Patents: Illumina Cambridge v MGI Tech
|By John Schmidt - en:Image:Sequencing.jpg, CC BY-SA 3.0, |
Patents Court (Mr Justice Birss) Illumina Cambridge Ltd v Latvia MGI Tech SIA and others  EWHC 57 (Pat) (20 Jan 2021)
This was an action for patent infringement and a counterclaim for revocation. The defendants, referred to collectively as "MGI", wish to sell DNA sequencing systems in the UK. The claimant, Illumina Cambridge Ltd ("Illumina") contended that 4 of those systems infringed its patents. MGI denied infringement and alleged that the patents were invalid for obviousness, insufficiency and added matter, The action and counterclaim came on for trial before Mr Justice Birss on 9 to 13, 16 to 20, 25, 26 Nov and 9 Dec 2020. Judgment was delivered on 20 Jan 2021 (see Illumina Cambridge Ltd v Latvia MGI Tech SIA and others  EWHC 57 (Pat) (20 Jan 2021).
The patents upon which Illumina relied are as follows:
- EP (UK) No. 1 530 578,
- EP (UK) No. 3 002 289
- EP (UK) No. 3 587 433
- EP (UK) 1 828 412, and
- EP (UK) 2 021 415
"An invention shall be taken to involve an inventive step if it is not obvious to a person skilled in the art, having regard to any matter which forms part of the state of the art by virtue only of section 2 (2) above (and disregarding section 2(3) above)."
If an invention as represented by a claim in the specification would have been obvious to a person skilled in the art having regard to a scientific paper or previous invention it can be declared invalid. If the claim is invalid it cannot be infringed by the manufacture or sale of a product or the use of a process that falls within its wording.
In Actavis Group PTC EHF and others v ICOS Corporation and another,  UKSC 15,  Bus LR 1318, Lord Hodge said at para  of his judgment:
"In addressing the statutory question of obviousness in section 3 of the 1977 Act it is common for English courts to adopt the so-called Windsurfing/Pozzoli structure which asks these questions:'(1) (a) Identify the notional ‘person skilled in the art’;
(b) Identify the relevant common general knowledge of that person;
(2) Identify the inventive concept of the claim in question or if that cannot readily be done, construe it;
(3) Identify what, if any, differences exist between the matter cited as forming part of the 'state of the art’ and the inventive concept of the claim or the claim as construed;
(4) Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention?”
(Pozzoli SPA v BDMO SA  EWCA Civ 588;  FSR 37, para 23 per Jacob LJ). The fourth question is the statutory question and the first three questions or tasks, the second and third of which involve knowledge and consideration of the invention, are a means of disciplining the court’s approach to that fourth question: DSM NV’s Patent  RPC 35, para 55 per Neuberger J; Actavis UK Ltd v Novartis AG  EWCA Civ 82;  FSR 18, para 21 per Jacob LJ."
"An alternative approach which the EPO often adopts is the so-called 'problem-and-solution approach#. The EPO has described the approach in these terms:
'the Boards of Appeal consistently decide the issue of obviousness on the basis of an objective assessment of the technical results achieved by the claimed subject-matter, compared with the results obtained according to the state of the art. It is then assumed that the inventor did in fact seek to achieve these results and, therefore, these results are taken to be the basis for defining the technical problem (or, in other words, the objective) of the claimed invention. … The next step is then to decide whether the state of the art suggested the claimed solution of this technical problem in the way proposed by the patent in suit …' (Agrevo/Triazoles (above) para 2.4.3)
The test is helpfully summarized in the EPO’s Guidelines for Examination in the EPO (November 2017) (Part G - Chapter VII) para 5:
In order to assess inventive step in an objective and predictable manner, the so-called ‘problem-and-solution approach’ should be applied. Thus deviation from this approach should be exceptional.
In the problem-and-solution approach there are three main stages:
(i) determining the ‘closest prior art’,
(ii) establishing the ‘objective technical problem’ to be solved, and
(iii) considering whether or not the claimed invention, starting from the closest prior art and the objective technical problem, would have been obvious to the skilled person.”
Lord Hodge did not seem to have a preference for either approach. He said ar :
"While both approaches focus on the inventive concept put forward in the claims, neither approach should be applied in a mechanistic way. Both are glosses on the text of section 3 of the 1977 Act and article 56 of the EPC and neither require a literalist approach to the wording of the claim in identifying the inventive concept."
