Patent Strategies for Second-Generation Antibodies
Second-generation antibody patents are granted to antibodies that are considered novel and inventive, against a target that is already known. The novelty requirement of the claimed antibody is met if the antibody has unique or improved properties and functions. Defining an antibody by its structure and amino acid sequence, and by binding characteristics, such as epitope, affinity, and avidity can be possible options:
Structure and Sequence Specification
Specification by amino acid sequence of the claimed antibody provides a narrow, but clearly defined scope of protection. Amino acid sequence specifications for antibody patents may discourage the emergence of “biosimilars” in the market – as biosimilars are classified by having an identical amino acid sequence.
Sequence specification often includes reference to one or more complementarity determining regions (CDRs) of heavy and light chains of the immunoglobulin. A majority of antibody claims disclose the entire immunoglobulin sequence or 6 CDR sequences in claim. Antibody claims that are defined by sequence and CDR structures may also be coupled with a degree of flexibility for sequence identity and functional limitations. For example, a claim can define antibody sequences with 90% sequence identity to the disclosed sequences of the antibody. Additionally, some sequence claims also restrict the sequence to a specific functional capability of the antibody, such as neutralizing or inhibiting activity.
Describing the epitope for the claimed antibody can be used to fulfill the requirements of patent law. Additionally, epitope information may allow for freedom-to-operate rights, as binding epitopes on the antigen can differentiate between later-generation and earlier-generation antibodies that target the same antigen. If it is demonstrated that they have distinct binding epitopes, an antibody can target the same antigen as another antibody already patented. However, an existing antibody that binds to the same epitope and produces the same effect or outcome, even if the epitope was not previously described, can undermine the novelty of the claim.
Function by Binding Kinetics
Kinetic analysis can be used to define a claimed antibody with improved functional properties, based on its affinity, avidity, and binding kinetics. Claims such as these require additional evidence to describe the improved property of the antibody, and how it was developed in order to support the inventive step requirements. For example, affinity claims can define an antibody by improved affinity for its target by affinity maturation processes. Improved affinity for the target antigen can thus provide a greater therapeutic advantage. Typically, improved antibody kinetics are the result of alterations to the CDR sequences or antibody structure, which should be communicated as well.
Production Processes and Hybridoma Deposits
In combination with sequence specification, antibodies may be claimed based on a deposit of biological material from which the antibody can be produced from, such as a hybridoma cell line. These claims may refer to only part of the deposited antibody, such as a specific CDR domain. As such, the patent may extend to structural variations such as humanized or chimeric antibody formats derived from the same hybridoma cell line. Methods of production, such as immunization regimes or expression systems may also be used to claim antibodies. These claims are referred to as “product-by-process” which describe the methods and materials used to generate the resulting antibody.