T 0020/83 (Benzothiopyran derivates) of 17.3.1983

Summary of Facts and Submissions

I. European patent application No. 79 100 325.4 received on 5 February 1979 and published on 14 November 1979 (publication number 0 005 141)... was refused by decision of the Examining Division of the European Patent Office dated 2 September 1982 on the basis of the claims received on 7 December 1981.

II. The aforementioned claims fulfilled all the purely formal requirements of the EPC. The sole issue decisive to refusal was whether inventive step was present in a representative number of compounds out of the whole range of substances according to Claim 1. Such was deemed to be the case. Claim 1 reads as follows: Effective anti-allergic compounds having the same basic structure as the compounds according to the application, i.e. 4-oxo-4H-1-benzothiopyran, were already known from US-A-4 013 771 (Citation 1). DE-A-2 509 547 (Citation 2) suggested to the skilled man that the oxaloamino residue, when connected to a particular sulphur-containing heterocyclic system represented a group contributing a pharmacological effect manifested in anti-allergic properties. It was therefore a matter of course for a pharmaceutical chemist to combine the oxaloamino group with the above-mentioned basic structure to create new anti-allergic preparations. Consequently, to be patentable, the compounds claimed would have to have surprising anti-allergic properties...

III. On 13 October 1982, the appellant filed an appeal and, on 23 December 1982, a Statement of Grounds the substance of which was as follows: the only point in dispute was whether the subject-matter of the claim ... involved an inventive step. The EPC did not substantiate a contention that all the compounds covered by a claim had to show inventive step as a positive attribute; that patentability criterion was fulfilled if the negative attribute of obviousness having regard to the state of the art was absent.

Reasons for the Decision

1. The appeal complies with Articles 106 to 108 and Rule 64 EPC, and is, therefore, admissible.

2. The admissibility of the current version of the claim, established in the decision of the department of first instance without reference to sources in the initial disclosure, seems questionable to the Board in more than one respect...

3. The Examining Division adjudged the subject-matter of the claim, having regard to the state of the art as contained in citations 1 and 2, to be obvious and made patentability dependent on substantiation of a surprising anti-allergic effect, which it deemed not to be present. The Board, however, views the subject-matter of Claim 1 as qualitatively surprising, so that the question of surprising quantitative superiority can be left aside...

4. As the Examining Division quite rightly finds in the impugned decision, the nearest citation (Citation 1) describes 2-aminothiochromones, which also form the basic structure of the compounds according to Claim 1 of the present application, insofar as 4-oxo-4H-1-benzothiopyrans are claimed (cf. also Formula 1b on page 10 of the description). The known compounds contain in the two-position an amino group and in the 3-position a cyano or carboxamido residue, i.e. residues that are not present at all in the claimed compounds. These two positions can, according to the application, be unsubstituted or substituted by certain residues with the meaning indicated for R1 and R2. Furthermore, according to the application, the benzene ring (Ph) fused to the thiopyran ring contains the residue R-CO-NH-, which is again absent from the known compounds. Citation 2 relates to anti-allergic thiophenes, benzothiophenes or thiophenes to which a saturated residue -either carbocyclic or containing N or S -is joined in the 4,5-position. The common feature of all these known compounds is the basic thiophene structure substituted in the 2-position by the - possibly esterified - oxamino acid group. It is primarily in the basic structure that the claimed compounds differ from these known ones and the subject-matter of the application is therefore new.

5. When assessing chemical substances for inventive step, it is often their surprising properties that are considered, as in the present case. It is the prevailing opinion that such properties are essentially determined by the substances'structure, which according to current thinking is comprised of characteristic structural elements, the basic structure and the type and position of substituents. Since scientifically attested connections between the structure and properties of chemical substances are the exception rather than the rule, empirical data and analogy have to be relied upon, more often than not, in predicting the properties of such substances having regard to their structure. The legitimacy of conclusions based on analogy depends primarily on how much is known and on the particular specialist field. As a rule, prediction by persons skilled in the art is no longer possible where the substances whose properties have to be assessed have been theoretically synthesised, by interchanging all the structural elements from compounds forming the state of the art and having the same kind of effect. Such is the case in this instance.

