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    PROINSULIN DERIVATIVES
    1.
    发明申请
    PROINSULIN DERIVATIVES 审中-公开

    公开(公告)号：US20190263881A1

    公开(公告)日：2019-08-29

    申请号：US16330154

    申请日：2017-09-05

    申请人： CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A.

    发明人： Dimitrios GATOS ,  Alexandra ANASTASIOU ,  Kleomenis Barlos

    IPC分类号： C07K14/62 ,  A61P3/10

    摘要： A first aspect of the invention relates to a polypeptide compound of formula (I): A-C-B   (I) wherein: A is the A chain of insulin or a functional derivative or variant thereof; B is the B chain of insulin or a functional derivative or variant thereof; C is a peptide of the formula: (X1)p—(X2)n—(X3)q wherein: each X1 and X3 is independently a basic amino acid; each X2 is independently a natural or unnatural amino acid; p is 1 or 2; q is 0, 1 or 2; n is 0, 1, 2 or 3. Further aspects of the invention relate to pharmaceutical compositions comprising said polypeptide compound, and therapeutic uses thereof. Another aspect relates to the use of said polypeptide compounds in the preparation of insulin and derivatives thereof.

    A PROCESS FOR PRODUCING EGF
    4.
    发明公开
    A PROCESS FOR PRODUCING EGF 审中-公开

    公开(公告)号：US20240002460A1

    公开(公告)日：2024-01-04

    申请号：US18251493

    申请日：2021-11-05

    申请人： CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A.

    发明人： Kleomenis Barlos ,  Konstantinos Barlos

    IPC分类号： C07K14/495

    CPC分类号： C07K14/495

    摘要： The present invention relates to a process for preparing an epidermal growth factor-like peptide (EGF-like peptide) comprising the following amino acid sequence, C1(X)7C2(X)4-5C3(X)10-13C4(X)C5(X)8C6 [SEQ NO: 49] wherein C1-C6 are each cysteine and each X is independently a natural or unnatural amino acid, and wherein said EGF-like peptide has three intramolecular disulfide bonds; said process comprising the steps of: (I) preparing a first peptide fragment wherein the N-terminal amino acid is protected by a protecting group PG1, which is selected from Boo and Fmoc; (II) preparing a second peptide fragment wherein the C-terminal amino acid is protected by a protecting group PG2, which is selected from trityl, chlorotrityl and t-butyl; and wherein the amino acid side chains in said first and second peptide fragments are optionally protected; (III) coupling the C-terminal amino acid of said first peptide fragment with the N-terminal amino acid of said second peptide fragment in solution to form a linear protected EGF-like peptide; (IV)(a)(i) treating the linear protected EGF-like peptide formed in step (III) with iodine to form an oxidized mixture; (ii) globally deprotecting the oxidized mixture obtained in step (IV)(a)(i) by treating with trifluoroacetic acid (TFA); (iii) treating the deprotected oxidized mixture obtained in step (IV)(a)(ii) with DMSO/DTT to form a cmde EGF-like peptide; or (IV)(b)(i) globally deprotecting the linear protected EGF-like peptide obtained in step (III) by treating with trifluoroacetic acid (TFA); (ii) treating the deprotected mixture obtained in step (IV)(b)(i) with DMSO to form a cmde EGF-like peptide; and (V) optionally purifying the crude EGF-like peptide. Further aspects of the invention relate to processes for preparing EGF-like peptides using various fragment condensations.

    Proinsulin derivatives
    7.
    发明授权
    Proinsulin derivatives 有权

    公开(公告)号：US11230585B2

    公开(公告)日：2022-01-25

    申请号：US16330154

    申请日：2017-09-05

    申请人： CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A.

    发明人： Dimitrios Gatos ,  Alexandra Anastasiou ,  Kleomenis Barlos

    IPC分类号： A61K38/28 ,  C07K14/62 ,  A61P3/10 ,  A61K38/00

    摘要： A first aspect of the invention relates to a polypeptide compound of formula (I): A-C-B  (I) wherein: A is the A chain of insulin or a functional derivative or variant thereof; B is the B chain of insulin or a functional derivative or variant thereof; C is a peptide of the formula: (X1)p-(X2)n-(X3)q wherein: each X1 and X3 is independently a basic amino acid; each X2 is independently a natural or unnatural amino acid; p is 1 or 2; q is 0, 1 or 2; n is 0, 1, 2 or 3. Further aspects of the invention relate to pharmaceutical compositions comprising said polypeptide compound, and therapeutic uses thereof. Another aspect relates to the use of said polypeptide compounds in the preparation of insulin and derivatives thereof.

    Biologically active insulin derivatives
    8.
    发明授权
    Biologically active insulin derivatives 有权

    公开(公告)号：US10195287B2

    公开(公告)日：2019-02-05

    申请号：US15101597

    申请日：2014-12-04

    申请人： Chemical & Biopharmaceutical Laboratories of Patras S.A.

    发明人： Kleomenis Barlos ,  Dimitrios Gatos ,  Kostas Barlos ,  Michail Ziovas

    IPC分类号： A61K38/28 ,  A61K47/65 ,  C07K14/62

    摘要： A first aspect of the invention relates to a single chain insulin analog comprising: (A) the A-chain of human or animal insulin, or an analog or derivative thereof; (B) the B-chain of human or animal insulin, or an analog or derivative thereof; (C) one or more disulfide bonds between said A-chain and said B-chain; and (D) a further covalent link, L, between a functional group of an amino acid in the A-chain and a functional group of an amino acid in the B-chain, at least one of said functional groups being an amino acid side chain functional group. Further aspects of the invention relate to pharmaceutical compositions comprising said single chain insulin derivatives, and therapeutic uses thereof.

    Biologically Active Insulin Derivatives
    9.
    发明申请
    Biologically Active Insulin Derivatives 审中-公开
    生物活性胰岛素衍生物

    公开(公告)号：US20160375146A1

    公开(公告)日：2016-12-29

    申请号：US15101597

    申请日：2014-12-04

    申请人： Chemical & Biopharmaceutical Laboratories of Patras S.A.

    发明人： Kleomenis Barlos ,  Dimitrios Gatos ,  Kostas Barlos ,  Michail Ziovas

    IPC分类号： A61K47/48 ,  A61K38/28

    CPC分类号： A61K47/65 ,  A61K38/28 ,  C07K14/62

    摘要： A first aspect of the invention relates to a single chain insulin analogue comprising: (A) the A-chain of human or animal insulin, or an analogue or derivative thereof; (B) the B-chain of human or animal insulin, or an analogue or derivative thereof; (C) one or more disulfide bonds between said A-chain and said B-chain; and (D) a further covalent link, L, between a functional group of an amino acid in the A-chain and a functional group of an amino acid in the B-chain, at least one of said functional groups being an amino acid side chain functional group. Further aspects of the invention relate to pharmaceutical compositions comprising said single chain insulin derivatives, and therapeutic uses thereof.

    摘要翻译： 本发明的第一方面涉及单链胰岛素类似物，其包含：（A）人或动物胰岛素的A链或其类似物或衍生物; （B）人或动物胰岛素的B链或其类似物或衍生物; （C）所述A链和所述B链之间的一个或多个二硫键; 和（D）A链中的氨基酸的官能团与B链中的氨基酸的官能团之间的另外的共价连接基团L，所述官能团中的至少一个为氨基酸侧 链官能团。 本发明的其它方面涉及包含所述单链胰岛素衍生物的药物组合物及其治疗用途。