‘I also believe sources of CGK for the Skilled Microbiologist would have included key lipid-related developments published in the following journals: Lipids, Applied Microbiology, World Journal of Microbiology and Biotechnology, Advances in Applied Microbiology, Applied and Environmental Microbiology, Nature Microbiology, and Nature Biotechnology. The Skilled Microbiologist may have attended conferences such as the AOCS Annual Meeting, International Conference on Algal Biomass, Biofuels and Bioproducts, Algae Biomass Summit and the Annual Meeting of the Society for Industrial Microbiology and Biotechnology.’
‘The basic scientific principles underpinning the work of the Skilled Bioprocessing Engineer would be found in standard university chemistry, biochemistry and bioprocessing textbooks. More specific, industrially applicable techniques would also be taught at various continuing education courses such as those by the American Institute of Chemical Engineers (AIChE) and the American Chemical Society (ACS). These organizations host conferences and events at which industry-specific knowledge relevant to the field of extraction of oil from microbes and plants was discussed, although typically at a high level as many companies kept the more specific details of their processes confidential as trade secrets or until they were patented. For the same reason there were relatively few pieces of academic literature addressing more industry-specific issues facing the Skilled Bioprocessing Engineer. In addition the key companies in the field kept informed of others’ activities, including via their regulatory submissions and patent filings.’
‘Both microorganisms considered in this section are protected by extremely tough cell walls. In order to release their cellular contents, a number of methods for cell disintegration have been developed. These methods fall into three major categories: chemical, biological and physical. Some of the methods have severe limitations with regard to large-scale application, compatibility with the product, or cost. Knowledge of cell wall structure and composition is, therefore, important to optimize chemical methods and achieve cell lysis without damage to the DHA oils. For mechanical methods, size, shape and degree of cross-linking of structural polymers are important factors to determine the ease of disruption. Nevertheless, mechanical methods, especially wet milling in high-speed agitator bead mills and high-pressure homogenizers, have demonstrated good performance on a large scale for cell disruption of microorganisms with tough cell walls, including microalgae. It is desirable to achieve as complete cell disruption as possible through the optimisation of processing variables including flow-rate, pressure, temperature and disruption chamber design and operation. Some of the variables involved in cell disruption have been reviewed (ref 13). The disintegration process, therefore, will strongly influence the solid-liquid separation in the downstream processing and the overall extraction yield. The ease of cell disruption is also related to fermentation growth conditions. Fast growth rates, in general, produce cells having weaker cell walls since they do not have time to produce material to reinforce the cell wall structures. Schizochytrium sp. a faster growing algae than C. cohnii, possesses an intrinsically weaker cell wall and, as a consequence, energy requirements for its disruption are significantly lower.’
‘The paper …. is a general discussion of a host of lysis techniques (with sections on physical/mechanical, chemical and biological methods including enzymatic lysis) which could potentially be deployed in a number of contexts. The abstract notes that physical/mechanical methods are mostly “universally suited”, while a chemical and biological method “offers improved selectivity” but “requires individual procedures for each product”. Again, microbial oil production was not a process that required selectivity when it came to lysis, and the mindset of the Skilled Bioprocessing Engineer is important in this respect. If the Skilled Bioprocessing Engineer was asked a general question whether enzymes could lyse cells, I think they would say that it could probably be done, but they would have to investigate which enzyme(s) might lyse which particular cell(s) and under which conditions, and for that purpose would seek assistance from the Skilled Microbiologist. However, that was not the mindset of those in the field of microbial oil production at the time, and there was simply no need to consider the question in the first place, as the field was focused on using simple physical/mechanical methods that had been successfully used for years.’
‘19. Kyle 1 paragraph 113 discusses biological methods to break open cells. I agree that the Skilled Microbiologist would have known that biological methods could be used to break open the cells of certain types of microorganisms and that this method had been applied in certain contexts. However, SCO production was not one of those contexts. 20. As noted by Dr Kyle in paragraph 114 and supported by the article provided as Exhibit DJK-7, some knowledge of the cell wall structure and composition was important for developing biological (and chemical) methods of cell lysis. As I explain further below, this meant that biological methods were only considered by scientists when there was a specific need that warranted the research to identify the correct enzyme (or enzyme combinations) that would work to break open the cell wall of the microorganism. However, this need had not arisen in microbial oil production, where simple techniques such as mechanical lysis had been established, scaled up and economically deployed. 23 …DHA could be extracted from Crypthecodinium and Schizochytrium cells using mechanical methods to produce a high-quality oil. Further, whilst there are capital costs associated with physical methods, enzymatic methods themselves involved significant cost (e.g. sourcing the enzyme itself). At the EP 155 Priority Date, the Skilled Microbiologist would not have been motivated to explore enzymatic methods of extracting lipids from microbial cells. 29. Therefore, regardless of whether the biological methods of breaking open cells discussed by Dr Kyle would have been familiar to the Skilled Microbiologist in a general sense: 1) Enzymatic methods had not been used to in the processes for single cell oil extraction and there was no motivation to do this at the EP 155 Priority Date; and 2) The application of enzymatic methods to break open one type of microbial cell does not assist the Skilled Microbiologist in understanding what type of enzyme (or combination of enzymes) could be used to break open a different type of microorganism without knowledge of its cell wall structure and composition.’
‘The present invention relates to the extraction (and then isolation) of a microbial (or single cell) oil, preferably comprising one or more polyunsaturated fatty acids (PUFAs), from single cell (or micro-) organisms. The process of the invention involves the disruption or lysis of microbial cell walls, followed by separating the oil from the resulting cell debris. The invention additionally relates to a microbial oil recovered by this process, preferably having a PUFA.’
