Wednesday, 22 December 2010

T 716/08 – Does It Work?

This decision deals with the refusal of an application by the Examining Division (ED).

Claim 1 of the main request on file read:

1. Use of an 48 kD infectious Salmon anaemia virus (ISAV) protein or an immunogenic fragment of said protein, said protein or immunogenic fragment thereof having an amino acid sequence that is at least 70% homologous to the amino acid sequence as depicted in SEQ ID NO: 2, for the manufacturing of a vaccine for combating ISAV infections.

The Board carries out an inventive step assessment, and dwells on one of the less known steps of the problem-solution approach (incidentally, the one which, as far as I can see, candidates are not expected to implement in papers B and C of the EQE): the evaluation of whether the objective technical problem is indeed solved.

[11] Starting from document D6 and in the absence of evidence of an improvement over the subject-matter disclosed in that document, the problem to be solved is considered to be the provision of an alternative vaccine against ISAV.

[12] The solution to this problem as stated in the claims is the use of a 48 kDa protein having the sequence described in SEQ ID No. 2, variants thereof or related compounds, such as recombinant DNA molecules.

[13] A first issue in the present case is whether or not the disclosure in the application provides evidence that the problem [...] above has been solved. In the decision under appeal the ED held that it was not plausible, on the basis of the disclosure in the application and in particular Examples 4 and 5, that the solution, as then claimed in claims 10 to 16, solved the problem underlying the application.

[14] The boards have regularly considered in the context of the evaluation of inventive step whether or not “the problem is solved” (see for example T 187/93 [19] or T 939/92 [2.4.1 or 2.5.1]) and have in cases where they were not satisfied that this was so, i.e. that what was claimed was de facto a solution to the problem, denied an inventive step (see for example T 210/02 [5, § 10 et seq.] or T 1329/04 [6-11]) or required a reformulation of the problem (see for example T 939/92 [2.5-6] or T 87/08 [6.3]).

[15] The verification of whether or not the claimed solution actually solves the problem, i.e. that the claimed subject-matter actually provides the desired effect, is according to T 1329/04 [12] to be made on the basis of data in the application. Common general knowledge at the priority date may be used to interpret the teaching in an application or a patent (see for example T 293/04 [21] or T 665/05 [16]). Post-published evidence can only be used to back-up the teaching derivable from the application (for example T 1329/04 [12]).

[16] As to the quality of the evidence, “absolute proof” of the achievement of an effect is not required for the effect to be plausible. Thus, in the case of a vaccine, it is not required that protective immunity is actually demonstrated in the target organism. It suffices that the data indicate that a compound could be a useful candidate for a vaccine (for example T 903/05 [19]; T 391/07 [20]; T 394/06 [13, in combination with page 6, last paragraph to page 8, first paragraph of “Facts and Submissions”.)

[17] The present application discloses in Example 2 that the 48 kDa protein of ISAV was found by screening of a bacteriophage lambda cDNA library with an anti-ISAV polyclonal rabbit serum.

[18] In a lambda bacteriophage cDNA library each bacteriophage particle expresses on its surface a protein corresponding to the cDNA contained in that particle. By probing such a library with a monoclonal antibody preparation or a polyclonal serum, proteins reacting with the antibodies, and thus also the corresponding cDNAs, are identified.

[19] In the present case the antibodies used for probing the library are in the form of a polyclonal serum obtained from rabbits immunized with whole ISAV particles.

[20] At the priority date it was known from document D4 that ISAV had four structural proteins having molecular masses as determined on an SDS-gel of 74, 53, 43 (or 46 depending on the virus isolate) and 26.5 kDa [...].

[21] The appellant submits that the 53 kDa protein disclosed in document D4 is equivalent to the 48 kDa protein of the application. The board has no reason to doubt this submission.

Thus, it is concluded that the 48 kDa protein of the application is one of the four viral structural proteins of ISAV as disclosed in document D4.

