oripavine.

14. Example 3 describes production of a high codeine poppy.  High thebaine plants prepared in Example 1 were crossed with poppy lines producing morphine as the predominant alkaloid.  All plants of the F1 generation contained morphine, oripavine, codeine and thebaine.  Multiple plants of the F2 generation were identified as producing high levels of codeine and low levels of other alkaloids.

15. Example 4 describes field grown high codeine poppies.  Examples 9-12 describe F3 and F4 generations of the high codeine plants, demonstrating stable inheritance of the high codeine characteristic and high yields of codeine per hectare.

16. Examples 2, 5 and 6 describe latex extraction and analysis methods.  Examples 7 and 8 describe alkaloid analysis methods.  Example 13 describes a method of confirming the identity of codeine.

    The invention as claimed

17. The principles to be applied in construing claims are well established,[26] and a “generous measure of common sense should be used” in construing claims.[27]  There was no disagreement between the parties as to the construction of the claims.

    [26] H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70; 81 IPR 228 at 254, [118]-[120].

    [27] Product Management Group Pty Ltd v Blue Gentian LLC [2015] FCAFC 179 at [36].

18. The entire claim set is reproduced at Annex A.  Claim 1 reads:

    An isolated plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine, and having a codeine content above 2% in the poppy straw on a dry weight basis.

    This claim encompasses any isolated Papaver somniferum plant which upon harvesting yields the defined codeine levels, with no limitation as to how that poppy is obtained.  I understand “isolated” in the context of these claims to refer to a single plant.[28]

    [28] Gerlach at [58].

1. Claim 2 is directed to a plant having the same features as claim 1, but wherein the plant is “stably reproducing by self pollination in respect of said codeine fraction and said codeine content.”  That is, the progeny resulting from self pollination of such plants should have substantially the same codeine fraction and absolute content as the parent plant.

2. Claims 3-19 define further isolated plants of Papaver somniferum by reference to codeine content in poppy capsules or latex and specifying the presence and absence of other alkaloids. 

3. Claim 20 reads:

   An isolated plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw containing greater than 2% codeine on a dry weight basis and wherein the ratio of codeine and thebaine to an alkaloid combination comprising morphine, codeine, thebaine and oripavine is between about 0.90 and about 1.00.

4. Claims 21 and 22 are dependent on claim 20 and further define the ratio.  I construe these claims to include poppies in which either thebaine or codeine is the predominant alkaloid, but which require a high absolute yield of codeine.

5. Claims 23 and 24 further define the components of the alkaloid combinations of the preceding claims.  Claim 25 is directed to the plant of various preceding claims “wherein the plant is stably reproducing.”  The term “stably reproducing” is defined in the specification as discussed above.

6. Claims 26 reads:

   An isolated plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination comprising morphine, codeine, thebaine and oripavine, wherein when said plant is crossed with a plant grown from seed deposited under accession number ATCC PTA-9147 or ATCC PTA-9294 thereby to obtain an F1 progeny plant, said F1 progeny plant will upon harvesting of its poppy capsules yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination comprising morphine, codeine, thebaine and oripavine.

7. Claim 27 is in the same terms as claim 26, but the codeine fraction is to be measured in the opium of the plant rather than the poppy straw.  I understand these claims to be directed to a plant which (a) itself exhibits the required codeine fraction and (b) when crossed with plants grown from the specified deposited seed gives rise to progeny having the required codeine fraction.[29] 

   [29] Graham 2 at [22]; Gerlach at [136].

8. Claim 28 defines a part of the plant of any one of claims 1-25 maintained for the production of an alkaloid selected from codeine or thebaine.  Claims 29 defines a seed of the plant of any one of claims 1-25.

9. Claim 30 defines Papaver somniferum seed selected from seed deposited under accession numbers ATCC PTA-9147 or ATCC PTA-9242 and plants derived from that seed.  Claims 39 and 40 define progeny of a plant grown from the deposited seed, said progeny yielding a poppy straw having a codeine fraction of about 40% or about 55% by weight or greater of an alkaloid combination comprising morphine, codeine, thebaine and oripavine.  Claims 41 and 42 define a mutant or variant of a plant grown from the deposited seed having a codeine fraction of about 40% or about 55% by weight or greater of an alkaloid combination comprising morphine, codeine, thebaine and oripavine.

10. Claims 31-35 define poppy straw, concentrate of poppy straw (CPS), opium or latex of a plant of any one of claims 1-25.  Claim 36 defines a stand of the plant of any one of claims 1-25.  Claims 37 and 38 define methods of producing codeine by extracting codeine from the poppy straw or opium, respectively, of the plants defined in any one of claims 1-25.  Claims 43 and 44 define a plant cell and plant root, respectively, derived from the plant of any one of claims 1-25.  Claim 45 defines codeine extracted from the poppy straw, CPS, opium or latex of claims 31-35.  I understand this as limited to codeine only when extracted from the defined sources.

11. Claim 46 is an omnibus claim which defines the isolated plants, part of the plant, seed, poppy straw, concentrate of poppy straw, opium, latex, stand, methods, progeny, mutant or variant, plant cell, plant root and codeine of the relevant preceding claims, “substantially as hereinbefore described with reference to any one of more of the examples but excluding comparative examples.”  Accordingly, this claim defines the subjects of the previous claims wherein the features of those claims are limited by reference to the examples.

    Utility

12. Paragraph 18(1)(c) of the Act requires that the claimed invention be useful.  The principles of utility were recently summarised by the Full Court of the Federal Court in Artcraft Urban Group Pty Ltd v Streetworx Pty Ltd[30] (with references omitted): 

    “The ‘basic principle’ of inutility is that if an invention ‘does what it is intended by the patentee to do, and the end attained is itself useful, the invention is a useful invention’. What the invention is ‘intended’ to do is a matter to be gathered from ‘title and the whole of the specification’.

    Put another way, the two questions are: first, what is the promise of the invention derived from the whole of the specification?; second, by following the teaching of the specification, does the invention, as claimed in the patent, attain the result promised for it by the patentee? Further, ‘everything’ that is within the scope of a claim must be useful, that is, attain the result promised for the invention by the patentee.”

    [30] [2016] FCAFC 29 at [120]-[121].

13. Relevantly, in considering the specification to identify the promise of the invention, the result promised by the specification for the invention is to be distinguished from the promise of preferred embodiments of the invention,[31] and whether there is utility depends upon whether by following the teaching of the specification the claimed result is produced, not whether that result is commercially practicable.[32]

    Morphine content

    [31] [2016] FCAFC 29 at [122].

    [32] Advanced Building Systems Pty Ltd v Ramset Fasteners (Aust) Pty Ltd [1998] HCA 19; (1998) 194 CLR 171 at [24].

14. Sun submitted that “the alleged invention is proposed to be useful as a source of codeine from non-morphine containing poppies” and accordingly insofar as the claims do not require the absence of morphine from the alkaloid combination, the claims do not meet this requirement.  To support this promise, Sun pointed to the following passages of the specification:

    “More particularly, the present invention relates to the use of an improved Papaver somniferum poppy plant to produce codeine in higher yield, allowing codeine to be produced without the need to grow poppies containing morphine.”[33]

    “The major part of the world’s licit morphine production is to support the manufacture of codeine.  If codeine could be sourced from non-morphine-containing poppies it would greatly decrease the growing of morphine poppies with the potential for diversion and abuse.”[34]

    “The claimed invention now provides codeine CPS which has great commercial potential because it allows production of codeine CPS and derivatives without the need to grow poppies containing morphine.”[35]

    [33] Page 1, lines 5-7.

    [34] Page 1, lines 24-27.

    [35] Page 5, lines 14-17.

15. Sun also pointed to the definition given in the specification for “substantially no” morphine, which means less than 1% by weight (preferably less than 0.5%, more preferably less than 0.3% and most preferably between 0 and 0.2% by weight) of the alkaloid combination of the poppy straw, CPS or opium.[36]

    [36] Page 19, lines 15-20.

16. TasAlk responded that the specification is directed towards a poppy having a high concentration of codeine, referring to the title of the specification “Papaver somniferum with high concentration of codeine” and the more general descriptions of the invention.  Accordingly, in TasAlk’s submission the promise of the invention is improved production of codeine; the absence of morphine is not essential.  TasAlk submitted that references to growing poppies not containing morphine should be understood in the context of the specification as a reference to poppies containing less morphine than conventional poppies which contain high levels of morphine. In addition to understanding the passages referred to above in this context, TasAlk referred to the specification at page 4 as supporting the nature of the invention as predominantly codeine rather than the absence of morphine:

    “A poppy producing predominantly codeine, e.g., as 55% or more of the total alkaloids, would enable a simpler extraction/purification process, resulting in higher yields, better quality and throughput and lower costs.”[37]

    [37] Page 4, lines 16-18.

17. TasAlk submitted that even the definition of substantially no morphine encompasses the presence of some morphine, and indeed the presence of substantially no morphine is a preferred embodiment of the invention:

    “In a preferred embodiment, there is substantially no morphine, thebaine or oripavine in the alkaloid combination.”[38]

    [38] Page 6, lines 9-11.

