T 1317/13 - Examples already published / bonus effect

Key points

• In this examination appeal, D1 is a PCT application "published shortly before the priority date of the present application. The applications have two inventors in common. The disclosure content of document D1 is largely identical to that of the latter, and in particular, all three examples are identical." Hence, the complete experimental disclosure of the application at issue was already prior art by D1.
•  Claim 1 is directed to a medicament for the treatment of  " gout, gouty arthritis or pseudogout" using an antibody, the antibody ACZ885 was used in the examples of the application and also in D1.
• The closest prior art is D5 about the colchicine standard therapy of gout.
• " the board is satisfied that document D5 teaches the skilled person that: (i) increased production of IL-1beta is the trigger for the auto-inflammation in gout as in other auto-inflammatory diseases; (ii) administration of colchicine completely blocks the crystal-induced production of IL-1beta and leads to greatly reduced inflammation and, (iii) gout patients were anticipated to benefit from treatments designated to block IL-1beta." 
• " Document D1 discloses compounds suitable for blocking IL-1ß in patients suffering in general from auto-inflammatory syndromes, in particular also the ACZ885 antibody as an embodiment of the antibodies defined in claim 1." 
• The Board concludes that claim 1 is obvious. 
• The applicant argues a surprising further effect. " The appellant further argued that anti-IL-1beta antibodies had an additional effect on pain perception which was not reported in any of the cited prior art, in particular not in documents D1 and D5, which was however an effect which was indeed achieved by the antibody ACZ885 as demonstrated by the results in the post-published document D9." 
• The Baord considers this a bonus effect.
• The applicant "has further submitted that "arguments about a 'bonus effect' were often used when there was effectively a 'one-way-street' situation", which according to the appellant was a situation "in which the skilled person was inevitably guided towards a particular destination, such that any surprising effects would be a 'bonus' which would have been achieved anyway." However, the present situation was not a one-way-street situation since document D20 described various different approaches to inhibiting the IL-1 system." 
• This argument does not convince the board to change its conclusion in point 22 above either. In fact, decision T 21/81, supra, considers a situation in which it was already obvious that the skilled person would arrive at something falling within the terms of a claim, because an advantageous effect was expected to result from the combination of teachings of the prior art documents, resulting in a situation in which an extra effect cannot establish inventive step. Accordingly, a "one-way-street" situation in the sense defined by the appellant cannot be inferred as a mandatory prerequisite for the principle established in this decision.

EPO T 1317/13 - link

Main request - claim 1

3. The claimed subject-matter (see section II) is a medicament for use in the treatment of auto-inflammatory syndromes, namely gout, gouty arthritis or pseudogout (for the ease of reading the three disorders will in the following be referred to as "gout"). The medicament is defined as comprising a human interleukin (IL)-1beta binding antibody characterised by comprising a first and second domain defined by particular amino acid sequences. The anti-human IL-1beta monoclonal antibody ACZ885, an example of an antibody falling under this definition, was used in the examples of the application. The antibody ACZ885 was known to the skilled person from the disclosure in document D1.

Closest prior art

4. A frequently applied line of therapy for treating patients suffering from auto-inflammatory diseases such as gout at the priority date of the application was the oral administration of colchicine. This treatment is in particular able to resolve the initial inflammatory phase of gout but was also known to be poorly tolerated because of predictable gastrointestinal side-effects (see e.g. document D5, page 238, right-hand column, lines 15 to 17; page 239, right-hand column, lines 10 to 12, and document D12, e.g. abstract, last sentence, and Table 1, final part).

5. The appellant agreed with the board and the examining division that document D5, disclosing inter alia the colchicine standard therapy of gout (see point 4), represented the closest prior art for the assessment of inventive step for the claimed subject-matter.

The problem to be solved

6. Instead of administering colchicine for treating patients suffering from gout, the claimed invention provides for the administration of antibodies which bind to IL-1beta, such as the specific antibody "ACZ885".

