Patent

Infringement - Validity of patent - Revocation of patent

Medimmune Ltd v Novartis Pharmaceuticals UK Ltd and another: Chancery Division, Patents Court (Mr Justice Arnold): 5 July 2011

The claimant company and the second defendant (the defendant) were the joint proprietors of European patents (UK) Nos 0 774 511 (511) and 2 055 777 (777) (together 'the patents').

The claimant was the exclusive licensee of the defendant's interest in the patents. The patents were a family of European patents based on International Patent Application No PCT/GB91/01134 filed on 10 July 1991 (the application). Each of the patents in the family claimed priority from five priority documents, filed on 10 July 1990, 19 October 1990, 12 November 1990 (PD3), 6 March 1991 and 15 May 1991 respectively.

511 was a divisional of the parent, European Patent No 0 589 877, while 777 was a divisional of 511. Claim 5 of 511 included the following integers: '[2] producing a population of filamentous bacteriophage particles displaying at their surface a population of binding molecules having a range of binding specificities' and '[4] and wherein each filamentous bacteriophage particle contains a phagemid genome comprising nucleic acid with a nucleotide sequence encoding the binding molecule expressed from the nucleic acid and displayed by the particle at its surface'. Claim 8 of 511 was as follows: '[1] A method for producing a binding molecule specific for a particular target epitope or antigen, which method comprises: [2] performing the method according to claim 7; [3] isolating from separated filamentous bacteriophage particles recovered according to the method of claim 7 nucleic acid encoding the binding molecule; [4] inserting nucleic acid encoding the binding molecule, or a fragment or derivative thereof with binding specificity for the target epitope or antigen, in a recombinant system; and [5] producing the binding molecule, or fragment or derivative thereof with binding specificity for the target epitope or antigen, in the recombinant system separate from filamentous bacteriophage particles'. Integer [4] of claim 1 of 777 stated: 'wherein the binding molecules are displayed at the surface of the filamentous bacteriophage particles by fusion with a gene III protein of the filamentous bacteriophage particles'.

The core inventive concept of the patents could be summarised as a method consisting of two steps: '(i) producing a population of phage particles displaying at their surface binding molecules having a range of binding specificities wherein each particle contains nucleic acid encoding the binding molecule; and (ii) selecting particles displaying a binding molecule with a desired specificity by contacting the population of particles with a target epitope or antigen to which the binding molecule of interest binds'.

The first defendant company (the defendant) sold a pharmaceutical product whose international non-proprietary name was ranibizumab and which was sold under the trade mark 'Lucentis'. Lucentis was approved for the treatment of an eye condition known as wet age-related macular degeneration, which could lead to loss of vision.

The claimant commenced proceedings against the defendant, alleging that the defendant had infringed the patents by sales of Lucentis. The second defendant had been joined to the claim so as to be bound by the result, but had not played an active role in the proceedings. Ranibizumab was developed by G Inc (GI), which was not a party to the proceedings.

The claimant claimed that the defendant had infringed the process claims set out in claims 5-8 of 511 and claim 1 of 777 by virtue of s 60(1)(c) of the Patents Act 1977 (the 1977 Act). The defendant disputed infringement and counterclaimed for revocation of the patents on the grounds of obviousness, insufficiency, and added matter.

The defendant further disputed that Lucentis had been produced by a process which fell within the scope of the patents' claims, and challenged the entitlement of the patents to priority. Attention was focussed on the entitlement to priority from PD3, since the claimant accepted that the patents were invalid if they were not entitled to priority from that document. The specification in PD3 was entitled 'Binding substances' and contained, inter alia, a number of applications of the invention, descriptions of specific embodiments of the invention, followed by 15 examples.

The parties' submissions centred, inter alia, around certain issues. First, the identity of the skilled person or team. The claimant submitted that the patents were addressed to a team consisting of an immunologist and a molecular biologist, with the immunologist taking the lead, perhaps assisted by a biochemist.

However, the defendant contended that the patents were addressed to a team of scientists with differing backgrounds in areas such as immunology (in particular antibody structural biology), molecular biology and protein chemistry, but with a common interest in antibody engineering.

The essential difference between the two formulations lay in the degree of specialisation of the team in the field of antibody engineering. Secondly, the construction of claim 5 of 511 and claim 1 of 777. In respect of claim 5 of 511, the defendant contended that the word 'each' in integer [4] of claim 5 of 511 meant that 'each particle contains a phagemid genome encoding the binding molecule displayed by the particle on its surface'.

