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1. 发明授权

US09278146B2 Peptide derivative and use of the same 有权
标题翻译：肽衍生物和使用相同
公开(公告)号：US09278146B2
公开(公告)日：2016-03-08
申请号：US13269345
申请日：2011-10-07
申请人： Hideo Saji , Nobuya Inagaki , Hiroyuki Kimura , Kentaro Toyoda , Konomu Hirao , Hirokazu Matsuda
发明人： Hideo Saji , Nobuya Inagaki , Hiroyuki Kimura , Kentaro Toyoda , Konomu Hirao , Hirokazu Matsuda
IPC分类号： A61K51/00 , A61M36/14 , A61K51/08 , C07K14/575
CPC分类号： A61K51/08 , A61K51/088 , C07K14/57563
摘要： A new peptide derivative is provided. The peptide derivative is represented by the following general formula (I), where polypeptide ExP is polypeptide that contains completely or partially the amino acid sequence of exendin-4, and a -L-Z group represents a group represented by the following formula (II) that is bonded to an amino acid side chain of or the α-amino group at the N-terminus of the polypeptide ExP,
摘要翻译：提供了一种新的肽衍生物。肽衍生物由以下通式（I）表示，其中多肽ExP是完全或部分含有毒蜥外泌肽-4的氨基酸序列的多肽，-LZ基团表示由下式（II）表示的基团，与多肽ExP的N末端的氨基酸侧链或α-氨基键合，

2. 发明授权

US09238083B2 Molecular probe for imaging of pancreatic islets and use of the same 有权
标题翻译：胰岛成像用分子探针及其用途
公开(公告)号：US09238083B2
公开(公告)日：2016-01-19
申请号：US12893896
申请日：2010-09-29
申请人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： A61K51/08 , C07K14/00
CPC分类号： A61K51/08
摘要： A molecular probe for imaging of pancreatic islets is provided. The molecular probe includes a polypeptide represented by the following formula (1), or a polypeptide that has a homology with the foregoing polypeptide. (SEQ ID NO. 1) Z-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSX-NH2 (1) Wherein “X” represents a lysine residue, an amino group of a side chain of the lysine residue being labeled with a group represented by the following chemical formula (I), wherein A represents an aromatic hydrocarbon group or an aromatic heterocyclic group; R1 represents a substituent that contains 11C, 13N, 15O, 18F, 64Cu, 67Ga, 68Ga, 75Br, 76Br, 77Br, 99mTc, 111In, 123I, 124I, 125I, or 131I; R2 represents either a hydrogen atom, or a substituent different from that represented by R1; and R3 represents any one of a bond, an alkylene group having 1 to 6 carbon atoms, and an oxyalkylene group having 1 to 6 carbon atoms.
摘要翻译：提供了用于胰岛成像的分子探针。分子探针包括由下式（1）表示的多肽，或与前述多肽具有同源性的多肽。（SEQ ID NO.1）Z-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSX-NH2（1）其中，“X”表示赖氨酸残基，赖氨酸残基的侧链的氨基用下述化学式（I）表示的基团标记，其中A表示芳族烃基或芳族杂环基; R1表示含有11C，13N，150C，18F，64Cu，67Ga，68Ga，75Br，76Br，77Br，99mTc，111In，123I，124I，125I或131I的取代基; R2表示氢原子或与R1表示的取代基不同的取代基; R3表示碳原子数1〜6的亚烷基，碳原子数1〜6的氧亚烷基。

