The present invention is directed to novel and improved methods for humanizing rabbit heavy and light variable regions. The resulting humanized rabbit heavy and light chains and antibodies and antibody fragments containing are well suited for use in immunotherapy and immunodiagnosis as they retain the antigen binding affinity of the parent antibody and based on their very high level of sequence identity to human antibody sequences should be essentially non-immunogenic in humans. The invention exemplifies the protocol for the manufacture of therapeutic humanized anti-human TNF-alpha and anti-human IL-6 antibodies.本發明係針對兔重可變區及輕可變區之新穎改良式人化方法。所得經人化之兔重鏈及輕鏈及其抗體及抗體片段極為適合用於免疫治療及免疫診斷，原因在於其保有親代抗體之結合親和力且基於其與人抗體序列之極為高度序列相同度，故須大致上於人體為非免疫原性。本發明舉例說明治療性經人化之抗人TNF－α抗體及抗人IL－6抗體之製造方案。
