PROBLEM TO BE SOLVED: To provide a novel specific-binding molecule, particularly a human antibody as well as a fragment, derivative, and variant thereof, which recognize a neo-epitope of a disease-associated protein derived from a native endogenous protein but is prevalent in the body of a patient in a variant form and/or out of its normal physiological context； and also provide a pharmaceutical composition comprising such a novel specific-binding molecule and an antibody and mimic thereof, and a method for screening for the novel binding molecule.SOLUTION: The present invention provides a human-derived recombinant antibody against a pathological variant of an endogenous protein, which is prepared by purifying memory B cells, which do not express IgM antibodies, from a sample comprising antibodies that do not bind to corresponding tissues of a healthy subject, and amplifying fragments corresponding to the heavy chains and κ-light chains of antibodies from the obtained mRNA.SELECTED DRAWING: None【課題】天然内因性タンパク質から派生するが、異型において、及び／又は、それらの正常な生理学的状況から患者の体内に蔓延している、疾病関連タンパク質のネオエピトープを認識する、新規の特異的結合分子、特に、ヒト抗体、並びに、そのフラグメント、誘導体、及び変異体の提供。新規の特異的結合分子、その抗体及び模倣体を含む医薬組成物、並びに、新規の結合分子に対するスクリーニング方法の提供。【解決手段】健康な対象の対応する組織には結合しない抗体を含むサンプルから、ＩｇＭ抗体を発現しない記憶Ｂ細胞を精製し、取得したｍＲＮＡから抗体の重鎖およびκ軽鎖に対応するフラグメントを増幅して調製した、内因性タンパク質の病理学的変異体に対するヒト由来組換え抗体。【選択図】なし
