JPWO2019185717A5 - - Google Patents

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JPWO2019185717A5
JPWO2019185717A5 JP2020552716A JP2020552716A JPWO2019185717A5 JP WO2019185717 A5 JPWO2019185717 A5 JP WO2019185717A5 JP 2020552716 A JP2020552716 A JP 2020552716A JP 2020552716 A JP2020552716 A JP 2020552716A JP WO2019185717 A5 JPWO2019185717 A5 JP WO2019185717A5
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JP2021519100A (en
JP7458569B2 (en
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抗ＣＤ４７抗体又はその抗原結合部分であって、前記抗体は、重鎖可変（ＶＨ）領域及び軽鎖可変（ＶＬ）領域を含有し、
（ａ）ＶＨ領域のアミノ酸配列が、ＧＹＴＦＴＮＹＡＭＨ（配列番号４８）のＨＣＤＲ１、ＭＧＴＩＹＰＧＮＤＤＴＫＹＮＱＫＦＱＧ（配列番号４９）のＨＣＤＲ２、及びＧＧＦＲＡＭＤＹ（配列番号５０）のＨＣＤＲ３を含み、ＶＬ領域のアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＡＮＴＹＬＧ（配列番号５５）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＦＱＡＳＨＶＰＹＴ（配列番号５３）のＬＣＤＲ３を含む、
（ｂ）ＶＨ領域のアミノ酸配列が、ＧＹＴＦＴＮＹＡＭＨ（配列番号４８）のＨＣＤＲ１、ＭＧＴＩＹＰＧＮＤＤＴＫＹＮＱＫＦＱＧ（配列番号４９）のＨＣＤＲ２、及びＧＧＦＲＡＭＤＹ（配列番号５０）のＨＣＤＲ３を含み、ＶＬ領域のアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＧＮＴＹＬＧ（配列番号５１）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＦＱＡＳＨＶＰＹＴ（配列番号５３）のＬＣＤＲ３を含む、
（ｃ）ＶＨ領域のアミノ酸配列が、ＧＹＴＦＴＮＹＡＭＨ（配列番号４８）のＨＣＤＲ１、ＭＧＴＩＹＰＧＮＤＤＴＫＹＮＱＫＦＱＧ（配列番号４９）のＨＣＤＲ２、及びＧＧＦＲＡＭＤＹ（配列番号５０）のＨＣＤＲ３を含み、ＶＬ領域のアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＡＹＮＹＬＧ（配列番号５６）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＦＱＡＳＨＶＰＹＴ（配列番号５３）のＬＣＤＲ３を含む、
（ｄ）ＶＨ領域のアミノ酸配列が、ＧＹＴＦＴＮＹＡＭＨ（配列番号４８）のＨＣＤＲ１、ＭＧＴＩＹＰＧＮＤＤＴＫＹＮＱＫＦＱＧ（配列番号４９）のＨＣＤＲ２、及びＧＧＦＲＡＭＤＹ（配列番号５０）のＨＣＤＲ３を含み、ＶＬ領域のアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＡＹＮＹＬＧ（配列番号５６）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＦＱＡＳＱＶＰＹＴ（配列番号５４）のＬＣＤＲ３を含む、
（ｅ）ＶＨ領域のアミノ酸配列が、ＧＹＴＦＴＮＹＡＭＨ（配列番号４８）のＨＣＤＲ１、ＭＧＴＩＹＰＧＮＤＤＴＫＹＮＱＫＦＱＧ（配列番号４９）のＨＣＤＲ２、及びＧＧＦＲＡＭＤＹ（配列番号５０）のＨＣＤＲ３を含み、ＶＬ領域のアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＡＮＴＹＬＧ（配列番号５５）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＦＱＡＳＱＶＰＹＴ（配列番号５４）のＬＣＤＲ３を含む、
（ｆ）ＶＨ領域のアミノ酸配列が、ＧＹＴＦＴＮＹＡＭＨ（配列番号４８）のＨＣＤＲ１、ＭＧＴＩＹＰＧＮＤＤＴＫＹＮＱＫＦＱＧ（配列番号４９）のＨＣＤＲ２、及びＧＧＦＲＡＭＤＹ（配列番号５０）のＨＣＤＲ３を含み、ＶＬ領域のアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＧＮＴＹＬＧ（配列番号５１）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＦＱＡＳＱＶＰＹＴ（配列番号５４）のＬＣＤＲ３を含む、
