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公开(公告)号：US09458220B2
公开(公告)日：2016-10-04
申请号：US14563362
申请日：2014-12-08
Inventor： Richard D. DiMarchi , Yulia Azriel , Zachary Kaur , Jonathan Meyers , Todd Parody , Yan Zhao
Abstract: Single chain insulin analogs are provided having high potency and specificity for the insulin receptor. As disclosed herein optimally sized linking moieties can be used to link human insulin A and B chains, or analogs or derivatives thereof, wherein the carboxy terminus of the B25 amino acid of the B chain is linked to the amino terminus of the A1 amino acid of the A chain via the intervening linking moiety. In on embodiment the linking moiety comprises a polyethylene glycol of 6-16 monomer units and in an alternative embodiment the linking moiety comprises a non-native amino acid sequence derived form the IGF-1 C-peptide and comprising at least 8 amino acids and no more than 12 amino acid in length. Also disclosed are prodrug and conjugate derivatives of the single chain insulin analogs.
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公开(公告)号：US10233225B2
公开(公告)日：2019-03-19
申请号：US15229942
申请日：2016-08-05
Inventor： Richard D. DiMarchi , Yulia Azriel , Zachary Kaur , Jonathan Meyers , Todd Parody , Yan Zhao
Abstract: Single chain insulin analogs are provided having high potency and specificity for the insulin receptor. As disclosed herein optimally sized linking moieties can be used to link human insulin A and B chains, or analogs or derivatives thereof, wherein the carboxy terminus of the B25 amino acid of the B chain is linked to the amino terminus of the A1 amino acid of the A chain via the intervening linking moiety. In on embodiment the linking moiety comprises a polyethylene glycol of 6-16 monomer units and in an alternative embodiment the linking moiety comprises a non-native amino acid sequence derived form the IGF-1 C-peptide and comprising at least 8 amino acids and no more than 12 amino acid in length. Also disclosed are prodrug and conjugate derivatives of the single chain insulin analogs.
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公开(公告)号：US09593156B2
公开(公告)日：2017-03-14
申请号：US14431040
申请日：2013-09-25
Inventor： Richard D. Dimarchi , Yan Zhao
Abstract: Disclosed herein are insulin analog dimers having unique insulin receptor agonist activity based on insulin polypeptide sequences, the site of dimerization and the length of the dimerization linker that connects the two insulin polypeptides. In accordance with one embodiment the first and second insulin polypeptide are independently a two chain insulin analog or a single chain analog and the first and second insulin polypeptides are linked to one another via a B29-B29′, B1-C8, B1-B1 or C8-C8 linkage.
Abstract translation: 本文公开了具有基于胰岛素多肽序列，二聚化位点和连接两个胰岛素多肽的二聚连接体长度的独特的胰岛素受体激动剂活性的胰岛素类似物二聚体。 根据一个实施方案，第一和第二胰岛素多肽独立地是双链胰岛素类似物或单链类似物，并且第一和第二胰岛素多肽通过B29-B29'，B1-C8，B1-B1或 C8-C8键。
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公开(公告)号：US20150274802A1
公开(公告)日：2015-10-01
申请号：US14431040
申请日：2013-09-25
Inventor： Richard D. Dimarchi , Yan Zhao
Abstract: Disclosed herein are insulin analog dimers having unique insulin receptor agonist activity based on insulin polypeptide sequences, the site of dimerization and the length of the dimerization linker that connects the two insulin polypeptides. In accordance with one embodiment the first and second insulin polypeptide are independently a two chain insulin analog or a single chain analog and the first and second insulin polypeptides are linked to one another via a B29-B29′, B1-C8, B1-B1 or C8-C8 linkage.
Abstract translation: 本文公开了具有基于胰岛素多肽序列，二聚化位点和连接两个胰岛素多肽的二聚连接体长度的独特的胰岛素受体激动剂活性的胰岛素类似物二聚体。 根据一个实施方案，第一和第二胰岛素多肽独立地是双链胰岛素类似物或单链类似物，并且第一和第二胰岛素多肽通过B29-B29'，B1-C8，B1-B1或 C8-C8键。
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