FIRST DIVISION, INNER HOUSE, COURT OF SESSION

 

Lord President

Lord Kingarth

Lord Clarke

 

 

 

 

 

[2008] CSIH31

 

 

OPINION OF THE LORD PRESIDENT

 

in

 

RECLAIMING MOTION

 

by

 

ARROW GENERICS LIMITED

Petitioner and Respondent;

 

against

 

AKZO NB (Represented in Scotland by ORGANON LABORATORIES LIMITED

Respondent and Reclaimer:

 

for

 

Revocation of claims 1-3 and 5 of European Patent EP 0 389 035

 

_______

 

 

 

Act: Currie, Q.C., Higgins; Maclay Murray & Spens (Petitioners and Respondents)

Alt: McNeill, Q.C., Delibegović-Broome; McClure Naismith (Respondents and Reclaimer)

 

20 May 2008

 

Introduction

 

[1] In these proceedings the petitioner (the respondent in the reclaiming motion), which I shall refer to as "Arrow", seeks revocation of claims 1 to 3 and 5 of European Patent 0 389 035 ("the patent") granted to the respondent (the reclaimer in this reclaiming motion), which I shall refer to as "Akzo". Akzo is represented in Scotland by Organon Laboratories Limited. The patent has as its active ingredient the steroid known conventionally as tibolone. That compound has been known since the 1960s and, since about 1988, has in one composition been marketed as Livial. It has combined oestrogenic, progestagenic and androgenic characteristics. In tablet form, it is used for treating menopausal complaints, for modulating the immune system and for combating osteoporosis. The patent is concerned with tibolone in a high degree of crystalline purity, that is, with a high degree of one form as against any other form of the crystals of that compound. The priority date of the patent is 18 March 1989.

 

The patent

[2] The claims in the patent are, in their English language version, in the following terms:

"1. A pharmaceutical composition which contains a pharmaceutically suitable solid carrier and the compound having the structure (7ά, 17ά) - 17 - hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn-3-one, characterized in that the compound is crystalline pure, which purity is greater than 90%.

2. The pharmaceutical composition of claim 1, characterized in that the crystalline purity is greater than 95%.

3. The pharmaceutical composition according to claim 1, characterized in that the crystalline pure compound has the monoclinic P21 form.

4. The pharmaceutical composition according to claim 1, characterized in that the crystalline pure compound has the triclinic P1 form.

5. A method for the preparation of a crystalline pure compound for use in a pharmaceutical composition accordingly to claim 3, characterized in that the polymorphous compound is crystallized from mixtures of water and acetone or ethanol, or from ethyl acetate, acetonitrile, or acetone-hexane mixtures.

6. A method for the preparation of a crystalline pure compound for use in a pharmaceutical composition according to claim 4, characterized in that the polymorphous compound is crystallized from an apolar solvent."

[3] Claims 4 and 6 are not challenged in these proceedings. Of the challenged claims, claims 1, 2 and 3 are claims to a product; claim 5 is a claim to a process (for the preparation of the monoclinic crystalline form).

[4] In the Description of the patent the patentee narrates that the compound in question, its chemical and structural formulae being given, is known from two American patents, which are identified. The method described in these patents has, it is narrated, led to a compound having certain characteristics, which have led to its use in medicaments having gonadomimetic, ovulation-inhibiting or immuno-modulating action.

[5] The Description continues:

"Surprisingly, it has now been found that the compound having the formula [in question] prepared in accordance with the method described in the above-mentioned patents, is polymorphous and consists of two crystalline pure forms.

It may be expected of polymorphous compounds that their biological activity is comparable or identical to the biological activities of the crystalline pure forms of which the polymorphous compound consists. Nevertheless, if the polymorphous compound is used as a medicament great drawbacks are associated therewith compared with its crystalline pure components. The differences in crystal structure can lead to a difference in physico-chemical parameters such as stability, rate of dissolution, melting point, analytical data and the like, which frequently are strongly influenced by the crystal forms in the polymorphous compound. This is all the more obvious since in practice it is virtually impossible to make each batch of a polymorphous compound exactly identical in respect of composition. As a consequence of these differences, it is frequently regarded as undesirable to incorporate polymorphous compounds in medicaments and it is sometimes demanded that only one of the crystalline pure components of the polymorphous compound is used.

The aim of the present invention is, therefore, to obtain a pharmaceutical composition which contains a crystalline pure form according to the formula [in question], which is completely or virtually completely free from the other crystalline form.

The term 'crystalline pure form which is virtually completely free from the other crystalline form' denotes a form which contains less than 10% and preferably less than 5% of the other crystalline form.

It has now been found that by using specific crystallization techniques two crystalline pure forms, which here are designated form I and II respectively, can be obtained from the polymorphous compound [in question].

It has moreover been found that form I is chemically appreciably more stable than the already known polymorphous compound [in question]. This improvement in stability yields great advantages in respect of the shelf-life of the pharmaceutical product in which form I is incorporated.

The invention therefore relates to a pharmaceutical composition which contains a pharmaceutically suitable carrier and the compound having the structure [in question], characterized in that the said compound is a crystalline pure or virtually pure form which is completely or virtually completely free from the other crystalline form.

A pharmaceutical composition of this type has the advantage that the reproducibility is appreciably increased and that the physical data, within acceptable limits, are always identical.

The pure crystalline compounds, and in particular the compound with form I, are suitable for treating menopausal complaints or for modulating the immune system, and also for combating osteoporosis.

Form I is obtained by crystallizing the polymorphous compound [in question] from mixtures of water and acetone or ethanol. A suitable method is to dissolve the polymorphous compound in acetone or ethanol, after which the solution is added to water. Conversely, water can also be added to a solution of the polymorphous compound in acetone or ethanol. Other suitable solvents are, for example, ethyl acetate, acetonitrile and acetone/hexane mixtures. Mixtures of methanol and water, from which only mixtures of the two crystalline forms always crystallize, are unsuitable.

Form II can be obtained by crystallizing the polymorphous compound from a selection of apolar solvents. Toluene is very suitable, as is also hexane to which a little ethyl acetate has been added. Another suitable solvent is trichloroethylene.

The rate of crystallization, which is influenced most strongly by the crystallization temperature, can also play a role in obtaining crystalline pure forms. Thus, in general good results are obtained from anhydrous acetone only when the crystallization is carried out at a relatively low temperature."

The patentee then explains that forms I and II can readily be differentiated from one another - in particular by three methods, which are then described.

[6] The Description continues:

"Each of the crystalline pure forms is mixed with a suitable pharmaceutical carrier and administered parenterally or orally, for example as a solid pharmaceutical administration form, such as a tablet, pill, capsule or suppository.

The dosage schemes are the same as described in the abovementioned patents. An oral daily dose of 1-5 mg is particularly suitable for administration to humans.

A pharmaceutical composition in which form I is incorporated is preferred. A composition of this type has the additional advantage that a much better stability is obtained, so that the shelf-life, even under changing storage conditions, is notably improved."

[7] Nine Examples by way of illustration are then set out. As certain of these were discussed before us it is convenient to narrate them at this stage. Since Example 9, which relates to determination of structural data, is not material, it may be omitted. The other Examples are as follows:

"Example 1

4.0 g of the polymorphous compound [in question] were recrystallized under nitrogen from 20ml of acetone to which a trace of pyridine had been added. During this operation the temperature was slowly brought from room temperature to - 10 C. The crystals were filtered off and washed with acetone at -20 C and dried under vacuum at 40-45 C. Yield 3.0g of form I (purity according to DRIFT 94%, calculated from [a certain relationship]) ... .

Example 2

1 kg of the polymorphous compound [in question] was dissolved at 20-25 C in a mixture of 23 l of acetone and 6 ml of pyridine. The solution was filtered dust-free and the filter was washed twice with 1 l of acetone. At a temperature of 15-20 C the filtrate was poured as rapidly as possible, under nitrogen, into 25 l of dust-free distilled water, to which seed crystals of form I had been added. The suspension was cooled to 0-5 C and stirred for one hour at this temperature. The crystals were filtered off, washed with dust-free distilled water and dried under vacuum at 40 C. Yield 0.95 kg of form I (purity according to DRIFT 97.2%).

Example 3

In a manner comparable to that described in Example 2, four batches of form I were obtained with a purity of, respectively, 100%, 95.2%, 93.3% and 99.2% (all determined by means of DRIFT).

Example 4

2.3 kg of the polymorphous compound [in question] were dissolved in a mixture of 63 l of 96% ethanol and 114 ml of pyridine. This mixture was then poured as rapidly as possible, while stirring well, into a dust-free mixture of 53.5 l of water and 268 ml of pyridine at 18-20 C, to which seed crystals of form I had been added. Rinsing was carried out with 3 l of ethanol and the mixture was stirred for 15 min at 18-20 C. The crystals were filtered off, washed twice with a mixture of 10 l of dust-free distilled water and 2 ml of pyridine and then washed three times with 18 l of dust-free distilled water at 50 C. The crystals were dried under vacuum at 40 C. Yield 2.1 kg of form I (purity according to DRIFT 94.7%).

Example 5

5.0 g of the polymorphous compound [in question] were dissolved in 50 ml of ethyl acetate, to which a trace of pyridine had been added, at 40 C. 300 ml of hexane at about 35 C were added while stirring vigorously, after which the mixture was cooled to 0 C and stirred for a further 30 min. The crystals were filtered off and washed with hexane at 0 C. Yield 4.25 g of form II (purity according to DRIFT 100%).

Example 6

A tablet having the following composition was prepared:

form I (obtained in accordance with example 2)

 

2.5 mg

 

starch

10 mg

 

ascorbyl palmitate

0.2 mg

 

magnesium stearate

0.5 mg

 

lactose

to make up to 100 mg

 

Base granules were prepared by mixing the lactose with a portion of the starch. The remainder of the starch was mixed to a slurry with water and added to the mixture. The whole was granulated and dried. These base granules were mixed with ascorbyl palmitate and form I, sieved, finely mixed with magnesium stearate and then tabletted.

Example 7

A tablet having the same composition as in Example 6 was prepared by first mixing form I with 10% of the lactose and the ascorbyl palmitate and then mixing this mixture with the lactose, starch and starch slurry. The mixture was dried, finely mixed with magnesium stearate and tabletted.

Example 8

A capsule having the following composition was prepared:

form II (obtained in accordance with example 5)

 

2.5 mg

 

starch

10 mg

 

ascorbyl palmitate

0.2 mg

 

magnesium stearate

0.5 mg

 

Avicel(r)

to make up to 100 mg

 

The components were mixed with one another in the manner described in Example 6, granulated and filled into gelatin capsules."

 

The statutory provisions

[8] The Patents Act 1977 (as amended) provides:

"1(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.

...

2(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 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 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 ...

...

72 Subject to the following provisions of this Act, the court ... may by order revoke a patent for an invention on the application of any person (including the proprietor of the patent) on (but only on) any of the following grounds, that is to say -

(a) the invention is not a patentable invention;

...

125(1) For the purposes of this Act an invention for a patent ... for which a patent has been granted shall, unless the context otherwise requires, be taken to be that specified in a claim of the specification of the ... patent ... as interpreted by the description and any drawings contained in that specification, and the extent of the protection conferred by a patent ... shall be determined accordingly.

...

(3) The Protocol on the Interpretation of Article 69 of the European Patent Convention (which Article contains a provision corresponding to subsection (1) above) shall, as for the time being in force, apply for the purposes of subsection (1) above as it applies for the purposes of that Article."

The power in this court to revoke a patent for an invention which is not a patentable invention extends to a European Patent (see section 77).

 

The Convention and the Protocol on its Interpretation

[9] Article 69 of the European Patent Convention provides:

"(1) The extent of the protection conferred by a European Patent ... shall be determined by the terms of the claims. Nevertheless, the description and drawings shall be used to interpret the claims.

... ".

The Protocol on the Interpretation of Article 69 of the Convention provides:

"Article 69 should not be interpreted in the sense that the extent of the protection conferred by a European Patent is to be understood as that defined by the strict, literal meaning of the wording used in the claims, the description and drawings being employed only for the purpose of resolving an ambiguity found in the claims. Neither should it be interpreted in the sense that the claims serve only as a guideline and that the actual protection conferred may extend to what, from a consideration of the description and drawings by a person skilled in the art, the patentee has contemplated. On the contrary, it is to be interpreted as defining a position between these extremes which combines a fair protection for the patentee with a reasonable degree of certainty for third parties."

 

The challenges

[10] Arrow challenges the validity of the patent on grounds both of anticipation and of obviousness. The Lord Ordinary upheld that challenge on the basis of anticipation but rejected it on the ground of obviousness. Akzo has reclaimed against the Lord Ordinary's interlocutor. It contends that, properly construed, the patent was not anticipated by any relevant prior art. Arrow resists that contention and further cross-appeals, contending that the Lord Ordinary erred in holding that the invention was not obvious.

 

The prior art

[11] The prior art upon which Arrow primarily, but not exclusively, relies is an article published in May 1984 in the Annual of the Royal Netherlands Chemical Society. The title of the article is in the following terms:

"Conformational analysis of 3-oxo 5(10)-unsaturated steroids.

Single-crystal X-ray structure analysis of

17-hydroxy-7ά-methyl-19-nor-17ά-pregn-5(10)-en-20-yn-3-one (Org OD 14)".

Its authors were J.-P. Declercq and M. Van Meerssche, apparently academic scientists at the University of Louvain, and a third person, F.J. Zeelen, described in the heading as of "Organon Scientific Development Group, 5340 BH Oss, The Netherlands". A note advises that Mr. Zeelen is the author to whom correspondence should be addressed. The abstract of the article narrates:

"Two crystallographically independent molecules with differing half-chair conformations of ring A were found in the analysis of Org OD 14. These results are compared with published X-ray structure analyses and Westheimer-type calculations of related steroids. It is concluded that the energy differences between the half-chair and envelope conformations of ring A of 3-oxo 5(10)-unsaturated steroids are small."

Org OD 14 would appear to denote a compound by then identified by Organon as of interest for the purposes of pharmaceutical development. The authors introduce their article and continue:

"We now report a single-crystal X-ray analysis of another representative of [the steroid class in question]: 17-hydroxy-7ά-methyl-19-nor-17ά-pregn-5(10)-en-20-yn-3-one (Org OD 14)."

A footnote to this sentence is in the following terms:

"Org OD 14 is a compound of interest for the treatment of menopausal complaints."

Certain references are then given. Under the heading 'Experimental" the authors give the experimental parameters within which the analysed single crystal was obtained. These include the following:

"

Crystallisation medium

Acetone

 

...

 

 

System

monoclinic

 

... ".

 

It is not disputed that the "system" described in these parameters as "monoclinic" is the monoclinic P21 form referred to in claim 3 of the patent.

[12] Under the heading "Results" the authors state:

"Two independent molecules were found and their coordinates are given in Table II. The two structures found show many of the features often observed in steroids such as the 13β-envelope conformations of the D-ring and the chair conformations of the C-ring. The B-rings in both conformations are half-chair with the 7ά-methyl group in an axial position."

The coordinates in Table II are (subject to errors of calculation) consistent with that described in the patent.

[13] The authors then discuss these results; but that discussion is not germane to the issues arising in this litigation. For convenience I shall refer to this article as "Declercq".

[14] Other documentary material comprised in the prior art - though more relevant to obviousness than to novelty - includes (1) US Patent No. 3,340,279, with a priority date of 5 September 1967, which claims steroids of a described formula, tibolone, though not named as such, being among the compounds disclosed by way of example ("patent 279") and (2) UK Patent No. 1,117,845, with a priority date of 13 June 1967, which again disclosed the compound tibolone, the crude product being, in one of the examples, recrystallised from acetone with one drop of pyridine ("patent 845").

 

The expert testimony and matters agreed therein

[15] The Lord Ordinary heard evidence from two expert witnesses, Dr. Newton (led by Arrow) and Professor Bernstein (led by Akzo). Each had prepared reports which were before the court. The Lord Ordinary found both these witnesses to be impressive, with impressive credentials, although their respective backgrounds and experiences differed. The Lord Ordinary summarised these differences as follows:

"Dr. Newton has recently retired as resident medicinal chemist in the chemistry department of the University of Cambridge, a position he held since 1996, and he is visiting professor at the University of Sussex. He holds a number of posts with various scientific companies and, possibly most relevant to the present proceedings, was employed by Glaxo from 1971 to 1996, originally as a senior research chemist and subsequently as director of various research projects. Professor Bernstein is and has been since 1971 professor of chemistry at Ben-Gurion University of the Negev, Beersheva, Israel. He teaches courses in general chemistry, crystallography and organic state chemistry, including polymorphism and crystallisation. He has specialised and built an international reputation in the field of crystallography and has participated in a large number of conferences on the subject. Indeed, Dr. Newton was willing to defer to Professor Bernstein on matters of pure crystallography."

[16] There was, the Lord Ordinary found, little or no difference between these experts on the identity for present purposes of "the skilled man". Adopting Professor Bernstein's description, with which Dr. Newton broadly agreed, the skilled man here was the composite, namely, "a process research chemist working with an analytical chemist in the pharmaceutical industry" having a bachelor's degree in chemistry and about 2-3 years experience (perhaps more) in the industry, and having some familiarity and experience in dealing with solids and the analytical techniques used to characterise and distinguish the two forms of tibolone under discussion. Before us it was accepted that the skilled man was as so described.

[17] The Lord Ordinary also found that there was nothing between the experts on the question whether tibolone of the purity and form claimed in claims 1 to 3 of the patent was revealed in Declercq. It was agreed between them that the data recorded in Table 1 of Declercq showed that the compound under discussion there was the monoclinic form of tibolone i.e. form I. It was also agreed that, the analysis being of a single crystal, the analysed subject was by definition 100% pure.


The issues before the Lord Ordinary and his disposal of them

[18] These agreed matters, the Lord Ordinary observed, enabled "Arrow to say, simply, that clauses 1-3 were anticipated by Declercq". The Lord Ordinary then proceeded to consider and reject various arguments advanced by Akzo to counter that inference of anticipation. One of these arguments (based upon an analogy with the first (English) Queen Elizabeth being referred to as Queen Elizabeth I only after Queen Elizabeth II ascended the throne) was not insisted on before us. As will appear, other arguments (though, it seems, expressed somewhat differently before us) were then considered and rejected by the Lord Ordinary.

