JPWO2021155380A5 - - Google Patents

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JPWO2021155380A5
JPWO2021155380A5 JP2022547063A JP2022547063A JPWO2021155380A5 JP WO2021155380 A5 JPWO2021155380 A5 JP WO2021155380A5 JP 2022547063 A JP2022547063 A JP 2022547063A JP 2022547063 A JP2022547063 A JP 2022547063A JP WO2021155380 A5 JPWO2021155380 A5 JP WO2021155380A5
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Priority claimed from PCT/US2021/016104 external-priority patent/WO2021155380A1/en
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二重特異性分子であって、A bispecific molecule,
(1)scfvフォーマットの第1の抗DLL3抗体の抗原結合断片と、scfvフォーマットの抗CD3抗体の抗原結合断片とを含む、第1のポリペプチド鎖であって、(1) a first polypeptide chain comprising an antigen-binding fragment of a first anti-DLL3 antibody in scfv format and an antigen-binding fragment of an anti-CD3 antibody in scfv format,
前記第1の抗DLL3抗体の抗原結合断片は、配列番号7に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号14に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号27に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号31に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号40に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号47に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む、第1のポリペプチド鎖、The antigen-binding fragment of the first anti-DLL3 antibody has a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 7, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 14, and a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 27. A heavy chain variable region comprising a heavy chain CDR3 comprising at least the amino acid sequence; a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 31; a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 40; and SEQ ID NO: 47. a first polypeptide chain comprising a light chain variable region comprising a light chain CDR3 comprising at least the amino acid sequence set forth in
(2)第2の抗DLL3抗体の重鎖を含む第2のポリペプチド鎖、及び(2) a second polypeptide chain comprising a heavy chain of a second anti-DLL3 antibody, and
(3)第2の抗DLL3抗体の軽鎖を含む第3のポリペプチド鎖、(3) a third polypeptide chain comprising a light chain of a second anti-DLL3 antibody;
の3つのポリペプチド鎖を含む、二重特異性分子。A bispecific molecule containing three polypeptide chains.
前記第2のポリペプチド鎖は、第2の抗DLL3抗体の重鎖を含み、前記第2の抗DLL3抗体の重鎖は、配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域を含み、かつThe second polypeptide chain comprises a heavy chain of a second anti-DLL3 antibody, and the heavy chain of the second anti-DLL3 antibody comprises a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, SEQ ID NO: a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24, and
前記第3のポリペプチド鎖は、第2の抗DLL3抗体の軽鎖を含み、前記第2の抗DLL抗体の軽鎖は、配列番号33に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域を含む、請求項1に記載の二重特異性分子。The third polypeptide chain comprises a light chain of a second anti-DLL3 antibody, and the light chain of the second anti-DLL3 antibody comprises a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 33, SEQ ID NO: 49. The bispecific molecule according to claim 1, comprising a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 49.
前記第1のポリペプチド鎖中の抗CD3抗体の抗原結合断片は、配列番号256を含む重鎖可変領域及び配列番号261を含む軽鎖可変領域を含む、請求項1に記載の二重特異性分子。2. The bispecific antibody of claim 1, wherein the antigen-binding fragment of the anti-CD3 antibody in the first polypeptide chain comprises a heavy chain variable region comprising SEQ ID NO: 256 and a light chain variable region comprising SEQ ID NO: 261. molecule. 前記第1のポリペプチド鎖中の第1の抗DLL3抗体の抗原結合断片は、配列番号72を含む重鎖可変領域及び配列番号76を含む軽鎖可変領域を含み、The antigen-binding fragment of the first anti-DLL3 antibody in the first polypeptide chain comprises a heavy chain variable region comprising SEQ ID NO: 72 and a light chain variable region comprising SEQ ID NO: 76;
前記第1のポリペプチド鎖中の抗CD3抗体の抗原結合断片は、配列番号256を含む重鎖可変領域及び配列番号261を含む軽鎖可変領域を含み、The antigen-binding fragment of the anti-CD3 antibody in the first polypeptide chain comprises a heavy chain variable region comprising SEQ ID NO: 256 and a light chain variable region comprising SEQ ID NO: 261;
前記第2のポリペプチド鎖中の第2の抗DLL3抗体の重鎖は、配列番号58に記載のアミノ酸配列を含み、かつThe heavy chain of the second anti-DLL3 antibody in the second polypeptide chain comprises the amino acid sequence set forth in SEQ ID NO: 58, and
前記第3のポリペプチド鎖中の第2の抗DLL3抗体の軽鎖は、配列番号78に記載のアミノ酸配列を含む、請求項1に記載の二重特異性分子。78. The bispecific molecule of claim 1, wherein the light chain of the second anti-DLL3 antibody in the third polypeptide chain comprises the amino acid sequence set forth in SEQ ID NO:78.
