1.

The Italian jurisprudence has been among the first in Europe to react against an excessive interpretation of those kinds of product claims in a chemical patents that are called (in the international patent terminology) Markush claims [1] .

A Markush claim refers to a chemical structure by means of symbols indicating substituent groups. In such a claim, one or more parts of the claimed compound comprise multiple functionally equivalent chemical entities.

An example of Markush claim is claim 1 of the patent granted to Eugene Markush [2] :

“1. The process for the manufacture of dyes which comprises coupling with a halogen-substituted pyrazolone, a diazotized unsulphonated material selected from the group consisting of aniline, homologues of aniline and halogen substitution products of aniline.”

It is a surprisingly simple example, compared to more recent cases.

A more recent example is claim 1 of EP 0 697 157, which was litigated in England [3] .

In this paper I intend to examine what should be the scope of protection in Europe [4] of a Markush claim for chemical compounds.

2.

A Markush claims cover a wide series of possible compounds. Sometimes, the series may encompass billions or trillions of variants; sometimes the series is unlimited. For patent EP 0 535 152 [5] , for instance (by no means the more complex Markush patent), I have calculated (perhaps conservatively) that the minimum number of compounds covered by the literal wording of the patent could be 10 followed by 60 zeroes, namely: 1.000.000.000.000.000.000.000.000.000.000.000.000.000.000.000.000.000. 000.000.000 [6] .

Now, if we have also to take into consideration that the scope of protection could perhaps be enlarged beyond the literal wording of the claim, to encompass equivalent compounds, we see that there is a risk of protecting too much [7] .

3.

The Italian jurisprudence was confronted with Markush claims in the Cefatrizine and in the Cimetidine cases [8] . The Supreme Court limited the scope of protection from two points of view:

a) first, it stated that the protection is not absolute, for all possible uses of the compound, but limited instead to the claimed use;

b) secondly, it stated that what are covered are the compounds which are specifically indicated, as well as the compounds which are not expressly claimed, provided that the skilled man would have found them without inventive effort (said effort to be evaluated at the time of the application).

“The chemical invention is not to be identified in the simple formulation of a molecular structure, but in the structure as aimed to have a certain function thanks to the properties of the compound; and in relation to the possibility of protection of a compound which is not singularly identified in the patent application but “selected” with following integration and added claims it has to be pointed out that a compound which a skilled person in the art would have been able to derive, at the time of the patent application, only by adding a further inventive step does not fall within the protection scope of the patent.”

It seems to me that these limitations are sensible. However,

- the first could perhaps have been justified on different grounds, such as the fact that the protection can only correspond to the technical contribution, and that the technical contribution in the specific case was limited to the use indicated (therefore, the protection is limited not because of particular principles applicable to chemical patents, but because it can only correspond to the invention);

- the second limitation cannot be intended as the only possible one, since it still leaves an enormous area of protection, well beyond the scope of the invention (the scope of the patent being greater than the scope of the invention).

I believe more refined rules of interpretation have to be indicated.

4.

The English jurisprudence has also been confronted with Markush claims. In the Biogen v. Medeva case [9] , the House of Lords (per Hoffmann, L.J.) developed the theory that, in addition to the classical case of enablement (which is an aspect akin – but not identical - to sufficiency of disclosure, as we would call it in Italy), there is another criteria.

“The specification must enable the invention to be performed to the full extent of the monopoly claimed. If the invention discloses a principle capable of general application, the claims may be in correspondingly general terms. The patentee needs not to show that he has proved its application in every individual instance. On the other hand, if the claims include a number of discrete methods or products, the patentee must enable the invention to be performed in respect of each of them…

Thus if the patentee has hit upon a new product which has a beneficial effect but cannot demonstrate that there is a common principle by which that effect will be shared by other products of the same class, he will be entitled to a patent for that product but not for the class, even though some may subsequently turn out to have the same beneficial effect… …

