Synthon B.V v Smithkline Beecham Plc

SmithKline Beecham Plc (SB) are the proprietors of Patent No. 2336364 (the patent) in respect of an invention entitled “Paroxetine salt”. It was filed on 23rd April 1999 and for the purposes of this appeal it is accepted that it has a priority date of 6th October 1998.

Synthon BV (Synthon) are the applicants for a patent having the international publication number WO 98/56787 (the application). It was filed on 10th June 1997 and is for an invention entitled “4-Phenylpiperidine Compounds”. It was not published until 17th December 1998.

By claim form dated 7th March 2001, Synthon started proceedings seeking revocation of the patent. They alleged that the patent was not new at its priority date having regard to what was disclosed in the application. That was an appropriate allegation as section 2(3) of the Patents Act 1977 required the application to form part of the state of the art. Thus the issue before the judge and before this court was whether the patent was new having regard to the description in the application. That depended upon the ambit of the invention claimed in the patent, the disclosure in the application and the application of the law on novelty.

The judge decided that Synthon had established that the patent was invalid as it was not new. He therefore ordered its revocation. Against that order SB appeal.

The Statutory Background – Section 125 of the Act states that an invention for a patent shall, unless the context otherwise requires, be taken to be that specified in a claim. Section 72 enables revocation if the invention of a patent is not a “patentable invention”. A patentable invention is defined by section 1 of the Act in this way.

“1.

- Patentable inventions.

(1)

A patent may be granted only for an invention in respect of which the following conditions are satisfied, that is to say -

(a)

the invention is new;

(b)

it involves an inventive step;

…

and references in this Act to a patentable invention shall be construed accordingly.

…”

Novelty is governed by section 2.

“2.

- Novelty.

(1)

An invention shall be taken to be new if it does not form part of the state of the art.

(2)

The state of the art in the case of an invention shall be taken to comprise all matter (whether a product, a process, information about either, or anything else) which has at any time before the priority date of that invention been made available to the public (whether in the United Kingdom or elsewhere) by written or oral description, by use or in any other way.

(3)

The state of the art in the case of an invention to which an application for a patent or a patent relates shall be taken also to comprise matter contained in an application for another patent which was published on or after the priority date of that invention, if the following conditions are satisfied, that is to say -

(a)

that matter was contained in the application for that other patent both as filed and as published; and

(b)

the priority date of that matter is earlier than that of the invention.

…”

It is important to have in mind section 3 as it makes clear that an application, deemed to form part of the state of the art under section 2(3), cannot be relied on to attack a patent on the ground of obviousness.

The Law – At the hearing of the appeal I believe there was no dispute as to the general principles to be applied when deciding whether the Synthon application made the invention of the patent available to the public. They were set out by me in my judgment of 31st July 2002 ([2002] EWCA Civ 1162) in the appeal between the same parties at paragraphs 14 to 17.

“14.

For the purposes of this appeal, there is no dispute of substance between the parties as to the principles that have to be applied when considering whether a prior published document renders a claim invalid on the ground of novelty (see sections 2(1) and 2(2)). A classic statement of the law is contained in the judgment of the Court of Appeal in General Tire and Rubber Company v Firestone Tyre and Rubber Company Ltd [1972] RPC 457 at 485:

“When the prior inventor’s publication and the patentee’s claim have respectively been construed by the court in the light of all properly admissible evidence as to technical matters, the meaning of words and expressions used in the art and so forth, the question whether the patentee’s claim is new for the purposes of section 32(1)(e) falls to be decided as a question of fact. If the prior inventor’s publication contains a clear description of, or clear instructions to do or make, something that would infringe the patentee’s claim if carried out after the grant of the patentee’s patent, the patentee’s claim will have been shown to lack the necessary novelty, that is to say, it will have been anticipated. The prior inventor, however, and the patentee may have approached the same device from different starting points and may for this reason, or it may be for other reasons, have so described their devices that it cannot be immediately discerned from a reading of the language which they have respectively used that they have discovered in truth the same device; but if carrying out the directions contained in the prior inventor’s publication will inevitably result in something being made or done which, if the patentee’s patent were valid, would constitute an infringement of the patentee’s claim, this circumstance demonstrates that the patentee’s claim has in fact been anticipated.

If on the other hand, the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee’s claim, but would be at least as likely to be carried out in a way which would not do so, the patentee’s claim will not have been anticipated, although it may fail on the ground of obviousness. To anticipate the patentee’s claim the prior publication must contain clear and unmistakable directions to do what the patentee claims to have invented: Flour Oxidizing Co. Ltd v. Carr & Co Ltd. ((1908) 25 RPC 428 at 457 line 34, approved in B.T.H. Co. Ltd v Metropolitan Vickers Electrical Co. Ltd (1928) 45 RPC 1 at 24, line 1). A signpost, however clear, upon the road to the patentee’s invention will not suffice. The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee.”

15.

To that can be added the statement of Lord Oliver in Asahi Kasei Kogyo KK’s Application [1991] RPC 485 at 539 line 22:

“… for anticipation under subsection (2), published information requires to contain an enabling disclosure …”

16.

In that statement Lord Oliver was concluding that for matter to be “made available to the public” and therefore to form part of the state of the art, it had to enable the public to implement the disclosure.

17.

