T 0423/04 (Staphylococcal antigens/JACKSON FOUNDATION) 11-04-2006

Summary of Facts and Submissions

I. European patent No. 0 635 132 with the title "Broadly reactive opsonic antibodies that react with common staphylococcal antigens" was granted with 5 claims for all Designated Contracting States, on the basis of European patent application No. 93 907 460.5.

Granted claims 1 and 3 read as follows:

"1. An antigen preparation isolatable from Staphylococcus epidermidis strain Hay ATCC 55133, wherein said preparation generates broadly reactive opsonic antibody which specifically reacts in an assay with Staphylococcus epidermidis serotypes I, II and III.

3. A pharmaceutical composition comprising:

(a) the isolated antigen preparation of claim 1; and

(b) a pharmaceutically acceptable carrier."

Claim 2 related to the antigen preparation of claim 1 further defined by a method for obtaining it. Claim 4 was directed to a purified culture comprising strain Hay and claim 5 related to a method for obtaining broadly reactive opsonic immunoglobulin making use of the antigen preparation of claim 1.

II. An opposition was filed under Article 100(a) to (c) EPC. The opposition division maintained the patent on the basis of auxiliary request B then on file comprising granted claim 4 as the single claim. The main request comprising granted claims 1 to 3 and 5 and an amended claim 4 was refused because the requirements of Article 84 EPC were not fulfilled. Claims 1 to 4 (granted claims 1 to 3 and 5) of Auxiliary request A were found to be novel but sufficiency of disclosure was denied. The main request and auxiliary request A were not assessed for inventive step.

III. Appellant I (Patentee) and appellant II (Opponent) filed appeals, submitted statements of grounds of appeal and paid appeal fees in due time. Appellant I's appeal was accompanied by a new main claim request and by a request that the case be remitted to the opposition division for a consideration of inventive step if the board was able to acknowledge novelty and sufficiency of disclosure.

IV. Appellant II filed a further submission in answer to appellant I's grounds of appeal.

V. The board sent a communication pursuant to Article 11(1) of the Rules of Procedures of the Boards of appeal, stating its preliminary, non-binding opinion.

VI. Appellants I and II answered to this communication with submissions dated 10 March 2006. Appellant I's submissions were accompanied by new documents (35) to (38)- document (36) being the curriculum vitae of Dr. J.F.Kokai-Kun -, an amended main request and two auxiliary requests for all Designated Contracting States other than Portugal (PT). The corresponding requests were filed for PT. The amended main request for all Designated Contracting States other than PT comprised five claims.

Claims 1, 3 and 5 thereof read as follows:

"1. An antigen preparation isolatable from Staphylococcus epidermidis strain Hay ATCC 55133, wherein said preparation generates broadly reactive opsonic antibody which specifically reacts in an assay with Staphylococcus epidermidis serotypes I, II and III, for use in the prevention, diagnosis or treatment of Staphylococcus infections.

3. A pharmaceutical composition comprising:

(a) an antigen preparation isolatable from Staphylococcus epidermidis strain Hay ATCC 55133, wherein said preparation generates broadly reactive opsonic antibody which specifically reacts in an assay with Staphylococcus epidermidis serotypes I, II and III; and

(b) a pharmaceutically acceptable carrier.

5. The use of an antigen preparation isolatable from Staphylococcus epidermidis strain Hay ATCC 55133, wherein said preparation generates broadly reactive opsonic antibody which specifically reacts in an assay with Staphylococcus epidermidis serotypes I, II and III, in the manufacture of an agent for use in the prevention, diagnosis or treatment of Staphylococcus infections."

VII. Appellant II filed a further submission requesting that the documents (35), (37) and (38) filed by Appellant I be disregarded.

VIII. Further submissions on this point were made by both appellants.

IX. Oral proceedings took place on 11 April 2006. During oral proceedings, the first auxiliary request filed on 10 March 2006 was replaced by an amended first auxiliary request which in the version for all Designated Contracting States other than PT comprised three claims.

Claims 1 and 3 read as follows:

"1. The use of an antigen preparation isolatable from Staphylococcus epidermidis strain Hay ATCC 55133, wherein said preparation generates broadly reactive opsonic antibody which specifically reacts in an assay with Staphylococcus epidermidis serotypes I, II and III, in the manufacture of an agent comprising said antigen preparation for use in the prevention or treatment of Staphylococcus infections.

3. A pharmaceutical composition comprising :

(a) a prophylactically or therapeutically effective amount of an antigen preparation isolatable from Staphylococcus epidermidis strain Hay ATCC 55133, wherein said preparation generates broadly reactive opsonic antibody which specifically reacts in an assay with Staphylococcus epidermidis serotypes I, II and III; and

(b) a pharmaceutically acceptable carrier."