‘[0003] In most microbial PUFA production processes a microorganism is first cultured in a fermenter in a suitable medium. The microbial biomass is then harvested and treated to enable subsequent extraction of a lipid from the biomass with a suitable solvent. The lipid is usually subjected to several refining steps. Care must be taken during the process because degradation can occur if the lipids are subjected to lipolysis or oxidising conditions, for example heating (in the presence of oxygen) and/or due to lipases or lipoxygenases. The art teaches that to avoid oxidation (such as resulting from breaking open the cells and so exposing the contents to oxygen) PUFAs can be extracted from whole intact cells using a solvent (see WO-A-97/36996 and WO-A- 97/37032). The use of solvents is a common way of removing lipids from microbial biomass (WO-A-98/50574).’
‘Although these extraction processes [i.e. using a solvent] have been used for several years, the solvent needs to be removed and this results in extra cost. In addition, if the lipid is to be used in a foodstuff, it is important that certain solvents, such as hexane, are removed completely, or only remain in very small quantities. If the hexane is removed by evaporation then this may involve heating and that not only adds to costs but can cause lipid degradation. Furthermore, with increasing environmental considerations, the use of solvents for the extraction of lipids is becoming increasingly expensive and unpopular.’
‘[0007] Recent PUFA preparation processes advocate keeping the microbial cells intact (WO-A-97/36996). The PUFA is then extracted from the intact cells inside the granules by contact with a solvent, usually hexane. The hexane is then evaporated to produce a crude oil. Throughout this process the cells are kept intact to prevent oxygen in the atmosphere contacting the PUFAs and causing undesirable oxidation. However, it has now been found that a good quality PUFA oil can be achieved if the cells are in fact lysed: any potential oxidation by the atmosphere is more than compensated by the advantage of avoiding the need for solvents.’
‘[0014] The cell walls of the microbial cells can then be disrupted (or lysed). This can be achieved using one or more enzymatic, physical or mechanical methods or techniques, for example at high shear conditions. Physical techniques include heating and/or drying the cells to a sufficient temperature whereby the cell walls are ruptured. This may comprise boiling. [0015] Enzymatic methods include lysis by one or more enzymes, e.g. cell wall degrading enzymes. The cell wall degrading enzyme may be a lytic enzyme. Other enzymes include (e.g. alkaline) proteases, cellulases, hemicellulases, chitinases and/or pectinases. Other cell wall degrading substances may be used instead of or in combination with one or more enzymes, e.g. salts, alkali, and/or one or more surfactants or detergents. A combination of physical, mechanical and/or enzymatic methods is also contemplated.’
‘[0021] The microbial oil is then separated from at least part of the cell wall debris formed. At this stage the PUFA may be in an oily or lipid layer. This may be a top or upper layer, which is (or has risen) above an aqueous layer containing cell wall debris. The oily layer comprising the PUFA can then be separated from the aqueous phase. One or more surfactants or detergents may be present or added to assist this process. [0022] The separation of the oil from at least some of the cell wall debris is preferably achieved or assisted by using a mechanical method, in particular by centrifugation.’
‘Centrifugation may result in either a 2-phase system (a fatty or oily top layer and a lower aqueous layer) or a 3-phase system (a fatty or oily top layer, a middle aqueous layer and a bottom layer, usually containing the cell debris).’
‘9. A process according to any preceding claims wherein the disruption of the cell walls is assisted by one or more cell wall degrading enzymes or surfactants.’
‘(e) disrupting or lysing the cell walls of the microbial cells, for example by a physical, enzymatic or mechanical technique (such as homogenisation, e.g. with an homogeniser or a ball mill). This releases some of the oil and/or PUFA present in the microbial cells. The (mechanical) disruption may be supplemented with or substituted by chemical and/or enzymatic disruption.’
‘(f) separation of the microbial oil (or PUFA) from the cell wall debris, for example separation of the oil phase from the resultant cell wall debris and/or aqueous phase. This may comprise centrifugation, optionally with the addition of one or more salts, a pH shift (towards alkaline), and may involve the presence of one or more cell degrading enzymes, surfactants or emulsifiers;’
‘Problems with prior methods include poor product quality due to chemically aggressive conditions of high temperature and high pH, high costs due to the need to dry the biomass or for the additional equipment such as homogenizers and pressure vessels.’
‘For different oil-containing materials, different enzymes and reaction conditions can be employed. For these different materials, an important enzyme selection criterion is to select an enzyme that will attack and degrade a portion of the material (such as the proteins, polysaccharides, cell wall, cell outer membrane, peptidoglycan layer, cellulose, chitin, hemicellulose, lignin, lignin-related compounds, etc.) that is otherwise impeding recovery of the oil. Preferably, nonspecific protease enzymes such as trypsin, chymotrypsin, or the like are used to degrade protein components of the oil-containing materials and carbohydrase enzymes such as amylase can be used to degrade carbohydrate components of the oil-containing materials.’
‘The lipids are effectively liberated from Schizochytrium sp organisms by treating the cells with a protease enzyme. It is surprising that this particular class of enzymes is effective for this organism due to the relatively small amount of protein normally found in the cell wall of this organism.’
“In a sense, it does not matter whether the statement about the amount of protein normally found in the cell wall is right or wrong. What matters is the teaching that the structure and composition of Schizochytrium cells is such that proteases will in fact work.”
‘Bijl describes the extraction and subsequent isolation of a microbial oil comprising one or more PUFAs directly from microbial cells via an extraction process which uses enzymatic lysis.’