It is I believe also apposite to cite passages from the speech of Lord Hoffmann in Merrell Dow Pharmaceuticals Inc v H.N. Norton & Co Ltd [1996] RPC 76 at 89:

“My Lords, I think that on this point the Patents Act 1977 is perfectly clear. Section 2(2) does not purport to confine the state of the art about products to knowledge of their chemical composition. It is the invention which must be new and which must therefore not be part of the state of the art. It is therefore part of the state of the art if the information which has been disclosed enables the public to know the product under a description sufficient to work the invention.

…

Other decisions of the EPO seem to me to make it clear that, at least for some purposes, products need not be known under their chemical description in order to be part of the state of the art. In BAYER/Diastereomers Decision T12/81 [1979-85] E.P.O.R. Vol. B. 308, 312, the Technical Board of Appeal said:

" ... [T]he concept of novelty must not be given such a narrow interpretation that only what has already been described in the same terms is prejudicial to it. The purpose of Art. 54(1) EPC is to prevent the state of the art being patented again. Art. 54(2) EPC defines the state of the art as comprising everything made available to the public before the date of filing in any way, including by written description. There are many ways of describing a substance in chemistry and this is usually done by giving its precise scientific designation. But the latter is not always available on the date of filing ... [It] is the practice of a number of patent offices to accept the process parameter, in the form of a product-by-process claim, for closer characterisation of inventions relating to chemical substances. To the Board's knowledge this is also the practice at the European Patent Office. If inventions relating to chemical substances defined by claims of this kind are patented, it necessarily follows that the resulting patent documents, once they enter the state of the art, will be prejudicial to the novelty of applications claiming the same substance although in a different and perhaps more closely defined form.

…

Anticipation by disclosure … relies upon the communication to the public of information which enables it to do an act having the inevitable consequence of making the acid metabolite. The terfenadine specification teaches that the ingestion of terfenadine will produce a chemical reaction in the body and for the purposes of working the invention in this form, this is a sufficient description of the making of the acid metabolite. Under the description the acid metabolite was part of the state of the art.””

Those statements of the law are consistent with the Guidelines for Examination in the European Patent Office. A typical application of those guidelines is shown in the Nissan Fuel Injection Valve case T167/84; [1987] 6 EPOR 344 at 348.

“6.

… For this reason, Part C, chapter IV, 7.2 of the Guidelines expressly states that "when considering novelty, it is not correct to interpret the teaching of a document as embracing well-known equivalents which are not disclosed in the document; this is a matter of obviousness". This approach has been consistently followed in the practice of the European Patent Office and the appellant completely failed to satisfy the Board that it is wrong on any ground.”

Another example of the approach of the European Patent Office is contained in Union Carbide T/396/89 [1992] EPOR 312 at paragraph 4:

“4.

Novelty in relation to document (1)

4.1 The respondents did not allege that there is any written disclosure of a product having the properties here in issue, but instead they relied on the well established alternative basis for asserting lack of novelty; viz. that the inevitable result of carrying out an example in accordance with a document forming part of the state of the art is that the product has all the properties of the alleged invention, as defined in its claims.

4.2

In the present case, an Experimental Report of an alleged repetition of Example 4 of document (1) was submitted by the second respondent in its Statement of Opposition filed on 28 October 1986. It is not disputed by the appellant that the polymer obtained had the properties of the polymer as claimed, before the introduction of the amendment mentioned above. However, what was disputed by the appellant, both before the Opposition Division and on appeal, was the validity of the repetition for the purposes of proving an inevitable result. In particular, attention was drawn by the appellant to what it alleged were significant differences in both the composition and concentration of the catalyst, and of the residence time, which, so it contended, affected the properties of the end product.

4.3

The respondents did not dispute the existence of these differences, but they denied their significance, contending that insofar as there was any departure in the repetition of Example 4 from that Example as actually described in document (1), those variations fell clearly within the general teachings of that document. The Board rejects this argument as being inconsistent with the logical basis of the test of "inevitable result". The word "inevitable" is used to convey the sense that one result, and one result only, is obtainable from the repetition of a given example. As soon as an element of option is introduced into an alleged repetition, inevitability disappears.

4.4

It may be easy, given a knowledge of a later invention, to select from the general teachings of a prior art document certain conditions, and apply them to an example in that document, so as to produce an end result having all the features of the later claim. However, success in so doing does not prove that the result was inevitable. All that it demonstrates is that, given knowledge of the later invention, the earlier teaching is capable of being adapted to give the same result. Such an adaptation cannot be used to attack the novelty of a later patent.

4.5

An opponent relying on inevitable result as a ground of invalidity must do one of two things; either reproduce the earlier example so closely that there is no scope for serious challenge to the validity of the repetition, or, if some material deviation is unavoidable, show convincingly that the deviation is not material to the end result.”

The dispute between the parties essentially involves a dispute of fact, namely what is explicitly and implicitly disclosed in the application. Thereafter the court has to decide whether that disclosure is sufficient to make the invention of the patent available. Although the general principles of law were not in dispute, there was a difference as to the input that the notional skilled addressee could make to produce the claimed product before the case passed from novelty to obviousness. I will come back to the law on that issue when the facts have been set out.

