http://ipkitten.blogspot.com/2022/04/epo-board-of-appeal-maintains.html
Antibodies may be defined in a patent claim by their amino acid sequence, by their target (epitope) and/or their functional characteristics. Functional and epitope antibody claims can capture a whole class (“genus”) of antibody therapeutics, whereas sequence claim language captures a far narrower field molecules. A recent Board of Appeal decision confirmed that genus antibody claims are not only allowable, but when put to the test, can survive appeal (T 1964/18).
Legal background: Antibody genus claims
As previously discussed hereon IPKat, there is currently a stark contrast between how the USPTO approaches functional claim language in the biotech field and the approach taken by patent offices in other major jurisdictions, including Europe. It is all but impossible to achieve grant of a functional or epitope antibody claim in the US in view of the stringent sufficiency (written description and enablement) requirements. By contrast, the EPO Guidelines for Examination (which were updated in 2020 to include an entire section devoted specifically to antibodies), explicitly state that an antibody may be defined in a patent claim by its epitope or function (G.II, 5.6). Despite this, there is a dearth of EPO Boards of Appeal case law on the allowability of epitope and broadly functional language in antibody claims.
| NK-cell mediated cell killing |
Board of appeal considers antibody epitope claim
T 1964/18 related to an appeal of the Opposition Division decision to revoke EP 1831258. The patent claimed an epitope and functionally defined genus of anti-NKG2A antibodies. The physiological function of NKG2A is as a receptor on NK cells. NK cells are a type of immune cell that target and kill harmful cells. The NKG2A receptor inhibits NK-cell mediated cell killing. As described in the patent spec, blocking NKG2A with a monoclonal antibody enhances NK-cell mediated cell killing. Importantly, the related NK cell receptors NKG2C and NKG2E activate NK-cell mediated cell killing. The claimed antibody was specific for NKG2A. Claim 1 of the main request was particularly directed to a monoclonal antibody or fragment thereof that a) specifically blocks NKG2A but not the related receptors NKG2C and E, and b) binds the same epitope on NKG2A as a deposited antibody, such that binding of the antibody to its target on a NK cell activates NK-cell killing.
The prior art cited against the inventive step of the claim disclosed the sequence of an anti-NKG2A antibody. This prior art antibody differed from the claimed antibody in that it bound not only NKG2A but also NKG2C and NKG2E. The technical effect in view of the prior art was thus identified by the Board of Appeal as the claimed antibody’s NKG2A-specific binding and consequent improved activation of NK-cell mediated cell killing.
The question thus became whether it would have been obvious to modify the prior art antibodies such that they only blocked the activity of NKG2A and not NKG2C and NKG2E. Importantly, contrary to the teaching of the patent, the prior art document proposed that an antibody blocking all three of NKG2A, C and E would lead to NK cell activation, partly due to the assumption that NKG2A expression on NK cells was far greater relative to NKG2C and E expression. The Board of Appeal was convinced that a skilled person would thus not have been motivated by this prior art document to produce antibodies that only bound NKG2A.
The Board of Appeal further rejected the argument that the skilled person would have combined the closest prior art document with another document relating to the expression of NKG2 receptors on NK cells. Particularly, the Board of Appeal found that combining the documents would involve hindsight, given that the lack of motivation from the closest prior art document to change the antibodies disclosed therein to solve the technical problem. Furthermore, the second document was not concerned with NK cell activation and so would not be considered relevant by a skilled person to the problem to be solved. The inventive step of broad functional epitope claim of the main request was thus accepted by the Board of Appeal.
What happened in the US?
Unsurprisingly, the outcome in Europe contrasts with the fate of the corresponding US patents. The US patents granted in the same family claim the specific hybridoma (US 8,993,319), or were limited to the antibody CDR sequences (US 10,160,810) following an objection from the Examiner that the epitope claims failed to satisfy the written description requirement. Particularly, the US Examiner raised the objection that there was “insufficient written description to demonstrate that applicant was in possession of the claimed genus of monoclonal antibodies that specifically bind NKG2A and do not specifically bind to NKG2C”.
Final thoughts
The decision of the Board of Appeal in T 1964/18 confirms that, in contrast to the USPTO, the EPO Boards of Appeal are perfectly happy to accept antibody claims limited with broad functional language, without limitation to specific antibody sequences. This Kat would be interested to hear from readers of any other recent cases in which claims directed to a genus of antibodies defined only by function and/or epitope have been maintained on appeal. In another notable case, T 1911/17, an epitope claim was not allowed, but this was due to a lack of clarity (Article 84 EPC) in the claim language with respect to how the epitope was defined (reasons 7-14). The claims of the auxiliary request in T 1911/17 related to a particular antibody produced by a deposited hybridoma (for more on hybridoma claims, see here). As biologic therapeutics continue to grow in clinical and economic importance, we can expect to see more consideration of these types of antibody cases by the Boards of Appeal.
Further reading
Reference to a hybridoma does not limit a product-by-process antibody claim (T 0032/17)
Strict US written description requirement applied to CAR-T-cell therapy (Juno v Kite)
Patenting Antibodies: The epitope claim is dead, long live the epitope claim
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