前記第1のポリペプチド鎖は、配列番号347に記載のアミノ酸配列を含み、前記第2のポリペプチド鎖は、配列番号276に記載のアミノ酸配列を含み、前記第3のポリペプチド鎖は配列番号297に記載のアミノ酸配列を含む、請求項1に記載の二重特異性分子。The first polypeptide chain comprises the amino acid sequence set forth in SEQ ID NO: 347, the second polypeptide chain comprises the amino acid sequence set forth in SEQ ID NO: 276, and the third polypeptide chain comprises the amino acid sequence set forth in SEQ ID NO: 276. Bispecific molecule according to claim 1, comprising the amino acid sequence according to 297. 請求項1に記載の二重特異性分子を含む、癌治療において使用するための医薬組成物。A pharmaceutical composition for use in cancer therapy comprising a bispecific molecule according to claim 1. 前記癌が、乳癌、肺癌、腎癌、膀胱癌、尿路癌、尿道癌、陰茎癌、外陰癌、膣癌、子宮頸癌、結腸癌、卵巣癌、前立腺癌、膵臓癌、胃癌、脳癌、頭頸部癌、皮膚癌、子宮癌、精巣癌、食道癌及び肝臓癌からなる群から選択される、請求項6に記載の医薬組成物。The cancer is breast cancer, lung cancer, kidney cancer, bladder cancer, urinary tract cancer, urethral cancer, penile cancer, vulvar cancer, vaginal cancer, cervical cancer, colon cancer, ovarian cancer, prostate cancer, pancreatic cancer, stomach cancer, brain cancer. , head and neck cancer, skin cancer, uterine cancer, testicular cancer, esophageal cancer, and liver cancer. 前記癌が、小細胞肺癌(SCLC)又は神経内分泌起源の癌である、請求項6に記載の医薬組成物。7. The pharmaceutical composition according to claim 6, wherein the cancer is small cell lung cancer (SCLC) or a cancer of neuroendocrine origin. 癌治療のための医薬の製造における、請求項1に記載の二重特異性分子の使用。Use of a bispecific molecule according to claim 1 in the manufacture of a medicament for the treatment of cancer. 前記癌が、乳癌、肺癌、腎癌、膀胱癌、尿路癌、尿道癌、陰茎癌、外陰癌、膣癌、子宮頸癌、結腸癌、卵巣癌、前立腺癌、膵臓癌、胃癌、脳癌、頭頸部癌、皮膚癌、子宮癌、精巣癌、食道癌及び肝臓癌からなる群から選択される、請求項9に記載の使用。The cancer is breast cancer, lung cancer, kidney cancer, bladder cancer, urinary tract cancer, urethral cancer, penile cancer, vulvar cancer, vaginal cancer, cervical cancer, colon cancer, ovarian cancer, prostate cancer, pancreatic cancer, stomach cancer, brain cancer. , head and neck cancer, skin cancer, uterine cancer, testicular cancer, esophageal cancer and liver cancer. 前記癌が、小細胞肺癌(SCLC)又は神経内分泌起源の癌である、請求項9に記載の使用。10. The use according to claim 9, wherein the cancer is small cell lung cancer (SCLC) or a cancer of neuroendocrine origin. 請求項1に記載の二重特異性分子を含む、DLL3発現細胞に対するT細胞の活性化において使用するための、医薬組成物。A pharmaceutical composition comprising a bispecific molecule according to claim 1 for use in the activation of T cells against DLL3 expressing cells. 請求項1に記載の前記二重特異性分子をコードするヌクレオチド。A nucleotide encoding the bispecific molecule of claim 1. CD3、CD28又はCD137を活性化するアゴニスト抗体と対を形成したDLL3に結合する抗体であって、
(1)配列番号7に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号14に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号27に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号31に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号40に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号47に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(2)配列番号1に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号11に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号22に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号32に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号39に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号54に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(3)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号33に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(4)配列番号5に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号33に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(5)配列番号2に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号10に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号22に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号32に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号46に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号55に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(6)配列番号1に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号11に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号22に記載のアミノ酸配列を少なくとも含む重鎖CDR3と、配列番号32に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号46に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号55に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(7)配列番号3に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号13に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号28に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号32に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号46に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号54に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(8)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号15に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号25に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号33に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号51に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(9)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号25に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号33に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号51に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(10)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号18に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号25に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号33に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号51に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(11)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号25に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号33に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号51に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(12)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号15に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号34に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(13)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含むCDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号34に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(14)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号18に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号34に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(15)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号34に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(16)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号15に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号25に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号37に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号42に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号51に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(17)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号25に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号37に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号42に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号51に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(18)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号18に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号25に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号37に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号42に