What are Antibodies
Antibodies are a class of proteins that are generated by the immune system to neutralize foreign pathogens such as bacteria, fungi and viruses. Although the general structures of different antibodies are very similar, only the relatively small “variable” regions, located near the tip of the protein, are involved in the binding of an antibody to a particular target, or antigen. Within these variable regions are six “hypervariable” regions, also known as complementarity determining regions (CDRs). The diversity contained within these CDRs represents a significant portion of the overall diversity amongst antibodies, and is responsible for the ability of otherwise structurally similar antibodies to specifically bind vastly different antigens. (see also: http://en.wikipedia.org/wiki/Monoclonal_antibody_therapy)
Therapeutic antibodies were first isolated by injecting antigens into mice to generate mouse (or murine) antibodies. While similar to human antibodies in their general structure, the protein sequence of mouse antibodies is very different from that of human antibodies. Because of this difference, when mouse antibodies are used therapeutically in humans, they are recognized as foreign by the human immune system. This results in the generation of human anti-mouse antibodies (HAMAs), which neutralize the mouse antibodies and thereby eliminate their therapeutic value.
To begin to address this immunogenicity problem, scientists created “chimeric” antibodies by grafting the variable regions of mouse antibodies onto the constant domains of human antibodies. Chimeric antibodies alleviated some, but not all, of the immunogenicity issues encountered with mouse antibodies. Further humanization was therefore desired. This came through advances in computational approaches which enabled the identification of the specific regions within an antibody that confer binding. Transferring these specific binding regions (i.e., the CDRs) from mouse antibodies into otherwsie human variable regions allowed for the “humanization” of mouse-derived antibodies, resulting in “humanized” antibodies. While humanized antibodies generally do not induce an immune response in most patients, the humanization process is iterative, and therefore very time-consuming.
Recent advances in molecular and computational biology have enabled the de novo creation of antibodies that are, to varying extents, human in nature. Fully human antibodies are generally superior, in terms of both safety and efficacy, when compared to mouse or chimeric antibodies. Adimab’s libraries contain only fully human antibodies. Moreover, Adimab’s proprietary library design strategy is the first to recreate the diversity contained within the natural human pre-immune repertoire by explicitly accounting for the recombination of the human immunoglobulin gene segments (i.e., V, D, and J). The result is a unique antibody library that can be readily screened to identify large numbers of IgGs specific to a particular target, with very broad sequence diversity and epitopic coverage.