JPWO2019226973A5 - - Google Patents

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JPWO2019226973A5
JPWO2019226973A5 JP2020565405A JP2020565405A JPWO2019226973A5 JP WO2019226973 A5 JPWO2019226973 A5 JP WO2019226973A5 JP 2020565405 A JP2020565405 A JP 2020565405A JP 2020565405 A JP2020565405 A JP 2020565405A JP WO2019226973 A5 JPWO2019226973 A5 JP WO2019226973A5
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antibody
amino acid
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acid sequence
sirpa
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JP2021525082A (en
JP7337099B2 (en
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ヒトＳＩＲＰＡに結合する単離された抗体であって、抗体が、重鎖可変領域および軽鎖可変領域を含み、重鎖可変領域が、配列番号２０のアミノ酸配列を含むＨＶＲ－Ｈ１；配列番号２１のアミノ酸配列を含むＨＶＲ－Ｈ２；配列番号２２、２３、および２４から選択されるアミノ酸配列を含むＨＶＲ－Ｈ３を含み；軽鎖可変領域が、配列番号９のアミノ酸配列を含むＨＶＲ－Ｌ１；配列番号１０のアミノ酸配列を含むＨＶＲ－Ｌ２；ならびに配列番号１１、１２、１３、１４、１５、１６、１７、１８、および１９から選択されるアミノ酸配列を含むＨＶＲ－Ｌ３を含む、抗体。 An isolated antibody that binds to human SIRPA, the antibody comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 20; HVR-H1; SEQ ID NO: 21. HVR-H2 comprising the amino acid sequence of SEQ ID NO: HVR-H3 comprising the amino acid sequence selected from SEQ ID NOs: 22, 23, and 24; HVR-L1 in which the light chain variable region comprises the amino acid sequence of SEQ ID NO: 9; An antibody comprising HVR-L2 comprising the amino acid sequence of No. 10; and HVR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 11, 12, 13, 14, 15, 16, 17, 18, and 19. 重鎖可変領域が、配列番号２５のアミノ酸配列を含むＶＨ ＦＲ１、配列番号２６のアミノ酸配列を含むＶＨ ＦＲ２、配列番号２７のアミノ酸配列を含むＶＨ ＦＲ３、および配列番号２８のアミノ酸配列を含むＶＨ ＦＲ４から選択される１つ、２つ、３つまたは４つのフレームワーク領域を含む；かつ／または軽鎖可変領域が、配列番号２９のアミノ酸配列を含むＶＬ ＦＲ１、配列番号３０のアミノ酸配列を含むＶＬ ＦＲ２、配列番号３１のアミノ酸配列を含むＶＬ ＦＲ３、および配列番号３２のアミノ酸配列を含むＶＬ ＦＲ４から選択される１つ、２つ、３つまたは４つのフレームワーク領域を含む、請求項１に記載の抗体。 The heavy chain variable region includes VH FR1 containing the amino acid sequence of SEQ ID NO: 25, VH FR2 containing the amino acid sequence of SEQ ID NO: 26, VH FR3 containing the amino acid sequence of SEQ ID NO: 27, and VH FR4 containing the amino acid sequence of SEQ ID NO: 28. Contains one, two, three or four framework regions selected from ; and / or the light chain variable region is VL FR1 containing the amino acid sequence of SEQ ID NO: 29, VL containing the amino acid sequence of SEQ ID NO: 30. 1 according to claim 1 , comprising one, two, three or four framework regions selected from FR2, VL FR3 comprising the amino acid sequence of SEQ ID NO: 31, and VL FR4 comprising the amino acid sequence of SEQ ID NO: 32. Amino acid. 重鎖可変領域が、配列番号３３、３４、および３５から選択されるアミノ酸配列と少なくとも９０％、または少なくとも９５％、または少なくとも９９％同一であるアミノ酸配列を含む、請求項１または２に記載の抗体。 10. The claim 1 or 2 , wherein the heavy chain variable region comprises an amino acid sequence that is at least 90%, or at least 95%, or at least 99% identical to the amino acid sequence selected from SEQ ID NOs: 33, 34, and 35. antibody. 軽鎖可変領域が、配列番号３６、３７、３８、３９、４０、４１、４２、４３、および４４から選択されるアミノ酸配列と少なくとも９０％、または少なくとも９５％、または少なくとも９９％同一であるアミノ酸配列を含む、請求項１から３のいずれか一項に記載の抗体。 Amino acids whose light chain variable region is at least 90%, or at least 95%, or at least 99% identical to the amino acid sequence selected from SEQ ID NOs: 36, 37, 38, 39, 40, 41, 42, 43, and 44. The antibody according to any one of claims 1 to 3 , which comprises a sequence. ヒトＳＩＲＰＡに結合する単離された抗体であって、抗体が、重鎖可変領域および軽鎖可変領域を含み、重鎖可変領域が、配列番号２０のアミノ酸配列を含むＨＶＲ－Ｈ１；配列番号２１のアミノ酸配列を含むＨＶＲ－Ｈ２；配列番号２４から選択されるアミノ酸配列を含むＨＶＲ－Ｈ３を含み；軽鎖可変領域が、配列番号９のアミノ酸配列を含むＨＶＲ－Ｌ１；配列番号１０のアミノ酸配列を含むＨＶＲ－Ｌ２；および配列番号１６のアミノ酸配列を含むＨＶＲ－Ｌ３を含む、抗体。 An isolated antibody that binds to human SIRPA, the antibody comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 20; HVR-H1; SEQ ID NO: 21. HVR-H2 comprising the amino acid sequence of SEQ ID NO: 24; containing HVR-H3 comprising the amino acid sequence selected from SEQ ID NO: 24; the light chain variable region is HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9; amino acid sequence of SEQ ID NO: 10. An antibody comprising HVR-L2; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16. 重鎖可変領域が、配列番号２５のアミノ酸配列を含むＶＨ ＦＲ１、配列番号２６のアミノ酸配列を含むＶＨ ＦＲ２、配列番号２７のアミノ酸配列を含むＶＨ ＦＲ３、および配列番号２８のアミノ酸配列を含むＶＨ ＦＲ４から選択される１つ、２つ、３つまたは４つのフレームワーク領域を含む；かつ／または軽鎖可変領域が、配列番号２９のアミノ酸配列を含むＶＬ ＦＲ１、配列番号３０のアミノ酸配列を含むＶＬ ＦＲ２、配列番号３１のアミノ酸配列を含むＶＬ ＦＲ３、および配列番号３２のアミノ酸配列を含むＶＬ ＦＲ４から選択される１つ、２つ、３つまたは４つのフレームワーク領域を含む、請求項５に記載の抗体。 