by various embodiments of the present invention stems from the recognition that germline antibody genes are more likely than mature antibody genes to conserve essential amino acid sequence structures characteristic of individuals in the species hence less likely to be recognized as from a foreign source when used therapeutically in that species as used herein the term u201c key u201d residues refer to certain residues within the variable region that have more impact on the binding specificity and or affinity of an antibody in particular a humanized antibody a key residue includes but is not limited to one or more of the following a residue that is adjacent to a cdr a potential glycosylation site can be either n or o glycosylation site a rare residue a residue capable of interacting with the antigen a residue capable of interacting with a cdr a canonical residue a contact residue between heavy chain variable region and light chain variable region a residue within the vernier zone and a residue in the region that overlaps between the chothia definition of a variable heavy chain cdr1 and the kabat definition of the first heavy chain framework as used herein the term u201c humanized antibody u201d is an antibody or a variant derivative analog or fragment thereof which immunospecifically binds to an antigen of interest and which comprises a framework fr region having substantially the amino acid sequence of a human antibody and a complementary determining region cdr having substantially the amino acid sequence of a non human antibody as used herein the term u201c substantially u201d in the context of a cdr refers to a cdr having an amino acid sequence at least.