Commonwealth Scientific & Industrial Research Organisation and Meat & Livestock Australia Limited v Agriculture Victoria Services Pty Limited
[2016] APO 32
•3 June 2016
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Commonwealth Scientific & Industrial Research Organisation and
Meat & Livestock Australia Limited v
Agriculture Victoria Services Pty Limited [2016] APO 32
Patent Application: 2007335195
Title:Artificial Selection Method and Reagents
Patent Applicant: Agriculture Victoria Services Pty Ltd
Opponent: Meat & Livestock Australia Limited &
Commonwealth Scientific & Industrial Research Organisation
Delegate: L. L. Press
Decision Date: 3 June 2016
Hearing Date: 24 February 2016, in Melbourne
Catchwords: PATENTS – section 59 – opposition to grant of a patent – whether the claimed invention involves an inventive step – lack of inventive step not established on evidence filed – whether invention is a manner of manufacture – invention is a manner of manufacture – opposition unsuccessful
Representation: Patent applicant: Ben Fitzpatrick of Counsel, instructed by Dr Amanda Stark and Dr Tony Davies, Griffith Hack, Melbourne
Opponent 1: Ian Horak of Counsel, instructed by instructed by Dr Victor Arget, of Davies Collison Cave, Brisbane
Opponent 2: Craig Smith of Counsel, instructed by instructed by Dr Tom Gumley, Dr Sarah Hennerbry of Freehills, Melbourne
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2007335195
Title:Artificial Selection Method and Reagents
Patent Applicant: Agriculture Victoria Services Pty Limited
Date of Decision: 3 June 2016
DECISION
The opposition is unsuccessful.
Costs are awarded against Commonwealth Scientific & Industrial Research Organisation and Meat & Livestock Australia Limited.
REASONS FOR DECISION
Background
Patent application 2007335195 was filed by Agriculture Victoria Services Pty Limited (Agriculture Victoria) via the PCT on 21 December 2007, claiming priority from provisional application US 60/876,623 filed on 21 December 2006. The application was examined and advertised as accepted on 19 December 2013.
The Commonwealth Scientific & Industrial Research Organisation (CSIRO) filed a notice of opposition on 19 March 2014, and filed a statement of grounds and particulars on 19 June 2014. On 11 September 2014, CSIRO filed a request for an extension of time to 19 December 2014 to file evidence in support. After being granted an extension of time in which to file evidence in support. This opponent subsequently requested amendment of the statement of grounds and particulars to add additional references of alleged prior art. That request was allowed on 10 December 2014. Evidence in support was completed on 18 December 2014, evidence in answer on 20 March 2015 and evidence in reply on 25 April 2015.
Meat & Livestock Australia Limited (MLA) filed a notice of opposition on 19 March 2013, and filed a statement of grounds and particulars on 19 June 2014. MLA’s evidence in support was completed on 19 September 2014, evidence in answer 23 December 2014 March 2015 and evidence in reply on 6 March 2015.
Grounds of opposition
CSIRO’s statement of grounds and particulars identified manner of manufacture, novelty, inventive step, utility and lack of clarity as grounds of opposition.
MLA’s statement of grounds and particulars identified manner of manufacture, inventive step, utility and the section 40 requirements of lack of sufficiency, lack of fair basis and lack of clarity as grounds of opposition.
At the hearing the grounds of opposition pressed by both opponents were limited to manner of manufacture and inventive step.
Evidence
The following evidence was filed in this matter:
Opposition by CSIRO
Evidence in support
- Statutory declaration of Dorian Garrick dated 15 October 2014 (Garrick-1) together with exhibits DGJ-1 to DJG-21
- Statutory declaration of Dorian Garrick dated 18 November 2014 (Garrick-2) together with exhibits DJG-1 to DJG-7
- Statutory declaration of Dorian Garrick dated 16 December 2014 (Garrick-3) together with exhibits DJG-1 to DJG-6
Evidence in answer
- Statutory declaration of James Hetzel dated 19 March 2015 (Hetzel-1) together with exhibits JH-1 to JH-10
Evidence in reply
- Statutory declaration of Dorian Garrick dated 22 May 2015 (Garrick-4) together with exhibits DJG-4-1 to DJG-4-41
Opposition by MLA
Evidence in support
- Statutory declaration of Bruce Tier dated 10 September 2014 (Teir-1) together with exhibits BT-1 to BT-18
- Statutory declaration of Bruce Tier dated 17 September 2014 (Tier-2) together with exhibits BT-19 to BT-21
- Statutory declaration of Catherine Winbanks dated 12 September 2014 (Winbanks) together with exhibits CEW-1 to CEW-34
Evidence in answer
- Statutory declaration of James Hetzel dated 23 December 2015 (Hetzel-2) together with exhibits JH-1 to JH-10
Evidence in reply
- Statutory declaration of Bruce Tier dated 6 March 2015 (Tier-3) together with exhibits BT-22 to BT-24
Standard of proof
The request for examination in relation to the patent application was filed on December 2010. As a consequence, the substantive amendments of the Patents Act brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 do not apply to the present patent 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 has been made out. Instead, the onus of proof in this opposition lies with the opponent, who must establish that it is clear that a valid patent cannot be granted (F.Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283 at [29], [67]; [2000] FCA 283; 50 IPR 305; Commissioner of Patents v Sherman [2008] FCAFC 182 at [18], [22]; [2008] FCAFC 182; 79 IPR 426).