The heavy chain variable region includes VH FR1 containing the amino acid sequence of SEQ ID NO: 25, VH FR2 containing the amino acid sequence of SEQ ID NO: 26, VH FR3 containing the amino acid sequence of SEQ ID NO: 27, and VH FR4 containing the amino acid sequence of SEQ ID NO: 28. Contains one, two, three or four framework regions selected from; and / or the light chain variable region is VL FR1 containing the amino acid sequence of SEQ ID NO: 29, VL containing the amino acid sequence of SEQ ID NO: 30. 5. The fifth aspect of claim 5, comprising one, two, three or four framework regions selected from FR2, VL FR3 comprising the amino acid sequence of SEQ ID NO: 31, and VL FR4 comprising the amino acid sequence of SEQ ID NO: 32. Amino acid. 重鎖可変領域が、配列番号３５のアミノ酸配列と少なくとも９０％、または少なくとも９５％、または少なくとも９９％同一であるアミノ酸配列を含む、請求項５または６に記載の抗体。 The antibody according to claim 5 or 6, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90%, or at least 95%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 35. 軽鎖可変領域が、配列番号４１のアミノ酸配列と少なくとも９０％、または少なくとも９５％、または少なくとも９９％同一であるアミノ酸配列を含む、請求項５から７のいずれか一項に記載の抗体。 The antibody according to any one of claims 5 to 7, wherein the light chain variable region comprises an amino acid sequence that is at least 90%, or at least 95%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 41. ヒトＳＩＲＰＡに結合する単離された抗体であって、抗体が、重鎖可変領域および軽鎖可変領域を含み、重鎖可変領域が、配列番号３３、３４、および３５から選択されるアミノ酸配列を含み、軽鎖可変領域が、配列番号３６、３７、３８、３９、４０、４１、４２、４３、および４４から選択されるアミノ酸配列を含む、抗体。 An isolated antibody that binds to human SIRPA, wherein the antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region having an amino acid sequence selected from SEQ ID NOs: 33, 34, and 35. An antibody comprising, the light chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 36, 37, 38, 39, 40, 41, 42, 43, and 44 . ヒトＳＩＲＰＡに結合する単離された抗体であって、抗体が、重鎖可変領域および軽鎖可変領域を含み、重鎖可変領域が、配列番号３５のアミノ酸配列を含み、軽鎖可変領域が、配列番号４１のアミノ酸配列を含む、抗体。 An isolated antibody that binds to human SIRPA, wherein the antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 35, and the light chain variable region comprises. An antibody comprising the amino acid sequence of SEQ ID NO: 41. モノクローナル抗体である、請求項１から１０のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 10 , which is a monoclonal antibody. ヒト化抗体である、請求項１から１１のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 11 , which is a humanized antibody. Ｆａｂ断片、Ｆａｂ’断片、Ｆａｂ’－ＳＨ断片、Ｆ（ａｂ’）２断片、Ｆｖ断片、またはｓｃＦｖ断片である、請求項１から１２のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 12 , which is a Fab fragment, a Fab'fragment, a Fab'-SH fragment, an F (ab') 2 fragment, an Fv fragment, or an scFv fragment. 多価抗体である、請求項１から１３のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 13 , which is a polyvalent antibody. ＩｇＧクラス、ＩｇＭクラス、またはＩｇＡクラスの抗体である、請求項１から１４のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 14 , which is an IgG class, IgM class, or IgA class antibody. ＩｇＧクラスの抗体であり、ＩｇＧ１アイソタイプ、ＩｇＧ２アイソタイプ、ＩｇＧ３アイソタイプ、またはＩｇＧ４アイソタイプとしての抗体である、請求項１５に記載の抗体。 15. The antibody of claim 15 , which is an IgG class antibody and is an antibody as an IgG1 isotype, an IgG2 isotype, an IgG3 isotype, or an IgG4 isotype. 阻害型Ｆｃ受容体に結合する、請求項１から１６のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 16 , which binds to an inhibitory Fc receptor. 阻害型Ｆｃ受容体が、阻害型Ｆｃガンマ受容体ＩＩＢ（ＦｃｇＲＩＩＢ）である、請求項１７に記載の抗体。 17. The antibody of claim 17 , wherein the inhibitory Fc receptor is an inhibitory Fc gamma receptor IIB (FcgRIIB). ＦｃｇＲＩＩＢの細胞レベルを低下させる、請求項１８に記載の抗体。 The antibody according to claim 18 , which lowers the cellular level of FcgRIIB. 抗ＳＩＲＰＡ抗体が、ヒトのＩｇＧ１アイソタイプを有し、Ｎ２９７Ａ、Ｄ２６５Ａ、Ｄ２７０Ａ、Ｌ２３４Ａ、Ｌ２３５Ａ、Ｇ２３７Ａ、Ｐ２３８Ｄ、Ｌ３２８Ｅ、Ｅ２３３Ｄ、Ｇ２３７Ｄ、Ｈ２６８Ｄ、Ｐ２７１Ｇ、Ａ３３０Ｒ、Ｃ２２６Ｓ、Ｃ２２９Ｓ、Ｅ２３３Ｐ、Ｌ２３４Ｖ、Ｌ２３４Ｆ、Ｌ２３５Ｅ、Ｐ３３１Ｓ、Ｓ２６７Ｅ、Ｌ３２８Ｆ、Ａ３３０Ｌ、Ｍ２５２Ｙ、Ｓ２５４Ｔ、Ｔ２５６Ｅ、Ｎ２９７Ｑ、Ｐ２３８Ｓ、Ｐ２３８Ａ、Ａ３２７Ｑ、Ａ３２７Ｇ、Ｐ３２９Ａ、Ｋ３２２Ａ、Ｎ３２５Ｓ、Ｌ３２８Ｆ、Ｔ３９４Ｄ、およびこれらの任意の組合せ（残基の番号付けはＥＵ番号付けに従う）からなる群から選択される、Ｆｃ領域内のアミノ酸残基における１つもしくは複数のアミノ酸置換を含むか、またはＦｃ領域内のグリシン２３６に対応する位置におけるアミノ酸欠失を含む、請求項１から１９のいずれか一項に記載の抗体。 The anti-SIRPA antibody has a human IgG1 isotype and has N297A, D265A, D270A, L234A, L235A, G237A, P238D, L328E, E233D, G237D, H268D, P271G, A330R, C226S, C229S, E234L , P331S, S267E, L328F, A330L, M252Y, S254T, T256E, N297Q, P238S, P238A, A327Q, A327G, P329A, K322A, N325S, L328F, T394D, and any combination thereof (residues). A claim comprising one or more amino acid substitutions at an amino acid residue in the Fc region or an amino acid deletion at the position corresponding to glycine 236 in the Fc region, selected from the group consisting of (according to the appendix). The antibody according to any one of 1 to 19 . 抗体が、Ｃ１２７Ｓ、Ｌ２３４Ａ、Ｌ２３４Ｆ、Ｌ２３５Ａ、Ｌ２３５Ｅ、Ｓ２６７Ｅ、Ｋ３２２Ａ、Ｎ３２５Ｓ、Ｌ３２８Ｆ、Ａ３３０Ｓ、Ｐ３３１Ｓ、Ｅ３４５Ｒ、Ｅ４３０Ｇ、Ｓ４４０Ｙ、およびこれらの任意の組合せ（アミノ酸残基の番号付けは、ＥＵ番号付けまたはカバット番号付けに従う）からなる群から選択される残基位置における１つまたは複数のアミノ酸置換を含む、請求項１から２０のいずれか一項に記載の抗体。 