Hepatitis B virus (HBV) is a double-stranded DNA virus in the family Hepadnaviridae having an envelope that is a lipid bilayer, a nucleocapsid that is a protein, a DNA polymerase, and a genomic DNA. The envelope has S protein, M protein and L protein bound thereto, and a surface antigen (HBsAg) on S protein is involved in viral infection. HBsAg is a polypeptide consisting of 226 amino acids, and in HBsAg, there are 4 kinds of subtypes, that is, adw, ayw, adr and ayr. The adw has lysine as amino acid at each of positions 122 and 160 in HBsAg. The ayw has arginine as amino acid at position 122 and lysine as amino acid at position 160 in HBsAg. The adr has lysine as amino acid at position 122 and arginine as amino acid at position 160. The ayr has arginine as amino acid at each of positions 122 and 160.
Upon HBV infection, HBV releases a large amount of genomic DNA-free spherical or rod-shaped particles (pseudo-particles) into the blood. These particles contain HBsAg. Accordingly, the presence of HBsAg in a blood sample obtained by blood collection can be examined by using an anti-HBs antibody in order to examine the presence of HBV infection.
Since the evolution of viruses such as HBV is rapid, there is a high probability of mutation on the genome. By such mutation on the HBV genome, the amino acid sequence of HBsAg may be mutated to change its structure. When the structure of HBsAg is changed, an anti-HBs antibody used conventionally in HBV diagnosis cannot bind to HBsAg, and thus a patient infected with HBV may be diagnosed to be HBV-negative (false negative). If HBsAg having a mutation (mutant HBsAg) cannot be detected, a HBV host is not only influenced, but infection may also spread thorough afforded blood products and organs. Accordingly, use of anti-HBs antibody capable of binding not only to wild type HBsAg but also to mutant HBsAg is important for examination of HBV.
From this view point, various monoclonal antibodies capable of binding to both wild type HBsAg and mutant HBsAg have been developed so far. For example, a monoclonal antibody described in US2004/0219154A1 can bind to wild type HBsAg and 6 kinds of mutant HBsAgs.
However, various mutant HBsAgs have been reported besides the mutant HBsAgs that can be recognized by the monoclonal antibody described in US2004/0219154A1. There is a demand for development of a monoclonal antibody capable of binding not only to wild type HBsAg but also to mutant HBsAg that could not be detected so far.
USPTO Backgrounds
USPTO Backgrounds