The specification
The specification indicates that the invention relates to methods of artificial selection of species of agricultural importance, particularly marker assisted selection (MAS) in animals and plants.
10. By way of background, the specification explains the shortcomings of the traditional approach to population improvement which is founded on selecting for quantitative traits on the basis of the phenotype. Selection based on the phenotype typically involves time consuming and expensive progeny-testing to determine an individual’s estimated breeding value (EBV) for a trait of interest. Genomic solutions, such as MAS, are described in the specification as facilitating selection based on a genotype-based EBV.
11. Current MAS methods include sparse and dense marker maps constructed from markers and single nucleotide polymorphisms (SNPs). The specification identifies advantages of dense marker mapping over sparse marker mapping. Despite these advantages, methods of selection based on dense mapping are expensive because large numbers of SNPs are required to be genotyped. Strategies for inferring haplotypes from a minimum number of informative SNPs, known as SNP tagging, have been utilised with some success, especially with respect to the human genome. Unfortunately, SNP tagging methods also require a large number of SNPs to be genotyped and therefore the methods are also subject to cost constraints. The specification says at page 5:
“Methods for the cost effective implementation of genome-wide selection using dense marker maps are not routinely available.”
12. The specification indicates that the aim of the invention is the provision of cost-effective methods for performing artificial selection using a genomics based approach.
At page 14, the specification commences a detailed explanation of the invention. According to the specification, the invention originated from the inventors realising that costs related to selecting breeding candidates from a population could be reduced if candidates could be genotyped for a relatively small number of markers. A saving could be realised by genotyping the key ancestors of the selection candidate for useful markers and genotyping candidates for a subset of markers, thereby tracing the useful markers in a candidate to their chromosomal lineage in a key ancestor. This permits markers known on chromosome segments in the ancestor to be inferred for the corresponding chromosome segments in the selection candidate. This strategy is said to be particularly effective in species having a small effective population size (Ne), with a small number of key ancestors relative to the number of selection candidates, as is the case for many livestock breeding programs.
13. The specification proceeds to explain that the invention is predicated on the notion that in populations with a small Ne, the genetic diversity/variability of the population is explained by the sum of the ancestors making a long term contribution to the population.
14. A preferred method of selection based on genome wide selection for estimating EBV of breeding candidates using SNPs, incorporates steps to determine the minimum set of ancestors/founders representative of the current population and genotyping ancestors/founders for known SNPs and inferring genotypes of individuals from ancestral genotypes.
15. The usefulness of the method for computational estimation of EBV based on inferred genotypes is demonstrated by the method set out at Example 1.This method relates to the identification of the minimum set of key ancestors that represent most of the chromosome segments. The specification indicates that the computational method reduces costs of genomic selection because fewer markers are required to be typed on selection candidates, because the genotype of the candidates can be inferred from ancestors.
The claims of the specification
16. The specification as accepted consists of 22 claims, which are reproduced at Annex A.
Claims construction
17. The approach to the construction of claims was discussed by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70, 81 IPR 228 at [118] - [120]:
“the words in a claim should be read through the eyes of the skilled addressee in the context in which they appear … while the claims define the monopoly claimed in the words of the patentee’s choosing, the specification should be read as a whole … it is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification … terms in the claim which are unclear may be defined or clarified by reference to the body of the specification”.
18. Before commencing to construe the specification, I note what Middleton J said in Eli Lilly and Company Limited v Apotex Pty Ltd [2013] FCA 214, 100 IPR 451 at [139]:
"It is well settled that the Court should, from the outset, approach the task of patent construction with a generous measure of common sense. The Court must place itself in the position of a person skilled in the relevant art, being the subject matter of the patent. From this perspective, the patent is to be read as a whole, in the context of the specification and in light of the prevailing common general knowledge and state of the relevant art at the priority date."
19. The specification at pages 6 to 12 provides dictionary definitions of the meaning of the technical terms and nomenclature used in the claims. These definitions do not depart from the standard meanings of the terms in the field of quantitative genetics and animal and plant breeding.
Claim 1
20. Claim 1 is directed to a method of selective breeding which relies on determining a genotype-based EBV for an individual in a population.
21. In essence, the claim defines a method of determining the genotype of a breeding candidate for the absence or presence of a subset of informative markers in chromosome segments and inferring additional genotypic markers from an ancestor/founder (reference population) for which more extensive genotypic marker information has been determined. The inferred genotype is used to estimate a genotype-based EBV for the breeding candidate. A selection decision as to whether the animal is included or excluded from a breeding program is made based on the individual’s EBV.