[19] The Lord Ordinary then considered submissions advanced by parties in relation to the anticipation/novelty of claim 5. This issue, as will appear, involves issues of interpretation of the claim and of the general law, to which I shall return. It also involves some consideration of the evidence and the Lord Ordinary's conclusions on this topic. The Lord Ordinary held that claim 5 had been anticipated by Declercq.

Accordingly, the Lord Ordinary held that all the claims in issue had been anticipated and on that basis revoked the patent in its entirety.

[20] Although unnecessary for his decision, the Lord Ordinary then addressed Akzo's challenge based on obviousness. For reasons which he gave, he rejected that challenge. By cross-appeal Arrow renews that attack.

 

Submissions by junior counsel for Akzo

[21] Mrs Delibegović-Broome submitted that, properly construed, each of claims

1-3 involved the integers (i) a pharmaceutical composition; (ii) containing a pharmaceutically suitable solid carrier; (iii) where the active ingredient was crystalline pure tibolone to at least 90%. Each concerned a crystalline pure pill. Claim 5 was a method of producing such a pill. Arrow's challenge of lack of novelty was based on Declercq. That paper was of interest as much for what it did not contain, as for what it did: it did not suggest that tibolone was polymorphous; it did not disclose how one would obtain a product in a form suitable as a pill; and there was no detailed information about the crystallisation process. The issue of construction was for the court alone, it having been instructed as to the notional skilled addressee's knowledge (Terrell on the Law of Patents, 16th Edition, paragraphs 6-103 to 6-106). Expert evidence in relation to critical issues was admissible though it did not have to be accepted by the court, which must look to the reasoning behind such evidence (Technip France SA's Patent [2004] RPC 46, per Jacob LJ at pages 927-8). Obviousness being a matter of fact, an appeal court should be reluctant to intervene unless there was a matter of legal principle (Biogen v Medeva [1997] RPC 1 at page 45; Saint-Gobain v Fusion Provida [2005] EWCA Civ 117 (CA)). This did not necessarily apply to the question of novelty (Technip France, per Jacob LJ at pages 958-9). The question of what could be taken from the prior art was one of fact for the judge (Merck & Co. Inc.'s Patents [2004] FSR 330, per Vice-Chancellor Sir Andrew Morritt, at page 345). In the present case, leaving aside the question of obviousness, there were no significant differences between the experts as to what Declercq demonstrated, and no substantial challenge to the Lord Ordinary's findings-in-fact. This court was in as good a position as the Lord Ordinary to assess the question of novelty.

[22] As he did not address construction as a separate exercise, it was necessary to consider the Lord Ordinary's reasoning regarding novelty in order to understand how he had construed the claims. In his reasoning, he had referred to Merrell Dow Pharmaceuticals Inc. v H.N. Norton & Company Ltd. [1996] RPC 76, in which it had been held that the novelty of an invention must be coextensive with its monopoly, and that a claim to a compound per se lacks novelty where it is already in the state of the art (per Lord Hoffmann at pages 82-3). However, it had also been made clear that, prior to considering novelty, one must be clear about what the invention was. The Lord Ordinary had found that claim 3 was to the monoclinic form of tibolone, per se. In effect he had treated claims 1 and 2 in the same way. That approach ignored the integers of the claim. The correct approach required a "purposive" construction of the claims (Kirin-Amgen Inc. v Hoechst Marion Roussel Ltd. [2005] RPC 169 per Lord Hoffmann at paras 18 ff). There was a distinction between a pharmaceutical composition containing a product, and that product as such, in whatever form it is found (Generics (UK) Ltd. v H Lundbeck A/S [2007] RPC 729 per Kitchin J at paras. 61-2). The claims here were to pharmaceutical compositions, which was a different monopoly from that of products per se. Monoclinic tibolone, when created, would not necessarily infringe the patent. This was clear from the language of the claims, and the specification of the patent. On a purposive approach, the only reasonable construction of each of claims 1 to 3 was that they concerned a dosage form, comprising crystalline pure tibolone and a pharmaceutically solid carrier.

[23] Akzo had included an obviously deliberate limitation in its claims. That limitation must have a meaning. (Kirin-Amgen at para. 34; Halliburton Energy Services Inc. v Smith International (North Sea) Ltd. [2006] RPC 25, per Pumfrey J at paras. 68-9; and Palmaz's European Patents (UK) [1999] RPC 47, at page 77). It was unfair to construe the claims beyond what was intended, as to do so might make the patent invalid (Wheatley v Drillsafe Ltd. [2001] RPC 7, per Aldous LJ at paras. 20-2; and Kirin-Amgen, at para. 47). The Lord Ordinary seemed to suggest that the integers relating to a pharmaceutical composition made no difference to the inventive concept. Even if this were true, which was not accepted, they should not have been ignored for the purposes of construction. Every part of the claim mattered (Socit Technique de Pulverisation STEP v Emson Europe Ltd ("STEP") [1993] RPC 513, per Hoffmann LJ, at page 522). One should not re-write the claim from a pharmaceutical composition with a number of features, to a claim to just one of those features (Terrell, para. 6-68).

[24] Another error of construction concerned the "single crystal" argument. Properly construed, claims 1-3 concerned a pharmaceutical composition; by implication, a single crystal was not sufficient. The Lord Ordinary rejected this argument, saying that it confused the claim to the method with the product claims. However, disclosure also encompassed the concept of enablement. Method was important if the product claimed was to be enabled by the prior art. Akzo also challenged the Lord Ordinary's conclusion that the claims were not limited by some quantitative criteria; they required crystalline purity of greater than 90 or 95% in the pharmaceutical composition. Purity was measured on a weight percentage basis. A single crystal, by definition 100% pure, would, if it sufficed, render references to 90 and 95% crystalline purity in the claims otiose. This could not be correct. Examples 6, 7 and 8 in the patent also made it clear that the claim was not to a single crystal. It was a principle of construction that a foolish result, if avoidable, should be rejected (Terrell, para. 6-59). It would be foolish to suggest that a single crystal would suffice for a pill. It had never been so suggested in evidence.

[25] The fact that the claims involved a pill with greater than 90% purity of a particular crystalline form was important. While the Lord Ordinary set out the benefits of using a crystalline pure compound in medicine, he failed to consider the relevance of this in relation to construction. The patent claimed a practical application of the discovery that tibolone was polymorphous. Polymorphism was at the heart of the patent.

[26] The Lord Ordinary also erred in construing claim 5. He again ignored the integers of this claim. Claim 5 was to (a) a method for the preparation of a crystalline pure compound for use in a pharmaceutical composition of claim 3: characterised in that (b) the compound was crystallised from, inter alia, mixtures of water and acetone. The Lord Ordinary found that it claimed a monopoly over "every process of crystallising the polymorphous compound using acetone". However, the phrase "mixture of water and acetone" had a meaning, which had to be given effect. It could not simply be construed as acetone diluted by water (bench acetone). Two separate liquids were involved as part of a specific process. Dr Newton accepted that the process described in the prior art was not the same as claim 5. Example 1 in the specification did not involve the use of water, but it was not part of the process claimed. The Lord Ordinary's construction was inconsistent with his finding that not every crystallisation using acetone necessarily produced monoclinic tibolone. Later, he formulated the question as being whether using acetone as a solvent would normally result in form I. However, claim 5 incorporated a reference to claim 3. The method had to produce form I with a crystalline purity of greater than 90%. A process which failed to achieve this objective would not infringe the claim.

[27] Novelty involved two concepts, namely disclosure and enablement, which were distinct and subject to their own rules. Disclosure meant that the prior art must disclose subject-matter which, if performed, would necessarily infringe the patent. This might be because the prior art disclosed the same invention, or because it contained information which, if performed, would infringe the patent (SmithKline Beecham plc's (Paroxetine Methanesulfonate) Patent [2006] RPC 323, per Lord Hoffmann at para. 20 ff, referring to the cases of Hill v Evans (1862) 31 LJ Ch (NS) 457 and General Tire and Rubber Co. v Firestone Tyre and Rubber Co. Ltd. [1972] RPC 457). Enablement meant that an ordinary skilled man could perform the invention by using the disclosed material and common general knowledge (SmithKline Beecham per Lord Hoffmann at para. 14; Asahi Kasei Kogyo KK's Application (1991) RPC 485, per Lord Oliver of Aylmerton at pages 531-2 and Lord Jauncey of Tullichettle at pages 551-2). To constitute anticipation the same subject-matter must be disclosed and enabled in the prior art as was disclosed and enabled in the patent. The prior art must contain all the elements of the claims; one could not "mosaic" using different sources (ITP SA v Coflexip Stena Offshore Limited 2003 SLT 1197, at para. [44]; and General Tire).

[28] Anticipation concerned prior art which disclosed subject matter which, if performed, would necessarily result in an infringement of the patent (SmithKline Beecham at para. 22) or must inevitably yield identical products (per Lord Hoffmann at page 90 of Merrell Dow). A disclosure which was "capable" of being carried out in a manner which did not fall within the claim did not anticipate it (Inhale Therapeutic Systems Inc. v Quadrant Healthcare plc [2002] RPC 419, per Laddie J at para. 45). It was not enough that it allowed a skilled man, without undue burden, to come up with an invention which infringed the patent. Reference was made to SmithKline Beecham, per Lord Hoffmann and Lord Walker of Gestingthorpe, passim.

[29] Declercq was not sufficient on a proper construction of the claims to found anticipation. The European Patents Office had considered it before granting the patent; it was cited on the front of the patent in suit. There was no disclosure, express or implicit, let alone an enabling disclosure, of anything which would necessarily infringe the patent. It merely disclosed the conformation of a single crystal of monoclinic tibolone, and that the crystal came from a batch which was crystallised from acetone. To infringe claims 1 to 3 the directions given in Declercq must inevitably provide a pill which comprised a pharmaceutically suitable solid carrier and tibolone of a crystalline purity in excess of 90%. That meant that the inevitable result of crystallisation from acetone had to be greater than 90% of form I. If the only evidence before the Lord Ordinary was Declercq, that would not be sufficient to satisfy that test. Moreover, on the evidence, the Lord Ordinary had found that not every use of acetone would inevitably give form I. It was not necessary to make any further findings-in-fact.

[30] As regards claim 5, Declercq did not disclose any process whereby monoclinic tibolone of the requisite purity could be achieved. The Lord Ordinary had referred to Professor Bernstein's evidence that one would expect to get form I when crystallising from acetone. This was said in the context of the skilled man seeing Declercq in 1984, when it was not known that tibolone was polymorphous. Declercq did not disclose a method of producing a crystalline pure pill. While it did indicate that the crystal analysed had been obtained using acetone, there was no evidence about whether other crystal forms were obtained. Moreover, there was no information about the correct conditions of temperature and so on. Similarly, it did not disclose that tibolone was polymorphous. Polymorphism was unpredictable. It was not enough that the skilled man might have known that steroids were often polymorphous; he would not have known how to identify and isolate the polymorphs, and why one would want to obtain them. Arrow had not put forward any experiments proving the inevitable result which followed from the disclosures in the prior art (cf. Inhale Therapeutic Systems, at paras. 44 and 45). There was no enabling disclosure.

[31] The reclaiming motion should be allowed and the prayer of the petition refused.

 

Submissions by junior counsel for Arrow

[32] Miss Higgins submitted that, as regards claims 1 to 3, Declercq anticipated the patent in that it disclosed (i) the monoclinic form of tibolone; (ii) at the level of purity set out in the claims; and (iii) for use as a pharmaceutical product. As regards claim 5, Declercq anticipated the patent in that it disclosed (i) the method of crystallising from acetone to provide the monoclinic form of tibolone; and (ii) its use as a pharmaceutical product. The respondents supported the findings-in-fact of the Lord Ordinary regarding novelty and construction, with one exception. The integers "pharmaceutical composition which contains a pharmaceutically suitable solid carrier" should not have been read out. This caused no difficulty to Arrow's case, given the Lord Ordinary's finding that tibolone had been used in pharmaceutical compositions for many years. He correctly read Declercq as disclosing that tibolone was used as a pharmaceutical composition.

[33] While Declercq had been considered by the European Patents Office, it worked on a challenge procedure; searches undertaken by it were not always extensive. Patent 279, contained a reference to the chemical name for tibolone and to its use as a pharmaceutical dosage. Patent 845, also made reference to the chemical name for tibolone, and its oestrogenic, progestational and ovulation-inhibiting properties. It also described a method of making tibolone which corresponded to the first example in the patent in suit. The witness Vrighof indicated that tibolone was first marketed in 1988.

[34] Akzo's counsel had fundamentally misconstrued Lord Hoffmann's reasoning in SmithKline Beecham. She had mixed up the concepts of (i) "necessarily infringed" and (ii) "inevitable result". Properly understood, the test for anticipation had been met in the present case. A patent was anticipated if (i) the prior art contained a clear description of, or clear instructions to do or make, something that would infringe the claim, or (ii) the carrying out of directions in the prior art would inevitably result in something being made or done which would infringe the claim (Lord Hoffmann at paras. 19 to 24). Either route was sufficient. Arrow relied on the first formulation of the test of anticipation: the prior art itself disclosed something which would breach the patent. Declercq had "planted his flat" at the end point of the invention prior to Akzo. The second test, involving inevitable result, only applied if the prior art did not specifically disclose the patented product.

[35] The argument that a single crystal in a pharmaceutical composition was not sufficient to anticipate the patent was not accepted by Arrow. There was no dispute that Declercq disclosed a crystal of monoclinic tibolone, which, by definition, was 100% pure. A single crystal came within the scope of the claims (Inhale Therapeutics, per Laddie J., at para. 43). There was nothing in the language of the claims which would support the limitation relied on by Akzo. While claims had to be read in the context of the patent as a whole, it was not pertinent to put a gloss on them by reference to words contained in the specification (Conoco Speciality Products (Inc.) v Merpro Montassa Ltd. 1992 SLT 444 at page 448). Even if it were, it was not clear what part of the specification was relevant. Reliance had been placed on examples 6, 7 and 8. These referred to 2.5mg of tibolone in a tablet, but Akzo had never submitted that this was an appropriate limit. The specification referred to a normal daily dosage of 1 - 5mg, suggesting that less than 2.5mg was a possible dose. There had been no evidence about the quantity of tibolone used in a pill, nor about the size of crystal used in a pharmaceutical composition. No attempt was made to contextualise the phrase "pharmaceutical composition"; it did not permit the inference sought. Claims must delineate the limits of the patent, to allow third parties to know the areas on which they must not trespass. In any event, if Arrow was correct in its formulation of the construction of the claims, it only had to say that Declercq anticipated form I for use as a pharmaceutical.

[36] The argument that Declercq could not anticipate the patent, since it did not disclose polymorphism in tibolone, was rejected. A product, or invention, did not have to be described in exactly the same terms as the patent in order to anticipate it, as long as both products or inventions were the same (Merrell Dow, per Lord Hoffmann at pages 87-9). Declercq identified monoclinic tibolone. It did not need to show that this form was one of two polymorphs. While it did not disclose any advantage in the use of the monoclinic form, no advantage formed part of the claims. It was merely commented upon within the specification of the patent. Generics (UK) Ltd did not cause difficulties for Arrow. It concerned prior art which had not specifically disclosed an isolated product. Declercq disclosed monoclinic tibolone in its isolated form. Akzo sought to read a special factor into the discovery of polymorphism in tibolone. However, an invention was a practical product or process, not information about the natural world (Kirin-Amgen per Lord Hoffmann, at paras. 76-7).

[37] The argument that Declercq did not disclose the use of tibolone as a pharmaceutical was also challenged. The footnote in Declercq indicated that tibolone was of interest in the treatment of menopausal complaints. The crystal examined had been sent for analysis by Organon, a pharmaceutical company, for whom one of the co-authors worked in the scientific development group. A continuing theme emerged in the evidence, particularly from Dr Newton, that the crystal had been taken for conformational analysis because a drug was being developed by Organon. More particularly, Declercq disclosed the monoclinic form as being of interest for pharmaceutical purposes. It was implicit that the reason that particular crystal had been sent for analysis was that this crystalline form was under development. As at 1984, there was no knowledge of any other form of tibolone. There would be no question of any other polymorph being of use. Moreover, the substance analysed in Declercq contained a reference number prefixed by the letters "Org", suggesting that Organon had identified this particular structure as being of interest.

[38] While the footnote only indicated that tibolone was "of interest" in the treatment of menopausal complaints, it contained sufficient direction that it was to be used in a pharmaceutical context. An indication of "potential use" for clinical applications still constituted a clear and unmistakeable direction (Merck & Co. Inc.'s Patents, per Vice-Chancellor Sir Andrew Morritt at para. 28). It was not necessary for the prior art specifically to disclose the compound within a pharmaceutical composition for the argument on anticipation to be successful. The integers of a pharmaceutically suitable solid carrier in a pharmaceutical composition were the plain consequences of the use of tibolone as a drug. The skilled man would take from Declercq that this compound with this structure was a drug under development by Organon.

[39] The concepts of disclosure and enablement were distinct: "inevitable result" was not the test to be applied for the purposes of enablement. For the purposes of enablement, some trial and error was permitted (SmithKline Beecham, per Lord Hoffmann at para. 30). The hypothetical addressee must be prepared to address errors in the specification if means to do so were readily available. It was sufficient that, if crystallising using acetone, the skilled man would expect at least some monoclinic tibolone. It was not necessary to show that that would be the inevitable exclusive result. In the examples, form I had been obtained from acetone. At least in relation to Example 1, this had been acetone alone. According to Dr Newton, the skilled man would be aware of polymorphism and would therefore have a reason to check for such a crystal within a sample. He would be able to tell the difference between crystals under the microscope and look to see whether he had achieved the crystal disclosed in Declercq. Declercq satisfied the test of enablement for the purposes of anticipation.