（ｇ）ＶＨ領域のアミノ酸配列が、ＧＹＳＦＴＮＹＮＩＨ（配列番号５７）のＨＣＤＲ１、ＭＧＴＩＹＰＧＮＳＤＴＳＹＮＰＳＦＱＧ（配列番号６１）のＨＣＤＲ２、及びＧＧＶＲＡＭＤＹ（配列番号６２）のＨＣＤＲ３を含み、ＶＬ領域のアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＧＮＴＹＬＧ（配列番号５１）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＭＱＡＳＱＶＰＹＴ（配列番号６３）のＬＣＤＲ３を含む、
（ｈ）ＶＨ領域のアミノ酸配列が、ＧＹＳＦＴＮＹＮＩＨ（配列番号５７）のＨＣＤＲ１、ＭＧＴＩＹＰＧＤＳＤＴＲＹＮＰＫＦＱＧ（配列番号５８）のＨＣＤＲ２、及びＧＧＹＲＡＥＤＹ（配列番号５９）のＨＣＤＲ３を含み、ＶＬ領域のアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＧＮＴＹＬＧ（配列番号５１）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＭＱＧＳＨＶＰＹ（配列番号６０）のＬＣＤＲ３を含む、又は
（ｉ）ＶＨ領域のアミノ酸配列が、ＧＹＳＦＴＮＹＮＩＨ（配列番号５７）のＨＣＤＲ１、ＭＧＴＩＹＰＧＤＳＤＴＳＹＮＰＫＦＱＧ（配列番号９４）のＨＣＤＲ２、及びＧＧＹＲＡＥＤＹ （配列番号５９）のＨＣＤＲ３を含み、ＶＬ領域のアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＧＮＴＹＬＧ（配列番号５１）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＭＱＧＳＨＶＰＹＴ（配列番号９７）のＬＣＤＲ３を含む、
抗ＣＤ４７抗体又はその抗原結合部分。 An anti-CD47 antibody or antigen-binding portion thereof, said antibody containing a heavy chain variable (VH) region and a light chain variable (VL) region.
(A) The amino acid sequence of the VH region contains HCDR1 of GYTFTNYAMH (SEQ ID NO: 48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO: 49) , and HCDR3 of GGFRAMDY (SEQ ID NO: 50), and the amino acid sequence of the VL region is RSSQSLLHSNANTYLG (SEQ ID NO: 50). Includes LCDR1 of No. 55), LCDR2 of KGSNRFS (SEQ ID NO: 52) , and LCDR3 of FQASHVPYT (SEQ ID NO: 53).
(B) The amino acid sequence of the VH region contains HCDR1 of GYTFTNYAMH (SEQ ID NO: 48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO: 49) , and HCDR3 of GGFRAMDY (SEQ ID NO: 50), and the amino acid sequence of the VL region is RSSQSLLHSNGNTYLG. Includes LCDR1 of No. 51), LCDR2 of KGSNRFS (SEQ ID NO: 52) , and LCDR3 of FQASHVPYT (SEQ ID NO: 53).
(C) The amino acid sequence of the VH region contains HCDR1 of GYTFTNYAMH (SEQ ID NO: 48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO: 49) , and HCDR3 of GGFRAMDY (SEQ ID NO: 50), and the amino acid sequence of the VL region is RSSQSLLHSNAYLG (SEQ ID NO: 50). Includes LCDR1 of number 56), LCDR2 of KGSNRFS (SEQ ID NO: 52) , and LCDR3 of FQASHVPYT (SEQ ID NO: 53).
