TPI Enterprises Ltd v Tasmanian Alkaloids Pty Ltd

[2018] APO 8

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

TPI Enterprises Ltd v Tasmanian Alkaloids Pty Ltd [2018] APO 8

Patent Application:                2009253741

Title:Papaver somniferum with high concentration of codeine

Patent Applicant:                   Tasmanian Alkaloids Pty Ltd

Opponent:  TPI Enterprises Ltd

Delegate:  Dr S. J. Smith

Decision Date:  31 January 2018

Hearing Date:  15 June 2017 in Canberra

Catchwords:  PATENTS – opposition to the grant of a patent – grounds of manner of manufacture and inventive step – 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 Gerard Dalton QC

Solicitor for the opponent: Mr Zaven Mardirossian and Ms Claire Southwell of Arnold Bloch Leibler

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 Sun Pharmaceutical Industries (Australia) Pty Ltd v Tasmanian Alkaloids Pty Ltd [2018] APO 7 I direct that the application proceed to grant.

I award costs according to Schedule 8 against TPI Enterprises 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.  TPI Enterprises Ltd (TPI) filed a notice of opposition under section 59 on 7 September 2015 and a hearing was held in Canberra on 15 June 2017.  This decision relates to the opposition by TPI.  Sun Pharmaceutical Industries (Australia) Pty Ltd also opposed grant of the application and the decision in relation to that opposition is reported as Sun Pharmaceutical Industries (Australia) Pty Ltd v Tasmanian Alkaloids Pty Ltd [2018] APO 7 (the Sun 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 set out the following grounds of opposition: manner of manufacture, inventive step and fair basis.  Manner of manufacture and inventive step were pressed at the hearing, with manner of manufacture limited to the particular basis that the claims include naturally-occurring subject matter.  An amended statement of grounds and particulars reflecting those grounds was filed on 20 June 2017 and the amendment allowed 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	Peter James Facchini	PJF-1 to PJF-17	4 March 2016	Facchini 1
	Chris Murray	CM-1 to CM-2	6 March 2016	Murray 1
	Matthew David Lees	MDL-1 to MDL-19	4 March 2016	Lees 1
	Matthew David Lees	MDL-20	7 March 2016	Lees 2
In Answer	Wayne Lyle Gerlach	WLG-1 to WLG-5	1 July 2016	Gerlach 1
	Anthony Millgate	AM-1 to AM-5	4 July 2016	Millgate 1
In Reply	Peter James Facchini	-	4 September 2016	Facchini 2
	Chris Murray	CM-3 to CM-4	2 September 2016	Murray 2

1. After completion of the evidence periods a delegate of the Commissioner decided that Tookey H.L et al. (1973) ‘Codeine and morphine in Papaver somnifuerum grown in a controlled environment’, Planta Medica, vol. 30, pages 340-348 (Tookey) would be relied on under regulation 5.23.  TasAlk in response filed further declarations from Wayne Lyle Gerlach (Gerlach 2), dated 12 January 2017 and accompanied by exhibit WLG-6, and Anthony Millgate (Millgate 2), dated 11 January 2017 and accompanied by exhibit AM-6. 

   Onus

2. 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

3. 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. 

4. 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

5. 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].

6. 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].

7. 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.

8. The key declarants in this opposition are Professor Facchini, Dr Gerlach and Dr Millgate.

9. Professor Facchini is a Professor of Plant Biochemistry at the University of Calgary whose research has focused on understanding opiate and other benzylisoquinoline alkaloid biosynthesis in Papaver somniferum.[6]  He was the leader of one of the three major research groups working to develop variants of opium poppy before the priority date.[7]  I note that Professor Facchini was familiar with the present application and had been aware of it since 2010 or 2011.[8]  While this is a factor I am conscious of in considering his evidence, I note the comments of Bennett J in Austal Ships Pty Ltd v Stena Rederi Aktiebolag:[9]

   “The mere fact that a witness is aware of the patentspecification and the subject matter of the claims is not, in my opinion, of itself sufficient to cause his or her evidence to be disregarded. The Court must assess the evidence and the approach of the witness. Courts have long allowed for "the insidious effects of hindsight" in patentcases. This applies equally to evidence going to obviousness and evidence going to the extent of disclosure in a prior art publication that does not explicitly state the essential integers.”

   [6] Facchini 1 at [7]-[11].

   [7] Millgate 1 at [24].

   [8] Facchini 1 at [66].

   [9] [2005] FCA 805; (2005) 65 IPR 420 at [155]

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 he kept generally up to date with research on Papaver somniferum.[10]

    [10] Gerlach 1 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 has kept abreast of developments in the field of morphinan biosynthesis for a number of years following conferral of his PhD.[11]

    [11] Millgate 1 at [5]-[7].

12. Both parties accept that each of these declarants is qualified to give evidence in this matter.  However, TPI noted that neither Dr Gerlach nor Dr Millgate is independent from the applicant and submitted that their evidence should be treated with caution.

13. I am satisfied that these 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.

14. TPI also adduced evidence from Dr Murray, the Research and Development Director of TPI, who has a background in chemical processes for synthetic, semi-synthetic and high potency opiates and opioids, poppy straw extraction, opiate and opioid manufacturing facilities and technical evaluation of narcotic raw materials.[12]  TasAlk submitted that his evidence should be treated with caution given his association with the opponent. 

    [12] Murray 1 at [1], [5]-[10].

    The invention as described

    Background of the invention

15. 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%.[13] 

    [13] Page 4, lines 3-10.

16. 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:[14]

    [14] 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.[15]  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.[16]

   The aim of the invention

   [15] Page 1, lines 18-24.

   [16] 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.”[17]

   Nature of the invention

   [17] 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.[18]  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.[19]

   [18] Page 5, lines 20-30.

   [19] Page 6, lines 9-11.

7. In an embodiment of the invention the poppy plant is “stably reproducing”.[20]  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.”[21]

   [20] Page 6, lines 13-14.