18. TasAlk referred to the evidence of Drs Gerlach and Millgate in support of the proposition that the specification is directed to a high level of codeine.[39]  I also note Professor Graham’s initial statement that the “Opposed Application is directed towards Papaver somniferum poppy plants which produce codeine in higher levels relative to other alkaloids”,[40] although he later stated that the claimed invention is “to provide plants with high codeine and no morphine”.[41]

    [39] Millgate at [74], [75]; Gerlach at [49].

    [40] Graham 1 at [120].

    [41] Graham 1 at [147].

19. I am satisfied that the promise of the invention from a reading of the specification as a whole, is, consistent with TasAlk’s submissions, a poppy plant producing a high proportion of codeine relative to conventional morphine poppies.  While the absence or substantial absence of morphine is clearly a preferred embodiment, I do not consider that failure to define this preferred embodiment results in a failure of the claims to achieve the promised benefit.

    Stably reproducing

20. Sun further submitted that the claims which do not require the plant to be stably reproducing fail to meet the promise of the invention.  In this regard, Sun pointed to the process of preparing the poppies of interest described in the specification:

    “The M2 generation is screened for alkaloid production.  Of course, it is possible to screen the M1 generation, but there are several advantages to screening the M2 generation.  Firstly, screening the M2 generation insures that the trait resulting from mutagenesis can be inherited.  Secondly, by growing the M2 generation, the basic hardiness of the plant is proven before screening.  Thirdly, traits resulting from mutagenesis are generally inherited as recessive genes.  Typically the mutated gene will be in the heterozygous state in the M1 generation, and thus the mutation will be masked by the dominant (non-mutated) form of the gene.  In the M2 generation, however, in a proportion of the plants the gene will be in the homozygous state and the affect of the mutation apparent.”[42]

    [42] Page 16, lines 4-14.

21. In my view it is clear from this passage that heritability of the relevant mutation is desirable, and Sun submitted that a stably reproducing plant is inherently part of the promise of the invention, otherwise the phenotype would not persist more than a generation and would not be useful.

22. TasAlk submitted that Sun has not identified any promise in the specification that all embodiments of the invention must be stably reproducing, and that such a requirement is clearly only in an embodiment of the invention, for example, the specification states: “In still another embodiment, the plant is stably reproducing.”[43]

    [43] Page 6, lines 13-14.

23. I agree with TasAlk that the specification discloses as one embodiment (and not all embodiments) of the invention that the poppy is stably reproducing.  Accordingly, I am not satisfied that the omission of this feature leads to a failure to achieve the promised benefit.

    Conclusion on utility

24. Sun has not established that the claims lack utility.

    Manner of manufacture

25. Paragraph 18(1)(a) of the Act requires that the invention, so far as claimed in any claim, must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies.  In D’Arcy v Myriad Genetics Inc[44] (Myriad) the High Court confirmed that the question posed by the application of s 18(1)(a) may be framed as in National Research and Development Corporation v Commissioner of Patents[45] (NRDC):

    “Is this a proper subject of letters patent according to the principles which have been developed for the application of s 6 of the Statute of Monopolies?”

    [44] [2015] HCA 35; 89 ALJR 924 at [18].

    [45] [1959] HCA 67; 102 CLR 252 at 269.

26. In Myriad at [28] the High Court set out factors relevant to the characterisation of a claimed invention as a manner of manufacture. The first of these is: “Whether the invention as claimed is for a product made, or a process producing an outcome as a result of human action.” The High Court also stated:

    “…an invention is something which involves “making”.  It must reside in something.  It may be a product.  It may be a process.  It may be an outcome which can be characterised, in the language of NRDC, as an “artificially created state of affairs”.  Whatever it is, it must be something brought about by human action.”[46]

    [46] [2015] HCA 35; 89 ALJR 924 at [6].

27. TasAlk submitted that it was established in Grain Pool of WA v Commonwealth[47] that “there is no intrinsic impediment to the patentability of plant varieties”.  While I accept that this is clearly the case, there was no dispute that this principle does not extend to patenting naturally-occurring plant varieties.

    [47] [2000] HCA 14; 202 CLR 479 at [46].

28. Sun submitted that other than those relying on deposits made under the Budapest treaty, the claims encompass a poppy which produces the requisite quantities and proportions of codeine defined in the claims regardless of how that poppy arose.  In particular, the claims do not define any requirement for mutagenesis or other human intervention.  In Sun’s submission the claims therefore are broad in scope and potentially encompass naturally occurring poppies, that is, poppies having a naturally-occurring mutation giving rise to the high codeine phenotype.  Such poppies may already exist, or may arise during the term of the patent.  Sun also pointed to the passage of the specification stating that “even conventional breeding approaches may ultimately be used to develop such plants.”  Accordingly, in Sun’s submission, the claims include subject matter which does not satisfy the manner of manufacture requirement, in accordance with the finding in Myriad that nucleic acids encoding genetic information which was not artificially created are not a manner of manufacture.

29. However, there is nothing in evidence that supports a conclusion that any naturally-occurring poppy does have a level of codeine falling within the scope of the claims.  TasAlk submitted that it was unlikely that a poppy with a mutation giving rise to the defined phenotype would occur naturally.  While the specification suggests that such plants may ultimately be developed by conventional breeding, that does not conclusively establish that such plants are or will be naturally-occurring.  Accordingly, I consider that the situation contemplated in Myriad can be distinguished from the present case in that in Myriad the genetic information in question was, in fact, naturally-occurring.

30. An analogous situation was considered by a delegate of the Commissioner in Cargill Incorporated v Dow AgroSciences LLC[48](Cargill) in relation to canola plants producing seed having a defined oil fraction and the seed produced by those plants.  The opponent in that case submitted that the claims were highly likely to include naturally-occurring plants and seeds.  As in the present case, there was no evidence to suggest that any naturally-occurring plants did, in fact, fall within the scope of the claims, and the delegate found that the opponent had not established a lack of manner of manufacture.  TasAlk submitted that there is no distinction on the facts between the present case and Cargill.

    [48] [2016] APO 43 at [46]-[50].

31. While I accept that it is possible that a naturally-occurring mutant poppy having the defined phenotype might exist now or in the future, there is no evidence of the current existence of such a plant.  While Sun argued that requiring evidence on this point impermissibly conflates the grounds of novelty and manner of manufacture, I cannot agree.  I consider that in an opposition proceeding, where the opponent bears the onus of establishing to the level of practical certainty that the claims are invalid, a finding that the claims are invalid on the basis that they encompass subject matter which is naturally occurring requires more than a speculative prospect that that might be so.  Accordingly Sun has not established that the claims do not define a manner of manufacture.

    Inventive step

32. Subsection 7(2) states that an invention is taken to involve an inventive step unless it would have been obvious to a person skilled in the art in light of the common general knowledge as it existed in the patent area before the priority date of the relevant claim when considered alone or together with the information mentioned in s 7(3). 

33. Subsection  7(3) defines the relevant information as:

    i.The information for the purposes of subsection (2) is:

    (a)     any single piece of prior art information; or

    (b)     a combination of any 2 or more pieces of prior art information;

    ii.being information that the skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood, regarded as relevant and, in the case of information mentioned in paragraph (b), combined as mentioned in that paragraph.

34. Having identified the common general knowledge and any relevant information as defined in s 7(3), the test for whether an invention is obvious is to ask whether it would have been a matter of routine to proceed to the claimed invention, as set out by Aickin J in Wellcome Foundation Ltd v V.R. Laboratories (Aust.) Pty Ltd: [49]

    “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.”

    [49] [1981] HCA 12; (1981) 148 CLR 262 at 286.

35. The High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd (Alphapharm)[50]  approved this approach, noting that matters of routine are to be distinguished from other courses of action:

    “The tracing of a course of action which was complex and detailed, as well as laborious, with a good deal of trial and error, with dead ends and the retracing of steps is not the taking of routine steps to which the hypothetical formulator was taken as a matter of course.”[51]

    [50] [2002] HCA 59; (2002) 212 CLR 411 at 432-433, [50]-[53].

    [51] [2002] HCA 59; (2002) 212 CLR 411 at 436, [58].

36. The High Court in Alphapharm also approved the approach taken in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd,[52] of asking whether the person skilled in the art would be directly led as a matter of course to try what was claimed in the expectation that it might well produce a useful or desired result.

    [52] [1970] RPC 157 at 187.

37. TasAlk submitted that this last question is the most authoritative test, and should be applied in this case, but noted that properly understood, the reformulated Cripps question and the “routine steps” approaches are similar.

38. In both of these approaches a person skilled in the art must have a reasonable expectation of success.  This is explicit in the expectation that an approach “might well” succeed, and implicit in the characterisation of steps as to be taken as a matter of routine.[53]  The reasonable expectation of success does not require that success is guaranteed, and allows for some possibility that the steps taken might not achieve the intended result.[54]  However, the taking of routine steps with a reasonable expectation of success is distinguished from steps which the skilled addressee would consider “worthwhile to try”.[55]

    [53] Generic Health Pty Ltd v Bayer Pharma Aktiengesellschaft [2014] FCAFC 73; 314 ALR 91 at [71].

    [54] [2002] HCA 59; (2002) 212 CLR 411 at [74], [76].

    [55] Generic Health Pty Ltd v Bayer Pharma Aktiengesellschaft [2014] FCAFC 73; 314 ALR 91 at [71].