The Judge’s Approach to the Law – The judge set out the relevant passage from the General Tire case and extracts from other cases. He then analysed the law and concluded that there were “two ways of proving anticipation, the enabling disclosure and the inevitable result routes.” In practice that may be the way cases are presented, but it must be remembered that the statutory requirement is that the invention must be “made available to the public”. Any route which makes the invention available to the public anticipates the claim and any route that does not cannot meet the statutory requirement. No doubt a disclosure cannot make an invention available unless the invention can be made using the disclosure and also it would be the result of the disclosure.

The judge came to consider the concept of enabling disclosure in paragraph 86 of his judgment. He said:

“86.

I turn to the other, more central, concept -- enabling disclosure. This is not a rule about "inevitable result." It is about whether the two inventors have in substance reached the same invention. I think that is central to this case .”

Mr Waugh QC for SB rightly criticised that statement of the law and Mr Silverleaf QC for Synthon did not try to defend it as stated. The test is not whether the two inventors have in substance reached the same invention. The comparison is between the claimed invention and the disclosure to decide whether in fact, not in substance, the disclosure makes the claimed invention available to the public.

At paragraph 92 of his judgment the judge cited a paper of Judge Rogge. The judge said:

“92.

An important article by Judge Rogge equally focussed on the informational nature of an invention. Judge Rogge was for many years the President of the Bundespatentsgericht. He argued for a rational concept of novelty in his lecture to the 8^th Symposium of European Patent Judges, 1996. It was entitled "The Concept of Novelty with Particular Regard to Conflicting Patent Applications", 28 IIC 6/1997 at p.794. I quote some important passages:

"3.

A closer examination should begin by focusing on the wording of the relevant provisions. Under Art.54(2) EPC (and the relevant provisions of the national patent laws) any matter is novelty- destroying which has been made available to the public "by means of a written or oral description, by use, or in any other way". This clearly goes beyond a written or diagrammatical description; the content of the information, not the form in which it is imparted, is decisive. This allows a number of conclusions to be drawn, some of which also find expression in EPO jurisprudence.
(a) The information may to a certain degree be hidden, provided the skilled practitioner would ultimately be able to discover it without undue effort. The language used is irrelevant. It may even be a computer language. The chemical composition of a product that has been made available to the public also forms part of the state of the art if the skilled practitioner is able to analyse it. Conversely, disclosure of a process also discloses its inevitable result.
(b) Furthermore, matter will have to be viewed as also having been disclosed which the skilled practitioner is required to add from his technical knowledge as a matter of course or as being virtually essential to carrying out a given teaching.
Let us consider a simple example: A cook who finds that a soup being prepared from a recipe is lacking in flavour may well add salt, regardless of whether the recipe makes any mention either of adding any salt at all, or of adding a smaller amount than actually used. The addition of salt does not result in a new recipe. Quite the reverse: to a person skilled in the art it is so obvious as not to warrant particular mention."

"4.

The practice of taking a broad view of the disclosed content of a particular item of prior art is supported by the fact that the content of an earlier, unpublished patent application is also viewed as comprised in the state of the art (Art. 54(3) EPC).
This meets the requirements of the Strasbourg Convention of 1963 (Arts. 4(3) and 6) and is intended to prevent matter from being patented that is already, or could become, the subject-matter of another patent. In that respect it does not genuinely contribute to the advance of the state of the art, and hence there is no objective justification for rewarding it with the grant of a patent. Added to which, double patenting clouds the legal position and is therefore undesirable.

It would be to ignore this legislative imperative if inventions exhibiting only the slightest of differences were to be described as "new". (Further) patents would then have to be granted for subject- matter which, although not literally anticipated, would predictably fall entirely or primarily within the scope of protection of an earlier patent, scope which should, however, remain the exclusive preserve of the owner of the prior right. Were this not so, we would have no way of effectively restricting double patenting.

It would therefore seem consistent to regard an earlier patent application as simultaneously anticipating, so as to be novelty- destroying, the entire range of subject-matter which it could conceivably cover, and in particular all possible equivalents. In fact, this view is encountered not infrequently in the relevant literature."

"6.

One could argue about a number of points, and it will not always be possible to decide cases on logical grounds alone. We should not however lose sight of two things:
-- Examination as to novelty should not be restricted to a purely formal comparison with known prior art, but must include the actual information content which goes beyond the words used.
-- Earlier applicants must be given reasonable scope to defend their inventions.".”

It is unfortunate that the judge failed to cite paragraph 5 of Judge Rogge’s paper which explained that the German Federal Supreme Court in the Electric Plug-In decision 1995 GRUR 330 had failed to follow what Judge Rogge called the consistent approach.

The judge proceeded from Judge Rogge’s article in this way:

“93.

When it comes to the "enabling disclosure branch Judge Rogge's two conclusions are in my view essential if one is not to have a purely formalist approach to anticipation. The earlier document must certainly be "enabling." The key question is whether the two inventors have for practical purposes disclosed the same invention and told you how to make it. This does not involve a claim comparison exercise as in the old law of prior claiming. It involves the question of whether the prior inventor has in substance disclosed what the later inventor claims. It is no good, because it is not enabling, if he discloses as the invention a particular chemical compound with a novel use but the skilled man does not know how to make it. Asahi was such a case. On the other hand if he discloses the compound and the skilled man would know how to make it, it does not matter if the earlier man does not supply the detail. It is not detail material to his invention (the compound itself).”

That approach was the basis for the judge’s conclusion that the patent was not new. For example he said:

“96.