22. Claim 1 is the only independent claim and the preamble reads:
“A method of selective breeding based on an estimated breeding value of an individual in a population having a genetic diversity equivalent to an effective population size (Ne)of less than 1000”
23. Selective or artificial breeding programs typically utilise populations having a small effective population size (specification at pages 16 & 36-37; Tier-2 at [41]; Garrick-1 at [32] & Garrick-3 at [11]). This means that the method of claim 1 (and the dependent claims) applies to the selective breeding of an extensive range of species of animals, fishes and plants of agricultural importance. However, the effective population size, being required to be less than 1000, means that the actual number of individuals in the population which are ancestors or founders could be few, relative to the current population of selection candidates.
24. Given that the size of the effective population is required to be less than 1000, the method does not extend to human populations (Tier-1 at [41]; Garrick-3 at [11]).
Parts (i) to (v) of claim 1 specify the steps utilised in the method.
Part (i) of claim 1 reads:
“(i) genotyping an individual in a current population for the presence or absence of informative markers in one or more chromosome segment(s), wherein at least one chromosome segment comprises a gene or locus of interest, and wherein said genotyping comprises determining genotypes at a subset of the informative markers at the gene or locus of interest and wherein genotype information for one or more other informative markers is missing from said determined genotypes;”
25. Step (i) identifies that the individual to be genotyped is an individual that is a candidate for breeding and that genotyping of the individual is for a subset or some, but not all, informative markers within one or more chromosome segments. This equates to sparse genotyping of the individual.
Step (ii) reads:
“(ii) comparing the determined genotypes of the individual in the current population to the genotypes of informative markers in an ancestor and/or founder contributing at least 0.1% of the total genetic variance to the current population to thereby determine lineage of the chromosome segment of the individual from an ancestor and/or founder of the current population from which the chromosome segment is derived, wherein the genotype of the ancestor and/or founder is known for the subset of the informative markers and for at least one informative marker for which genotype information is missing from the determined genotype of the individual in the current population;”
26. Step (ii) requires a comparison of the genotype of the individual as determined in part (i), with the known (predetermined) genotype of an ancestor/founder to establish the ancestral lineage of the individual’s chromosomal segment. The genotype of the ancestor is more informative relative to the individual’s genotype because the ancestor has been mapped at a higher density compared with the individual. There is a requirement that the ancestor/founder necessarily contributes at least 0.1% of the total genetic variance to the current population.
Step (iii) reads:
“(iii) inferring at least one informative genotype missing from the genotypes determined at (i) for the individual to be the same as for an ancestor and/or founder based on the lineage of the chromosome segments determined at (ii) to thereby produce at least one inferred genotype;”
Step (iii) specifies inferring the incomplete or missing genotype information of the individual at (i) from the relatively more complete and predetermined genotype of the ancestor/founder at (ii).
Steps (iv) and (v) read:
“(iv) estimating the breeding value of the individual based on genotypes comprising at least one inferred genotype to produce an estimated breeding value (EBV) for said individual; and
(v) breeding or propagating said individual in a breeding program, or removing said individual from a breeding population in a breeding program, based on the EBV of the individual.”
28. Steps (iv) and (v) refer to estimating the breeding value of the individual based on the inferred genotype determined at step (iii), and breeding or propagating the individual or excluding the individual from breeding or propagating, based on the individual’s EBV.
Claim 15 depends from any one of claims 1 to 14 and further defines that breeding or propagating comprises obtaining reproductive or regenerative material from the individual. The claim is drawn to a method and the scope of the claim does not extend to the reproductive or regenerative material as such. Claim 20 claims the material obtained by the method of claim 15.
Claim 16 depends from any one of claims 1 to 15 and recites additional process steps. Implementing the additional steps, functions to identify a reference group of key ancestors contributing the highest proportion of genes to a current population. The method effectively identifies the minimum number of key ancestors that explain the genetic variance in the current population.
31. Claim 20 is understood to be a “product by process” claim, in that its scope covers animals and plants when produced by any one of the methods of claims 1 to 18, or the process of claim 19.
Inventive Step
32. CSIRO and MLA opposed claims 1-22 for lack of inventive step in light of common general knowledge in the art alone. CSIRO also challenged the inventiveness of the claims on the basis of common general knowledge in combination with the following prior art document:
“In silico method for inferring genotypes in pedigrees”, Burdick J T et al, Nature Genetics 2006, 1002-1004. (Burdick)
33. It is a requirement of subsection 18(1) of the Act that the invention, so far as claimed in any claim, involves an inventive step. Subsection 7(2) states that an invention is taken to involve an inventive step unless it would have been obvious to a person skilled in the art in the light of common general knowledge, considered alone or together with the information specified in subsection 7(3). This information includes one piece or a combination of pieces of prior art information, being information that the person skilled in the art could reasonably expected to have ascertained, understood and regarded as relevant.