(D) The amino acid sequence of the VH region comprises HCDR1 of GYTFTNYAMH (SEQ ID NO: 48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO: 49) , and HCDR3 of GGFRAMDY (SEQ ID NO: 50), and the amino acid sequence of the VL region is RSSQSLLHSNAYLG (SEQ ID NO: 50). Includes LCDR1 of number 56), LCDR2 of KGSNRFS (SEQ ID NO: 52) , and LCDR3 of FQASQVPYT (SEQ ID NO: 54).
(E) The amino acid sequence of the VH region contains HCDR1 of GYTFTNYAMH (SEQ ID NO: 48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO: 49) , and HCDR3 of GGFRAMDY (SEQ ID NO: 50), and the amino acid sequence of the VL region is RSSQSLLHSNANTYLG (SEQ ID NO: 50). Includes LCDR1 of No. 55), LCDR2 of KGSNRFS (SEQ ID NO: 52) , and LCDR3 of FQASQVPYT (SEQ ID NO: 54).
(F) The amino acid sequence of the VH region comprises HCDR1 of GYTFTNYAMH (SEQ ID NO: 48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO: 49) , and HCDR3 of GGFRAMDY (SEQ ID NO: 50), and the amino acid sequence of the VL region is RSSQSLLHSNGNTYLG. Includes LCDR1 of No. 51), LCDR2 of KGSNRFS (SEQ ID NO: 52) , and LCDR3 of FQASQVPYT (SEQ ID NO: 54).
(G) The amino acid sequence of the VH region comprises HCDR1 of GYSFTNYNIH (SEQ ID NO: 57), HCDR2 of MGTIYPGNSDTSYNPSFQG (SEQ ID NO: 61) , and HCDR3 of GGVRAMDY (SEQ ID NO: 62), and the amino acid sequence of the VL region is RSSQSLLHSNGNTYLG. Includes LCDR1 of No. 51), LCDR2 of KGSNRFS (SEQ ID NO: 52) , and LCDR3 of MQASQVPYT (SEQ ID NO: 63).
(H) The amino acid sequence of the VH region contains HCDR1 of GYSFTNYNIH (SEQ ID NO: 57), HCDR2 of MGTIYPGDSDTRYNPKFQG (SEQ ID NO: 58) , and HCDR3 of GGYRAEDY (SEQ ID NO: 59), and the amino acid sequence of the VL region is RSSQSLLHSNGNTYLG. Includes LCDR1 of No. 51), LCDR2 of KGSNRFS (SEQ ID NO: 52) , and LCDR3 of MQGSHVPY (SEQ ID NO: 60) , or
(I) The amino acid sequence of the VH region contains HCDR1 of GYSFTNYNIH (SEQ ID NO: 57), HCDR2 of MGTIYPGDSDTSYNPKFQG (SEQ ID NO: 94), and HCDR3 of GGYRAEDY (SEQ ID NO: 59), and the amino acid sequence of the VL region is RSSQSLLHSNGNTYLG. Includes LCDR1 of No. 51), LCDR2 of KGSNRFS (SEQ ID NO: 52), and LCDR3 of MQGSHVPYT (SEQ ID NO: 97).