[22] It is, as the appellant agreed at oral proceedings, common general knowledge that structural proteins of a virus, i.e. the proteins involved in formation of the viral capsid, or in the case of enveloped viruses, additionally those situated in the viral envelope, are potential candidates for the inclusion in subunit vaccines. This is so because structural proteins are present at the outside of the virion and are thus exposed to the immune system. Therefore, it is expected that upon infection with ISAV, antibodies are preferably elicited against these structural proteins and that these antibodies may achieve neutralization of the virus. Therefore, vaccine preparations containing, instead of for example the whole inactivated virus, only one (or more) of the structural proteins, i.e. so-called subunit vaccines, would also be expected to have the same effect, i.e. to elicit neutralizing antibodies.
[23] That common general knowledge of the skilled person is reflected by the disclosure in document D6. It reports that one of the structural proteins of ISAV, SP-1 which, as submitted by the appellant at the oral proceedings, corresponds to the 74 kDa protein disclosed in document D4, was identified by screening with a polyclonal anti-ISAV rabbit serum [...] and that this protein is expected to induce a protective immune response in fish against infection with ISAV [...]. 
[24] In view of the case law referred to in points [15] and [16] above and in the light of the observations in points [17] to [23], in particular point [22] above, the board considers that the mere presence of antibodies against the 48 kDa protein in the rabbit serum used for screening the lambda bacteriophage cDNA library according to Example 2 of the application is evidence that the 48 kDa protein is antigenic and, consequently, could also be a useful constituent of a subunit vaccine. 
[25] The polyclonal serum according to the application was obtained after immunisation of rabbits with ISAV particles. The target organism for vaccination with the 48 kDa protein is however salmon. In the decision under appeal the examining division states that immunogenicity in rabbits does not provide a basis to a claim to vaccines for fish [...]. The board notes however, that there is no evidence before it demonstrating that the properties of the immune system of salmon and rabbits are of a totally different nature. 
[26] Thus, in conclusion the board is satisfied in view of Example 2 that the subject-matter of the claims is a solution to the problem formulated above, i.e. the provision of an alternative vaccine against ISAV. 
[27] As a consequence the post-published evidence, i.e. document D7, is not needed to back up the disclosure in the application. However, for completeness, the board notes the following with regard to the examining division’s view on document D7 [...]. 
[28] Document D7 discloses that salmon were vaccinated with the 48 kDa protein expressed in E. coli (two groups) or with saline (two groups), respectively. All groups were challenged eight weeks after vaccination by infection with ISAV. The cumulative mortality of the saline group was 75%, that of the vaccinated group 57% [...]. 
Thus, in the board’s view, these data demonstrate that the E. coli-expressed 48 kDa ISAV protein has a protective effect against IASV infection. Whether or not this effect is “very significant” is irrelevant, since absolute proof of the usefulness of the compound as a vaccine is not necessary […].

Finally the Board found the claims on file to be inventive.

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Anonymous said...

Whilst it's probably the right decision, the reasoning is probably a bit off.

T939/92 is only applicable in situations where a claim is directed to a product per se and the claims are therefore not explicitly restricted to solutions to the problem (in such a case, it needs to be determined whether all the claimed products achieve the effect and therefore solve the problem).

In the present situation, however, the claims have been drafted in a medical use format and so they therefore implicitly require that the therapeutic effect is achieved (i.e. inoperative embodiments have been at least implicitly excluded).

See e.g. T87/08, T 601/05, T 05/06, T1079/08, T435/04 and T1031/06. Also see the Enlarged Board of Appeal Decision G1/03, which said:

"If… there is lack of reproducibility of the claimed invention, this may become relevant under the requirements of inventive step or sufficiency of disclosure. If an effect is expressed in a claim, there is lack of sufficient disclosure. Otherwise, i.e. if the effect is not expressed in a claim but is part of the problem to be solved, there is a problem of inventive step (T 939/92, OJ EPO 1996, 309)."