3. 发明授权

US08980220B2 Molecular probe for imaging of pancreatic islets and use of the same 有权
标题翻译：胰岛成像用分子探针及其用途
公开(公告)号：US08980220B2
公开(公告)日：2015-03-17
申请号：US12964486
申请日：2010-12-09
申请人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： C07K14/605 , G01N33/74 , A61K51/08
CPC分类号： G01N33/74 , A61K51/088 , C07K14/605
摘要： A molecular probe for use in imaging of pancreatic islets is provided. The molecular probe comprises a polypeptide represented by the following formula (1), (2), or (3), or a polypeptide having homology with the foregoing polypeptide, (SEQ ID NO. 1) Z-HGEGTFTSDLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (1) (SEQ ID NO. 2) Z-HGEGTFTSDLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2 (2) (SEQ ID NO. 3) B-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (3) where, in the formulae (1) and (2), “X” represents a lysine residue, an amino group of a side chain of the lysine residue being labeled with a radioactive nuclide, and “Z—” indicates that an α-amino group at an N-terminus is not modified, or is modified with a modifying group having no electric charge; in the formula (3), “B—” indicates that an α-amino group at an N-terminus is labeled with a radioactive nuclide; and in the formulae (1), (2), and (3), “—NH2” indicates that a carboxyl group at a C-terminus is amidated.
摘要翻译：提供了一种用于胰岛成像的分子探针。分子探针包含由下式（1），（2）或（3）表示的多肽，或与前述多肽具有同源性的多肽（SEQ ID NO.1）Z-HGEGTFTSDLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（1）（ SEQ ID NO.2）Z-HGEGTFTSDLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2（2）（SEQ ID NO.3）B-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（3）其中，在式（1）和（2）中，“X”表示赖氨酸残基，赖氨酸残基的侧链的氨基被放射性核素标记，“Z-”表示N末端的α-氨基未被修饰，或者是用不具有电荷的修饰基团修饰 ; 在式（3）中，“B-”表示N末端的α-氨基用放射性核素标记; 在式（1），（2）和（3）中，“-NH 2”表示C末端的羧基被酰胺化。

4. 发明申请

US20110206605A1 Molecular Probe for Imaging of Pancreatic Islets and Use of the Same 有权
标题翻译：胰岛成像用分子探针及其用途
公开(公告)号：US20110206605A1
公开(公告)日：2011-08-25
申请号：US12964486
申请日：2010-12-09
申请人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： A61K51/08 , C07K14/00 , C07K1/13 , C12Q1/02
CPC分类号： G01N33/74 , A61K51/088 , C07K14/605
摘要： A molecular probe for use in imaging of pancreatic islets is provided. The molecular probe comprises a polypeptide represented by the following formula (1), (2), or (3), or a polypeptide having homology with the foregoing polypeptide, (SEQ ID NO. 1) Z-HGEGTFTSDLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (1) (SEQ ID NO. 2) Z-HGEGTFTSDLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2 (2) (SEQ ID NO. 3) B-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (3) where, in the formulae (1) and (2), “X” represents a lysine residue, an amino group of a side chain of the lysine residue being labeled with a radioactive nuclide, and “Z—” indicates that an α-amino group at an N-terminus is not modified, or is modified with a modifying group having no electric charge; in the formula (3), “B—” indicates that an α-amino group at an N-terminus is labeled with a radioactive nuclide; and in the formulae (1), (2), and (3), “—NH2” indicates that a carboxyl group at a C-terminus is amidated.
摘要翻译：提供了一种用于胰岛成像的分子探针。分子探针包含由下式（1），（2）或（3）表示的多肽，或与前述多肽具有同源性的多肽（SEQ ID NO.1）Z-HGEGTFTSDLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（1）（ SEQ ID NO.2）Z-HGEGTFTSDLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2（2）（SEQ ID NO.3）B-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（3）其中，在式（1）和（2）中，“X”表示赖氨酸残基，赖氨酸残基的侧链的氨基被放射性核素标记，“Z-”表示N末端的α-氨基未被修饰，或者是用不具有电荷的修饰基团修饰 ; 在式（3）中，“B-”表示N末端的α-氨基用放射性核素标记; 在式（1），（2）和（3）中，“-NH 2”表示C末端的羧基被酰胺化。