Antibodies are C127S, L234A , L234F, L235A, L235E, S267E, K322A, N325S, L328F, A330S, P331S, E345R, E430G, S440Y, and any combination thereof (amino acid residue numbering is EU numbering. The antibody according to any one of claims 1 to 20 , comprising one or more amino acid substitutions at a residue position selected from the group consisting of (or according to Kabat numbering). Ｎ３２５Ｓ及びＬ３２８Ｆ置換を含む、請求項２１に記載の抗体。 21. The antibody of claim 21, comprising N325S and L328F substitutions. 全長抗体であり、重鎖がＣ末端リジン残基を含む、請求項１から２２のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 22, which is a full-length antibody and the heavy chain contains a C-terminal lysine residue. 重鎖がＣ末端リジン残基を欠く、請求項１から２２のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 22, wherein the heavy chain lacks a C-terminal lysine residue. 重鎖が配列番号５３のアミノ酸配列を含む、請求項１から２０のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 20, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 53. 重鎖が、配列番号５３のＣ末端リジン残基を除く配列番号５３のアミノ酸配列を含む、請求項１から２０のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 20, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 53 excluding the C-terminal lysine residue of SEQ ID NO: 53. 軽鎖が配列番号５０のアミノ酸配列を含む、請求項１から２４のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 24, wherein the light chain comprises the amino acid sequence of SEQ ID NO: 50. ヒトＳＩＲＰＡに結合する単離された抗体であって、配列番号５３のアミノ酸配列を含む重鎖および配列番号５０のアミノ酸配列を含む軽鎖を含む、抗体。 An isolated antibody that binds to human SIRPA, comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 53 and a light chain comprising the amino acid sequence of SEQ ID NO: 50. ヒトＳＩＲＰＡに結合する単離された抗体であって、配列番号５３のＣ末端リジン残基を除く配列番号５３のアミノ酸配列を含む重鎖を含み、かつ配列番号５０のアミノ酸配列を含む軽鎖を含む、抗体。 An isolated antibody that binds to human SIRPA, comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 53 excluding the C-terminal lysine residue of SEQ ID NO: 53, and a light chain comprising the amino acid sequence of SEQ ID NO: 50. Including antibodies. ヒトＳＩＲＰＡに結合する単離された抗体であって、配列番号５３のアミノ酸配列からなる重鎖および配列番号５０のアミノ酸配列からなる軽鎖を含む、抗体。 An isolated antibody that binds to human SIRPA, comprising a heavy chain consisting of the amino acid sequence of SEQ ID NO: 53 and a light chain consisting of the amino acid sequence of SEQ ID NO: 50. ヒトＳＩＲＰＡに結合する単離された抗体であって、配列番号５３のＣ末端リジン残基を除く配列番号５３のアミノ酸配列からなる重鎖を含み、かつ配列番号５０のアミノ酸配列からなる軽鎖を含む、抗体。 An isolated antibody that binds to human SIRPA, comprising a heavy chain consisting of the amino acid sequence of SEQ ID NO: 53 excluding the C-terminal lysine residue of SEQ ID NO: 53, and a light chain consisting of the amino acid sequence of SEQ ID NO: 50. Including antibodies. ヒトＳＩＲＰＡに結合する単離された抗体であって、抗体が重鎖および軽鎖を含み、
ａ）重鎖が配列番号４７のアミノ酸配列を含み、軽鎖が配列番号５０のアミノ酸配列を含む；
ｂ）重鎖が配列番号４８のアミノ酸配列を含み、軽鎖が配列番号５０のアミノ酸配列を含む；
ｃ）重鎖が配列番号４９のアミノ酸配列を含み、軽鎖が配列番号５０のアミノ酸配列を含む；
ｄ）重鎖が配列番号５４のアミノ酸配列を含み、軽鎖が配列番号５０のアミノ酸配列を含む；
ｅ）重鎖が配列番号５１のアミノ酸配列を含み、軽鎖が配列番号５０のアミノ酸配列を含む；
ｆ）重鎖が配列番号５２のアミノ酸配列を含み、軽鎖が配列番号５０のアミノ酸配列を含む；
ｇ）重鎖が配列番号５５のアミノ酸配列を含み、軽鎖が配列番号５０のアミノ酸配列を含む；
ｈ）重鎖が配列番号５６のアミノ酸配列を含み、軽鎖が配列番号５０のアミノ酸配列を含む；または
ｉ）重鎖が配列番号５７のアミノ酸配列を含み、軽鎖が配列番号５０のアミノ酸配列を含む、
抗体。 An isolated antibody that binds to human SIRPA, wherein the antibody comprises heavy and light chains.
a) The heavy chain contains the amino acid sequence of SEQ ID NO: 47 and the light chain contains the amino acid sequence of SEQ ID NO: 50 ;
b) The heavy chain contains the amino acid sequence of SEQ ID NO: 48 and the light chain contains the amino acid sequence of SEQ ID NO: 50;
c) The heavy chain contains the amino acid sequence of SEQ ID NO: 49 and the light chain contains the amino acid sequence of SEQ ID NO: 50;
d) The heavy chain contains the amino acid sequence of SEQ ID NO: 54 and the light chain contains the amino acid sequence of SEQ ID NO: 50;
e) The heavy chain contains the amino acid sequence of SEQ ID NO: 51 and the light chain contains the amino acid sequence of SEQ ID NO: 50;
f) The heavy chain contains the amino acid sequence of SEQ ID NO: 52 and the light chain contains the amino acid sequence of SEQ ID NO: 50;
g) The heavy chain contains the amino acid sequence of SEQ ID NO: 55 and the light chain contains the amino acid sequence of SEQ ID NO: 50;
h) The heavy chain comprises the amino acid sequence of SEQ ID NO: 56 and the light chain comprises the amino acid sequence of SEQ ID NO: 50;
i) The heavy chain comprises the amino acid sequence of SEQ ID NO: 57 and the light chain comprises the amino acid sequence of SEQ ID NO: 50.