   [21] 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.[22]  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.[23]  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[24] and discloses a rapid and efficient screening method, allowing for over 1000 samples to be analysed daily.[25] 

   [22] Example 1.

   [23] Page 20-21, bridging paragraph.

   [24] Page 17.

   [25] 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.” [26]

    [26] 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.”[27]

    The Examples

    [27] 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,[28] and a “generous measure of common sense should be used” in construing claims.[29]  There was no disagreement between the parties as to the construction of the claims.

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

    [29] 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.[30]

    [30] Gerlach 1 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.

   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.[31] 

   [31] Facchini 2 at [66], [67]; Gerlach 1 at [70].

7. 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.

8. 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.

9. 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.

10. 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.

    Manner of manufacture

11. 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[32] (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[33] (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?”

    [32] [2015] HCA 35; 89 ALJR 924 at [18].

    [33] [1959] HCA 67; 102 CLR 252 at 269.

12. At the hearing TPI indicated that it pressed this ground only in relation to the question of whether the claims encompass naturally-occurring poppies.

13. 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.”[34]

    [34] [2015] HCA 35; 89 ALJR 924 at [6].

14. TPI submitted that the claims do not define a manner of manufacture because they include naturally-occurring counterparts of the poppies described in the specification.  TPI emphasised that in considering manner of manufacture regard must be had to the scope of the claims, that is, the claims must be for a manner of manufacture across their entire scope and the claims in this case are not limited to those brought about by human intervention.  TPI submitted that the evidence establishes a real possibility that the claims encompass plants which may occur naturally by way of naturally-occurring genetic mutations, environmental conditions or both. 

15. TPI submitted that if a mutant poppy accumulating codeine can be arrived at by mutagenesis, it can arise naturally, and noted that naturally-occurring mutants have been identified with different alkaloid levels to the wild type morphine poppy.[35]

    [35] Millgate 1 at [62].

16. With regard to the possibility of a poppy within the scope of the claims occurring naturally due to environmental conditions, TPI relied on Tookey as evidence of the natural variation in alkaloids in poppies consequential to environmental conditions.  Tookey discloses standard (non-mutant) poppies grown under controlled environmental conditions producing a high proportion of codeine.  In particular, Tookey discloses a codeine to morphine abundance of 1.35 (corresponding to ~57% codeine) in capsules, which represents a substantial alteration relative to the corresponding poppy variety when field grown in Arizona, which is attributed to some (unknown) environmental influence.  Tookey does not report the content of any other alkaloids present in the capsules (and therefore the relative abundance of codeine to all alkaloids), or the required absolute yield of codeine.

17. In considering the disclosure of Tookey, Dr Millgate stated:

    “The gist of the Tookey publication is that by applying high levels of environmental stress to a plant, an increased level of codeine relative to morphine can be obtained.  While the plants in Tookey were grown under controlled conditions the plants were all uniformly smaller than comparable field grown plants of the same cultivar indicating that the plants were not grown at full potential or vigour and leading one to assume that the plants were stressed either in lower light levels/humidity or some other such factor that the authors could not control.

    Based on my knowledge and experience altering the growth conditions of plants, including applying stress, can in some cases lead to significant variation in relation to the outcome.

    However, in my view, it is very unlikely that the poppy plants in Tookey could ever be modified by external stress to provide both a high ratio of codeine:morphine/ codeine/thebaine/oripavine, and a high absolute yield of codeine.”[36]

    In line with this conclusion there was some discussion at the hearing as to whether or not the poppies described in Tookey were stressed, however, for the reasons that follow I do not need to decide whether that was the case or the significance of that question.

    [36] Millgate 2 at [7]-[9].

18. TPI referred to NV Philips’ Gloeilampenfabrieken Application[37] to support its argument that variants of naturally-occurring plants which occur as a result of environmental variations are not a manner of manufacture.  The alleged invention in NV Philips’ Gloeilampenfabrieken Application lay in the modification of the growing conditions of poinsettia such that an improved form of poinsettia resulted.  Lloyd-Jacob J found that while the modifications described were drastic, the production of the product was “the inevitable result of that which is inherent in the plant” and the application did not disclose a manner of manufacture.[38] 

    [37] (1954) 71 RPC 192.

    [38] (1954) 71 RPC 192 at 194.

19. However, the facts in the present case are distinguished from those in NV Philips’ Gloeilampenfabrieken Application in which there was no question that the relevant claimed plant phenotype was achieved under the particular growing conditions.  In the present case it is apparent that the poppies described in Tookey do not display the phenotype defined in the present claims, and there is no evidence that poppies with the claimed phenotype arise from naturally-occurring poppies under any environmental conditions.

20. TPI also referred to the decision by a delegate of the Commissioner in Cargill Incorporated v Dow AgroSciences LLC[39](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.  In the absence of evidence to support that submission, the delegate found that the opponent had not established a lack of manner of manufacture.  TPI submitted that the present situation is distinguished in that it appears in Cargill there was no evidence at all in relation to the prospect of naturally-occurring plants falling within the scope of the claims, whereas in the present case there is some evidence such that the proposition is not entirely speculative.  However, the evidence in this case does not go so far as to establish the existence of any naturally-occurring plant falling within the scope of the claims.

    [39] [2016] APO 43 at [46]-[50].

21. I understand TPI’s submission to be that the plants reported in the Tookey publication contained a low yield of alkaloids, including morphine, relative to modern commercial plants, such that if the same procedure was undertaken with a modern plant having a higher alkaloid content a poppy falling within the scope of the claims may well result.  While I accept that may be a logical argument, there is no evidence before me to support TPI’s contention, and it remains the case that Tookey does not disclose the content of other alkaloids present in the capsules.  Similarly, there is no evidence of any naturally-occurring mutant falling within the scope of the claims.  I cannot agree with TPI’s submission that requiring evidence on this point impermissibly conflates the grounds of novelty and manner of manufacture.  In an opposition proceeding where the opponent bears the onus of establishing that the claims are invalid to a matter of practical certainty, I consider that a finding that the claims are invalid on the basis that they encompass naturally-occurring subject matter must be based on more than a possibility that that is the case.  In the absence of evidence that the present claims do not define a product resulting from human action I cannot be “practically certain” that the claims do not define a manner of manufacture and it follows that TPI has not discharged its onus in relation to this ground.