34. The test for obviousness is to ask if it would have been a matter of routine to proceed to the claimed invention. In Wellcome Foundation Ltd v V.R. Laboratories (Aust) Pty Ltd [1981] HCA 12 at [45]; 148 CLR 262 at 286, Aicken J stated:
“The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not.”
35. The High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd (Alphapharm) [2002] HCA 59; 212 CLR 411 at 433 also approved the use of the “Cripps question”:
“Would the notional research group at the relevant date, in all the circumstances, which include a knowledge of all the relevant prior art and the facts, directly be led as a matter of course to try the invention as claimed in the expectation that it might well produce a solution to the problem.”
36. Where the invention lies in a combination of features, the question is whether the combination, not each individual feature is, is obvious when compared to the prior art base (Alphapharm) at [41]; Minnesota Mining & Manufacturing Co Beiersdorf (Australia) Ltd [1980] HCA 9 at [116]; (1980) 144 CLR 253 at 293).
The problem to be solved
37. The description of the opposed application discusses cost constraints associated with dense marker genotyping (page 4, line 24 to page 5, line 5). This paragraph concludes with the statement:
“Methods for the cost-effective implementation of genome-wide selection using dense marker maps are not routinely available.”
38. And further at page 6, line 10-11, there is a statement that:
“… there remains a need for informative and cost-effective methods of performing artificial selection using a genomics-based approach.”
39. CSIRO relied on similar statements and passages in the specification to contend that the problem intended to be solved is “substantial cost associated with selecting animals for inclusion in a selective breeding program” the (CSIRO at [33]-[36]).
40. In general, MLA’s submissions on the nature of the problem were in keeping the view held by CSIRO (MLA at [36]).
41. The evidence of CSIRO’s expert, Professor Garrick, supports the view that high costs related to dense marker analysis was the major reason dense genotyping was not commonly used at the priority date (Garrick-1at [27] & [64]; Garrick-3 at [4]).
42. The applicant submitted that costs were not the principle reason selection based on genotypic markers was not practiced. Relying on the evidence of their expert, Dr Hetzel, counsel for the applicant argued that at the priority date, marker assisted selection was in its infancy. As a consequence, uncertainty surrounding the accuracy of associating genotypic markers with phenotypic traits was the primary, practical reason that marker assisted selection was not implemented in animals (Hetzel-1 at [48] & [57]-[60]). Dr Hetzel states a “very large number of individuals would need to be genotyped for a very large number of markers to obtain accurate estimates of genetic merit” (Hetzel-1 at [119]). However, Dr Hetzel’s evidence also indicates that costs were a significant factor contributing to the problem of marker based selection (Hetzel-2 at [38]; [48] & [119]).
43. In light of a reading of the specification as a whole, including the claims, overall, I consider that a reasonable formulation of the problem addressed by the application is the provision of the need for a more cost effective and accurate method of artificial selection based on genotypic information.
The person skilled in the relevant art
44. In general, it was not in dispute that the person skilled in the art in this case is a person or team of people with expertise in quantitative genetics, working in the fields of animal or plant breeding.
45. Having regard to their qualifications and professional experience detailed in their declarations, I am satisfied that each of the declarants, namely Professors Tier and Garrick, and Dr Hetzel, is a relevant person skilled in the art for the purposes of this opposition.
The common general knowledge in the art
46. The concept of common general knowledge was described in Minnesota Mining and Manufacturing Company and Another v Beiersdorf (Australia) Limited (1980) HCA9; 144 CLR 235 at 292 as involving:
“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 product, or the making of improvements in old, and it must be treated as being used by an individual as a general body of knowledge.”
47. The common general knowledge covers material that is retained in the memory of the skilled person, as well as material that the person knows of, and to which they might refer as a matter of course, or habitually consult. The material could include standard texts and handbooks (ICI Chemicals & Polymers Ltd v Lubrizol Corporation Inc [199] FCA 345; 45 IPR 577 at [112]).
48. The fundamental principles of quantitative genetics including the concepts of heritability, linkage, identity by descent (IBD), effective population size, and EBV, along with the application of these concepts to selection and breeding based on a genotype EBV, is irrefutably part of the common general knowledge, at least in a theoretical, if not practical sense.
49. The evidence establishes that the common general knowledge in the art before the priority date also includes the following:
Genotypic information had been incorporated into EBVs (Tier -1 [71]; Tier-2 at [35] & [99]; Hetzel-2 at [57]; Garrick-1 at [19] & [22]).
Inferring or reconstructing haplotypes from parents to offspring in livestock and vice versa was well known (Tier-1at [89]; Garrick-1at [55]-[56]; Garrick-3 [8]-[10]).
In general, the transfer of technology relating to genetics and the statistical methods for prediction, usually flows in the direction of livestock to humans (Garrick-1 at [40]). However, with respect to haplotype reconstruction the transfer is in the direction of humans to livestock (Garrick-1 at [42]; Hetzel-1 at [62] & [65]).