antibody. 抗ＳＩＲＰＡ抗体が、ＳＩＲＰＡの細胞表面レベルを低下させるか、ＳＩＲＰＡの細胞内レベルを低下させるか、ＳＩＲＰＡの全細胞レベルを低下させるか、またはこれらの任意の組合せである、請求項１から３２のいずれか一項に記載の抗体。 13 . The antibody according to any one of the above. 抗ＳＩＲＰＡ抗体が、ＳＩＲＰＡの分解を誘導するか、ＳＩＲＰＡの切断を誘導するか、ＳＩＲＰＡの内部移行を誘導するか、ＳＩＲＰＡの放出を誘導するか、ＳＩＲＰＡの発現を下方調節するか、またはこれらの任意の組合せである、請求項１から３３のいずれか一項に記載の抗体。 Whether the anti-SIRPA antibody induces the degradation of SIRPA, the cleavage of SIRPA, the internal translocation of SIRPA, the release of SIRPA, the downregulation of the expression of SIRPA, or these. The antibody according to any one of claims 1 to 33 , which is an arbitrary combination. ｉｎ ｖｉｔｒｏおよび／またはｉｎ ｖｉｖｏのＳＩＲＰＡの細胞表面レベルを低減する、請求項１から３４のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 34 , which reduces the cell surface level of in vitro and / or in vivo SIRPA. ヒト単球および／またはヒトマクロファージ内のＳＩＲＰＡの発現を下方調節する、請求項１から３５のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 35 , which down-regulates the expression of SIRPA in human monocytes and / or human macrophages . ヒトマクロファージ内のＳＩＲＰＡの発現を約７０～９５％下方調節する、請求項３６に記載の抗体。 36. The antibody of claim 36 , which down-regulates the expression of SIRPA in human macrophages by about 70-95%. ６ｎＭ未満の、ヒトＳＩＲＰＡ ｖ１に対する親和性（ＫＤ）を有する、請求項１から３７のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 37 , which has an affinity (KD) for human SIRPA v1 and is less than 6 nM. 約０．１ｎＭ～２ｎＭの、ヒトＳＩＲＰＡ ｖ１に対する親和性（ＫＤ）を有する、請求項１から３８のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 38 , which has an affinity (KD) for human SIRPA v1 of about 0.1 nM to 2 nM. ｉｎ ｖｉｔｒｏにおけるＳＩＲＰＡの細胞表面レベルを、フローサイトメトリーにより測定される、ヒトＳＩＲＰＡ ｖ１に対して約０．０５～０．２０ｎＭ、ヒトＳＩＲＰＡ ｖ２に対して約０．０５～０．１０ｎＭ、および／またはカニクイザルＳＩＲＰＡに対して約０．０５～１ｎＭの５０％効果濃度（ＥＣ５０）で低減する、請求項１から３９のいずれか一項に記載の抗体。 Cell surface levels of SIRPA in vitro are measured by flow cytometry from about 0.05 to 0.20 nM for human SIRPA v1, about 0.05 to 0.10 nM for human SIRPA v2, and /. The antibody according to any one of claims 1 to 39 , which is reduced at a 50% effect concentration (EC50) of about 0.05 to 1 nM against cynomolgus monkey SIRPA. ヒトＳＩＲＰＡ、ヒトＳＩＲＰＡ ｖ１、ヒトＳＩＲＰＡ ｖ２、カニクイザルＳＩＲＰＡ、マーモセットＳＩＲＰＡ、およびヒトＳＩＲＰβ３に結合する、請求項１から４０のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 40 , which binds to human SIRPA, human SIRPA v1, human SIRPA v2, cynomolgus monkey SIRPA, marmoset SIRPA, and human SIRPβ3. 配列番号１のヒトＳＩＲＰＡ ｖ１のＤ３ドメインに結合する、請求項１から４１のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 41 , which binds to the D3 domain of human SIRPA v1 of SEQ ID NO: 1. 配列番号１のヒトＳＩＲＰＡ ｖ１のアミノ酸残基Ｒ２８２、Ｑ２８４、およびＧ３３７に結合する、請求項１から４２のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 42 , which binds to amino acid residues R282, Q284, and G337 of human SIRPA v1 of SEQ ID NO: 1. 抗ＳＩＲＰＡ抗体が、Ｍ１マクロファージ内の腫瘍細胞に対する食作用を増大させ、Ｍ２マクロファージ内の腫瘍細胞に対する食作用を増大させ、マクロファージ内のＣＤ１４の発現を下方調節し、かつ／またはこれらの任意の組合せである、請求項１から４３のいずれか一項に記載の抗体。 Anti-SIRPA antibodies increase phagocytosis of tumor cells in M1 macrophages, increase phagocytosis of tumor cells in M2 macrophages, downregulate the expression of CD14 in macrophages, and / or any of these. The antibody according to any one of claims 1 to 43 , which is a combination. 抗ＳＩＲＰＡ抗体が、Ｔ細胞の増殖を増強する、請求項１から４４のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 44 , wherein the anti-SIRPA antibody enhances the proliferation of T cells. 抗ＳＩＲＰＡ抗体が、ＳＩＲＰＡとＣＤ４７との相互作用を遮断せずに、Ｔ細胞の増殖を増強する、請求項１から４５のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 45 , wherein the anti-SIRPA antibody enhances the proliferation of T cells without blocking the interaction between SIRP A and CD47. 抗ＳＩＲＰＡ抗体が、単球内のＲＯＳの産生を刺激し、かつ／または単球内のＩＬ－８の発現を増大させる、請求項１から４６のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 46 , wherein the anti-SIRPA antibody stimulates the production of ROS in monocytes and / or increases the expression of IL-8 in monocytes. 抗ＳＩＲＰＡ抗体が、ｉｎ ｖｉｖｏにおける腫瘍増殖を阻害する、請求項１から４７のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 47 , wherein the anti-SIRPA antibody inhibits tumor growth in vivo. 抗ＳＩＲＰＡ抗体が、末梢血中のＣＤ１４＋骨髄細胞の数を低減し、かつ／または腫瘍内のＣＤ１４＋骨髄細胞の数を増大させる、請求項１から４８のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 48 , wherein the anti-SIRPA antibody reduces the number of CD14 + bone marrow cells in peripheral blood and / or increases the number of CD14 + bone marrow cells in a tumor. ヒトＳＩＲＰＡに結合するが、ＳＩＲＰＡへのＣＤ４７の結合を実質的に遮断しない、請求項１から４９のいずれか一項に記載の抗体。 The antibody according to any one of claims 1 to 49 , which binds to human SIRPA but does not substantially block the binding of CD47 to SIRPA. 