[40] Arrow supported the Lord Ordinary's construction of claim 5 as being a monopoly over every process of crystallising monoclinic tibolone using acetone. Dr Newton's position was that none of the examples given in the patent specifically included adding water to the acetone solvent. From the information provided in the examples, the acetone used was "bench acetone", which would contain some water. Since water was a polar solvent, its presence in the acetone would increase the polarity, favouring the formation of monoclinic tibolone. Despite the terms of the specification and the claim itself suggesting a mixture, the expert evidence allowed the Lord Ordinary to put himself in the position of a skilled man. The correct construction was that the phrase "mixture of acetone and water" included bench acetone. There was no evidence from the experts that ran contrary to that interpretation. Akzo's submission that Example 1 did not fall within claim 5 was unusual. If that were Akzo's position, one might have expected it to have been put to the expert witnesses. Immediately prior to Example 1 the specification stated that "The invention is illustrated with the aid of the following examples". This all suggested an "ex post facto" attempt to deal with Example 1, when submitting that claim 5 did not cover crystallisation from acetone.

[41] Arrow's position as regards enablement for claim 5 was essentially the same as for claims 1 to 3. There was no need for Arrow to establish by evidence that crystallisation from acetone inevitably gave monoclinic tibolone, only that the skilled man would be able to get some. The respondents again relied on the first of the two possible paths of disclosure, the descriptive route. Declercq showed that one can produce form I tibolone at the required level of crystalline purity by crystallising from acetone, and that this was for use as a pharmaceutical.

[42] Arrow accepted that an issue of novelty might be opened up more readily by an appellate court than an issue of obviousness, but only where a question of principle arose (Technip France per Jacob LJ at paras. 71-4). If the matter concerned evidence of what was disclosed by the prior art, or what was meant by technical terms, one should adopt the Biogen approach and be slow to interfere with the findings of the judge at first instance (SmithKline Beecham plc v Apotex Europe Ltd. [2005] FSR 524, per Jacob LJ at para. 36). That principle applied where there was a conflict of expert testimony, or, as here, where only one expert had given evidence on the meaning of a technical term. The reclaiming motion should be refused.

[43] As to obviousness, the Lord Ordinary had erred in law in holding that the invention in claims 1 to 3, and 5, was not obvious, having regard to the state of the art. The correct approach to obviousness on appeal was that expressed by Lord Hoffmann in Biogen at page 45 (see also Pozzoli SPA v BDMO SA [1007] FSR 872, per Jacob LJ at para.13). Arrow challenged the findings that there was no reason why the skilled man would want to look for a pure polymorphic form of tibolone at the priority date, and that he would not have had the motive or the means to develop such a form. It also challenged the Lord Ordinary's approach to the "Windsurfing" test (Windsurfing International v Tabur Marine (G.B.) Ltd. [1985] RPC 59). The findings that the skilled addressee would have known of tibolone and that steroids were likely to be polymorphous was not challenged per se, but the manner in which the findings had been applied was in issue.

[44] We were referred to various authorities, from which Arrow took five principles of general application (Section 3, as read with section 2(2), of the Patents Act 1977; Pfizer Ltd's Patent [2001] FSR 201, per Laddie J at para. 62; ITP SA, per Lord Nimmo Smith at paras. [61]-[66]). First, the test for obviousness was wholly objective, being whether the inventive step was obvious to a person skilled in the art, having regard to any matter forming part of the state of the art. Secondly, the skilled man was to be considered as lacking inventive capacity. Thirdly, the skilled man was deemed to have read all the prior art. Fourthly, unlike novelty, when considering obviousness, one could consider more than one document (or "mosaic"). Finally, the question was whether the inventive step was objectively obvious, rather than commercially obvious.

[45] There were three possible approaches to the issue of obviousness. The first two involved the application of the Windsurfing steps, the third was independent of it. The court should consider the inventive concept of each claim distinctly; the Lord Ordinary had considered the patent as a whole (cf. Pozzoli, per Jacob LJ at para. 17, referring to his earlier decision in Unilever plc v Chefaro Proprietaries Ltd. [1994] RPC 567 at page 580). On the first approach, the inventive concepts would be: in claim 1, tibolone with a crystal purity of greater than 90%; in claim 2, tibolone with a crystal purity of greater than 95%; in claim 3, form I tibolone with a purity of greater than 90%; and in claim 5, certain methods, including crystallisation from acetone, for the preparation of form I tibolone with a crystal purity of greater than 90%.

[46] The phrase "pharmaceutical composition" and "pharmaceutically suitable solid carrier" could not form part of the inventive concept. Tibolone had been on the market since 1988, a year before the priority date. The lack of significance in the term "pharmaceutical composition" was seen in the specification of the patent, which claimed the application of the discovery that tibolone was polymorphous as the aim of the invention. It also referred to patent 279, which outlined the pharmaceutical use of tibolone. Thus, at the priority date, there was nothing inventive about using tibolone as a pharmaceutical. Arrow did not challenge the Lord Ordinary's formulation of the skilled addressee as "a process research chemist working with an analytical chemist in the pharmaceutical industry". Neither did it challenge the Lord Ordinary's answer to the second Windsurfing question, although it ought to have been addressed separately as regards each claim.

[47] The Lord Ordinary's approach to the third step was challenged. Again, he had failed to ask this question in relation to each of the claims. He had held that the difference between the state of the art and the inventive step was the "discovery of polymorphism in tibolone and the identification of the method of producing one of the two different polymorphic forms". This finding was one that no reasonable judge could have made, and proceeded on a misconstruction of the invention claimed. It contradicted his earlier finding that Declercq disclosed pure form tibolone and a method of making it. It was not possible to identify any difference between the inventive concept of the claims and the information in Declercq. The answer to the question posed at the fourth step was "Yes".

[48] The second approach presumed that there was something inventive in the incorporation of monoclinic tibolone in a pharmaceutical composition. On this hypothesis, the inventive concept for each of the claims was as outlined in the first approach, with the additional component of a "pharmaceutical composition". The difference, if any, for the third step of the Windsurfing test was that Declercq showed 100% pure form I tibolone for use as a pharmaceutical, whereas the present invention showed the form and purity outlined in the first approach in a pharmaceutical composition. As regards claim 5, the difference was that Declercq showed a method, using acetone, for the preparation of 100% pure form I tibolone for use as a pharmaceutical, whereas the present invention described a method using, inter alia, acetone for the preparation of form I tibolone with a crystalline purity of greater than 90% for use in a pharmaceutical composition.

[49] On this approach, the fourth step was to ask whether it would have been obvious to use monoclinic tibolone as a pharmaceutical in a pharmaceutical composition. On the basis of the evidence, and the prior art (Declercq, the 845 patent and the marketing of Livial), it would have been. The Lord Ordinary's finding that the incorporation of tibolone into a pharmaceutical composition could not be inventive was not challenged by Arrow, had been expressly accepted by Akzo at the proof, and was noted in Akzo's written submissions which had been produced at that proof regarding the other patent then in suit. Therefore, claims 1 to 3, and 5, fell to be revoked for lack of inventive step.

[50] The third approach proceeded on the "simple" case of obviousness set out in the evidence and in Dr Newton's report. The test was that outlined in section 3 of the Patents Act. Windsurfing (which had been referred to with approval in the House of Lords - Sabaf v MFI [2005] RPC 209) was only of relevance where it was of specific assistance. A skilled man wishing to develop tibolone as a pharmaceutical product would need to identify a robust and repeatable process. Patent 279 provided the synthetic route to tibolone. The skilled man would be aware that most steroids exhibit polymorphism. He would want to define a single polymorph, since he would know that different steroidal polymorphs had different properties. He would be aware that Declercq defined a crystal of tibolone analytically. By crystallising from acetone, as taught by Declercq, he would have a method of preparing pure monoclinic tibolone. Claims 1 to 3 of the patent were obvious. Claim 5 was also obvious because Declercq described crystallisation from acetone, rather than from anhydrous acetone, and one would expect the former solvent to contain some water.

[51] The Lord Ordinary had highlighted the difference between knowing about polymorphism as a phenomenon, and the ability to apply that knowledge. Arrow did not challenge these comments per se; however, the argument set out by Dr Newton was not predicated on the fact that the skilled man might be looking for polymorphism in tibolone. Rather, he would know that steroids were likely to be polymorphous, and a paper identifying one crystalline form of a particular steroid would be of interest to him. For the purposes of obviousness, one was placing oneself in the position of the skilled man looking at the prior art. As indicated, different steroidal polymorphs may have importantly different properties. The skilled man would want to define a single polymorph having a suitable physical and bio-availability profile. He would be interested as he would be aware of the likelihood of polymorphism within such a steroid.

[52] The skilled person in question was defined as having an interest in pharmaceutical products and the properties a potential polymorph would have in the pharmaceutical world. The burden was not on the party claiming obviousness to show why the skilled man's interest would be aroused. One could not assume he was uninterested. He was taken to appreciate and understand the prior art, and to consider, in light of his knowledge and experience, whether and how it would work (Windsurfing per Oliver LJ at pages 71-4). It was not arguable that it would not have been obvious to put a particular isolated crystalline form into a pharmaceutical composition. As indicated, Declercq related to one such form. That was what the skilled man must be taken to have seen. In failing to make a finding of obviousness on this "simple" basis, the Lord Ordinary did not deal with part of the evidence led at proof. He had made findings-in-fact regarding obviousness that no reasonable judge would have made.

[53] The finding that a skilled man would not have the means of achieving a pure polymorphic form of tibolone was one which no reasonable judge could have made. It was accepted that Declercq disclosed a method of producing pure monoclinic tibolone. The Lord Ordinary's finding in this regard was not that one would not be able to get a batch of form I; it was that one would not be able to obtain solely form I. The evidence of both experts was that one crystal is a pure crystalline form. The Lord Ordinary himself stated that Declercq disclosed a means of producing monoclinic tibolone.

[54] As regards motivation, Dr Newton was clear that Declercq identified a method which was good enough to commercialise. Alternatively, on the basis of the Lord Ordinary's own assumptions, the motive was that the skilled man would be aware that tibolone was a steroid and therefore likely to be polymorphous. As indicated, according to Dr Newton, he would want to define a single form. The finding of no motivation ran wholly contrary to the evidence presented at proof. In any event, the Lord Ordinary erred in law in holding that the lack of motivation was a bar to a finding of obviousness. Motivation, while relevant, was not a prerequisite for a conclusion of obviousness (Pharmacia Corp. v Merck & Co. Inc. [2002] RPC 775, per Aldous LJ at para. 124). The question was whether the claimed technical step would be obvious to a skilled man.

[55] On that basis, the cross-appeal should be allowed and claims 1 to 3, and 5, of the patent found to be invalid for lack of inventive step.

 

Response by senior counsel for Akzo

[56] Mr McNeill submitted that Arrow's arguments on anticipation were notable for what they did not say. No submissions had been made as to the proper construction of the patent. It had been suggested on more than one occasion in argument that the patent was for monoclinic tibolone. This led to the structure of Arrow's arguments, which did not respond to specific submissions made by Akzo. The only reasonable construction of the patent was that the claims were not to monoclinic tibolone per se; they concerned a pharmaceutical (as against, say, a cosmetic) composition involving a suitable solid (as against, say, a liquid) carrier. Adopting this approach, it became evident that Arrow's arguments sought to impose on the patentee something which was not claimed by it.

[57] There was no evidence supporting the contention that a single crystal could be used as a pharmaceutical, or that a skilled person would read the patent as being a pill with a single crystal contained therein. The onus was on Arrow to establish this. The reference to crystalline purity of 90 to 95% by weight suggested, prima facie, a multiplicity of crystals within a compound. Another, smaller, contra-indication was the reference to the need for a microscope to distinguish between crystalline forms. One was entitled to look at the specification in construing the claims. This outlined the aim of the invention as involving a plurality of forms. Akzo's construction of the patent was that it concerned batches of tibolone adequate for effective pharmaceutical use, being greater than 90 to 95% pure, of a particular form, according to the claim.

[58] There was in fact information, not referred to at proof, which could have rebutted the "single crystal" argument. Professor Bernstein's report referred to a paper by Schouten and Kanters, which provided the dimensions of a single crystal of the triclinic form of tibolone. It suggested a weight of 0.0334mg. This would need to be multiplied by a factor of 30 in order to gain 1mg, and by a factor of about 150 in order to gain 5mg, these being the daily dosages referred to in the patent. Upon the assumption that the Declercq crystal had the same rough size, a single crystal could not suffice for a pharmaceutical dosage. There was no reasoned basis on which the court could hold that a skilled person would read the claims as including a single crystal of the active ingredient.

[59] Arrow had submitted that there might be circumstances where it was not necessary to show that the prior art necessarily infringed the patent. However, while there were two ways to approach anticipation, the underlying principle was that of necessary infringement or inevitable result. (SmithKline Beecham, per Lord Hoffmann at paras. 22 to 33). One had to distinguish between disclosure and enablement. However, the importance of keeping the two distinct could vary with the complexity of the invention. There might be something so obvious that little skill at all is involved in realising how to make it (SmithKline Beecham, per Lord Walker at paras. 62-4).

[60] It was clear that the footnote in Declercq only identified the compound tibolone as being of interest in the treatment of menopausal complaints, not its monoclinic form; the case of Merck, relied on by Arrow, could be distinguished. There was no suggestion of any prior use of the monoclinic form for therapeutic purposes. It was not a plain consequence of Declercq that the monoclinic form was useful for pharmaceutical purposes. As compared to claims 1 to 3, Declercq did not disclose: how to make tibolone, far less anything else; a robust and reliable method for obtaining tibolone in crystalline form, as desiderated by Dr Newton; the creation of a crystalline pure pill; the use of monoclinic tibolone as a pharmaceutical; or the fact that tibolone was polymorphic. The Lord Ordinary found that not every crystallisation from acetone would give form I tibolone. Any direction in Declercq was at least as likely to not infringe the patent as it was to infringe it (cf. SmithKline Beecham and General Tire).

[61] The fact that there was no direction to obtain crystalline pure monoclinic tibolone in Declercq was relevant to the matter of enablement. As a matter of commonsense, without the discovery of polymorphism, one would not expect Declercq to teach the skilled man how to distinguish the monoclinic form from any other form. The evidence of Dr Newton relied on by Arrow (report para. 7.8) in this regard was dealing with obviousness, not novelty, and referred to patent 279 as well as Declercq. A patent specification was not part of the common general knowledge unless this was proved as such (General Tire at page 482). Moreover, one could not mosaic for the purposes of novelty; the prior art was thus Declercq alone. Dr Newton identified the importance of a robust and reliable method of producing a particular form for industrial purposes. This could not be encompassed by an academic exercise producing a single crystal. The Examples in the patent involved substantial amounts of tibolone. The specification spoke of "batches". The phrase "pharmaceutical composition" involved an amount of crystalline pure tibolone adequate for effective pharmaceutical use. The claims referred to a pill which could be used as a pharmaceutical as the result of a large scale commercial process.

[62] Arrow had no pleadings challenging claim 5 as lacking in novelty and no submissions had been made to the Lord Ordinary in that regard. It was not suggested in evidence that a skilled person would read out water from the mixture described in the patent. The evidence of Dr Newton relied on by the respondents related to obviousness, the state of the art, and what could be taken from Declercq. Other passages of his evidence undermined such a claim. He described the solvent as "acetone water", and indicated that "in the patent they actually dissolve in acetone and then add water". Professor Bernstein's evidence made it clear that Examples 2 and 3 involved the use of water. There was no support for the Lord Ordinary's construction that claim 5 included every crystallisation from acetone. It sat uneasily with his acceptance that not every use of acetone would inevitably give form I.

[63] The word "mixture" could mean a number of things, but the Examples gave an indication of the process. One could identify, for the purposes of enablement, what had been done. Acetone had been used first and the resultant solution had then been added to water, which acted as an anti-solvent, not merely as a dilutant of the acetone. Crystallisation took place from the mixtures of water and acetone. The matter was one of construction. The claims included a reference to water. The patentee had the right not to claim everything disclosed, or enabled, in the specification (Kirin-Amgen, per Lord Hoffmann at para. 33). Example 1 could be excluded from the claim. The method outlined in Example 1 was different as regards the temperature, process and yield. That Example might be a special method for producing seed crystals.

[64] As to enablement in respect of claim 5, the Lord Ordinary had not specifically addressed this. Declercq did not give a method for making tibolone; it did not disclose a particular method of crystallising from acetone; and it contained no suggestion that one should crystallise using water and acetone. Dr Newton's evidence that one would necessarily get form I from acetone, but might need to re-crystallise to improve purity, was based on his method of crystallisation. This was different from that outlined in claim 5. There was no reference to the use of water specifically as an anti-solvent to increase precipitation, or specifically to the use of acetone in the crystallisation process. It was different from the robust technique which was being taught by the patent. While Windsurfing indicated that the skilled person was not looking for commercialisation, it did suggest that one had to look at the nature of the relevant skilled person. Here, he was a person working for a pharmaceutical company and looking for a robust, reliable, process which was capable of commercialisation. That was the aim of the patent. A method which merely gave the possible expectation of some form I did not bring one within the framework of the claim.

[65] As regards obviousness, Akzo accepted that one must normally identify the inventive concept in relation to each claim distinctly. However, there might be patents where the claims were so interlinked that there was little purpose to be served by seeking to find a different inventive concept in each claim. The Lord Ordinary's definition of the inventive concept was the identification of a crystalline pure form of tibolone and a method for producing it. Even if he had set out to deal with each claim separately, he would have been likely to answer the first question of the Windsurfing test in the same way for each claim. While technically he may have been in error, his conclusions were sound and were supported by Akzo. A distinction was to be drawn between the addressee identifying something which could be improved, and the addressee being inventive. Polymorphic screening of pharmaceuticals was standard practice at the priority date for substances known to be polymorphic. However, the Lord Ordinary found that a skilled addressee would not know in advance how to obtain knowledge of polymorphism in any particular material. Therefore, it would not be obvious to ascertain if polymorphic forms were present.

[66] When asked for Akzo's formulation of the inventive concept in claim 1, Mr McNeill submitted that it was the identification of polymorphism in tibolone and the isolation of a crystalline pure form for pharmaceutical purposes. He accepted the Lord Ordinary's formulation at para. [45] of the inventive concept. This did not refer to a pharmaceutical composition but did refer to a crystalline pure form. Given what was said elsewhere by the Lord Ordinary about the issue being whether knowledge pointed a way to discovery of polymorphism in any particular case, the inventive concept predicated the discovery of polymorphism in tibolone. That was a prerequisite of the isolation of a crystalline pure form. What had been invented was a "non-polymorphic" pill, that is, one of sufficient purity to have advantageous properties. The aim of the invention, set out in the specification, related to a pharmaceutical composition containing pure form I tibolone.