50. I note that in his second declaration, Professor Garrick introduces the Burdick paper in support of his view that it was known to impute genotypes from densely mapped human individuals to augment knowledge of genotype in sparsely mapped offspring (Garrick-2 at [18]). However, I have no persuasive evidence before me that Burdick is common general knowledge in the art, and given that Professor Garrick did not refer to the Burdick paper in his first declaration which addressed his common general knowledge, on balance, I do not consider the Burdick article to be common general knowledge in the art.
Is the invention obvious?
51. Before the opposed specification was made available to him, Professor Garrick was asked a question which he understood to be, what would he have done to minimize costs associated with selecting animals for inclusion into a breeding program (Garrick-2 at [3]). Professor Garrick has framed the problem to be solved in broader terms compared with the problem I have identified above. Although, he sees the problem as being the costs associated with artificial selection in general rather than costs and efficiencies relating to genetic based selection, I do not think this difference has any significant bearing on the outcome of my decision on inventive step.
52. In answering, Professor Garrick, stated he would first conduct a literature search to identify all the relevant literature, including literature in the field of human genetics. He stated he would then densely genotype a reference set of animals, chosen from the population or from relatives of the breeding candidates, using SNP chips. Having densely genotyped a reference population, Professor Garrick, indicated he would then determine EBVs applying two readily apparent strategies (Garrick-2 at [5]-[9]).
53. With the first approach, (Solution 1), Professor Garrick explained that he would identify specific markers from the reference population’s set of dense markers which are important for the trait of interest. He would then construct a panel of the important markers, and then use the panel of the smaller number of specific and informative markers to genotype all animals that are breeding candidates (Garrick-2 at [10]-[13]). Professor Garrick’s evidence details that he abandons solution 1 as the means to address the problem, because he readily appreciated that cost advantages would not be realised if the approach was adopted, because SNP chips with a smaller number of informative markers would need to be generated for each trait of interest (Garrick-2 at [13]).
54. Professor Garrick proposed a second strategy (Solution 2) to overcome the cost issues associated with his first suggested solution. Solution 2 relies on inferring/imputing “missing” genotypes in candidate animals mapped at low density, from densely mapped genotypes of a reference population to establish an EBV (Garrick-2 at [14]-[19]).
55. In his second declaration, Professor Garrick elaborates on solution 2 and states at [24]:
“In summary, in order to determine which candidates to select for use as parents in a breeding program I would genotype a reference population such as the sires at high density, and genotype candidates using a more sparsely-spaced marker panel. In order to actually understand or provide a good estimate of the breeding value, I would impute the full genotype of an individual animal of a candidate breeding population based on the dense marker genotypes obtained for the sires. I would then calculate EBV from the animal’s genotype so imputed as if I had high density genotypes on all individuals.”
56. After being provided with a copy of the opposed specification, in his third declaration Professor Garrick acknowledges that proposed solution 2 differs from the opposed specification in two respects and he says at [13]:
“The only features not discussed explicitly in my second declaration are:
“(a) a population having a genetic diversity equivalent to an effective population (Ne) size of less than 1000; and
(b) an ancestor and/or founder that contributes at least 0.1% of the total genetic variance to the current population.”
57. Professor Garrick goes on to contend that the feature, Ne, is merely a feature inherent to any population of animals or plants that would be bred in a breeding program (Garrick-3 at [14]). With respect to the feature related to genetic variance, Professor Garrick emphasises the distinction and states in his third declaration at [15]:
“Although I would not have selected a reference population (eg., ancestors or founders) on the basis of their genetic contribution to the current population, individuals of the reference population used in my selective breeding method, would have been selected on the basis of the accuracy of their EBV and many animals in this reference population would inherently contribute at least 0.1% of the total genetic variance to the current population.”
58. Professor Garrick indicates that in adopting solution 2, he would have chosen the reference population for genotyping on the basis of the number of an ancestor’s phenotyped progeny, because such animals have the most accurate EBV (Garrick-3 at [17]).
59. In his evidence in answer to Professor Garricks’s first 3 declarations, Dr Hetzel at [92] and [95] notes that Professor Garrick, in his second declaration, when deciding on solution 2, does not indicate what parameters he would employ to assemble his reference population for dense mapping. Dr Hetzel then goes on the say that he was not aware of any programs selecting ancestors or founders as a reference population on the basis of their contribution to the total genetic variance to the current population of selection candidates, at the priority date (Hetzel-1at [98]).
60. I accept Dr Hetzel’s evidence that when selecting a reference population according to the method detailed by Professor Garrick, it would not always be the case that an individual in the reference population contributed 0.1% to the total genetic variance of the population (Hetzel-1at [100] & [101]). This is consistent with Professor Garrick’s own evidence. He indicates that using solution 2, there would be significant overlap between ancestors in his reference population and ancestors chosen on the basis of 0.1 % genetic contribution to the candidate population (Garrick-4 at [75]). Professor Garrick also states that if he was practicing his method in a larger population he would employ different thresholds wherein “at least some (my emphasis) of the individuals selected for inclusion in the reference population would contribute at least 0.1% genetic variance to the current population” (Garrick-4 at [79]).