1. Sun considered the following principle in Raychem Corp.’s Patents[56] (Raychem) relevant to inventive step in this case, submitting that the claims merely define a known goal in the art:

   “If the patent claim consists of no more than a product or process selected by reference to a set of obviously desirable parameters, then the technical contribution is the selection of those parameters.  Since that selection is obvious, so is the claim.”[57]

   [56] [1998] RPC 31.

   [57] [1998] RPC 31 at 41.

2. The law on inventive step in the UK and Australia has diverged.[58]  While Sun referred to a number of Office decisions referring to Raychem in relation to inventive step, TasAlk noted that these were decided pre-Alphapharm.  I will follow the approach set out by the High Court for considering inventive step.

   The problem

   [58] [2002] HCA 59; (2002) 212 CLR 411 at [48].

3. It is apparent from the specification that the problem it addresses is the provision of a high codeine poppy.  There was no dispute that a high codeine poppy was a known and desirable goal in the art, and had been for many years.[59]

   Common general knowledge

   [59] Millgate at [74]; Graham 1 at [43]-[44].

4. Common general knowledge is the background knowledge and experience available to all those working in the relevant art:

   “The notion of common general knowledge itself involves the use of that which is known or used by those in the relevant trade.  It forms the background knowledge and experience which is available to all in the trade in considering the making of new products, or the making of improvements in old, and it must be treated as being used by an individual as a general body of knowledge.”[60]

   [60] Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd [1980] HCA 9; (1980) 144 CLR 253 at 292.

5. Relevantly, the evidence establishes and the parties agreed that the common general knowledge at the priority date included the knowledge that:

   ·   codeine is a valuable alkaloid produced by poppy plants;[61]

   ·   there were issues associated with the production of codeine from prior art poppy varieties because they produced predominantly morphine;

   ·   an improved poppy variety producing high levels of codeine without high levels of, or even any, morphine, would be commercially attractive and desirable (with Dr Millgate stating that “production of a high codeine plant was considered the ‘Holy Grail’”[62]);[63]

   ·   forward genetics approaches incorporating mutagenesis and selection were widely used throughout the world to develop many improved plant varieties;[64]

   ·   forward genetics incorporating mutagenesis and selection had already been successfully used to generate an improved poppy variety producing high levels of thebaine and oripavine (the top1 poppy);[65]

   ·   there were regulatory issues with genetically modified organisms (GMOs) produced by reverse genetics approaches (but these were not insurmountable).[66]

   [61] Graham 1 at [62]; specification, page 1 lines 20-25.

   [62] Millgate at [74].

   [63] Graham 1 at [43]-[44].

   [64] Graham 1 at [47]; Grof at [27].

   [65] Graham 1 at [47].

   [66] Graham 1 at [49]-[51]; Gerlach at [210]; Millgate at [140].

6. The evidence establishes that at the priority date it was known that there were three broad methods for developing new plant varieties: traditional plant breeding; forward genetics – an approach to select for plants in a mutagenised population with a phenotype of interest by screening; and reverse genetics – determining the function of a gene via examination of the phenotypic effect of interference with expression of that gene.[67]  Each of these approaches had been applied to poppies, and as indicated above, the forward genetics approach had been used to arrive at a poppy producing high levels of thebaine and oripavine.  However, up to the priority date, new poppy varieties were generally developed by conventional breeding.[68]

   [67] Graham 1 at  [46]-[51]; Gerlach at [92]; Millgate at [23], [137]-[139].

   [68] Graham 2 at [44]; Gerlach at [92]; Millgate at [93].

7. There was some discussion at the hearing as to the extent to which the biochemical pathways involved in alkaloid synthesis in poppies were known at the priority date.  However, the parties were generally in agreement, and I accept, that while the bifurcated pathway was known, the underlying genetics were not well understood.[69]  This conclusion is consistent with the schematic of the morphinan pathway referred to by Professor Graham[70] which indicates that cognate cDNAs have not been isolated for the enzymes associated with conversion of thebaine to neopinone and oripavine, oripavine to morphinone and codeine to morphine.

   [69] Graham 1 at [48], [53].

   [70] Graham 1 at [95]; Exhibit IAG-7, Figure 1.

8. The evidence establishes that the top1 poppy itself was common general knowledge.  Sun submitted that it was common general knowledge that the top1 poppy had been characterised as having a block in the 6-O-demethylase step in both branches of the bifurcated pathway from thebaine to morphine, probably due to a single mutation in a 6-O-demethylase active in both branches of the pathway.  TasAlk disputed this, noting that Millgate, A.G. et al. (2004) ‘Morphine-pathway block in top1 poppies’, Nature, vol. 43, pages 413-414 (the Millgate article)[71] presents several alternative hypotheses for the observed phenotype.  While it is apparent that there were alternative possible explanations, I am satisfied that the evidence establishes that it was well known at the priority date that the preferred hypothesis was that the observed phenotype was due to a mutation in an enzyme acting in both branches of the pathway.[72]

   [71] Exhibit IAG-3.

   [72] Gerlach at [126]; Graham 1 at [71].

9. The parties also disagreed regarding the extent to which the flux through the bifurcated pathway was known at the priority date.  Professor Graham stated that “it was well known by 2008 that the metabolic flux … significantly favoured the production of morphine from thebaine through codeine”[73] and referred to two articles published in the 1980s on which his understanding was based.[74]  It has not been established that these documents or the information contained therein formed part of the common general knowledge.  Professor Grof stated that “there is a flux in the pathway such that the conversion of neopinone to codeinone is spontaneous, and therefore morphine is produced predominantly via codeine”[75] – this conclusion appears to rely on different reasoning to Professor Graham.  In contrast, Dr Millgate considered that “in the mid 2000’s, there was no convincing evidence of this”[76] and Dr Gerlach indicated that “it was not widely believed before 29 May 2008 that metabolic flux significantly favoured the production of morphine from thebaine through codeine.”[77]  On balance, while it is apparent that it was known to Professors Graham and Grof, the basis for this knowledge differs and I am not satisfied that it has been established that it was common general knowledge at the priority date that morphine was produced predominantly via codeine.

   Matters of routine

   [73] Graham 1 at [61].

   [74] Graham 2 at [57].

   [75] Grof at [48].

   [76] Millgate at [150].

   [77] Gerlach at [109].

10. Before I turn to the ultimate question, I will consider the evidence of the experts as to how they would have approached the pursuit of a new poppy variety having a desired alkaloid level before the priority date. 

11. At the outset it is worth considering the nature of the forward genetics approach.   This approach involves mutagenesis of, in this case, plant seed, using a chemical mutagen or radiation, which gives rise to random mutations in the genome.[78]  I understand from the evidence that the outcome therefore relies on chance; it is not possible to control or direct the mutation events.[79]  Unpredictability is inherent in this approach, as is the inability to specifically target any particular phenotype.  Nevertheless, I have found that it is common general knowledge that this approach has been widely used to develop many plant varieties.  Accordingly, in my view the question to be answered is whether a person skilled in this art would, as a matter of routine, adopt this approach, knowing of its randomness and the element of luck or chance involved, and the expectation of success required should be considered within this context. 

    Evidence on matters of routine

    [78] Graham 1 at [55]; Grof at [30]-[31], [34].

    [79] Millgate at [95]; Gerlach at [99].

12. Professor Graham stated that the two major approaches he would have considered in seeking to develop an opium poppy having a desired alkaloid profile were forward and reverse genetics.  In either approach “the likelihood of generating a mutant with the desired phenotype is high.”[80]  Professor Graham indicated that the forward genetics approach had been used to generate many plants, and that in seeking a poppy with a desired alkaloid profile, he would have favoured a forward genetics approach:

    “as at 2008, there were already thousands of varieties of commercially available plants generated from forward genetic screens.  Forward genetics is an approach to select for plants with a phenotype of interest in a mutagenized population, using screening techniques.  This approach allows the generation and identification of plants having a desired phenotype without knowledge of the one of more genes that may be responsible for a phenotype.  I am aware that as at 2008, there was precedent for using forward genetics approaches to generate opium poppies have a desired alkaloid profile…”[81]

    “A new plant variety developed by a forward genetics approach using mutagenesis is not considered ‘genetically modified’.  From a commercial perspective, once the variety is uniform and stable, it can be grown commercially without the need for regulatory approval.”[82]

    “Plants of Papaver somniferum are diploid and lend themselves to a mutagenesis approach as opposed to polyploids for which mutagenesis tends to be less successful.  Opium poppies are susceptible to mutagenesis including chemical mutagens such as ethyl methanesulfonate (EMS) and irradiation methods including fast neutron bombardment.  The genetic inheritance in opium poppies is Mendelian which allows a rapid mutagenesis and screening approach.”[83]

    “as at 2008 given the fact that at that time, the enzymes responsible for the synthesis of codeine had not been fully identified and characterised, I would have approached the development of a new poppy variety having an alkaloid profile of interest using a forward genetics approach, that is, through mutagenesis followed by screening for the phenotype of interest.”[84]

    [80] Graham 1 at [64]-[65].

    [81] Graham 1 at [47].

    [82] Graham 1 at [49].

    [83] Graham 1 at [54].

    [84] Graham 1 at [66].

