T1435/20 - Art.83 and secret antibody

Key points

• The patent application is directed to a second medical use. 
• "Claim 1 is formulated in a further-medical-use format in which the binding of the recited antibody to C5 is the mechanistic explanation for the therapeutic effect, i.e. the suitability thereof in the medical use. In its decision G 2/21, the Enlarged Board of Appeal recently held that the proof of a claimed therapeutic effect has to be provided in the application as filed" (note, the decision was taken on 21.09.2023 and issued in writing on 20.02.2024).
• "The parts of the application as filed which purportedly provide experimental data in support of the further-medical-use format of the claim, the so-called "TRIUMPH trial" on pages 27 to 40, were conducted with an antibody designated "eculizumab". Throughout the appeal, the appellant has maintained that this "eculizumab" antibody used in the TRIUMPH trial was not the antibody as it is now defined in the claim,"
• Note, this has to do with an alleged clerical error in SEQ ID NO:4 of the patent application. However, it seems to me that the intention was to specify eculizumab in the claim.
• "The sole indication in the application as filed of the origin and identity of "eculizumab" used in the TRIUMPH trial is on page 28, lines 7 to 9 of the application as filed, where it is disclosed that "Patients were randomly assigned on a one-on-one basis to receive either placebo or eculizumab (Soliris**(TM), Alexion Pharmaceuticals, Inc.) within 10 days of the qualifying transfusion."
• " substantial part of the appellant's case in appeal (e.g. inventive step) has been based on arguments to the effect that the structure of the antibody designated "eculizumab" was not derivable from any of the disclosures in the state of the art and that all scientists working with eculizumab prior to the filing date were in fact bound by confidentiality with regard to the structure of eculizumab. However, and without having to go into any detail on these arguments, which were based on various items of documentary evidence and declarations, by the same token accepting the appellant's argument means that without the identification of the structure of eculizumab in the form of Soliris**(TM) obtainable from Alexion Pharmaceuticals, Inc. in the application as filed, the structural particularities of the antibody designated eculizumab used in the TRIUMPH trial and reported on in the application were equally not available to the skilled person at the filing date. In fact, this conclusion of non-availability based on confidentiality seems, indeed, to find corroboration in the appellant's press release, one day after the filing date of the application, announcing that the company had received marketing approval from the U.S. Food and Drug Administration (FDA) for Soliris**(TM) (eculizumab), the first therapy approved for PNH"
• "52. As a consequence of these considerations based on the appellant's arguments, it must be concluded that the structure of the antibody used in the TRIUMPH trial was not known to the skilled person (at all) when the application was filed. It however follows from this fact that the disclosed results of this TRIUMPH trial cannot be verified to apply equally to the C5-binding antibody now referred to in the claim which comprises a heavy chain consisting of SEQ ID NO: 2 and a light chain consisting of SEQ ID NO: 4. The TRIUMPH trial can therefore not serve as evidence for the C5-binding activity of this antibody and the resulting therapeutic effect as required by the claim.

  53. Accordingly, and in the absence of any indications that the unusual antibody defined in the claim has the required therapeutic effect, the patent application fails to sufficiently disclose the claimed invention of auxiliary request 4 (Article 83 EPC)." 
  
  

• As a comment, the antibody was hence not actually commercially available at the priority date and, of course, the actual statement  'eculizumab (Soliris**(TM), Alexion Pharmaceuticals, Inc.) ' does not say "commercially available from Alexion Pharmaceuticals, Inc.".

The link to the decision is provided after the jump, as well as (an extract of) the decision text.

https://www.epo.org/en/boards-of-appeal/decisions/t201435eu1

Fourth and eighth auxiliary requests - sufficiency of disclosure

46. Claim 1 of the fourth auxiliary request is identical to claim 1 of auxiliary request 3 dealt with by the examining division, and reads:

"1. A pharmaceutical composition comprising an antibody that binds C5 in a 300mg single unit dosage form comprising 30 ml of a 10 mg/ml sterile, preservative free solution, wherein the antibody comprises a heavy chain consisting of SEQ ID NO: 2 and a light chain consisting of SEQ ID NO: 4, for use in treating a patient suffering from paroxysmal nocturnal hemoglobinuria (PNH)." (emphasis added by the board)

47. Claim 1 is formulated in a further-medical-use format in which the binding of the recited antibody to C5 is the mechanistic explanation for the therapeutic effect, i.e. the suitability thereof in the medical use. In its decision G 2/21, the Enlarged Board of Appeal recently held that the proof of a claimed therapeutic effect has to be provided in the application as filed (see in particular reasons 74 and 77). Thus the evidence for the binding of the antibody claimed to C5 had to be in the application as filed.

