T 2500/12 - Plausibility strikes again (Alzheimer)

Key points

• In this examination appeal, a claim for a pharmaceutical composition "for use in the treatment, prevention or amelioration in an animal of Alzheimer's disease or other diseases characterized by amyloid deposits" was found to be insufficiently disclsoed. 
• The Board: "the question to be answered is whether or not either the application discloses that an immunogen containing the polyamino acid, defined in the claim, would be suitable (i.e. would plausibly be considered to be useful) for the treatment, prevention or amelioration in an animal, for example a human, patient of Alzheimer's disease [] (i.e. for the therapeutic use defined in the claim), or if the skilled person at the priority date would have known this." 
• " Even if it were accepted that it is at least plausible that the claimed constructs can elicit an immune response to Abeta, the board has seen no evidence in the application, that at the effective date, a direct and unambiguous link, for example, by means of an animal or in vitro model, had been established between the observed effect of eliciting anti-Abeta antibodies and the effective treatment of disease." 

EPO T 2500/12 - link

Reasons for the Decision

Main request - claim 1

Article 83 EPC - Disclosure of the invention

1. Article 83 EPC requires that the European patent application "disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art". In the case of a therapeutic use, it is established case law that the application must disclose the suitability of the product to be manufactured for the claimed therapeutic application, unless this was already known to the skilled person at the priority date. In this respect, showing a pharmaceutical effect in vitro may be sufficient if for the skilled person this observed effect directly and unambiguously reflects such a therapeutic application, or, if there is a clear and accepted relationship between the shown physiological activities and the disease (see Case Law of the Boards of Appeal of the European Patent Office, 8th edition, II.C.6.2 and decision T 609/02, reasons 9).

2. In the case at hand, the question to be answered is whether or not either the application discloses that an immunogen containing the polyamino acid, defined in the claim, would be suitable (i.e. would plausibly be considered to be useful) for the treatment, prevention or amelioration in an animal, for example a human, patient of Alzheimer's disease or other diseases characterized by amyloid deposits (i.e. for the therapeutic use defined in the claim), or if the skilled person at the priority date would have known this.

3. The appellant presented two main lines of argument in response to the above question.

3.1 Firstly, it was widely accepted in the art that Alzheimer's disease or other diseases characterized by amyloid deposits could be treated by generating an immune response to Abeta. It was therefore sufficient that the application made it plausible that such an immune response was generated. The application did this by showing, in a mouse model, that Abeta constructs including tetanus toxoid epitopes P2 and P30 were able to break self-tolerance and generate a suitable immune response.

3.2 Secondly, concerns about unsuitability based on potential negative side effects, such as those seen in clinical trials of AN1792, had been addressed by designing the claimed constructs to omit native T-cell epitopes. Data presented in the Pedersen declaration supported the thesis that the claimed constructs elicited a different immune response from that generated by vaccine AN1792. The former unexpectedly induced a specific IgG response while the latter induced an IgG and an IgM response.

4. As to the first line of argumentation, Example 2 of the application, relied upon by the appellant, concerns the immunogenicity of a construct, the so-called "construction 34", that contains three identical Abeta-43 fragments separated by tetanus toxoid epitopes P30 and P2 and shows that this construct can elicit an immune response in a mice transgenic for human APP, i.e. it is able to break self tolerance. However, this construct is not an embodiment of claim 1. It differs from the claimed constructs in that it contains full-length Abeta-43 rather than shorter sub-sections of said peptide. The application does not contain any evidence that the claimed constructs will behave in the same way as "construction 34" in the mouse model.

5. Even if it were accepted that it is at least plausible that the claimed constructs can elicit an immune response to Abeta, the board has seen no evidence in the application, that at the effective date, a direct and unambiguous link, for example, by means of an animal or in vitro model, had been established between the observed effect of eliciting anti-Abeta antibodies and the effective treatment of disease.

6. Thus, the application on its own does not disclose the suitability of the claimed constructs for the claimed therapeutic purpose. It remains to be assessed whether this suitability was already known to the skilled person at the relevant date of the application, for example because of a known clear and accepted relationship between the physiological activities shown in the application and the disease.

7. In this context, the appellant argued that the fact that the AN1792 vaccine had been tested in clinical trials illustrated that an Abeta based immunotherapy was commonly regarded as effective by the skilled person at the effective date of the patent, i.e. it was a widely accepted concept.

8. However, while these trials do illustrate that Abeta directed immunotherapy was widely regarded as attractive, the board has seen no evidence showing that these trials were regarded in the art as experimental proof of concept for the above mentioned type of therapy. Thus, the board is not satisfied that the clinical trials of the AN1792 vaccine show that ability to elicit an Abeta specific immune response was generally accepted in the art as proof that there was a known, clear and accepted relationship between Abeta based immunotherapy and the successful treatment, prevention or amelioration in an animal of Alzheimer's disease or other diseases characterized by amyloid deposits.

9. The data contained in the Pedersen declaration is not evidence for this either, as none of the reported experiments relate to treatment of clinical disease or models thereof. In fact, like example 2 of the application, the experiments described in said declaration relate to the ability to generate Abeta specific immunogenicity.

10. Thus, in the present case, the board is not satisfied that evidence of the ability to elicit an Abeta specific immune response is also evidence of the ability to successfully treat, prevent or ameliorate in an animal, Alzheimer's disease or other diseases characterized by amyloid deposits.

11. The line of argument relating to concerns about potential unsuitability of the claimed constructs in view of potential negative side effects is moot in view of the above considerations.

12. Thus, the board concludes that the suitability of the immunogen containing a polyamino acid defined in the claim for the treatment, prevention or amelioration in an animal of Alzheimer's disease or other diseases characterized by amyloid deposits (i.e. for the therapeutic use defined in the claim) is not shown by either the application or the prior art. The application therefore does not disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.