公开(公告)号：US20060116322A1

公开(公告)日：2006-06-01

申请号：US11241649

申请日：2005-09-30

申请人： Chadler Pool

发明人： Chadler Pool

IPC分类号： A61K38/18 ,  C07K14/505

CPC分类号： B82Y5/00 ,  A61K47/543 ,  A61K47/544 ,  A61K47/60 ,  A61K47/665 ,  A61K47/67

摘要： The invention provides biologically active erythropoietin (EPO) conjugate compositions wherein a transglutaminase reaction is employed to covalently and site specifically conjugate the EPO molecule to a non-antigenic hydrophilic polymer that can also be covalently linked to an organic molecule either of which modification increases the circulating serum half-life of the composition.

公开(公告)号：US20090239790A1

公开(公告)日：2009-09-24

申请号：US12476268

申请日：2009-06-02

申请人： Chadler Pool ,  Juliane Mills ,  Mark Cunningham

发明人： Chadler Pool ,  Juliane Mills ,  Mark Cunningham

IPC分类号： A61K38/22 ,  C07K14/61

CPC分类号： C07K1/1075 ,  C07K1/1077 ,  C07K14/505

摘要： The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula: (M)n-X-A-cys-EPO   (I) where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position -1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of -1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.

摘要翻译： 本发明涉及具有N-末端游离硫醇的新型修饰蛋白，其可通过重组方法制备并准备进一步化学衍生化。 特别地，本发明涉及具有改变的生物化学，生理化学和药代动力学性质的红细胞生成素缀合物化合物。 更具体地，本发明的一个实施方案涉及下式的促红细胞生成素缀合物化合物：<？in-line-formula description =“In-line Formulas”end =“lead”→（M）nXA-cys-EPO（I） 其中EPO是选自红细胞生成素或促红细胞生成素变体的红细胞生成素，其具有不同于野生型人EPO的至少一种氨基酸，其中，“=”在线公式“end =”tail“ 或其具有引起骨髓细胞增加红细胞产生的生物学特性的任何药物可接受的衍生物; cys代表氨基酸半胱氨酸并且发生在相对于促红细胞生成素部分的氨基酸序列的位置-1; A表示用于将X化学连接到-1Cys的硫醇基上的残留部分的结构; X是水溶性聚合物，例如聚亚烷基二醇或其它聚合物; M是增加构建体的循环半衰期的有机分子（包括肽和蛋白质） N为0〜15的整数。

公开(公告)号：US20050170457A1

公开(公告)日：2005-08-04

申请号：US11021516

申请日：2004-12-23

申请人： Chadler Pool ,  Juliane Mills ,  Mark Cunningham

发明人： Chadler Pool ,  Juliane Mills ,  Mark Cunningham

IPC分类号： C07H21/04 ,  C07K1/00 ,  C07K1/107 ,  C07K14/505 ,  C12N9/96 ,  C12N15/85 ,  C12P21/02

CPC分类号： C07K1/1075 ,  C07K1/1077 ,  C07K14/505

摘要： The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula: (M)n-X-A-cys-EPO   (I) where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position −1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of −1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.

摘要翻译： 本发明涉及具有N-末端游离硫醇的新型修饰蛋白，其可通过重组方法制备并准备进一步化学衍生化。 特别地，本发明涉及具有改变的生物化学，生理化学和药代动力学性质的红细胞生成素缀合物化合物。 更具体地，本发明的一个实施方案涉及下式的促红细胞生成素缀合物化合物：<？in-line-formula description =“In-line Formulas”end =“lead”？>（M） -XA-cys-EPO（I）<？in-line-formula description =“In-line Formulas”end =“tail”？>其中EPO是选自促红细胞生成素或具有至少一个氨基酸的促红细胞生成素变体的红细胞生成部分 不同于野生型人EPO，或其具有引起骨髓细胞增加红细胞产生的生物学特性的任何药物可接受的衍生物; cys代表氨基酸半胱氨酸并且发生在相对于促红细胞生成素部分的氨基酸序列的位置-1; A表示用于将X化学连接到-1Cys的硫醇基上的残留部分的结构; X是水溶性聚合物，例如聚亚烷基二醇或其它聚合物; M是增加构建体的循环半衰期的有机分子（包括肽和蛋白质） N为0〜15的整数。

