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1. 发明申请

US20030208046A1 Pseudo native chemical ligation 失效
标题翻译：伪天然化学结扎
公开(公告)号：US20030208046A1
公开(公告)日：2003-11-06
申请号：US10332386
申请日：2003-01-08
发明人： Christie L. Hunter , Paolo Botti , James A. Bradburne , Shiah-yun Chen , Sonya Cressman , Stephen B.H. Kent , Gerd G. Kochendoerfer , Donald W. Low
IPC分类号： A61K038/19 , C07K014/53
CPC分类号： C07K14/505 , A61K38/00
摘要： The present invention concerns methods and compositions for extending the technique of native chemical ligation of a wider range of peptides, polypeptides, other polymers and other molecules via an amide bond (see FIG. 1). The invention further provides methods and uses for such proteins and derivatized proteins. The invention is particularly suitable for use in the synthesis of optionally polymer-modified, synthetic bioactive proteins, and of pharmaceutical compositions that contain such proteins. 1
摘要翻译：本发明涉及通过酰胺键扩展更宽范围的肽，多肽，其它聚合物和其它分子的天然化学连接技术的方法和组合物（参见图1）。本发明还提供了这些蛋白质和衍生化蛋白质的方法和用途。本发明特别适用于合成任选的聚合物改性的合成生物活性蛋白质和含有这种蛋白质的药物组合物。

2. 发明申请

US20040241806A1 G-CSF polypeptides and conjugates 审中-公开
标题翻译： G-CSF多肽和缀合物
公开(公告)号：US20040241806A1
公开(公告)日：2004-12-02
申请号：US10705745
申请日：2003-11-10
申请人： Maxygen Holdings, Ltd.
发明人： Torben Lauesgaard Nissen , Kim Vilbour Andersen , Christian Karsten Hansen , Jan Moller Mikkelsen , Hans Thalsgard Schambye
IPC分类号： C07K014/53 , C07H021/04 , C12P021/02
CPC分类号： A61K9/0019 , A61K38/00 , A61K47/42 , C07K14/535
摘要： The invention relates to polypeptide conjugates comprising a polypeptide exhibiting G-CSF activity and having an amino acid sequence that differs from the amino acid sequence of human G-CSF in at least one specified introduced and/or removed amino acid residue comprising an attachment group for a non-polypeptide moiety, and having at least one non-polypeptide moiety attached to an attachment group of the polypeptide. The attachment group may e.g., be a lysine, cysteine, aspartic acid or glutamic acid residue or a glycosylation site, and the non-polypeptide moiety may e.g., be a polymer such as polyethylene glycol or an oligosaccharide. The conjugate has one or more improved properties such as increased biological half-life and reduced side effects.
摘要翻译：本发明涉及多肽缀合物，其包含显示G-CSF活性的多肽，并且具有不同于至少一个指定的引入和/或去除的氨基酸残基中的人G-CSF的氨基酸序列的氨基酸序列，所述氨基酸残基包含用于非多肽部分，并且具有连接到多肽的连接基团的至少一个非多肽部分。连接基团可以例如是赖氨酸，半胱氨酸，天冬氨酸或谷氨酸残基或糖基化位点，并且非多肽部分可以例如是聚合物，例如聚乙二醇或低聚糖。缀合物具有一个或多个改进的性质，例如增加的生物半衰期和减少的副作用。