    Inventive step

22. 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). 

23. Subsection  7(3) defines the relevant information:

    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.

24. 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:

    “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.”[40]

    [40] Wellcome Foundation Ltd v V.R. Laboratories (Aust.) Pty Ltd [1981] HCA 12; (1981) 148 CLR 262 at 286.

25. The High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd[41] (Alphapharm)  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.”[42]

    [41] [2002] HCA 59; (2002) 212 CLR 411 at 432-433, [50]-[53].

    [42] [2002] HCA 59; (2002) 212 CLR 411 at 436, [58]

26. The High Court in Alphapharm also approved the approach taken in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd,[43] 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.  While TasAlk submitted that this last question is the most authoritative test and should be applied in this case, properly understood the reformulated Cripps question and the “matter of routine” approaches are similar.  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.[44]  While the reasonable expectation of success does not require that success is guaranteed,[45] the taking of routine steps with a reasonable expectation of success is distinguished from steps which the skilled addressee would consider “worthwhile to try”.[46]

    [43] [1970] RPC 157 at 187.

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

    [45] [2002] HCA 59; (2002) 212 CLR 411 at 441-443, [74]-[76].

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

27. TPI pointed to Raychem Corp.’s Patents[47] (Raychem) as relevant to inventive step in this case, where Laddie J stated:

    “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.”[48]

    While Australian courts have referred recently to Raychem in relation to the concept of parametritis,[49] the law on inventive step in Australia has diverged from that in the UK.[50]  Consequently I will follow the approach set out by the High Court for considering inventive step.

    The problem

    [47] [1998] RPC 31.

    [48] [1998] RPC 31at 41.

    [49] Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4) [2015] FCA 634; Austal Ships Pty Ltd v Stena Rederi Aktiebolag [2005] FCA 805.

    [50] [2002] HCA 59; (2002) 212 CLR 411 at 431, [48]

28. It is apparent from the specification that the problem it addresses is the provision of a high codeine poppy.   There is no dispute that a high codeine poppy was a known and desirable goal in the art, and had been for many years.[51] 

    Common general knowledge

    [51] Facchini 1 at [42]; Millgate 1 at [74]; Gerlach 1 at [96].

29. 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.”[52]

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

30. Relevantly, the evidence establishes that the common general knowledge at the priority date included the knowledge that:

    • codeine is a natural alkaloid of the opium poppy and is the most widely used opiate in the world, but typically the yield of codeine, thebaine and oripavine in Papaver somniferum is less than that of morphine;[53]
    • the major part of the world’s licit morphine production is to support the manufacture of codeine (via O-methylation of morphine);[54]

    ·an improved poppy variety producing high levels of codeine without high levels of morphine was a desirable goal (with Dr Millgate stating that “production of a high codeine plant was considered the ‘Holy Grail’”[55]);[56]

    • a Papaver somniferum having a high thebaine and oripavine content had previously been produced by mutagenesis (the top1 poppy);[57]
    • a variety of Papaver somniferum having a high reticuline content had been achieved by mutagenesis;[58]
    • the morphine biosynthetic pathway is bifurcated and the underpinning genetics were not well understood.[59]

    [53] Specification page 1, lines 11-20; Facchini 1 at [37]; Gerlach 1 at [92].

    [54] Facchini 1 at [36].

    [55] Millgate 1 at [74].

    [56] Facchini 1 at [69].

    [57] Facchini 1 at [38]; Millgate 1 at [101]; Gerlach 1 at [103]

    [58] Facchini 1 at [38]; Millgate 1 at [101].

    [59] Facchini 2 at [25]; Millgate 1 at [90].

31. The evidence establishes that at the priority date it was known that there were three general methods for developing new plant varieties: traditional plant breeding, forward genetics (mutagenesis and screening) and reverse genetics.[60]  Each of these approaches had been applied to poppies, and as indicated above, the forward genetics approach had been used to arrive at poppies producing high levels of reticuline and high levels of thebaine and oripavine at the expense of codeine and morphine.

    [60] Millgate 1 at [23]; Gerlach 1 at [41]-[42].

1. I am satisfied that the top1 poppy itself formed part of the common general knowledge.[61]  However, the basis for the observed high thebaine and oripavine phenotype in this poppy was not known.  In the patent application relating to the top1 poppy it was postulated that production or activity of codeinone reductase (NADPH) had been inhibited.[62]  Subsequently, several alternative hypotheses for the observed phenotype were proposed in Millgate, A.G. et al. (2004) ‘Morphine-pathway block in top1 poppies’, Nature, vol. 43, pages 413-414 (the Millgate article; Exhibit PJF-3), including a likely hypothesis that the top1 poppy has a defect in a 6-O-demethylase acting in both branches of the bifurcated pathway from thebaine to morphine:

   “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.”

   [61] Facchini 1 at [38]; Millgate 1 at [101]; Gerlach 1 at [103].

   [62] WO 98/02033 at page 13 (Exhibit PJF-7).

2. Professor Facchini stated that he had incorporated the Millgate article into his knowledge[63] and Dr Millgate agreed that it would have been familiar to those working in the field of poppies.[64]  Accordingly, I accept that the information regarding the top1 poppy contained in the Millgate article forms part of the common general knowledge.

   [63] Facchini 1 at [21].

   [64] Millgate 1 at [96].