Anti-CD47 antibody or antigen-binding portion thereof. （ａ）前記ＶＨ領域のアミノ酸配列が配列番号１を含有し、かつ、前記ＶＬ領域のアミノ酸配列が配列番号２を含む、
（ｂ）前記ＶＨ領域のアミノ酸配列が配列番号３を含み、かつ、前記ＶＬ領域のアミノ酸配列が配列番号４を含む、
（ｃ）前記ＶＨ領域のアミノ酸配列が配列番号５を含み、かつ、前記ＶＬ領域のアミノ酸配列が配列番号６を含む、
（ｄ）前記ＶＨ領域のアミノ酸配列が配列番号７を含有し、かつ、前記ＶＬ領域のアミノ酸配列が配列番号８を含む、
（ｅ）前記ＶＨ領域のアミノ酸配列が配列番号９を含み、かつ、前記ＶＬ領域のアミノ酸配列が配列番号１０を含む、
（ｆ）前記ＶＨ領域のアミノ酸配列が配列番号１１を含み、かつ、前記ＶＬ領域のアミノ酸配列が配列番号１２を含む、
（ｇ）前記ＶＨ領域のアミノ酸配列が配列番号１３を含み、かつ、前記ＶＬ領域のアミノ酸配列が配列番号１４を含む、又は
（ｈ）前記ＶＨ領域のアミノ酸配列が配列番号１５を含み、かつ、前記ＶＬ領域のアミノ酸配列が配列番号１６を含む、
請求項１記載の抗体又は抗原結合部分。 (A) The amino acid sequence of the VH region contains SEQ ID NO: 1 and the amino acid sequence of the VL region contains SEQ ID NO: 2.
(B) The amino acid sequence of the VH region comprises SEQ ID NO: 3, and the amino acid sequence of the VL region comprises SEQ ID NO: 4.
(C) The amino acid sequence of the VH region comprises SEQ ID NO: 5, and the amino acid sequence of the VL region comprises SEQ ID NO: 6.
(D) The amino acid sequence of the VH region contains SEQ ID NO: 7, and the amino acid sequence of the VL region contains SEQ ID NO: 8.
(E) The amino acid sequence of the VH region comprises SEQ ID NO: 9, and the amino acid sequence of the VL region comprises SEQ ID NO: 10.
(F) The amino acid sequence of the VH region comprises SEQ ID NO: 11 and the amino acid sequence of the VL region comprises SEQ ID NO: 12.
(G) The amino acid sequence of the VH region comprises SEQ ID NO: 13, and the amino acid sequence of the VL region comprises SEQ ID NO: 14.
(H) The amino acid sequence of the VH region comprises SEQ ID NO: 15, and the amino acid sequence of the VL region comprises SEQ ID NO: 16.
The antibody or antigen-binding moiety according to claim 1. 前記抗体が、ヒト化抗体又はキメラ抗体である、請求項１又は２に記載の抗体又は抗原結合部分。 The antibody or antigen-binding moiety according to claim 1 or 2, wherein the antibody is a humanized antibody or a chimeric antibody. 前記ＶＨ領域、前記ＶＬ領域、又は前記ＶＨ領域及び前記ＶＬ領域の両方が、１つ又は複数のヒトフレームワーク領域のアミノ酸配列を含有する、請求項１から３のいずれか一項に記載の抗体又は抗原結合部分。 The antibody according to any one of claims 1 to 3 , wherein the VH region, the VL region, or both the VH region and the VL region contain an amino acid sequence of one or more human framework regions. Or the antigen binding part. 前記ＶＨ領域、前記ＶＬ領域、又は前記ＶＨ領域及び前記ＶＬ領域の両方が、前記ＣＤＲが挿入されたヒト可変領域フレームワークスキャホールドのアミノ酸配列を含有する、請求項１から４のいずれか一項に記載の抗体又は抗原結合部分。 