Monoclonal antibodies are important human therapeutic agents and represent some of the largest selling drugs in the world. Patents relating to antibodies are treated differently to some other compounds (e.g., small molecule drugs) in some jurisdictions. We have previously reported on some of the important similarities and differences in approaches of the USA and European Patent Offices to antibody patents, and what you may face if you propose to take a patent application directed to an antibody into prosecution or litigation in either region. This article touches on some of the important requirements for antibody patenting in some major Asian jurisdictions, namely Japan, China and South Korea.
Japan, China and South Korea have much in common when it comes to antibody patenting. Similar to the US and Europe, these jurisdictions will grant a patent for an antibody to a new antigen without production of an actual antibody, provided that the antigen is structurally described and has been ascribed some function.
To obtain a granted claim to an antibody where the antigen is known, all jurisdictions generally require that at least the antibody is structurally defined (e.g., by defining the six CDRs or both variable region sequences). Furthermore, similar to European practice, structural non-obviousness per se may be insufficient and it may be necessary to demonstrate that the antibody produces unexpected technical effect or was produced using non-conventional techniques.
The JPO Examination Guidelines indicate that a claim directed to an antibody may be defined by specifying the antigen recognized by it, the hybridoma that produces it, or by cross-reactivity with another antibody.
Similar to European practice structural non-obviousness per se is insufficient where there are other previously described antibodies against the same antigen. For an antibody claim to be considered inventive by the JPO, it may be necessary to demonstrate that the antibody has “unexpected properties” or there were difficulties overcome in obtaining the antibody even if well-known or routine methods are used (Glaxo Group Ltd. v. Commissioner Japan Patent Office, Heisei 15 (Gyo-ke) 104, 2003 (Tokyo H. Ct.)). It follows that if the antigen is known and the antibody is produced by routine methods and does not show an unexpected property, it may be considered obvious. These requirements can raise difficulties when faced with prior art that describes an antibody prophetically, to which you cannot compare to show an “unexpected property”.
Therefore, it is important to include in the description as many properties of your antibodies as possible (e.g., specificity, cross-reactivity, neutralising potency, stability, etc.). A recent decision by the IP High Court has opened the doors to allow post-filing comparative experimental data for establishing non-obviousness over a cited reference (The Procter & Gamble Company v. Commissioner Japan Patent Office, Heisei 21 (Gyo-ke) 10238, 2010 (Intellectual Property H. Ct.)). Thus, by including a general description of a variety of properties of your antibodies, you may later be able to produce evidence that such properties provide an advantage over prior art antibodies. If routine methods were used to produce or improve your antibody, you may also consider describing any difficulties overcome.
Pursuing claims to a class of antibodies defined by the functional properties, as opposed to the structural properties, can be difficult. This is not surprising given the JPO’s requirement for unpredictability to establish non-obviousness. The Japanese courts have conclusively determined that usefulness in regard to all peptides included in the scope of a claim should be clearly described in the specification or be easily identified by a person skilled in the art from the common general technical knowledge (Stanford University v. Commissioner Japan Patent Office, Heisei 10 (Gyo-ke) 95, 2000 (Tokyo H. Ct.)). If excessive trial and error or an innovation beyond that which can be expected from the skilled person is required, the support requirements may not be met.
It is worth keeping in mind that to satisfy the support requirements, the JPO requires that the specification describe actual data relating to a claimed composition (Astellas & Fujisawa v. Commissioner Japan Patent Office, Heisei 17 (Gyo-ke) 10312, 2005 (Intellectual Property H. Ct.)). Post-filing data showing such activity is not permissible under Japanese law to overcome a support rejection.