請求項１から５０のいずれか一項に記載の抗体および薬学的に許容される担体を含む、薬学的組成物。 A pharmaceutical composition comprising the antibody according to any one of claims 1 to 50 and a pharmaceutically acceptable carrier. 請求項１から５０のいずれか一項に記載の抗体をコードする核酸配列を含む、単離された核酸。 An isolated nucleic acid comprising the nucleic acid sequence encoding the antibody according to any one of claims 1 to 50. 請求項５２に記載の核酸を含むベクター。 The vector containing the nucleic acid according to claim 52. 請求項５２に記載の核酸または請求項５３に記載のベクターを含む、単離された宿主細胞。 An isolated host cell comprising the nucleic acid of claim 52 or the vector of claim 53. 請求項１から５０のいずれか一項に記載の抗体を発現する、単離された宿主細胞。 An isolated host cell expressing the antibody according to any one of claims 1 to 50. 対象におけるがんの治療における使用のための、治療的有効量の請求項１から５０のいずれか一項に記載の抗ＳＩＲＰ抗体を含む組成物。 A composition comprising an anti-SIRP antibody according to any one of claims 1 to 50 in a therapeutically effective amount for use in the treatment of cancer in a subject . がんが、肉腫、膀胱がん、脳がん、乳がん、結腸がん、直腸がん、子宮内膜がん、腎臓がん、腎盂がん、白血病、肺がん、小細胞肺がん、メラノーマ、リンパ腫、膵臓がん、前立腺がん、卵巣がん、および線維肉腫、多形神経膠芽腫；腎明細胞癌；副腎皮質癌；膀胱尿路上皮癌、びまん性大細胞型Ｂ細胞リンパ腫、肺腺癌；膵腺癌、腎細胞がん、ホジキンリンパ腫、非ホジキンリンパ腫、無痛性Ｂ細胞リンパ腫、侵襲性Ｂ細胞リンパ腫、Ｔ細胞リンパ腫、急性リンパ芽球性白血病（ＡＬＬ）、急性骨髄性白血病（ＡＭＬ）、慢性リンパ性白血病（ＣＬＬ）、慢性骨髄性白血病（ＣＭＬ）、多発性骨髄腫、骨髄異形成症候群、骨髄増殖性新生物、浸潤性乳癌、子宮頸部扁平上皮癌、子宮頸部腺癌、胆管癌、結腸腺癌、びまん性大細胞型Ｂ細胞リンパ腫、食道癌、頭頸部扁平上皮癌、腎嫌色素細胞、腎乳頭細胞癌、低悪性度神経膠腫、肝細胞癌、肺扁平上皮癌、中皮腫、卵巣漿液性嚢胞腺癌（ｃｙｓｔａｄｅｎｏｍｃａｒｃｉｎｏｍａ）、膵腺癌、クロム親和性細胞腫および傍神経節腫、前立腺腺癌、直腸腺癌、皮膚黒色腫、胃腺癌、精巣生殖細胞腫瘍、甲状腺癌、胸腺腫（ｔｈｙｕｍｏｍａ）、子宮体内膜癌、子宮（ｕｔｅｒｎｉｎｅ）癌肉腫、ならびにブドウ膜メラノーマから選択される、請求項５６に記載の組成物。 Cancers include adenocarcinoma, bladder cancer, brain cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, renal pelvis cancer, leukemia, lung cancer, small cell lung cancer, melanoma, lymphoma, Pancreatic cancer, prostate cancer, ovarian cancer, and fibrosarcoma, polymorphic glioblastoma; clear renal cell carcinoma; adrenal cortical cancer; bladder urinary tract epithelial cancer, diffuse large B-cell lymphoma, lung adenocarcinoma Pancreatic adenocarcinoma, renal cell carcinoma, Hodgkin lymphoma, non-Hodgkin lymphoma, painless B-cell lymphoma, invasive B-cell lymphoma, T-cell lymphoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) , Chronic lymphocytic leukemia (CLL), Chronic myeloid leukemia (CML), Multiple myeloma, Myelodystrophy syndrome, Myelodysplastic neoplasm, Invasive breast cancer, Cervical squamous cell carcinoma, Cervical adenocarcinoma, Bile duct cancer, colon adenocarcinoma, diffuse large B-cell lymphoma, esophageal cancer, head and neck squamous epithelial cancer, renal chromophobe cells, renal papillary cell cancer, low-grade glioma, hepatocellular carcinoma, lung squamous epithelial cancer , Middle dermatoma, ovarian serous cystadenocarcinoma, pancreatic adenocarcinoma, chromium-affinitive cell adenocarcinoma and paraganglioma, prostate adenocarcinoma , rectal adenocarcinoma, cutaneous melanoma, gastric adenocarcinoma, testicular reproductive cell tumor, The composition according to claim 56 , which is selected from thyroid cancer, thyumoma, endocarcinoma, uternine carcinosarcoma, and vegetative melanoma. 使用が、ＰＤ１、ＰＤＬ１、ＣＤ４０、ＯＸ４０、ＩＣＯＳ、ＣＤ２８、ＣＤ１３７／４－１ＢＢ、ＣＤ２７、ＧＩＴＲ、ＣＴＬＡ４、ＰＤ－Ｌ２、Ｂ７－Ｈ３、Ｂ７－Ｈ４、ＨＶＥＭ、ＬＩＧＨＴ、ＢＴＬＡ、ＣＤ３０、ＴＩＧＩＴ、ＶＩＳＴＡ、ＫＩＲ、ＧＡＬ９、ＴＩＭ１、ＴＩＭ３、ＴＩＭ４、Ａ２ＡＲ、ＬＡＧ３、ＤＲ－５、ＣＤ２、ＣＤ５、ＣＤ３９、またはＣＤ７３を阻害するか、またはアゴナイズする治療剤の対象への投与をさらに含む、請求項５６または請求項５７に記載の組成物。 Used are PD1, PDL1, CD40, OX40, ICOS, CD28, CD137 / 4-1BB, CD27, GITR, CTLA4, PD-L2, B7-H3, B7-H4, HVEM, LIGHT, BTLA, CD30, TIGIT, VISTA. 56 . _ Alternatively, the composition according to claim 57 . 使用が、阻害性チェックポイント分子に特異的に結合する少なくとも１つの抗体の対象への投与をさらに含む、請求項５６から５８のいずれか一項に記載の組成物。 The composition of any one of claims 56-58 , wherein use further comprises administration of at least one antibody specifically to the inhibitory checkpoint molecule to the subject . 阻害性チェックポイント分子に特異的に結合する少なくとも１つの抗体が、抗ＰＤ－Ｌ１抗体、抗ＣＴＬＡ４抗体、抗ＰＤ－Ｌ２抗体、抗ＰＤ－１抗体、抗Ｂ７－Ｈ３抗体、抗Ｂ７－Ｈ４抗体、および抗ＨＶＥＭ抗体、抗ＢＴＬＡ（Ｂ－ ａｎｄ Ｔ－ｌｙｍｐｈｏｃｙｔｅ ａｔｔｅｎｕａｔｏｒ）抗体、抗ＫＩＲ（Ｋｉｌｌｅｒ ｉｎｈｉｂｉｔｏｒｙ ｒｅｃｅｐｔｏｒ）抗体、抗ＧＡＬ９抗体、抗ＴＩＭ－１抗体、抗ＴＩＭ３抗体、抗ＴＩＭ－４抗体、抗Ａ２ＡＲ抗体、抗ＣＤ３９抗体、抗ＣＤ７３抗体、抗ＬＡＧ－３抗体、抗ホスファチジルセリン抗体、抗ＣＤ２７抗体、抗ＣＤ３０抗体、抗ＴＮＦα抗体、抗ＣＤ３３抗体、抗Ｓｉｇｌｅｃ－５抗体、抗Ｓｉｇｌｅｃ－７抗体、抗Ｓｉｇｌｅｃ－９抗体、抗Ｓｉｇｌｅｃ－１１抗体、アンタゴニスト性抗ＴＲＥＭ１抗体、アンタゴニスト性抗ＴＲＥＭ２抗体、抗ＴＩＧＩＴ抗体、抗ＶＩＳＴＡ抗体、抗ＣＤ２抗体、抗ＣＤ５抗体、ならびにこれらの任意の組合せから選択される、請求項５９に記載の組成物。 