Claim 2 related to the use as claimed in claimed 1 wherein the antigen preparation was further characterised by the method for obtaining it.

The amended first auxiliary request for the Designated Contracting State PT consisted of granted claims 1 to 3 and 5 (renumbered as 1 to 4), the only amendment being the insertion of the qualifier "non-human" before the term "mammal".

Appellant I withdrew its request that the case be remitted to the first instance for assessment of inventive step whereas appellant II made this same request for the first time.

X. The following documents are mentioned in this decision:

(1) WO 93/17044 published on 2 September 1993 claiming priority from US 804 317 filed on 25 February 1992;

(17) Ohshima, Y. et al., Ann. Microbiol. (Inst. Pasteur), Vol. 135A, pages 353 to 365, 1984;

(32) Ichiman, Y. et al., J. of Applied Bacteriology, Vol. 56, pages 311 to 316, 1984;

(35) Fischer, G.W. et al., The J. of Infectious Diseases, Vol. 169, pages 324 to 329, 1994;

(37) Oshima, Y. et al., Zbl.Bakt., Vol. 274, pages 417 to 425, 1990;

(38) Oshima, Y., Zbl.Bakt.Hyg.A, Vol. 270, pages 219 to 227, 1988.

XI. Appellant I's submissions in writing and during oral proceedings insofar as relevant to the present decision may be summarised as follows:

Admissibility of documents (35), (37) and (38)

Documents (35), (37) and (38) were brief and relevant. Document (35) provided further support for the fact that strain Hay had, as stated in the patent in suit, a type II capsule. Documents (37) and (38) were simply cited to show that serotype II and III strains could be readily identified at the priority date on the basis of their carbohydrate constituents. These documents should be admitted in the proceedings.

Main request for all Designated Contracting States other than PT.

Articles 123(2) and 84 EPC; claim 1

A basis was found on page 1, lines 11 to 14 of the application as filed for re-drafting claim 1 as a first medical use claim (Article 123(2) EPC).

In accordance with the case law (T 190/99 of 6 March 2001), a claim was to be construed by the mind of a person willing to understand. In the present case, the skilled person would have no problems in understanding what the term "for use in the prevention, diagnosis or treatment of Staphylococcus infections" meant, nor would he/she be in doubt after reading the description that this use was intended to be carried out with, in particular, strain Hay (Article 84 EPC).

Article 123(3) EPC; claim 5

Granted claim 1 was a product claim directed to the Hay antigen preparation per se and, therefore, protected the use of the antigen for any purpose including, of course, the use of the antigen preparation in the manufacture of an agent for diagnostic purposes as claimed in claim 5. The scope of protection had, thus, not been extended.

Article 54(3)(4) EPC; claims 1 and 5

Document (1) did not teach in a clear and unambiguous manner the use of an antigen preparation isolatable from strain Hay in the prevention, diagnosis or treatment of staphylococcus infections as required by claims 1 and 5. It had to be kept in mind that the whole thrust of the document was not towards isolating an antigenic preparation for medical purposes but rather towards using the preparation for screening immunoglobulin samples for the presence of broadly reactive opsonic antibodies. Even if the data described on pages 19 and 22 related to a S.epidermidis vaccine, it was not clear that this vaccine had been made from strain Hay, nor whether it was in the form of an antigenic preparation rather than in the form of whole cells. Furthermore, the sentence on page 22 mentioning that "... S.epidermidis vaccine induced antibody could be used for prevention and treatment of S.epidermidis infections..." could not be interpreted as disclosing a first or second medical use because it did not relate to the use of the vaccine per se for prevention and treatment, but to its use for inducing an antibody which could then be used for prevention and treatment.

The subject-matter of claims 1 and 5 was, thus, novel.

First auxiliary request for all Designated Contracting States other than PT.

Rule 57a EPC, Articles 123(2) and 84 EPC; claim 3

The expression "a prophylactically and therapeutically effective amount.." had been introduced in claim 3 to make it unambiguous that the claimed pharmaceutical composition did not comprise the S. epidermidis vaccine disclosed in document (1) for injection into rabbits for the purpose making Directed Immune Globulin. The claim was, thus, admissible pursuant to Rule 57a EPC. Furthermore, the claimed subject-matter found a basis in the passage bridging pages 27 and 28 of the application as filed (Article 123(2) EPC). The skilled person willing to understand would have no doubts as to the significance of the expression "A pharmaceutical composition comprising a prophylactically and therapeutically effective amount of an antigen preparation..." (Article 84 EPC).