In Genentech I/ Polypeptide expression the Technical Board (of the European Patent Office) [10] spoke of the need for the patent to give protection against other ways of achieving the same effect “in a manner that could not have been envisaged without the invention”. This shows that there is more than one way in which the breath of a claim may exceed the technical contribution to the art embodied in the invention. The patent may claim results which it does not enable, such as making a wide class of products when it enables only one of those products and discloses no principle which would enable others to be made. Or it may claim every way of achieving a result when it enables only one way and it is possible to envisage other ways of achieving that result which make no use of the invention” [11]

And in a later passage Hoffmann said:

“Does this contribution justify a claim to a monopoly of any recombinant method of making the antigens? In my view it does not. The claimed invention is too broad. Its excessive breath is due, not to the inability of the teaching to produce all the promised results, but to the fact that the same results could be produced by different means. Professor Murray had won a brilliant Napoleonic victory in cutting through the uncertainties which existed in his day to achieve the desired result. But his success did not in my view establish any new principle which his successors had to follow if they were to achieve the same result. The inventive step, as I have said, was the idea of trying to express unsequenced eucaryotic DNA in a prokaryotic host. Biogen

discloses… the way to do it…. This, if anything, was the original element in what Professor Murray did. But once the DNA had been sequenced, no one would choose restriction enzymes on this basis. …The metaphor use by one of the witnesses was that before the genome had been sequenced every one was working in the dark. Professor Murray invented a way of working with the genome in the dark. But he did not switch on the light and once the light was on his method was no longer needed”.

The fundamental principle is that the monopoly should correspond to the “technical contribution”. For that part of the claim that exceeds the tecnical contribution there is an insufficiency, which has been called “Biogen insufficiency”.

Hoffmann said:

“It is said that what Professor Murray showed by his invention was that it could be done. HBV antigens could be produced by expressing Dane particle DNA in a host cell. Those who followed, even by different routes, could have greater confidence by reason of his success. I do not think that that is enough to justify a monopoly of the whole field. I suppose it could be said that Samuel Morse had shown that electric telegraphy could be done. The Wright brothers showed that heavier-than-air flight was possible, but that did not entitle them to a monopoly of heavier-than-air flying machines. It is inevitable, in a young science like electricity in the 19th century or flying at the turn of the last century or recombinant DNA technology in the 1970s, that dramatically new things will be done for the first time. The technical contribution made in such cases deserves to be recognised. But care is needed not to stifle further research and healthy competition by allowing the first person who has found a way of achieving an obviously desirable goal to monopolise every other way of doing so.”

The concept of technical contribution is fundamental for the interpretation of Markush claims.

In the decision of the Technical Board in T409/91, Exxon/Fuel Oils [12] it was said:

“The claims must be supported by the description, in other words, it is the definition of the invention in the claims that needs support. In the Board’s judgement, this requirement reflects the general legal principle that the extent of the patent monopoly, as defined by the claims, should correspond to the technical contribution to the art in order for it to be supported or justified”.

And also the Italian Supreme Court [13] found that reference to the technical contribution was essential for limiting the Cefatrizine patent:

“ The general principle that applies to patent matters (is that) the scope of protection must correspond to the actual contribution brought by the inventor to the state of the art. To sustain a different view would imply to permit, especially for the chemical sector, to extend patent protection to all possible combinations which can be hypothetically derived from a basic formula, allowing them to be inserted in the scope of protection even though they are not described, in their specific properties and uses, in the original application".

Furthermore, “the original description and claim determine the scope of exploitation of one’s own invention, defining the subject and the content of the protection itself. …protection is asked for a compound which is the result of research carried out until that moment… The lower Court has correctly observed that the inventor can not reserve for himself any possible (developments and) inventions following the first discovery, as otherwise he would be granted a sort of inadmissible anticipated monopoly related to all discoveries which in some way are connected to the first one.”

5.