One of claims 1 to 4 , wherein the VH region, the VL region, or both the VH region and the VL region contain the amino acid sequence of the human variable region framework scaffold into which the CDR is inserted. The antibody or antigen binding moiety according to. 前記ＶＨ領域が、前記ＨＣＤＲ１、ＨＣＤＲ２、及びＨＣＤＲ３のアミノ酸配列が挿入された、ＩＧＨＶ５－５１又はＩＧＨＶ１－３のヒト生殖細胞系列スキャホールドのアミノ酸配列を含有する、請求項１に記載の抗体又は抗原結合部分。 The antibody or antigen according to claim 1, wherein the VH region contains the amino acid sequence of a human germline scaffold of IGHV5-51 or IGHV1-3 into which the amino acid sequences of HCDR1, HCDR2, and HCDR3 have been inserted. Joining part. 前記ＶＬ領域が、前記ＬＣＤＲ１、ＬＣＤＲ２、及びＬＣＤＲ３のアミノ酸配列が挿入されたＩＧＫＶ２－２８ヒト生殖細胞系列スキャホールドのアミノ酸配列を含有する、請求項１又は６に記載の抗体又は抗原結合部分。 The antibody or antigen binding moiety according to claim 1 or 6 , wherein the VL region contains the amino acid sequence of IGKV2-28 human germline scaffold into which the amino acid sequences of LCDR1, LCDR2, and LCDR3 are inserted. 前記抗体が、免疫グロブリン定常領域を含有する、請求項１から７のいずれか一項に記載の抗体又は抗原結合部分。 The antibody or antigen-binding moiety according to any one of claims 1 to 7 , wherein the antibody contains an immunoglobulin constant region. 前記免疫グロブリン定常領域が、ＩｇＧ、ＩｇＥ、ＩｇＭ、ＩｇＤ、ＩｇＡ又はＩｇＹである、請求項８に記載の抗体又は抗原結合部分。 The antibody or antigen binding moiety according to claim 8, wherein the immunoglobulin constant region is IgG, IgE, IgM, IgD, IgA or IgY. 前記免疫グロブリン定常領域が、ＩｇＧ１、ＩｇＧ２、ＩｇＧ３、ＩｇＧ４、ＩｇＡ１又はＩｇＡ２である、請求項９に記載の抗体又は抗原結合部分。 The antibody or antigen binding moiety of claim 9, wherein the immunoglobulin constant region is IgG1, IgG2, IgG3, IgG4, IgA1 or IgA2. 前記免疫グロブリン定常領域が、免疫学的に不活性である、請求項８に記載の抗体又は抗原結合部分。 The antibody or antigen-binding moiety according to claim 8, wherein the immunoglobulin constant region is immunologically inactive. 前記免疫グロブリン定常領域が、野生型ヒトＩｇＧ４定常領域、Ｓ２２８Ｐのアミノ酸置換を含有するヒトＩｇＧ４定常領域、野生型ヒトＩｇＧ１定常領域、Ｌ２３４Ａ、Ｌ２３５Ａ及びＧ２３７Ａのアミノ酸置換を含有するヒトＩｇＧ１定常領域、又は野生型ヒトＩｇＧ２定常領域であり、番号付けがＫａｂａｔにあるＥＵインデックスに従う、請求項８に記載の抗体又は抗原結合部分。 The immunoglobulin constant region is a wild-type human IgG4 constant region, a human IgG4 constant region containing an amino acid substitution of S228P, a wild-type human IgG1 constant region, a human IgG1 constant region containing amino acid substitutions of L234A, L235A and G237A, or a human IgG1 constant region. The antibody or antigen binding moiety of claim 8, wherein it is a wild-type human IgG2 constant region, numbered according to the EU index in Kabat . 