Article 54(3)(4) EPC

The passage on page 22 of document (1) argued by appellant II to be novelty destroying disclosed the use of a vaccine for the manufacture of an agent comprising an antibody ("S.epidermidis vaccine induced antibody") for use for medical purposes but it did not disclose the use of a vaccine in the manufacture of an agent comprising said vaccine for said purposes. Therefore, document (1) did not affect the novelty of claim 1. In the same manner, there was no disclosure in document (1) of a pharmaceutical composition falling within the scope of claim 3. Novelty was to be acknowledged.

Article 83 EPC, sufficiency of disclosure in relation to claim 1

- Claim 1 extended to antigenic preparations made from other strains than strain Hay. This generalisation simply reflected the scientific contribution made to the art by the invention, namely that there existed an antigen common to Staphylococcus strains in general. Example 13 showed that the common antigen could be obtained from another strain than the Hay strain. A protocol was, thus, described which could be followed to extract said antigen from any Staphylococcus strains.

- Starting from the claimed antigenic preparation, the skilled person would have achieved a better characterisation (purification) of the relevant specific antigen without undue burden.

- Strains of serotypes I, II and III were either available to the public or identifiable anew on the basis of the teachings of document (17). A serotype I strain was on deposit (ATCC 31432). As shown by the declarations on file, at least three different scientists had been able to obtain a serotype III strain from their colleagues either before or well after the effective date of the patent.

In document (17) a comparison of the cell wall structure of three serologically different strains of S.epidermidis designated as capsular types I, II and III was carried out. The biochemical and serological properties of the cell walls were said to correlate with the capsular types of these organisms. Accordingly, the skilled person would have no problem in identifying the serotype of a given strain via its biochemical properties.

For these reasons, sufficiency of disclosure could be acknowledged.

Article 56 EPC

The problem to be solved could be defined as how to prevent or treat Staphylococcus infections. In this framework, document (32) could be regarded as the most relevant piece of prior art as it was concerned with S.epidermidis capsular antigens, teaching that the three strains representative of the capsular types I, II and III were serologically different and that their protection-inducing capacity was capsular-type specific.

Starting from this knowledge, the obvious route to take to solve the above mentioned problem would be to produce a polyvalent vaccine comprising a mixture of antigens from the three capsular types.

The provided solution was completely different as it relied on the finding that there existed one antigen common not only to the three S.epidermidis serotypes but also to other Staphylococcus species, and that antibodies against it were broadly reactive and also opsonic ie. protective against many of the tested Staphylococci.

There was no suggestion in the art that an antigen other than those characterising the three serotypes could be of medical use. The argument that an antigenic preparation obtained from strains with a mixed polyvalent capsular type (I/II/III) would serve the same purpose as the claimed preparation was not convincing because it had not been shown that antibodies against it would be opsonic nor that their protecting effect would extend to protecting against other species than S.epidermidis.

In summary, the state of the art did not mention other antigens than those linked to the serotype and, furthermore, the properties of the antigenic preparation obtained from strain Hay were fully unexpected.

For these reasons, inventive step could be acknowledged.

XII. Appellant II's submissions in writing and during oral proceedings insofar as relevant to the present decision may be summarised as follows:

Admissibility of documents (35), (37) and (38)

The contents of these documents should be disregarded. Document (35) did not go any further than the prior art on file in identifying strain Hay as a type II strain. Documents (37) and (38) did not provide reliable information on the carbohydrate contents of the serotypes I, II and III and were, thus, irrelevant for the purpose of demonstrating that a given serotype strain could be identified on the basis of its carbohydrate constituents.

Main request for all designated Contracting States other than PT.

Article 84 EPC; claim 1

Claim 1 had been re-worded in the first medical indication format by adding the words "for use in the prevention, diagnosis or treatment of Staphylococcus infections". The sentence on page 1, line 5 of the patent: "This invention relates to antigens used to prevent, diagnose or treat Staphylococcus infections" was inadequate to support the amended claim because, firstly, it did not constitute anything of substance as regard the technical disclosure in the specification and, secondly, it did not specifically refer to the claimed antigenic preparation.

Article 123(3) EPC; claim 5

Being formulated as a use claim, claim 5 covered eg. directed standard intravenous immunoglobulin (IVIG) as the end product of said use. None of the granted claim related to IVIG and, therefore, the scope of protection had been extended.

Article 54(3)(4) EPC; claims 1 and 5

Document (1) disclosed a S.epidermidis vaccine on page 19. As the document only referred to three strains of S.epidermidis including strain Hay, the skilled person would readily understand that the generic term "S.epidermidis vaccine" covered, in particular, a S.epidermidis strain Hay vaccine. Furthermore, being aware that whole cells from a pathogen would not be used for immunisation purposes, he/she would also understand the S.epidermidis vaccine as being an antigenic preparation such as the one described on page 14 of document (1). The extraction protocol for the antigenic preparation therein described was the same as in the patent in suit, which left no doubt that the antigenic preparations were the same, ie that they had the same property of being capable of generating broadly reactive opsonic antibody specifically reacting in an assay with S.epidermidis serotypes I, II and III.