6. The applicant set himself the task of preparing additional anti-allergic compounds, a task accomplished by the preparation of the compounds whose structure is defined in detail in Claim 1. These compounds are essentially arrived at mentally in 3 steps by selecting from the thiophenoxamine acid derivatives according to Citation 2 one of the substituents, namely the oxamino acid substituent (Step 1), and combining this with the 4-oxo-benzothiopyran basic structure of the anti-allergic compounds according to Citation 1 (Step 2) and especially attaching this to the fused benzene ring (Step 3). Even the chain of thoughts leading to the first two steps was in itself not obvious from the viewpoint of a person skilled in the art, for both citations show that the anti allergic properties of the substances require the combined action of all their structural components, i.e. either the combination of the 4-oxo-benzothiopyran basic structure with the amino residue and the cyano or carbamido substitutents or the combination of the thiophene basic structure with the amino acid group and the cyano residue. The idea of exchanging the basic structure in the two combinations may be inventive per se, because it is contingent on the knowledge that the amino and oxamino acid group have the same effect. However, this need not be gone into, because the application contains the new and surprising finding as regards Steps 1 and 2 that the cyano group, considered in the state of the art to be an essential structural element, can be dispensed with. As evidence to the contrary, the Examining Division produced Citation 3 (Negwer: Organisch-Chemische Arzneimittel und ihre Synonyma, Vol. I, Berlin 1978, 354, 364), drawing attention to compounds 2017, 2018, 1955 and 1957. These substances are appetite suppressants from the phenethylamine series whose nitrogen atom is substituted by the 3-chloropropyl, 2-hydroxypropyl, ethyl and 2-cyanoethyl residues. The intention was apparently to show that the appetite-suppressing effect of the phenethylamines does not depend on the presence or absence of the cyano residue. This finding in what is, in terms of structure and effects, a very narrow specialist field would not have been applied by a skilled person to the -in this respect far-removed - field of anti-allergic 4-oxo-benzothiopyrans. He would instead have relied on the information according to Citation 1 to the effect that the cyano residue in conjunction with the last-mentioned basic structure formed an important structural element for anti-allergic effectiveness. Finally, the ideas required for step 3, i.e. of shifting the oxamino acid residue from the heterocyclic to the carbocyclic part of the basic structure, were likewise not obvious, because it can be seen from both citations that the amino or oxamino acid residue has to be in the 2-position with respect to the heterocyclic sulphur atom.

7. These ideas are all the more relevant to the 2-oxo-benzothiopyrans according to Claim 1..., because a basic structure modified in this way is structurally unprecedented...

8. In the Board's opinion, the question raised by the Examining Division as to whether the requisite inventive step had to be present in a representative number of compounds out of the whole range of substances according to Claim 1 really amounts to a request to substantiate the alleged effect. Article 96(2) EPC prescribes that the Examining Division must draw all obstacles to patentability to the applicant's attention. Such an obstacle may consist in the Examining Division concluding from its own specialist knowledge that information supplied or assertions made by the applicant which are material to patentability, e.g. information concerning potentially patentable effects, are objectively not true, at least to the extent alleged. If such objectively necessary information is not substantiated, the application may be refused in accordance with Article 97(1) EPC. As already explained in point 6 above, the applicant in this case has accomplished the task he set himself, of preparing further anti-allergic substances, by creating the claimed oxobenzothiopyrans; of this the Board is in no doubt, not even in the light of the far-removed Citations 3 and 4 (Medizin und Chemie, Leverkusen - Weinheim/Bergstr. 1963, 296-314). The anti-allergic effects do not therefore have to be specially substantiated.

9. The grounds for refusal accordingly do not support the impugned decision. However, the patent applied for cannot be granted at present owing to the absence of allowable claims and pending termination of the examination at first instance...

ORDER

For these reasons, it is decided that:

1. The decision of the Examining Division of the European Patent Office dated 2 September 1982 is set aside.

2. The case is remitted to the first instance for further substantive examination.