前記免疫グロブリン定常領域が、配列番号１７～２３のいずれか１つを含有する、請求項８に記載の抗体又は抗原結合部分。 The antibody or antigen-binding moiety according to claim 8, wherein the immunoglobulin constant region contains any one of SEQ ID NOs: 17 to 23. 前記抗体又は抗原結合部分が、Ｆａｂ、Ｆａｂ’、Ｆ（ａｂ’）２、Ｆｖ、ｓｃＦｖ、マキシボディ、ミニボディ、ダイアボディ、トリアボディ、テトラボディ、又はｂｉｓ－ｓｃＦｖである、請求項１から１３のいずれか一項に記載の抗体又は抗原結合部分。 From claim 1, the antibody or antigen-binding moiety is Fab, Fab', F (ab') 2 , Fv, scFv, maxibody, minibody, diabody, triabody, tetrabody, or bis-scFv. 13. The antibody or antigen-binding moiety according to any one of 13. 前記抗体がモノクローナルである、請求項１から１４のいずれか一項に記載の抗体又は抗原結合部分。 The antibody or antigen-binding moiety according to any one of claims 1 to 14 , wherein the antibody is monoclonal. 前記抗体が、四量体抗体、四価抗体、又は多特異性抗体である、請求項１から１５のいずれか一項に記載の抗体又は抗原結合部分。 The antibody or antigen-binding moiety according to any one of claims 1 to 15 , wherein the antibody is a tetramer antibody, a tetravalent antibody, or a polyspecific antibody. 前記抗体が第一の抗原及び第二の抗原に特異的に結合する二特異性抗体であり、前記第一の抗原がＣＤ４７であり、前記第二の抗原がＣＤ４７ではない、請求項１から１６のいずれか一項に記載の抗体又は抗原結合部分。 Claims 1-16 , wherein the antibody is a bispecific antibody that specifically binds to the first and second antigens, the first antigen is CD47 and the second antigen is not CD47. The antibody or antigen-binding moiety according to any one of the above. 前記抗体又は抗原結合部分が、（ａ）ヒトＣＤ４７に特異的に結合する、又は（ｂ）ヒトＣＤ４７及びカニクイザルＣＤ４７に特異的に結合する、請求項１から１７のいずれか一項に記載の抗体又は抗原結合部分。 The antibody according to any one of claims 1 to 17 , wherein the antibody or antigen-binding moiety specifically binds to (a) human CD47 or (b) human CD47 and cynomolgus monkey CD47. Or the antigen binding part. 重鎖可変（ＶＨ）領域及び軽鎖可変（ＶＬ）領域を含む単一鎖Ｆｖ（ｓｃＦｖ）であって、
（ａ）ＶＨアミノ酸配列が、ＧＹＳＦＴＮＹＮＩＨ（配列番号５７）のＨＣＤＲ１、ＭＧＴＩＹＰＧＤＳＤＴＳＹＮＰＫＦＱＧ（配列番号９４）のＨＣＤＲ２、及びＧＧＹＲＡＥＤＹ（配列番号５９）のＨＣＤＲ３を含み、
（ｂ）ＶＬアミノ酸配列が、ＲＳＳＱＳＬＬＨＳＮＧＮＴＹＬＧ（配列番号５１）のＬＣＤＲ１、ＫＧＳＮＲＦＳ（配列番号５２）のＬＣＤＲ２、及びＭＱＧＳＨＶＰＹＴ（配列番号９７）のＬＣＤＲ３を含む、
ｓｃＦｖ。 A single chain Fv (scFv) containing a heavy chain variable (VH) region and a light chain variable (VL) region.
(A) The VH amino acid sequence comprises HCDR1 of GYSFTNYNIH (SEQ ID NO: 57), HCDR2 of MGTIYPGDSDTSYNPKFQG (SEQ ID NO: 94), and HCDR3 of GGYRAEDY (SEQ ID NO: 59).
(B) The VL amino acid sequence comprises LCDR1 of RSSQSLLHSNGNTYLG (SEQ ID NO: 51), LCDR2 of KGSNRFS (SEQ ID NO: 52), and LCDR3 of MQGSHVPYT (SEQ ID NO: 97).