On page 19, the S.epidermidis vaccine was said to be used for producing Directed Immune Globulin in rabbits which produced survival similar to Directed Human Immune Globulin produced by screening immunoglobulin for antibody to S.epidermidis. These data were interpreted on page 22, in particular, as showing that S.epidermidis vaccine-induced antibody could be used for prevention and treatment of S. epidermidis infections. Document (1) thus taught the use of an S.epidermidis antigenic preparation made from strain Hay for preventive treatment of Staphylococcus infections. Consequently, the subject-matter of claims 1 and 5 was not novel.

First auxiliary request for all designated Contracting States other than PT.

Article 84 EPC; claim 3

The subject-matter of claim 3 was unclear insofar as the term "... effective amount" only made sense in relation to a method of treatment and not in relation to a pharmaceutical composition.

Article 54(3)(4) EPC

Document (1) disclosed on page 22 the use of the antigenic preparation as a vaccine against Staphylococcus infections. Otherwise stated, it disclosed the use of the antigenic preparation in the manufacture of an agent comprising said preparation for use in the treatment of Staphylococcus infections, thus destroying the novelty of claim 1. Claim 3 also lacked novelty as the vaccine disclosed on page 22 was a pharmaceutical composition which by definition contained a prophylactically effective amount for the purpose of immunisation.

Article 83 EPC; sufficiency of disclosure in relation to claim 1

Sufficiency of disclosure was lacking in three respects:

- Claim 1 extended to antigenic preparations from other strains than strain Hay by virtue of the use of the term "isolatable". In contrast, the patent in suit provided no guidance on how to identify these further antigenic preparations.

- Claim 1 extended to single antigens in addition to the TCA-produced antigenic preparation. There again, the patent in suit did not provide any guidance for isolating such antigens; it did not even show that one such antigen existed.

- Strains of serotype II and III which were needed in order to identify the claimed antigenic preparation were not available. The evidence on file showed that it required an undue amount of effort to obtain the capsular type III strain SE-10. SE-360; a representative of capsular type II could not be obtained at all.

Furthermore, there was no evidence in the prior art on file that strains representing each of the serotypes could be re-isolated without undue burden. Document (17) defined the carbohydrate contents of three specific strains said to represent capsular types I, II and III; yet, it did not disclose the relationship between a given carbohydrate content and a given capsular type (serotype), in general. Before a strain of a given serotype could be identified by its carbohydrate contents, the link between the two would have to be established without ambiguity. This implied that the carbohydrate content of the different capsular types would have to be exactly identified, ie that it should have been determined for many strains of each type. Otherwise stated, the results shown in document (17) were insufficient to provide a reliable, albeit indirect test for serotyping. Consequently, S.epidermidis strains of the three serotypes could not be identified without undue burden, which was all the more true of serotype III strains which were quite rare. It also followed that antigenic preparations such as claimed could also not be obtained without undue burden.

For these reasons, the requirements of Article 83 EPC were not fulfilled.

Article 56 EPC

- The case should be sent back to the first instance for the assessment of inventive step as the now claimed subject-matter was quite different from that considered by the opposition division.

- The problem to be solved was to provide something useful in the prevention, treatment and diagnosis of Staphylococcus infections.

Document (32) could be regarded as the closest prior art. In its introductory part, it reminded the skilled person that Staphylococcus strains were divided in three groups on the basis of their capsular types. Each of the three groups was serologically different and the protection-inducing capacity was capsular-type specific. Document (32) also reported the occurrence of "polyvalent" capsular type strains ie broadly reactive across all three serotypes. Even if it did not disclose that antibodies raised against a polyvalent strain were opsonic, it must be so, since they were protective and the opsonic activity of anti-peptidoglycan antibodies had been demonstrated. Accordingly, S.epidermidis strains capable of generating broadly reactive opsonic antibody which specifically reacted in an assay against S.epidermidis serotypes I, II and III were already known at the priority date, as was, by necessary implication, their use in diagnosis and treatment. The properties exhibited by antigenic preparations made from strain Hay as regards the generation of antibodies as specified in the claim were not obviously different from those of antibodies raised against antigenic preparations made from the polyvalent strains. Therefore, the basis underlying the current claims lacked inventive step.

XIII. Appellant I requested that the decision under appeal be set aside and that the patent be maintained on the basis of the main request filed on 10 March 2006 or the first auxiliary request filed at the oral proceedings or the second auxiliary request filed on 10 March 2006, all with corresponding sets of claims for the Contracting State PT.

Appellant II requested that the decision under appeal be set aside and that the patent be revoked.