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    Antagonists with position 13 modification
    13.
    发明授权
    Antagonists with position 13 modification 失效
    具有13位修饰的拮抗剂

    公开(公告)号：US5093233A

    公开(公告)日：1992-03-03

    申请号：US514394

    申请日：1990-04-25

    申请人： Michael Rosenblatt ,  Eliahu Roubini ,  Michael Chorev ,  Ruth F. Nutt

    发明人： Michael Rosenblatt ,  Eliahu Roubini ,  Michael Chorev ,  Ruth F. Nutt

    IPC分类号： A61K38/00 ,  C07K14/635

    CPC分类号： C07K14/635 ,  A61K38/00

    摘要： The present invention relates to the use of peptide hormone analogues as inhibitors of their respective naturally occurring peptide hormone. The structure of the peptide hormone analogues is exemplified by parathyroid hormone (PTH), wherein Lys.sup.13 is substituted to increase the biological activity of the PTH analogues. Thus, there are disclosed peptides having the formulae:PTH(7-34)NH.sub.2 ;[Tyr.sup.34 ]PTH(7-34)NH.sub.2 ;[D-Trp.sup.12, Tyr.sup.34 ]PTH(7-34)NH.sub.2 ;[Nle.sup.8,18, D-Trp.sup.12, Tyr.sup.34 ]PTH(7-34)NH.sub.2 ;[Nle.sup.8,18, Tyr.sup.34 ]PTH(7-34)NH.sub.2 ;desamino[Nle.sup.8,18, D-Trp.sup.12, Tyr.sup.34 ]PTH(7-34)NH.sub.2 ; and,desamino[Nle.sup.8,18, D-Trp.sup.12, Tyr.sup.34 ]PTH(8-34)NH.sub.2wherein Lys.sup.13 is modified in the epsilon-amino acid group by N,N-diisobutyl or 3-phenylpropanoyl.

    摘要翻译： 本发明涉及肽激素类似物作为其各自天然存在的肽激素的抑制剂的用途。 肽激素类似物的结构以甲状旁腺激素（PTH）为例，其中Lys13被取代以增加PTH类似物的生物学活性。 因此，公开了具有下式的肽：PTH（7-34）NH 2; [Tyr34] PTH​​（7-34）NH2; [D-Trp12，Tyr34] PTH​​（7-34）NH2; [Nle8,18，D-Trp12，Tyr34] PTH​​（7-34）NH2; [Nle8,18，Tyr34] PTH​​（7-34）NH2; 脱氨基[Nle8,18，D-Trp12，Tyr34] PTH​​（7-34）NH 2; 和脱氨基[Nle8,18，D-Trp12，Tyr34] PTH​​（8-34）NH2，其中Lys13在ε-氨基酸基团中被N，N-二异丁基或3-苯基丙酰基修饰。

    SURROGATES OF POST-TRANSLATIONALLY MODIFIED PROTEINS AND USES THEREOF
    14.
    发明申请
    SURROGATES OF POST-TRANSLATIONALLY MODIFIED PROTEINS AND USES THEREOF 有权
    翻译后修饰蛋白质的现象及其用途

    公开(公告)号：US20140024056A1

    公开(公告)日：2014-01-23

    申请号：US13984423

    申请日：2012-02-10

    申请人： Michael Chorev ,  Joes A. Halperin

    发明人： Michael Chorev ,  Joes A. Halperin

    IPC分类号： G01N33/68 ,  C07K16/28 ,  C07K14/705

    CPC分类号： G01N33/6893 ,  C07K14/70596 ,  C07K16/2896 ,  C07K16/44 ,  G01N33/564 ,  G01N33/6872 ,  G01N2333/70596 ,  G01N2440/00 ,  G01N2440/38 ,  G01N2800/042

