Paris, October 13, 2021 – While European case law has long since limited the cases in which an antibody can be claimed solely by functional features, U.S. case law has recently moved in the same direction. Following two decisions by the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) involving Amgen and Sanofi, it could be argued that the U.S. case law has taken a more drastically limited view on claiming antibody functional features.
It is tempting to try to protect an antibody by its functional rather than structural features, thus allowing to cover any antibody having this function rather than only the antibody or antibodies developed by the applicant at the time of filing. Such functional protection allows one to obtain patent protection of new antibodies or derivatives generated during the development of the project, including the final candidate, which may be distinct from the antibodies initially identified. Such protection also hinders competitor’s development of competing antibodies.
However, the practice of patent offices as modified by court decisions has increasingly rejected this type of very broad claim for some time now in Europe and more recently in the United States.
The case law of the European Patent Office (EPO)
The case law of the EPO’s Technical Boards of Appeal has long established the principle that a claim is not insufficiently described simply because of a broad scope (see in particular decision T19/10).
Nevertheless, for some time now, the EPO’s Technical Boards of Appeal have held invalid certain claims defining an antibody solely by functional features, considering in a number of cases that implementing the invention in the whole scope of the claims would involve undue burden.
For example, in 2007, a claim to an antibody defined solely by its ability to bind to pyridinoline only when bound to a peptide and not in free form was held to be insufficiently described in T1466/05, in the absence of guidance in the application explaining how to obtain antibodies having this property beyond the one antibody exemplified in the patent.
In T601/05, a claim to an antibody broadly defined by its ability to bind TNFα and inhibit LPS-induced secretion by monocytes of TNFα was also found to be insufficiently described because the only method described in the patent specification for obtaining antibodies was shown by the patent’s opponents to be inadequate for obtaining the claimed antibodies.
More recently, a claim to an antibody defined by its antigen and its ability to inhibit the growth of a cancer cell expressing the antigen was also found to be insufficiently described (see T1389/13). The methods described in the patent for generating the antibodies of interest were found to demonstrate a broader function than that claimed, for which the patent did not provide sufficient guidance to be able to implement the invention without undue burden.
Thus, it is clear that many cumulative conditions, which must be verified on a case-by-case basis, are necessary to allow the issuance of claims directed to antibodies defined only by functional features. For such claims, the need for carefully assessing “whether the application provides an enabling disclosure across the whole scope claimed” is indeed now embodied in the new section G-II.5.6 of the Guidelines effective March 1, 2021, regarding the patentability of antibodies (see more particularly on this point subsection G-II-220.127.116.11).
However, when an application describes several antibodies having the claimed properties as well as a method for actually obtaining other antibodies having these properties, claims for antibodies defined only by functional features may still sometimes be granted. In such cases, it is difficult to challenge the sufficiency of disclosure in opposition, as the burden of proof of showing that it is not possible to implement the claim in their whole scope lies with the opponents.
When the conditions are met, claims directed to antibodies defined only by functional features can thus be granted by the EPO and survive opposition (see e.g. T2045/09).
Nevertheless, cases in which all the conditions are met to demonstrate sufficiency of disclosure of such claims remain rare and, despite the attractiveness of purely functional antibody claims, some patentees may prefer the security of claims including structural features, whose sufficiency of disclosure is much easier to defend.
A recent example is EP2215124B1 in the name of Amgen, which was granted with a claim 1 defining the antibody only by functional features. Claim 1 as granted was directed to an antibody defined by its antigen (PCSK9), its ability to reduce PCSK9 binding to the LDLR receptor, and its ability to compete for binding to PCSK9 with two antibodies defined by their heavy chain (VH) and light chain (VL) variable domain sequences.
This patent was the subject of an opposition procedure and followed by an appeal (T845/19). Despite a favorable decision of the Opposition Division regarding the sufficiency of disclosure of the claims, the patentee took the initiative to limit the claims during the appeal procedure to an antibody defined both by its antigen, its ability to reduce the binding of PCSK9 to the LDLR receptor, and by structural features (VH/VL pairs with at least 90% identity or presence of the 6 CDRs of exemplified antibodies), probably fearing that the purely functional claims would be considered insufficiently disclosed by the Board of Appeal.
Recent U.S. decisions
The Amgen patent family including EP2215124B1 contains several U.S. patents, among them US Patent Nos. 8,829,165 and 8,859,741. Amgen has brought an infringement action against various third parties, including Sanofi, on the basis of these patents.