‘1. A microbial oil comprising a triglyceride fraction of at least 70% by weight, wherein the docosahexaenoic acid content of the triglyceride fraction is at least 50% by weight, and wherein the oil comprises 5% by weight or less of heptadecanoic acid.’
‘2B. The microbial oil of claim 1B, wherein said docosahexaenoic acid content of the triglyceride fraction is from at least 60% to 65% by weight.’
‘The present invention relates to a method for producing natural PUFA-enriched PUFA-triglyceride mixtures ... having a minimum PUFA content of >55% by weight of TFA (Total Fatty Acids), the great majority of those consisting of triglycerides. These are obtained by winterization in one or more organic solvents from natural PUFA oils having a PUFA content >39% by weight of TFA.’
‘138. In Kirin-Amgen the House of Lords had to consider the novelty of an overt product by process claim. This is dealt with in the speech of Lord Hoffmann at paragraphs 86 to 101. A number of points arise. Lord Hoffmann dealt with the history of product by process claims and noted that the advantage they had before the 1977 Act was removed by s60(1)(c) (paragraphs 88-89). He noted that the idea that a process could confer novelty on a known product was not particularly logical since the history by which it was made is not an attribute which it carries around and makes it new (paragraph 88). He dealt with the EPO’s practice starting from the 1980s, referring to the IFF/claim Categories T150/82 decision and the EPO’s practice (paragraphs 90-91). He was puzzled by an earlier decision of the EPO relating to the patent in suit which appeared to be based on inconsistent findings of fact as to whether the process of making recombinant erythropoietin (rEPO) did or did not necessarily give rise to differences with known urinary erythropoietin (uEPO) (paragraphs 92-95) and noted that the trial judge (Neuberger J as he then was) had found as a fact that there was no necessary distinction between rEPO and uEPO (paragraph 96). 139. In Kirin-Amgen the Court of Appeal had held that the product by process claim (claim 26) was novel because of the novel process feature. The Court of Appeal had refused to follow the EPO’s practice about permitting such claims only in certain circumstances because that was a rule of practice of no concern to national courts. Lord Hoffmann (with whom the other lords agreed) did not agree with the Court of Appeal’s reasoning (paragraphs 98-101). He held that a difference in the method of manufacturing did not make a product new and that was so as a matter of law. On that basis the claim could only be novel if the process definition gave the product a new characteristic of some kind. On the finding of fact in Kirin-Amgen, therefore claim 26 lacked novelty since the process did not necessarily do so. The decision of the Court of Appeal was wrong. The UK should follow the approach of the EPO.’
‘147. I derive the following principles from this consideration of the EPO and UK authorities: i) A new process which produces a product identical to an old product cannot confer novelty on that product. To be novel a product obtained or obtainable by a process has to have some novel attribute conferred on it by the process as compared to the known product. ii) This rule is a rule of the law of novelty. It is not a principle of claim construction. Although in effect the rule treats “obtained by” language as “obtainable by” language, nevertheless as a matter of claim construction a claim to a product “obtained by” a process means what it says. That will be the relevant scope of the claim as far as infringement and sufficiency are concerned. iii) Although normally a patent is drafted by the inventor “in words of his own choosing”, the EPO will not permit overt product by process language unless there is no other alternative available. By no other alternative, they mean no other way of defining a particular characteristic of the product in question.’
‘[157]…. Since the EPO’s practice runs counter to the idea that a patentee is entitled to use words of his own choosing in describing his invention, it must be based on some principle. The principle underlying the EPO’s practice is shown by the Johnson Matthey case. It is a principle of clarity (Art 84 EPC, s14 of the 1977 Act) and amounts to a trade off between clarity and fairness, tolerating an increased lack of clarity in that limited class of cases. If a patentee can identify a characteristic or parameter disclosed in the patent for which no other definition is available in the specification other than an “obtainable by” process definition, then a product by process claim may be allowed as a way of claiming that attribute. It is impossible to apply that approach properly without knowing what characteristic the process feature is to be used to define. That would be best stated in the claim expressly but it may be clear from the specification.’
‘‘…different microbial oils are derived from different microorganisms i.e. Thraustochytrid oils are derived from Thraustochytrid microorganisms and Crypthecodinium oils are obtained from Crypthecodinium microorganisms. The resulting oils produced from these different sources are fundamentally different products with different physiochemical properties that alters oil stability and organoleptic characteristics (i.e. taste/flavour). The Skilled Microbiologist can identify the differences between them by examining the characteristics of the oil. 68. For example, the Skilled Microbiologist would know the type of the microorganism determines the fatty acid profile of the oil and could analyse this characteristic. The simplest way to differentiate between Thraustochytrid and Crypthecodinium oils is to analyse for the presence of DPA, as this fatty acid is not present in Crypthecodinium oils.’ [233] Dr Wynn is therefore saying that an oil derived from a thraustochytrid can be identified by examining its characteristics – for instance, the fatty acid profile differs. In that case, it follows that the product can be characterised by reference to its structure or composition. The claim therefore does not fall within the narrow exception to the prohibition on product by process features, and the claim is bad for lack of clarity or conciseness. [234] The situation is similar for the “crude oil… without further processing” feature, which again is a process feature. It appears that DSM may seek to suggest that “crude oil” is a feature of the product per se, and therefore legitimate to claim as such, but this cannot be right since it would require all “crude oil” to be distinguishable (without looking at its history) from all oil that has been processed even to a small extent.’