[67] As regards the third Windsurfing stage, Arrow had suggested that there was an inherent contradiction in the Lord Ordinary's approach. However, there was a distinction in the approach taken by the Lord Ordinary to the issues of novelty and obviousness. In relation to novelty, he was constrained by his belief that the product claims were to form I tibolone itself. A single crystal would on that approach have been sufficient for anticipation. When considering obviousness, he had correctly identified the difference between what was known by a skilled person and what was disclosed by the patent as being the application of the discovery of polymorphism in tibolone to produce one of two different forms in a crystalline pure form.

[68] One should approach obviousness in light of the proper construction of the claims, including the concept of a pharmaceutical composition and all that entailed. In correcting the Lord Ordinary's thinking on novelty, one was not making any change to the essential reasoning he employed for the purposes of obviousness, where he identified a particular inventive concept as the essence of the invention. However, even if this was wrong, Akzo could still rely on the concept not being obvious; a non-polymorphic pill was not obvious.

[69] As to the "simple" case of obviousness, Dr Newton's evidence was habile to support a number of findings. In Arrow's favour, it supported the fact that polymorphism, as a concept likely to appear in steroids, would have been known to the skilled addressee at the relevant time. In Akzo's favour, the nature of polymorphism, and the extent of its understanding, was not such as to make it easy for the skilled person to identify a particular polymorph, or to establish what its properties would be. What was important was the guarantee of stability provided by the pure crystalline form. When one considered the evidence and the reports of Dr Newton, there was evidence to support the Lord Ordinary's findings-in-fact.

[70] It was not clear that the skilled man would have known that tibolone was probably polymorphous, or that the Declercq Paper would have given him information allowing him to make at least some form I. In evidence, Dr Newton moved somewhat away from para. 7.7 of his report, indicating that the skilled man would want a robust method of producing a particular polymorph. Moreover, Professor Bernstein was much less willing to accept that a skilled man would have known about polymorphism to the extent outlined by Dr Newton. The simple argument of obviousness relied upon by Arrow was merely the anticipation argument recast. Once a discovery and its practical application had been identified the question, under the statute, or the Windsurfing test, was whether the difference between the patent and the prior art was one without inventive step. The Lord Ordinary was entitled to ask not only whether there was an awareness of the likelihood of polymorphism in tibolone, but also whether Declercq and the common general knowledge "pointed the way" to polymorphism in the particular case.

[71] There was no indication as to what it was in Declercq that would take the skilled man into the realms of a guaranteed crystalline pure amount of tibolone for use in a pharmaceutical. There was not even anything directing the skilled man to a method of producing a single crystal of form I. There was no actual knowledge of polymorphism in tibolone at the time of Declercq, so there was no teaching in relation to how to obtain a single crystalline form and therefore no guarantee that the crystals obtained would be form I or form II, or a mixture of the two. The skilled man would not have the means of discovering polymorphism per se. As regards motive there had to be a real likelihood of something being in the mind of the skilled addressee. In the present case there was no likelihood that such a skilled addressee would look for polymorphism and attempt to screen out various crystals.

 

Submissions by senior counsel on behalf of Arrow

[72] Mr Currie accepted that construction of the claims was central to the issues in the case. Akzo's first argument regarding the "single crystal" issue suggested "pharmaceutical composition" implied pharmaceutical efficacy. However, on a proper construction of claims 1 to 3, there was no lower limit to the amount of monoclinic tibolone in the pharmaceutical composition. Arrow was not embarrassed by the absence of evidence that a single crystal would be pharmaceutically effective. It was clear from Dr. Newton's report that Arrow relied on the single crystal disclosed in Declercq for the purposes of anticipation. Akzo's attempts to specify or identify a lower limit had failed to produce anything specific enough to be expressed or implied in the claim of a patent. The function of the claims was to define clearly and with precision the monopoly claimed, in order that others might know the boundaries within which they would be trespassers (Conoco, per Lord Sutherland at pages 447D to 448C, quoting from Electric and Musical Industries Ltd v Lissen Ltd. [1939] RPC 23 per Lord Russell of Killowen at page 39).

[73] It was not in dispute that any pill containing a single crystal of tibolone would have a purity of greater than 90 or 95%. Prima facie, this would come within the definition of the pharmaceutical compound described in claim1. Akzo had not drawn the line between what was pharmaceutically efficacious and what was pharmaceutically inefficacious. The problem did not lie, as had been submitted by Mr McNeill, in the lack of evidence from Arrow, but in the language which Akzo had chosen to define its monopoly. If it wanted to avoid the plain language used in the claims, and exclude a single crystal as being sufficient, it ought to have led evidence in that regard. The word "pharmaceutical" did not itself imply some form of efficacy. It merely meant that the substance was found in a pill. Before the Lord Ordinary Akzo had not attempted to argue that a purposive construction would exclude a single crystal [see Lord Ordinary at para. [27]].

[74] Akzo's second argument suggested that the claims concerned crystalline purity within a particular percentage range, which implied a mixture. However, "crystalline pure" was defined as being "greater than 90%". This did not exclude a compound of 100% pure crystalline tibolone. The specification referred to the aim of obtaining a pill which was "completely or virtually completely free from the other crystalline form". Examples 3 and 5, included an experiment resulting in 100% yield. Akzo deliberately wanted to claim 100% purity. As a matter of construction, the language in the patent failed, by either of the routes suggested, to exclude a pharmaceutical composition including a single crystal.

[75] As regards the construction of claim 5, Arrow accepted that there were arguments in favour of both parties, particularly with regard to the phrase "mixtures of water and acetone". However, a fundamental problem for the reclaimers was that this phrase was capable of embracing bench acetone alone, as that had both substances in it. Moreover, Example 1 in the specification did not involve the use of water. Nothing in the specification suggested Example 1 was excluded from the monopoly claimed. Therefore, the proper construction of claim 5 included the use of bench acetone as a re-crystallisation medium.

[76] Mr Currie submitted that, if we accepted Arrow's contentions as to the proper construction of claims 1 to 3 and rejected attempts to exclude a single crystal, there was an irresistible argument for Arrow on the question of obviousness. The issue of construction ought not to be confused with that of the inventive concept (Pozzoli, per Jacob LJ at paras. 14-21). Akzo tended to conflate the two issues. The inclusion of the words "pharmaceutical composition which contains a pharmaceutically suitable solid carrier" in the claims did not make them part of the inventive concept. Mr McNeill seemed to accept initially the definition of the inventive concept adopted by the Lord Ordinary, but then suggested that some interpretation of that finding was required. When the specification was considered Arrow's characterisation of the inventive concept was clearly the correct one. The discovery of the polymorphism of tibolone could not be an inventive step; it was a discovery about the natural world. The inventive step which had been identified by the patentee was obtaining the crystalline purity of the active ingredient. There was no difference between the inventive step, as properly identified, and the prior art, as read by the skilled man.

[77] On Arrow's second approach to obviousness, it would have been obvious to use only the pure crystalline form in a pill and to crystallise from acetone in order to get this form. It was the very thing which the prior art was instructing you to do. It was permissible to mosaic for the purposes of the third Windsurfing step. The prior art showed that tibolone, as a compound, had been known about since the 1960s (patent 279); that a skilled man would understand that tibolone was being developed as a drug by Organon, a pharmaceutical company; that it was of interest for menopausal complaints; that its crystalline structure had been disclosed in monoclinic form (Declercq); and that in 1988 tibolone had been put on the market as a pill (Mr Vrijhof). The evidence suggested you would get at least some monoclinic tibolone by crystallising from acetone. In any event, it was not necessary for Arrow to demonstrate enablement for the purposes of obviousness.

[78] The suggestion that the skilled man could not find out if there was a second polymorph at the priority date missed the point. A skilled man, aware that tibolone might be polymorphous, would recognise the advantage of obtaining a pure form. This was shown by the exercise Organon carried out in identifying the structure of the crystal, despite not being aware of any other form. If Declercq did not disclose that the monoclinic form had any particular advantage, nowhere in the law of obviousness did it state that any such advantage was required. In any event, the skilled man would associate the form disclosed in Declercq with the drug which was under development by Organon. Declercq took place in a "mono-morphic world"; form II was not discovered. The evidence of Dr Newton suggested that a skilled man could identify the monoclinic crystalline structure in a sample. This undermined any suggestion that what was inventive was the discrimination between forms.

[79] Arrow's third approach to obviousness suggested it was instructive simply to apply the statutory test (Terrell, para. 7-53). What was disclosed by the patent could hardly be seen as inventive. One could not say that the clock stopped when Declercq was printed; it would be obvious for the skilled man to move forward with the information disclosed within it. Looking at the matter in broader terms, the only inventive step which could be identified was that which related to the monopoly claimed for form II tibolone. Importantly, even though Declercq disclosed the monoclinic form, Akzo did not simply claim a monopoly in relation to form II, but tried to patent that which was already known.

[80] On anticipation, Arrow's position was that the first route to demonstrate lack of novelty was to show that the prior art actually disclosed the invention. The second was to show that the prior art provided a method which inevitably produced that invention. For present purposes Arrow had relied on the first route: Declercq disclosed every element of the invention. Whatever route was chosen, what was disclosed in the prior art must necessarily infringe the patent. Akzo repeatedly confused the terms "necessarily infringe" and "inevitable result". An inevitable result was only relevant for the second route. Again, enablement did not require an inevitable result. Trial and error was permitted. Arrow had to show that performing (in the sense of making) the invention would necessarily infringe the patent. That was different from the concept of "inevitable result" which concerned the process involved.

[81] Declercq disclosed monoclinic pure tibolone in the context of the development of a drug known to be of interest for the treatment of menopausal complaints. Merck suggested that reference to the "potential use" of a substance in a pharmaceutical composition did not detract from what was a clear and unmistakable direction to use it as an active ingredient in the production of a pharmaceutical (paras. 15-19, 21-22 and 27-28 per Vice-Chancellor Sir Andrew Morritt). The distinction which Akzo sought to draw between the circumstances in that case and those in the case in suit was not valid. The skilled man would understand from Declercq that monoclinic tibolone was being developed as a drug for the treatment of menopausal complaints, since it was under development by a pharmaceutical company. Similarly, the use of a pharmaceutical carrier could not be considered novel. It was a plain consequence of the teaching to use tibolone as a pharmaceutical (Merck, per the Vice-Chancellor at para. 22). Declercq carried the implication that one would use such a carrier.

[82] On enablement, Declercq taught crystallisation from acetone, from which the skilled man would expect to get at least some form I. He could identify that form using a microscope, according to Dr Newton. For the purposes of enablement it was not necessary to show that crystallisation from acetone would have the "inevitable result" of a batch exclusively of form I, or even that form I tibolone would be obtained on every occasion. Declercq was an enabling disclosure.

[83] Mr Currie adopted, in their entirety, the submissions of Miss Higgins. He moved us to uphold the Lord Ordinary's decision that the claims were invalid for want of novelty and to refuse the reclaiming motion. In addition, or alternatively, he moved us to grant Arrow's cross-appeal.

 

Discussion

The role of an appellate court

[84] The approach which an appellate court should adopt in patent cases has been considered both as regards novelty and obviousness. In Biogen v Medeva at page 45 Lord Hoffmann said:

"The question of whether an invention was obvious had been called 'a kind of jury question' ... and should be treated with appropriate respect by an appellate court ... Where the application of a legal standard such as negligence or obviousness involves no question of principle but is simply a matter of degree, an appellate court should be very cautious in differing from the judge's evaluation."

In Buchanan v Alba Diagnostics Ltd. 2004 SC (HL) 9 Lord Hoffmann at para. [31] agreed with an observation made by Lord Clarke (sitting in the First Division) to the effect that an appellate court should not substitute its opinion for that of the judge of first instance unless it considers that he has made some error of principle (see 2001 SCLR 307 at para. [34]). Lord Hoffmann added that the question in that case (whether a particular invention was an "improvement" over an earlier one) was in that respect:

"similar to that as to whether an invention is obvious (Biogen Inc v Medeva at page 45) or whether a substantial part of a copyright work has been copied (Designers Guild Ltd. v Russell Williams (Textiles) Ltd.)"

The other members of the Appellate Committee agreed with Lord Hoffmann. In the last-mentioned case (reported at [2000] 1 WLR 2416) Lord Hoffmann had said at page 2423:

"Secondly, because the decision involves the application of a not altogether precise legal standard to a combination of features of varying importance, I think that this falls within the class of case in which an appellate court should not reverse a judge's decision unless he has erred in principle."

[85] In Technip France Jacob, L.J. distinguished an appeal court's function in relation to a question of novelty. At para. 74 he said:

"I do not think the question of novelty involves the application of a 'not altogether precise legal standard'. It involves a precise standard. Nor is it applied to a 'combination of features of varying importance'. On the contrary one must look for every claim element to see whether it is fully disclosed in the prior art. It may be that in some cases, Biogen-type principles may come into the question at an earlier stage. I have in mind, for instance, where the court has to evaluate evidence as to what a particular prior use actually was and whether it was enabling or where there is an evaluation of what is exactly disclosed by something like a photograph ... , or even, perhaps, the meaning of a technical term or phrase where experts have disagreed. But in a case such as this, where the issue is simply what does the prior art describe and does it fall within the claim, the Biogen principle does not apply."

Mummery and Pill L.Js agreed.

[86] In Merck the Court of Appeal had earlier emphasised that an appellate court should in patent appeals (generally) interfere with the view of the trial judge only if he could be shown to have erred "in principle" - see, in particular, per the Vice-Chancellor (Sir Andrew Morritt) at para. 61 and per Buxton L.J. at para. 64. In Smithkline Beecham plc v Apotex Europe Ltd. [2005] FSR 524 Jacob L.J. said at para. 36 (under reference to the approach on appeal to questions of novelty and obviousness):

"These I restated in Technip France SA's Patent ... at paras. [71] - [74]. In brief, the Biogen appeal principle ... applies to obviousness but not to novelty, save in special cases, for instance where there is a conflict of expert testimony on the meaning of a technical term or as to what exactly is disclosed by the prior art. The Biogen appeal principle itself is, in short, that an appellate court must exercise caution in differing from the trial judge's evaluation of the facts unless he has erred in principle."

[87] Although there may be some difference, on the matter of review of an issue of novelty, between the views expressed in the Court of Appeal in Merck and those subsequently expressed in Technip France and SmithKline Beecham, it is, in my view, unnecessary in this case to resolve any such difference. The parties before us were not seriously in dispute about the appropriate approach. As I shall explain, whichever approach is taken, this court requires to look again at each of the issues of novelty and obviousness.

 

Novelty

[88] On any issue of novelty the first question to be addressed is the construction of the patent in suit - and in particular the pertinent claims of that patent (Patents Act 1977, section 125; Article 69 of the European Patent Convention). The requisite canon of construction has been said to be one between the extremes of strict and literal meaning on the one hand and a guideline approach on the other, which canon "combines a fair protection for the patentee with a reasonable degree of certainty for third parties" (Protocol on The Interpretation of Article 69 of the Convention). In Kirin-Amgen at para. 25 Lord Hoffmann observed:

"It is often said, on the basis of the words 'a position between these extremes', that the Protocol represents a compromise between two different approaches to the interpretation of claims. But that is not quite accurate. It is a protocol on the interpretation of art. 69, not a protocol on the interpretation of claims. The first sentence does deal with interpretation of the claims and, to understand it, one needs to know something about the rules which English courts used to apply, or impose on themselves, when construing not merely patents but documents in general. The second sentence does not deal with the interpretation of claims. Instead, it makes it clear that one cannot go beyond the claims to what, on the basis of the specification as a whole, it appears that 'the patentee has contemplated'. But the last sentence indicates that, in determining the extent of protection according to the content of the claims but avoiding literalism, the courts of the Contracting States should combine 'a fair protection for the patentee with a reasonable degree of certainty for third parties'."

Lord Hoffmann then explained the principles upon which, at common law, the English courts had traditionally approached the issue of construction. He continued:

"32. Construction, whether of a patent or any other document, is of course not directly concerned with what the author meant to say. There is no window into the mind of the patentee or the author of any other document. Construction is objective in the sense that it is concerned with what a reasonable person to whom the utterance was addressed would have understood the author to be using the words to mean. Notice, however, that it is not, as is sometimes said, 'the meaning of the words the author used', but rather what the notional addressee would have understood the author to mean by using those words. The meaning of words is a matter of convention, governed by rules, which can be found in dictionaries and grammars. What the author would have been understood to mean by using those words is not simply a matter of rules. It is highly sensitive to the context of, and background to, the particular utterance. It depends not only upon the words the author has chosen but also upon the identity of the audience he is taken to have been addressing and the knowledge and assumptions which one attributes to that audience ...

33. In the case of a patent specification, the notional addressee is the person skilled in the art. He (or, I say once and for all, she) comes to a reading of the specification with common general knowledge of the art. And he reads the specification on the assumption that its purpose is both to describe and to demarcate an invention - a practical idea which the patentee has had for a new product or process - and not to be a textbook in mathematics or chemistry or a shopping list of chemicals or hardware. It is this insight which lies at the heart of 'purposive construction'. ...

34. 'Purposive construction' does not mean that one is extending or going beyond the definition of the technical matter for which the patentee seeks protection in the claims. The question is always what the person skilled in the art would have understood the patentee to be using the language of the claim to mean. And for this purpose, the language he has chosen is usually of critical importance. The conventions of word meaning and syntax enable us to express our meanings with great accuracy and subtlety and the skilled man will ordinarily assume that the patentee has chosen his language accordingly. As a number of judges have pointed out, the specification is a unilateral document in words of the patentee's own choosing. Furthermore, the words will usually have been chosen upon skilled advice. A specification is not a document inter rusticos for which broad allowances must be made. On the other hand, it must be recognised that the patentee is trying to describe something which, at any rate in his opinion, is new; which has not existed before and of which there may be no generally accepted definition. There will be occasions upon which it will be obvious to the skilled man that the patentee must in some respects have departed from conventional use of language or included in his description of the invention some element which he did not mean to be essential, but one would not expect that to happen very often."