In this case, MGI relied upon both the Windsurfing/Pozzoli and the EPO's Problem and Solution approaches.
The first 3 issues of Illumina's list of ssues were concerned with the Windsurfing/Pozzoli approach:
"1) The identity of the Skilled Team;
2) Whether sequencing using reversible chain terminators (RCTs) was common general knowledge at the priority date;
3) Whether claims 1, 12 & 24 of EP 578 (claim set A) are obvious in light of:
a) Zavgorodny 1991; or b) Zavgorodny 2000,"
The third of those issues was also the first of those identified by MGI:
i) To start by asking what problem does the invention aim to solve?
ii) That leads one in turn to consider what the established field which existed was, in which the problem in fact can be located.
iii) It is the notional person or team in that established field which is the relevant team making up the person skilled in the art."
"In order to identify the differences the next task is to address the disclosure of the cited prior art."
"In a way the difference between Zavgorodny 1991 and claim 1 of 578 is quite small. Claim 1 claims a nucleotide (i.e. with the 5' phosphates) with an azidomethyl group at the 3' oxygen whereas Zavgorodny 1991 discloses a nucleoside with such a group at the 3' oxygen. However in order to render claim 1 invalid the skilled person has to make the claimed molecule and for that to happen the skilled person has to have a reason to do so. As a result the inventive step(s) of all the relevant claims of the modified nucleotide patents stand or fall together. If performing sequencing by synthesis using a nucleotide with an azidomethyl blocked 3' oxygen as a reversible chain terminator is obvious over Zavgorodny 1991, then claim 1 also lacks inventive step because it would be obvious to make the relevant compound. If that exercise was not obvious then none of the claims, including claim 1 of 578, are obvious for the converse reason. Another way of approaching the same question would be to ask whether it was obvious to the skilled person given Zavgorodny 1991, with a reasonable prospect of success, to try out a sequencing by synthesis test using a nucleotide with an azidomethyl blocked 3' oxygen as a reversible chain terminator."
" Standing back, for the reasons explained above claim 1 of 578 is not obvious over Zavgorodny 1991. I reject MGI’s case on lack of inventive step. As mentioned at the outset, if the claim is not obvious over Zavgorodny 1991 then it is not obvious over Zavgorodny 2000 either.
. If claim 1 is not obvious then neither is claim 12 of claim set A (to a sequencing method) nor claim 24 of claim set A (an oligonucleotide comprising a modified nucleotide of claim 1)."
7. If the answer to issue 6 is no, are each of claims 1, 12 and/or 24 (claim set A) obvious over Barnes?"
Illumina claimed that the modified nucleotide patents were based on the British patent application GB 0230037 which was filed on 23 Dec 2002 some months before the US patent application. That claim was challenged by MGI.
In Icescape Ltd v Ice-World International BV and others  EWCA Civ 2219, the Court of Appeal had held that the test for priority was whether the priority document contained sufficient material to constitute an enabling disclosure of the claims in issue. In determining the question the court will consider the position through the eyes of the skilled person who reads the priority document with his or her common general knowledge.
"Whether claim 7 of EP 578 (claim set A) and claim 6 of EP 433 (claim set C) are invalid for Agrevo-obviousness / insufficiency".
"If the answer to issue 1 is no, are each of claims 1, 12 and/or 24 of EP 578 (claim set A) insufficient due to lack of enablement/lack of technical contribution?
The claim as originally drafted served no useful purpose and would have been invalid on Aggrevo grounds but the judge allowed the proposed amendments and upheld the claims' validity.
S.14 (3) of the Patents Act 1977 requires every patent specification to disclose the invention in a manner which is clear enough and complete enough for the invention to be performed by a person skilled in the art. If it fails to do that the patent may be revoked under s.72 (1) (c) on the ground that the specification does not disclose the invention clearly enough and completely enough for it to be performed by a person skilled in the art. Failure to comply with that requirement is known as "insufficiency".
" The first one relates to read length. The point is that claim 12 (for example) claims a method for determining the sequence of a target single stranded nucleotide wherein at least one incorporation (my emphasis) is of a nucleotide defined in previous claims such as claim 2, in other words an azidomethyl 3' blocked nucleotide in which the base is linked to a detectable label by a linker. MGI says that this claim is open ended in terms of the length of the nucleotide to be sequenced and submits that the data in the patent only present results for a limited number of cycles, as shown in figures 5 and 6. Therefore, it is said, the monopoly claimed exceeds the technical contribution and the specification does not enable the skilled person to perform a sequencing method across the breadth of the claim without undue burden. The same point is made about claim 7 of claim set A in its amended form (limited to a sequencing reaction). The issue can be decided by reference to claim 12. Claim 7 will stand or fall with it."
