As one of important functions of a protein, a capability to specifically bind to a specific molecule is exemplified. Such a capability plays an important role in an immunoreaction and signal transduction in a living body. A technology utilizing the capability has been developed for various purposes such as treatment and examination. An antibody can be exemplified as a protein which specifically binds to a specific molecule and which is one of particularly industrially utilized proteins. In addition, a protein which specifically binds to various antibodies in a manner except for an antigen-antibody reaction is also very industrially valuable, since such a protein can be used for detecting and purifying an antibody.
An industrially applicable antibody is basically an immunoglobulin G, i.e. IgG. As a IgG-binding protein, a cell wall protein of bacteria, such as Protein A, Protein G, Protein H and Protein L, has been well-known (Non-patent Document 1). Protein A is produced by gram-negative bacteria Staphylococcus aureus, and is a protein which binds to a Fc region of IgG. Protein G is produced by Streptococcus sp. classified into Group G, and is a protein which binds to a Fc region of IgG. Protein H is also produced by Streptococcus pyogenes classified into Group G as one of Streptococcus, and is a protein which binds to a Fc region of IgG. Protein L is produced by Peptostreptococcus spp., and is a protein which binds to a Fab region of IgG. Each protein contains a plurality of IgG-binding domains having 100 or less amino acid residues.
Recently, an antibody fragment which has a molecular structure of fragmented immunoglobulin G has been actively developed as a reagent for study use and clinical use. An immunoglobulin-binding protein which has a binding capability different from the above-described protein is also useful. For example, an immunoglobulin-binding protein which can bind to both of a Fc region and a Fab region is useful. It has been known that Protein A also binds to a Fab region; however, the Fab region to which Protein A can bind is only a Fab region of immunoglobulin G classified into the specific subfamily of VH germ cell gene, and the binding force to a Fab region is not strong in comparison with that to a Fc region (Non-patent Documents 1 and 2). It is known that Protein G binds to a Fab region though the binding force is weak; however, the association constant (KA) of Protein G to a Fab region is 10 times less than that to a Fc region (Non-patent Documents 1 and 2). As a protein which binds to both of a Fc region and a Fab region, a hybrid protein produced by coupling IgG-binding domains of Protein G or Protein A and Protein L has been developed (Patent Document 1 and Non-patent Document 3). However, such a protein leaves something to be desired in terms of versatility, since Protein L has a binding activity only to the Fab region consisting of κ chain.
USPTO Backgrounds
USPTO Backgrounds