[While efforts were made in Italy and England, the situation in Germany was and is different. With due respect, I believe that the German system, which is characterised by the separation of the evaluation of validity and infringement, may have great difficulties in dealing with Markush claims [14] . An example is the decision of the Duesseldorf Landgericht of Apr. 2, 1996 in a Erythropoietin (EPO) German case. [15]

The accused infringer (who did a O-glycosilation of the recombinant human EPO) was found to fall within the claims of the patent in suit. But since he was producing under a license of an older patent, the Court found a way out and said:

“Defendant can (be absolved if) he uses exclusively the features of the claims of the licensed patent and not additional features which can only be found in the claims of the patent asserted by the plaintiff…”

And in a subsequent passage:

“While the O-glycosilation of the recombinant human EPO protein as claimed in claim 8 of the patent in suit is not disclosed in the licensed patent, this fact does not permit the conclusion that the content of the disclosure of the licensed patent is limited to a recombinant human EPO without O-glycosilation… The sole decisive point in the present case is the fact that when repeating the teaching of the licensed patent the man skilled in the art will involuntarily arrive at an EPO glycoprotein with O-linked glycosilation of the kind practised by the defendant. Whether… the inventor of the licensed patent recognized the presence of O-glycosilation, or whether that remained concealed to him because of an analytical error, or whether he was unable to recognise O-glycosilation at all because he had used a mutagenic host cell, is irrelevant.”

(It seems to me that this is a way of applying with some anxiety a sort of modified Formstein theory) [16] .]

6.

The two theories above indicated in point 3 and 4 limit the scope of a Markush claim. But there are also some other reasons to limit such a claim. A Markush claim cannot encompass variants which are

- not new (in fact, due to the very wide extension of the formula, it may happen that some products were already described or obtained [17] );

- if new, not sufficiently distinct from the prior art (those products, according to the Formstein theory [18] , cannot be included in the scope of the patent. A patent in fact cannot cover what is not new because prior art, nor an obvious variation of the prior art, even if new);

- if new and distinct, not enabled in a classical manner (in fact, always due to the wide extension of the formula, some products can be not identified [19] or non-obtainable);

- or that do not have the effect indicated by the inventor.

7.

All the limits of the claim can result in the situation that I will better illustrate with a drawing.

If we design the vague area that may embrace all possible variants included in the Markush formula, and assuming for a moment that it can be a finished area (I will call it the Markush area), several areas can also be included.

a)The first area inside the Markush area encompasses those compounds which are not new, or are an obvious variation of the prior art, or do not present the technical effect indicated by the inventor, or are not workable, or can only be obtained, on the basis of the teaching of the patent, with undue burden [20] . I will call it the classical non-appropriable area. This area should be excluded from protection according to all classical theories. (In England, the lack of enablement for being the description insufficient to allow the production has been called “classic insufficiency”).

b)The second area, identified by the Italian Supreme Court, encompasses those products that can be found with inventive activity. I will call it the Cimetidine insufficiency area.

c)The third area, identified by the House of Lords, encompasses those products that do not correspond to the technical contribution of the inventor. I will call it the Biogen insufficiency area [21] .

c) The forth area corresponds to the technical contribution. The scope of the patent should be limited to this area. It can simply be called the scope of the patent [22] .

Avv. Prof. Mario Franzosi

[1] Markush claims were named after the U.S. patent application of Eugene Markush, although he was not the first inventor to include this type of claims. U.S. patent 1,506,316, granted on Aug. 26, 1924.

The expression “Markush claims” may also be used to express somehow different concepts. Here is used to indicate a kind of (too) broad claims.

[There are (too) broad claims of other kind, especially in life science:

i. reach-through;
ii. therapy regime;
iii. mechanism of action;
iv. target group.

A general configuration of these claims would be:

Use of a

i. ABC agent (e.g., inhibitor) in the preparation of a medicament
ii. for the (mode of) treatment
iii. of (disease or condition X)
iv. in a (target group) patient.

These claims are intended to secure a broader patent protection, in particular a “downstream protection” further down the development pipeline, starting from gene to protein, from protein to protein effectors or inhibitors of all possible kind. I do not intend to examine here these kinds of claims. In common with Markush claims is the fact that claims are too broad].

[2] See footnote 1.