3. TPI referred to the text Poppy: The Genus Papaver, which Professor Facchini identified as a publication “particularly relevant” to the skilled worker,[65] as providing information forming part of the common general knowledge:

   “The occurrence of biochemical mutants following mutagenic treatments indicates the good potential of this approach in altering the alkaloid profile of plants.  A codeine chemotype in which the demethylation to morphine is blocked would be most valuable both to the pharmaceutical industry and for the prevention of the illegal use of morphine.  So far, no codeine-only producing mutant of P. somniferum has been reported.  However, in several medicinal and aromatic plants, specific hereditary blocks have been induced along biosynthetic pathways (Levy, 1982).  The thebaine-rich mutant reported by Nyman and Hall (1976) strengthens this possibility in P. somniferum.”[66]

   Neither Drs Gerlach nor Millgate express an opinion regarding whether this text was routinely consulted, however, the quoted passage does not appear to extend further than the accepted common general knowledge, that is, that a high codeine poppy was desirable, and mutagenesis has been used to alter the alkaloid profile of poppies.

   Professsor Facchini’s evidence

   [65] Facchini 1 at [49].

   [66] Levy, A. and Milo, J. ‘Genetics and breeding of Papaver somniferum’ in Poppy: The Genus Papaver, Jeño Bernáth (ed). Harwood Academic Publishers, Amsterdam, 1998 (Exhibit PJF-13).

4. As noted previously, I am conscious that Professor Facchini was familiar with the patent application prior to giving his evidence.  I am also mindful that, as “a major contributor to the discovery, characterization and biotechnological application of novel genes, enzymes, and metabolic processes derived from the opium poppy and related plants”,[67] Professor Facchini appears to have exceptional skill and knowledge in this field.

   [67] Facchini 1 at [18].

5. Professor Facchini expected that a skilled worker would have the ability to undertake mutagenesis,[68] describing it as “a well-established plant breeding technique to produce genetic variants”[69] and stated that:

   “techniques applied to the breeding of opium poppy in Australia prior to (and after) 28 May 2008 involved the standard practices of (i) random mutagenesis to generate individual plants with a wide range of genetic variability (e.g. knock-outs for individual or multiple genes), (ii) phenotypic screening to identify individuals displaying a desired trait (e.g. high thebaine and oripavine levels at the expense of morphine and codeine), and (iii) genetic crosses (e.g. backcrossing, recombinant inbreeding) aimed at establishing inbred or isogenic lines to maximise and maintain the phenotype.

   In general, the advantages of the aforementioned breeding approach are (i) no knowledge of the underlying genetics or biochemistry responsible for the phenotype in the plant is required, and (ii) the principal phenotype can potentially be achieved relatively quickly.  The disadvantages are (i) the potential that random mutagenesis will not yield a line with the desired phenotype, (ii) establishing inbred lines is a relatively slow, multigenerational process requiring several years to complete, and (iii) the ‘black box’ nature of the resulting cultivar presents limitations to more elegant approaches to refine the quality of the line owing to a lack of knowledge concerning the genetic and biochemical basis for the phenotype.
   …

   It could be expected that before 28 May 2008, a Skilled Worker in the Field in Australia, using established plant-breeding techniques would produce new varieties of opium poppy with certain diverse phenotypes (e.g. high levels of codeine and thebaine, and upstream biosynthetic pathway intermediates such as salutaridine and reticuline) depending on which gene(s) was mutated.”[70]

   [68] Facchini 1 at [30].

   [69] Facchini 2 at [9].

   [70] Facchini 1 at [46]-[48].

6. Professor Facchini’s evidence is consistent with the specification which states that “production of mutagenized seed is well known in the art”[71], the description of the approach to mutagenesis and breeding given in the present specification and in the patent specifications associated with the high reticuline and top1 poppies published in the late 1990s.[72]  Statements in contemporaneous documents 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.”[73]

   “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.”[74]

   [71] Page 12, line 4.

   [72] Exhibits PJF-7 and PJF-9.

   [73] Facchini, P.J. et al (2007) ‘Opium poppy: blueprint for an alkaloid factory’, Phytochem Rev, vol. 6, pages 97-124 at 115 (Exhibit PJF-16).

   [74] 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 PJF-17).

7. Professor Facchini stated that a poppy that accumulates codeine but not morphine had been a “common iteration of my research program from its inception in 1992”[75] and that:

   “the goal of a codeine-specific opium poppy variety was achievable once the molecular biology (i.e. the gene) and the biochemistry (i.e. the cognate enzyme) were established.  These goals were major objectives in my research program long before the Priority Date and were actually achieved shortly afterward.”[76]

   [75] Facchini 1 at [69].

   [76] Facchini 1 at [43].

8. In TasAlk’s submission this statement provides strong support for the proposition that before the priority date there was no expectation that a high codeine poppy could be achieved.  However, in the context of Professor Facchini’s evidence as a whole I understand this statement to mean that Professor Facchini believed before the priority date that a high codeine poppy was likely to be achievable by genetic manipulation.

9. Although Professor Facchini’s own research methodology followed primarily a reverse genetics approach focussed on identifying genes, rather than “simply the creation of a phenotype”[77] I am satisfied that he is in a position to provide evidence as to whether a person skilled in the art could expect to achieve a high codeine poppy via a forward genetics approach.  To that end, Professor Facchini stated that mutagenesis and conventional breeding “would have been seen as an obvious way to attempt to generate new alkaloid phenotypes.”[78]  In particular, Professor Facchini considered that it would be clear to a skilled person that a poppy having a higher yield of codeine would be achievable via mutation and breeding.[79]  Furthermore, Professor Facchini indicated that the top1 poppy was a source of confidence that other alkaloids could be targeted for specific increases in abundance,[80] and in particular that a high codeine poppy could be achieved.[81]  He stated that he had used mutagenesis in research programs in association with industrial research contracts from 2003-2006 and 2006-2008 and:

   “The ‘inspiration’ for the research proposals (and, indeed, the ability to “sell” the mutagenesis approach to industrial sponsors) was substantially based on the published patent regarding the top1 mutant line.

   The purpose was to mutate and breed Papaver somniferum plants to produce stable varieties with commercially or scientifically useful altered phenotypes, including but not limited to alkaloid composition.  The programs were limited by the resources available to screen plants grown from the mutagenized seed.  However, interesting plants with altered alkaloid content were obtained.  Our relatively limited resources did not enable the screening of tens of thousands of plants, which undoubtedly would have increased the number of phenotypic mutants.”[82]

   [77] Facchini 2 at [15].