… What I have is a general disclosure of a wide variety of methods of making crystalline paroxetine mesylate. And the later disclosure, for all practical purposes, is an equivalent wide disclosure. So Synthon got there first. All that can be said for SB is that their disclosure is to a readier way of making the crystals, but Synthon's is clear enough.

..

100.

Mr Waugh also points out that even if there is only one crystalline form of anhydrous paroxetine mesylate, there are at least three hydrates (crystals containing solvate). So, he submitted, there is nothing inevitable about the production of the SB form from the general teaching of Synthon. Even if you make crystals you may get a hydrate. This is true but I do not think relevant. Both patents say that. They are both at the same level of generality. SB is not teaching the reader anything new in relation to hydrates.

101.

In the end I conclude that this is indeed a case of anticipation. It was Synthon who first invented paroxetine mesylate, including the crystals of the SB form. And they gave enough information on how to make it. If that were not so, then SB would have a valid patent covering the very heart of the Synthon invention. That is not the purpose of s.2(3) or Art. 54(3).”

To avoid double patenting the judge appears to have adopted an approach similar to that advocated in Judge Rogge’s paper. He concluded that the two inventors disclosed the same invention at the same level of generality and that Synthon got there first. It followed that the purpose of section 2(3) was satisfied. The patent was not new.

Mr Waugh accepted that the purpose of section 2(3) was to avoid double patenting. However he, rightly in my view, submitted that the judge had adopted an approach that was inconsistent with the Patents Act 1977 which adopted the method of dealing with double patenting set out in the EPC. That method is different from that which had been the law in the United Kingdom prior to 1977 and that applied in the USA. The law requires the earlier application to form part of the state of the art. Thereafter the law of novelty applies. There is no room for a different approach to novelty in section 2(3) cases to section 2(1) cases. I therefore cannot support the legal basis for the judge’s conclusion.

Mr Silverleaf did not support the legal basis upon which the judge decided the case. He argued his case upon more classic lines. He submitted that having regard to the findings of fact made by the judge, claim 1 of the patent was not new according to the law as stated in General Tire. I therefore turn to consider the submissions of the parties starting with the disclosures in the patent and the application.

The Patent – General Tire states that “it is necessary to compare the earlier publication with the patentee’s claim”. In this case there is no dispute of substance as to the ambit of claim 1 of the patent. It claims Paroxetine methanesulfenate, which I will refer to as PMS. It is in this form:

“Paroxetine methanesulfonate in crystalline form having inter alia the following characteristic IR peaks: 1603, 1513, 1194, 1045, 946, 830, 776, 601, 554, and 539 +- 4 cm^-1.; and/or the following characteristic XRD peaks: 8.3, 10.5, 15.6, 16.3, 17.7, 18.2, 19.8, 20.4, 21.5, 22.0, 22.4, 23.8, 24.4, 25.0, 25.3, 25.8, 26.6, 30.0, 30.2, and 31.6 +-0.2 degrees 2 theta.”

That claim is supported by a specification which states at its outset that the invention is PMS as a novel compound. In one aspect PMS is provided in non-crystalline form which may be a solid or an oil. In another aspect the PMS is crystalline. It may also be obtained as a solvate. A further aspect of the invention is the process for the preparation of PMS. The specification states:

“In a further aspect the present invention provides a process for the preparation of a paroxetine methanesulfonate by precipitation from a solution of a paroxetine methanesulfonate, spray drying or freeze drying a solution of a paroxetine methanesulfonate, evaporating a solution of a paroxetine methanesulfonate to a glass, or by vacuum drying of oils of a paroxetine methanesulfonate, or solidification of melts of a paroxetine methanesulfonate.
Preferably such process provides crystalline paroxetine methanesulfonate by crystallization or re-crystallization from a solution of a paroxetine methanesulfonate, and especially on a commercial scale in a reproducible manner.
Paroxetine methanesulfonate may be prepared by chemical modification of a precursor methanesulfonate salt. Suitable precursors are those which may be converted to the methanesulfonate salt by hydrogenation. For example, the N-benzyl derivative of paroxetine methanesulfonate in a suitable solvent (such as a C1-4alkanol) may be hydrogenated using a catalyst such as palladium on charcoal to generate a solution of paroxetine methanesulfonate.
Alternatively paroxetine methanesulfonate may be prepared by treating paroxetine free base or a labile derivative thereof with methanesulfonic acid or a labile derivative thereof. For example paroxetine methanesulfonate may be prepared by contacting stoichiometric amounts of the acid and paroxetine base, alternatively an excess of the acid may be used. Preferably the base is in solution and the methanesulfonic acid is used as a solid, liquid, or as a solution, for example in water, ethers, or lower alcohols such as methanol, ethanol, and propan-2-ol, or a mixture of solvents. There is no need for a pure form of paroxetine base to be used as a starting material in the preparation of the methanesulfonate salt.”

The specification proceeds with general directions for the preparation of crystalline PMS. At page 7 line 10 it states:

“A crystalline salt may be prepared by various methods such as directly crystallizing the material from a solvent in which the product has limited solubility or by triturating for example with ethers such as diethyl ether or otherwise crystallizing a non-crystalline salt.