At paragraph 47 Lord Hoffmann added:

"The Protocol, as I have said, is a Protocol for the construction of art. 69 and does not expressly lay down any principle for the construction of claims. It does say what principles should not be followed, namely the old English literalism, but otherwise it says only that one should not go outside the claims. It does however say that the object is to combine a fair protection for the patentee with a reasonable degree of certainty for third parties. How is this to be achieved? The claims must be construed in a way which attempts, so far as is possible in an imperfect world, not to disappoint the reasonable expectations of either side. What principle of interpretation would give fair protection to the patentee? Surely, a principle which would give him the full extent of the monopoly which the person skilled in the art would think he was intending to claim. And what principle would provide a reasonable degree of protection for third parties? Surely again a principle which would not give the patentee more than the full extent of the monopoly which the person skilled in their art would think that he was intending to claim. Indeed, any other principle would also be unfair to the patentee, because it would unreasonably expose the patent to claims of invalidity on grounds of anticipation or insufficiency."

The other members of the Appellate Committee agreed with Lord Hoffmann.

[89] In STEP 513 Hoffmann L.J. (as he then was) said at page 522 (in the context of discussion of a patent for an atomiser where the claim included the integer "conduit means extending upwardly within the cylinder to define therewith a pump chamber"):

"The well known principle that patent claims are given a purposive construction does not mean that an integer can be treated as struck out if it does not appear to make any difference to the inventive concept. It may have some other purpose buried in the prior art and even if this is not discernible, the patentee may have had some reason of his own for introducing it. In my judgment therefore the claim requires that something which can fairly be described as a conduit must extend upwards within the cylinder and its outer surface must, together with the walls of the cylinder, define the pump chamber."

[90] In Wheatley Aldous L.J., having referred with approval to Hoffmann L.J's dictum just cited, added at para. 22:

"The object of interpretation is to ascertain the intention of the author, in this case the patentee. This involves examining the words of the claim through the eyes of a person to whom the specification is directed, in the context of the specification as a whole. If the reader skilled in the art would have understood that the patentee intended that the claim should have a particular ambit, then to construe it as not confined to that ambit, by either strict or liberal construction, would be unfair to the patentee. It is the patentee that chooses the words and to widen the ambit contrary to his intention would invalidate the patent and to restrict the ambit could allow use of the invention without payment."

[91] Applications of these principles can be found in Generics (UK) and Halliburton.

[92] The Lord Ordinary does not directly address the question of construction of claims 1-3 - and in particular the need to have regard to the whole integers of these claims. At one point (para. [23] of his Opinion) he says:

" ... claim 3 is a claim to a particular product, namely tibolone of a particular crystalline structure".

That statement was challenged by Akzo on the ground that it posited that the claim was to a compound of a particular crystalline structure without regard to the integer(s) "A pharmaceutical composition which contains a pharmaceutically suitable solid carrier and ... ". Reference to construction of claims 1-3 is made by the Lord Ordinary also at para. [24] where he says:

"Akzo's second argument was that the fact that Declercq revealed a single crystal of Form I, which was by definition 100% pure, was irrelevant on a proper construction of claims 1-3. The claims in the patent were to a 'pharmaceutical composition' containing the compound, i.e. tibolone. That must involve a recognition that a crystal is not sufficient; a pharmaceutical compound clearly cannot be made of a single crystal."

That reference, however, is made only in the context of the "single crystal" argument (to which I shall return), not in the context of construing the whole integers of the claim. In para. [28] the Lord Ordinary records an argument that

" ... any challenge to claims 1-3 on grounds of lack of novelty would have to demonstrate not just that the form and purity of the crystal were anticipated but also that the incorporation of the tibolone of the requisite form and purity into the pharmaceutical composition similarly lacked novelty".

The argument, as recorded, then continued:

"The incorporation of the tibolone into a pharmaceutical composition was not anticipated in Declercq. A challenge to the whole of claims 1-3, properly construed, would, [counsel] submitted, involve Arrow in 'mosaicing', i.e. building a case on anticipation by putting together a mosaic of different sources of prior disclosure".

In response to this argument the Lord Ordinary at para. [29] said:

"It cannot be, and was not, suggested that there is anything novel about the making of pharmaceutical composition incorporating tibolone." (emphasis added).

That sentence may in terms be accurate, though as I shall explain the de quo is not whether there was anything novel about the making of a pharmaceutical composition incorporating tibolone but whether there was anything novel in making a pharmaceutical composition which contained (a pharmaceutically suitable solid carrier and) tibolone with a certain minimum crystalline purity. The Lord Ordinary added towards the end of that paragraph:

"I consider that the addressee of the patent would not understand the incorporation of the compound into the pharmaceutical composition to be part of the invention claimed by the patent. Nor is this a realistic interpretation of the claims read in context, even if construed by the Court without looking through the eyes of the notional addressee."

These propositions were not supported by Arrow in seeking to maintain the Lord Ordinary's conclusion on anticipation. They are plainly, as a matter of construction, wrong.

[93] The construction of claims is a matter for the court (General Tire at page 485). If a judge of first instance has failed to construe the claims or has misinterpreted them, that is an error "in principle" which is open to review by an appeal court. In the absence of any clear indication that the Lord Ordinary took into account the whole integers of claims 1-3, his interlocutor is, in my view, open to review by this court.

[94] Before returning to the question of general construction, it is convenient to deal with certain other arguments advanced by Akzo.

[95] It was contended that claims 1-3 had not been anticipated by Declercq because a pharmaceutical composition could not have as its active ingredient a single crystal; the prior art (Declercq) had disclosed only a single crystal. The prior description of a single crystal (ex hypothesi 100% pure and thus having a purity "greater than 95%") was accordingly, so ran the argument, not "something falling within [the claims'] scope" - see Inhale Therapeutic Systems, per Laddie J. at para. 43.

[96] In my opinion, this argument fails for want of any evidence that a pharmaceutical composition could not be constituted by a pharmaceutically suitable solid carrier and a single crystal. A pharmaceutically suitable carrier, as envisaged in the patent, includes material to make up a tablet, pill, capsule or suppository; it may be administered either parenterally (that is, not via the digestive tract) or orally (see patent, page 3, lines 29-31). While one's initial reaction is to suppose that crystals of tibolone are likely to be small in size (there was some evidence that different forms of crystals might be distinguished under a microscope), there was no evidence that all solid forms of administration inevitably included a plurality of crystals. There was no evidence directed to whether the relative addressee (the skilled man) would understand the patentee as including or excluding from his claim a composition of which a single crystal of tibolone was the active ingredient. Although the onus of proving lack of novelty rested on Arrow, in my view it succeeds on this issue on the language of the claim as drafted. These claims might have been construed otherwise if there had been contextual material that a plurality of crystals in any composition was inevitable. It is true that in the Examples every reference is to "crystals" (in the plural) but these exercises are inevitably concerned with batches of materials, presumably designed for manufacturing a multiplicity of doses. So far as I can find, there is no reference to crystals (or to crystal) in the Description itself. The language of the patent as a whole accordingly does not assist Akzo on this argument. I bear in mind that the claims require to be construed purposively i.e. "to describe and to demarcate an invention" (Kirin-Amgen, per Lord Hoffmann at para. 33) but am of opinion that there is no demarcation in these claims which excludes a single crystal of crystalline pure tibolone as the active ingredient in a single pharmaceutical composition. The patentee may have had good reason for drawing the patent sufficiently comprehensively to encompass a single crystal in an administrative unit. I should add in this regard that Mr. McNeill sought to persuade us of the minuteness of the relevant crystals by a calculation based on material referred to in Professor Bernstein's report about the volume, density and weight of the triclinic form and an assumption that monoclinic crystals were of the same order. But this calculation was not put in evidence and I am unable to place any reliance upon it.

[97] A related argument advanced on behalf of Akzo was that the references in claims 1 and 2 (and by incorporation in claim 3) to crystalline purity "greater than 90%"/"greater than 95%" imported a plurality of crystals in any composition. The percentages related to percentages by weight. But it seems plain that, while the claims embrace mixtures of form and thus more than one crystal, they are wide enough to include tibolone of 100% crystalline purity. Apart from the language of the claims, the description in the specification makes it clear that the aim of the invention is to obtain a pharmaceutical composition which contains a crystalline pure form of tibolone which is "completely (emphasis added) or virtually completely free from the other crystalline form". The examples given include some at 100% purity. A single crystal of tibolone is (as was accepted in evidence) tibolone of 100% crystalline purity.

[98] Akzo also argued that the reference to "pharmaceutical composition" implicitly imported that the amount of the pure crystalline form was adequate in amount to be of "effective pharmaceutical" use. But even if "pharmaceutical composition" implies some minimal therapeutic or other pharmaceutical effectiveness (which I doubt), there is no evidence before the court by which such effectiveness could be measured relative to the size of a crystal. In any event, as Mr. Currie contended, the notion of effectiveness in this context is so vague that nothing could be implied of sufficient precision to support the claimed monopoly. As the Lord Ordinary said at para [27]:

"it would have been open to Akzo to limit claims 1-4 by reference to some quantitive criteria but, for whatever reason, they have not done so. It was not suggested that, even adopting a purposive construction, those claims should be read as incorporating some such criteria capable of being expressed with sufficient precision."

[99] There remains, however, the wider question whether Declercq discloses

"a pharmaceutical composition which contains a pharmaceutically suitable solid carrier and the compound having the structure [specified], characterised in that the compound is crystalline pure, which purity is greater than [90 or 95%]",

such that it could be said to have anticipated claims 1 or 2, or such a composition where the crystalline pure compound has the monoclinic form, such that it could be said to have anticipated claim 3. Taking account of the whole integers, that imports, in my view, a combination of a pharmaceutically suitable solid carrier with tibolone in a crystalline purity of more than the stated percentages and, so far as claim 3 is concerned, of a particular crystalline form. The issue is whether that combination was anticipated by Declercq.

[100] To answer that question it is necessary for the court to put itself in the position of the relative skilled man reading that paper and possessed of the relevant common general knowledge as at its date (May 1984). The skilled man would, it seems clear, view this paper as a report of the findings on analysis of the molecular conformation of a single crystal selected for examination. The single crystal was of the monoclinic form. He would, from the co-authorship of Mr. Zeelen, apparently an employee in the Organon Scientific Development Group, presumably a pharmaceutically related body, and the circumstances that tibolone had been given a reference ("Org OD 14") apparently by that body, conclude that a pharmaceutical enterprise was at that time interested in the possible development of tibolone for pharmaceutical purposes. He would know (or at least be so instructed by footnote 5) that tibolone was a compound of interest for the treatment of menopausal complaints. He would know, as part of the common general knowledge at that time, that tibolone was a steroid and that steroids were commonly but not universally polymorphous. He would not have known that tibolone was in fact polymorphous. So far as then known, tibolone might in fact be monomorphous, that is found only in the monoclinic form. He would not know that in a pure or virtually pure crystalline form tibolone had advantages, in terms of consistency of medicament or of storage longevity, over tibolone not in such form. Declercq does not identify any advantages of crystalline purity; it was not the function of its authors to do so.

[101] Miss Higgins submitted, on the basis of evidence given by Dr. Newton, that it was the crystalline form of tibolone identified and described in Declercq, which was of interest for the treatment of menopausal complaints. No evidence was led from any of the authors of Declercq. The Lord Ordinary made no findings in relation to events surrounding the instruction and completion of this analysis. Dr. Newton gave some evidence about his understanding, from the terms of the paper, of what had promoted it. Much of that evidence was necessarily speculative. In my view all that can be taken by way of inference from Declercq is that a pharmaceutical organisation, which had an interest in tibolone as a medicament for the treatment of menopausal complaints, instructed an analysis by academic experts of the structure of a crystal of that compound as part of its development research. How and by whom the single crystal was selected is not known. Nor is the crystalline composition of the sample from which it was selected disclosed or known. The skilled man would not, in my view, have taken from Declercq any suggestion that the monoclinic crystal described there had, as a crystal, any advantages for pharmaceutical purposes. The paper does not commend the use for such purposes of the crystalline form analysed in it. It does not in any way suggest that a single crystal on its own would be suitable for such use. Nor does it in any way disclose the use of any particular percentage of one form of crystal in a pharmaceutical composition. Nor will it do to suggest (as it was late in the argument) that it did disclose use of 100% monoclinic form tibolone in a pharmaceutical - even if the sample from which the crystal was taken was not 100% pure - because the reader was ignorant of its polymorphism. If that were sound any previous reference to tibolone for pharmaceutical use could be said to anticipate claims 1 and 2 which even Arrow do not seek to argue. The circumstances, in so far as known to the skilled man, fell well short of the circumstances in Merk's Patent, where the document constituting the prior art (a patent application by Blum) had contained an express statement that the product discussed was suitable for use for pharmaceutical purposes.

[102] In these circumstances the prior art, as interpreted by the skilled man, did not, in my view, disclose the invention claimed in claims 1-3 viz.

"a pharmaceutical composition which contains ... the compound [tibolone] characterised in that the compound is crystalline pure, which purity is greater than [90 or 95% or, as regards claim 3, in the monoclinic form]".

I leave out of account for present purposes the integer of "a pharmaceutically suitable solid carrier" because, if I had been persuaded that Declercq did disclose the use of tibolone of the requisite crystalline purity for pharmaceutical purposes, the possibility of its combination with a suitable solid carrier would not to the skilled man, in my view, have been novel.

[103] For a disclosure to constitute anticipation it must be an "enabling disclosure" (Asehi Kasei Kogyo KK's Application, per Lord Jauncey of Tullichettle at p. 543). This gave rise to an argument by Akzo that Declercq was not, in any event, "enabling". Although I have found for the reasons given above that claims 1-3 were not anticipated by the prior art, it is appropriate, having regard to the attention paid to it before us, that I express my views on that argument.

[104] A party seeking revocation of a patent on the ground that it has been anticipated by the prior art has to satisfy the court on two points, namely, whether the prior art disclosed the invention which had been patented ("disclosure") and whether an ordinary skilled man would be able to perform the disclosed invention if he attempted to do so using the disclosed matter and common general knowledge ("enablement") - see Smithkline Beecham, per Lord Hoffmann at para. 14. These two concepts are distinct and are separately dealt with by Lord Hoffmann - paras. 20- 25 and 26 - 27; the importance of keeping them distinct is emphasised at paras. 28 - 33. In my view a failure by Akzo to keep these concepts distinct led its counsel at times to misconstrue what Lord Hoffmann had said, in the context of disclosure, when discussing and summarising two earlier judgments, including a well-known passage from the judgment of the Court of Appeal in General Tire. As Arrow contended, a distinction falls to be made between enablement of a patent on the one hand and on the other a situation where performance of the directions contained in the prior art will "necessarily result" in the infringement of the patent (one of the ways in which the patent may by prior disclosure have been anticipated, the other being by direct comparison of the prior art with the patent). For the purposes of enablement the carrying out of the directions in the prior art need not, in my view, inevitably result in the obtaining (in the case of a product patent) of that product. As Buckley L.J. said in Valensi v British Radio Corp [1973] RPC 337 at page 377 (an observation cited with approval by Lord Hoffmann in Smithkline at para. 27):

" ... [The effect of the cited cases as a whole is to show that] the hypothetical addressee is not a person of exceptional skill and knowledge, that he is not to be expected to exercise any invention nor any prolonged research, enquiry or experiment. He must, however, be prepared to display a reasonable degree of skill and common knowledge of the art in making trials and to correct obvious errors in the specification if a means of correcting them can readily be found."

[105] Accordingly, it is unnecessary for the purposes of valid enablement that the addressee of Declercq should, if following the experimental parameters described in that paper, have always got crystals which were exclusively of the monoclinic form. The Lord Ordinary found on the evidence that, by following the experimental parameters in Declercq of using acetone as the medium, one would expect to get form I tibolone (see paras. [33] - [34]). That finding followed upon a conclusion that on the evidence it had not been demonstrated to the Lord Ordinary's satisfaction "that every crystallisation using acetone will necessarily produce Form I tibolone" and an acceptance by him of evidence from Professor Bernstein that "It cannot be inferred from the materials before the court that any use of acetone will inevitably give Form I" (the Lord Ordinary's emphasis). The Lord Ordinary added that the:

"amount of water and the temperature and rate of the crystallisation may impact upon the result and the serendipitous nature of the discovery of different polomorphic forms means that one can, in any event, never have absolute certainty in this field".

If the Lord Ordinary's findings are read in context, his conclusion was, in my view, to the effect that, using acetone, that is, following the procedure envisaged in the prior art, the skilled person would ordinarily obtain crystals, some at least of which were monoclinic. That conclusion is consistent with the experimental examples given in the patent which envisage polar solvents (including acetone and water) producing a high percentage of the monoclinic form.

[106] However, the circumstance that following the experimental parameters described in Declercq the skilled person would ordinarily obtain crystals, some at least of which were monoclinic, does not entail that "the invention" would thereby be performed. The invention, properly understood, was constituted by a pharmaceutical composition having a high degree of crystalline purity in the active ingredient. While the skilled person, following Declercq, might be expected to obtain a mixture of crystalline forms (including some monoclinic), from which a particular crystal might by some process under the laboratory microscope have been isolated, Declercq did not teach how to obtain a product of high crystalline purity for pharmaceutical use - even if the skilled person for some reason was alert to the need to isolate a particular form, notwithstanding his ignorance of polymorphism in tibolone.

[107] In these circumstances, while Declercq enabled the skilled person to take certain steps, it did not enable him "to perform the invention".

 

Claim 5

[108] Although a challenge to claim 5 was not made in Arrow's pleadings, such a challenge was advanced before the Lord Ordinary, who upheld it. Before us Miss Higgins advanced submissions in support of it. Mr. Currie did not depart from these, while recognising that, on the matter of interpretation of that claim, "there were arguments in favour of both constructions".