"i) When examining any aspect of claim scope for the purposes of the enablement it is necessary to distinguish between ranges relevant in the Regeneron sense and other ranges.
ii) For ranges relevant in the Regeneron sense, to be sufficient, there must be enablement across the whole scope of the claim within that relevant range (subject to de minimis exceptions) at the relevant date. If a type or embodiment within such a range is not enabled at that date then the fact it could be made later, as a result of further developments not enabled by the patent, even though it never could have been made without the invention, will not save the claim from insufficiency.
iii) Not all claims will necessarily contain a range relevant in the Regeneron sense but if they do, then this principle applies to that range.
iv) An example of an other 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.
vi) When examining enablement of any kind, the test is always about what the skilled person is able to do without undue burden. The patentee is entitled to expect that the skilled person, in seeking to make the invention work, will exercise that skill. If need be that exercise will involve testing and experiments, as long as it is not unduly burdensome."
"There is no evidence which would allow me to make a finding on the balance of probabilities that the limit of what the skilled person is enabled to do, without an undue burden, is anything less than what they would reasonably regard as what had been promised by the patent, or claimed if, contrary to my finding, claim 12 does represent a range of read lengths in the Regeneron sense."
Mr Justice Birss gave the squeeze argument short shrift:
" ....... Part of MGI’s case, based as it is on a squeeze on inventive step, is that the need to select suitable types presents an undue burden for the skilled person. I reject that. On the facts I have found the skilled person can select suitable types of the various components without difficulty. The exercise of skill and some routine testing may be needed but I am not satisfied any burden of undertaking that work is undue. I reject this limb of the insufficiency.
 Moreover there is no squeeze with inventive step. The position of the skilled person is entirely different from the position they were in based on the prior art. Taking polymerases as an example, the fact that Metzker 1994 showed inconsistent results with a variety of the polymerases and blocking groups tested in that paper is not evidence that, armed with the patent, the skilled person has an undue difficulty selecting suitable polymerases to make the invention work with 3'–O–azidomethyl blocked nucleotides. I reach the same conclusions for linkers, cleavage conditions and detectable labels."
"No amendment will be allowed if it has the result that the matter disclosed extends beyond that disclosed in the application for the patent as filed."
"The issue relates to claim 9 (claim set B) of 289 (claim 13 as granted). Claim 9 adds to the sequencing method claims of 289 (claim 6 of claim set B et al) a requirement to remove the blocking group using a water soluble phosphine. Illumina seek to amend that claim to add the words “under neutral, aqueous conditions”. MGI says this amendment adds matter. The reason why is a bit of a paper chase. It is true (as Illumina points out) that there is textual support for the amendment at p43 ln 10 of the application as filed (this happens to be the same text about removing the azidomethyl group which has been quoted above from the priority document P2). The same passage also seems to have become para  as granted in 289. However MGI says that in the application as filed there was also a limiting definition of an aqueous solution. It was at p5 ln 26-34. The definition places a lower limit on the amount of water in the liquid of at least 20%. This definition has not been carried forward into the granted patent. Therefore, it is said by MGI, whereas in the application as filed “aqueous conditions” would be understood to be at least 20% water, as amended the claim will add matter because it uses the general phrase and could be understood to envisage aqueous conditions with less than 20% water."
His lordship noted that neither party devoted much effort to this point and no evidence was drawn to his attention which was said to have a bearing on the issue. He rejected the objection at [3-5] for the following reasons:
"I am not satisfied this amendment amounts to added matter for three reasons. First, for the argument to succeed it would have to be established that the skilled person (with the common general knowledge) would actually think that “neutral, aqueous conditions” disclosed the idea of conditions in which the water content was less than 20%. That would require evidence. There is none. Second it must be remembered that coverage is not the same as disclosure of information. Even if the claim could be said to cover solutions with less than 20% water, I am not satisfied there is a disclosure of such a solution by the amendment. Third I do not accept that the skilled reader of the application as filed would necessarily think that the definition given in one context was necessarily relevant to the reference to neutral, aqueous conditions in another context."