‘109. A claim in a patent does not need to be drafted to a standard which removes all conceivable doubt about what it means, but it “needs to be as clear as the subject matter reasonably admits of”: LG Philips LCD Co. Ltd v Tatung (UK) Ltd, at [20] per Neuberger LJ; see also [26]. Absolute clarity would impose an unreasonable standard and would undermine fair protection for inventions under the patent system. On the other hand, a patent defines an intellectual property right and the scope of the patentee's legally protected monopoly, and potential competitors are entitled to fair warning and a reasonable indication from the face of the patent what its scope is.’
‘The only case in which the EPO will accept a claim to a product defined in terms of its process of manufacture is when the product is new in the sense of being different from any existing product in the state of the art but the difference cannot be described in chemical or physical terms. As the Board said in International Flavors (at paragraph 8): "This may well be the only way to define certain natural products or macromolecular materials of unidentified or complex composition which have not yet been defined structurally."’
‘The EPO's approach to overt product by process claims today is settled. They will be permitted (and only permitted) if there is no other way of defining the product open to the patentee. This is a decision based on policy. Such claims present clarity problems and are best avoided but if there is no alternative way of defining the characteristic in question, then they will be permitted.’
‘Claims for products defined in terms of a process of manufacture are allowable only if the products as such fulfil the requirements for patentability, i.e. inter alia that they are new and inventive, and it is impossible to define the claimed product other than in terms of a process of manufacture. A product is not rendered novel merely by the fact that it is produced by means of a new process.’
‘With regard to product-by-process claims, the requirement of clarity means that the skilled person should be able to determine, either from the claim alone or, by construction of the claim in the light of the description, or by construction in the light of the skilled person's common general knowledge, which identifiable and unambiguous technical features are imparted to the product by the process by which it is defined (T 967/10, T 1988/12, T 354/17, T 2243/18).’
‘…isolated thraustochytrids vary in the identity and amounts of LC-PUFAs produced..’
‘But the fact that the skilled man following the teaching of Biogen 1 would have been able to make HBcAg and HBsAg in bacterial cells, or indeed in any cells, does not conclude the matter. I think that in concentrating upon the question of whether Professor Murray's invention could, so to speak, deliver the goods across the full width of the patent or priority document, the courts and the E.P.O. allowed their attention to be diverted from what seems to me in this particular case the critical issue. It is not whether the claimed invention could deliver the goods, but whether the claims cover other ways in which they might be delivered: ways which owe nothing to the teaching of the patent or any principle which it disclosed.’
‘52. I draw the following from the speeches in these two cases: 1. The principle in Biogen is concerned with permissible scope of claim in the light of the patentee's contribution to the art. 2. In general, that principle is that the claim must not extend to embodiments which owe nothing to the patentee's contribution to the art. 3. In the case of a claim to a single novel chemical compound, the patentee's technical contribution is that compound. Such a claim will not be insufficient if the single compound is enabled by a method in the specification, notwithstanding the fact that there may be other methods of making it which owe nothing to the disclosed method. 4. The same must be true of a claim to a class of compounds, each of which can be made by the application of a method disclosed in the specification. There is no requirement that the patentee disclose more than one method, where one method will do. 5. This does not mean that all claims to a class of products by definition comply with the Biogen principle. The conclusion in Biogen shows that a claim which is formally to a class of products may cover embodiments which owe nothing to the patentee's technical contribution. 6. The reason why the claim in Biogen offended the principle was not because it had "process components" but because the language of the claim was so generalised (both in relation to the manner in which the product was made and in relation to its function) that it extended to embodiments which owed nothing to the patentee's contribution to the art. A claim to a product defined by its function (e.g. any heavier than air flying machine referred to by Lord Hoffmann at page 52 in Biogen) is capable of extending to subject matter which owes nothing to the patentee's contribution to the art.’
‘61. So, for example, if a man finds a particular way of making a new substance which is 10 times harder than diamond, he cannot just claim "a substance which is 10 times harder than diamond." He can claim his particular method and he can claim the actual new substance produced by his method, either by specifying its composition and structure or, if that cannot be done, by reference to the method (see Kirin-Amgen at [90-91]) but no more. The reason he cannot claim more is that he has not enabled more – he has claimed the entire class of products which have the known desirable properties yet he has only enabled one member of that class.’
‘… The requirement to show enablement across the whole scope of the claim applies only across a relevant range. Put broadly, the range will be relevant if it is denominated by reference to a variable which significantly affects the value or utility of the product in achieving the purpose for which it is to be made.’
‘iv) An example of another range, not relevant in the Regeneron sense, will be a descriptive feature in a claim (whether structural or functional) which can cover a variety of things, but for which that variety does not significantly affect the value or utility of the claimed product or process in achieving its relevant purpose. The relevant purpose is judged in all the circumstances, starting from the terms of the claim itself but also, where appropriate, by reference to the essence or core of the invention. v) For a claim feature which amounts to a range in this other sense, the skilled person must still be able to make a suitable selection, without undue burden, in order for the claim to be sufficiently disclosed. However provided that is so at the relevant date, such a claim feature will not be insufficient simply because it is capable of also covering within its scope things which had not been invented at that relevant date.’
‘59. To establish that the claim offended against the Biogen principle as explained in Lundbeck, however, [the defendants] had to go further. They had positively to establish that there were structures which were covered by the claim which could not be made with the benefit of that teaching. There is no reason for the court to assume that the claim covers structures which owe nothing to [the patentee’s] contribution to the art.’
‘Many new research teams had implemented the Barclay method to attempt to identify and isolate new and improved strains, whilst some teams had identified strains with different ratios of omega-3 fatty acids, the Skilled Microbiologist would not be aware of any team that had isolated a strain that materially outperformed the production strain (ATCC 20888) in relation to DHA levels, despite having been trying for around 17 years.’