61. CSIRO contended that given claim 1 only specifies that a single ancestor or founder contribute at least 0.1% to the total genetic variance which means that an ancestor or founder will inherently contribute at least 0.1% variance to the candidate population. MLA contended that the at least 0.1% threshold was not, in practice, a limitation.
62. As Dr Tier explained, 0.1%, is a “moderate” contribution of genes to the candidate population (Tier-1 at [86]). Be that as it may, I have already decided above that in light of
Dr Hetzel’s evidence, it is not the case that with respect to solution 2, a reference ancestor will always inherently contribute at least 0.1% to the total genetic variance of the candidate population: it is possible that ancestors contribute less than 0.1% to the total genetic variance in the candidate population.
63. I have no compelling evidence before me that the feature of at least 0.1% genetic contribution as defined in part (ii) of claim 1, is an arbitrary feature or inessential to the method, rather I have only evidence that in some circumstances, it may be that reference ancestors will indeed contribute at least 0.1% or greater to the total genetic variance of the candidate population. Nor do I have evidence that the skilled person would be directly led to rely on total contribution to the genetic variance of the current population as a parameter in the first instance, when challenged with the problem.
64. I consider that the two parameters that distinguish the method of claim 1 of the opposed application from Professor Garrick’s second solution, namely, effective population size and at least 0.1% contribution to the total genetic variance in the candidate population, have been chosen to have a specific technical effect that solves the problem identified above. As stated by Dr Hetzel in his first declaration at [115]:
“The composition and size of the reference population is carefully chosen in order to both produce accurate genomic predictions in the current population at the same time as minimising costs.”
65. I consider Dr Hetzel’s statement about the composition and size of the reference population of ancestors to be applicable to genotyping one candidate individual by inferring missing genotype information from an individual ancestor who contributes at least 0.1% to the total genetic variance in the candidate population.
66. Thus the skilled person in seeking to solve the problem and without the benefit of hindsight would not be directly led to try a method of selective breeding that incorporated a limitation of an effective population size of less than 1000 and selection of a reference population of ancestors or founders on the basis of a minimum percentage contribution of 0.1% to the total genetic variance of the candidate population.
67. In this present case, the question of inventiveness arises in respect of an invention involving a combination of features, it is the inventiveness of the combination as a whole that must be reviewed: the “inventiveness of particular integers is irrelevant to the inventiveness of a combination of them” (Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (Doric)[2004] HCA 58; 217 CLR 274; ALR 1 at [78]). This principle set out in Doric can be applied to the method steps of claim 1.
68. As already discussed, the opponents have not established that the features of claim 1, with respect to effective population size and the percentage total contribution to the candidate population, would be combined in a multistep application to arrive at the invention of claim 1, although certainly each separate concept is known to the skilled person.
69. In summary, the evidence does not establish that a breeding method with the combination of features set out in any one of claims 1 to 22 is obvious in light of common general knowledge.
Inventive Step based on Burdick
70. CSIRO relies on Burdick for inventive step under s 7(3).
71. The paper authored by Burdick et al., teaches an in-silico inference of incomplete genotype information in sparsely mapped human individuals from a comparison with more densely mapped immediate relatives. The method focused on 3-generation families. The cost advantages of the in silico method of inferring genotype is reported.
Ascertained, understood, regarded as relevant
72. As to the ascertainability of the document, Professor Garrick declared he would use broad terms such as “imputation” and “haplotypes” (Garrick-2 at [4]).
73. CSIRO drew on Dr Hetzel’s evidence to suggest that Professor Garrick would not have ascertained the article using the stated search terms “imputation” and “haplotype” (Hetzel-1at [91]). CSIRO also asserted that even if it had been ascertained it would not be considered relevant by skilled persons working in the area of livestock and plant selection and breeding.
74. I consider that the search terms proposed by Professor Garrick are representative of the terms he would use in a search. I also note that Dr Hetzel does not dispute or disregard Professor Garrick’s view that there is a flow of knowledge in the technology area from humans to livestock. For these reasons, I conclude that the Burdick paper could reasonably have been expected to have been located and understood by the skilled person in the art seeking to provide a solution to the stated problem.
75. CSIRO submitted that even if ascertained, Burdick, would not be considered to be relevant because Burdick relates to reference populations of small size, and human populations are not representative of inbred animal and plant populations (Hetzel-1 at [88]).
76. I note that Professor Garrick’s evidence in reply relates mainly to whether the paper would be considered to be common general knowledge or whether it would have been ascertained in a search (Garrick-4 at [60]-[65] & [67]).
77. I agree with CSIRO. Although the method taught in Burdick is based on the fundamental concept of IBD and inference of genotype, which are both concepts well known to the skilled person, the application of the Burdick approach to livestock and plant breeding was not thought to be relevant at the priority date (Hetzel-1 at [88]-[89].)