scFv. 免疫グロブリン定常領域又は免疫グロブリン定常領域の部分をさらに含む、請求項１９に記載のｓｃＦｖ。 19. The scFv of claim 19 , further comprising a portion of an immunoglobulin constant region or an immunoglobulin constant region. 前記免疫グロブリン定常領域が、配列番号１７から２３のいずれか１つを含有する、請求項２０に記載のｓｃＦｖ。 The scFv according to claim 20, wherein the immunoglobulin constant region contains any one of SEQ ID NOs: 17 to 23. 治療剤に結合された請求項１から１８のいずれか一項に記載の抗体又は抗原結合部分、又は請求項１９から２１のいずれか一項に記載のｓｃＦｖを含有する免疫結合体。 An immunoconjugate containing the antibody or antigen-binding moiety according to any one of claims 1 to 18 bound to a therapeutic agent, or the scFv according to any one of claims 19 to 21 . 前記治療剤が、細胞毒素、放射性同位体、化学療法剤、免疫調節剤、細胞増殖抑制酵素、細胞溶解性酵素、治療用核酸、抗血管新生剤、抗増殖剤、又はアポトーシス促進剤である、請求項２２に記載の免疫結合体。 The therapeutic agent is a cytotoxin, a radioisotope, a chemotherapeutic agent, an immunomodulator, a cell growth inhibitor, a cytolytic enzyme, a therapeutic nucleic acid, an antiangiogenic agent, an antiproliferative agent, or an apoptosis-promoting agent. The immune conjugate according to claim 22 . 請求項１から１８のいずれか一項に記載の抗体又は抗原結合部分、請求項１９から２１のいずれか一項に記載のｓｃＦｖ、又は請求項２２又は２３に記載の免疫結合体と、
薬学的に許容可能な担体、希釈剤、又は賦形剤と、
を含有する医薬組成物。 The antibody or antigen-binding moiety according to any one of claims 1 to 18 , the scFv according to any one of claims 19 to 21 , or the immunoconjugate according to claims 22 or 23 .
With pharmaceutically acceptable carriers, diluents , or excipients ,
A pharmaceutical composition containing. 核酸分子であって、
請求項１から１８のいずれか一項に記載の抗体又は抗原結合部分、又は請求項１９から２１のいずれか一項に記載のｓｃＦｖの
（ａ）ＶＨ領域のアミノ酸配列、
（ｂ）ＶＬ領域のアミノ酸配列、又は
（ｃ）ＶＨ領域及びＶＬ領域の両方のアミノ酸配列
をコードする核酸分子。 It ’s a nucleic acid molecule.
The antibody or antigen-binding moiety according to any one of claims 1 to 18 , or the amino acid sequence of the (a) VH region of scFv according to any one of claims 19 to 21 .
(B) Amino acid sequence of VL region or
(C) A nucleic acid molecule encoding both the amino acid sequences of the VH region and the VL region. 請求項２５に記載の核酸分子を含有する発現ベクター。 An expression vector containing the nucleic acid molecule according to claim 25 . 請求項２５に記載の核酸分子、又は請求項２６に記載の発現ベクターを含有する組換え宿主細胞。 A recombinant host cell containing the nucleic acid molecule of claim 25 or the expression vector of claim 26 . 抗ＣＤ４７抗体又はその抗原結合部分を作製する方法であって、
核酸分子が発現される条件下で、請求項２６に記載の発現ベクターを含有する組換え宿主細胞を培養し、それにより抗体又は抗原結合部分を作製することと、
前記宿主細胞又は培養物から、前記抗体又は抗原結合部分を単離することと、
を含む、方法。 A method for producing an anti-CD47 antibody or an antigen-binding portion thereof.
Culturing a recombinant host cell containing the expression vector according to claim 26 under conditions in which a nucleic acid molecule is expressed , thereby producing an antibody or antigen-binding moiety.