A number of solvents may be used for the crystallization process including those that are useful industrially; e.g. paroxetine methanesulfonate may be crystallized from a relatively crude feedstock such as is commonly produced during the final stage of the chemical synthesis of paroxetine. In particular solvent systems which are suitable for preparation of paroxetine methanesulfonates can also be used for recrystallization (including crystallization), for example toluene or lower alcohols followed by precipitation with ether or hexane. Alternatively, paroxetine methanesulfonate may be crystallized or recrystallized by cooling and optionally seeding a hot solution in a suitable solvent such as propan-2-ol. An improved yield of the salt is obtained by evaporation of some or all of the solvent or by crystallization at elevated temperature followed by controlled cooling, preferably in stages. Careful control of precipitation temperature and seeding may be used to improve the reproducibility of the production process and the particle size distribution and form of the product.

One method for preparing crystalline paroxetine methanesulfonate salt from solution comprises forming a supersaturated solution of the salt in a solvent and allowing the crystalline salt to precipitate from solution, for example by maintaining the solution in relatively quiescent conditions, e.g. under gentle stirring or leaving the solution to stand. Seeding of the solution is optional. By selection of a suitable solvent medium and concentration the present invention provides a process in which crystalline paroxetine methanesulfonate precipitates at temperatures above -- 20° C e.g. above 0° C e.g. around ambient conditions of 10 to 25° C. Suitable solvent media for this method comprise C1-5 alkyl benzenes such as toluene, alcohols e.g. C1-5 alkanols such as 2-propanol, di- C1-5 alkyl ketones such as acetone, ethers such as C4-6 cyclic ethers such as tetrahydrofuran or mixtures thereof, and in particular mixtures of such alkyl benzenes with such alkanols or ketones e.g. toluene and 2-propanol or toluene-acetone mixtures.

Another method of preparing crystalline paroxetine methanesulfonate salt comprises forming a solution of the salt, for example as defined herein, and subsequently supersaturating the solution for example by evaporation of the solvent and/or the addition of an anti-solvent to precipitate the crystalline salt from solution. An "anti-solvent", as referred to herein, is a medium such as an organic liquid, which is miscible with a solvent for paroxetine methanesulfonate salt but in which the paroxetine methanesulfonate salt is less soluble than in the solvent. Preferably the solubility of paroxetine methanesulfonate salt in the anti-solvent is less than 1mg/ml, preferably less than 0.2 mg/ml, especially less than 0.1 mg/ml. Examples of anti-solvents include ethers, e.g. di- C1-5 alkyl ethers and alkanes, such as C5-10 alkanes which may be straight chain, branched chain or cyclic such as hexane. Solvent systems which are suitable for preparation of paroxetine methanesulfonate, e.g. those discussed above, e.g. with reference to the solvent systems used for the deprotection reactions discussed above, can also be used for recrystallization by precipitation with an anti-solvent.”

A preferred method of production is described and there follows a large number of examples. The invention of claim 1 is illustrated using Examples 1-25, 31-32, 35 to 42 and 44 to 50 which describe in detail the way to obtain the product of claim 1.

The application – General Tire next requires that the application should be interpreted by the skilled reader.

As stated in its title, the application relates to an invention for “4-Phenylpiperidine compounds”. The specification starts by stating that the invention relates to a group of tri-substituted, 4- Phenylpiperidines, to a process for making them, to a medicament comprising such compounds and the use of them for the manufacture of a medicament. The skilled reader would therefore realise that the application related inter alia to an invention for a very wide range of compounds.

The application then states that paroxetine is known and has been used as a medicament in the form of a salt with pharmaceutically acceptable acids. It specifies the hydrochloride salt as one known to be a useful salt of paroxetine and explains that both the anhydrous and the hydrated forms have been described. There follows the statement that “most of these known salts of paroxetine salts have unsuitable physico-chemical characteristics”. The specification explains why they are unsuitable and then states that an object of the invention is to provide a compound with improved characteristics. This is achieved according to the invention which has six aspects.

The first aspect is that claimed in claim 1. It comprises a compound and pharmaceutically acceptable salts having the following formula.

Preferences are given for R, X and R² groups, but not R¹. As R² preferably represents a C1 to C2 alkyl group there is some limitation pointing to PMS. However the preferred compounds are many.

The second aspect of the invention relates to a process for preparing the general class of compounds. A 4-Phenylpiperidine compound or its salt or base is mixed with a sulfonic acid to form a solution. The solid is then separated from the solution. The teaching becomes more specific at page 5 line 20 where it is stated:

“The compounds of the invention can be prepared from the free base of the 4 phenylpiperidine, having the formula II, this preferably being paroxetine, by treatment with a sulfonic acid as defined above in a suitable solvent to form a solution of the desired acid addition salt, whereafter this is precipitated out of the solution.”

There follows general directions such as “the forming of a solution may preferably proceed at temperatures from about 0^o to the boiling point of the solvent.” In essence a wide range of conditions and methods are suggested to be suitable.

The third aspect of the invention is a compound obtainable by the process of the second aspect. The fourth aspect is the compound for use as a medicament and the fifth is the medicament for treating certain disorders. The sixth aspect is the use of the compound as an agent in further syntheses. The application also contains a suggestion that the compounds of the invention can be used as a starting agent for forming further acid addition salts. An example is the formation of paroxetine maleate. There are also general statements that the new compounds of the first aspect of the invention can also form hydrates and/or solvates.