78. I conclude that Burdick would not be considered part of the prior art base with respect to s (7) 3.
79. Even if I am incorrect as to the relevance of Burdick, I do not see the invention of claim1 as being obvious in light of Burdick. This is because Burdick does not directly lead the skilled person to a solution based on a small effective population size in combination with a reference population contributing at least 0.1% of the total genetic variance to the current population.
80. In summary, the invention defined in claims 1 to 22, is not obvious over Burdick together with common general knowledge.
Manner of Manufacture
81. Subsection 18(1)(a) requires that an invention must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies.
82. The High Court in National Research Development Corp (NRDC) v Commissioner of Patents [1959] HCA 67; [1959] 102 CLR 252, has provided a convenient statement of the law in this regard. At page 275, it was stated that "a process, to fall within the limits of patentability which the context of the Statute of Monopolies has supplied, must be one that offers some advantage which is material, in the sense that the process belongs to a useful art as distinct from a fine art ...- that its value to the country is in the field of economic endeavour".
83. The need to consider the substance of the claimed invention was reiterated by the High Court in D’Arcy v Myriad Genetics Inc [2015] HCA 35, where it was observed at [94]:
“Although it may be said in a formal sense that the invention as claimed, referring to isolated nucleic acids, embodies a product created by human action, that is not sufficient to support its characterization as a manner of manufacture. The substance of the invention as claimed and the considerations flowing from its substance militate against that characterization.”
84. It is clear from the above decisions that for a claimed invention to define a manner of manufacture within the meaning of Section 18(1)(a) of the Patents Act 1990, it is important to go beyond the form of words used and consider the substance of the claimed invention in the context of the specification as a whole.
85. At the hearing, both the opponents pressed a want of manner of manufacture on the basis that the claims do not define patentable subject matter because they embody intellectual information or a mere scheme which cannot be considered an “artificially created state of affairs”.
86. MLA also submitted that claims 15, 20 and 21 embody products of nature which are not patent eligible subject matter. MLA also contended that even if claims 15 and 20 are considered to define products produced by the particular claimed methods, the claims reach through to pre-existing material. That is, the material was not created by the claimed process, rather it was identified or categorised according to the claimed method.
87. CSIRO submitted that Research Affiliates LLC v Commissioner of Patents (2014) 109 IPR 364 and Commissioner of Patents v RPL Central Pty Ltd [2015] FCAC 177), instruct that the correct approach to take when considering manner of manufacture is to determine the substance of the invention. The opponent asserted that the substance of the invention of claim 1, being confined to parts (i), (ii) and (iii), thereby represents patent ineligible information.
88. The applicant argued that elements (iv) and (v) should not be read out of claim 1 and that the claimed method does not constitute mere information because the method provides a practical means of using genetic information to improve accuracy in estimating the breeding value of an individual, so as to include or remove the individual from a breeding program, and thereby improve the genetic gain the population.
89. Although the scope of claim 1 covers in silico execution of the method, it is clear that the claimed method relates to a technological problem, in that it pertains to artificial selection and breeding of animals and plants. Even if the substance of the invention is confined to steps (i) to (iii) only, it is clear that these 3 steps are integral to solving the problem of providing an improved and cost effective method of selecting individuals based on genotype.
90. Therefore, I conclude that the invention defined in claim 1-14, 16-19 and 22 is for a manner of manufacture.
91. With respect to claims 15, 20 and 21, I have previously found that claim 15 is limited to the use of reproductive or regenerative material necessarily obtained by any one of the methods of claims 1 to 14, for breeding purposes. Similarly claims 20 and 21 cannot be said to define naturally occurring biological material or individuals per se, but rather, biological material and non-human individuals that are necessarily obtained through working the methods defined in the claims. The substance of these claims is not genetic information per se, but incorporates elements of the methods. It follows that the subject matter of these particular claims are considered to be a manner of manufacture.
92. I find all claims are for a manner of manufacture.
Conclusion
The opposition fails on all grounds raised in this opposition.
Costs
The opposition is unsuccessful. Accordingly I award costs in accordance with Schedule 8 of the Patents Regulations 1991 against the opponents, Commonwealth Scientific & Industrial Research Organisation and Meat & Livestock Australia Limited.