“what I have found in my experience was doing that [mutagenesis] with algae, it never came back as a stable mutation”
‘However, the Skilled Microbiologist would not consider the teaching/invention of EP 740 in such a limited way, but would rather have understood that the value and utility of a microbial oil with the properties of claim 1B is the high quantities of DHA from a crude oil extracted from a Thraustochytrid biomass without further processing (i.e. they do not need to rely on expensive and complex post-extraction processing techniques). Further, the Skilled Microbiologist would recognise that these benefits would be realised irrespective of the particular Thraustochytrid strain used (provided it produces a microbial oil with the other features of claim 1B). As I note at paragraph 69 above, the value and utility of this particular feature resides in the processing benefits of using a Thraustochytrid microorganism.’
‘[291] … Where a specification contains a series of lists of variables, but does not point to a particular combination of choices from the respective lists, an amendment that narrows to that particular combination will ordinarily add matter. As counsel for MSD submitted, this principle is traceable back to the important early decision in T 12/81 Bayer/ Diastereomers [1979-85] EPOR B308. In that case, the Board was considering the novelty of a selection from two lists. It held at [13]: “However, the disclosure by description in a cited document of the starting substance as well as the reaction process is always prejudicial to novelty because those data unalterably establish the end product. If on the other hand two classes of starting substances are required to prepare the end products and examples of individual entities in each class are given in two lists of some length, then a substance resulting from the reaction of a specific pair from the two lists can nevertheless be regarded for patent purposes as a selection and hence as new.” Such a selection from two lists can be novel for the purposes of patentability, and by the same logic it will also constitute added matter if it was not disclosed in the application as filed.’
‘247. A similar issue was considered by Arnold J in Idenix v Gilead. At [609]–[610] Arnold J found in relation to some proposed amended claims that deleting options from the possibilities for R1 and R2 (it does not matter what they were) disclosed a new sub-class of compounds, not previously disclosed. He also accepted a submission that this was made worse by the fact that it was done to remove from the granted claims compounds which, the patentee's own expert had said, were not plausibly effective. 248. The Court of Appeal said ([2016] EWCA Civ 1089 at [206]–[210]) that Arnold J was right for the reasons he had given.’
‘274. I do not see anything inconsistent in G2/10 with the notion that when asking whether an amendment adds matter, which is the fundamental question, it will be relevant to ask whether it presents a different invention, and that part of that inquiry may be whether it provides a new technical contribution. One is not inquiring whether there is a new technical contribution instead of asking whether there is added matter, but simply recognising it as a likely symptom of there being added matter. 275. Furthermore, there is no sign in the EPO's case law of its thinking that G2/10 meant that the existing law about deleting from lists was wrong. The Case Law book cites decisions from before and after G2/10 and they are all to the same effect. 276. I also noted above that in Idenix v Gilead Arnold J accepted an argument that the provision of a technical contribution across the scope of the claim for the first time was relevant to added matter, and the Court of Appeal upheld him.’
‘126. The gold standard formulation above refers to the whole document and to the common general knowledge. I accept, of course, that the whole document has to be considered, but that does not mean that it is a reservoir from any part of which a feature can be taken to combine with a feature from some other part, in the absence of a clear teaching to do so. Similarly, the CGK informs, as ever, what the skilled person understands from the document but it does not make the CGK a reservoir from which features can freely be drawn to be plugged in at will. …’
‘139. I do not think there is any conceptual limit on what may be a pointer in this sense, but a particularly common one is a statement of preference within a list in the document in question. I note however that in a number of the EPO cases it was held that there was added matter in combining a preferred member of one list with a member of another list for which no preference was expressed. In general, too, what the EPO looks for is a pointer to the combination; this cannot be an absolute rule, but it makes sense. See for example the references to T2273/10 and T1032/12 on pages 524 and 525 of the Case Law. 140. Other pointers could potentially be dependent claims (see e.g. T583/93), or members of a list which feature strongly in the preferred embodiments (in T583/93 the Board linked these by saying that dependent claims are inherently indicators of preferred embodiments - see 4.7 of the reasons), but again there cannot be a rigid rule. …’
‘142…. This is the difference between using the CGK to assess the skilled person's understanding of what is disclosed, and using the CGK as a reservoir of additional disclosure. The former is mandatory and the latter is illegitimate.’
‘[0054] In some embodiments, the microbial oil and/or one or more fractions thereof, selected from the triglyceride fraction, the free fatty acid fraction, the sterol fraction, the diglyceride fraction, and combinations thereof, comprises at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, or at least about 80% by weight DHA. In some embodiments, the microbial oil and/or one or more fractions thereof selected from the triglyceride fraction, the free fatty acid fraction, the sterol fraction, the diglyceride fraction, and combinations thereof, comprises from about 40% to about 45%, about 40% to about 50%, about 40% to about 60%, about 50% to about 60%, about 55% to about 60%, about 40% to about 65%, about 50% to about 65%, about 55% to about 65%, about 40% to about 70%, about 40% to about 80%, about 50% to about 80%, about 55% to about 80%, about 60% to about 80%, or about 70% to about 80% by weight DHA.’
‘a microbial oil comprising a triglyceride fraction of at least about 70% by weight, wherein the docosahexaenoic acid content of the triglyceride fraction is at least about 60% by weight’
‘Overall, there was no recognized effective way of breaking the emulsion that would form in an aqueous extraction process on a commercial scale. As such even by 2010 the Skilled Bioprocessing Engineer would be aware that solventless extraction was not being used in practice, mainly due to this emulsion problem.’