Up to page 9 line 29, PMS has not been mentioned. It is one compound of a number within the general formula of the first aspect and the preferred formula. Further there is no mention of producing a crystalline form. This all changes at page 9 line 30 where the specification “elucidates” the invention “by way of the following examples and results”. The first is described as “Experimental”, but as it is in reality part of example 1 I will refer to both the experimental passage and example 1 as example 1. It is in this form:

“A seeding crystal of paroxetine methane sulfonate was made as follows:
2.7 g (8.2 mmol) of paroxetine was dissolved in 15 ml of hot ethanol.
1.0 g (10.4 mmol) of methanesulfonic acid in 15 ml of ethanol was added and the mixture was cooled to room temperature. When the mixture had reached room temperature the mixture was put in the freezer at -20^°C overnight. No crystalline compound was obtained.
The mixture was evaporated to dryness leaving an oil.
After 1 month at room temperature a waxy solid was obtained.
Part of this solid was taken apart and the rest was dissolved in 10 ml of EtOAc. The waxy crystals were added and the mixture was put in the freezer of -20^°c overnight. A white crystalline product was precipitated. After filtration and drying in a vacuum oven 2.5g (5.9 mmol) of paroxetine methane sulfonate was obtained. Yield 72%.”

The seeding crystal of PMS was then used in example 1 to produce crystalline PMS. In essence paroxetine solution, methane sulfonic acid and boiling acetate were left to cool. The mixture was seeded and the white solid was filtered off. It was dried overnight. The yield was 99.5% and it was 98% pure. Its analysed properties were set out in Table I which were stated to be that the IR peaks were 531, 546, 777, 838, 931, 962, 1038, 1100, 1169, 1208, 1469, 1500, 1515, 1615, 2577, 2869, 2900, 3023.

Example 2 concerns preparation of paroxetine benzene sulfonate; example 3 paroxetine p-toluene sulfonate; example 4, paroxetine p-chlorobenzene; example 5, paroxetine maleate; example 6, paroxetine acetate; and example 7 paroxetine free base. There follows Table I which contains the characteristics of the compounds produced in the examples.

Finally there are the claims. They are in general form following the six aspects of the invention. PMS is not mentioned, but falls within the generality of the formulae. No claim is made to a crystalline form.

There is no dispute that the only relevant mention of PMS is in experiment 1 and that the product of experiment 1 had different IR peaks to those set out in claim 1 of the patent. Thus the skilled reader would conclude that the PMS made by Synthon was a different form of crystalline PMS to that claimed in the patent.

The Experiments – Having regard to the disclosure in the application, SB contended that the PMS disclosed in the application was a different form to that claimed in the patent. Thus there was no anticipation of claim 1 of the patent. Synthon contended that the peaks, while being different, could be and were consistent with the PMS made according to example 1, being the same as that claimed in the patent. In essence Synthon contended that there was only one form of crystalline PMS and that if the process of example 1 was carried out, it was inevitable that the crystalline form of claim 1 of the patent would be obtained. They therefore served a Notice of Experiments seeking to establish that fact. Those experiments were carried out by Dr Robert Adlington under the supervision of Professor Sir Jack Baldwin FRS, the Waynflete Professor of Chemistry at Oxford University. Dr Adlington was described by the Professor as the best organic chemist he has ever had working for him to conduct experiments.

The experiments ran into difficulties and the judge held that example 1 was not repeatable so as to obtain crystalline PMS: just giving the Synthon recipe was not enough to enable the skilled reader to produce crystals and certainly not inevitably so. That conclusion was supported by work done on behalf of SB in Israel. The Israeli workers sought to work according to experiment 1 of the application and expected to get PMS crystals. They failed.

The Submissions and Conclusion – Mr Waugh submitted that the application did not make PMS as claimed in claim 1 available to the public. The only mention of PMS in the application described PMS of a different form. The skilled addressee was entitled to carry out example 1 and to use any product obtained. But repetition of example 1 did not produce crystalline PMS and therefore the procedure of example 1 did not make available the crystalline form of PMS claimed in claim 1 of the patent.

The failure of the Adlington/Baldwin team to reproduce example 1 required Synthon to reformulate its case. That they did but to understand Mr Silverleaf’s submissions it is necessary to record another finding of fact made by the judge. The unsuccessful work carried out by the Adlington/Baldwin team was extensive with the result that they ultimately achieved success by altering the conditions. As the judge held:

“59.

... To me there is a fairly strong inference – that just giving the Synthon recipe is not enough to enable the skilled man to produce crystals and certainly not inevitably so. The trouble that the Adlington/Baldwin team then had in making crystals confirms this. I need not go into the detail. It is all in two helpful fold-out documents showing the efforts that were made. Perhaps the most revealing comment was by Prof. Baldwin. Halfway through their ultimately successful efforts he formed the theory that the problem was caused by using ethanol as a solvent. Since there was excess methanesulphonic acid he thought it possible that water was being formed by a reaction between these two components. And since the product is extremely soluble in water this might be the problem. Prof. Baldwin's evidence went like this:

“A. If someone had told us or if he [Dr Adlington] had been smart enough to realise that ethanol and methanesulfonic acid give ether and water, we could have run the NMR spectrum on the following day after the (inaudible) experiment.
Q. If you had been smart enough to realise?
A. Yes. We were not smart enough to realise that.””