13. The process described by Professor Graham by which he would develop a poppy having a desired alkaloid profile using forward genetics is as follows:

    “Initially seed is mutagenized, a mutant population of plants are grown from that seed, the  mutant plants are then screened for the desired phenotype of interest, and plants selected on the basis of having the desired phenotype are ‘selfed’ (self-pollinated).”[85]

    [85] Graham 1 at [64].

14. I note that in his second declaration Professor Graham accepted Dr Gerlach’s comment[86] that in his first declaration he omitted to point out that it is the M2 population of mutants which is screened.[87]  

    [86] Gerlach at [111].

    [87] Graham 2 at [59].

15. Professor Graham’s evidence is consistent with the specification which states that “production of mutagenized seed is well known in the art.”[88]  Statements in contemporaneous documents in the evidence also support a view that applying a forward genetics approach to poppies is not unusual:

    “Opium poppy has been a popular target for EMS- and/or ionizing radiation-induced mutagenesis.”[89] 

    “Indeed, genetic modification with the goal of developing new opium poppy varieties has been underway for decades.  A traditional method of altering metabolic profiles that remains popular today for plants, animals and microorganisms is the mutagenesis of a population using chemicals or ionizing radiation.  Chemical mutagens, such as ethylmethanesulfonate (EMS), primarily cause point mutations and are favoured because they generate a relatively high density of irreversible genetic lesions.  Furthermore, the production of commercially valuable, non-transgenic plant varieties has particular appeal within the industry.  … The top1 variety is now extensively cultivated in Tasmania (Table 1), demonstrating the potentially powerful impact of mutagenesis on the opium poppy industry.”[90]

    [88] Page 12, line 4.

    [89] Facchini, P.J. et al. (2007) ‘Opium poppy: blueprint for an alkaloid factory’, Phytochem Rev, vol. 6, pages 97-124 at 115 (Exhibit IAG-8).

    [90] Hagel, J.M. et al (2007) “Opium Poppy” in Transgenic Crops VI, Biotechnology in Agriculture and Forestry, E.C. Pua and M.R. Davey (eds) vol. 61, pages 169-187 at 183 (Exhibit IAG-10).

16. Professor Graham did indicate that the mutagenesis approach may need to be iterative:

    “using a mutagenesis approach to obtain a plant with the phenotype of interest can be progressive.  This is particularly so if there are multiple genes involved or where there may be alternative steps in the pathway to a particular end point.  The mutagenesis may result in progressive improvement towards the phenotype of interest and may require a double or triple mutant.  If the mutant populations reach saturation point in terms of screening, it may also be necessary to use a different mutagenesis technique using a mutant individual as a starting point, for example if multiple genes are involved in the step or steps in the pathway being targeted.  For example, the combination of different mutagens with different mutation-inducing processes may increase the mutation frequency and alter the spectrum of mutations.”[91]

    “Because the morphine synthesis pathway is branched, it might be necessary to disrupt or block out two separate genes.  In such a case it is conceptually straightforward to generate double mutants and this has been done with other biosynthetic pathways.”[92]

    Accordingly, Professor Graham stated that by the priority date it was well known that it was possible to obtain plants via mutagenesis that are mutant at multiple loci,[93] and while acknowledging that “a mutagenesis approach may be progressive”, Professor Graham indicated that “it is a standard approach.”[94]  Professor Graham described it as “common and routine practice” to cross a mutant plant with a plant exhibiting good agronomic characteristics.[95]

    [91] Graham 1 at [56].

    [92] Graham 1 at [70].

    [93] Graham 1 at [57].

    [94] Graham 1 at [58].

    [95] Graham 1 at [75].

17. The routine nature of the forward genetics approach is contrasted with its potentially lengthy character, which is acknowledged by Professor Graham: “I do not dispute that these methods are time consuming, … although some optimisation is required the techniques and approach can be routinely implemented.”[96] Indeed, Professor Graham stated that the success of the forward genetics approach would effectively come down to the number of plants screened:

    “the success or otherwise of forward genetics approaches will generally come down to the ability to generate a mutagenized population and the number of plants that are able to be screened in any given day, week and the number of generations able to be grown each year.  This part of the process of developing plants of interest is laborious and time consuming, although straightforward.  In my experience, utilising high throughput screening methods it would not be unreasonable to screen tens of thousands of plants and certainly up to around 50,000 plants in order to identify a single plant having the phenotype of interest.  While these numbers seem large, where large numbers of plants can be screened each week, finding a plant with a desired phenotype is merely routine experimentation.”[97]  

    [96] Graham 2 at [71].

    [97] Graham 1 at [67].

18. TasAlk referred me to passages in Professor Graham’s evidence where he uses less emphatic language, e.g. “I consider that it would be possible to develop bespoke poppy varieties”[98] in contrast to other passages indicating higher levels of confidence, e.g. “the chances of generating a mutant with the phenotype of interest is high but is likely to require the screening of a significant number of plants.”[99]  Considering this evidence in context I do not think that Professor Graham’s evidence is inconsistent.  I understand him to mean that he considered it likely that poppies with altered alkaloid levels could be arrived at by a forward genetics approach.

    [98] Graham 1 at [62].

    [99] Graham 1 at [65].

19. While Professor Grof does not have experience working with poppies, his evidence is consistent with that of Professor Graham.  Professor Grof indicated that genetic manipulation to produce transgenic plants and mutagenesis and screening were the two main approaches to developing new plant varieties at the priority date[100] and that “forward genetic approaches (using mutagenesis followed by screening) have long been used in generating plants with desired phenotypes.”[101]  Professor Grof stated that in his experience “generating a large mutant population for identifying plants with a desired phenotype is straightforward, although the phenotype analysis can be time-consuming.”[102] 

    [100] Grof at [26].

    [101] Grof at [27].

    [102] Grof at [31].

20. In contrast, Dr Millgate took the view that the expectation of successfully obtaining a poppy having a particular desired alkaloid level was very low[103] and with regard to adoption of a forward genetics approach he stated:

    “In order to carry out a mutagenesis approach to produce a specific phenotype you need to have an efficient way to screen plants for the desired phenotypes, and you should have good reason to suspect that those phenotypes can be achieved by mutagenesis.  Before my practical experience with poppies, I would have thought that a mutagenesis approach was probably more attractive than a reverse genetics approach back in 1996.  However, in the mid-2000s and in 2008 I would not have regarded either the forward or reverse genetics approach as being more or less attractive … a conventional breeding approach would possibly be the most attractive.”[104]

    However, Dr Millgate indicated that the only stable poppy variants produced by traditional plant breeding techniques were those producing high levels of morphine.[105]  I note that in the TPI opposition Dr Millgate seemed to suggest that a skilled person would be more inclined to follow the reverse genetics approach,[106] however, I draw no inference from this apparent inconsistency.

    [103] Millgate at [22], [55], [90].

    [104] Millgate at [139].

    [105] Millgate at [91].

    [106] Declaration of Anthony Millgate dated 4 July 2016 and filed as evidence in answer in the TPI opposition at [121].

21. Further, Dr Millgate indicated that:

    “Although I agree with Professor Graham’s statements that the process of developing plants of interest is laborious and time consuming, I disagree with his conclusion that the process of developing a plant with a desired or particular alkaloid profile was “straightforward”.  In my view, even if up to 50,000 plants had been screened, there is still every chance that a plant having the phenotype of interest may not have been produced.”[107]

    [107] Millgate at [101].

22. With regard to approaches for developing new poppies, Dr Gerlach stated:

    “In my opinion, conventional breeding was by far the most widely used method of developing new varieties of poppies before 29 May 2008, and the majority of these efforts were directed at increasing morphine levels rather than increasing the levels of other alkaloids.  In fact, the only variety of poppy that had been producing using forward genetics was the top1 poppy.  Aside from Tasmanian Alkaloids, I am not aware of any other research groups that were using forward genetics to develop new varieties of poppy before 29 May 2008.  However, many research groups in Australia and around the world were producing transgenic poppies using reverse genetics methodologies before 29 May 2008.”[108]

    [108] Gerlach at [92].

1. Dr Gerlach also indicated that:

   “In my experience, it was generally accepted by 29 May 2008 that in order to engineer a plant to produce products based on plant secondary metabolites, at least in a predictive manner, it is important at least to understand the mechanism of metabolite biosynthesis.”[109]

   and

   “While the principles of forward and reverse genetics are generally applicable to many plant species, a detailed understanding of the species in question is required before either method can be applied.  The methods associated with forward and reverse genetics may be performed differently depending on the plant species being studied.”[110]

   [109] Gerlach at [30].

   [110] Gerlach at [86].

2. Dr Gerlach was involved in the project which gave rise to the top1 poppy in the early to mid-1990s and, in relation to that project, indicated that in seeking to “generate new genetic variants and then possibly select plants with useful characteristics”,[111] while conventional breeding and transgenic approaches were possible, “mutagenesis was chosen as an approach to generate metabolite diversity, although the likelihood of success was unknown.”[112]  Nevertheless, in undertaking this project “it was hoped that variants might arise which produce alkaloid yields in different amounts compared to the commercial cultivar.”[113]  In contrast to Professor Graham’s view regarding mutations at multiple loci, Dr Gerlach stated that “mutagenesis will rarely be employed to produce a phenotype which can only be observed when more than one gene is compromised.”[114]

   [111] Gerlach at [40].

   [112] Gerlach at [42].