    摘要： The present invention provides compounds that are surrogates of post-translationally modified proteins and uses thereof. Numerous diseases are associated with post-translationally modified proteins that are difficult to obtain in homogenous form and in quantities needed for immunization and use as convenient standards, calibrators, and/or reference compounds that facilitate the detection and analysis of endogenous post-translationally modified proteins. The surrogate compounds of the invention typically comprise antigenic epitopes (one of which carries a post-translational modification) that are tethered by a flexible and hydrophilic linker. The resulting compound behaves like a surrogate of the post-translationally modified protein because it preserves the character of the included antigens and allows recognition by specific antibodies targeting the individual antigens. The surrogate compounds may be prepared by covalently joining two or more polypeptide epitopes using one or more linkers, wherein at least one of the epitopes comprises a post-translational modification. In one aspect, the surrogate compounds of the invention comprise a C-terminal epitope and a glycated epitope of human CD59. The inventive methods allow quantification of the levels of glycated CD59 in the serum in human subjects, particularly those with diabetes or pre-diabetes. This technological platform of post-translationally modified protein surrogates can be applied to other diseases associated with post-translationally modified proteins (e.g., autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus). In another aspect, the invention provides antibodies that bind specifically to the compounds of the invention and methods for producing such antibodies.

    摘要翻译： 本发明提供了作为翻译后修饰的蛋白质的替代物的化合物及其用途。 许多疾病与翻译后修饰的蛋白质相关，其难以以均匀形式获得，并且以免疫和使用所需的量作为方便的标准品，校准物和/或参考化合物获得，其有助于内源性翻译后修饰的蛋白质的检测和分析 。 本发明的替代化合物通常包含被柔性和亲水接头连接的抗原表位（其中一个携带翻译后修饰）。 所得化合物表现为翻译后修饰的蛋白质的替代物，因为其保留所包含的抗原的特征，并允许通过针对各个抗原的特异性抗体进行识别。 替代化合物可以通过使用一种或多种接头共价连接两个或多个多肽表位来制备，其中至少一个表位包含翻译后修饰。 一方面，本发明的替代化合物包含人CD59的C-末端表位和糖基化表位。 本发明的方法允许定量人受试者，特别是糖尿病或前期糖尿病患者血清中糖基化CD59的水平。 翻译后修饰的蛋白质替代物的这种技术平台可以应用于与翻译后修饰的蛋白质（例如自身免疫性疾病如多发性硬化症，类风湿性关节炎和系统性红斑狼疮）相关的其它疾病。 另一方面，本发明提供了与本发明化合物特异性结合的抗体以及用于产生此类抗体的方法。

    Osteogenic growth oligopeptides and pharmaceutical compositions containing them
    17.
    发明授权
    Osteogenic growth oligopeptides and pharmaceutical compositions containing them 失效
    成骨生长寡肽和含有它们的药物组合物

    公开(公告)号：US5814610A

    公开(公告)日：1998-09-29

    申请号：US530277

    申请日：1996-01-05

    申请人： Itai Bab ,  Andras Muhlrad ,  Michael Chorev ,  Arie Shteyer ,  Zvi Greenberg ,  Nura Mansur

    发明人： Itai Bab ,  Andras Muhlrad ,  Michael Chorev ,  Arie Shteyer ,  Zvi Greenberg ,  Nura Mansur

    IPC分类号： A61K38/00 ,  A61K38/22 ,  A61P19/00 ,  A61P43/00 ,  C07K5/08 ,  C07K5/10 ,  C07K7/06 ,  C07K14/51 ,  C12N15/06 ,  A61K35/18 ,  A61K37/02 ,  C07K7/08

    CPC分类号： C07K14/51 ,  A61K38/00

    摘要： The invention relates to biochemically pure oligopeptides having stimulatory activity on osteoblastic and/or fibroblastic cells having a molecular weight between 200 and 2,000. Preferred oligopeptides according to the invention comprise the amino acid sequences Tyr-Gly-Phe-His-Gly (SEQ.ID.No.2) and Gly-Phe-Gly-Gly (SEQ.ID.No.3). The invention further relates to pharmaceutical compositions for the stimulation of formation of osteoblastic or fibroblastic cells, enhanced bone formation in osteogenic pathological conditions, fracture repair, healing of wounds, intraosseous implants and bone supplementation, or other conditions requiring enhanced bone formation cells comprising a therapeutically effective amount of an oligopeptide according to the invention.

