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The present invention provides methods of re-engineering or re-shaping an antibody from a first species, wherein the re-engineered or re-shaped antibo dy does not elicit undesired immune response in a second species, and the re- engineered or re-shaped antibody retains substantially the same antigen binding-ability of the antibody from the first species. In accordance with t he present invention, a combinatorial library comprising the CDRs of the antibo dy from the first species fused in frame with framework regions derived from a second species can be constructed and screened for the desired modified antibody. In particular, the present invention provides methods utilizing lo w homology acceptor antibody frameworks for efficiently humanizing an antibody or a fragment thereof. The present invention also provides antibodies produc ed by the methods of the invention.