   [113] Gerlach at [45].

   [114] Gerlach at [108].

3. Drs Gerlach and Millgate provided a number of reasons why a forward genetics approach would not be attractive or routine in seeking a poppy with a particular altered alkaloid profile (or more specifically a high codeine poppy).  These include:

   ·   the inability to target a poppy with a specific desired profile;[115]

   ·   the difficulty in predicting the phenotype arising from suppression of gene activity – noting the surprising finding that suppression of a gene encoding codeinone reductase resulted in accumulation of (S)-reticuline, a product seven enzymatic steps upstream of codeinone;[116]

   ·   the experimental design needs to be undertaken carefully to increase the likelihood that a mutant of interest will be identified – and there remains a chance that it might not be;[117]

   ·   if the relevant gene does not exist as a single copy in the genome of the plant a mutation might result in no visible effect, and if two or more genes must be mutated it becomes “exceedingly unlikely” that mutagenesis will knock out each relevant gene;[118]

   ·   the phenomenon of pleiotropy (where one gene controls multiple phenotypes) can complicate the identification of a particular phenotype;[119]

   ·   the possibility that the alkaloid may be toxic to the plant in high levels.[120]

   [115] Millgate at [95], [110], [144].

   [116] Gerlach at [104], [118]; Millgate at [149].

   [117] Gerlach at [105], [106]; Millgate at [101].

   [118] Gerlach at [99], [102]; Millgate at [103].

   [119] Gerlach at [100].

   [120] Gerlach at [91]; Millgate at [106].

4. Contemporaneous documents support a view that such an approach is not guaranteed:

   “In the future, new varieties exhibiting desirable metabolite profiles, such as increased morphine or codeine content, might be derived through a combination of classic breeding, mutagenesis, and genetic transformation.”[121]

   “BIA metabolism in plants and cell cultures is amenable to manipulation. However, empirical metabolic engineering efforts have proven less predictable than expected. While gene discovery is a major focus of current research, more work on the regulation of alkaloid biosynthesis and the transport of pathway intermediates and products is required. A better understanding of the subcellular localization and macromolecular organization of alkaloid biosynthetic enzymes will provide a framework to explain published metabolic engineering results in the context of predictive metabolic flux analysis.”[122]

   [121] Hagel, J.M. et al (2007) “Opium Poppy” in Transgenic Crops VI, Biotechnology in Agriculture and Forestry, E.C. Pua and M.R. Davey (eds) vol. 61, pages 169-187 at 184 (Exhibit IAG-10).

   [122] Liscombe, D.K & Facchini, P.J. (2008) ‘Evolutionary and cellular webs in benzylisoquinoline alkaloid biosynthesis’, Current Opinion in Biotechnology, vol. 19, pages 173-180 at 179-180 (Exhibit IAG-7).

5. It is apparent that the forward genetics approach is random in effect and the generation of a particular plant or poppy of interest cannot be guaranteed.  It is also, however, apparent that this is an approach which has been widely used in the field of plants generally, and there is a high profile example of its use to generate a poppy with modified alkaloid characteristics. 

   Conclusion on matters of routine

6. In summary, it is apparent that Professor Graham considers that the application of a forward genetics program to poppies in seeking varieties with altered alkaloid levels, including high codeine, would be undertaken as a matter of routine.  I understand the basis for this conclusion to be: a) such an approach has been used widely in other plants, b) the approach does not need a good understanding of the underpinning genetics, c) poppy plants are diploid and exhibit Mendelian genetics, d) forward genetics had been used in poppies previously and e) plants generated by forward genetics are not characterised as GMOs.  These seem to me to be inherently reasonable and logical considerations.

7. Dr Gerlach accepted that the principles of forward genetics are generally applicable to many plant species, but he indicated that a detailed understanding of the species being considered is required before either a reverse or forward genetics method can be applied, and the biosynthetic pathway for alkaloid compounds is complex. However, it is apparent that Dr Gerlach was involved in a forward genetics program applied to poppies before the priority date, albeit a program that it was accepted “could ultimately fail”.[123]  While Dr Gerlach points to the complexity and unpredictability of a forward genetics approach, he primarily focuses on the likelihood of whether a forward genetics approach could give rise to a high codeine poppy, rather than whether a forward genetics approach might be undertaken at all.  Dr Gerlach also indicates that the design of a forward genetics experiment is often not routine.  While I accept that there may be complexities, it is apparent having regard to the qualifications of the declarants that this is a high technology art, and as such I think it is reasonable to expect that complex work is routinely undertaken, consistent with Professor Graham’s evidence.[124] 

   [123] Gerlach at [40].

   [124] Graham 2 at [54].

8. I think it is fair to conclude that Dr Millgate does not accept that such an approach would be undertaken as a matter of routine; in his view it would not have been possible at the priority date for a skilled worker to undertake any project seeking a poppy producing a high yield of a particular alkaloid with an expectation of success.  Dr Millgate’s evidence appears to focus largely on the general lack of knowledge regarding the underpinning genetics of the morphine biosynthetic pathway, which appears consistent with the focus of his PhD on investigation of differential gene expression in poppy germplasm having varying alkaloid profiles.  In the context of the present invention I will give more weight to the evidence of Professor Graham and Dr Gerlach in considering what would have been done as a matter of routine, given their more relevant experience in the generation of plants exhibiting new phenotypes.  

9. Accordingly, I understand from the evidence that the nature of forward genetics is such that there can be no guarantee of success, and it may be a laborious and time consuming process.  Despite this, the evidence establishes that this approach is routinely undertaken by skilled workers in relation to plants generally, including poppies.  I am satisfied that the person skilled in the art could be expected to adopt such an approach as a matter of routine when seeking, in a general sense, a poppy with an altered alkaloid profile. 

10. This conclusion is consistent with Mr Bowser’s evidence that at the relevant date the forward genetics approach was, in fact, being pursued by the predecessor of the opponent as a means of obtaining poppies with an altered alkaloid profile.[125]

    Inventive step in light of the common general knowledge alone

    [125] Bowser at [36]-[37].

11. Sun submitted that claims 1-29, 31-38 and 43-46 lack an inventive step in light of the common general knowledge alone.  Sun submitted that a person skilled in the art seeking a high codeine poppy would be motivated to adopt a forward genetics approach as a matter of routine, given its wide application in other plants and previous use in poppies, and subject poppy seeds to mutagenesis and screen the resulting plants with an expectation of arriving at a high codeine plant as defined in the present claims.  Notably, this is not the approach taken by the inventors and described in the specification.  However, as mentioned above, the specification states that mutagenesis and screening of morphine-containing poppies is an approach that can be adopted to arrive at the claimed invention. 

12. In summary, Sun submitted that mutagenesis and screening was the obvious way of addressing the problem and that the expectation of success would be high for a number of reasons, including (i) the top1 poppy ‘proof of principle’ that morphinan alkaloids could be altered by that approach; (ii) the likely mutation of a single gene encoding a 6-O-demethylase acting in both branches of the biosynthetic pathway in the top1 poppy increasing the expectation that a single 3-O-demethylase also acts in both branches; and (iii) the major flux down the codeine branch of the bifurcated pathway.  I have discussed the knowledge of the flux in the pathway previously and found that the evidence does not establish that this was common general knowledge at the priority date.  

13. In TasAlk’s submission it does not follow that a process producing a poppy with one alkaloid profile could provide an expectation of producing a poppy having a different alkaloid profile; that in adopting a forward genetics approach it is not possible to target a specific profile and every chance that the desired phenotype would not be achieved; and it was not known before the priority date that a high codeine poppy could be achieved, let alone a poppy having the particularly high levels of codeine defined in the claims, and there could therefore not be a reasonable expectation of success.

14. A high codeine poppy was a well known goal.  TasAlk asserted that the specific characteristics of the poppy defined in the claim were not known to be desirable.  However, while the claim specifies the minimum threshold requirements of a high codeine poppy for the purpose of defining the monopoly, I view the scope of the claims to be consistent with the evidence as to desirable levels of codeine.  For example, Professor Graham stated in relation to bespoke poppies producing a particular alkaloid of interest that he would aim for the relative concentration of the alkaloid of interest being “as close to 100% as possible and certainly around 90%”[126] which he calculated would result in around 1.08-3.6% of the alkaloid of interest in the poppy straw.  The desirability of such alkaloid levels was not contradicted.

    [126] Graham 1 at [73].

15. A question then arises as to whether it could be expected that such a poppy was attainable at all.  I have considered above whether a forward genetics approach would be adopted as a matter of routine when seeking a poppy with an altered alkaloid content.  The consideration is then whether, accepting the random nature of the forward genetics approach, there could be a reasonable expectation, rather than a hope, of obtaining a poppy as defined in the present claims.  In this regard I note that the claims define both a predominance of codeine over morphine, and a high absolute quantity of codeine in poppy straw.

16. Professor Graham’s understanding was that “introducing mutations in the genes responsible for different states of the pathway could lead to an increase in production of particular alkaloids”[127] and in particular that “to obtain a high codeine phenotype it would be necessary to compromise one or more genes encoding the enzymes responsible for the relevant steps in the biochemical pathway”.[128]  Professor Graham also referred to knowledge of the existence of natural variation of alkaloid levels in poppies and the morphinan biosynthetic pathway, along with the top1 poppy as providing confidence that a high codeine phenotype was achievable.[129]  Professor Grof had a similar view.[130]

    [127] Graham 1 at [57].