   [78] Facchini 2 at [19].

   [79] Facchini 1 at [71].

   [80] Facchini 2 at [16].

   [81] Facchini 2 at [33].

   [82] Facchini 2 at [11]-[12].

10. I note that the objective of these studies was the production of varieties with altered phenotypes in a general sense, rather than pursuit of any particular phenotype of interest.

11. Professor Facchini accepted that with mutagenesis there could not be a “guarantee of success”,[83] but he explained that:

    “the chance of success would be subject to the inherent randomness of mutagenesis.  The greater the number of seeds mutagenized and the greater the number of mutated plants screened; the greater the prospects of success.  That random risk can be moderated by the application of time and resources.”[84]

    [83] Facchini 2 at [22].

    [84] Facchini 2 at [29].

12. While Professor Facchini has, as set out above, indicated that this would be an obvious approach to generate poppies having new alkaloid phenotypes and that it would be clear that a codeine poppy would be achievable by forward genetics, he also stated:

    “The scientific basis for the high-codeine and low-morphine phenotype obtained is unknown.  Based on this, I would suggest that the breeding strategy was ‘worth a try’, but in my opinion (at least from the perspective of how I personally approach scientific research questions and their translation to solve applied problems) it does not appear to define a typically ‘rational’ inventive process.”[85]

    [85] Facchini 1 at [75].

13. While this statement is in reference to the specific approach taken in the present application rather than mutagenesis in general, characterisation of an approach as ‘worth a try’ is in my view inconsistent with it being undertaken as a matter of routine with an expectation of success, noting that the Court has found that steps that are “worthwhile to try” are not routine steps undertaken with an expectation of success.[86]  Furthermore, as discussed above, a high codeine poppy had been a goal of Professor Facchini’s research since 1992 but it had not been achieved by the priority date of the present application, and while Professor Facchini had undertaken mutagenesis studies, a limitation in resources prevented the screening of large numbers of plants.  In my view this is also a consideration that weighs against such an undertaking being a matter of routine in specifically seeking a high codeine poppy.

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

14. Professor Facchini accepted that some phenotypes do not occur naturally, for example, if the mutation necessary is lethal or deleterious to the plant,[87] and that alkaloid biosynthesis is complex[88] and “suppression of a gene responsible for a specific biosynthetic conversion does not guarantee a predicted metabolic outcome”, for example due to biochemical regulatory mechanisms.[89]

    [87] Facchini 2 at [18].

    [88] Facchini 2 at [78].

    [89] Facchini 2 at [76].

15. Nevertheless, Professor Facchini explained his expectation of success based on the biosynthetic pathway and the top1 poppy as follows:

    “It had been known  since the mid 1980’s that approximately 89% of morphine is produced via Pathway A [from codeine] and 11% via Pathway B [from morphinone].

    …codeine is the immediate upstream biosynthetic pathway intermediate to morphine in Papaver somniferum.  Codeine is converted to morphine by O-demethylation at the C3 position.  It was known in 2008 that, within the plant, O­-demethylation would be catalysed by an enzyme.  Although the gene and cognate enzyme responsible for the O-demethylation of codeine to morphine was not known in 2008, it was widely appreciated by those in the field that knocking out, or knocking down, the expression of this gene would likely result in the accumulation of codeine at the expense of morphine by preventing or restricting the conversion of codeine to morphine.

    It would also have been known by a Skilled Worker that Pathway B commences with the conversion of thebaine to oripavine and that that conversion is also effected by a regiospecific 3-O-demethylation.  The gene and cognate 3-O-demethylase responsible for regulating the conversion of thebaine to oripavine had not been identified and was not known in 2008.  It was also unknown whether the gene and enzyme responsible for the conversion of thebaine to oripavine was the same as that responsible for the conversion of codeine to morphine.  However, that was known to be one possibility which, if true, would mean that the silencing or inhibition of the expression of the gene would be likely to result in further accumulation of codeine at the expense of morphine by also blocking or inhibiting the conversion of thebaine to oripavine and therefore the production of morphine via Pathway B.”[90]

    “Given that the inhibition of the enzyme active in both pathways caused the accumulation of thebaine and oripavine at the expense of codeine and morphine, there had to be a second independent gene and cognate enzyme in Papaver somniferum responsible for the conversion of thebaine to oripavine.  It was possible, and perhaps likely, that that enzyme would also operate in both pathways and, as stated above, also regulate the conversion of codeine to morphine.

    For these reasons, it is my opinion that the top1 poppy patent application would have given confidence to a Skilled Worker that adopting the process disclosed in the patent might well produce a Papaver somniferum plant that accumulated codeine at the expense of morphine.”[91]

    I note that Professor Facchini’s comments in relation to the likelihood of a single enzyme converting thebaine to oripavine and codeine to morphine are in speculative terms and the parties did not point to any contemporaneous evidence of such a hypothesis being well known.

    Drs Gerlach’s and Millgate’s evidence

    [90] Facchini 2 at [24]-[26].

    [91] Facchini 2 at [28]-[29].

16. The evidence of Drs Gerlach and Millgate is largely directed to the expectation of successfully obtaining a poppy having a particular desired alkaloid level, with Dr Gerlach stating:

    “The application of any plant breeding technique as at May 2008 would have been speculative at best.  Before 29 May 2008, no high codeine poppy had been produced after decades of poppy breeding.”[92]

    [92] Gerlach 1 at [102].

