The US Patent Office recently issued a Memorandum following the decision by the US Court of Appeals in the case of Amgen v Sanofi.
USPTO Memorandum, 22 February 2018
The Memorandum suggests that the US Patent Office may be raising the bar on the written description requirement (as set out in 35 U.S.C. § 112) for antibody claims. The US Patent Office is currently preparing new training materials for examiners and an update to the Manual of Patent Examining Procedure (MPEP), both of which should shed some light on the new requirements for such claims.
Amgen v Sanofi
The patents forming the basis of the dispute were directed to antibodies that help reduce low-density lipoprotein cholesterol (LDL-C), or "bad cholesterol”, by inhibiting PCKS9 (a naturally occurring protein that binds to and causes the destruction of liver cell receptors (LDL[-]R) that are responsible for extracting LDL-C from the bloodstream).
In the first instance decision (District Court) Amgen’s patents were held to be valid and infringed by Sanofi’s therapeutic monoclonal antibody (‘Praluent®’). Sanofi appealed the decision on a number of legal grounds, the most significant of which being that the claims were allegedly invalid on the ground that they failed to meet the written description requirement as set out in 35 U.S.C. § 112.
The claim in question that Sanofi alleged was invalid reads as follows:
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 LDL[-]R.
This claim is a generic antibody claim wherein each of the claimed species (antibodies) falling within the genus are characterised in terms of their binding antigens (“binds to at least one of the following residues”) and functional properties (“blocks binding of PCSK9 to LDL[-]R”).
As a brief recap, antibodies are typically produced by injecting a mammal (usually a rabbit or mouse) with an antigen (such as a protein fragment or short synthetic peptide) that is usually bound to a carrier (such as albumin or keyhole limpet hemocyanin). This induces an immune response in the mammal, with antibodies that are reactive with the antigen being produced in vivo. The mammal is then sacrificed, and the antibody-producing cells of interest are harvested. After production of the corresponding antibody-producing hybridoma in the laboratory, the antibodies produced by the cells are collected. This is a well-understood and routine laboratory procedure, hence why claiming an antibody by reference to its binding antigen is generally an acceptable way of doing so.
The US Court of Appeals reviewed the case law surrounding such antibody claims. It was stated by the Court that an adequate written description must contain enough information about the actual makeup of the claimed products — "a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials," - which may be present in "functional" terminology "when the art has established a correlation between structure and function." The Court reiterated that in order to achieve such a “precise definition” for a generic antibody claim, a patentee must disclose "a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can `visualize or recognize' the members of the genus."
Referring to the case law and the present case, the Court noted that knowledge of the chemical structure of an antigen does not necessarily give the required kind of structure-identifying information about the corresponding antibodies (both expert witnesses in this case agreed that “an antibody [that] binds to a particular amino acid on PCSK9 ... does not tell you anything at all about the structure of the antibody”). Citing its decision in Ariad Pharmaceuticals v Eli Lilly, the Court stressed that the "newly characterized antigen" test could not stand because it contradicted the “quid pro quo” of the patent system, whereby one must describe an invention in order to obtain a patent.
This decision therefore suggests that it may no longer be enough to characterise an antibody by reference to an antigen, as it would allow the patentee “to claim antibodies by describing something that is not in the invention, i.e., the antigen.” If correct, then this may require a new approach to drafting claims to antibodies in the US.
It is not exactly clear to what extent this decision and corresponding Memorandum will impact upon the validity of generic antibody claims. That said, the Memorandum notes that “[i]n view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen , even when preparation of such an antibody is routine and conventional”. Similarly, the Memorandum states that “[t]he archived training materials are outdated and should not be relied upon as reflecting the current state of the law regarding 35 U.S.C. § 112”. It is therefore likely that the written description requirement for supporting generic antibody claims will change, which may prompt a change in the way in which a patentee claims antibodies in the US.
Of course, it is business as usual in other jurisdictions, notably Europe, where there remains no issue with claiming an antibody by reference to its binding antigen.
We will provide a further update regarding the written description requirements for antibody claims in the US upon publication of the new training materials and MPEP update. Should you have any concerns in the interim, then please feel free to contact us.