    [128] Graham 1 at [61].

    [129] Graham 1 at [72]; Graham 2 at [33], [68].

    [130] Grof at [49]-[51].

17. While Professor Graham accepted that factors such as toxicity and feedback mechanisms may exist, he stated that: “the example of the top1 mutant is of a plant with high thebaine which is perfectly healthy.  I do not consider that the factors would necessarily pose a barrier to higher alkaloid levels in poppy varieties.”[131]  He further stated that there was “nothing robust or definitive in the public domain which indicated that it was not possible to produce high codeine poppies by mutagenesis and screening.”[132]

    [131] Graham 2 at [82]

    [132] Graham 2 at [64]

18. Mr Bowser stated the GlaxoSmithKline was undertaking mutagenesis to develop new poppy varieties and that he “assumed we would be able to obtain plants with the desired high codeine phenotype”.[133]  However, while Mr Bowser stated that “in research trials, single plants would commonly have dry weight amounts of alkaloids exceeding 4% in straw, suggesting cytotoxicity was a low risk in the development of new poppy variants”[134] he did not provide any other technical reason beyond the existence of the top1 poppy and other poppy variants for the assumption that a high codeine plant would be achievable.

    [133] Bowser at [36].

    [134] Bowser at [51].

19. While accepting that it was possible that mutagenesis would generate poppies with altered levels of alkaloids, Dr Gerlach did not accept that the production of a high codeine poppy was predictable:

    “Although mutants in the alkaloid biosynthesis pathway could be expected to accumulate altered levels of alkaloids, it was not known which specific alkaloids would accumulate if a particular gene was mutated or if a particular step in the biosynthetic pathway was disrupted.  Prof Graham states ‘For example, if the genes were disrupted to the extent that they no longer encoded a functional enzyme, the substrate of that enzyme would be expected to accumulate in the plant’.  This is a very simplistic view based on a linear biochemical pathway wherein different enzymes catalyse each different step of the pathway with no feedback mechanisms, no multi-enzyme complexes operating, no regulatory systems, no transportation of substrates in the plant, no production of compounds that are toxic to the plant and no production of compounds that are unstable in the plant.  In Prof Graham’s example, one would not necessarily expect the substrate to accumulate if the pathway were highly branched and bifurcated, or if any of the factors I have just mentioned were affecting the pathway.”[135]

    [135] Gerlach at [103].

20. Dr Millgate was of the same opinion:

    “given that there was very limited understanding of the pathway and its regulation, it would have been impossible to reliably predict whether a particular alkaloid profile could be achieved in a poppy let alone how such a poppy might be produced.”[136]

    [136] Millgate at [79].

21. Further, both Drs Gerlach and Millgate referred to the uncertainty of being able to produce a poppy having the claimed high absolute level of codeine:

    “Even if it were possible to produce a plant which produced 90% of a particular alkaloid relative to other alkaloids, there is no certainty that it would accumulate to 1.08% to 3.6% on a dry weight basis in the poppy straw.  The alkaloid may, for example, be toxic to the plant, it may be rapidly degraded, it may have feedback controls exerted on it, or it may only accumulate in certain cell types.”[137]

    “production of secondary metabolites competes with the energy the plant needs in order to otherwise thrive and grow.  As such, it would be expected that the amount of alkaloids produced would be limiting.  Equally, there may not be enough capacity within the plant to store such high levels of codeine, and, even if the codeine was stored elsewhere in the plant, this may in fact be toxic to the plant.”[138]

    [137] Gerlach at [121].

    [138] Millgate at [106].

22. Although Drs Gerlach and Millgate did not point to any examples in which a high level of a particular alkaloid was toxic, contemporaneous evidence is consistent with their concerns:

    “It has proven difficult to predict those steps in a pathway whose modification is most likely to influence product accumulation.  The reasons for this are varied: biosynthetic intermediates may be transported across a number of subcellular compartments (De Luca and St Pierre, 2000); intermediates may be trafficked between cell types (Bird et al., 2003; Weid et al. 2004; Murata and De Luca, 2005); intermediates may be handled by interdependent multienzyme complexes (Burbulis and Winkel-Shirley, 1999); and there may be competition between alternative biosynthetic pathways (Liu et al., 2002).”[139]

    “The increase in total alkaloids observed was generally attributable to increases in morphine, codeine and thebaine.  Increases in morphine and codeine can be expected from an increase in codeinone reductase; however, increases in thebaine were not expected given that this intermediate occurs prior to codeinone reductase in the pathway. Because there are still uncertainties about the cellular and subcellular localization of the various steps of the morphinan pathway, we can only speculate how this is happening. It may be that increases in morphine or codeine result in feedback inhibition of the demethylation steps or inhibition of thebaine transport to the vesicles in which codeine and morphine accumulate.”[140]   

    While specific steps in the biosynthetic pathway are not targeted in the random mutagenesis technique, I understand these passages as relevant to the capacity to predict whether accumulation of a particular alkaloid is possible.

    [139] Larkin, P.J. et al. (2007) ‘Increasing morphinan alkaloid production by over-expressing codeinone reductase in transgenic Papaver somniferum’, Plant Biotechnology Journal, vol. 5, pages 26-37 at 26 (Exhibit IAG-14).

    [140] Larkin, P.J. et al. (2007) ‘Increasing morphinan alkaloid production by over-expressing codeinone reductase in transgenic Papaver somniferum’, Plant Biotechnology Journal, vol. 5, pages 26-37 at 32 (Exhibit IAG-14).

23. Dr Gerlach also referred to complexities associated with the bifurcated nature of the biosynthetic pathway:

    “If one branch of the pathway was blocked, whether it was the more efficient branch or the less efficient branch, it is possible that the plant would compensate for the blockage by upregulating the flux through the other branch, and still maintain a morphine phenotype.”[141]

    [141] Gerlach at [109].

24. Drs Gerlach and Millgate did not believe that the existence of the top1 poppy or the natural variation in alkaloid levels could provide a source of confidence that a high codeine poppy could be produced:

    “The fact that mutagenesis had been used to identify a high thebaine, high oripavine poppy does not suggest that a high codeine [poppy] can be obtained by mutagenesis.  They are completely different alkaloids whose production is controlled by different genetic and biochemical mechanisms.  Indeed, the top1 screen failed to produce a high codeine poppy.  In my opinion, this would not lead those working in the poppy industry to expect that mutagenesis could be used to produce a high codeine poppy.”[142]

    “If one is trying to achieve a poppy that produces high levels of codeine, the fact that there was naturally occurring variation in the alkaloid profiles of poppy varieties, but that none of them accumulated high levels of codeine as the predominant alkaloid, suggested that such a phenotype might not be achievable.”[143] 

    “…I do not agree that natural variation in the alkaloid profiles of poppy plants, or indeed the fact that there was a precedent for using mutagenesis, would lead a researcher in the field to have any expectation of being able to produce specific phenotypes of interest.”[144]

    [142] Gerlach at [119].

    [143] Gerlach at [113].

    [144] Millgate at [100].

1. The factors contributing to uncertainty identified by Drs Gerlach and Millgate have been commented on by Professor Graham and Mr Bowser to some extent.  However, insofar as the expectation of success is based on the identification of the top1 poppy, to my mind this cannot counter the evidence of Drs Gerlach and Millgate relating to uncertainties regarding the accumulation of a specific particular alkaloid of interest, such as codeine – the top1 poppy demonstrates accumulation of thebaine and oripavine and the utility of forward genetics in identifying a new poppy variety, but does not provide any indication of the capacity of the poppy to accumulate the claimed level of codeine. 

2. I also note that in his initial declaration Professor Graham stated that it is “conceptually straightforward to generate double mutants”.[145]   Generally responding to this proposition, Dr Gerlach stated that “it was not known whether a single enzyme from a single gene (ie, not a gene family) catalysed the conversion of codeine to morphine as well as the conversion of thebaine to oripavine”[146] noting that:

   “If two or more genes must be mutated in order for a particular phenotype of interest to be observed, it becomes exceedingly unlikely, but not impossible, that mutagenesis will, by chance, knock out each relevant gene conferring the specific phenotype.  … a single round of mutagenesis, on its own, can be a very large undertaking.  Conducting multiple successive rounds of mutagenesis may not be feasible as a practical matter.”[147]

   “mutagenesis will rarely be employed to produce a phenotype which can only be observed when more than one gene is compromised.  If it were necessary to compromise more than one gene to achieve a particular phenotype, reverse genetic approaches are likely to be more attractive.”[148]

   [145] Graham 1 at [70].

   [146] Gerlach at [55].

   [147] Gerlach at [102].

   [148] Gerlach at [108].