[109] Among the modes by which the crystalline pure compound tibolone may, in accordance with claim 5, be prepared for use in a pharmaceutical composition is crystallisation "from mixtures of water and acetone or ethanol ... ". In Declercq the medium by which the analysed crystal was obtained was "acetone". Dr. Newton understood that reference was to bench acetone (see e.g. pages 370 and 390). Patent 845, with a priority date in June 1967, described the compound tibolone (though not named as such) as "recrystallised from acetone with one drop of pyridine". The Lord Ordinary (having regard to the specification as a whole, and in particular the specific reference to anhydrous acetone (at page 3 lines 6-7) read references in the patent to "acetone" as being references to "bench acetone", that is, absolute acetone with such water in it as is conventionally found on a laboratory bench. I would also so read the references to "acetone" in Declercq and in the 845 patent.

[110] The first issue (which does not appear to have been raised before the Lord Ordinary) is whether the skilled addressee would regard the reference in claim 5 to a "mixture[s] of water and acetone" as a reference simply to bench acetone or to some process of mixing water with bench acetone. Some assistance on that matter of construction may be obtained from the Description and from the Examples. At page 2 lines 53-57 of the patent, after a reference to "mixtures of water and acetone or ethanol", it is stated:

"A suitable method is to dissolve the polymorphous compound in acetone or ethanol, after which the solution is added to water. Conversely, water can also be added to a solution of the polymorphous compound in acetone or ethanol."

It is not clear to me what is the difference between these methods - we were not enlightened on this - but each appears to envisage a step whereby the compound dissolved in acetone is added to water (or vice versa). This would be consistent with evidence from Professor Bernstein (at para. 75 of his report, which was accepted by Dr. Newton at page 389) that water so added acts as an anti-solvent giving rise to precipitation of the crystals. Examples 2 and 4 appear to envisage a similar procedure.

[111] A difficulty is caused to Akzo by the terms of Example 1, which illustrates the invention by a procedure which involves the use of acetone but does not refer to any mixture of it with water (a purity of 94% being obtained). An answer to this difficulty may be that the procedure for obtaining the crystals illustrated in Example 1 is not a method covered by claim 5 of the patent. A patent may, for one reason or another, claim less than it teaches (Kirin-Amgen, per Lord Hoffmann at para. 33). However that may be, the terms of the claim, as read in the general context of the Description, point, in my view, to "mixture[s] of water and acetone" involving more than the use simply of bench acetone. Neither Declercq nor patent 845 "teaches" anything beyond the use of bench acetone. Dr. Newton did not seek to suggest that claim 5 was anticipated by reference to crystallisation with acetone in Declercq. Rather he acknowledged the method disclosed in Declercq was "similar but not the same process that was used in the patent for obtaining the monoclinic form. In the patent they actually dissolve in acetone then add water." (pp. 57 and 58). In these circumstances claim 5 is not, in my view, anticipated by these publications. In so far as the Lord Ordinary construed claim 5 as claiming "a monopoly over every process of crystallising the compound using acetone" (page 34) this cannot be supported.

[112] But, even if I am wrong in that conclusion, it is necessary in construing claim 5 to have regard to what is incorporated in it by reference. Claim 5 is to a method "for the preparation of a crystalline pure compound for use in a pharmaceutical composition according to claim 3 ... ". Claim 3 in turn incorporates claim 1. So, what is in effect claimed by claim 5 is a method for preparing monoclinic crystalline pure tibolone (with a purity greater than 90%) for use in a pharmaceutical composition. As with claims 1-3 in relation to a product, Declercq does not, in my view, teach anything about the use of crystalline pure monoclinic tibolone for use in a pharmaceutical composition. Nor does patent 845. Accordingly, for this additional reason claim 5 was not, in my view, anticipated by either of these publications.

 

Obviousness

[113] As Lord Hoffmann observed in Biogen v Medeva at page 45:

"Where the application of a legal standard such as negligence or obviousness involves no question of principle but is simply a matter of degree, an appellate court should be very cautious in differing from the judge's evaluation."

The corollary of that proposition is that, where the judge of first instance has erred upon a matter of principle, his decision is open to review by an appellate court.

[114] In addressing the issue of obviousness the Lord Ordinary adopted and sought to apply the four-stage test expressed in Windsurfing International v Tabur Marine Limited, a test approved in the House of Lords - see Sabaf v MFI at para. 27. In applying the Windsurfing approach the Lord Ordinary at para [45] of his Opinion identified the relevant four stages as follows:

"(i) the inventive concept in the patent is the identification of a crystalline pure form of tibolone and a method of producing it; (ii) the skilled addressee would have known of tibolone and would have knowledge that steroids are likely, though not certain, to be polymorphous; (iii) the difference is the discovery of polymorphism in tibolone and the identification of the method of producing one of the two different polymorphic forms. Stage (iv) requires one to ask whether the steps required to achieve this would have been obvious to the skilled man."

He answered the question posed in the last stage with a clear "No".

[115] The Lord Ordinary, in seeking to apply the approved test, adopted a comprehensive view of the claims in question. He spoke of the inventive concept "in the patent". However, in Unilever Jacob J. (as he then was) observed at page 580:

"It is the inventive concept of the claim in question which must be considered, not some generalised concept to be derived from the specification as a whole. Different claims can, and generally will, have different inventive concepts. The first stage of identification of the concept is likely to be a question of construction: what does the claim mean? It might be thought there is no second stage - the concept is what the claim covers and that is that. But that is too wooden and not what courts, applying Windsurfing stage one, have done. It is too wooden because if one merely construes the claim one does not distinguish between portions which matter and portions which, although limitations on the ambit of the claim, do not. One is trying to identify the essence of the claim in this exercise."

That passage was cited with approval by Jacob L.J. in Pozzoli SPA v BDMSO SA at paras. 17-18; in the latter paragraph he added:

"So what one is seeking to do is to strip out unnecessary verbiage, to do what Mummery L.J. described as make a prcis."

Mummery and Keene LJs agreed. Neither of these cases appears to have been cited to the Lord Ordinary - the latter was, of course, issued after his decision. The import of them appears to be that it will, at least commonly, be important in seeking to identify any inventive concept to have regard to the claims discretely. The Lord Ordinary did not undertake such an exercise. His failure to do so might be regarded as an error in principle, though in the circumstances of this case, where claims 2 and 3 are so closely related to claim 1, I doubt whether, as regards these claims, the absence of a discrete treatment was a fundamental flaw. It may be otherwise as regards claim 5, which is a process rather than a product claim.

[116] More importantly, in my view, the Lord Ordinary's treatment of obviousness is flawed by his failure to bring into account, in dealing with that chapter, the significance of claims 1-3 being to pharmaceutical compositions comprised of two elements (carrier and active ingredient) rather than simply to tibolone at particular crystalline purities; and of claim 5 being a method of producing one of these specific compositions. That flaw may stem from the way in which parties' cases were argued in the Outer House. Additionally, the Lord Ordinary fell into error, in my view, in describing at step (iii) the difference, so far as concerned claims 1-3, as being "the discovery of polymorphism in tibolone". A discovery, such as that of polymorphism in tibolone, is the acquisition of knowledge about the real world. What is required for step (iii) is the identification of some practical difference or differences between the patented claim and the prior art (such as the shape of the sail in the Windsurfing case), which differences can then be judged (at stage (iv)) as to whether they involve a degree of invention. I shall return in due course, to identify what is, in respect of each claim, the practical application in the present case.

[117] In these circumstances the Lord Ordinary's treatment of obviousness is, in my view, open to review by this court. That is not to say, however, that all his findings of fact in this chapter are open to successful challenge.

[118] In Pozzoli SPA at para. 15 Jacob L.J. suggested that stages (i) and (ii) as described in Windsurfing should be inverted, that is, the first step was for the court to assume the mantle of the normally skilled but unimaginative addressee in the art at the priority date and to impute to him what was, at that date, the common general knowledge in the art in question. I am content to follow that order.

[119] In the present case the skilled man would be attired with knowledge of a number of matters. He would be familiar with the 845 and the 279 patents, each of which told him that tibolone as a compound had been synthesised and that that compound had medicinal advantages. These patents would have told him nothing about the number or characteristics of any crystalline forms of tibolone. He would know that tibolone was a steroid and that steroids were commonly, but not universally, polymorphous. He would know from Declercq that a single crystal of tibolone, obtained by a process of crystallisation through acetone, had been examined, its (monoclinic) structure disclosed and its molecular conformation reported on. He would not know whether the monoclinic form was or was not the only crystalline form of tibolone - there might be one or more other forms. He would know, again from Declercq, that a pharmaceutical company, with awareness of certain therapeutic advantages of tibolone, was sufficiently interested to instruct a conformational analysis of a single crystal of that compound and had obtained the results of that analysis. He would know that tibolone, without so far as he was aware any attention having been given to its crystalline purity, had been marketed under the name Livial.

[120] Laddie J. in Pfizer Limited's Patent at para. 62 described the skilled but non-inventive man as follows:

"This is not a real person. He is a legal creation. He is supposed to offer an objective test of whether a particular development can be protected by a patent. He is deemed to have looked at and read publicly available documents and to know of public uses in the prior art. He understands all languages and dialects. He never misses the obvious nor stumbles on the inventive. He has no private idiosyncratic preferences or dislikes. He never thinks laterally. He differs from all real people in one or more of these characteristics."

No quarrel was taken with that description and I am content to adopt it.

[121] I turn then to identify the inventive concept(s) in the patent. That should, strictly, be done, as I have said, by identifying the inventive concept in each claim. That involves seeking to identify the essence of each claim. I accordingly begin with claim 1. The inventive concept in that claim is, in my view, a product, being a pharmaceutical composition which contains (in addition to a carrier) tibolone with a high degree of crystalline purity. The inventive concept in claim 2 is likewise a product, a pharmaceutical composition of the same kind but with a yet higher degree of crystalline purity. The inventive concept in claim 3 is likewise a product, a pharmaceutical composition of the same degree of crystalline purity as in claim 1 but where the purity lies in a high degree of the monoclinic form. For present purposes I leave aside the identification of the inventive concept in claim 5.

[122] The third of the four stages of the Windsurfing approach requires the identification of the differences, if any, between "the state of the art" and the alleged invention (Pozzoli SPA, para. 22). In respect of claim 1 the essential difference, in my view, is that, while in the prior art tibolone as a compound had been recognised as of medicinal importance and while a crystalline form of that compound (as it happened the monoclinic form) had been isolated and analysed for its conformation, the claim for the first time identified the use of tibolone to a high degree of crystalline purity as the active ingredient in a pharmaceutical composition. In respect of claim 2, the essential difference is the use of tibolone to a yet higher degree of crystalline purity as the active ingredient in a pharmaceutical composition. In respect of claim 3, the essential difference is the use of tibolone to a high degree of crystalline purity where that purity is in the monoclinic form as the active ingredient in a pharmaceutical composition.

[123] The final stage involves the court, with such assistance as it may obtain from experts in the field, putting itself in the position of the skilled but unimaginative man, seised of comprehensive knowledge of the prior art but with no knowledge of the alleged invention, and asking, in respect of each claim, the question whether the difference identified at the third stage, constituted a step which was obvious. The answer to each question is a matter of fact and the court would expect to hear appropriately qualified evidence upon it.

[124] Dr. Newton addressed the matter in paragraphs 7.6 to 7.10 of his initial report and he was examined by Arrow's counsel upon it. The Lord Ordinary sets out the relative passages at paragraph [40] of his Opinion. I repeat them here, omitting for the present the references to claim 5:

"7.6 A skilled man wishing to develop Tibolone as a pharmaceutical product would need to identify a robust and repeatable process for making a well defined stable form of the drug.

7.7 The synthetic route to the compound is described in the 279 [patent]. ... The skilled man would be well aware of the fact that most steroids exhibit polymorphism (see references to common general knowledge at paragraph 5.1.9). Since he would have known that different steroidal polymorphs may have different melting points, densities, spectroscopic properties, bioavailabilities and stabilities ... he would want to define a single polymorph having suitable physical and bioavailability profiles.

7.8 The skilled man would have been aware of the prior art and of the 1984 [Declercq] Paper. The latter would have been a very important document since it teaches how to make a pure polymorph and defines it analytically. Thus, by following the teaching of the 279 to make the compound and then recrystallising it from acetone as taught by the 1984 [Declercq] Paper the skilled man would have a method of preparing pure Form I polymorph.

7.9 For these reasons I think that claims 1 and 2 of the Patent are obvious since the 1984 [Declercq] Paper already described Form I Tibolone. Claim 3 is likewise obvious since the 1984 [Declercq] Paper precisely describes the crystal structure referred to in the Patent as monoclinic P21 form ...

7.10 In my opinion it would have been obvious at the priority date of the Patent to obtain and use the polymorph claimed at claims 1-3 in its pure crystalline form ... ".

[125] So far as I have been able to discover - and we were not referred to any relevant passage in the transcript - Dr. Newton was not directly cross-examined by Akzo's counsel on the views expressed by him in these paragraphs. However, Professor Bernstein's views were extensively put to Dr. Newton in cross-examination for his comment. With some of these Dr. Newton agreed; with others he disagreed. At paragraph 84 of his report Professor Bernstein discusses inter alia para.7.7 of Dr Newton's report. He disagrees with the observations made there. Professor Bernstein adhered to that view in evidence. In cross-examination he expressly disagreed with the proposition that a person skilled in the art would, on the basis of information contained in Declercq, be able to get a robust, repeatable synthesis. Dr. Newton's recited views cannot therefore be said to have gone unchallenged or uncontradicted. The Lord Ordinary, having narrated Dr Newton's views, continues (para. [41]) - "Professor Bernstein took a different view". He added that, as he understood the evidence, the difference between Professor Bernstein and Dr. Newton lay in the former's assessment of the level of common awareness of polymorphism and the uncertainties in that aspect of the science. Having summarised Professor Bernstein's views on that matter, the Lord Ordinary said (at para. [42]):

"Despite Professor Bernstein's undoubted eminence in his field, I prefer the evidence of Dr. Newton to the effect that by the late 1980s polymorphism as a phenomenon would have been well-known to a process research chemist working in the pharmaceutical industry; and they would have known that it was widespread in pharmaceuticals, particularly steroids."

That is a finding of fact by the Lord Ordinary. Neither side before us sought to challenge it. At paragraph [43] the Lord Ordinary continued:

"But there is a difference between, on the one hand, knowing of polymorphism as a phenomenon, or even knowing that it is likely to be found in steroids; and, on the other hand, being able to use or apply that knowledge. The point Professor Bernstein was making, for example in para. 12 of his Report, was that polymorphism in any particular compound was usually discovered by serendipity rather than by systematic research. The important conclusion from this was that set out at para. 56 of that Report, that: ' ... even the skilled person could not know in advance that any steroid might be polymorphic. He certainly would not know in advance how to obtain it, or what its properties might be.' Despite the existence of polymorphic screening - which was less common in the 1980s than it is today - I did not understand Dr. Newton to disagree strongly with this opinion; and, in any event, I accept it as correct."

Again, that is a finding of fact, in this instance accepting as well-founded the quoted passage. Again, neither side before us sought to challenge it, though there was some discussion about the first sentence - its import it was suggested, was that "even the skilled person could not know in advance that any [particular] steroid [was] polymorphic".

[126] The Lord Ordinary concluded that there did not seem to be as much between Dr. Newton and Professor Bernstein (on this matter) as at first appeared. He then said:

"The relevant issue is not so much whether there was an awareness of polymorphism amongst the relevant people at the relevant time, but whether that knowledge pointed the way to a discovery of polymorphism in any particular case."

I shall return to that sentence in due course.

[127] In a critical passage (para. [44]) the Lord Ordinary continued:

"The obviousness attack on the claims in the patent has to be considered against this background. Let it be assumed that the skilled but unimaginative addressee of the patent knows of tibolone, and knows that there is a likelihood that tibolone, being a steroid, is polymorphous. Without the benefit of hindsight, I do not see why he would want to look for a pure polymorphic form of tibolone. After all, tibolone had been known from the 1960s, and there was no evidence of any concerted effort to find out if it was polymorphous. Nor do I see how he would go about finding a new polymorphic form. He might know of the Declercq paper, which would tell him about what is now called Form I, and about the use of acetone, but not about tibolone being polymorphic. If he carried out a crystallisation using acetone, he would probably have produced what we now know as Form I tibolone. But that would support Arrow's argument on anticipation rather than obviousness (see para. 34 above). It seems to me that the 'obviousness' line of attack, as distinct from that based on anticipation, assumes that the skilled but unimaginative addressee of the patent would be looking to develop a pure polymorphic form of tibolone and would have had the knowledge of how to achieve it. Without the benefit of knowing (with hindsight) that such a form had been found, I do not consider that he would have had either the motivation or the means."

[128] Arrow, in furtherance of its cross-appeal, challenged the soundness of two sentences in that paragraph, namely - (1) "Without the benefit of hindsight, I do not see why he would want to look for a pure polymorphic form of tibolone." and (2) "It seems to me that the 'obviousness' line of attack, as distinct from that based on anticipation, assumes that the skilled but unimaginative addressee of the patent would be looking to develop a pure polymorphic form of tibolone and would have had the knowledge of how to achieve it." It also consequentially challenged the final sentence of that paragraph in which the Lord Ordinary concluded that the skilled but unimaginative man would not "have had either the motivation or the means".

[129] On the matter of motivation (the first sentence challenged) it was submitted that the Lord Ordinary had failed to have regard to clear evidence from Dr. Newton that Declercq identified a method of producing a composition which was good enough to commercialise. Alternatively, it was argued, the finding of an absence of motivation ran wholly contrary to the evidence. In any event the Lord Ordinary had erred in law in that motivation, while relevant, was not an essential requirement for obviousness (Pharmacia Corp v Merck & Co. Inc., per Aldous L.J. at paras. 122-4). On the matter of means, (essentially the latter part of the second sentence challenged), it was submitted that no reasonable judge could have made such a finding given that the Lord Ordinary had already found that Declercq provided a method for producing (at least some) crystalline pure tibolone.

[130] It is clear that an appellate court must be very cautious in differing from the judge of first instance on a matter of obviousness, where that involves simply a matter of degree (Biogen, per Lord Hoffmann at page 45). In Merck & Co. Inc's Patents Buxton L.J., having expressed at para. 64, the opinion that an appeal court should interfere with the view of the trial judge only if he can be shown to have erred "in principle", added:

"In particular, it is likely to be very difficult to establish that such matters of principle are involved in decision made by the judge in assessing technical evidence and its bearing on the issues that he has to decide."