Isolating the antibody or antigen-binding moiety from the host cell or culture and
Including, how. 対象における免疫反応を強化するために使用される、請求項１から１８のいずれか一項に記載の抗体又は抗原結合部分、請求項１９から２１のいずれか一項に記載のｓｃＦｖ、請求項２２又は２３に記載の免疫結合体、又は請求項２４に記載の医薬組成物。 The antibody or antigen binding moiety of any one of claims 1-18 , the scFv of any one of claims 19-21 , used to enhance an immune response in a subject, claim. The immunoconjugate according to claim 22 or 23 , or the pharmaceutical composition according to claim 24 . 癌、自己免疫性疾患、炎症性疾患、心血管疾患、又は線維症の治療における使用のための請求項１から１８のいずれか一項に記載の抗体又は抗原結合部分、請求項１９から２１のいずれか一項に記載のｓｃＦｖ、請求項２２又は２３に記載の免疫結合体、又は請求項２４に記載の医薬組成物。 The antibody or antigen-binding moiety according to any one of claims 1 to 18 , according to claims 19 to 21 , for use in the treatment of cancer, autoimmune disease, inflammatory disease, cardiovascular disease, or fibrosis. The scFv according to any one, the immune conjugate according to claim 22 or 23 , or the pharmaceutical composition according to claim 24 . 前記癌が、消化管間質癌（ＧＩＳＴ）、膵臓癌、メラノーマ、乳癌、肺癌、気管支癌、結腸直腸癌、前立腺癌、胃癌、卵巣癌、膀胱癌、脳腫瘍又は中枢神経系の癌、末梢神経系の癌、食道癌、子宮頸癌、子宮癌又は子宮内膜癌、口腔又は咽頭の癌、肝癌、腎癌、精巣癌、胆管癌、小腸癌又は虫垂癌、唾液腺癌、甲状腺癌、副腎癌、骨肉腫、軟骨肉腫、又は血液組織の癌である、請求項３０に記載の使用のための抗体又は抗原結合部分、免疫結合体、又は医薬組成物。 The cancers are gastrointestinal stromal cancer (GIST), pancreatic cancer, melanoma, breast cancer, lung cancer, bronchial cancer, colorectal cancer, prostate cancer, gastric cancer, ovarian cancer, bladder cancer, brain cancer or central nervous system cancer, peripheral nerve. System cancer, esophageal cancer, cervical cancer, uterine cancer or endometrial cancer, oral or pharyngeal cancer, liver cancer, renal cancer, testis cancer, bile duct cancer, small intestinal cancer or pituitary cancer, salivary adenocarcinoma, thyroid cancer, adrenal cancer The antibody or antigen binding moiety, immune conjugate, or pharmaceutical composition for use according to claim 30 , which is an osteosarcoma, chondrosarcoma, or cancer of blood tissue. 前記自己免疫性疾患又は前記炎症性疾患が、関節炎、喘息、多発性硬化症、乾癬、クローン病、炎症性腸疾患、ループス（ｌｕｐｕｓ）、グレーブス病、橋本甲状腺炎、又は強直性脊椎炎である、請求項３０に記載の使用のための抗体又は抗原結合部分、免疫結合体、又は医薬組成物。 The autoimmune disease or the inflammatory disease is arthritis, asthma, multiple sclerosis, psoriasis, Crohn's disease, inflammatory bowel disease, lupus, Graves' disease, Hashimoto thyroiditis, or tonic spondylitis. , The antibody or antigen-binding moiety, immune conjugate, or pharmaceutical composition for use according to claim 30 . 前記心血管疾患が、冠動脈心疾患又はアテローム性動脈硬化症である、請求項３０に記載の使用のための抗体又は抗原結合部分、免疫結合体、又は医薬組成物。 The antibody or antigen binding moiety, immune conjugate, or pharmaceutical composition for use according to claim 30 , wherein the cardiovascular disease is coronary heart disease or atherosclerosis. 前記線維症が、心筋梗塞、狭心症、変形性関節症、肺線維症、嚢胞性線維症、気管支炎又は喘息である、請求項３０に記載の使用のための抗体又は抗原結合部分、免疫結合体、又は医薬組成物。 The antibody or antigen binding moiety for use according to claim 30 , wherein the fibrosis is myocardial infarction, angina, osteoarthritis, pulmonary fibrosis, cystic fibrosis, bronchitis or asthma. Bounds, or pharmaceutical compositions. 医薬品としての使用のための、請求項１から１８のいずれか一項に記載の抗体又は抗原結合部分、請求項１９から２１のいずれか一項に記載のｓｃＦｖ、請求項２２又は２３に記載の免疫結合体、又は請求項２４に記載の医薬組成物。 The antibody or antigen-binding moiety according to any one of claims 1 to 18 , scFv according to any one of claims 19 to 21 , according to claim 22 or 23 , for use as a pharmaceutical product. The immune conjugate or the pharmaceutical composition according to claim 24 .
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