17. Similarly, Dr Millgate stated that:

    “the development of new poppy plants was, at least by the mid-2000s, still a potentially very long process which offered no confidence in being successful.  Furthermore, any development work towards producing a variant that could produce elevated or improved yields of any given alkaloid or combination of alkaloids, although possibly based on “educated guesses”, was still unpredictable at best.”[93]

    “by the mid-2000s, it was widely recognised that the study of the morphine pathway was limited by several factors.  Firstly, morphinan alkaloids are only found in appreciable amounts in the Papaver species … Secondly, very few mutants had been reported in the literature and very few of those mutants were stable or well characterised.  Thirdly, although a transformation system was available for opium poppy, few genes had been characterised or cloned in order to retransform them into the plant.”[94]

    “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.”[95]

    “At the time high codeine plants were not known and it was not clear whether any insurmountable barriers to high codeine plants may be present.”[96]

    [93] Millgate 1 at [22].

    [94] Millgate 1 at [55].

    [95] Millgate 1 at [79].

    [96] Millgate 1 at [99].

18. Given the existence of the top1 and reticuline poppies, and the failure to achieve a high  codeine poppy, Dr Millgate considered that a skilled person would be likely to conclude that a codeine accumulating poppy was more difficult (if it was in fact possible) to attain than the high reticuline or top1 poppies.[97]  Indeed, Dr Millgate stated that:

    “A person working in the field would also have known that, before 29 May 2008, Tasmanian Alkaloids were the world leader in poppy research and, at the time, the only successful producer of altered alkaloid poppies.  A person skilled in the art would not think a codeine poppy was easily achievable given that a cutting-edge and well-resourced company like Tasmanian Alkaloids had not achieved that in the decade following realisation of the top1 poppy.”[98]

    “…Professor Facchini indicates that the skilled worker should be able to produce new varieties of opium poppy with certain diverse phenotypes depending on which genes were mutated.  In my view this is an oversimplification.  In natural plants, morphine is the predominant alkaloid.  It was only after considerable work and significant investment of time and money that Tasmanian Alkaloids were able to produce the reticuline and top1 poppies.  A great deal of time and money was involved in the generation of a codeine plant.  As explained earlier, the interactions within the plant such as transportation, storage, enzyme access, the possible relationship of multi-enzyme complexes, a potential lack of specificity of certain enzymes, toxicity and other homeostatic and regulatory processes within the plant make it far from certain that the desired outcome can be obtained.”[99]

    “While the biosynthetic scheme for alkaloids shows the conversion of one compound to the next, that scheme is an oversimplification of the complex processes which take place in the plant.  For example, the various conversions are known to take place at different locations in the plant, as noted above.  Before the mid 2000’s (and even today) very little was known about the storage and transport of the intermediate compounds in the biosynthetic pathway.  As indicated in paragraph 17 of Professor Facchini’s declaration, even recently, discoveries are still being made about the different sites of intermediate conversion within the plant.  There are various shuttling mechanisms to move the intermediates to and from the relevant enzyme before and after conversion.  These processes, among others, all need to be properly regulated in order for the synthetic scheme to progress.

    In addition, plants contain various feedback loops that act against the build-up of potentially toxic intermediates by shutting down upstream processes.  This is particularly relevant in the production of secondary metabolites, such as morphine, which are not vital for the plant’s survival.”[100]

    [97] Millgate 1 at [101], [103].

    [98] Millgate 1 at [119].

    [99] Millgate 1 at [109].

    [100] Millgate 1 at [92]-[93].

1. Dr Millgate noted that a person working in this field at the relevant time would have been aware that Tasmanian Alkaloids was undertaking mutagenesis work but other groups were pursuing a reverse genetics approach[101] and expressed the view that a skilled person would be more inclined to follow the reverse genetics approach.[102]   Dr Millgate stated that “reverse and forward genetics may potentially be used to produce a high codeine poppy, but in either case, one could not be confident that it would be achieved.”[103]  I note that in the Sun opposition Dr Millgate indicated that he would not have considered “the forward or reverse genetic approach more or less attractive” and that possibly a conventional breeding approach would be the most attractive,[104] but I draw no inference from this apparent inconsistency.

   [101] Millgate 1 at [96].

   [102] Millgate 1 at [121].

   [103] Millgate 1 at [105].

   [104] Declaration of Anthony Millgate dated 4 July 2016 and filed as evidence in answer in the Sun opposition at [139].

2. Dr Gerlach agreed with Dr Millgate that there could be no expectation or prediction of success in seeking a high codeine poppy.  While Dr Gerlach was involved in the project which gave rise to the top1 poppy in the early to mid 1990s, he stated that the aim of that project was to “generate new genetic variants and then possibly select plants with useful characteristics”[105] and that “mutagenesis was chosen as an approach to generate metabolite diversity, although the likelihood of success was unknown.”[106]  Nevertheless, in undertaking this project:

   “It was hoped that variants might arise which produce alkaloid yields in different amounts compared to the commercial cultivar… Even though it was acknowledged that an improved yield of certain alkaloids, such as thebaine, oripavine and codeine, was highly desirable, there was no predictability or expectation that such variants could or would be produced.”[107] 

   [105] Gerlach 1 at [40].

   [106] Gerlach 1 at [42].

   [107] Gerlach 1 at [45].

3. Dr Gerlach stated:

   “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. However, many factors can make it difficult to understand the mechanisms of plant secondary metabolite biosynthesis such as the duplication of genes encoding certain biosynthetic enzymes, the operation of multi-enzyme complexes, feedback and homeostatic mechanisms that regulate the pathway, tissue-specific synthesis and containment, and the possible activity of single enzymes at multiple steps in the pathway.

   It has long been widely known that the biosynthetic pathway for alkaloid compounds is very complex.  Many different precursors are involved for the various pathways, and for several alkaloids, two different precursors are needed for the biosynthetic pathways.”[108]

   [108] Gerlach 1 at [30]-[31].