7. The appellant argued that the application explicitly or implicitly taught that the technical effect of the different treatment consisted in three improvements over the therapy with colchicine. Firstly, it was derivable from example 3 that ACZ885 had a long duration of action and could therefore be administered once every few weeks, rather than every hour as was the case with the therapy with colchicine. Secondly, example 3, which assessed inter alia the safety of ACZ885 in humans, was silent on negative effects of the administration for a time span of at least 134 days. Finally and thirdly, based on the knowledge that IL-1beta was involved in pain perception and amplified neurogenic signals, the application disclosed the usefulness of ACZ885 in various pain conditions. Therefore, whereas colchicine and ACZ885 both relieved pain by inhibiting its cause (i.e. the inflammatory aspects of gout due to uric acid crystals), ACZ885 additionally provided indirect pain relief by interfering with pain perception pathways.

8. The appellant accordingly held that the technical problem to be solved by the claimed invention was the provision of an improved medicament, as compared to colchicine, for the treatment of gout, gouty arthritis and pseudogout in a patient.

9. The board can concur with the formulation of this problem and is satisfied that in view of the disclosure in example 3 this problem is solved by the claimed invention. Therefore, it is to be determined whether the skilled person, starting from the known colchicine- based treatment and addressing the problem to be solved, would have arrived at implementing the claimed invention in an obvious manner.

Obviousness

10. Document D5, i.e. the document representing the closest prior art, provides insight into the molecular mechanisms underlying the chronic inflammatory responses induced by the deposition of monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals in joints and periarticular tissues, typical of gout. Both crystals were found to engage the caspase-1-activating NALP3 inflammasome, resulting in the processing and production of active IL-lbeta. These findings in the context of gout were considered to support the known pivotal role of the inflammasome also in several auto-inflammatory diseases (see abstract, last sentence) and to confirm that "Increased production of IL-1beta was the cause of several auto-inflammatory diseases, providing clear evidence for a pivotal role of this cytokine in triggering auto-inflammation" (see page 237, left-hand column, lines 7 to 10). Document D5 refers in this context in particular to familial auto-inflammatory diseases such as Muckle-Wells syndrome, familial cold auto-inflammatory syndrome, chronic infantile neurologic cutaneous and articular syndrome and hereditary periodic fevers in which particular mutations in the NALP3 inflammasome protein itself lead to a constitutive processing and resultant production of active IL-1beta (see page 240, left-hand column, lines 10 to 21).

11. The board considers document D5 to be of particular further interest for a skilled person searching to identify and validate targets for treatments of gout with a view to solving the objective problem. In particular document D5 contains a report on the disclosure in the prior art of the observation that pre-treatment of experimental animal models of gout with intravenous colchicine (the therapeutic compound known in the prior art for treatment of gout, see point 4 above) before intra-articular MSU crystal injections greatly reduced crystal-induced inflammation, and the observation of the authors of document D5 that pre-treatment with colchicine completely blocked in vitro the processing and production of IL-1beta (see passage on page 238, right-hand column, line 15 to page 239, left-hand column, line 2 and page 239, right hand column, lines 9 to 11). Of similar further interest is the reference in document D5 to knowledge of the person skilled in the art that "[i]mportantly, inflammation in hereditary periodic fevers patients with mutations in NALP3 can be markedly improved by treatments designated to block IL-1beta**(20,21). Owing to the similarity between NALP3-mediated hereditary periodic fevers and gout and pseudogout, we can anticipate that similar treatments could benefit gout and pseudogout patients." (see page 240, left-hand column, lines 19 to 24; emphasis added).

12. In summary, the board is satisfied that document D5 teaches the skilled person that: (i) increased production of IL-1beta is the trigger for the auto-inflammation in gout as in other auto-inflammatory diseases; (ii) administration of colchicine completely blocks the crystal-induced production of IL-1beta and leads to greatly reduced inflammation and, (iii) gout patients were anticipated to benefit from treatments designated to block IL-1beta.

13. The board therefore concludes that document D5 itself suggests to the skilled person the treatment of gout by blocking IL-1beta.

14. Document D1 is an international patent application published shortly before the priority date of the present application. The applications have two inventors in common. The disclosure content of document D1 is largely identical to that of the latter, and in particular, all three examples are identical. The complete experimental disclosure of the application as filed was thus already known to the skilled person.