48. The parts of the application as filed which purportedly provide experimental data in support of the further-medical-use format of the claim, the so-called "TRIUMPH trial" on pages 27 to 40, were conducted with an antibody designated "eculizumab". Throughout the appeal, the appellant has maintained that this "eculizumab" antibody used in the TRIUMPH trial was not the antibody as it is now defined in the claim, i.e. comprising "a light chain consisting of SEQ ID NO: 4" (including, as argued by the appellant, an N?terminal 22 amino acid long ER signal peptide, see points 3. and 4. above).

49. Accordingly, in order to assess whether the application sufficiently discloses the technical effect claimed, i.e. C5 binding of the antibody for treating a patient suffering from paroxysmal nocturnal hemoglobinuria (PNH), it needs to be established what exactly the sequence of the eculizumab antibody of the TRIUMPH trial was.

50. The sole indication in the application as filed of the origin and identity of "eculizumab" used in the TRIUMPH trial is on page 28, lines 7 to 9 of the application as filed, where it is disclosed that "Patients were randomly assigned on a one-on-one basis to receive either placebo or eculizumab (Soliris?, Alexion Pharmaceuticals, Inc.) within 10 days of the qualifying transfusion."

51. A substantial part of the appellant's case in appeal (e.g. inventive step) has been based on arguments to the effect that the structure of the antibody designated "eculizumab" was not derivable from any of the disclosures in the state of the art and that all scientists working with eculizumab prior to the filing date were in fact bound by confidentiality with regard to the structure of eculizumab. However, and without having to go into any detail on these arguments, which were based on various items of documentary evidence and declarations, by the same token accepting the appellant's argument means that without the identification of the structure of eculizumab in the form of Soliris? obtainable from Alexion Pharmaceuticals, Inc. in the application as filed, the structural particularities of the antibody designated eculizumab used in the TRIUMPH trial and reported on in the application were equally not available to the skilled person at the filing date. In fact, this conclusion of non-availability based on confidentiality seems, indeed, to find corroboration in the appellant's press release, one day after the filing date of the application, announcing that the company had received marketing approval from the U.S. Food and Drug Administration (FDA) for Soliris**(TM) (eculizumab), the first therapy approved for PNH (see document D16, first paragraph and the declaration in document D31, point 2).

52. As a consequence of these considerations based on the appellant's arguments, it must be concluded that the structure of the antibody used in the TRIUMPH trial was not known to the skilled person (at all) when the application was filed. It however follows from this fact that the disclosed results of this TRIUMPH trial cannot be verified to apply equally to the C5-binding antibody now referred to in the claim which comprises a heavy chain consisting of SEQ ID NO: 2 and a light chain consisting of SEQ ID NO: 4. The TRIUMPH trial can therefore not serve as evidence for the C5-binding activity of this antibody and the resulting therapeutic effect as required by the claim.

53. Accordingly, and in the absence of any indications that the unusual antibody defined in the claim has the required therapeutic effect, the patent application fails to sufficiently disclose the claimed invention of auxiliary request 4 (Article 83 EPC).

54. Claim 1 of the eighth auxiliary request is identical to claim 1 of auxiliary request 5 dealt with by the examining division and is identical to claim 1 of the current auxiliary request 4 (see point 46.), with the additional feature "wherein the pharmaceutical composition is to be administered by intravenous infusion" at the end of the claim.

55. This claim thus comprises the same definition of the antibody as claim 1 of auxiliary request 4, and consequently and mutatis mutandis the application as filed also fails to sufficiently disclose this claimed invention, contrary to the requirements of Article 83 EPC.

Auxiliary requests 9 to 17

56. Claim 1 of these auxiliary requests corresponds to claim 1 of the main request, auxiliary request 1, auxiliary request 2A, the third to sixth auxiliary requests, auxiliary request 7A and the eighth auxiliary request, respectively, with the additional feature that the claimed composition has a pH of 7. The appellant has not submitted dedicated arguments that this amendment would overcome the deficiencies of the higher-ranking auxiliary requests. The board accordingly has seen no reason to admit and consider these requests in the proceedings (Article 12(4) RPBA for auxiliary requests 10 to 13 and 15 to 17 filed with the statement of grounds of appeal and

Article 13(2) RPBA for auxiliary requests 9 and 14 filed during the oral proceedings).

Order

For these reasons it is decided that:

The appeal is dismissed.