4. Dr Gerlach agreed with Professor Facchini that in forward genetics “luck is at least as important as skill because you cannot confidently predict that you will find a mutant with the target trait(s)”[109] and explained that various factors can impact whether a particular phenotype is achievable:

   “The reason that mutagenesis is often referred to as “random” mutagenesis is because the mutagen induces mutations randomly throughout the genome.  Many mutations will not occur in genes and will have no visible consequence on the phenotype of the plant.  For the mutation to have an observable effect on the plant, it must occur in a gene which, when mutated, is not lethal to the plant but will give rise to a visible phenotype, hopefully a phenotype of interest.  Moreover, within that gene, the mutation must occur in a region which confers functionality such as a region coding for the activity of an enzyme.  In addition, the gene should naturally exist as a single copy in the genome of the plant.  If there are multiple copies of the gene in the genome, a mutation in one gene may have no observable effect on the plant due to the redundant activity of the other genes.  Not all genes, when rendered non-functional by mutagenesis, will have a visible effect on the phenotype of the plant.  Some genes may act quantitatively on a particular phenotype and will have no observable phenotypic affect on their own.

   Another factor that can complicate the identification of a particular mutant phenotype is the phenomenon of pleiotropy.  This occurs when one gene controls multiple phenotypes.  For example, one gene may encode an enzyme which acts in two separate biochemical pathways making it difficult, or practically impossible, to isolate a mutant defective in only one pathway.  For at least these reasons, mutagenesis can only be used to identify particular mutant phenotypes and cannot be predictive of any particular characteristic.”[110]

   [109] Gerlach 1 at [90].

   [110] Gerlach 1 at [98]-[99].

5. Drs Gerlach and Millgate also noted the unpredictability of increasing or decreasing expression of a given enzyme in the alkaloid biosynthetic pathway with reference to a paper describing the silencing of codeinone reductase.  Surprisingly, this resulted in accumulation of (S)-reticuline, an alkaloid seven enzymatic steps upstream of codeinone.[111]  Accordingly, Dr Gerlach stated that:

   “it is not possible to accurately predict the effect of increasing or decreasing the expression of a particular enzyme in the alkaloid biosynthesis pathway.  The enzyme may catalyse multiple steps in the pathway or it may act as part of a multi-enzyme complex.  Feedback or homeostatic mechanisms could act within the pathway.  Certain intermediates may be more toxic to the plant than others.  As Prof Facchini mentioned in paragraph 17 of his declaration, transport and compartmentalisation of certain alkaloids occur within the plant, further adding to the complexity of the pathway.”[112]

   [111] Gerlach 1 at [111]; Millgate 1 at [105].

   [112] Gerlach 1 at [112].

6. Similarly, Dr Millgate stated:

   “the interactions within the plant such as transportation, storage, enzyme access, the possible relationship of multi-enzyme complexes, a potential lack of specificity of certain enzymes, toxicity and other homeostatic and regulatory processes make it far from certain that the desired outcome can be obtained.”[113]

   and

   “it does not necessarily follow that low morphine leads to high codeine, for instance, the natural mechanisms in the plant may use a feedback mechanism to prevent codeine build up.”[114]

   [113] Millgate 1 at [109].

   [114] Millgate 1 at [112].

7. Contemporaneous evidence is consistent with the concerns expressed by Drs Gerlach and Millgate:

   “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).”[115]

   “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.”[116]   

   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 or not accumulation of a particular alkaloid is possible.

   Inventive step in light of the common general knowledge alone

[115] 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 PJF-6).

[116] 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 PJF-6).

1. TPI submitted that claims 1-29, 31-38 and 43-46 lack an inventive step in light of the common general knowledge alone.  While the claim defines the poppy phenotype, not the process by which the poppy is made, the tests for inventive step direct attention to whether the invention would be arrived at as a matter of routine, or whether a person skilled in the art would be directly led to the claimed invention.  TPI submitted that a person skilled in the art seeking a high codeine poppy would have been directly led to try to obtain a high codeine poppy using the routine technique of mutagenesis and screening with an expectation that it might well produce a high codeine poppy.  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 could be taken to arrive at the claimed invention. 

2. In summary, TPI submitted that the reticuline accumulating and top1 poppies would have taught the skilled worker that it was possible to breed other poppy varieties having altered alkaloid contents and there was nothing known about the biosynthetic pathway that would teach a skilled worker a high codeine poppy could not or was sufficiently unlikely to be achieved that success could not be reasonably expected.

3. Responding, TasAlk submitted that 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 the required reasonable expectation of success.

1. I have found above that it was common general knowledge at the priority date that a high codeine poppy was a desired 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 do not view the scope of the claims as inconsistent with the evidence that a poppy which accumulates codeine at the expense of, in particular, morphine was desirable, and a greater than 55% relative proportion of codeine would be expected if expression of the relevant gene was silenced.[117]

   [117] Facchini 2 at [39].

2. I am satisfied that the evidence establishes that mutagenesis and screening is an approach that could be expected to have been undertaken when seeking poppies with an altered alkaloid profile in a general sense.  While I note that Dr Millgate considered that a mutagenesis process was not standard in Australia at the priority date,[118] I have given more weight to the views of Professor Facchini and Dr Gerlach given their more relevant experience in the generation of plants exhibiting new phenotypes, and the indication in contemporaneous documents that mutagenesis of poppies is not unusual.

   [118] Millgate 1 at [106].

3. The key area of disagreement between the experts is in relation to whether it could be reasonably expected that a high codeine poppy was attainable.  It is apparent that before the poppy had been achieved there could be no guarantee that it could be attained.  The question is whether there was reasonable expectation of success such that a forward genetics approach would be undertaken as a matter of routine in seeking such a poppy.

4. As discussed above, Drs Gerlach and Millgate identified a number of matters as engendering substantial uncertainty as to whether the claimed poppy was attainable, including possible toxicity, feedback or homeostatic mechanisms in the plant and/or complexities associated with transport and storage.  There is no dispute that the conversion of codeine to morphine is under genetic control – the uncertainties relate to the regulation of the biosynthetic pathway in planta and while I understand that Professor Facchini considers that “predictability dominates”[119]  the evidence of Drs Gerlach and Millgate, and the statements in contemporaneous documents referred to above, suggest that the level of this predictability is not high.  This leads me to a view that pursuit of a high codeine poppy via forward genetics is more in the nature of a “worthwhile to try” research project, than a routine undertaking.  Further, to the extent that Professor Facchini’s expectation of success is based on the identification of the top1 poppy,[120] I am not satisfied that this reasoning can overcome the evidence of Drs Gerlach and Millgate relating to specific uncertainties regarding the accumulation of any 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 it does not provide any indication of the capacity of a poppy to accumulate the claimed level of codeine. 

