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    PH-dependent polypeptide aggregation and its use
    1.
    发明申请
    PH-dependent polypeptide aggregation and its use 审中-公开
    PH依赖多肽聚集及其应用

    公开(公告)号：US20040192887A1

    公开(公告)日：2004-09-30

    申请号：US10397059

    申请日：2003-03-25

    Inventor： Ralph Zahn

    IPC: C07K016/00 ,  C12Q001/70 ,  G01N033/53 ,  C07K007/00 ,  C07K017/00 ,  A61K038/04 ,  C07K001/00 ,  C07K014/00 ,  C07K005/00

    CPC classification number: C07K14/47

    Abstract: The invention provides an alternative method of reversible aggregation and/or dissociation of polypeptides. Proteins or polypeptides according to the invention have an inherent aggregation capability, wherein the aggregation is an oligomerization of the polypeptide that is based on the presence and the strucuture of peptide repeats localized in a flexibly disordered domain of this polypeptide. The flexibly disordered domain comprising the peptide repeats preferrably is located in close proximity with the N-terminus of the protein amino acid sequence. Preferably, each of the peptide repeats has a sequence that comprises one to four identical octapeptides with the amino acid sequence: PHGGGWGQ. Preferred proteins are selected from the group comprising cellular prion proteins (PrPC) and engineered polypeptides or fusion proteins with a respective inherent reversible aggregation and dissociation capability. Because of the new mechanism of aggregation, the oligomerization reaction of the protein is reversible in a fluidic environment depending on the pH of this fluidic environment. Oligomerization occurs at a pH of 6.2 to 7.8, and the dissociation into monomers is reported to be at a pH range of 4.5 to 5.5. 1

    Abstract translation: 本发明提供了多肽的可逆聚集和/或解离的替代方法。 根据本发明的蛋白质或多肽具有固有的聚集能力，其中聚集是多肽的寡聚化，其基于定位于该多肽的柔性无序结构域中的肽重复序列的存在和结构。 优选地，包含肽重复序列的柔性无序结构域位于蛋白质氨基酸序列的N-末端附近。 优选地，每个肽重复序列具有包含1-4个与氨基酸序列PHGGGWGQ相同的八肽的序列。 优选的蛋白质选自包含细胞朊蛋白（PrP））和具有相应固有的可逆聚集和解离能力的工程改造的多肽或融合蛋白。 由于聚合的新机制，蛋白质的低聚反应在流体环境中是可逆的，这取决于该流体环境的pH。 低聚发生在6.2至7.8的pH下，据报导单体的解离在4.5至5.5的pH范围内。

    Pulmonary administration of chemically modified insulin
    4.
    发明申请
    Pulmonary administration of chemically modified insulin 失效
    肺部给予化学修饰的胰岛素

    公开(公告)号：US20030216542A1

    公开(公告)日：2003-11-20

    申请号：US10405190

    申请日：2003-04-01

    Inventor： John S. Patton ,  Mei-Chang Kuo ,  J. Milton Harris ,  Chester Leach ,  Kimberly Perkins ,  Blaine Bueche

    IPC: C07K005/00 ,  A61K038/28

    CPC classification number: A61K38/28 ,  A61K47/60

    Abstract: The present invention provides active, hydrophilic polymer-modified derivatives of insulin. The insulin derivatives of the invention are, in one aspect, suitable for delivery to the lung and exhibit pharmakokinetic and/or pharmacodynamic properties that are significantly improved over native insulin.

    Abstract translation: 本发明提供胰岛素的活性亲水性聚合物改性衍生物。 在一个方面，本发明的胰岛素衍生物适合于递送至肺并表现出比天然胰岛素明显改善的药物动力学和/或药效学性质。

    Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) structure and uses thereof in drug identification and screening
    5.
    发明申请
    Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) structure and uses thereof in drug identification and screening 审中-公开
    癌胚抗原细胞粘附分子1（CEACAM1）的结构及其在药物鉴定和筛选中的应用

    公开(公告)号：US20030211477A1

    公开(公告)日：2003-11-13

    申请号：US10138176

    申请日：2002-05-01

    Inventor： Kathryn V. Holmes ,  Bruce D. Zelus ,  Kemin Tan ,  Jia-Huai Wang ,  Rob Meijers

    IPC: C12Q001/70 ,  C12Q001/68 ,  C07K002/00 ,  C07K004/00 ,  C07K005/00 ,  C07K007/00 ,  C07K014/00 ,  C07K016/00 ,  C07K017/00 ,  A61K038/00 ,  C07K001/00

    CPC classification number: C07K14/70503 ,  A61K38/1709 ,  G01N33/57473 ,  G01N2500/02 ,  G01N2500/04