3. Responding, Professor Graham did not directly contradict these statements.  Instead, he stated that it was “certainly possible in my view to hypothesise that a single gene catalysed the conversion of codeine to morphine as well as conversion of thebaine to oripavine”.[149]  While in other parts of his declaration Professor Graham indicated greater confidence in this hypothesis,[150] this statement is in highly speculative terms, and seems more the language associated with a research project “worthwhile to try” than the basis of the taking of routine steps with a reasonable expectation of success.  Mr Bowser also indicated that it “seemed highly probable” that “the enzyme that catalysed the conversion of thebaine to oripavine could be the enzyme carrying out the almost identical demethylation reaction from codeine to morphine”.[151]  Again, this language seems to me, in context, to be quite speculative.  While I am satisfied that at the priority date the preferred hypothesis was that the top1 phenotype was due to a mutation in a single enzyme acting in both branches of the pathway, it is not apparent that it was widely thought at the priority date that that would also be the case for an enzyme catalysing the conversion of codeine to morphine and thebaine to oripavine.  Indeed, Professor Graham did not strongly express this view until after he had reviewed the specification (which describes this hypothesis).[152]  The parties have not pointed to any evidence that such a hypothesis was well known or accepted, and Dr Gerlach’s evidence is such a view was not widely held[153] but was a “bold and risky hypothesis”.[154]  Considering his reasoning against the use of a forward genetics approach where two or more genes must be mutated, I am not satisfied that the evidence establishes to the level of practical certainty that the notional skilled person would, even if it is accepted that the claimed poppy was considered attainable, adopt a forward genetics approach as a matter of routine when specifically seeking a poppy as defined in the present claims.

   [149] Graham 2 at [38].

   [150] See, e.g. Graham 2 at [68].

   [151] Bowser at [57].

   [152] See, e.g. Graham 1 at [70]; Graham 2 at [58].

   [153] Gerlach at [134].

   [154] Gerlach at [55].

4. I accept that the evidence establishes that a skilled person when seeking poppies with an altered alkaloid profile in a general sense would adopt a forward genetics approach.  However, considering the evidence as a whole I am not satisfied that it establishes to the level of practical certainty that the notional person skilled in the art would, without the benefit of hindsight, have a reasonable expectation of success in achieving specifically the claimed high codeine poppy, or in doing so by a forward genetics approach.

5. For completeness, I note that the parties made submissions in relation to secondary indicia of inventive step.  In particular, TasAlk referred to the failure to identify a high codeine poppy in the study which identified the top1 poppy and the twelve year delay between the development of the top1 poppy and the poppy of the present application, despite the long felt desire for such a poppy and three research groups seeking to achieve this goal.  Responding, Sun submitted that it was the publication of the Millgate article in 2004 (four years before the priority date) which provided the high profile proof of principle regarding the top1 poppy.  Sun also submitted that the propensity of research groups in this field not to publish work led to idiosyncratic knowledge within groups, and that this, together with the highly regulated nature of the industry should be taken into consideration. 

6. I am conscious of the High Court’s caution that Australian courts “should be slow to ignore secondary evidence”, but I note that the weight given to such evidence will vary.[155]  In this case, it is apparent that there has been an absence in reported progress towards the known goal of high codeine poppy for a significant period.  However, the small number of participants in this field, and the evidence of the impact of the Millgate article relative to the publication of the top1 patent[156] leads me to give the absence of reported progress less weight relative to the expert evidence.  Nevertheless, to the extent that consideration of the long lack of progress and long felt desire for a high codeine poppy are useful as secondary indicators they support the presence of an inventive step.

   [155] Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (No 2) [2007] HCA 21; 235 CLR 173 at [116].

   [156] Graham 2 at [31], [37], [40].

7. Sun has not established that the claims lack inventive step in light of the common general knowledge alone.

   Inventive step in light of the prior art documents

8. Sun submitted that claims 1-29, 31-38 and 43-46 lack inventive step in light of the Millgate article and US 6067749 (US’749; Exhibit IAG-5) each considered together with the common general knowledge.  Both documents were published before the priority date of the present application.

9. The first question to be considered is whether the documents meet the threshold for s 7(3) and would have been ascertained, understood, and regarded as relevant.  Ascertained means found or discovered.[157]  A document would be ascertained “if it was published in such a manner or form that it could reasonably have been expected to be found by a person skilled in the art”.[158]  Understood means that a person would have comprehended the information, or “appreciated its meaning or import”.[159]  Relevant means that a person “will be likely to recognise the document in question as being particularly pertinent to, though it may not specifically solve the problem”.[160] 

   [157] Commissioner of Patents v Emperor Sports Pty Ltd [2006] FCAFC 26; 67 IPR 488 at 494-495, [29]-[30].

   [158] Nippon Kayaku Kabushiki Kaisha and Sankyo Company, Limited v Rohm and Haas Company [1997] APO 40.

   [159] Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (No 2) [2007] HCA 21; 235 CLR 173 at [132].

   [160] Beecham Groups Limited's (Amoxycillin) Application [1980] RPC 261 at 282.

10. The Millgate article discloses the identification of the top1 mutant poppy, which as discussed previously accumulates thebaine and oripavine but not codeine or morphine, by treatment of poppy seeds with a mutagen and screening of the progeny plants.  The Millgate article indicates that the segregation of F2 individuals was Mendelian and consistent with the involvement of a single gene.  The article also states:

    “Feeding of radioactive intermediates (see supplementary information) confirmed that there is a block in both arms of the bifurcated pathway at thebaine and oripavine in top1.  This block may be due to a defect in the enzyme thebaine demethylase, which is likely to be responsible for the 6-O-demethylation of both thebaine and oripavine.”

11. The Millgate article goes on to propose a number of possible explanations for the top1 phenotype:

    “… the gene encoding the 6-O-demethylase that acts on thebaine and oripavine might be affected, as could a gene that regulates its function or expression (such as a transcriptional regulator or a protein in a multiprotein complex).  Alternatively, there may be an alteration in a structural or transport component that prevents the substrates thebaine and oripavine from arriving at the subcellular compartment where O-demethylation occurs.”

12. US’749 is a patent document titled ‘Papaver somniferum strain with high concentration of thebaine and oripavine’ and, similar to the Millgate article, describes the identification of the thebaine and oripavine accumulating top1 mutant poppy via mutagenesis of poppy seeds using EMS and screening of the M2 generation.  The document describes screening 900 plants per week and indicates that a “plant having high thebaine and oripavine and substantially no morphine or codeine was found after screening approximately 8,000 plants.”[161]  US’749 states that “it is believed, for the Papaver somniferum variety described herein, that the production or activity of codeinone reductase (NADPH) has been substantially inhibited.”[162]

    [161] Column 10, lines 44-47.

    [162] Column 12, lines 10-13.

13. Both parties accepted that the Millgate article could be relied on under s 7(3).  TasAlk submitted that US’749 would not be ascertained in view of the evidence of Drs Gerlach and Millgate, who worked in the industry and did not routinely search for patents.[163]  However, Dr Gerlach indicated that patent databases were occasionally searched[164] and the evidence of Mr Bowser indicates that he searched patents[165] and that because the poppy industry is highly commercial, much research and development is reported in patent documents.[166]  Similarly, Professor Graham also stated that he frequently looked at patents, and found them to be “a useful source of information particularly with regards to the activities of the various companies in the opium poppy field who may not publish their research in the scientific literature.”[167]  I conclude from this evidence that some researchers in the poppy industry read the patent literature while others did not.  In the circumstances I consider that the notional person skilled in the relevant art could reasonably be expected to consult the patent literature in order to ascertain relevant documents.

    [163] Gerlach at [11]; Millgate at [11].

    [164] Gerlach at [88].

    [165] Bowser at [9].

    [166] Bowser at [16].

    [167] Graham 1 at [27].

14. Neither the Millgate article nor US’749 are directed to the same problem as the present application.  However, they are directed towards the preparation of a poppy plant having an altered alkaloid profile – the broad area of the invention, and accordingly I am satisfied that having been ascertained, they would be understood and regarded as relevant.     

15. I have already found above that the claimed invention does not lack inventive step in light of the common general knowledge alone.  Both the Millgate article and US’749 provide further detail concerning the top1 poppy, its generation by forward genetics and its possible underlying genetic basis.  US’749 also notes that the “production of mutagenized seed is well known in the art.”[168] 

    [168] Column 9, lines 6-7.

16. Professor Graham stated that the Millgate article provided a “proof of principle” that poppy plants having desired levels of alkaloids can be generated by forward genetics, and confidence that that approach could be used to obtain a further mutant poppy plant having a desired alkaloid profile.[169]

    [169] Graham 1 at [82]-[83].

17. Similarly, Professor Graham stated that the US’749 document:

    “highlights that knowledge of the genes encoding the enzymes involved in alkaloid synthesis are not required in order to obtain a plant with a desired phenotype.  This is a good demonstration that plants with an alkaloid profile of interest, can be obtained using a forward genetics approach in the absence of full knowledge of the genes and enzymes involved in the biosynthesis pathway.”[170]

    [170] Graham 1 at [90].

18. In contrast, Dr Gerlach was of the view that the fact that mutagenesis had been used to produce a high thebaine, high oripavine poppy does not suggest that a high codeine poppy could be obtained.[171]  Indeed, he stated that the absence of a report of high codeine poppies following the top1 screen “would have led many to believe it may not be feasible to obtain such a plant.”[172]  In response Professor Graham indicated that he would not assume that the EMS screen reported had been “done to exhaustion” or that other mutagens had been evaluated.[173]

    [171] Gerlach at [124], [127].

    [172] Gerlach at [124].

    [173] Graham 2 at [73].