‘…it is not the act of changing the pH in EP 801 which aids demulsification and recovery of an oil that is not dispersed in an emulsion. Rather it is the state of being at that elevated pH, as pH is simply a physicochemical property and measure of the acidity/basicity of a solution. If the pH is already at 8 or above when a lysed cell composition forms the emulsion which arises may be weaker, raising the pH to 8 or above would weaken an existing emulsion by the same action. 289. Accordingly, maintaining the pH of a lysed cell composition that is already at pH 8 or above has, from a technical perspective, the same effect as raising the pH of a lysed cell composition to that same level.’
‘It is, we would accept, still not the practice to adopt Lord Moulton's approach to deciding conventional patent actions where both validity and infringement are in issue. The court will resolve those issues individually by reference to the claims of the patent, rather than take the short cut of deciding whether the defendant's product is old or obvious. That is because, as we think Lord Moulton was recognising, the validity of a granted patent involves more than just the private interests of the parties. If the patent is indeed to be impaled on the validity horn of Lord Moulton's dilemma, then it is in the public interest that it be decided and the patent revoked. That same policy is visible in Traction Corporation v Bennett (cited above). That consideration does not, however, detract from the potential usefulness of the principle that Lord Moulton was espousing. In a conventional patent action a determination that there is nothing new or inventive about the defendant's product may operate as a cross-check on the outcome of the action as a whole.’
‘38. As I have said, the approach to be adopted to the interpretation of claims containing a numerical range is no different from that to be adopted in relation to any other claim. But certain points of particular relevance to claims of this kind do emerge from the authorities to which I have referred and which are worth emphasising. First, the scope of any such claim must be exactly the same whether one is considering infringement or validity. Secondly, there can be no justification for using rounding or any other kind of approximation to change the disclosure of the prior art or to modify the alleged infringement. Thirdly, the meaning and scope of a numerical range in a patent claim must be ascertained in light of the common general knowledge and in the context of the specification as a whole. Fourthly, it may be the case that, in light of the common general knowledge and the teaching of the specification, the skilled person would understand that the patentee has chosen to express the numerals in the claim to a particular but limited degree of precision and so intends the claim to include all values which fall within the claimed range when stated with the same degree of precision. Fifthly, whether that is so or not will depend upon all the circumstances including the number of decimal places or significant figures to which the numerals in the claim appear to have been expressed.’
‘…He first rejected an exact value understanding of the figures. The skilled addressee would not understand the patentee to have intended the limits to be read in that way. The question was what degree of precision was required. In that case, the question was whether the skilled addressee would apply a whole number approach or a significant figure approach to the construction of 1% to 25%. The difference between the two was that the whole number approach would cover a range =0.5% to <25.5, whereas the significant figure approach would cover a range =0.95% to =25.5%. He held that the whole number approach was correct, for the reasons he expressed at [60] as follows: "In my judgment there can be no logical basis for preferring the significant numbers approach over the whole number (or zero decimal places) approach in construing the claim in issue. The purpose of expressing numbers to a particular degree of precision may be to convey to the reader the degree of accuracy with which he needs to make a particular measurement or carry out a calculation. In the context of the claimed method, it is to convey to the reader the range of permissible binding agent concentrations and the accuracy with which those concentrations need to be determined. There is no reason to suppose that this can vary depending upon whether the bottom of the range is 1%, 2% or 5%, or whether 10% is at the top or bottom of the range. It seems to me that Professor Kennedy therefore put it entirely correctly in saying as he did in his first expert report that it is not the number of significant figures that is important in this context, and instead it is the precision with which a number is written. I consider that Professor Kennedy was also right to say that the skilled person would understand the 1% and 25% limits to have been expressed to the nearest whole number."’
‘55 I would accept that there may be circumstances where a prior disclosure of a numerical range, such as a range of temperatures to be used in a process, may carry with it an implicit disclosure that the skilled person may choose any value within the range. Whether that is so will depend on the disclosure of the document understood with the benefit of the common general knowledge. It is wrong, however, to elevate that possible conclusion into a rule of law, so that every numerical range must be so understood, whatever the context.’
‘The present invention relates to processes for obtaining a lipid from a cell by lysing the cell, raising a pH of the cell and/or contacting the cell with a salt, and separating the lipid. The scope of protection is defined by the process as set out in the claims.’
‘Therefore, there is a need for a process for obtaining lipids from a cell which does not use an organic solvent. Several processes have been proposed for separating a lipid from a cell without the use of an organic solvent. For example, U.S. Patent No. 6,750,048 discloses an aqueous washing process whereby an emulsion is washed with aqueous washing solutions until a substantially non-emulsified lipid is obtained. However, in some embodiments, this process requires multiple washing steps, which require substantial cost and time. U.S. Patent No. 7,431,952 discloses a process whereby lysed cells are centrifuged to remove cell wall debris and then oils are extracted and purified. However, this process provides a crude oil that requires extensive further purification. Thus, what is needed is a process that does not utilize a volatile solvent to extract a lipid from a cell, and which can be performed using readily available equipment and a minimum number of steps to provide a highly pure lipid.’
‘[0086] Generally, the processes of the present invention do not utilize an organic solvent in order to extract or otherwise separate a lipid. Thus, in some embodiments, an organic solvent is not added to a cell broth comprising plant material or fermentation broth comprising a microbial cell, is not added to a cell composition, is not added to a lysed cell composition, or is not added to a lipid during a process of the present invention in an amount or concentration sufficient to extract a lipid. In some embodiments, an organic solvent can be added to a cell composition, a lysed cell composition, or a demulsified cell composition. In such embodiments, the organic solvent is added in a concentration less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, less than 0.1%, or less than 0.05% by volume.’