The defendant stated that in practice that meant that substantially all of the particles had to contain such a genome on the basis that the skilled team would know that it was not technically attainable for 100 of the particles to contain phagemid genome. The consequence of the defendant's construction was that the claim was limited to the use of phagemid systems with gene III deletion helper phage.

The claimant's real answer to the defendant's construction did not lie in integer [4] of claim 1 of 511 at all, but in integer [2] of claim 1 of 777 and in particular the words 'a population of filamentous bacteriophage particles'. The claimant contended that those words should be construed purposively having regard to the underlying science. So construed, the claimant stated that, the claim did read on to the use of conventional helper phage, as well as gene III deleted helper phage.

In respect of claim 1 of 777, the defendant contended that 'the words 'a gene III fusion' meant a complete, or at least substantially complete, gene III protein. The claimant contended that they embraced part of a gene III protein, and in particular a part consisting of a C-terminal domain with a no N-terminal domain (being less than half of the complete protein). Thirdly, priority of the patents, which involved consideration of s 5(2)(a) of the 1977 Act.

The defendant disputed that the claimed inventions were entitled to priority, focussing in particular on PD3. The defendant contended that claim 8 of 511 was not entitled to priority from PD3 on two bases: (a) PD3 did not expressly or implicitly disclose a filamentous bacteriophage particle containing a phagemid genome comprising nucleic acid with a nucleotide sequence encoding a Fab antibody molecule expressed from the nucleic acid and displayed by the particle at its surface as required by integers [3] and [4] of claim 5; and (b) the introduction of the definition of the term 'derivative', which featured in integers [4] and [5] of claim 8 of 511 and integers [11] and [13] of claim 1 of 777. The defendant contended that the introduction of that definition in and of itself broadened the scope of the invention, with the result that the patents disclosed and covered post-phage display mutation of the antibody fragment when that had not been disclosed by PD3.

Fourthly, obviousness of the patents. The defendant challenged the validity of the claims of the patents on the basis that they were obvious over, inter alia, 'Parmley and Smith', a priority document (focussing on improved fusion phage vectors and the improved affinity purification method) published in December 1988 by a professor (S) and another author, and a subsequent talk given by S at a conference in Banbury (the Banbury conference) in April 1990 which dealt, inter alia, with the creation of fusion phages with foreign DNA insert in gene III and the consequential effects. Fifthly, the insufficiency of the specification. The defendant argued that the patents were insufficient, pursuant to 72(1)(c) of the 1977 Act on the basis that the breadth of claim 8 of 511 and claim 1 of 777 exceeded the technical contribution to the art made by the invention.

The claimant contended that the invention disclosed by the patents was a principle of general application and that accordingly, the claims were sufficient. Sixthly, added matter. The defendant argued that the patents were invalid pursuant to s 72(1)(d) of the 1977 Act on the basis that claim 31 of the application embraced a class of processes which expressed fragments or derivatives of a member of a specific binding pair including fragments or derivatives which had no binding specificity for the target epitope or antigen.

The defendant contrasted that with claim 5 of 511 and claim 1 of 777, in both of which the fragments or derivatives had to have binding specificity for the target epitope or antigen. The defendant contended that that amounted to an impermissible intermediate generalisation. Seventhly, the manufacturing process of ranibizumab.

The court ruled:(1) A patent specification was addressed to those likely to have a practical interest in the subject matter of the invention, and such persons were those with practical knowledge and experience of the kind of work in which the invention was intended to be used. The addressee came to a reading of the specification with the common general knowledge of persons skilled in the relevant art, and he or she read it knowing that its purpose was to describe and demarcate an invention. He or she was unimaginative and had no inventive capacity.

In some cases the patent was addressed to a team of persons with different skills. Further, in considering the skills of the notional 'person skilled in the art' for the purposes of obviousness, the court would have regard to the reality of the position at the time. What the combined skills (and mind-sets) of real research teams in the art was what mattered when one was constructing the notional research team to whom the invention should be obvious if the patent was to be found invalid on that ground (see [91], [93] of the judgment).

In the instant case, the evidence showed that real research teams in the field to which the patents were directed were teams of the kind contended for by the defendant, namely a team of scientists with differing backgrounds in areas such as immunology (in particular antibody structural biology), molecular biology and protein chemistry, but with a common interest in antibody engineering. The specifications of the patents were consistent with that characterisation of the skilled team (see [94] of the judgment). Dyson Appliances Ltd v Hoover Ltd [2001] All ER (D) 41 (Oct) applied.