Assuming any antibodies specifically described in an application are non-obvious over the art, it is generally straightforward to obtain claims defining a new antibody by all six complementarily determining regions (CDRs) or one or both variable regions. However, like the US, the JPO is reluctant to grant claims defining an antibody by the sequence of its variable regions or CDRs, where the claim defines variation in the sequence (e.g., by defining a percentage identity or a consensus sequence). Unless all variations are disclosed in the specification, the courts have considered that it is doubtful whether all fragments or variations are biologically active (Stanford University v. Commissioner Japan Patent Office, Heisei 10 (Gyo-ke) 95, 2000 (Tokyo H. Ct.)).
Although claims to specific antibody sequences can be limiting, if they cover your commercial embodiment, such claims may be very valuable for protecting a product that is potentially very valuable.
Chinese practice to patenting of antibodies is very similar to Japan. In particular, the support and disclosure requirements share similar elements, that is, whether the scope of the claim is supported by the specification.
The Chinese Patent Re-examination Board have confirmed that broad claims defined by function and homology cannot be considered to be supported by the specification unless experimental data showing functionality of all homologous proteins is provided (Novo Nordisk vs. Longda Co.and Boli Co., Civil Judgments (2012) No.41 and 42 Tianjin High People's Court). Thus, Examiners (and their Guidelines) generally require that at least the specific sequences of all six CDRs (or both variable regions) of an antibody, as well as the target antigen, be included in the claims.
Similar to Japan and Europe, structural non-obviousness per se may be insufficient to establish patentability in view of other known antibodies before the Chinese Patent Office. For an antibody claim to be considered non-obvious under Chinese practice, “unexpected technical effects” must be shown in the specification. This includes properties that were not foreseeable from the prior art and any existing antibody against the target antigen. As for Japan, such properties may include binding affinity, selectivity of the binding, inhibitory activity etc. Post-filing data may be permissible to substantiate the non-obviousness or industrial applicability of the invention provided it is consistent with the teachings of the application. Post-filing data to show sufficiency of description, can be difficult to rely on in China.
Similar to Japan and China, the KIPO Guidelines require claiming the antibody by sequence unless the target antigen is novel, in which case the antibody can be defined by the target sequence.
In South Korea, where the antigen is known structural non-obviousness per se is insufficient and it is necessary to specify the technical features or functional significance of the antibody in the specification (e.g., antigen specificity, affinity etc.) (1998 Won 2040; 2000 Her 297). It is worth noting that the intellectual property tribunal has held that post-filing data can be relied on to establish the non-obviousness of a compound over the prior art, even when those data are not anticipated by the specification as filed.
To satisfy the description requirements in South Korea the specific means of production of the antibody (e.g., hybridoma) as well as antibody activity (e.g., epitope reactivity) must be disclosed in the specification (1998 Won 3919). However, unlike Japan and China, the submission of post-filing data is permitted in support of establishing enablement.
The scope of subject matter claimed in South Korea is generally limited to the disclosure or specific examples in the specification. Therefore, it is necessary to recite all six CDR sequences, as well as the target antigen in the claims. Thus, it is advisable that the specification includes more than one example. In practice, broader protection can be obtained when supported by multiple examples.
In light of the strict requirements towards antibody patenting in Japan, China and South Korea it is important to include sufficient information in the specification to obtain the broadest level of protection possible. Similar to our previous suggestions in relation to prosecuting claims to antibodies in Europe, some approaches that may assist with prosecuting in these jurisdictions, include:
- Including some form of structure in your claims (e.g., the sequence of the epitope and/or the sequence of the CDRs/variable region(s) of your antibody)
- Disclosing as many functional characteristics as possible in the specification (e.g., binding affinity, dissociation rates, cross reactivity and stability (this can assist in identifying an “unexpected property”)
- Comparing your antibodies to the prior art antibodies of which you are aware (this can assist with arguments of non-obviousness)
- Establishing the level of skill or unpredictability in the art at the time of filing (this can also assist in establishing non-obviousness), and
- Be willing to obtain claims specifically defining your preferred commercial antibody (or an antibody comprising all six CDRs or both variable region sequences), at least at first instance.