    Abstract: Disclosed is the first crystal structure in the carcinoembryonic antigen (CEA) family, the mouse CEACAM1anull1,4null, containing the N-terminal functional domain that is characterized as having a uniquely folded CCnull loop. This novel feature could not be predicted based on sequence analysis alone. The structure has provided a prototypic architecture for modeling human homologues within the CEA family. These tertiary structures are used in a number of screening methods for identifying candidate molecules that have a binding affinity for the tertiary structure of the CCnull loop and its vicinity. Pharmaceutical preparations that include one or more of such identified candidates may then be provided and used in treatments for certain bacterial and viral infections, certain tumors and disorders of angiogenesis or immune responses and autoimmune disease.

    Abstract translation: 公开了癌胚抗原（CEA）家族中的第一晶体结构，小鼠CEACAM1a [1,4]，其含有特征在于具有独特折叠的CC'环的N末端功能结构域。 这种新特征不能仅基于序列分析来预测。 该结构提供了一种用于在CEA家族内建模人类同源物的原型架构。 这些三级结构用于多种筛选方法，用于鉴定对CC'环及其附近的三级结构具有结合亲和性的候选分子。 然后可以提供包括一种或多种这样的鉴定的候选物的药物制剂，并用于某些细菌和病毒感染，某些肿瘤和血管发生或免疫应答和自身免疫疾病的病症的治疗中。

    Method for making insulin precursors and insulin precursor analogs
    7.
    发明申请
    Method for making insulin precursors and insulin precursor analogs 有权
    制备胰岛素前体和胰岛素前体类似物的方法

    公开(公告)号：US20030191277A1

    公开(公告)日：2003-10-09

    申请号：US10316421

    申请日：2002-12-11

    Inventor： Thomas Borglum Kjeldsen ,  Svend Ludvigsen ,  Niels C. Kaarsholm

    IPC: C07K005/00 ,  C07K007/00 ,  C07K016/00 ,  C07K017/00 ,  A61K038/28 ,  A61K038/00 ,  A61K038/06

    CPC classification number: C07K14/62

    Abstract: Novel insulin precursors and insulin precursor analogs having a mini C-peptide comprising at least one aromatic amino acid residue have an increased folding stability. The novel insulin precursors and insulin precursor analogs can be expressed in yeast in high yields and are preferably not more 15 amino acid residues in length. Also provided are polynucleotide sequences encoding the claimed precursors or precursor analogs, and vectors and cell lines containing such polynucleotide sequences.

    Abstract translation: 具有包含至少一个芳族氨基酸残基的迷你C肽的新型胰岛素前体和胰岛素前体类似物具有增加的折叠稳定性。 新型胰岛素前体和胰岛素前体类似物可以以高产率在酵母中表达，并且长度优选不超过15个氨基酸残基。 还提供了编码所要求保护的前体或前体类似物的多核苷酸序列，以及含有该多核苷酸序列的载体和细胞系。

    ANTIGENICALLY REACTIVE REGIONS OF THE HEPATITIS A VIRUS POLYPROTEIN
    8.
    发明申请
    ANTIGENICALLY REACTIVE REGIONS OF THE HEPATITIS A VIRUS POLYPROTEIN 失效
    乙型肝炎病毒抗体的抗原区域

    公开(公告)号：US20030187184A1

    公开(公告)日：2003-10-02

    申请号：US09171432

    申请日：1998-11-23

    Inventor： HOWARD A. FIELDS ,  YURY E. KHUDYAKOV

    IPC: A61K039/29 ,  C07K002/00 ,  C07K004/00 ,  C07K005/00 ,  C07K007/00 ,  C07K014/00 ,  C07K016/00 ,  C07K017/00 ,  A61K038/00 ,  A61K038/04 ,  C07K001/00 ,  C12P021/08

    CPC classification number: C07K14/005 ,  A61K38/00 ,  A61K39/00 ,  C07K2319/00 ,  C12N2770/32422 ,  Y02A50/464

    Abstract: It is to be understood that the above description is intended to be illustrative and not restrictive. Many embodiments will be apparent to those of skill in the art upon reading the above description. The scope of the invention should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. The disclosures of all articles and references, including patent applications and publications, are incorporated herein by reference for all purpose.

    Abstract translation: 应当理解，上述描述旨在是说明性的而不是限制性的。 在阅读上述说明之后，许多实施例对于本领域技术人员是显而易见的。 因此，本发明的范围不应参照上述描述来确定，而应该参照所附权利要求来确定，以及这些权利要求的等同物的全部范围。 所有文章和参考文献（包括专利申请和出版物）的披露通过引用并入本文。

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