‘An organic solvent as defined herein can be optionally added to a lysed cell composition, for example, as a component of a base and/or a salt for contacting with the lysed cell composition. However, in such embodiments the organic solvent is present in a concentration such that the lipid is not substantially extracted from the cell composition, lysed cell composition, or demulsified cell composition by the solvent (i.e., in a concentration of less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, less than 0.1%, or less than 0.05% by volume or weight).’
‘[0114] As used herein, chemically treating includes, but is not limited to, raising a pH of a cell, contacting a cell with a chemical or the like. [0115] Raising a pH of a cell can include, but is not limited to, adding a base to a cell composition. [reference is made to various bases and their form (e.g. solid or liquid)]. … In some embodiments, the pH of the cell composition is raised to 8 or above, 9 or above, 10 or above, 11 or above, 12 or above, or a pH of 7 to 13, 7 to 12, 7 to 11, 7 to 10, 7 to 9, 8 to 13, 8 to 12, 8 to 11, 8 to 10, 8 to 9, 9 to 12, 9 to 11, 9 to 10, 10 to 12, or 10 to 11.’
‘[0118] As used herein, a "lysed cell composition" refers to a composition comprising one or more lysed cells, including cell debris and other contents of the cell, in combination with a lipid (from the lysed cells), and optionally, broth that contains microbial cells or plant material.’
‘[0122] In some embodiments, treating a lysed cell composition with a first base breaks up (i.e., demulsifies) an emulsified lysed cell composition. In some embodiments, treating a lysed cell composition with a second base breaks (i.e. demulsifies) an emulsified lysed cell composition. In some embodiments, treating a lysed cell composition with a salt breaks (i.e., demulsifies) an emulsified lysed cell composition. In some embodiments, heating a lysed cell composition breaks (i.e., demulsifies) an emulsified lysed cell composition. In some embodiments, agitating a lysed cell composition breaks (i.e., demulsifies) an emulsified lysed cell composition. In some embodiments, simultaneous heating and agitating of a lysed cell composition breaks (i.e., demulsifies) an emulsified lysed cell composition. In some embodiments, one or more of the preceding treatments breaks up (i.e., demulsifies) an emulsified lysed cell composition. [0123] The process of the invention comprises raising the pH of the lysed cell composition to demulsify the lysed cell composition. Raising the pH comprises contacting the lysed cell composition with a base. The process of the invention comprises contacting the lysed cell composition with a base to demulsify the lysed cell composition. … In some embodiments, the pH of a lysed cell composition or a demulsified cell composition is raised a second time. In some embodiments, the second raising of the pH comprises contacting a lysed cell composition or demulsified cell composition with a second base.’
‘Thus, a solvent can be optionally present in a base for use with the present invention.’
‘[0126] Contacting the lysed cell composition with a base raises the pH of the lysed cell composition to 8 or above, 9 or above, 10 or above, 11 or above, 12 or above.’
‘…raise the pH of the treated cell composition or the treated lysed cell composition to 7 or above, 7.5 or above, 8 or above, 8.5 or above, 9 or above, 9.5 or above, 10 or above, 10.5 or above, 11 or above, 11.5 or above, or 12 or above. In some embodiments, a treated cell composition or a treated lysed cell composition is contacted with a second base to raise the pH of the treated lysed cell composition to 7 to 13, 7 to 12, 7 to 11, 7 to 10, 7 to 9, 7 to 8, 7 to 7.5, 7.5 to 8, 8 to 13, 8 to 12, 8 to 11, 8 to 10, 8 to 9, 8 to 8.5, 8.5 to 9, 9 to 12, 9 to 11, 9 to 10, 9 to 9.5, 9.5 to 10, 10 to 12, or 10 to 11.’
‘A second base (NaOH, 50% w/w solution,40 kg) was then added to the lysed cell composition until the pH was above 8.’
‘…treated with a first base… to adjust the pH of the lysed cell composition to 10.5’. ‘A second base was added …until the pH was 8.3’ iii) Example 5: ‘…to adjust the pH ….to 10.5’. ‘[held at 95°C plus agitation for 1 hour] and the pH dropped to 8.5.’ iv) Example 6: ‘…to adjust the pH ….to 10.62’. [various actions performed] ‘…until the pH was 8.13…9.02….10.12.’ v) In many of these examples, the first base was added to adjust the pH of the lysed cell composition to 10.5. vi) Since DSM placed specific reliance on Example 18, I will quote the relevant parts. Following the addition of Alcalase ‘to lyse the cells and form an emulsified lysed cell composition, it is stated: ‘The emulsified lysed cell composition was treated with a base (i.e., a 12.5% solution of NaOH) to adjust the pH of the lysed cell composition from 7.21 to 10.52.’ ‘The broth was then separated into 4 portions … The individual trials were then centrifuged without further pH adjustment.’
‘The lysed cell composition was treated with a base (i.e., NaOH, 10 g of a 50% w/w solution) until the pH of the lysed cell composition was 10.4 to 10.6.’ ‘The pH of the lysed cell composition during centrifuging was maintained at 6.5 to 8.5.’ ii) Example 7: ‘…to adjust the pH ….to 10.5’. [various actions performed] ‘…until the pH was 8.07…9.11….10.09.’ iii) Example 8: ‘…the pH was adjusted to 10.5’. [salt added plus heating] ‘…and the pH had dropped to 9.5 after 1-2 hours….’ iv) Since DSM placed particular reliance on Example 17, I set it out here: ‘The lysed cell composition was treated with a base (i.e., a 12.5% solution of NaOH) until the lysed cell composition reached a pH of 7.8 to 8.2. A salt (solid Na2SO4, in an amount of 5% by weight of the lysed cell composition) was added to the lysed cell composition. The lysed cell composition was then heated to a temperature of 60° C and held at that temperature. The pH of the lysed cell composition was maintained at the 7.8 to 8.2 level by the addition of base…’ ‘This resulted in an oil layer of about 2 ml in a sample of 40 ml. The extraction yield of the oil was 73% by weight.’
