PROBLEM TO BE SOLVED: To provide a method for obtaining an optimized humanized form of immunoglobulin which is not substantially immunogenic to a human, according to a technique based on structural data derived from crystallographic study and experimentally obtained.SOLUTION: The present invention provides a humanized anti-NGF antibody to NGF, or a fragment thereof which comprises (a) a VH region having a first CDR, a second CDR comprising a humanized amino acid sequence, and a third CDR； and (b) a VL region having the first CDR, the second CDR, and the third CDR； and is obtained by a method comprising steps of (i) obtaining crystal structures of the VH and VL region of anti-NGF antibody &alpha；D11, (ii) performing preliminary selection of a framework receptor of a human origin or humanized antibody, (iii) identifying the VH and VL region of the human origin of the anti-NGF antibody &alpha；D11, (iv) inserting a sequence of the CDR region of the anti-NGF antibody &alpha；D11 into a human sequence, (v) causing reverse mutation of one or more amino acid residues of the human VH and VL region.【課題】結晶学的研究に由来し実験的に得られる構造データに基づく手法による、ヒトに対して実質的に免疫原性でない最適化されたヒト化形態の免疫グロブリンを得る方法。【解決手段】NGFに対するヒト化抗NGF抗体またはその断片であって、(a)第一のCDR、ヒト化アミノ酸配列を含む第二のCDR、第三のCDRを有するVH領域；及び(b)第一のCDR、第二のCDR、第三のCDRを有するVL領域、を含み、(i)抗NGF抗体αD11のVHおよびVL領域の結晶構造を得、(ii)ヒト起源またはヒト化抗体のフレームワーク受容体予備選択し、(iii)前記抗NGF抗体αD11のヒト起源のVHおよびVL領域を同定し、(iv)ヒト配列内に前記抗NGF抗体αD11のCDR領域の配列を挿入し、(v)ヒトVHおよびVL領域の1つまたは複数のアミノ酸残基を復帰変異させる段階とを含む方法によって得た、ヒト化抗NGF抗体の提供。【選択図】なし