公开(公告)号：US20070021594A1

公开(公告)日：2007-01-25

申请号：US11472101

申请日：2006-06-21

申请人： Marian Kruszynski ,  Steven Lahr ,  Chadler Pool

发明人： Marian Kruszynski ,  Steven Lahr ,  Chadler Pool

IPC分类号： C07K1/12 ,  C07K14/775

CPC分类号： C07K14/505 ,  C07K1/12 ,  C07K1/22 ,  C07K14/775

摘要： This invention describes a method for removing unreacted activated lipid moieties using a bifunctional ligand containing a first functional group reactive with the activating group of the lipid and a second functional group capable of binding to an affinity reagent or support. These reagents can be used to quench reactions between peptides/proteins and other moieties such as activated PEGs or lipids. Once the reaction has been quenched, the reaction mixture can be passed over an affinity column that will bind the peptide, biotin or other ligand attached to the “quenched” reagent and thereby remove it from the reaction mixture.

摘要翻译： 本发明描述了使用含有与脂质的活化基团反应的第一官能团的双官能配体和能够结合亲和试剂或载体的第二官能团来除去未反应的活化脂质部分的方法。 这些试剂可用于淬灭肽/蛋白质和其它部分如活化的PEG或脂质之间的反应。 一旦反应已被猝灭，反应混合物可以通过亲和柱，其将结合肽，生物素或与“骤冷”试剂连接的其它配体，从而将其从反应混合物中除去。

公开(公告)号：US20060068426A1

公开(公告)日：2006-03-30

申请号：US11207573

申请日：2005-08-19

申请人： James Tam ,  Chadler Pool ,  Ying Zhang ,  Kristen Sadler

发明人： James Tam ,  Chadler Pool ,  Ying Zhang ,  Kristen Sadler

IPC分类号： C12Q1/70 ,  C12Q1/68

CPC分类号： C07K14/7158 ,  C07K16/2866 ,  C07K2317/622 ,  C07K2317/76

摘要： The present invention provides methods of preparing and identifying antibodies against a loop domain of a protein, such as an extracellular loop (ECL) domain of a transmembrane protein. Cyclic and end-to-end cyclized peptides corresponding to loop domains are employed in the present invention. Transmembrane proteins contemplated by the invention include the G-coupled protein receptor or a viral envelope protein.

摘要翻译： 本发明提供了制备和鉴定针对蛋白质（例如跨膜蛋白的细胞外环（ECL）结构域）的环结构域的抗体的方法。 对应于环结构域的环状和端对端环化肽用于本发明。 本发明考虑的跨膜蛋白包括G偶联蛋白受体或病毒包膜蛋白。

公开(公告)号：US06995245B2

公开(公告)日：2006-02-07

申请号：US10854854

申请日：2004-05-27

申请人： Chadler Pool

发明人： Chadler Pool

IPC分类号： A61K38/18 ,  C07K14/00

CPC分类号： B82Y5/00 ,  A61K47/543 ,  A61K47/544 ,  A61K47/60 ,  A61K47/665 ,  A61K47/67

摘要： The invention provides biologically active erythropoietin (EPO) conjugate compositions wherein a transglutaminase reaction is employed to covalently and site specifically conjugate the EPO molecule to a non-antigenic hydrophilic polymer that can also be covalently linked to an organic molecule either of which modification increases the circulating serum half-life of the composition.

摘要翻译： 本发明提供了生物活性促红细胞生成素（EPO）缀合物组合物，其中使用转谷氨酰胺酶反应来共价并且将EPO分子特异性缀合到非抗原性亲水性聚合物上，所述非抗原性亲水性聚合物也可共价连接到有机分子， 组合物的血清半衰期。