5. 发明申请

US20110059483A1 Molecular Probe for Imaging of Pancreatic Islets and Use of the Same 有权
标题翻译：胰岛成像用分子探针及其用途
公开(公告)号：US20110059483A1
公开(公告)日：2011-03-10
申请号：US12872837
申请日：2010-08-31
申请人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： C12Q1/04 , C07K14/00 , C12Q1/06
CPC分类号： A61K51/088
摘要： To provide a molecular probe for imaging of pancreatic islets. A molecular probe for use in imaging of pancreatic islets is provided. The molecular probe includes any one of the following polypeptides; polypeptides represented by the following formulae (1), (5), and (9); and polypeptides having homology with the foregoing polypeptides; Z-DLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (1) Z-DLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2 (5) B-DLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (9) where X in the formulae (1) and (5) and B—in the formula (9) indicate that an amino group is labeled with a group represented by the formula (I) below having an aromatic ring, wherein A represents either an aromatic hydrocarbon group or an aromatic heterocyclic group, R1 represents a substituent that contains radioactive iodine, R2 represents either a hydrogen atom or a substituent different from that represented by R1, and R3 represents any one of a bond, a methylene group, and an oxymethylene group.
摘要翻译：为胰岛成像提供分子探针。提供了一种用于胰岛成像的分子探针。分子探针包括以下多肽之一; 由下式（1），（5）和（9）表示的多肽; 和与上述多肽具有同源性的多肽; Z-DLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（1）Z-DLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2（5）B-DLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（9）其中式（1）和（5）中的X和式（9）中的B-表示氨基被具有芳环的式（I）表示的基团标记，其中A表示芳香族烃基或芳香族杂环基，R 1表示含有放射性碘的取代基，R 2表示氢原子或取代基与R1表示的不同，R3表示键，亚甲基和甲醛基中的任一个。

6. 发明授权

US08642008B2 Molecular probe for imaging of pancreatic islets and use of the same 有权
标题翻译：胰岛成像用分子探针及其用途
公开(公告)号：US08642008B2
公开(公告)日：2014-02-04
申请号：US12872837
申请日：2010-08-31
申请人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： A61K51/08
CPC分类号： A61K51/088
摘要： To provide a molecular probe for imaging of pancreatic islets. A molecular probe for use in imaging of pancreatic islets is provided. The molecular probe includes any one of the following polypeptides: polypeptides represented by the following formulae (1), (5), and (9); and polypeptides having homology with the foregoing polypeptides: Z-DLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (1) Z-DLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2 (5) B-DLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (9) where X in the formulae (1) and (5) and B- in the formula (9) indicate that an amino group is labeled with a group represented by the formula (I) below having an aromatic ring, wherein A represents either an aromatic hydrocarbon group or an aromatic heterocyclic group, R1 represents a substituent that contains radioactive iodine, R2 represents either a hydrogen atom or a substituent different from that represented by R1, and R3 represents any one of a bond, a methylene group, and an oxymethylene group.
摘要翻译：为胰岛成像提供分子探针。提供了一种用于胰岛成像的分子探针。分子探针包括以下多肽之一：由下式（1），（5）和（9）表示的多肽。和与前述多肽具有同源性的多肽：Z-DLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（1）Z-DLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2（5）B-DLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（9）其中式（1）和（5）中的X和式（9）表示氨基用具有芳环的下式（I）表示的基团标记，其中A表示芳香族烃基或芳香族杂环基，R 1表示含有放射性碘的取代基， R2表示氢原子或与R1表示的不同的取代基，R3表示键，亚甲基和氧亚甲基中的任一个。