The resulting crystalline PMS was analysed and had the same IR peaks as those claimed in claim 1. The judge accepted that the IR peaks in Table 1 of the application were the result of mistaken measurements. That, together with the oral evidence, persuaded the judge to hold that anhydrous PMS was a monomorph. It followed that crystalline anhydrous PMS, when made, would fall within claim 1.

In this Court, Mr Silverleaf did not dispute the finding of the judge that example 1 did not enable the skilled addressee to make crystalline PMS. His submission was that the application did make available the claim 1 form of PMS as crystalline anhydrous PMS was disclosed in the application and there was only one form of such PMS. It followed that that product had been made available to the public provided of course the skilled addressee could make it. Despite the fact that example 1 did not enable the skilled person to make crystalline PMS, he submitted that the general teaching of the application was sufficient to enable such a person to make the claimed form of PMS. That was, Mr Silverleaf submitted, established by the evidence, in particular that of Mr Ward and was evident from a comparison of the teaching in the patent and the application.

Mr Silverleaf, as did the judge, placed emphasis upon a passage of Mr Ward’s cross-examination. After taking him through the general teaching of the patent with the purpose of obtaining admissions that the general teaching in the patent enabled production of crystalline PMS, he turned to the application. He asked:

“Q. If you were looking at this document and considering making paroxetine mesylate, you would certainly start with the examples. That is right, is it not?
A. Yes, yes, I certainly would.
Q. But you certainly would not feel bound by them, would you? You would expect to make paroxetine mesylate using a variety of other reactions and conditions?
A. Yes, I think I would.
Q. And crystallize it successfully?
A. That is perhaps another matter. I think I might be inclined to say, "Once I have actually got some sort of crystals, then I might investigate a better way of making crystalline material." In order to get your seeds, then it might be sensible to do what is in the document rather than go shooting off and doing your own thing.
Q. I think we agree you would start with the examples. You start with the examples. Let me assume that you perform Experimental and it does not work. What do you do next?
A. I think I would do the sort of thing that I have mentioned in my expert report. I would look at the chemistry that I was trying to carry out and say, "Well, maybe I need to make some changes." I think I have suggested the sort of changes I would make. I might well readjust the stoichiometry, the molar equivalents.
Q. And you would get a hint that that might be a good idea from looking at example 1, would you not?
A. You might and you might not. I am not necessarily convinced by that. In my experience of making salts of bases, it is sometimes actually advantageous to make the first sample with an excess of acid. This is frequently done with things like hydrochloride salts. I am not necessarily convinced that you would necessarily always go down in molarity.
Q. You might go up?
A. You might go up, yes. You might change the concentration; you might change the solvent.
Q. But these would all be straightforward changes, and you would expect, fairly quickly, to succeed, based on what is in this document?
A. I would certainly have an expectation of success, yes.
Q. Let me put this to you. Based on what is in the SB patent, you would come to exactly the same conclusion, would you not?
A. Yes. I think you are asking me a slightly different question. I think when we started on this, you said clear your mind of all the information you have and let us talk about this document.
Q. I am now asking you a different question.
A. Right.
MR. JUSTICE JACOB: I think he is now asking you to put the Synthon patent out of your mind and the SB patent and supposing you had not been the inventor and it was given to you.
A. Yes. I agree that in that position I would have the same expectation, yes.”

In his submissions Mr Silverleaf drew a comparison between the general directions in the patent and those in the application. He submitted that the evidence established that both were sufficient to enable the skilled addressee to make the crystalline PMS. That being so, there was an enabling disclosure in the application of how to make PMS and of PMS as claimed. It followed that the claim 1 form of PMS had been made available to the public.

Mr Waugh disputed the suggested effect of Mr Ward’s evidence, but submitted that whatever the effect of that evidence the approach adopted by Mr Silverleaf was contrary to the law as stated in General Tire. It was not sufficient that there was general information in the application to enable the claim 1 form of PMS to be made. To anticipate there had to be clear and unmistakable directions which if carried out would make available PMS as claimed. There were none. The only directions, being those in example 1, did not produce claim 1 PMS and the general teaching did not give clear directions to make PMS, or how to make it, let alone the form claimed in claim 1.

Mr Silverleaf sought to equate the test for novelty with that of sufficiency (section 72(1)(c)). He submitted that if the application contained sufficient information to enable the skilled person to make PMS as claimed, then the patent lacked novelty. Mr Waugh submitted that the test of sufficiency was different. I do not propose to consider the law as to sufficiency as the only issue is whether claim 1 lacked novelty. Our task is to construe section 2(2) of the Act and to apply it in accordance with the case law.

In my view clear guidance can be obtained from the General Tire and the Union Carbide cases cited above. However Lord Westbury LC’s statement of the law in Hills v Evans (1862) 31 L.J. Ch 457, part of which was cited by Lord Jauncey in Asahi Kasei Kogyo K.K’s Application [1991] RPC 485 is also helpful to explain the amount of deviation allowed by the skilled reader. He said:

“Now the question is, what must be the antecedent statement? I apprehend the principle is correctly thus expressed: the antecedent statement must be such that a person of ordinary knowledge of the subject would at once perceive, understand and be able practically to apply the discovery without the necessity for making further experiments and gaining further information before the invention can be made useful. If something remains to be ascertained which is necessary for the useful application of the discover, that affords sufficient room for another valid patent.”