At least one antibody that specifically binds to the inhibitory checkpoint molecule is an anti-PD-L1 antibody, an anti-CTLA4 antibody, an anti-PD-L2 antibody, an anti-PD-1 antibody, an anti-B7-H3 antibody, an anti-B7-H4 antibody. , And anti-HVEM antibody, anti-BTLA (B-and T-lymphocyte antibody) antibody, anti-KIR (Killer inhibitory receptor) antibody, anti-GAL9 antibody, anti-TIM-1 antibody, anti-TIM3 antibody, anti-TIM-4 antibody, anti-A2AR. Antibodies, anti-CD39 antibody, anti-CD73 antibody, anti-LAG-3 antibody, anti-phosphatidylserine antibody, anti-CD27 antibody, anti-CD30 antibody, anti-TNFα antibody, anti-CD33 antibody, anti-Sigma-5 antibody, anti-Sigma-7 antibody, anti Selected from Sigma-9 antibody, anti-Sigma-11 antibody, antagonistic anti-TREM1 antibody, antagonistic anti-TREM2 antibody, anti-TIGIT antibody, anti-VISTA antibody, anti-CD2 antibody, anti-CD5 antibody, and any combination thereof. The composition according to claim 59 . 使用が、１つまたは複数の標準的な抗がん治療または治験中の抗がん治療の対象への投与をさらに含む、請求項５６から６０のいずれか一項に記載の組成物。 The composition according to any one of claims 56 to 60, wherein the use further comprises administration to one or more standard anti-cancer treatments or subjects of anti-cancer treatment under investigation. １つまたは複数の標準的な抗がん治療または治験中の抗がん治療が、放射線療法、細胞傷害性化学療法、ターゲティング療法、イマチニブ療法、トラスツズマブ療法、エタネルセプト療法、養子細胞移入（ＡＣＴ）療法、キメラ抗原受容体Ｔ細胞移入（ＣＡＲ－Ｔ）療法、ワクチン療法、およびサイトカイン療法から選択される、請求項６１に記載の組成物。 One or more standard anti-cancer treatments or anti-cancer treatments under investigation include radiation therapy, cytotoxic chemotherapy, targeting therapy, imatinib therapy, trussumab therapy, eternelcept therapy, adoptive cell transfer (ACT) therapy. The composition of claim 61 , which is selected from chimeric antigen receptor T cell transfer (CAR-T) therapy, vaccine therapy, and cytokine therapy. 使用が、阻害性サイトカインに特異的に結合する少なくとも１つの抗体の対象への投与をさらに含む、請求項５６から６２のいずれか一項に記載の組成物。 The composition according to any one of claims 56 to 62 , wherein the use further comprises administration of at least one antibody that specifically binds to the inhibitory cytokine to the subject. 阻害性サイトカインに特異的に結合する少なくとも１つの抗体が、抗ＣＣＬ２抗体、抗ＣＳＦ－１抗体、抗ＩＬ－２抗体、およびこれらの任意の組合せから選択される、請求項６３に記載の組成物。 13. The composition of claim 63 , wherein the at least one antibody that specifically binds to the inhibitory cytokine is selected from an anti-CCL2 antibody, an anti-CSF-1 antibody, an anti-IL-2 antibody, and any combination thereof. .. 使用が、刺激性チェックポイントタンパク質に特異的に結合する少なくとも１つのアゴニスト性抗体の対象への投与をさらに含む、請求項５６から６４のいずれか一項に記載の組成物。 The composition of any one of claims 56-64 , wherein use further comprises administration of at least one agonistic antibody to the subject that specifically binds to the irritant checkpoint protein. 刺激性チェックポイントタンパク質に特異的に結合する少なくとも１つのアゴニスト性抗体が、アゴニストの抗ＣＤ４０抗体、アゴニストの抗ＯＸ４０抗体、アゴニストの抗ＩＣＯＳ抗体、アゴニストの抗ＣＤ２８抗体、アゴニスト性抗ＴＲＥＭ１抗体、アゴニスト性抗ＴＲＥＭ２抗体、アゴニストの抗ＣＤ１３７／４－１ＢＢ抗体、アゴニストの抗ＣＤ２７抗体、アゴニストの抗グルココルチコイド誘導性ＴＮＦＲ関連タンパク質ＧＩＴＲ抗体、アゴニストの抗ＣＤ３０抗体、アゴニストの抗ＢＴＬＡ抗体、アゴニストの抗ＨＶＥＭ抗体、アゴニストの抗ＣＤ２抗体、アゴニストの抗ＣＤ５抗体、およびこれらの任意の組合せから選択される、請求項６５に記載の組成物。 At least one agonistic antibody that specifically binds to the stimulating checkpoint protein is an agonist anti-CD40 antibody, an agonist anti-OX40 antibody, an agonist anti-ICOS antibody, an agonist anti-CD28 antibody, an agonist anti-TREM1 antibody, an agonist. Sex anti-TREM2 antibody, agonist anti-CD137 / 4-1BB antibody, agonist anti-CD27 antibody, agonist anti-glucocorticoid-induced TNFR-related protein GITR antibody, agonist anti-CD30 antibody, agonist anti-BTLA antibody, agonist anti-HVEM 65. The composition of claim 65 , which is selected from an antibody, an agonist anti-CD2 antibody, an agonist anti-CD5 antibody, and any combination thereof. 使用が、少なくとも１つの刺激性サイトカインの対象への投与をさらに含む、請求項５６から６６のいずれか一項に記載の組成物。 The composition according to any one of claims 56 to 66 , wherein the use further comprises administration of at least one stimulating cytokine to the subject . 少なくとも１つの刺激性サイトカインが、ＩＦＮ－α４、ＩＦＮ－β、ＩＬ－１β、ＴＮＦ－α、ＩＬ－６、ＩＬ－８、ＣＲＰ、ＩＬ－２０ファミリーメンバー、ＬＩＦ、ＩＦＮ－γ、ＯＳＭ、ＣＮＴＦ、ＧＭ－ＣＳＦ、ＩＬ－１１、ＩＬ－１２、ＩＬ－１５、ＩＬ－１７、ＩＬ－１８、ＩＬ－２３、ＣＸＣＬ１０、ＩＬ－３３、ＭＣＰ－１、ＭＩＰ－１ベータ、およびこれらの任意の組合せから選択される、請求項６７に記載の組成物。 At least one stimulating cytokine is IFN-α4, IFN-β, IL-1β, TNF-α, IL-6, IL-8, CRP, IL-20 family members, LIF, IFN-γ, OSM, CNTF, From GM-CSF, IL-11, IL-12, IL-15, IL-17, IL-18, IL-23, CXCL10, IL-33, MCP-1, MIP-1 beta, and any combination thereof. The composition of claim 67 , which is selected.