7. 发明申请

US20110081663A1 Molecular Probe for Imaging of Pancreatic Islets and Use of the Same 有权
标题翻译：胰岛成像用分子探针及其用途
公开(公告)号：US20110081663A1
公开(公告)日：2011-04-07
申请号：US12893896
申请日：2010-09-29
申请人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： G01N33/53 , C07K14/00
CPC分类号： A61K51/08
摘要： A molecular probe for imaging of pancreatic islets is provided. The molecular probe includes a polypeptide represented by the following formula (1), or a polypeptide that has a homology with the foregoing polypeptide. (SEQ ID NO. 1) Z-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSX-NH2 (1) Wherein “X” represents a lysine residue, an amino group of a side chain of the lysine residue being labeled with a group represented by the following chemical formula (I), wherein A represents an aromatic hydrocarbon group or an aromatic heterocyclic group; R1 represents a substituent that contains 11C, 13N, 15O, 18F, 64Cu, 67Ga, 68Ga, 75Br, 76Br, 77Br, 99mTc, 111In, 123I, 124I, 125I, or 131I; R2 represents either a hydrogen atom, or a substituent different from that represented by R1; and R3 represents any one of a bond, an alkylene group having 1 to 6 carbon atoms, and an oxyalkylene group having 1 to 6 carbon atoms.
摘要翻译：提供了用于胰岛成像的分子探针。分子探针包括由下式（1）表示的多肽，或与前述多肽具有同源性的多肽。（SEQ ID NO.1）Z-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSX-NH2（1）其中，“X”表示赖氨酸残基，赖氨酸残基的侧链的氨基用下述化学式（I）表示的基团标记，其中A表示芳族烃基或芳族杂环基; R1表示含有11C，13N，150C，18F，64Cu，67Ga，68Ga，75Br，76Br，77Br，99mTc，111In，123I，124I，125I或131I的取代基; R2表示氢原子或与R1表示的取代基不同的取代基; R3表示碳原子数1〜6的亚烷基，碳原子数1〜6的氧亚烷基。

8. 发明申请

US20110033381A1 MOLECULAR PROBE FOR IMAGING OF PANCREATIC ISLET AND THE PRECURSOR, AND USE OF THE SAME 审中-公开
标题翻译：用于成像胰腺和前列腺的分子探针及其用途
公开(公告)号：US20110033381A1
公开(公告)日：2011-02-10
申请号：US12854007
申请日：2010-08-10
申请人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： A61K51/08 , C07K14/00 , A61K49/00
CPC分类号： A61K51/08 , C07K14/435 , C07K14/57563 , Y02P20/55
摘要： A precursor of molecular probe for imaging of pancreatic islets is provided. A polypeptide represented by any one of the following formulae (1) to (4), or a polypeptide having a homology with the foregoing polypeptide. *-DLSK* QMEEEAVRLFIEWLK* NGGPSSGAPPPSK-NH2(1) *-LSK* QMEEEAVRLFIEWLK* NGGPSSGAPPPSK-NH2(2) *-SK* QMEEEAVRLFIEWLK* NGGPSSGAPPPSK-NH2(3) *-K* QMEEEAVRLFIEWLK* NGGPSSGAPPPSK-NH2,(4) wherein *- indicates that an α-amino group at an N-terminus is protected by a protecting group or modified with a modifying group having no electric charge; K* indicates that an amino group of a side chain of a lysine is protected by a protecting group; and —NH2 indicates that a carboxyl group at a C-terminus is amidated.
摘要翻译：提供了用于胰岛成像的分子探针的前体。由下式（1）至（4）中任一项表示的多肽或与前述多肽具有同源性的多肽。 * -DLSK * QMEEEAVRLFIEWLK * NGGPSSGAPPPSK-NH2（1）* -LSK * QMEEEAVRLFIEWLK * NGGPSSGAPPPSK-NH2（2）* -SK * QMEEEAVRLFIEWLK * NGGPSSGAPPPSK-NH2（3）* -K * QMEEEAVRLFIEWLK * NGGPSSGAPPPSK-NH2，（4）其中 *表示N-末端的α-氨基被保护基保护或用不带电的修饰基团修饰; K *表示赖氨酸的侧链的氨基被保护基保护; 并且-NH 2表示C末端的羧基被酰胺化。