(2) In construing a patent, the task for the court was to determine what the person skilled in the art would have understood the patentee to have been using the language of the claim to mean. Further, the skilled reader was to be taken to know the purpose of: (i) including reference numerals in patent claims; (ii) dividing claims into pre-characterising and characterising portions; and (iii) filing of divisional applications, and to bring that knowledge to bear when he considered the scope of the claim (see [249], [250] of the judgment).

In the instant case, in relation to claim 5 of 511, the claimant's construction of the word 'each' in integer [4] of claim 5 of 511 could not be accepted. It was clear from the specification as a whole that 'population' referred to in integer [2] of claim 1 of 777 was to the contents of the library, and not a sub-population, and there was no hint in the lengthy and detailed specification that the claim was to be read in the way suggested by the claimant.

Further, if the claim was construed in that way, it meant that there was no reference in the claim to the starting population, which would be strange. Furthermore, if the skilled team read integer [2] of claim 1 of 777 as being restricted in that manner, it came close to making integer [4] of claim 1 of 777 superfluous.

Moreover, the claimant's argument did not really provide an answer to the defendant's submission that the relevant passages in the specification clearly pointed to the claims being limited to the use of gene III deletion helper phage. In relation to claim 1 of 777, the claimant's arguments in support of its construction of that claim were not persuasive.

Given that the focus of 777 was phage, rather than phagemid, that use of just a C-terminal fragment would not work in phage and that there was nothing in the specification to suggest that use of such a fragment was contemplated. In the circumstances, the skilled team would not think that the patentees had intended to claim use of such a fragment (see [290], [301] of the judgment). Kirin-Amgen Inc v Hoechst Marion Roussel Ltd; Hoechst Marion Roussel Ltd v Kirin-Amgen [2005] 1 All ER 667 applied; Virgin Atlantic Airways Ltd v Premium Aircraft Interiors UK Ltd [2009] All ER (D) 235 (Oct) applied.

(3) It was settled law that in order for a claimed invention to be entitled to priority from an earlier application, it should, in the words of s 5(2)(a) of the 1977 Act, be ‘supported by matter disclosed’ in that earlier application. Consequently, the important thing was not the consistory clause or the claims of the priority document but whether the disclosure as a whole was enabling and effectively gave the skilled person what was in the claim whose priority was in question. It had to ‘give’ it directly and unambiguously. It was not sufficient that it might be an obvious development of what was disclosed.

Further, the burden lay on the patentee to establish that the claims in issue were entitled to priority from the priority document in question, although it was usually convenient to proceed by considering the objections to the claim to priority advanced by the other party (see [303], [304] of the judgment).

In the instant case, PD3 did not clearly and unambiguously disclose combining the phagemid/helper phage alternative mentioned at the end of Example 1 with the expression of a Fab fragment described in Example 7 in such a way that both chains were encoded in the phagemid genome as required by integer [4] of claim 5. Further, it was not disputed that the patents disclosed an invention which involved 'using the mutated nucleic acid in a recombinant system to produce the mutated binding molecule separate from the phage'. However, PD3 did not disclose post-phage display mutation of antibodies (see [326], [343] of the judgment). Claims 5-8 of 511 were not entitled to priority from PD3 (see [326], [343] of the judgment).             Intervet UK Ltd v Merial [2010] All ER (D) 309 (Feb) applied.

(4) It was settled law that a patent would be invalid for lack of inventive step if the invention claimed in it was obvious to a person skilled in the art having regard to the state of the art at the priority date. Further, in assessing allegations of obviousness the court had to: (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 could not readily be done, construe it; (3) identify what, if any, differences existed 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; and consider whether (4) viewed without any knowledge of the alleged invention as claimed, those differences constituted steps which would have been obvious to the person skilled in the art or whether they required any degree of invention. The question of obviousness had to be considered on the facts of each case (see [375], [376] of the judgment).

In the instant case, the key difference between Parmley & Smith and the core inventive step was that Parmley and Smith only disclosed antigen phage display, whereas, the invention involved antibody phage display. Further, on the evidence, Parmley & Smith would not lead the skilled team to believe that phage display of antibody fragments had a reasonable prospect of success. Consequently, the claimed inventions were not obvious over Parmley & Smith.

In respect of S's talk at the Banbury conference, the main difference between that talk and the core inventive concept was that S had not actually got as far as doing an actual experiment involving antibody phage display.