I reject Mr Silverleaf’s submission. There are no clear and unmistakable directions to make PMS as claimed in claim 1 of the patent as required by the General Tire case. The general teaching of the application does not mention PMS. It is one of a number of compounds described by reference to formulae. The only specific reference is in example 1. That describes a different form. It follows that the skilled person would not expect to produce the PMS claimed in claim 1 by carrying out the general teaching of the application. If he attempted to carry out example 1, he would fail to obtain crystalline PMS. He would therefore not know that there was only one form of crystalline PMS and that was not the form described in the application.

Further the teaching is not such that skilled persons would at once perceive, understand and be able practically to apply the invention claimed in claim 1 of the patent without the necessity of doing further experiments. If they sought to produce PMS they would believe that the application led to a different form. If they sought to carry out the specific directions of production, they would fail as both the Adlington/Baldwin and Israeli teams did. The general statements in the application relied on did not disclose any particular method of production of any particular product. To suggest that they did when the specific method did not work is, I believe, fanciful. In my view the statement of the European Patent Office in the Union Carbide case (see paragraph 10 above) applies.

“4.4

It may be easy, given a knowledge of a later invention, to select from the general teachings of a prior art document certain conditions, and apply them to an example in that document, so as to produce an end result having all the features of the later claim. However, success in so doing does not prove that the result was inevitable. All that it demonstrates is that, given knowledge of the later invention, the earlier teaching is capable of being adapted to give the same result. Such an adaptation cannot be used to attack the novelty of a later patent.

4.5

An opponent relying on inevitable result as a ground of invalidity must do one of two things; either reproduce the earlier example so closely that there is no scope for serious challenge to the validity of the repetition, or, if some material deviation is unavoidable, show convincingly that the deviation is not material to the end result.”

The suggestion that the disclosure in the application was equivalent to that in the patent is not correct. As one would expect both contain general statements on production, but they are different. Perhaps with knowledge of the patent, it would be possible to extract the idea to make crystalline PMS and a process to do it other than that in example 1. But the differences in disclosure are considerable. The patent is directed at PMS, whereas the application is directed at a large number of compounds both in the general statements and in the preferred form. Second, the general statements as to how PMS can be obtained differ from those relating to the compounds in the application. Third, the examples in the patent give detailed instructions as to how crystalline PMS can be made, whereas the equivalent example in the application does not work. Fourth, the patent claims a different crystalline form of PMS to that described in the application.

As I have said, Mr Silverleaf placed considerable reliance upon parts of the cross-examination of Mr Ward (see paragraph 4653 above). In my view his evidence, when understood, does not establish that the application contains the clear and unmistakable directions to make the claimed form of PMS. Mr Ward was taken through the patent and asked about the products he would use to produce PMS. The purpose of the cross-examination was to establish that the skilled person could at the date of the patent produce PMS according to the general teaching of the application. At Evidence 4 page 586 he was asked:

“Q. There is no specialized trick to synthesising the material or to getting it to crystallize that you are aware of, is there?

A. I think it is probably true to say from my experience that if you use sensible conditions, if you use the right conditions, then it appears to crystallize quite readily, but, conversely, if perhaps you choose the wrong conditions, then it can be a problem to get it to crystallize.

Q. When you say “sensible conditions”, you mean the sort of conditions that a sensible chemist would choose?

A. I think that is putting a slightly different slant on it?

Q. I do not know, I am asking you?

A.

Really my answer has been given with an understanding of the chemistry of paroxetine mesylate. Once you have made it a few times and you understand how it behaves, you can then see perhaps with hindsight what are sensible things to do and what perhaps are silly things to do.”

Mr Ward was one of the inventors of the patent. He had more knowledge of making PMS than the skilled person would have had. That being so, that part of his evidence suggests that absent detailed instructions the skilled person would need more than general statements. Of course that was available in the examples in the patent.

The cross-examination then took Mr Ward through the general teaching of the patent and Mr Ward accepted that, after reading it, he would expect to be able to follow either a particular example or the general teaching and obtain the crystalline PMS disclosed. He would go to the examples and expect success. He was then taken to the application. He was asked to put out of his mind everything he had learnt about PMS when working for SB or during the litigation. He accepted that there was no suggestion that example 1 was the only way to make PMS, but it was his experience that chemists normally went to the example as it was usually the best place to go. The exchange particularly relied on by Mr Silverleaf (see paragraph 46 above) then occurred. When read in context that evidence establishes that Mr Ward would, if working from the application, have expected success, but that did not mean that it contained clear and unmistakable directions which would make the claim 1 form available. No doubt the Adlington/Baldwin team and the Israelis expected success. They started with example 1. When it failed I expect that they looked at the chemistry and contemplated changes. However nothing immediate appears to have sprung to their minds.

The crucial question was not whether the skilled addressee would expect success, but whether the application made available PMS as claimed. There was no attempt to ask Mr Ward whether there were directions in the application which, if followed, would produced the claimed form of PMS. No doubt that was because the answer would have been “No”. Once it had been established that example 1 did not disclose a successful route to PMS as claimed in the patent, the skilled addressee might have adopted obvious modifications. But such an approach is not permissible when considering novelty. Mr Ward’s evidence does not support the novelty attack.

Conclusion – The disclosure in the application does not make the PMS claimed in claim 1 of the patent available to the public. It follows that I would allow the appeal, set aside the order of the judge and dismiss the claim for revocation.

I agree.

I also agree.