‘The broth was chemically treated with a base (i.e., a 25% solution of NaOH) without a prior cell lysis step. The addition of the base raised the pH of the broth from 5.8 to 11.2. The addition of the base and the rise in the pH lysed the cells to form a lysed cell composition.’
‘5A. The process according to any preceding claim, wherein the process comprises heating the lysed cell composition to demulsify the cell composition. 6A. The process according to claim 5A, wherein the heating is performed after the adding a salt. 7A. The process according to any preceding claim, wherein the process comprises agitating the lysed cell composition to demulsify the cell composition.’
“a lysed cell composition”
“to demulsify the cell composition”
“wherein the lipid contains less than 5% by weight of an organic solvent”
“there is a need for a process for obtaining lipids from a cell which does not use an organic solvent”
“Generally, the processes of the present invention do not utilize an organic solvent in order to extract or otherwise separate a lipid”
“raising the pH of the lysed cell composition to 8 or above to demulsify the cell composition”
“the skilled person would understand that the patentee has chosen to express the numerals in the claim to a particular but limited degree of precision and so intends the claim to include all values which fall within the claimed range when stated with the same degree of precision”
“to demulsify the cell composition”
‘73. Ninthly, it is necessary to consider whether a feature of a claimed invention is an added benefit in a context in which the claimed innovation is obvious for another purpose. In Hallen & Co v Brabantia (UK) Ltd[1991] RPC 195 the Court of Appeal was concerned with an alleged selection patent for a self-pulling corkscrew which had a helix coated with polytetrafluoroethylene (PTFE) which was a known friction-reducing material. At the priority date PTFE had been used for several years to coat the helix of a twin-lever type corkscrew to aid its penetration into the cork. The PTFE-coated helix had this effect also on the self-pulling corkscrew, a fact which was obvious at the priority date. The PTFE coat when applied to a self-pulling corkscrew also had a non-obvious benefit of making a striking improvement in the extraction of the cork. The trial judge, Aldous J, held that the patent was invalid on the ground of obviousness because it was obvious to select the features of the claim for the first purpose notwithstanding that it was not obvious for the other purpose:[1989] RPC 307 , 326-327. The Court of Appeal agreed with the judge, holding (pp 215-216) that it was self-evident that a PTFE coating would improve the penetration by any corkscrew and that the “golden bonus” or added benefit of the dramatic improvement in extraction of the cork would not found a valid patent as the claimed innovation was obvious for another purpose. Mr Waugh does not challenge this principle but submits that the 181 patent does not involve such an added benefit.’
‘[0024] One preferred embodiment of the process of the present invention includes: [0025] Obtaining lipid-bearing single cell organisms [0026] Treating with protease or a combination of surfactant and protease [0027] Separating the lipid from the broth (may be an emulsion) [0028] May require additional treatment with a polar organic solvent, salt, precipitating agent, another enzyme (protease or other kind), heating, cooling. [0029] If the lipid from the above step is in the form of an emulsion, this product can be used “as is” or dried and used or treated to release the lipid from the emulsion [0030] Treatment can include treatment with a polar organic solvent, salt, precipitating agent, another enzyme (protease or other kind), heating, cooling, etc. [0031] The lipid can then be dried, refined, bleached, deodorized and/or reacted as needed.’
‘In some cases, after the lipids are liberated from the biomass, the lipids can be separated directly from the undesired materials (e.g., cellular debris), such as by centrifugation, or other appropriate methods. In other cases, an agent such as an alcohol or other polar organic solvent can be added to facilitate the separation of the liberated lipid from the other material. In still other cases, a solvent can be added that will dissolve the lipid and facilitate the separation of the liberated lipid from the other material, e.g., by solvent extraction.’
‘226. ... Powell Gilbert has explained to me the importance of avoiding hindsight in the context of inventive step, and I must put myself back in the position of the Skilled Bioprocessing Engineer at the EP 801 Priority Date but without knowledge of EP 801 itself. 227. In this context it is important to note that Kobzeff is not about solving the emulsion issue which arises with solventless extraction at all. Instead, as I have explained above at paragraph 151, the focus is on the lysis step. In particular using protease enzymes to lyse Schizochytrium cells. Kobzeff teaches that enzymatic lysis avoids the inconvenience and expense of the traditional drying step, and the mild conditions can also help in obtaining a high-quality oil. As I explained above, the Skilled Bioprocessing Engineer would consider Example 3, where enzymatic lysis was combined with an adapted FRIOLEX method using isopropanol to produce a good quality oil, interesting and would want to take this forward to investigate how the yield compared to traditional hexane extraction. 228. Therefore, although Kobzeff managed to avoid using the most problematic organic solvent, hexane, it used isopropanol and so did not even attempt to implement a truly solventless process. I do not believe it would be obvious to the Skilled Bioprocessing Engineer how to do a solventless process in light of Kobzeff, or whether such a process could be made to work, as there is little guidance on how an emulsion could be broken other than a generic list of options at paragraph [0030], which does not even mention considering the pH. I therefore do not believe it would be obvious to arrive at the method of the claims of EP 801.’