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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- 125000003275 alpha amino acid group Chemical group 0.000 claims 189
- 229920001184 polypeptide Polymers 0.000 claims 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims 15
- 102000004196 processed proteins & peptides Human genes 0.000 claims 15
- 229940127276 delta-like ligand 3 Drugs 0.000 claims 14
- 101000928513 Homo sapiens Delta-like protein 3 Proteins 0.000 claims 7
- 206010028980 Neoplasm Diseases 0.000 claims 7
- 201000011510 cancer Diseases 0.000 claims 7
- 239000000427 antigen Substances 0.000 claims 6
- 102000036639 antigens Human genes 0.000 claims 6
- 108091007433 antigens Proteins 0.000 claims 6
- 239000012634 fragment Substances 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 206010041067 Small cell lung cancer Diseases 0.000 claims 4
- 102000053255 human DLL3 Human genes 0.000 claims 4
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 4
- 102100036466 Delta-like protein 3 Human genes 0.000 claims 3
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 208000032271 Malignant tumor of penis Diseases 0.000 claims 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 2
- 206010033128 Ovarian cancer Diseases 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 208000002471 Penile Neoplasms Diseases 0.000 claims 2
- 206010034299 Penile cancer Diseases 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 206010038389 Renal cancer Diseases 0.000 claims 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 210000001744 T-lymphocyte Anatomy 0.000 claims 2
- 208000024313 Testicular Neoplasms Diseases 0.000 claims 2
- 206010057644 Testis cancer Diseases 0.000 claims 2
- 206010046431 Urethral cancer Diseases 0.000 claims 2
- 206010046458 Urethral neoplasms Diseases 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
- 208000006593 Urologic Neoplasms Diseases 0.000 claims 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 2
- 206010047741 Vulval cancer Diseases 0.000 claims 2
- 208000004354 Vulvar Neoplasms Diseases 0.000 claims 2
- 230000004913 activation Effects 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 201000010881 cervical cancer Diseases 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 201000004101 esophageal cancer Diseases 0.000 claims 2
- 206010017758 gastric cancer Diseases 0.000 claims 2
- 201000010536 head and neck cancer Diseases 0.000 claims 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims 2
- 201000010982 kidney cancer Diseases 0.000 claims 2
- 201000007270 liver cancer Diseases 0.000 claims 2
- 208000014018 liver neoplasm Diseases 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 230000000955 neuroendocrine Effects 0.000 claims 2
- 150000007523 nucleic acids Chemical group 0.000 claims 2
- 238000011275 oncology therapy Methods 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 201000000849 skin cancer Diseases 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- 201000003120 testicular cancer Diseases 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- 206010046766 uterine cancer Diseases 0.000 claims 2
- 206010046885 vaginal cancer Diseases 0.000 claims 2
- 208000013139 vaginal neoplasm Diseases 0.000 claims 2
- 201000005102 vulva cancer Diseases 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
Claims (23)
(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.
(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.
b)薬学的に許容される担体
を含む組成物。 15. A composition comprising a) an antibody according to claim 14 , and b) a pharmaceutically acceptable carrier .
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.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202062968999P | 2020-01-31 | 2020-01-31 | |
US62/968,999 | 2020-01-31 | ||
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WO2021173307A1 (en) * | 2020-02-25 | 2021-09-02 | Gensun Biopharma Inc. | Trispecific t cell engagers |
AU2021329378A1 (en) | 2020-08-19 | 2023-03-23 | Xencor, Inc. | Anti-CD28 compositions |
TW202342534A (en) * | 2022-02-10 | 2023-11-01 | 大陸商上海齊魯製藥研究中心有限公司 | A bispecific antigen-binding molecule and use thereof |
WO2023164474A1 (en) | 2022-02-23 | 2023-08-31 | Amgen Inc. | Cancer treatment targeting dll3 |
WO2023196953A2 (en) * | 2022-04-08 | 2023-10-12 | The Wistar Institute Of Anatomy And Biology | Combinations of bispecific t cell engagers and methods of use thereof |
WO2023204290A1 (en) * | 2022-04-21 | 2023-10-26 | 愛知県 | Multispecific nanoparticle |
WO2023222135A1 (en) * | 2022-05-20 | 2023-11-23 | I-Mab Biopharma Co., Ltd. | A method of treating solid tumor |
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JP6130097B2 (en) * | 2008-10-01 | 2017-05-17 | アムゲン リサーチ (ミュンヘン) ゲーエムベーハー | PSCA × CD3, CD19 × CD3, C-MET × CD3, endosialin × CD3, EpCAM × CD3, IGF-1R × CD3, or FAPalpha × CD3 cross-species specific bispecific single chain antibody |
CA2894879A1 (en) * | 2012-12-19 | 2014-06-26 | Amplimmune, Inc. | B7-h4 specific antibodies, and compositions and methods of use thereof |
GB201302447D0 (en) * | 2013-02-12 | 2013-03-27 | Oxford Biotherapeutics Ltd | Therapeutic and diagnostic target |
MA41613A (en) * | 2015-02-23 | 2018-01-02 | Abbvie Stemcentrx Llc | ANTI-DLL3 CHEMERICAL ANTIGENIC RECEPTORS AND METHODS FOR USING SUCH RECEIVERS |
TWI793062B (en) * | 2015-07-31 | 2023-02-21 | 德商安美基研究(慕尼黑)公司 | Antibody constructs for dll3 and cd3 |
TW202016151A (en) * | 2018-06-09 | 2020-05-01 | 德商百靈佳殷格翰國際股份有限公司 | Multi-specific binding proteins for cancer treatment |
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