He, therefore, allowed the amendments in annexe A.
" ........Following the Supreme Court’s decision in Actavis v Eli Lilly  UKSC 48, the correct approach to infringement by equivalents is to ask three questions (see  of Lord Neuberger’s judgment in Actavis):
(i) Notwithstanding that it is not within the literal meaning of the relevant claim(s) of the patent, does the variant achieve substantially the same result in substantially the same way as the invention, ie. the inventive concept revealed by the patent?
(ii) Would it be obvious to the person skilled in the art, reading the patent at the priority date, but knowing that the variant achieves substantially the same result as the invention, that it does so in substantially the same way as the invention?
(iii) Would such a reader of the patent have concluded that the patentee none the less intended that strict compliance with the literal meaning of the relevant claim(s) of the patent was an essential requirement of the invention?
 To establish infringement the answers have to be yes, yes and no.
 On equivalents, the only issue is the application of the third question. It is common ground that in both cases the first two questions are to be answered in the affirmative."
Applying these principles, his lordship considered whether:
- MGI's Cool MPS fell within claim 12 of 578 (Claim set A) [MGI MNP Issue 10 between paragraphs  and  [MGI MNP Issue 10]; and
- either of the 2 colour variant of Standard MPS or the DNBSEQ E method fell within the kit claims, claim 20 of 578 (claim set A) or claim 4 of 289 (claim set B) between paragraphs  and  [MGI MNP Issue 9].
". EP (UK) 1 530 578 with claims as amended in the form of claim set A is valid. All four of the MGI systems known as Standard MPS, Cool MPS, the two colour variant and DNBSEQ E infringe each of claims 1, 7, 12, 20, and 24 (claim set A) of that patent.
. EP (UK) 3 002 289 with claims as amended in the form of claim set B is valid. All four of Standard MPS, Cool MPS, the two colour variant and DNBSEQ E infringe each of claims 1, 5 and 6 of that patent. In relation to claim 4, it is infringed by Standard MPS and Cool MPS but not by the two colour variant or DNBSEQ E. The amendment to claim 9 is allowable but Illumina needs to explain what the amendment is for.
. EP (UK) 3 587 433 with claims as amended in the form of claim set C is valid. All four of Standard MPS, Cool MPS, the two colour variant and DNBSEQ E infringe each of claims 1 and 6 of that patent."
European Patent No 1 828 412
The Issues in respect of 412
MGI's Alternative Case
"that even if the skilled person did not think of adding ascorbate at the start, when they ran their experiments they would encounter a fading of the signal in successive cycles (just as reported in the patent at paragraph ). It would be obvious that the cause was photobleaching of the DNA and obvious to apply Buechler at that point and thereby add an antioxidant such as ascorbate."
"I find that even if it was not obvious to decide to add ascorbate to the buffers before carrying out any sequencing by synthesis tests in the first place, the skilled person who took that approach would, acting without any inventive step, encounter a problem of fading and would, without invention, find that it was caused by photodamage by adding ascorbate. The claims are obvious based on MGI’s alternative case too."
"The added matter argument here is an intermediate generalisation point directed to something missing from claim 1 as granted (and dependent kit claim 15). Claim 1 is set out above. What is absent from it is essentially any reference to the character of the illumination needed to cause the label to fluoresce (such as being intense). The allegation is that the application as filed (published as WO 2006/064199) only discloses the method of claim 1 together with the requirement that the detection step includes repeated or prolonged exposure to intense illumination. MGI refer to p3 ln3-8 and ln12-18 of the specification in the application and also to claim 1 as filed (at p50 ln3-8). As a matter of the words in the document, MGI is correct. The argument then goes that the difference between the disclosure in the application and the claim as granted is not trivial because although in sequencing by synthesis one generally would use intense illumination, Prof Johnsson explained that that is not necessarily the case. The precise intensity required will depend on the equipment used and the time of illumination and, he said, “I do not think that intense light would strictly be necessary”. Thus argues MGI the application discloses the invention as applicable to a sub-set of sequencing by synthesis processes, namely those which include exposure to intense illumination, whereas the teaching of the granted patent is that the ascorbate containing buffer can be applied to all sequencing by synthesis processes. "
Conclusions on 412
 Putting it another way, the molecule of claim 1 is a single invention. Its beneficial properties derive from the functional relationship, which includes non-interference, between the constituent parts. I find that claim 1 of the 415 patent is valid.