    摘要翻译： PCT No.PCT / GB94 / 00416 Sec。 371日期1996年1月5日 102（e）日期1996年1月5日PCT 1994年3月4日PCT公布。 出版物WO94 / 20529 日期1994年9月15日本发明涉及对成骨细胞和/或分子量在200和2,000之间的成纤维细胞和/或成纤维细胞具有刺激活性的生物化学纯的寡肽。 根据本发明的优选的寡肽包含氨基酸序列Tyr-Gly-Phe-His-Gly（SEQ.ID.No.2）和Gly-Phe-Gly-Gly（SEQ.ID.No.3）。 本发明进一步涉及用于刺激成骨细胞或成纤维细胞形成的药物组合物，在成骨病理状况下增强骨形成，骨折修复，伤口愈合，骨内植入物和补骨，或需要增强的骨形成细胞的其它条件，其包括治疗 有效量的根据本发明的寡肽。

    Surrogates of post-translationally modified proteins and uses thereof
    20.
    发明授权
    Surrogates of post-translationally modified proteins and uses thereof 有权
    翻译后修饰蛋白质的替代物及其用途

    公开(公告)号：US09417248B2

    公开(公告)日：2016-08-16

    申请号：US13984423

    申请日：2012-02-10

    申请人： Michael Chorev ,  Jose A. Halperin

    发明人： Michael Chorev ,  Jose A. Halperin

    IPC分类号： G01N33/68 ,  C07K16/28 ,  C07K14/705 ,  C07K16/44 ,  G01N33/564

    CPC分类号： G01N33/6893 ,  C07K14/70596 ,  C07K16/2896 ,  C07K16/44 ,  G01N33/564 ,  G01N33/6872 ,  G01N2333/70596 ,  G01N2440/00 ,  G01N2440/38 ,  G01N2800/042

    摘要： The present invention provides compounds that are surrogates of post-translationally modified proteins and uses thereof. Numerous diseases are associated with post-translationally modified proteins that are difficult to obtain in homogenous form and in quantities needed for immunization and use as convenient standards, calibrators, and/or reference compounds that facilitate the detection and analysis of endogenous post-translationally modified proteins. The surrogate compounds of the invention typically comprise antigenic epitopes (one of which carries a post-translational modification) that are tethered by a flexible and hydrophilic linker. The resulting compound behaves like a surrogate of the post-translationally modified protein because it preserves the character of the included antigens and allows recognition by specific antibodies targeting the individual antigens. The surrogate compounds may be prepared by covalently joining two or more polypeptide epitopes using one or more linkers, wherein at least one of the epitopes comprises a post-translational modification. In one aspect, the surrogate compounds of the invention comprise a C-terminal epitope and a glycated epitope of human CD59. The inventive methods allow quantification of the levels of glycated CD59 in the serum in human subjects, particularly those with diabetes or pre-diabetes. This technological platform of post-translationally modified protein surrogates can be applied to other diseases associated with post-translationally modified proteins (e.g., autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus). In another aspect, the invention provides antibodies that bind specifically to the compounds of the invention and methods for producing such antibodies.

    摘要翻译： 本发明提供了作为翻译后修饰的蛋白质的替代物的化合物及其用途。 许多疾病与翻译后修饰的蛋白质相关，其难以以均匀形式获得，并且以免疫和使用所需的量作为方便的标准品，校准物和/或参考化合物获得，其有助于内源性翻译后修饰的蛋白质的检测和分析 。 本发明的替代化合物通常包含被柔性和亲水接头连接的抗原表位（其中一个携带翻译后修饰）。 所得化合物表现为翻译后修饰的蛋白质的替代物，因为其保留所包含的抗原的特征，并允许通过针对各个抗原的特异性抗体进行识别。 替代化合物可以通过使用一种或多种接头共价连接两个或多个多肽表位来制备，其中至少一个表位包含翻译后修饰。 一方面，本发明的替代化合物包含人CD59的C-末端表位和糖基化表位。 本发明的方法允许定量人受试者，特别是糖尿病或前期糖尿病患者血清中糖基化CD59的水平。 翻译后修饰的蛋白质替代物的这种技术平台可以应用于与翻译后修饰的蛋白质（例如自身免疫性疾病如多发性硬化症，类风湿性关节炎和系统性红斑狼疮）相关的其它疾病。 另一方面，本发明提供了与本发明化合物特异性结合的抗体以及用于产生此类抗体的方法。