[131] Thus, in challenging, in a matter of obviousness, either the primary findings of the trial judge on the technical evidence or his secondary findings by way of inference from them, an appellant faces a formidable task. I am not persuaded that Arrow has demonstrated that the Lord Ordinary was not entitled to make the findings challenged. On the matter of means, Declercq, while giving the experimental parameters within which, by crystallisation through acetone, the single examined crystal had been obtained, did not purport to lay down a method of robustly and repeatably producing crystalline pure tibolone (such as Dr. Newton said a skilled person would wish to identify), far less such tibolone for use in a pharmaceutical composition. On the evidence it did not, contrary to Dr. Newton's cited report, "teach how to make a pure polymorph". So far as appears, a robust and repeatable method emerged only with the publication of claim 5 of the patent. The Lord Ordinary, accepting Professor Bernstein's evidence, had already held that the skilled but unimaginative addressee "certainly would not know how to obtain [a crystalline pure form]". On the matter of motive, I do not read the Lord Ordinary as proceeding on the basis that motive was necessary; rather that it was, as the cited authority demonstrates, relevant. The Lord Ordinary, for the purpose of his finding in the first sentence challenged, was prepared to assume that the skilled but unimaginative addressee knew that there was a likelihood that tibolone, being a steroid, was polymorphous. That assumption - in Arrow's favour - goes somewhat beyond what the Lord Ordinary was prepared to find as a fact, namely, that, while polymorphism was widespread in pharmaceuticals, particularly steroids, the skilled person would not know in advance of the discovery of more than one form whether or not a particular steroid, such as tibolone, was in fact polymorphous. But that assumption, which was carried forward by the Lord Ordinary into his answer to the second Windsurfing question, I am also prepared to make. However, even on that assumption, the Lord Ordinary was entitled, in my view, to question why the skilled person would, in the relevant state of the art, want to look for a pure polymorphic form of tibolone. He was entitled to reject, as his finding implicitly does, Dr. Newton's evidence that the skilled man "would want to define a single polymorph having suitable physical and bioavailability profiles" (Dr. Newton's Report para. 7.7) - at least for pharmaceutical purposes. As the Lord Ordinary said at para. [44] - "After all tibolone had been known from the 1960s and there was no evidence of any concerted effort to find out if it was polymorphous." Contrary to the submission made to us, Dr. Newton did not (at page 95) testify that Declercq identified a method of producing a composition good enough to commercialise. It plainly did nothing of the sort. All that Dr. Newton was able to say, as a matter of generality, was unsurprisingly that commercial pharmaceutical companies would be "looking for something that is good enough to commercialise". For these reasons Arrow's challenge to these findings of fact relative to the matter of obviousness, in my opinion, fails. If these findings cannot properly be disturbed, Arrow's challenge to the Lord Ordinary's conclusion on obviousness must, in my view, fail.

[132] I now consider, in relation to claim 1, the fourth stage of the Windsurfing approach. On this matter I arrive at the same answer as the Lord Ordinary but by a slightly different route. The use of tibolone to a high degree of crystalline purity as the active ingredient in a pharmaceutical composition was, in my opinion, not, on the basis of the Lord Ordinary's factual conclusions - unchallenged or not successfully challenged - obvious. Preliminary to that inventive step was the discovery by Akzo (not, of course, itself an invention) that tibolone was in fact polymorphous, with at least two crystalline forms. That discovery led in turn to the practical identification of the product, involving use in a pharmaceutical composition of crystalline pure tibolone having distinct advantages over a general mixture of forms, these advantages being stability and reproducibility. The skilled but unimaginative man, having the attributes so strikingly described by Laddie J. in Pfizer Ltd's Patent, would not, having regard to the Lord Ordinary's findings in relation to motivation and means, have taken these steps or any of them.

[133] I should add that I disagree with the Lord Ordinary in his identification (at the end of para. [43]) of the relevant issue as being "whether that knowledge pointed the way to the discovery of polymorphism in any particular case". The issue rather, in my view, is whether that knowledge pointed the way to the practical identification of the product, involving use in a pharmaceutical composition of crystalline pure tibolone with its attendant advantages. The discovery of polymorphism in tibolone was but a step on that journey.

[134] An identical answer falls, in my view, to be given at the fourth stage in respect of claims 2 and 3 to that in respect of claim 1. The contention that these claims are invalid by reason of lack of inventive step falls, in my opinion, to be rejected.

[135] The Lord Ordinary was also correct, in my view, in rejecting the challenge to claim 5 on the ground of obviousness. While Declercq provided the skilled man with the information that the single crystal there analysed had been obtained by crystallisation in acetone, that paper did not seek to lay down a method for preparing crystalline pure tibolone for use in a pharmaceutical composition. The difference (stage 3 of the Windsurfing test) was the subsequent admixture of water with a compound dissolved in bench acetone. The polar characteristics of water had, it seems, the effect of reliable crystallisation to a high degree (by weight) of monoclinic crystals. Indeed it was accepted by Arrow that if claim 5 fell to be construed as involving the use of (bench) acetone and water they would not seek to challenge the Lord Ordinary's decision on obviousness so far as that claim is concerned.

[136] Arrow also presented, under reference to SmithKline Beecham plc v Apotex, an argument on obviousness, in respect of claims 1-3, which was independent of the Windsurfing approach. That argument involved taking a simple and straightforward approach to the statutory criterion of inventive step (section 3 of the Patents Act 1977). But that argument, attractive as it was, proceeded on the basis that Declercq had disclosed tibolone at the levels of purity within claims 1-3 of the patent for use as a pharmaceutical, as well as a method of producing it using acetone. It also brought into account that as at the priority date tibolone (as Livial) had been marketed as a pharmaceutical. But there was no evidence to suggest that Livial involved any crystalline purity (in the sense discussed) of tibolone; and Declercq, although identifying and analysing a single crystal of tibolone and being work instructed by a pharmaceutical entity, did not disclose tibolone at the levels of purity within claims 1-3 for pharmaceutical purposes. In these circumstances this argument also falls, in my view, to be rejected.

[137] In the whole circumstances I move your Lordships to allow the reclaiming motion, to recall the Lord Ordinary's interlocutors of 11 and 25 October 2006, to refuse the cross-appeal, to sustain Akzo's third plea-in-law and to refuse the prayer of the petition.


FIRST DIVISION, INNER HOUSE, COURT OF SESSION

 

Lord President

Lord Kingarth

Lord Clarke

 

 

 

 

 

[2008] CSIH31

 

 

OPINION OF LORD KINGARTH

 

in

 

RECLAIMING MOTION

 

by

 

ARROW GENERICS LIMITED

Petitioner and Respondent;

 

against

 

AKZO NB (Represented in Scotland by ORGANON LABORATORIES LIMITED

Respondent and Reclaimer:

 

for

 

Revocation of Claims 1-3 and 5 of European Patent EP 0 389 035

 

_______

 

 

 

Act: Currie, Q.C., Higgins; Maclay Murray & Spens (Petitioners and Respondents)

Alt: McNeill, Q.C., Delibegović-Broome; McClure Naismith (Respondents and Reclaimer)

 

20 May 2008

 

[138] I have had the advantage of reading in advance the Opinion in draft of your Lordship in the chair, and I agree that the reclaiming motion should, for the reasons given, be disposed of in the way therein proposed. I would only seek to offer, in addition, a few comments to emphasise certain matters which appear to me to be of significance.

[139] The most difficult issue raised by the reclaiming motion relates to the question of the obviousness of claims 1-3. Despite the attractive simplicity of the position advanced by Arrow, I, like your Lordship in the chair, am not persuaded that it has been demonstrated that the Lord Ordinary was not entitled to make the underlying findings in fact which were challenged - in particular perhaps in relation to whether the notional skilled man could be said to have had the means to develop a pure polymorphic form of tibolone (of the purity described in the patent) for use in a pharmaceutical composition.

[140] Although Arrow sought to rely on Dr. Newton's evidence, in particular as summarised in paragraphs 7.6 to 7.10 of his report, referred to by the Lord Ordinary at paragraph [40] of his Opinion, it is, in my view, important to notice that the witness's starting point was that a skilled man wishing to develop tibolone as a pharmaceutical product would need to identify a robust and repeatable process for making a well defined stable form of the drug. Despite the witness's claim, at para.7.8 of the report, that the Declercq paper taught how to make a pure polymorph (by re-crystallisation from acetone), the Lord Ordinary not only rejected his evidence that it was likely that the whole sample from which the single crystal referred to in Declercq was selected consisted of crystals of the monoclinic form, but was, on the evidence, as your Lordship in the chair has noted, able to conclude only that, following the procedure envisaged in the prior art, the skilled person would ordinarily obtain crystals some at least of which were monoclinic. It was consistently accepted by all counsel before this court that, on the evidence, no more could be said (or indeed was found by the Lord Ordinary) than that. So far as appears, agreeing with your Lordship in the chair, a robust and repeatable method of producing tibolone completely or virtually completely free of crystals other than monoclinic crystals emerged only with the publication of claim 5 of the patent. That claim could not, Arrow themselves accept, be said to be obvious on the construction of it favoured by all the members of this court. Moreover, we were not, it appeared to me, referred to any clear evidence from which it could be said that the notional skilled man, having obtained tibolone consisting of a polymorphous mixture of crystals from crystallisation with acetone, would have been able readily to detect and isolate (not least on any robust and repeatable basis) some particular crystal or crystals for pharmaceutical use - even if he was motivated to do so, notwithstanding his accepted ignorance of the fact that tibolone was polymorphic.

[141] Further - although this would address, as I understood it, only part of the argument advanced by Arrow - while the Lord Ordinary, and the members of this court have held that the relevant claims of the patent are capable, as a matter of construction, of including a pharmaceutical composition with a single crystal of tibolone as the active ingredient, the question of whether it would be obvious to the notional skilled person to make such a product is, it seems to me, quite different. And we were not, I think, referred to any evidence to suggest that that would have been obvious, even using a single crystal of the form described in Declercq.

 

 


FIRST DIVISION, INNER HOUSE, COURT OF SESSION

 

Lord President

Lord Kingarth

Lord Clarke

 

 

 

 

 

[2008] CSIH31

 

 

OPINION OF LORD CLARKE

 

in

 

RECLAIMING MOTION

 

by

 

ARROW GENERICS LIMITED

Petitioner and Respondent;

 

against

 

AKZO NB (Represented in Scotland by ORGANON LABORATORIES LIMITED

Respondent and Reclaimer:

 

for

 

Revocation of Claims 1-3 and 5 of European Patent EP 0 389 035

 

_______

 

 

 

Act: Currie, Q.C., Higgins; Maclay Murray & Spens (Petitioners and Respondents)

Alt: McNeill, Q.C., Delibegović-Broome; McClure Naismith (Respondents and Reclaimer)

 

20 May 2008

 

[142] I am grateful to your Lordship in the chair for setting out the context in which this dispute arises and the relevant material placed before the court. I agree with your Lordship in the chair that the approach taken by the Lord Ordinary to the task of construction of the patent was misconceived for the reasons given by your Lordship and that that matter is now open for this court to decide.

[143] The proper construction of the patent, of course, impacts on the two questions of controversy before this court, namely, novelty and obviousness.

 

Construction of the Patent

[144] This issue was, in my judgement, left to be determined in a less than satisfactory basis, having regard to the state of the evidence before the Lord Ordinary. By that I mean that a good deal of discussion before this court revolved round the question as to whether or not claims 1-3 are capable of being properly construed as embracing a pharmaceutical composition containing one crystal of tibolone. That was a matter which, I suggest, could have been readily addressed in evidence before the Lord Ordinary. Given the apparent significance of this question - a question of fact - it is wholly unsatisfactory, in my judgement, that it was left to be determined ultimately by reference to counter-assertions from each side before us. For myself, therefore, I am left with a very distinct feeling of uneasiness as to whether this court has before it a complete and satisfactory basis for approaching the task of construction in respect of claims 1-3.

[145] Before the Lord Ordinary the "single crystal" issue was left by Akzo, the reclaimers, it seems, on the basis of a contention, recorded by the Lord Ordinary, at para [24] of his Opinion, in the following terms:

"The claims in the patent were to a 'pharmaceutical composition' containing the compound, i.e. tibolone. That must involve a recognition that a single crystal is not sufficient: a pharmaceutical compound clearly cannot be made of a single crystal" (my emphasis).

The Lord Ordinary's response to that argument, in part, is recorded at para. [27] of his Opinion where he states:

" ... it would have been open to Akzo to attempt to limit claims 1-4 by reference to some quantitative criteria. But, for whatever reason, they have not done so. It was not suggested that, even adopting a purposive construction, those claims should be read as incorporating some such criteria capable of being expressed with sufficient precision. Even if it had been so argued, I would have felt unable to construe the relevant claims as being restricted to pure Form 1 tibolone in some quantity greater than a single crystal. On that basis, the prior disclosure in Declercq of a single crystal of what we now know to be Form 1 tibolone and which, being a single crystal, is by definition 100% pure, is sufficient to invalidate claims 1-3".

As your Lordship in the chair has observed, this court has not been invited to make any new findings-in-fact. Whether or not claims 1-3 are capable of embracing a single crystal in a pill, capsule or tablet is left, therefore, to be determined by construing the words of the patent itself, without the assistance of any findings-in-fact based on the evidence of any skilled person or persons as to this issue.

[146] Senior counsel for Akzo, perhaps belatedly recognising the difficulty that the lack of relevant evidence on this point presented the court with, sought to support their contention as to the construction of claims 1-3 in this respect by carrying out certain calculations under reference, inter alia, to certain materials in Professor Bernstein's report, but these calculations were never put before the court below, far less as evidence before that court. They must, therefore, be disregarded.

[147] This case, to my mind, provides a salutary lesson for those who practice in this specialised area of the law of the very great need to explore, in evidence, questions of fact germane to the questions at issue, however obvious their answers may appear to them and their clients, so that the appropriate findings may be made by the court of first instance.

[148] In the foregoing state of affairs this court now has to interpret the words of claims 1-3, as they appear, applying the authoritative guidance provided in the cases referred to by your Lordship in the chair which require that a purposive approach be adopted in carrying out that task. As a matter of language, I am satisfied that the wording of these claims is capable of embracing a pharmaceutical composition containing a single crystal of tibolone. I think that Akzo themselves probably accepted this to be the case. Nevertheless they contended that, by adopting a purposive construction to the claims, under reference to the Description, a different conclusion should be arrived at. My consideration of the Description, however, does not lead me to put a qualification on the plain wording of claims 1-3 to exclude the possibility of a pharmaceutical composition containing a single crystal of tibolone. I have regard, in particular, to the statement in the Description at lines 45-48, page 2, which is to the following effect:

"The invention therefore relates to a pharmaceutical composition which contains a pharmaceutically suitable carrier and the compound having the structure (7ά, 17ά) - 17 hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn-3-one, characterized in that the said compound is a crystalline pure or virtually pure form which is completely or virtually completely free from the other crystalline form".

That statement does not exclude the possibility of such a composition comprising a single crystal of tibolone which would, ex hypothesi, be 100% pure. I have to remind myself that the notional addressee of this patent is the person skilled in the art and that I am not such a person. While a person skilled in the art may have said that a pharmaceutical composition consisting of a single crystal of tibolone would be regarded by someone like himself as either a nonsense or, alternatively, at least that it would be inherently improbable that it would be viable as an effective drug, no evidence to that effect was provided to the court below, and the position remains the same before this court. It would therefore be, in my view, quite illegitimate, in that state of affairs, for this court to speculate on such questions, far less to reach any conclusion by acting as if it were the skilled addressee. The court's task is one of construction of the words employed by the patentee. A purposive approach to the construction of those words does not, it seems to me, render it legitimate either to cut down or extend the clear meaning of the language of a claim, in the absence of relevant evidence pointing in that direction. Put another way, construction of the language must not lead to the court crossing into the forbidden territory of re-wording or amending the claim in the guise of construing it.

[149] For the foregoing reasons, I consider Akzo were inviting the court to trespass into that forbidden territory in suggesting that claims 1-3 did not include a claim of a monopoly in a pharmaceutical composition containing single crystal tibolone. It is, I think, of some interest to recall that Akzo contended that the references in claims 1-3 to "pharmaceutical composition" containing the compound tibolone involved a recognition that a single crystal was not sufficient. That contention seems to me to contain something of a non sequitur. As the Declercq paper itself states tibolone in a single crystal form is, scientifically speaking, a compound. The fact that the compound tibolone is to be contained in a pharmaceutical composition does not tell us anything about the quantity of the compound to be contained in the pharmaceutical composition and, accordingly, absent any other guidance from the language of the claims themselves and the Description, I reach the conclusion that claims 1-3 have to be read as embracing a pharmaceutical composition containing a single crystal of tibolone.

[150] That conclusion has, in my judgement, an important consequence when the question of obviousness falls to be addressed in due course.

 

Novelty

[151] Having reached the conclusion I have in relation to this issue then, along with your Lordship in the chair, I do not, however, accept the position of Arrow, otherwise, in relation to the question of novelty. I am not persuaded that the skilled addressee reading the Declercq paper, having regard to its scope and function, would have considered that it was addressing the advantages of having tibolone in a crystalline pure, or virtually pure, form for incorporation into a pharmaceutical composition. The Declercq paper, in my opinion, was designed simply to do what it says it was doing, namely to produce a structural analysis of the single crystal of tibolone presented to the writers of the paper for analysis. In a nut-shell, it seems to me, that Declercq did not disclose a pharmaceutical composition containing a pharmaceutical solid carrier and containing the compound tibolone in a crystalline pure form or virtually pure form. Nor did it disclose, in my view, a method for the preparation of such crystalline pure tibolone for use in pharmaceutical compositions according to claim 3, as claimed in claim 5. Arrow sought to bolster their case by emphasising that the scientific exercise carried out, upon which Declercq reported, was instigated by Organon themselves and that a member of Organon's scientific team, it seems, Dr. Van Zelen was involved in that exercise. To that matter should be added, it was said, the reference to be found in footnote 5 on the second page of the paper to the effect that tibolone was of interest for the treatment of menopausal complaints. Those features do not, in my view, go far enough to establish that the paper was disclosing the invention which has been patented. The nature and function of the Declercq paper is, for example, to be distinguished from the patent application by Blum in the Merk & Co. Inc's Patents 2004 7 FSR 16. I remind myself of the well-known dictum of Sachs LJ in the General Tire & Rubber Co. case where his Lordship said:

"To determine whether a patentees' claim has been anticipated by an earlier publication it is necessary to compare the earlier publication with the patentee's claim. The earlier publication must, for this purpose, be interpreted as at the date of its publication, having regard to the surrounding circumstances which then existed, and without regard to subsequent events. ... If the earlier publication, so construed, discloses the same device as the device which the patentee by his claim, so construed, asserts that he has invented, the patentee's claim has been anticipated, but not otherwise".