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Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3317297A4 (en) 2015-06-30 2019-03-20 Sanford-Burnham Medical Research Institute Btla fusion protein agonists and uses thereof
JOP20190009A1 (en) 2016-09-21 2019-01-27 Alx Oncology Inc Antibodies against signal-regulatory protein alpha and methods of use
CA3044684A1 (en) * 2016-12-09 2018-06-14 Alector Llc Anti-sirp-alpha antibodies and methods of use thereof
JOP20190248A1 (en) 2017-04-21 2019-10-20 Amgen Inc Trem2 antigen binding proteins and uses thereof
KR20200133376A (en) 2018-03-21 2020-11-27 알렉소 온콜로지 인크. Antibodies to signal-regulatory protein alpha and methods of use
MA52753A (en) 2018-05-25 2021-04-21 Alector Llc ANTI-SIRPA ANTIBODIES AND THEIR METHODS OF USE
WO2022110922A1 (en) * 2020-11-30 2022-06-02 启愈生物技术(上海)有限公司 ANTI-SIRPα ANTIBODY OR ANTIGEN-BINDING FRAGMENT THEREOF, AND USE THEREOF
CN113234159B (en) * 2021-05-12 2022-04-08 福州迈新生物技术开发有限公司 anti-LAG 3 protein monoclonal antibody, cell strain thereof, preparation method and application
WO2022254379A1 (en) 2021-06-04 2022-12-08 Boehringer Ingelheim International Gmbh Anti-sirp-alpha antibodies
WO2023010076A1 (en) * 2021-07-30 2023-02-02 Alector Llc Anti-sirp-alpha antibodies and methods of use thereof
CN113402621B (en) * 2021-08-02 2021-12-10 中山大学 Fusion protein containing chimeric antigen receptor and application thereof
WO2023077016A1 (en) * 2021-10-28 2023-05-04 Baylor College Of Medicine Targeting neuronal sirpα for treatment and prevention of neurological disorders
WO2023154578A1 (en) 2022-02-14 2023-08-17 Sana Biotechnology, Inc. Methods of treating patients exhibiting a prior failed therapy with hypoimmunogenic cells
WO2023183313A1 (en) 2022-03-22 2023-09-28 Sana Biotechnology, Inc. Engineering cells with a transgene in b2m or ciita locus and associated compositions and methods

Family Cites Families (112)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
JPS6023084B2 (en) 1979-07-11 1985-06-05 味の素株式会社 blood substitute
US4640835A (en) 1981-10-30 1987-02-03 Nippon Chemiphar Company, Ltd. Plasminogen activator derivatives
US4496689A (en) 1983-12-27 1985-01-29 Miles Laboratories, Inc. Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer
EP0206448B1 (en) 1985-06-19 1990-11-14 Ajinomoto Co., Inc. Hemoglobin combined with a poly(alkylene oxide)
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
US4791192A (en) 1986-06-26 1988-12-13 Takeda Chemical Industries, Ltd. Chemically modified protein with polyethyleneglycol
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
AU634186B2 (en) 1988-11-11 1993-02-18 Medical Research Council Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors
US5530101A (en) * 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
DE3920358A1 (en) 1989-06-22 1991-01-17 Behringwerke Ag BISPECIFIC AND OLIGO-SPECIFIC, MONO- AND OLIGOVALENT ANTI-BODY CONSTRUCTS, THEIR PRODUCTION AND USE
US5959177A (en) 1989-10-27 1999-09-28 The Scripps Research Institute Transgenic plants expressing assembled secretory antibodies
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
WO1991010741A1 (en) 1990-01-12 1991-07-25 Cell Genesys, Inc. Generation of xenogeneic antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
ES2108048T3 (en) 1990-08-29 1997-12-16 Genpharm Int PRODUCTION AND USE OF LOWER TRANSGENIC ANIMALS CAPABLE OF PRODUCING HETEROLOGICAL ANTIBODIES.
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
EP0564531B1 (en) 1990-12-03 1998-03-25 Genentech, Inc. Enrichment method for variant proteins with altered binding properties
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
JP4124480B2 (en) 1991-06-14 2008-07-23 ジェネンテック・インコーポレーテッド Immunoglobulin variants
GB9114948D0 (en) 1991-07-11 1991-08-28 Pfizer Ltd Process for preparing sertraline intermediates
WO1993006217A1 (en) 1991-09-19 1993-04-01 Genentech, Inc. EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab')2 ANTIBODIES
US5587458A (en) 1991-10-07 1996-12-24 Aronex Pharmaceuticals, Inc. Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
ES2202310T3 (en) 1991-12-13 2004-04-01 Xoma Corporation METHODS AND MATERIALS FOR THE PREPARATION OF VARIABLE DOMAINS OF MODIFIED ANTIBODIES AND THEIR THERAPEUTIC USES.
US5869619A (en) 1991-12-13 1999-02-09 Xoma Corporation Modified antibody variable domains
DE69334255D1 (en) 1992-02-06 2009-02-12 Novartis Vaccines & Diagnostic Marker for cancer and biosynthetic binding protein for it
US5789199A (en) 1994-11-03 1998-08-04 Genentech, Inc. Process for bacterial production of polypeptides
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5840523A (en) 1995-03-01 1998-11-24 Genetech, Inc. Methods and compositions for secretion of heterologous polypeptides
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
US5739277A (en) 1995-04-14 1998-04-14 Genentech Inc. Altered polypeptides with increased half-life
CA2219361C (en) 1995-04-27 2012-02-28 Abgenix, Inc. Human antibodies derived from immunized xenomice
EP0823941A4 (en) 1995-04-28 2001-09-19 Abgenix Inc Human antibodies derived from immunized xenomice
WO1997011971A1 (en) 1995-09-28 1997-04-03 Alexion Pharmaceuticals, Inc. Porcine cell interaction proteins
EP1500329B1 (en) 1996-12-03 2012-03-21 Amgen Fremont Inc. Human antibodies that specifically bind human TNF alpha
US6133426A (en) 1997-02-21 2000-10-17 Genentech, Inc. Humanized anti-IL-8 monoclonal antibodies
US6040498A (en) 1998-08-11 2000-03-21 North Caroline State University Genetically engineered duckweed
US6610833B1 (en) 1997-11-24 2003-08-26 The Institute For Human Genetics And Biochemistry Monoclonal human natural antibodies
BR9813365A (en) 1997-12-05 2004-06-15 Scripps Research Inst Method for Production and Humanization of a Mouse Monoclonal Antibody
GB9809951D0 (en) 1998-05-08 1998-07-08 Univ Cambridge Tech Binding molecules
EP1048299A1 (en) 1999-04-28 2000-11-02 Faculteit der Geneeskunde van de Vrije Universiteit Method for inhibiting cell functioning for use in anti-inflammatory and anti-tumour therapies
US7125978B1 (en) 1999-10-04 2006-10-24 Medicago Inc. Promoter for regulating expression of foreign genes
WO2001025454A2 (en) 1999-10-04 2001-04-12 Medicago Inc. Method for regulating transcription of foreign genes in the presence of nitrogen
WO2001040307A1 (en) 1999-11-30 2001-06-07 Eberhard-Karls-Universität Tübingen Universitätsklinikum Antibodies against signal regulator proteins
US20020090674A1 (en) * 2000-01-31 2002-07-11 Rosen Craig A. Nucleic acids, proteins, and antibodies
NZ521540A (en) 2000-04-11 2004-09-24 Genentech Inc Multivalent antibodies and uses therefor
US6946292B2 (en) 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
US7064191B2 (en) 2000-10-06 2006-06-20 Kyowa Hakko Kogyo Co., Ltd. Process for purifying antibody
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