   [119] Facchini 2 at [78]-[79].

   [120] Facchini 2 at [33].

5. I accept that the notional skilled person would not have known of the activities of TasAlk or other groups in pursuit of a high codeine poppy[121] and consequently that knowledge cannot in itself be a consideration contributing to a lack of expectation of success.  However, the evidence as a whole in my view is not conclusive with regard to why a skilled person would have an expectation of success versus why they would not.  Accordingly, I cannot be satisfied to the level of practical certainty that the notional person skilled in the art would have a reasonable expectation, rather than a hope, of successfully obtaining a high codeine poppy as defined in the present claims.  It follows that I cannot find that the claimed invention lacks inventive step in light of the common general knowledge alone.

   [121] Facchini 2 at [73]-[74].

6. 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.  TPI submitted that there was no long felt commercial need for a high codeine poppy, referring to the evidence of Dr Murray that there “is comparatively little demand in the global licit opiate industry”  reflected in the continuing production of most codeine from morphine at 2013.[122]  However, notwithstanding Dr Murray’s evidence as to commercial considerations, I am satisfied on the evidence of Drs Gerlach and Millgate, Professor Facchini and the contemporaneous evidence referred to previously, that a high codeine poppy was a highly desired outcome.

[122] Murray 1 at [87]; Murray 2 at [27].

1. I am conscious of the High Court’s caution that Australian courts “should be slow to ignore secondary evidence”, but the weight of such evidence will vary.[123]  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.  This is a consideration that potentially supports the presence of an inventive step.  However, the small number of participants in this field and the random and potentially lengthy nature of a mutagenesis approach would lead me to give less weight to this lack of reported progress relative to the evidence of the declarants.  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.

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

2. TPI has not established that the claimed invention lacks inventive step in light of the common general knowledge alone.

Inventive step in light of the prior art documents

1. TPI approached the question of inventive step on the basis that the top1 poppy forms part of the prior art base either as common general knowledge or as s 7(3) information, that is, the disclosure of WO 98/02033 (WO’033; Exhibit PJF-7) when considered together with the common general knowledge.[124]  WO’033 was published before the priority date of the present application.

   [124] I note that TasAlk accepted that the Millgate article could be relied on as a s 7(3) document, but the Millgate article does not form part of TPI’s particulars relating to inventive step and in any event I have found that the information in the Millgate article forms part of the common general knowledge.

2. The first question to be considered is whether this document meets the threshold for s 7(3) and would have been ascertained, understood, and regarded as relevant.  Ascertained means found or discovered.[125]  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”.[126]  Understood means that a person would have comprehended the information, or “appreciated its meaning or import”.[127]  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”.[128] 

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

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

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

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

3. WO’033 is a patent document titled ‘Improved production of thebaine and oripavine’ and 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.”[129]  WO’033 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”[130] and

   “it is highly unlikely that the production or activity of two different enzymes, one active in each pathway, was simultaneously inhibited in a given mutagenized plant.  It is far more likely that the production or activity of a single enzyme was inhibited that is active in both pathways.”[131]

   [129] Page 12, lines 20-21.

   [130] Page 12, lines 25-27.

   [131] Page 13, lines 20-24.

4. TasAlk submitted that WO’033 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, although Dr Gerlach indicated that he had done so occasionally.[132]  Professor Facchini stated that:

   “much of the research focused on altering the alkaloid profile of the opium poppy has been conducted by or on behalf of participants in the licit opiates industry.  For commercial reasons, typically that research is either not published at all or is published only after a patent application has been published.  For that reason, patent documents may be the first and best source of information about particular research projects.”[133] 

   This is consistent with Professor Facchini’s familiarity with the present application and indeed WO’033.[134]  I conclude from the evidence that some researchers in the poppy industry consulted the patent literature while others did not.  In the circumstances I consider that the person skilled in the relevant art could reasonably be expected to consult the patent literature in order to ascertain relevant documents.

   [132] Millgate 1 at [11]; Gerlach 1 at [11].

   [133] Facchini 2 at [7].

   [134] Facchini 1 at [50], [66].

1. WO’033 is not directed to the same problem as the present application.  However, it discloses 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, it would be understood and regarded as relevant.

2. WO’033 does not refer to a high codeine poppy (although I note it does refer to analysing mutant poppies for morphine, codeine, oripavine, thebaine and papaverine), but provides a fuller disclosure of the top1 poppy and its preparation than forms part of the common general knowledge.  Professor Facchini indicated that the statement in WO’033 that it is likely that a single enzyme active in both pathways had been mutated to give rise to the observed phenotpye provides a basis for concluding that it was “possible, and perhaps likely”[135] that a single enzyme would regulate conversion of both thebaine to oripavine and codeine to morphine, such that a skilled worker could have confidence that “adopting the process disclosed in the patent might well produce a Papaver somniferum plant that accumulated codeine at the expense of morphine”.[136]  This statement is in speculative terms and the parties have not pointed me to any evidence that such a view was widely held.  Indeed, Dr Gerlach’s evidence is that such a view was not widely held, and was a “bold and risky hypothesis”.[137]  I am not satisfied that the evidence establishes that in light of the disclosure of WO’033 the notional person skilled in the art would have an expectation of success different to that in light of the common general knowledge alone. 

   [135] Facchini 2 at [28].

   [136] Facchini 2 at [29].

   [137] Gerlach 1 at [120], [55].

3. It follows that for the same reasons as discussed in relation to common general knowledge alone, TPI has not established that the claimed invention lacks inventive step in light of WO’033.

Conclusion

1. The opposition is unsuccessful.  TPI has not established that the claims lack inventive step or are not for a manner of manufacture.

Costs

1. 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 TPI.

   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.