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号51に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(19)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号25に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号37に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号42に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号51に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(20)配列番号7に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号15に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号38に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号42に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(21)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号38に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号42に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(22)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号18に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号38に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号42に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(23)配列番号6に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号38に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号42に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号49に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(24)配列番号5に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号25に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号33に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号51に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(25)配列番号5に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号16に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号24に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号34に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号50に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(26)配列番号5に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号17に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号26に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号34に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号43に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号50に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;
(27)配列番号8に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号19に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号23に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号35に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号45に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号52に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体;及び
(28)配列番号9に記載のアミノ酸配列を少なくとも含む重鎖CDR1、配列番号21に記載のアミノ酸配列を少なくとも含む重鎖CDR2、及び配列番号29に記載のアミノ酸配列を少なくとも含む重鎖CDR3を含む重鎖可変領域と、配列番号32に記載のアミノ酸配列を少なくとも含む軽鎖CDR1、配列番号39に記載のアミノ酸配列を少なくとも含む軽鎖CDR2、及び配列番号54に記載のアミノ酸配列を少なくとも含む軽鎖CDR3を含む軽鎖可変領域とを含む抗体
からなる群から選択される抗体。
An antibody that binds to DLL3 paired with an agonist antibody that activates CD3, CD28 or CD137,
(1) Contains a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 7, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 14, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 27. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 31, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 40, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 47. an antibody comprising a light chain variable region comprising CDR3;
(2) Contains a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 1, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 11, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 22. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 32, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 39, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 54. an antibody comprising a light chain variable region comprising CDR3;
(3) Contains heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 33, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region comprising CDR3;
(4) Contains a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 5, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 33, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region comprising CDR3;
(5) Contains a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 2, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 10, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 22. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 32, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 46, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 55. an antibody comprising a light chain variable region comprising CDR3;
(6) heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 1, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 11, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 22; A light chain variable comprising a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 32, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 46, and a light chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 55. an antibody comprising a region;
(7) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 3, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 13, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 28. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 32, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 46, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 54. an antibody comprising a light chain variable region comprising CDR3;
(8) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 15, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 25. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 33, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 51. an antibody comprising a light chain variable region comprising CDR3;
(9) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 25. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 33, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 51. an antibody comprising a light chain variable region comprising CDR3;
(10) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 18, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 25. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 33, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 51. an antibody comprising a light chain variable region comprising CDR3;
(11) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 25. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 33, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 51. an antibody comprising a light chain variable region comprising CDR3;
(12) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 15, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 34, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region comprising CDR3;
(13) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 34, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region;
(14) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 18, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 34, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region comprising CDR3;