Lexie Press
Delegate of the Commissioner of Patents
Annex A: The claims
1. A method of selective breeding based on an estimated breeding value of an individual in a population having a genetic diversity equivalent to an effective population size (Ne) of less than 1000, said method comprising:
(i) genotyping an individual in a current population for the presence or absence of informative markers in one or more chromosome segment(s), wherein at least one chromosome segment comprises a gene or locus of interest, and wherein said genotyping comprises determining genotypes at a subset of the informative markers at the gene or locus of interest and wherein genotype information for one or more other informative markers is missing from said determined genotypes;
(ii) comparing the determined genotypes of the individual in the current population to the genotypes of informative markers in an ancestor and/or founder contributing at least 0.1% of the total genetic variance to the current population to thereby determine lineage of the chromosome segment of the individual from an ancestor and/or founder of the current population from which the chromosome segment is derived, wherein the genotype of the ancestor and/or founder is known for the subset of the informative markers and for at least one informative marker for which genotype information is missing from the determined genotype of the individual in the current population;
(iii) inferring at least one informative genotype missing from the genotypes determined at (i) for the individual to be the same as for an ancestor and/or founder based on the lineage of the chromosome segments determined at (ii) to thereby produce at least one inferred genotype;
(iv) estimating the breeding value of the individual based on genotypes comprising at least one inferred genotype to produce an estimated breeding value (EBV) for said individual; and
(v) breeding or propagating said individual in a breeding program, or removing said individual from a breeding population in a breeding program, based on the EBV of the individual.
2. The method of claim 1, wherein the genotype of the ancestor and/or founder is known for all informative marker(s) for which genotype information is missing from the determined genotype of the individual in the current population.
3. The method according to claim 1 or 2, wherein the gene or locus of interest is a single gene locus.
4. The method according to any one of claims 1 to 3, wherein steps (i) to (iii) of the method are performed on informative markers in a plurality of chromosome segments each segment having missing genotype information for one or more informative markers, to thereby infer a plurality of informative genotypes, and wherein the breeding value of the individual is based on genotypes comprising the plurality of inferred genotypes.
5. The method according to any one of claims 1 to 4, wherein the gene or locus of interest is a Quantitative Trait Locus (QTL).
6. The method according to any one of claims 1 to 5, wherein each ancestor or founder provides at least about 0.5% or at least about 1% or at least about 2% to about 10% of the total genetic variance to the current population.
7. The method according to any one of claims 1 to 6, wherein the population is a population of plants.
8. The method according to any one of claims 1 to 6, wherein the population is a population of animals.
9. The method according to claim 8, wherein the population is a population of animals selected from cattle, Holstein cattle, sheep, pigs, poultry, fish and crustaceans.
10. The method according to any one of claims 1 to 9, wherein the genotyping comprises detecting one or more informative markers in at least one nucleic acid isolated from the individual.
11. The method according to claim 10, wherein the genotyping comprises detecting one or more informative markers selected from an allele, haplotype, haplogroup, locus, quantitative trait locus, polymorphism, STR and combinations thereof in a nucleic acid isolated from the individual.
12. The method according to claim 10 or 11, wherein the wherein the informative markers are single nuclear polymorphisms (SNPs) and/or wherein the genotyping comprises hybridizing a probe or primer selectively to nucleic acid comprising a marker and detecting the hybridized probe or primer and/or wherein the genotyping comprises performing a primer extension reaction or an amplification reaction.
13. The method according to any one of claims 1 to 12, wherein comparing the determined genotypes of the individual in the current population to the genotypes of informative markers in an ancestor and/or founder comprises a use of markers linked to the genotypes.
14. The method according to any one of claims 1 to 13, wherein the genome sequences of the ancestors and/or founders are known, and wherein inferring at least one informative genotype missing from the determined genotypes of the individual of the current population comprises inferring genome sequences of individuals in the current population based on the genome sequences of the ancestors and/or founders.
15. The method according to any one of claims 1 to 14, wherein breeding or propagating the individual comprises obtaining reproductive or regenerative material from the individual.
16. The method according any one of claims 1 to 15, further comprising determining ancestors and/or founders representative of the total genetic variance of the current non-human population for use in inferring the missing genotypes, by performing a process comprising:
(i) selecting an ancestor or founder contributing the highest proportion of genes to the current population;
(ii) selecting an ancestor or founder that provides the highest marginal contribution of genes compared to the ancestor at (i);
(iii) conducting sufficient iterations of (ii) to describe the variance in the current population; and
(iv) assembling the selected ancestors describing the variance in the current population as ancestors and/or founders that are representative of the genetic variance of the current population.
17. The method according to any one of claims 1 to 16, further compnsmg genotyping one or more ancestor(s) and/or founder(s) for informative markers.
18. The method according to claim 17, wherein genotyping the one or more ancestor(s) and/or founder(s) for informative markers comprises:
(i) sequencing or microsequencing the genome of the one or more ancestor(s) and/or founder(s); or
(ii) inferring genotypes of the one or more ancestor(s) and/or founder(s) from data on relatives of the ancestor(s) and/or founder(s).
19. A process of producing genetic gain in a population having a genetic diversity equivalent to an effective population size (Ne) of less than 1000, said process comprises performing the method according to any one of claims 1 to 18 and breeding an individual having a high estimated breeding value.
20. Reproductive or regenerative material obtained by performing the method of claim 15.
21. A non-human individual when produced by performing the method according to any one of claims 1 to 17 or the process of claim 18.
22. The method according to any one of claims 1 to 18 or the process of claim 19 substantially as herein before described with reference to the accompanying Examples.
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