ATE378403T1 (en) 2000-11-30 2007-11-15 Medarex Inc TRANSCHROMOSOMAL TRANSGENIC RODENTS FOR PRODUCING HUMAN ANTIBODIES
US7282556B2 (en) 2001-05-15 2007-10-16 Emory University Polynucleotides and polypeptides relating to the modulation of SIRPα-CD47
EP1443961B1 (en) 2001-10-25 2009-05-06 Genentech, Inc. Glycoprotein compositions
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
EP1498490A4 (en) 2002-04-09 2006-11-29 Kyowa Hakko Kogyo Kk Process for producing antibody composition
JP4628679B2 (en) 2002-04-09 2011-02-09 協和発酵キリン株式会社 Cells in which the activity of a protein involved in GDP-fucose transport is reduced or deleted
JPWO2003085107A1 (en) 2002-04-09 2005-08-11 協和醗酵工業株式会社 Genome-modified cells
US7691568B2 (en) 2002-04-09 2010-04-06 Kyowa Hakko Kirin Co., Ltd Antibody composition-containing medicament
JP2006504971A (en) 2002-11-01 2006-02-09 ザ・リージェンツ・オブ・ザ・ユニバーシティ・オブ・コロラド，ア・ボディー・コーポレイト Quantitative analysis of protein isoforms by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry
RU2386638C2 (en) 2004-03-31 2010-04-20 Дженентек, Инк. Humanised anti-tgf-beta-antibody
AU2005323025A1 (en) 2004-12-31 2006-07-13 Biogen Idec Ma Inc. Polypeptides that bind BR3 and uses thereof
US7700099B2 (en) 2005-02-14 2010-04-20 Merck & Co., Inc. Non-immunostimulatory antibody and compositions containing the same
DK2359834T5 (en) 2006-03-15 2017-02-06 Alexion Pharma Inc Treatment of paroxysmal nocturnal hemoglobinuria patients with a complement inhibitor
AU2007249408A1 (en) 2006-05-09 2007-11-22 Genentech, Inc. Binding polypeptides with optimized scaffolds
US10118970B2 (en) 2006-08-30 2018-11-06 Genentech, Inc. Multispecific antibodies
UY30776A1 (en) 2006-12-21 2008-07-03 Medarex Inc CD44 ANTIBODIES
CN100592373C (en) 2007-05-25 2010-02-24 群康科技(深圳)有限公司 Liquid crystal panel drive device and its drive method
BRPI0816785A2 (en) 2007-09-14 2017-05-02 Adimab Inc rationally designed synthetic antibody libraries, and uses thereof
US8877688B2 (en) 2007-09-14 2014-11-04 Adimab, Llc Rationally designed, synthetic antibody libraries and uses therefor
JP2011500005A (en) 2007-10-11 2011-01-06 ユニバーシティー ヘルス ネットワーク Modulation of SIRPα-CD47 interaction to increase human hematopoietic stem cell engraftment and compounds therefor
WO2009089004A1 (en) 2008-01-07 2009-07-16 Amgen Inc. Method for making antibody fc-heterodimeric molecules using electrostatic steering effects
JP2011518313A (en) 2008-01-15 2011-06-23 ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティ Acute myeloid leukemia stem cell marker
ES2740823T3 (en) 2008-01-15 2020-02-06 Univ Leland Stanford Junior Methods for manipulating phagocytosis mediated by CD47
EP2111869A1 (en) 2008-04-23 2009-10-28 Stichting Sanquin Bloedvoorziening Compositions and methods to enhance the immune system
FR2945538B1 (en) 2009-05-12 2014-12-26 Sanofi Aventis HUMANIZED ANTIBODIES SPECIFIC TO THE PROTOFIBRILLARY FORM OF THE BETA-AMYLOID PEPTIDE.
EP2429574B1 (en) 2009-05-15 2015-05-06 University Health Network Compositions and methods for treating hematologic cancers targeting the sirp - cd47 interaction
MX360336B (en) 2010-07-16 2018-10-30 Adimab Llc Star Antibody libraries.
WO2012173153A1 (en) 2011-06-15 2012-12-20 旭硝子株式会社 Method for producing fluorine-containing copolymer
HUE038225T2 (en) 2011-08-23 2018-10-29 Roche Glycart Ag Bispecific t cell activating antigen binding molecules
WO2013056352A1 (en) 2011-10-19 2013-04-25 University Health Network Antibodies and antibody fragments targeting sirp-alpha and their use in treating hematologic cancers
US8945214B2 (en) 2011-12-19 2015-02-03 Allergan, Inc. Intravitreal applicator
RU2015115956A (en) * 2012-11-09 2017-01-10 Пфайзер Инк. ANTIBODIES SPECIFIC TO THE THROMBOCYTE B GROWTH FACTOR, AND THEIR COMPOSITION AND APPLICATION
EP3311824B1 (en) 2013-02-05 2020-03-25 The Board of Trustees of the Leland Stanford Junior University Cd47 targeted therapies for the treatment of infectious disease
SG11201506132PA (en) 2013-02-06 2015-09-29 Inhibrx Llc Non-platelet depleting and non-red blood cell depleting cd47 antibodies and methods of use thereof
SG11201607143UA (en) * 2014-03-11 2016-09-29 Univ Leland Stanford Junior Anti sirp-alpha antibodies and bi-specific macrophage enhancing antibodies
HRP20211710T1 (en) 2014-05-22 2022-02-04 Byondis B.V. Site-specific conjugation of linker drugs to antibodies and resulting adcs
SG10201913611QA (en) * 2014-08-08 2020-03-30 Alector Llc Anti-trem2 antibodies and methods of use thereof
EP3012271A1 (en) 2014-10-24 2016-04-27 Effimune Method and compositions for inducing differentiation of myeloid derived suppressor cell to treat cancer and infectious diseases
US10618976B2 (en) 2015-06-16 2020-04-14 The Board Of Trustees Of The Leland Stanford Junior University SIRP-α agonist antibody
EP4186927A1 (en) 2015-10-21 2023-05-31 Ose Immunotherapeutics Methods and compositions for modifying macrophage polarization into pro-inflammatory cells to treat cancer
EP3995139A1 (en) 2016-04-10 2022-05-11 Georgia State University Research Foundation, Inc. Composition for use in treating cancer
WO2017178653A2 (en) 2016-04-14 2017-10-19 Ose Immunotherapeutics NEW ANTI-SIRPa ANTIBODIES AND THEIR THERAPEUTIC APPLICATIONS
WO2017184553A1 (en) 2016-04-18 2017-10-26 Baylor College Of Medicine Cancer gene therapy targeting cd47
EP3458094A4 (en) 2016-05-19 2020-01-08 Adaerata, Limited Partnership Methods of preventing or treating slamf7 positive and slamf7 negative cancers
US10611842B2 (en) 2016-08-03 2020-04-07 The Board Of Trustees Of The Leland Stanford Junior University Disrupting FC receptor engagement on macrophages enhances efficacy of anti-SIRPα antibody therapy
JOP20190009A1 (en) * 2016-09-21 2019-01-27 Alx Oncology Inc Antibodies against signal-regulatory protein alpha and methods of use
CA3044684A1 (en) 2016-12-09 2018-06-14 Alector Llc Anti-sirp-alpha antibodies and methods of use thereof
US10851164B2 (en) 2017-04-13 2020-12-01 Aduro Biotech Holdings, Europe B.V. Anti-SIRPα antibodies
WO2018210793A2 (en) 2017-05-16 2018-11-22 Synthon Biopharmaceuticals B.V. ANTI-SIRPα ANTIBODIES
AU2018308191B2 (en) 2017-07-24 2023-12-21 Scenic Immunology B.V. Treating pathological conditions by direct and indirect targeting of SIRPa - CD47 interaction
SG11202000658PA (en) 2017-07-26 2020-02-27 Forty Seven Inc Anti-sirp-alpha antibodies and related methods
JP2021517130A (en) 2018-03-13 2021-07-15 オーセ イミュノセラピューティクスＯｓｅ Ｉｍｍｕｎｏｔｈｅｒａｐｅｕｔｉｃｓ Use of anti-human SIRPav1 antibody and method for producing anti-v1 antibody
MA52753A (en) 2018-05-25 2021-04-21 Alector Llc ANTI-SIRPA ANTIBODIES AND THEIR METHODS OF USE
BR112021005585A2 (en) 2018-09-27 2021-06-29 Celgene Corporation Sirpa binding proteins and methods of using them
MX2021005761A (en) 2018-11-15 2021-08-11 Byondis Bv HUMANIZED ANTI-SIRPa ANTIBODIES.
WO2020127373A1 (en) 2018-12-21 2020-06-25 Ose Immunotherapeutics Bifunctional anti-pd-1/sirpa molecule

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