On the basis of what Declercq itself said, and the particular context in which he had said it, I consider that it did not disclose what the patentee asserts he has invented in claims 1-3 and 5. I do not read any of the evidence in this case as justifying the opposite conclusion. For these reasons I consider that Arrow's attack on the novelty of claims 1-3 and 5 fail.

[152] On the view that I have reached regarding novelty it is strictly not necessary to address the question of enablement. I would merely add that I agree with what your Lordship in the chair has to say about this matter.


Obviousness

[153] I now turn to consider the question of obviousness. On this topic I find myself in disagreement with your Lordship in the chair and Lord Kingarth. I agree with your Lordship in the chair that on this branch of the case the Lord Ordinary, for the reasons given by your Lordship, also materially misdirected himself. It, therefore, falls upon this court to look at this matter afresh. I do this, of course, in the context of my conclusion that claims 1-3 require to be construed as covering a pharmaceutical composition containing a single crystal of tibolone which is ex hypothesi pure.

[154] It appears to me that this chapter of the case has been somewhat obscured by the issue of when, and how, the polymorphous character of tibolone could have been discovered and was discovered. I note, in this connection, that the evidence of Akzo's expert, Professor Bernstein, was to a very large extent focused on that issue. Having regard to his relevant expertise and that of Dr. Newton, I note that Professor Bernstein is a general chemist with a particular interest in polymorphism and crystallisation and that Dr. Newton was willing to defer to Professor Bernstein on matters of pure crystallography. Dr. Newton, on the other hand, is a medical chemist who has worked with scientific companies, including Glaxo. What the skilled addressee would have known at the priority date, and what he would have taken from that knowledge, is something that Dr. Newton's evidence addressed in a way which was not subject to serious challenge.

[155] The court must approach the question of obviousness, in the first place, by identifying what is the inventive concept in each claim - see Pozzoli Spa v VBD MO SA [2007] FSR 37 per Jacob LJ at paras. [14]-[18]. It has to be kept in mind, too, that since a discovery cannot be an inventive step any inventive step identified in the claims cannot embrace the discovery of the polymorphous character of tibolone. The mistake of including a discovery in the reading of claims, in cases like the present, was highlighted by Lord Hoffmann in Kirin-Amgem Inc. v Hoecst Marion Roussel [2005] RPC 169 at 195 where his Lordship said this:

"I think that the Court of Appeal was right in saying that Table VI could not have been the invention. Standing alone, it was a 'discovery ... as such' within the meaning of section 1(2) of the Act see Genentech Inc's Patent [1989] RPC 147, per Purchas LJ at page 204 and per Dillon LJ at page 237.

On the other hand, as Whitford J said in the Genentech case [1987] RPC 553, 556:

'It is trite law that you cannot patent a discovery, but if on the basis of that discovery you can tell people how it can be usefully employed, then a patentable invention may result. This in my view would be the case, even though once you have made the discovery, the way in which it can be usefully employed is obvious enough.'

In such a case, while it may be true to say, as the Court of Appeal did ([2003] RPC 3) that Table VI lay 'at the heart of the invention', it was not the invention. An invention is a practical product or process, not information about the natural world. That seems to me to accord with the social contract between the State and the inventor which underlines patent law. The state gives the inventor a monopoly in return for an immediate disclosure of all the information necessary to enable performance of the invention. That disclosure is not only to enable other people to perform the invention after the patent has expired. If that were all, the inventor might as well be allowed to keep it secret during the life of the patent. It is also to enable anyone to make immediate use of the information for any purpose which does not infringe the claims. The specification of valid and subsisting patents are an important source of information for further research, as is abundantly shown by a reading of the sources cited in the specification for the patent in suit. Of course a patentee may, in some cases, be able to frame his claim to a product or process so broadly that in practice it will be impossible to use the information he has disclosed, even to develop important improvements, in a way which does not infringe. But it cannot be right to give him a monopoly of the use of the information as such."

[156] Accordingly, in the present case, the patentee has no monopoly in the discovery of the polymorphous character of tibolone. Counsel for Arrow paraphrased Lord Hoffmann's dictum by saying that even if polymorphism lies at the heart of the patent in suit, it cannot be the inventive step for the purposes of determining the question of obviousness. To use Lord Hoffmann's words, the "practical product" was crystalline pure or practically pure tibolone (in claims 1 and 2) and (in claim 3) crystalline pure monoclinic tibolone.

[157] Counsel for Arrow submitted that if the court accepted their submission that it was necessary to construe the patent to the effect that in claims 1-3 a single crystal was sufficient to meet the compositional element of the claim, then the conclusion inevitably had to be arrived at that what was being claimed in claims 1-3 was obvious. That conclusion would be arrived at by appreciating that, when one came to the third Windsurfing question, there was no difference between the inventive step and the prior art. Counsel said, that being so, the question fell to be asked as to what was the role of obviousness in this discussion. The response to that question, it was said, was that the role for obviousness came into play because the inventive concept was not coextensive with the matters claimed, for the purposes of anticipation. The evidence of Dr. Newton was that the pharmaceutical company which did not know that tibolone was actually polymorphous would nevertheless want to define the crystalline structure of that compound. That was supported by what Dr. Newton said at para. 7.7 of his report. If the court took the view that Declercq did not describe the use of pure crystalline tibolone in a pharmaceutical composition, contrary Arrow's primary submission, it should still find against Akzo on the question of obviousness because at stage 3 of the Windsurfing approach, in determining the difference between the inventive concept and the prior art, it was permissible to "mosaic". What did the evidence show was the prior art the skilled man would be aware of at the priority date? In the first place tibolone was a compound known since the early 1960s. Secondly, from the time of the Declercq paper the skilled man would have known that tibolone was being developed by a drug company and was of particular interest with regard to the treatment of menopausal complaints. Thirdly, its crystalline structure had been discovered as monoclinic form. Fourthly, by 1988, tibolone had been placed on the market in pill form, under the name Livial. Against that background, in relation to claims 1-3 the first question, it was said, was would it have been obvious to use Form 1 tibolone in a pill? The evidence of Dr. Newton supported the proposition that that question fell to be answered in the affirmative. The evidence of Dr. Newton was that a skilled man would also know that tibolone was a steroid and therefore possibly polymorphous. He would recognise the advantages of using a pure form. The exercise instructed by Oregon which resulted in the Declercq paper and its finding was reflective of such interest. Even in a situation where it was not known that there was more than one form of tibolone, the skilled man would want to know the crystalline structure of tibolone.

[158] It may be noted that the established science with which the present case is concerned was clearly described by Lord Hoffmann in the case of SmithKline Beecham plc's (Paroxetine Methanesulfonat) Patent [2006] RPC 323 at 329 where his Lordship stated as follows:

"The notion of crystalline form may require some explanation. The same substance may exist in different solid forms, depending upon the arrangement of its molecules. In crystalline form the molecules arrange themselves in an organised pattern called a lattice which gives the crystal a distinctive shape. On the other hand, in an amorphous form or an oil, the molecules are randomly distributed in a substance that has no particular shape. Some substances have only one crystalline form. They are called monomorphic. But others have a variety of patterns into which the molecules may arrange themselves. They are polymorphic. Different crystalline forms can be distinguished by a number of conventional tests. Infra-red ration ('IR') will result in a spectrum of readings of absorbance which are characteristic of their particular crystal. X-ray diffraction ('XRD') will likewise give a characteristic series of readings. The IR and XRD readings are the crystal fingerprints. Some compounds form one or more types of crystals which include, as part of their crystalline structure, molecules of the solvent from which the crystal has been precipitated. They are called solvates or, if the solvent is water, hydrates".

The evidence of both Dr. Newton and Professor Bernstein, in the present case, was if you crystallised from acetone you would expect to get some Form 1 tibolone (see the Lord Ordinary at paragraph [37] of his Opinion). The conclusion therefore had to be, it was submitted on behalf of Arrow, that it was not inventive to use monoclinic tibolone as an ingredient in a pharmaceutical concept. Knowing, as he would, that the tibolone might be polymorphic the skilled man would be interested in having it in a pure form. If you are crystallising from acetone and you are obtaining some Form 1 tibolone then, for the purposes of the present discussion, it was said, it did not matter that in the course of that you might also come across some Form 2 tibolone. The basic point was that the placing of pure form tibolone (which ex hypothesi would include a single crystal) in a pharmaceutical composition could not be said to be inventive.

[159] I am bound to say that I waited, somewhat in vain, to hear from counsel for Akzo for the answer to these submissions. While senior counsel for Akzo did accept that the approach of Jacob LJ in the Pozzoli case (supra) was correct, in requiring that, in dealing with the question of obviousness, the inventive step in each claim had to be addressed, he did go on to say that this was subject to the proviso that there may be cases where the claims are so linked that you should treat them as having a single inventive step. Senior counsel, however, frankly accepted that he could refer to no authority expressly supporting this suggestion or illustrating its application. It did seem to me that in making that submission, senior counsel was, in effect, seeking to support the Lord Ordinary's approach to the question of obviousness, which your Lordship in the chair has, in my view, correctly exposed to be misconceived. What counsel for Akzo seemed to be doing, it seemed to me, was seeking to introduce, by implication, the process aspects of the patent into the product aspects which are covered by claims 1-3.

[160] I have a further difficulty with Akzo's position in this aspect of the case. As I read Professor Bernstein's report it does not really address the question of obviousness in relation to what the inventive steps, properly identified, in the claims are. Dr. Newton's report clearly does. I do not read the passages of evidence from Professor Bernstein, to which senior counsel for Akzo drew our attention, as addressing the issue. Professor Bernstein's main concern was to address the question of polymorphism and if and when it might have been discovered. It seems to me that the Lord Ordinary's treatment of the issue was driven by a concentration on the question of polymorphism, its discovery and how it might have been addressed. But for the reasons advanced by counsel for Arrow, I consider that that misses the point. The discovery of polymorphism and processes designed to deal with it or to employ the knowledge of the discovery are not embraced in claims 1-3. If one accepts, as I do, (1) that the inventive concept in claim 1 was tibolone with a crystalline purity of greater than 90% in a pharmaceutical composition, (2) that in claim 2 it was tibolone of crystalline purity greater than 95% in a pharmaceutical composition and (3) in claim 3 Form 1 tibolone with a crystalline purity greater than 95% in a pharmaceutical composition then, having regard to the evidence of the prior art and Dr. Newton's evidence as to the position of the skilled person at the priority date, it cannot be said, in my view, that there was anything inventive about using tibolone as a pharmaceutical. The only question then remains was there anything inventive in putting crystalline pure Form 1 tibolone in a pharmaceutical? I agree with counsel for Arrow that the Lord Ordinary at paras. [34] and [35] of his Opinion has held, at least in effect, that Declercq disclosed pure form tibolone and a method of making it. The Lord Ordinary also held that as a matter of fact the incorporation of tibolone into a pharmaceutical composition could not by itself be inventive - see paragraphs [29] to [33] of his Opinion. On the unchallenged finding of the Lord Ordinary a skilled person, at the priority date, knew of tibolone, knew that it was likely to be polymorphic and would be interested in Declercq, which disclosed a single form of pure tibolone and a method of producing it. I agree with counsel for Arrow that the skilled man would be someone interested in useful developments in the pharmaceutical field, particularly, in the context of this case, in the field of steroids. What was seen in Declercq is a crystalline form of tibolone which would have been of interest to the skilled man to put in a pharmaceutical. On the findings of fact of the Lord Ordinary, I have been unable to find any basis for rejecting Dr. Newton's evidence given at paragraphs 7.7 and 7.8 of his report. It seems to me that counsel for Akzo never produced an answer to the submissions made on behalf of Arrow to the effect that Declercq disclosed tibolone in the crystalline structure subsequently known as Form 1 at a level of purity contained in claims 1-3, with a method to produce it, using acetone. If full regard had been paid to these matters and the fact that at the priority date of the patent, tibolone was already being marketed as a pharmaceutical, the answer to the question as to whether it would have been obvious to the skilled person to use "Declercq" tibolone in a pharmaceutical composition would have been in the affirmative.

[161] As was accepted on both sides of the Bar the question of obviousness is a question of fact. It has been described as being in the nature of a jury question. Sometimes it has been described as involving questions of impression, or feel, based on the evidence, rather than on any exact definitive analysis. The "Windsurfing" approach is an attempt to address the question. It was reformulated, or summarised, by Jacob LJ in SmithKline Beecham plc v Appotex Europe Limited (2005) FSR 524 at 539 as follows:

"Often the nature of the enquiry is helped by the well-known Windsurfing steps, (1984) RPC 59 at page 74. I summarise:

a) identify the inventive concept of the claim;

b) identify the common general knowledge of the skilled man;

c) identify the difference(s) between the prior art under consideration and

that in the inventive concept of the claim;

d) ask whether the difference(s) would have been obvious or require

invention".

His Lordship went on to say

"No one suggests that this is always the appropriate test. In the end the enquiry is simply that posed by the statute, as for instance, Sir Donald Nicholls VC pointed out in Mlnyke v P & G (1994) RPC 49 at pp. 112-3. He went on to say, at p. 113:

'In applying the statutory criterion (i.e. as to whether an alleged inventive step was obvious) and making these findings (i.e. as to obviousness) the court will almost invariably require the assistance of expert evidence. The primary evidence will be that of properly qualified expert witnesses who will say whether or not in their opinions the relevant step would have been obvious to a skilled man having regard to the state of the art.'"

I have already, in another context, expressed some misgivings about the way in which the evidential basis of the parties' respective positions in this case were dealt with before the Lord Ordinary. I am of course conscious of the need for an appellate court to exercise great caution in differing from the trial judge's evaluation of facts, - see Biogen v Medeva [1997] RPC 1 at page 45. But in a situation like the present, where I consider that, in relation to the question of obviousness, there has been a serious misdirection by the court of first instance, I consider that this court has to do the best with the evidence led and the unchallenged findings-in-fact of the Lord Ordinary, in reaching its own evaluation. The conclusion on obviousness (a matter of fact) has to be evidence - based, drawing from witnesses who have the appropriate experience and qualifications. It seems to me that the evidence as regards prior art and the evidence of Dr. Newton, which alone specifically addressed the question of obviousness in the proper context of the inventive steps embraced in the claim, did provide adequate support for Arrow's contention that what is embraced in claims 1-3 involves no inventive step for the reasons advanced by them. In my view the only evidence led by Akzo, which came from Professor Bernstein, did not provide any evidential basis for rebutting the position advanced by Arrow and in particular contradicting Dr. Newton. Moreover, having regard to the respective qualifications and experience of these witnesses it seems to me that Dr. Newton's evidence carried with it greater authority, in any event, in relation to this chapter of the case than did Professor Bernstein's.

 

Conclusion

[162] To sum up, upon discovery of the polymorphous character of tibolone, the patentee, no doubt, sought to address the consequences of that discovery. In my judgment, however, they did so by virtue of what is addressed in claims 4, 5 and 6. In claims 1-3, however, as they are worded, what was being claimed was the incorporation of monoclinic P21 form tibolone, up to a level of purity greater than 90%, which would include 100%. Claims 1-3 do not address the means (whether robust or otherwise) whereby a purity of more than 90% of monoclinic P2 tibolone is to be produced. They are, as previously noted, product claims, not process claims. They seek a monopoly in the product so described. My acceptance, shared by all members of this court, of Arrow's submission that these claims required to be read as embracing single crystal pharmaceutical compositions has to be kept in mind. The composition, tibolone, had been known since the 1960s. I accept that the skilled man would, at the priority date, have known that it was being developed by a drug company and was of particular interest in relation to the treatment of menopausal complaints. After Declercq, he knew also that the crystalline structure had been discovered as monoclinic form. Prior to the priority date tibolone had been put on the market in pill form. The question then comes to be, whether it would have been an inventive step to do what claims 1-3 embrace. The answer to that question was, on the evidence, supplied by Dr. Newton at para. 7.8 of his report where he said:

" ... by following the teaching of the 279 to make the compound and then re-crystallising from acetone as taught by the 1984 (Declercq) Paper the skilled man would have a method of preparing pure form 1 polymorph".

Dr. Newton then continued at para. 7.9:

"For these reasons I think that claims 1 and 2 of the Patent are obvious since the 1984 (Declercq) Paper already described Form 1 Tibolone. Claim 3 is likewise obvious since the 1984 (Declercq) Paper precisely describes the crystal structure referred to in the Patent as monoclinic P21 form".

I repeat that the knowledge, or otherwise, of the discovery of the polymorphous character of tibolone seems to me to have bedevilled the discussion of this question and certainly led, in my view, the Lord Ordinary to misdirect himself when dealing with the matter. On this branch of the case, it seems to me that the question is, can it be said to be inventive to place a single crystal of monoclinic form 1 tibolone in a pill, tablet or capsule? Judging matters from the viewpoint of the skilled man who was aware of only Form 1 monoclinic tibolone as at the priority date, I agree with Arrow that, on the evidence, it cannot.

[163] Lastly, I agree with your Lordship in the chair for the reasons given by you that claim 5 does not fail the obviousness test and there is nothing that I can usefully add to what your Lordship has said on that subject.

[164] In the event, however, for the reasons given, I conclude that claims 1-3, as drafted, do fail that test and as Akzo have not sought to amend the patent, it falls to be revoked for that reason.