However, S had explicitly proposed antibody phage display, and the skilled team would have had a reasonable expectation that that would succeed in a reasonable period of time (see[392], [408], [456] of the judgment). Taking all of the different factors and evidence into account, the claimed inventions had been obvious in the light of S's talk at the Banbury conference (see [456] of the judgment).

Pozzoli SPA v BDMO SA [2007] All ER (D) 275 (Jun) applied; Generics (UK) Ltd v H Lundbeck A/S [2008] All ER (D) 152 (Apr) applied; Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] All ER (D) 107 (Jul) applied.

(5) Pursuant to s 72(1)(c) of the 1977 Act, a patent was invalid 'if the specification does not disclose the invention clearly enough and completely enough for it to be performed by a person skilled in the art'. Further, caselaw had established that a claim would be invalid for insufficiency if the breadth of the claim exceeded the technical contribution to the art made by the invention. The breadth of the claim would exceed the technical contribution of the claim if the claim covered ways of achieving the desired result which owed nothing to the patent or any principle it disclosed (see [458] of the judgment).

In the instant case, the claimant had been correct to characterise the invention disclosed in the patents as a principle of general application. At its core, it was a technique for selecting a binding molecule of interest from amongst a potentially large population of other binding molecules.

That technique did not depend on the precise identity of the binding molecule. On the contrary, part of the usefulness of technique was that it could be applied to a diverse range of binding molecules, fragments and derivatives. Nor did the technique depend on the precise application which the user had in mind. Nor did implementation of the technique for the purpose of a new application involve undue burden on the part of the skilled team (see [491] of the judgment).

Neither claim 8 of 511 nor claim 1 of 577 was invalid on the ground of insufficiency (see [492] of the judgment). Biogen Inc v Medeva plc [1997] RPC 1 applied; Kirin-Amgen Inc v Hoechst Marion Roussel Ltd; Hoechst Marion Roussel Ltd v Kirin-Amgen [2004] All ER (D) 286 (Oct) applied; Generics (UK) Ltd v H Lundbeck A/S [2009] All ER (D) 258 (Feb) applied.

(6) Pursuant to s 72(1)(d) of the 1977 Act, a patent was invalid if 'the matter disclosed in the specification of the patent extends beyond that disclosed in the application for the patent, as filed'. In considering whether a patent was invalid for added matter, the decision as to whether there had been an extension of disclosure should be made on a comparison of the two documents read through the eyes of a skilled addressee.

The task of the court was threefold: (1) to ascertain through the eyes of the skilled addressee what was disclosed, both explicitly and implicitly in the application; (2) to do the same in respect of the patent [as proposed to be amended]; and (3) to compare the two disclosures and decide whether any subject matter relevant to the invention had been added whether by deletion or addition. The comparison was strict in the sense that subject matter would be added unless such matter was clearly and unambiguously disclosed in the application either explicitly or implicitly.

The test of added matter was whether a skilled man would, upon looking at the amended specification, learn anything about the invention which he could not learn from the unamended specification (see [493] of the judgment).

In the instant case, there was a clear disclosure in the application of fragments and derivatives of binding molecules that had binding specificity. The fact that claim 31 of the application had been framed more broadly in that respect was immaterial (see [502] of the judgment).

The claims of the patents did not disclose any new matter (see [502] of the judgment). Bonzel v Intervention Ltd (No 3) [1991] RPC 553 applied; Vector Corpn v Glatt Air Techniques Inc [2007] All ER (D) 297 (Oct) applied; European Central Bank v Document Security Systems Inc [2007] All ER (D) 420 (Mar) considered.

(7) In the instant case, the evidence did not establish, even on a balance of probabilities, that GI had produced 'a range of specificities'. Accordingly, the process whereby GI had produced ranibizumab had not fallen within either claim 5 of 511 or claim 1 of 777 (see [527] of the judgment).

The defendant had not infringed claim 5 of 511 or claim 1 of 777 (see [527] of the judgment). Pioneer Electronics Capital Inc v Warner Music Manufacturing Europe GmbH [1997] RPC 757 applied; Halliburton Energy Services Inc v Smith International (North Sea) Ltd [2005] All ER (D) 292 (Jul) considered; Monsanto Technology LLC v Cargill International SA [2007] All ER (D) 118 (Oct) considered.

Richard Meade QC, Tom Mitcheson and James Whyte (instructed by Marks & Clerk Solicitors LLP) for the claimant. Simon Thorley QC, Justin Turner QC and Joe Delaney (instructed by Allen & Overy LLP) for the defendant. The second defendant did not appear and was not represented.