People in the art of the skill in this field knows Alteration of antibody framework while preserve the antibody function and features was not “obvious or “常规改造” with a reasonable expectation of success”. Antibody humanization is particularly an example in which CDRs of rodent antibodies are grafted to a suitable human framework while maintaining the original activity. Today, there is no well-identified strategy to create recombinant humanized antibody V-domains that preserve the antigen-binding characteristics of the parental antibody associated with high affinity, stability and solubility. The big challenging for this work is how to identify/screen for suitable human framework or generate mutations at key residues. As a result, many humanized antibodies in which only framework is changed have generated patents in the world (ref: Patents: US7732578B2 - Super humanized antibodies 2002).