(15) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 34, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region comprising CDR3;
(16) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 15, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 25. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 37, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 42, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 51. an antibody comprising a light chain variable region comprising CDR3;
(17) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 25. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 37, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 42, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 51. an antibody comprising a light chain variable region comprising CDR3;
(18) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 18, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 25. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 37, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 42, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 51. an antibody comprising a light chain variable region comprising CDR3;
(19) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 25. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 37, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 42, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 51. an antibody comprising a light chain variable region comprising CDR3;
(20) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 7, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 15, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 38, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 42, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region comprising CDR3;
(21) includes a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 38, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 42, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region comprising CDR3;
(22) includes a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 18, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 38, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 42, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region comprising CDR3;
(23) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 6, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 38, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 42, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 49. an antibody comprising a light chain variable region comprising CDR3;
(24) includes a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 5, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 25. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 33, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 51. an antibody comprising a light chain variable region comprising CDR3;
(25) includes a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 5, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 16, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 24. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 34, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 50. an antibody comprising a light chain variable region comprising CDR3;
(26) includes a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 5, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 17, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 26. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 34, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 43, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 50. an antibody comprising a light chain variable region comprising CDR3;
(27) Heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 8, heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 19, and heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 23. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 35, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 45, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 52. an antibody comprising a light chain variable region comprising CDR3; and
(28) includes a heavy chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 9, a heavy chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 21, and a heavy chain CDR3 comprising at least the amino acid sequence set forth in SEQ ID NO: 29. A heavy chain variable region, a light chain CDR1 comprising at least the amino acid sequence set forth in SEQ ID NO: 32, a light chain CDR2 comprising at least the amino acid sequence set forth in SEQ ID NO: 39, and a light chain comprising at least the amino acid sequence set forth in SEQ ID NO: 54. and a light chain variable region comprising CDR3.
そのCDRドメインが、変異している、欠失している、又は付加されている1、2、3、4又は5個のアミノ酸を有する、請求項14に記載の抗体。 15. The antibody of claim 14 , wherein the CDR domain has 1, 2, 3, 4 or 5 amino acids mutated, deleted or added. 前記抗体がヒト化されている、請求項14に記載の抗体。 15. The antibody of claim 14 , wherein said antibody is humanized. a)請求項14に記載の抗体、及び
b)薬学的に許容される担
を含む組成物。
15. A composition comprising a) an antibody according to claim 14 , and b) a pharmaceutically acceptable carrier .
DLL3発現細胞に対するT細胞の活性化において使用するための、請求項14に記載の抗体を含む医薬組成物 15. A pharmaceutical composition comprising an antibody according to claim 14 for use in the activation of T cells against DLL3 expressing cells. 癌治において使用するための、請求項14に記載の抗を含医薬組成物 15. A pharmaceutical composition comprising an antibody according to claim 14 for use in cancer therapy . 配列番号58又は72と少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%、少なくとも99%、又は少なくとも100%の配列同一性を有する重鎖可変ドメインを含むヒトDLL3タンパク質に結合するヒト化抗体。 A humanized human DLL3 protein that binds to a heavy chain variable domain that has at least 95 %, at least 96%, at least 97%, at least 98%, at least 99%, or at least 100% sequence identity with SEQ ID NO: 58 or 72. antibody. 配列番号76又は78と少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%、少なくとも99%、又は少なくとも100%の配列同一性を有する軽鎖可変ドメインを含むヒトDLL3タンパク質に結合するヒト化抗体。 A humanized human DLL3 protein that binds to a light chain variable domain that has at least 95 %, at least 96%, at least 97%, at least 98%, at least 99%, or at least 100% sequence identity with SEQ ID NO: 76 or 78. antibody. 配列番号58又は72と少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%、少なくとも99%、又は少なくとも100%の配列同一性を有するアミノ酸配列を含むヒト化ヒトDLL3抗体重鎖をコードする核酸配列。 Encodes a humanized human DLL3 antibody heavy chain comprising an amino acid sequence having at least 95 %, at least 96%, at least 97%, at least 98%, at least 99%, or at least 100% sequence identity to SEQ ID NO: 58 or 72 Nucleic acid sequences. 配列番号76又は78と少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%、少なくとも99%、又は少なくとも100%の配列同一性を有するアミノ酸配列を含むヒト化ヒトDLL3抗体軽鎖をコードする核酸配列。
Encodes a humanized human DLL3 antibody light chain comprising an amino acid sequence having at least 95 %, at least 96%, at least 97%, at least 98%, at least 99%, or at least 100% sequence identity to SEQ ID NO: 76 or 78 Nucleic acid sequences.
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