[3] Mentioned in the UK decision of Feb. 4, 2000 by Pumfrey J., Monsanto Co. et al. v. Merck & Co. Inc et al.
Claim 1 of said patents reads as follows:

“A compound of Formula I

I

wherein Y is selected from S, O and NR1;
wherein R1 is selected from hydrido and C1-C6 alkyl;
wherein X is one or more substituents selected from

a) (i) hydrido
(ii) halo
(iii) cyano
(iv) nitro
(v) hydroxy
(vi) acyl
(vii) lower alkyl substituted at a substitutable position with a substituent selected from halo, hydroxyl,
mino, acylamino, lower alkylamino, lower alkyl(acyl)amino, acyl, aryl optionally substituted with hydroxyl, a heterocyclic group, hydroxyimine and lower alkoxyimine,
(viii) lower alkonyl optionally substituted at a substitutable position with cyano,
(ix) amino optionally substituted at a substitutable position with a radical selected from acyl and lower alkylsulfonyl,
(x) sulfo,
(xi) sulfamoyl optionally substituted with a substituent selected from the group consisting of lower alkyl, halo(lower)alkyl, aryl, hydroxyl, lower alkylamino(lower)alkyl, a heterocyclic group and (esterified carboxy)lower alkyl,
(xii) N-containing heterocyclicsulfonyl,
(xiii) a heterocyclic group optionally substituted at a substitutable position with a substituent selected from the group consisting of hydroxyl, oxo, amino and lower alkylamino, provided that when Y is O or NR1 then X cannot be hydroxyalkyl,
(b) S(O)nR5, wherein R5 is C1-C6 alkyl optionally substituted at a substitutable position with fluoro, and n is 0, 1 or 2,
c) C(R6)(OR8)(R7) wherein R6 and R7 independently are selected from CF3, CF2H, CFCl2, CF2Cl, CClFH, CCl2F, CF3CF2 and C1-C2 alkyl, and wherein R8 is selected from hydrido, C1 -C4 alkyl, (C1-C3 alkyl)C(O) and CO2R9 wherein R9 is C1-C4 alkyl,
d) C(O)ZR4, wherein Z is O, N, or S, and R4 is selected from hydrido, C1-C5 alkyl and aryl, and when Z is N then R4 is independently taken twice, and
e) C(R9) (NHR11) (R10), wherein R9 and R10 are independently selected from CF3, CF2H, CFCl2, CF2Cl, CClFH, CCl2F, and R11 is selected from hydrido and C1-C3 alkyl, and
wherein R2 and R3 are independently selected from aryl or heteroaryl, wherein the aryl or heteroaryl radical is optionally substituted at a substitutable position with a radical selected from halo, lower alkyl lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, nitro, amide, amino, lower akylamino, sulfamyl and lower alkylsulfonylamino, provided that at least one of R2 and R3 is substituted with methylsulfonyl or sulfamyl;
or a pharmaceutically acceptable salt thereof”.

[4] I will consider European patents. The conclusions should be identical for national patents.

[5] Claim 1 of EP ‘152 takes more than 4 pages, and therefore I will not reproduce it.

[6] Bianchetti reports of a claim that may cover a number of compounds represented by 10 followed by 35 zeroes. In I nuovi Brevetti. Biotecnologie e invenzioni chimiche, Milano 1996.

[7] Also a claim for a mechanical invention covers myriad of possible realisations. For instance, a claim for two wood planks connected by a screw (assuming it is patentable) would cover myriad of kinds of planks, connected with myriad of kinds of screws. However, all kinds of planks, and all kinds of screws, are identifiable, and their way of operation is predictable by the notional addressee. (The expert can even extend the scope of the patent to equivalent embodiments, like planks connected with nails or glue). This does not occur for most chemical compounds, or most of them (if not all), whose behaviour has to be tested in the real word.

[8] Smith Kline & Beecham v. Biochimica Opos, Supreme Court March 6, 1995, n. 2575, GADI 1995, 3194 (Cefatrizine): Smith Kline & Beecham v. Bruschettini, Supreme Court Sept. 1, 1997, n. 8324, GADI 1997, 3574 (Cimetidine).