3. 发明申请

US20030083433A1 Outer layer having entanglement of hydrophobic polymer host and hydrophilic polymer guest 有权
标题翻译：外层具有疏水聚合物主体和亲水聚合物客体的缠结
公开(公告)号：US20030083433A1
公开(公告)日：2003-05-01
申请号：US10283760
申请日：2002-10-29
发明人： Susan P. James , M.S. Min Zhang , Guy Beauregard
IPC分类号： C08G063/48 , C08G063/91 , C07K014/52 , C07K014/53 , C08B037/00
CPC分类号： C08J9/42 , B05D5/00 , B29C67/24 , C08B37/00 , C08B37/0072 , C08L5/08 , C08L101/00 , Y10T428/249953 , Y10T428/31504 , Y10T428/31855 , Y10T428/31971 , C08L2666/02 , C08L2666/26
摘要： An outer layer having an entanglement comprising an intermingling of cloaked hydrophilic guest and a hydrophobic polymer host, wherein molecules of the guest have been crosslinked with each other. Under certain circumstances, using complexes of the guest may be desirable or even necessary. The intermingling of the guest and host includes a physical tangling, whether it also comprises crosslinking by primary bonding (e.g., chemical/covalent bonding) there-between. Also a method of producing an outer layer having such an entanglement, including the steps of: temporarily cloaking at least a portion of the hydrophilic groups of the guest; intermingling at least a portion of the cloaked groups with a porous polymeric structure by diffusing the guest with cloaked groups into at least a portion of the structure's pores; within the pores, crosslinking at least a portion of the molecules of the guest with the guest; and removing the cloaking. Cloaking may be performed by silylation or acylation. Intermingling may be performed by producing a mixture of guest and host (whether in solution, powdered, granular, etc., form); next, a crosslinking of the guest with itself is performed; then, the mixture is molded into the outer layer.
摘要翻译：具有缠结的外层，其包含掩蔽的亲水客体和疏水性聚合物主体的混合物，其中客体的分子彼此交联。在某些情况下，使用客人的复合物可能是理想的或甚至是必需的。客人和主持人的混合包括物理缠结，无论其是否还包括通过其间的初次键合（例如，化学/共价键合）的交联。还有一种制造具有这种缠结的外层的方法，包括以下步骤：暂时隐藏客人的至少一部分亲水基团; 通过将具有掩蔽基团的客体扩散到结构的孔的至少一部分中来将具有多孔聚合物结构的至少一部分掩蔽组混合; 在孔内，与客体交联客体的至少一部分分子; 并去除隐形。掩蔽可以通过甲硅烷基化或酰化进行。混合可以通过生产客体和主机的混合物（无论是溶液，粉末，颗粒等）形式进行; 接下来，进行客人与其自身的交联; 然后将混合物模塑成外层。

4. 发明申请

US20040175800A1 Cysteine variants of granulocyte colony-stimulating factor 有权
标题翻译：粒细胞集落刺激因子的半胱氨酸变体
公开(公告)号：US20040175800A1
公开(公告)日：2004-09-09
申请号：US10774149
申请日：2004-02-05
申请人： Bolder Biotechnology, Inc.
发明人： George N. Cox III
IPC分类号： C12P021/02 , C07H021/04 , C07K014/54 , C07K014/53 , C07K014/61 , C07K014/505
CPC分类号： C07K14/5431 , A61K38/00 , A61K47/60 , C07K14/475 , C07K14/505 , C07K14/52 , C07K14/535 , C07K14/5403 , C07K14/5406 , C07K14/5409 , C07K14/5412 , C07K14/5418 , C07K14/5425 , C07K14/5428 , C07K14/5434 , C07K14/5437 , C07K14/5443 , C07K14/55 , C07K14/555 , C07K14/56 , C07K14/565 , C07K14/57 , C07K14/61
摘要： The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby.
摘要翻译：生长激素超基因家族包含大于20个结构相关的细胞因子和生长因子。提供了一种用于产生这些蛋白质的位点特异性，生物活性缀合物的通用方法。该方法包括将半胱氨酸残基添加到蛋白质的非必需区域中，或者使用定点突变将蛋白质中的非必需氨基酸取代半胱氨酸残基，然后将半胱氨酸反应性聚合物或其它类型的半胱氨酸反应性部分共价偶联到通过添加的半胱氨酸残基的蛋白质。本文公开了用于添加半胱氨酸残基或将半胱氨酸取代引入蛋白质的优选位点，以及由此产生的蛋白质和蛋白质衍生物。

5. 发明申请

US20030139582A1 Composition containing biologically active polypeptides suitable for the oral administration 审中-公开
标题翻译：含有适于口服给药的生物活性多肽的组合物
公开(公告)号：US20030139582A1
公开(公告)日：2003-07-24
申请号：US10050017
申请日：2002-01-17
发明人： Kai Hua Wang
IPC分类号： A61K038/18 , C07K014/53
CPC分类号： C07K14/53 , A61K9/0053 , A61K38/193 , A61K47/183 , A61K47/24 , A61K47/46
摘要： A hydrophilic emulsion composition as a carrier fluid for the oral administration of biologically active polypeptides. The composition consists of a commercial therapeutic polypeptide product, e.g., Granulocyte Colony Stimulating Factor (G-CSF), and a carrier fluid containing a small molecule spleen extract and a fluid mixture of substances that are complimentary to said small molecule extract to protect the polypeptide and promote the absorption of the polypeptide by epithelium of intestinal mucosa.
摘要翻译：一种作为口服给药生物活性多肽的载体液的亲水性乳液组合物。组合物由市售的治疗性多肽产物，例如粒细胞集落刺激因子（G-CSF）和含有小分子脾提取物的载体流体和与所述小分子提取物互补以保护多肽的物质的流体混合物并通过肠粘膜上皮促进多肽的吸收。

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