The validity of the ‘165 and ‘741 patent claims was first appealed to the Federal Circuit in 2017, and the Federal Circuit issued a second decision on February 11, 2021. Amgen Inc. v. Sanofi-Aventis, LLC, 987 F.3d 1080 (Fed. Cir. 2021). Both decisions center on claims to an antibody defined by its ability to bind to certain amino acid residues of the PCSK9 antigen involved in cholesterol regulation.
The claims considered by the Federal Circuit included independent claim 1 of each of the ‘165 and ‘741 Patents are provided below:
US 8,829,165: 1. An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
US 8,859,741: 1. An isolated monoclonal antibody that binds to PCSK9, wherein the isolated monoclonal antibody binds an epitope on PCSK9 comprising at least one of residues 237 or 238 of SEQ ID NO: 3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
These claims attempt to define the antibody by functional characteristics only:
- an imprecise epitope: at least one residue selected in a list, and
- its ability to block PCSK9 binding to the LDLR.
First decision of the Federal Circuit in 2017
In 2017, the Federal Circuit overturned a district court decision in which the district court had refused to consider post-priority-date evidence related to the determination of whether the broadly claimed antibody was not enabled for failure to disclose a representative number of species of a claimed genus and incorrectly instructed the jury as to whether disclosure of a newly characterized antigen provides sufficient written description for a genus claim directed to corresponding antibodies. Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). Thus, the Federal Circuit cast doubt as to whether the claims of the ‘165 and ‘741 Patents would meet the enablement and written description requirements of 35 U.S.C. § 112.
The new decision of the Federal Circuit of February 11, 2021
Following this remand, the district court retried the case and a new decision was issued in which the claims were considered as not enabled. The Federal Circuit affirmed the district court’s finding of lack of enablement.
While not entirely questioning the theoretical possibility that functionally defined antibody claims may be enabled, the Federal Circuit considered that “such limitations pose high hurdles in fulfilling the enablement requirement for claims with broad functional language”, particularly where the scope is so broad that the experimental examples and guidance given in the application allow the invention to be implemented without undue experimentation in only a small portion of the claim scope. The evidence presented in the case “showed that the scope of the claim encompasses millions of candidates claimed with respect to multiple specific functions, and that it would be necessary to first generate and then screen each candidate antibody to determine whether it meets the double function claim limitations.”
Impact of the two decisions of the Federal Circuit
The two decisions of the Federal Circuit in Amgen v. Sanofi mark a turning point in U.S. practice regarding the assessment of antibody claims.
For example, since the 2017 Federal Circuit decision and following new examination guidelines issued by the USPTO, antibody claims defined solely by the antigen to which the antibody binds are now routinely rejected by the US office as lacking in written description. On the contrary, this type of claim remains acceptable in Europe when the antigen is novel and inventive (although such a case is rare).
The second 2021 decision is closer to European jurisprudence in those applications including broad functional claims must also include more experimental examples and guidance in the application to be certain that the invention may be implemented across the whole scope claimed.
However, it remains to be seen how this decision will be applied by the USPTO during examination and how much experimental effort will be considered undue leading to findings of lack of enablement. The EPO generally recognizes sufficiency of description (covering both US requirements of written description and enablement) when the invention can be implemented in substantially the whole claimed scope on the basis of guidance given in the application, even when numerous experiments are required, provided they merely apply the teaching of the patent and the general knowledge of the person skilled in the art, which is quite high in the field of antibodies.
It is not yet clear whether U.S. practice will also go this way or reject or invalidate as lacking enablement any antibody claim defined only functionally if many experiments (even routine ones) are required to implement the invention to its whole claimed scope. In the second case, the addition of structural features will certainly be necessary.
In any event, this second decision compromises the validity of U.S. patents already granted with antibody claims defined only functionally. In addition, although it is still too early to observe the effect of this decision on USPTO practice, it is likely to make it much more difficult to obtain issuance of such claims before the USPTO.
In view of the two Amgen v. Sanofi decisions that have significantly changed U.S. practice regarding antibody claims, it is more important than ever to determine at the patent application drafting stage whether or not the case may be suitable for antibody claims defined only functionally, and also to describe various structural features that can be used during examination or in litigation to overcome objections of insufficient disclosure that may be raised both in Europe and in the United States.
With its experience in defending antibody claims, REGIMBEAU’s Immunotherapy team is ready to advise you on the best strategies to implement to optimize the protection of your antibodies.