EP 3 666 797 B1 relates to antigen binding proteins that bind to proprotein convertase subtilisin kexin type 9 (PCSK9) and methods of using and making the antigen binding proteins.
EP 3 666 797 B1 results from a divisional application of EP 2 215 124.
The case is interesting in that there exists two decisions on the same patent.
The OD has rejected the opposition, whereas the UPC CD Munich revoked the patent.
There are similar conconclusions between the two fora. They relate to
- Added matter
- Priority
- Novelty
The difference lies in the appreciation of IS. For the CD UPC the claims lack IS.
The claim is identical in the wo decisions and claim 1 relates to a monoclonal antibody or an antigen-binding fragment thereof for use in treating or preventing hypercholesterolemia or an atherosclerotic disease related to elevated serum cholesterol levels; or for use in reducing the risk of a recurrent cardiovascular event related to elevated serum cholesterol levels.
The decision of the UPC CD Munich
Parties to the UPC proceedings were companies of the Sanofi group applying for revocation and Amgen as proprietor.
The skilled person
In the opinion of the CD, the skilled person in this case is a team including someone having a university degree in biological sciences (or biochemistry) and several years of (post-doctorate) experience in the field of antibody technology. The team also includes a researcher with a number of years post-doctorate research experience who is undertaking preclinical research into the treatment of cardiovascular diseases, and who has an interest in PCSK9 biology with respect to the role and function of PCSK9 in regulating LDL levels.
Claim interpretation
In view of the teaching of the patent as a whole, the skilled person would understand the claimed treatment not to be limited to a particular lowering of cholesterol levels as long as there is some (measurable) reduction of cholesterol levels in vivo and provided the therapy is safe.
The CD furthermore noted that the claimed use encompasses the administration of the claimed antibodies together with at least one other cholesterol-lowering agent, notably statins (claims 6 and 7 of the Patent). This confirms the understanding of the skilled person that also a (very) small cholesterol-lowering effect caused by the claimed antibodies can be “therapeutically effective” in the sense of the claimed treatments.
For the skilled person, it will be apparent that the patentee has chosen a broader claim wording instead of defining the claimed antibodies in a narrower way.
The actual decision
The CD Munich came to the conclusion that the Patent as granted is invalid because it does not involve an IS over Lagace. AR 1-17 lack IS for the same reasons.
The skilled person who was interested in developing a treatment for hypercholesterolemia targeting PCSK9 would, starting from and following the teaching of Lagace, without inventive skill develop antibodies against PCSK9 that block the interaction of PCSK9 with the LDLR and would thereby arrive at the claimed subject matter in an obvious way.
For the CD Munich there is no apparent causal technical connection between the feature “binds to the catalytic domain” and the reduction of the binding of PCSK9/LDRL and, ultimately, the therapeutic effect claimed.
The CD Munich was of the opinion that the feature of binding to the catalytic domain cannot contribute to IS. The skilled person knew at the relevant date that PCSK9 consisted of three domains.
Specifying that the antibodies bind to the catalytic domain as interpreted by the skilled person, is an arbitrary choice out of several possibilities that cannot render the claimed subject matter inventive.
The procedure before the EPO
Parties to the opposition procedure were a company of the Sanofi group, also party at the UPC and Regeneron Pharmaceuticals.
Lagace in UPC proceedings=D5 in opposition proceedings.
The OD decided to reject the oppositions. An appeal is pending before the BoA EPO.
Granted claim 1 is a second medical use claim. The OD agreed with the proprietor that D5 only suggests but does not provide therapeutic experimental evidence using monoclonal antibodies.
The OD considered that antibodies that block PCSK9’s interaction with the LDLR were not produced in D5, therefore, this represents a difference between the subject matter claimed and D5.
The OD agreed with the proprietor and considered that the objective technical problem, starting form D5, is the provision of a therapeutically effective treatment, prevention or risk reduction of the conditions related to elevated serum cholesterol levels referred to in the claims.
The problem is solved by the provision of monoclonal antibodies or antigen binding fragments thereof that bind to the catalytic domain of PCSK9 of the amino acid sequence of SEQ ID 1 and prevent or reduce the binding or PCSK9 to LDLR and which demonstrated – for the first time – in the patent an in vivo therapeutic effect of lowering serum cholesterol levels, as shown in example 26 of the opposed patent.
The OD was of the opinion that in view of all the evidence in D5, the skilled person would have been motivated to investigate the hypothesis as suggested in D5, last sentence on page 3002.
The OD shared the view of the opponents and was of the opinion that the feature “binding to the catalytic domain” is an arbitrary feature that does not give rise to a surprising special technical effect.
The OD considered that following the suggestion of D5 to provide anti-PCSK9 antibodies that block the interaction of PCSK9 with LDLR, the skilled person would be motivated to do so and would arrive at antibodies that bind to the catalytic domain,
The in vitro and in vivo experiments with exogenous PCSK9, together with the known genetic studies, as disclosed and discussed in D5 provide an indication that blocking PCSK9 might have an effect on LDLR, however, this does not equate to a reasonable expectation of success that antibodies that block the interaction of PCSK9 to LDLR would indeed be therapeutically effective in treating or preventing hypercholesterolemia or an atherosclerotic disease related to elevated serum cholesterol levels; or in reducing the risk of a recurrent cardiovascular event related to elevated serum cholesterol levels.
Therefore, the OD concluded that the subject matter of claim 1 involves an IS in view of D5 alone, D5 in combination with D7 or D5 in combination with D57.
Comments
It is interesting to see the OD and the CD, although they were starting from the same CPA, they nevertheless came to opposite conclusions.
Both came to the conclusion that the feature “binding to the catalytic domain” is an arbitrary feature that does not give rise to a surprising special technical effect.
They fundamentally differed in the expectation of success for a therapeutic effect.
For the OD, a therapeutic effect could not be inferred from D5 with a reasonable expectation of success.
For the CD, there is no apparent causal technical connection between the feature “binds to the catalytic domain” and the reduction of the binding of PCSK9/LDRL and the therapeutic effect claimed.
I am not in a position to decide which forum is right, but the difference in approach is striking.
It will be interesting to see what the CoA UPC and the BoA EPO will decide.
Should the patent be revoked in both fora, the matter is settled.
In case of diverging decisions
If both decisions remain different after the second instance, it could have dear consequences for the proprietor.
If the patent is revoked by the UPC, but not by the EPO, the question of compensation for the proprietor will have to be raised.
According to the chairman of the CoA UPC, expressed at a CEIPI meeting on “Two years of UPC” in the spring of 2025, the French solution should be adopted: no compensation for the proprietor.
I am not convinced that the solution will be as simple as that, as France seems isolated in this matter.
It is therefore to be hoped that the appeal at the EPO BoA will accelerate the procedure ex-officio, so that the decision of the EPO will become binding for the UPC.
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