9. 发明申请

US20130052132A1 Method for Producing Radioactively Labeled Polypeptide 审中-公开
标题翻译：生产放射性标记多肽的方法
公开(公告)号：US20130052132A1
公开(公告)日：2013-02-28
申请号：US13369903
申请日：2012-02-09
申请人： Hideo Saji , Nobuya Inagaki , Hiroyuki Kimura , Kentaro Toyoda , Konomu Hirao , Hirokazu Matsuda
发明人： Hideo Saji , Nobuya Inagaki , Hiroyuki Kimura , Kentaro Toyoda , Konomu Hirao , Hirokazu Matsuda
IPC分类号： C07K14/00 , A61K51/08
CPC分类号： C07K14/57563 , A61K51/088 , C07K1/13
摘要： The present invention relates to a method for producing a polypeptide. The method includes labeling a molecular probe precursor represented by an amino acid sequence of the formula (1) using a labeling compound capable of labeling a lysine or lysine derivative: (1) Y1-Leu-Ser-Xaa12-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg- Leu-Phe-Ile-Glu-Trp-Leu-Xaa27-Asn-Gly-Y2 where Y1 represents an amino acid sequence represented by the formula (2) or the amino acid sequence represented by the formula (2) with 1 to 8 amino acids from the N-terminus being deleted, Xaa12 represents a lysine or lysine derivative, Xaa27 represents a basic amino acid having no functional group at its side chain that reacts with the labeling compound or represents methyl lysine or acetylated lysine, and Y2 represents an amino acid sequence represented by the formula (3) or the amino acid sequence represented by the formula (3) with 1 to 9 amino acids from the C-terminus being deleted: (2) His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp (3) Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser
摘要翻译：本发明涉及一种生产多肽的方法。该方法包括使用能够标记赖氨酸或赖氨酸衍生物的标记化合物来标记由式（1）的氨基酸序列表示的分子探针前体：（1）Y1-Leu-Ser-Xaa12-Gln-Met-Glu- Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Xaa27-Asn-Gly-Y2，其中Y1表示由式（2）表示的氨基酸序列或由缺失N末端1〜8个氨基酸的式（2），Xaa12表示赖氨酸或赖氨酸衍生物，Xaa27表示其侧链上没有与标记化合物反应的官能团的碱性氨基酸，赖氨酸或乙酰化赖氨酸，Y2表示由式（3）表示的氨基酸序列或由式（3）表示的氨基酸序列，其中C末端具有1至9个氨基酸缺失：（2）His- Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp（3）Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro

10. 发明申请

US20120107239A1 Precursor of Molecular Probe for Pancreatic Islet Imaging and Use of the Same 审中-公开
标题翻译：胰岛成像分析探针前体及其应用
公开(公告)号：US20120107239A1
公开(公告)日：2012-05-03
申请号：US13148303
申请日：2010-03-16
申请人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa
发明人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa
IPC分类号： A61K51/04 , C07D209/44
CPC分类号： A61K51/0446
摘要： A precursor of a molecular probe for imaging of pancreatic islets is a compound expressed as the following formula (I): wherein -V-X represents a substituent on a benzene ring, V represents a bond, R1, of OR1, R1 represents a C1-C6 alkylene group, R2 represents H (hydrogen atom), a C1-C6 alkyl group, a C7-C10 aralkyl group, or a protecting group, X represents a OMs group, a OTs group, a OTf group, Br (bromine atom), or I (iodine atom), and carbon marked with * is an asymmetric carbon atom.
摘要翻译：用于胰岛成像的分子探针的前体是以下式（I）表示的化合物：其中-VX表示苯环上的取代基，V表示OR1的键，R1表示C1-C6 亚烷基，R2表示H（氢原子），C1-C6烷基，C7-C10芳烷基或保护基，X表示OMs基，OTs基，OTf基，Br（溴原子）或I（碘原子），标有*的碳是不对称碳原子。

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