[9] Biogen Inc. v. Medeva Plc, [1997] RPC 1

[10] Words in brackets added by me. The decision is T 292/85 [1989] O.J.E.P.O. 275.

[11] Pages 47 ff.

[12] 1994 OJ EPO 653

[13] March 6, 1995, n. 2575 quoted at footnote 8.

[14] And this even if the Courts may deduce a narrower teaching than that seemingly conveyed by the wording of a feature. Meier-Beck, The Latest Issues in German Patent Infringement Proceedings, 32 IIC 505.

[15] 4 O 58/92, Judges Meier-Beck, Becker and Schuh-Offermanns.

[16] See note 18.

[17] It would be practically impossible to conduct a complete search. In fact, the books that may contain the formulas of all the compound of the patent mentioned by Bianchetti in the footnote 6, above, would occupy all the space of an ideal sphere having as a radius the distance between the Earth and the Moon. Possibly the books reproducing the formulas of all the compounds of the patent mentioned at point 2 may occupy all the Solar system.

[18] The Formstein theory was developed by the German Supreme Court, with the decision BGH 1986 GRUR 803, 18 IIC 795. According to this theory, a patent cannot cover not only those embodiments which belong to the prior art, but also obvious variations of the prior art.

There is a difference between the theory as it is used here and the German Formstein defense. In Germany, the Formstein defence can only be used to avoid infringement by equivalence, but not literal. See BGH Kontaktfederblock 1999 GRUR 914, 32 IIC 93. See also Meier-Beck, 2000 GRUR 351). In case of a Markush claim an accused product can be covered by the broad literal scope of the claim; however it is not an infringement since it is an obvious derivation from the prior art.

A similar formulation of the Formstein defence, which is not limited to the case where there is no literal infringement, is in Wilson Sporting Goods Co. vs. David Geoffrey & Associates, CAFC (United States Court of Appeals fo the Federal Circuit) (1990) 904 F.2nd 677, and in the so called Gillette formula o Gillette defense: Gilette Industries Ltd v. Anglo American Trading Co. Ltd, (1913) 30 R.P.C. 465.

[19] In American Home Products Corp. v. Novartis, U.K. Court of Appeal July 27, 2000 Case A2/1999/1278, [2001] RPC 8, Aldous, LJ said: “There is a difference between on the one hand a specification which requires the skilled person to use his skill and application to perform the invention and, on the other, a specification which requires the skilled person to go to the expense and labour of trying to ascertain whether some product has the required properties. When carrying out the former the skilled person is trying to perform the invention, whereas the latter requires him to go further and to carry out research to ascertain how the invention is to be performed. If the latter is required the specification would appear to be insufficient”.

In the terminology used in this article, the former is a classic insufficiency; the second a Biogen insufficiency. The distinction was made in Amgen v. Roche, Apr. 11 2001 by Neuberger J., [2002] R.P.C. 1. See Curley-Toumi, Gene Genie: the United Kingdom Patent Court Uncorks Biogen Insufficiency, 24 EIPR 40 [2002]. The distinction was criticized by Aldous, L.J. in Kirin Amgen v. TKT, July 31, 2002: “Sect. 72 (1) provides just one ground of insufficiency”. See also Bostyn, A European Perpective on the Ideal Scope of Protection and the Disclosure Requirement for Biotechnological Inventions in a Harmonised Patent System, 5 J.W.I.P. 1013 at 1032; Sheraton-Sharples, The Court of Appeal Puts Bigen Insufficiency Back Where it Belongs, 24 EIPR 596 [2002]. I believe the question is a matter of terminology. Classic insufficiency means that the patent is invalid, at least to the extent it is insufficient. Biogen insufficiency means that the patent does not cover the area that exceeds the technical contribution.

[20] A patent cannot cover a product that can be obtained following the teaching of the patent, but only with “undue burden”. In this case the description is not enabling (or the patent is classically insufficient).

[21] See note 19.

[22] I reserve the point whether a Markush claim may have an area of equivalence, and whether it may cover a dependent invention.