19. The Millgate article and US’749 do not refer to a high codeine poppy (although I note that US’749 refers to analysing the mutant poppies for morphine, codeine, oripavine, thebaine and papaverine).  In the context of addressing the problem of producing a high codeine poppy, the evidence does not establish that these documents would alter the expectation of whether such a poppy was possible to achieve relative to the common general knowledge, which includes the top1 poppy, but these documents provide a fuller disclosure of the top1 poppy than what was part of the common general knowledge.  Therefore, for the reasons already given in relation to the common general knowledge alone, Sun has not established that the claims lack inventive step in light of either the Millgate article or US’749.

    Conclusion

20. The opposition is unsuccessful.  Sun has not established that the claims lack utility, lack inventive step or are not for a manner of manufacture.

    Costs

21. It is usual in matters before the Commissioner that costs should follow the event and I see no reason to depart from this approach.  TasAlk has been successful in this matter, and therefore I will award costs according to Schedule 8 against Sun.

    Dr S. J. Smith
    Delegate of the Commissioner of Patents

    Annex A

    1. An isolated plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine, and having a codeine content above 2% in the poppy straw on a dry weight basis.

    2. An isolated plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine, and having a codeine content above 2% in the poppy straw on a dry weight basis, wherein said plant is stably reproducing by self pollination in respect of said codeine fraction and said codeine content.

    3. An isolated plant of Papaver somniferum, which upon collection and drying of latex from its immature poppy capsules will yield an opium having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine, and which upon harvesting of its poppy capsules will yield a poppy straw having a codeine content above 2% on a dry weight basis, wherein said plant is stably reproducing by self pollination in respect of said codeine fraction and said codeine content.

    4. An isolated plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine, and having a codeine content above 2% in the poppy straw on a dry weight basis, wherein there is substantially no papaverine in the alkaloid combination.

    5. An isolated plant of Papaver somniferum, which upon collection and drying of latex from its immature poppy capsules will yield an opium having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine, and which upon harvesting of its poppy capsules will yield a poppy straw having a codeine content above 2% on a dry weight basis, wherein there is substantially no papaverine in the alkaloid combination.

    6. An isolated field-grown plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine, and having a codeine content above 2% in the poppy straw on a dry weight basis.

    7. An isolated field-grown plant of Papaver somniferum, which upon collection and drying of latex from its immature poppy capsules will yield an opium having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine, and which upon harvesting of its poppy capsules will yield a poppy straw having a codeine content above 2% on a dry weight basis.

    8. An isolated plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine, oripavine, papaverine and noscapine, and having a codeine content above 2% in the poppy straw on a dry weight basis.

    9. An isolated plant of Papaver somniferum, which upon collection and drying of latex from its immature poppy capsules will yield an opium having a codeine fraction of about 55% by weight or greater of an alkaloid combination, wherein the alkaloid combination comprises morphine, codeine, thebaine, oripavine, papaverine and noscapine, and which upon harvesting of its poppy capsules will yield a poppy straw having a codeine content above 2% on a dry weight basis.

    10. The plant of any one of claims 1 to 9, wherein thebaine constitutes about 40% by weight or less of the alkaloid combination.

    11. The plant of any one of claims 1 to 10, wherein codeine constitutes about 75% by weight or greater of the alkaloid combination.

    12. The plant of any one of claims 1 to 11, wherein thebaine constitutes about 25% by weight or less of the alkaloid combination.

    13. The plant of any one of claims 1 to 12, wherein codeine constitutes about 90% by weight or greater of the alkaloid combination.

    14. The plant of any one of claims 1 to 13, wherein thebaine constitutes about 10% by weight or less of the alkaloid combination.

    15. The plant of any one of claims 1 to 14, wherein codeine constitutes about 96% by weight or greater of the alkaloid combination.

    16. The plant of any one of claims 1 to 15, wherein thebaine constitutes about 2% by weight or less of the alkaloid combination.

    17. The plant of any one of claims 1 to 16, wherein there is substantially no morphine or oripavine in the alkaloid combination.

    18. The plant of any one of claims 1 to 17, wherein there is substantially no thebaine in the alkaloid combination.

    19. The plant of any one of claims 1 to 18 having a morphine content of about 0.05% or less in the poppy straw on a dry weight basis.

    20. An isolated plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw containing greater than 2% codeine on a dry weight basis and wherein the ratio of codeine and thebaine to an alkaloid combination comprising morphine, codeine, thebaine and oripavine is between about 0.90 and about 1.00.

    21. The plant of Claim 20 wherein the ratio is between about 0.98 and about 1.00.

    22. The plant of Claim 21 wherein the ratio is between about 0.99 and about 1.00.

    23. The plant of any one of claims 1 to 22 wherein the alkaloid combination further comprises salutaridine, reticuline and laudanine.

    24. The plant of any one of claims 1 to 7 or 20 to 22 wherein the alkaloid combination further comprises salutaridine, reticuline, laudanine, papaverine and noscapine.

    25. The plant of any one of claims 1, 4 to 9 or 20 to 22, wherein the plant is stably reproducing.

    26. An isolated plant of Papaver somniferum, which upon harvesting of its poppy capsules will yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination comprising morphine, codeine, thebaine and oripavine, wherein when said plant is crossed with a plant grown from seed deposited under accession number ATCC PTA-9147 or ATCC PTA-9294 thereby to obtain an F1 progeny plant, said F1 progeny plant will upon harvesting of its poppy capsules yield a poppy straw having a codeine fraction of about 55% by weight or greater of an alkaloid combination comprising morphine, codeine, thebaine and oripavine.

    27. An isolated plant of Papaver somniferum, which upon collection and drying of latex from its immature poppy capsules will yield an opium having a codeine fraction of about 55% by weight or greater of an alkaloid combination comprising morphine, codeine, thebaine and oripavine, wherein when said plant is crossed with a plant grown from seed deposited under accession number ATCC PTA-9147 or ATCC PTA-9294 thereby to obtain an F1 progeny plant, said F1 progeny plant will upon collection and drying of latex from its immature poppy capsules yield an opium having a codeine fraction of about 55% by weight or greater of an alkaloid combination comprising morphine, codeine, thebaine and oripavine.

    28. A part of the plant of any one of claims 1 to 25 such as a cell, a shoot or a root of the plant maintained for the production of an alkaloid selected from codeine or thebaine.

    29. A seed of the plant of any one of claims 1 to 25.

    30. Papaver somniferum seed selected from the seed deposited under accession number ATCC PTA-9147 or ATCC PTA-9294.

    31. A poppy straw comprising a poppy straw of the Papaver somniferum plant of any one of Claims 1-25.

    32. A concentrate of poppy straw comprising a concentrate of poppy straw concentrated from the poppy straw of Claim 31.

    33. A concentrate of poppy straw for the extraction of codeine comprising a concentrate of poppy straw of the Papaver somniferum plant of any one of Claims 1-25.

    34. An opium for the extraction of codeine comprising an opium of the Papaver
    somniferum plant of any one of Claims 1-25.

    35. A latex for the extraction of codeine comprising a latex of the Papaver somniferum plant of any one of claims 1-25.

    36. A stand of the Papaver somniferum plant of any one of claims 1-25.

    37. A method for the production of codeine which comprises the steps of:
    a) harvesting poppy capsules of the Papaver somniferum plant of any one of Claims 1-25 to produce a poppy straw; and
    b) extracting the codeine from the poppy straw.

    38. A method for the production of codeine which comprises the steps of:
    a) collecting and drying latex of immature poppy capsules of the Papaver somniferum plant of any one of Claims 1-25 to produce opium; and
    b) extracting the codeine from the opium.

    39. Progeny of a Papaver somniferum plant grown from seed deposited under accession number ATCC PTA-914 7 or ATCC PTA-9294, said progeny yielding a poppy straw having a codeine fraction of about 40% by weight or greater of an alkaloid combination wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine.

    40. The progeny of Claim 39 wherein said progeny yields a poppy straw having a codeine fraction of about 55% by weight or greater of the alkaloid combination.

    41. A mutant or variant of a Papaver somniferum plant grown from seed deposited under accession number ATCC PTA-9147 or ATCC PTA-9294, said mutant or variant yielding a poppy straw having a codeine fraction of about 40% by weight or greater of an alkaloid combination wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine.

    42. The mutant or variant of Claim 41 wherein said mutant or variant yields a poppy straw having a codeine fraction of about 55% by weight or greater of the alkaloid combination.

    43. A plant cell derived from the Papaver somniferum plant of any one of Claims 1-25.

    44. A plant root derived from the Papaver somniferum plant of any one of Claims 1-25.

    45. A codeine extracted from the poppy straw of Claim 31, the concentrate of poppy straw of Claim 32 or 33, the opium of Claim 34, or the latex of Claim 35.

    46. The isolated plant of Papaver somniferum of any one of claims 1 to 27; the part of the plant of claim 28; the seed of claim 29; the poppy straw of claim 31; the  concentrate of poppy straw of claim 32 or claim 33; the opium of claim 34; the latex of claim 35; the stand of claim 36; the method of claim 37 or claim 38; the progeny of claim 39 or claim 40; the mutant or variant of claim 41 or claim 42; the plant cell of claim 43; the plant root of claim 44; or the codeine of claim 45, substantially as herein described with reference to any one or more of the examples but excluding comparative examples.