COVALENTLY BONDED DIABODIES HAVING IMMUNOREACTIVITY WITH PD-1 AND LAG-3, AND METHODS OF USE THEREOF

• Main Authors: SCOTT KOENIG, JOHNSON LESLIE S, KALPANA SHAH, ROSS LA MOTTE- MOHS, PAUL A MOORE, EZIO BONVINI
• Format: Patent
• Language: English; Japanese
• Published: 14.05.2020
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

To provide pharmaceutical compositions that contain diabodies, and methods involving the use of the diabodies in treatment of cancer and other diseases and conditions.SOLUTION: The present invention is directed to bi-specific diabodies that comprise two or more polypeptide chains and possess at least one epitope-binding site that is immunospecific for an epitope of PD-1 and at least one epitope-binding site that is immunospecific for an epitope of LAG-3 (i.e., a "PD-1×LAG-3 bi-specific diabody"). More preferably, the present invention is directed to bi-specific diabodies that comprise four polypeptide chains and possess two epitope-binding sites that are immunospecific for one (or two) epitope(s) of PD-1 and two epitope-binding site that are immunospecific for one (or two) epitope(s) of LAG-3 (i.e., a "PD-1×LAG-3 bi-specific, tetra-valent diabody").SELECTED DRAWING: Figure 4 【課題】ダイアボディを含有する医薬組成物、並びに癌並びに他の疾患及び状態の治療におけるダイアボディの使用を伴う方法を提供する。【解決手段】２つ以上のポリペプチド鎖を備え、ＰＤ-１のエピトープに対して免疫特異的である少なくとも１つのエピトープ結合部位及びＬＡＧ-３のエピトープに対して免疫特異的である少なくとも１つのエピトープ結合部位を有する、二重特異性ダイアボディ（即ち「ＰＤ-１ｘＬＡＧ-３二重特異性ダイアボディ」）を対象とする。より好ましくは、４つのポリペプチド鎖を備え、ＰＤ-１の１つ（又は２つ）のエピトープに対して免疫特異的である２つのエピトープ結合部位及びＬＡＧ-３の１つ（又は２つ）のエピトープに対して免疫特異的である２つのエピトープ結合部位を有する、二重特異性ダイアボディ（即ち「ＰＤ-１ｘＬＡＧ-３二重特異性４価ダイアボディ」）を対象とする。【選択図】図４