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1. 发明申请

WO0219963A3 SYNTHETIC ERYTHROPOIESIS STIMULATING PROTEINS 审中-公开
标题翻译：合成红细胞生成素刺激蛋白
公开(公告)号：WO0219963A3
公开(公告)日：2003-02-06
申请号：PCT/US0121928
申请日：2001-07-12
申请人： GRYPHON THERAPEUTICS INC , KOCHENDOERFER GERD , BOTTI PAOLO , BRADBURNE JAMES A , CHEN SHIAH-YUN , CRESSMAN SONYA , HUNTER CHRISTIE L , KENT STEPHEN B H , LOW DONALD W
发明人： KOCHENDOERFER GERD , BOTTI PAOLO , BRADBURNE JAMES A , CHEN SHIAH-YUN , CRESSMAN SONYA , HUNTER CHRISTIE L , KENT STEPHEN B H , LOW DONALD W
IPC分类号： A61K38/00 , A61K38/02 , A61K38/22 , A61K47/34 , A61K47/42 , A61K47/48 , A61P7/00 , A61P7/06 , A61P9/10 , A61P11/02 , A61P11/06 , A61P17/00 , A61P19/02 , A61P29/00 , A61P31/12 , A61P37/06 , A61P37/08 , A61P43/00 , C07K1/00 , C07K1/06 , C07K14/47 , C07K14/505 , C07K14/52 , C07K17/08 , C07K19/00
CPC分类号： C07K14/505 , A61K38/00
摘要： Synthetic erythropoiesis stimulating proteins are provided. Also provided are methods for synthesizing the proteins. The invention further relates to derivatives of such synthetic erythropoiesis stimulating proteins that are polymer-modified in a defined manner. Methods and uses for such proteins and derivatized proteins are also provided.
摘要翻译：提供合成红细胞生成刺激蛋白。还提供了合成蛋白质的方法。本发明还涉及以定义的方式聚合物修饰的这种合成的红细胞生成刺激蛋白的衍生物。还提供了这些蛋白质和衍生化蛋白质的方法和用途。

2. 发明申请

WO0204015A9 POLYMER-MODIFIED BIOACTIVE SYNTHETIC CHEMOKINES, AND METHODS FOR THEIR MANUFACTURE AND USE 审中-公开
标题翻译：聚合物改性的生物合成化学品及其制造和使用方法
公开(公告)号：WO0204015A9
公开(公告)日：2003-08-07
申请号：PCT/US0121933
申请日：2001-07-12
申请人： GRYPHON THERAPEUTICS INC , KOCHENDOERFER GERD , BOTTI PAOLO , BRADBURNE JAMES A , CHEN SHIAH-YUN , CRESSMAN SONYA
发明人： KOCHENDOERFER GERD , BOTTI PAOLO , BRADBURNE JAMES A , CHEN SHIAH-YUN , CRESSMAN SONYA
IPC分类号： A61K47/30 , A61K38/00 , A61K38/19 , A61K45/00 , A61K47/34 , A61K47/48 , A61P9/10 , A61P11/06 , A61P17/00 , A61P27/16 , A61P29/00 , A61P35/00 , A61P37/00 , A61P37/08 , C07H21/04 , C07K14/47 , C07K14/52 , C07K14/715 , C07K19/00 , C12P21/02
CPC分类号： C07K14/7158 , A61K38/00 , A61K47/60 , A61K47/62
摘要： The invention relates to polymer-modified bioactive synthetic chemokines and to methods for their production and use. The bioactive synthetic chemokines of the invention comprises a polymer modified polypeptide chemokine backbone. The compounds and methods or the invention are useful for the treatment of disorders involving naturally occurring chemokines, such as for the treatment of HIV and AIDS related disorders and for the treatment of asthma, allergic rhinitis, atopic dermatitis, atheroma/atherosclerosis, organ transplant rejection, and rheumatoid arthritis.
摘要翻译：本发明涉及聚合物改性的生物活性合成趋化因子及其生产和使用方法。本发明的生物活性合成趋化因子包含聚合物修饰的多肽趋化因子主链。化合物和方法或本发明可用于治疗涉及天然存在的趋化因子的疾病，例如用于治疗HIV和AIDS相关疾病以及治疗哮喘，过敏性鼻炎，特应性皮炎，动脉粥样硬化/动脉粥样硬化，器官移植排斥和类风湿性关节炎。

3. 发明申请

WO0012536A2 LIPID MATRIX-ASSISTED CHEMICAL LIGATION AND SYNTHESIS OF MEMBRANE POLYPEPTIDES 审中-公开
标题翻译：脂质基辅助化学合成和膜多糖的合成
公开(公告)号：WO0012536A2
公开(公告)日：2000-03-09
申请号：PCT/US9919542
申请日：1999-08-26
申请人： GRYPHON SCIENCES , KOCHENDOERFER GERD G , HUNTER CHRISTIE L , KENT STEPHEN B H , BOTTI PAOLO
发明人： KOCHENDOERFER GERD G , HUNTER CHRISTIE L , KENT STEPHEN B H , BOTTI PAOLO
IPC分类号： G01N33/532 , A61K49/08 , A61K51/08 , C07C229/16 , C07K1/00 , C07K1/02 , C07K1/04 , C07K1/107 , C07K1/12 , C07K1/13 , C07K14/11 , C07K14/155 , C07K14/16 , C07K14/195 , C07K14/215 , C07K14/36 , C07K14/435 , C07K14/54 , C07K14/705 , C07K17/02 , C07K19/00 , G01N21/78 , G01N33/542 , G01N33/566 , G01N33/68
CPC分类号： A61K49/0056 , A61K49/0041 , C07C229/16 , C07K1/023 , C07K1/026 , C07K1/04 , C07K1/042 , C07K1/045 , C07K14/005 , C07K14/215 , C07K14/36 , C07K14/43522 , C07K14/5421 , C07K14/705 , C07K2319/00 , C12N2740/16322 , C12N2760/16022 , Y10S435/87
摘要： The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis. The methods and compositions of the invention have multiple uses. For example, they can be used to assay ligand binding to membrane polypeptides and domains comprising a receptor, and thus are extremely useful for structure/function studies, drug screening/selection/design, and diagnostics and the like, including high-throughput applications. The methods and compositions of the invention are particularly suited for FRET analyses of previously inaccessible membrane polypeptides.
摘要翻译：本发明涉及掺入脂质基质中的脂质基质辅助化学连接和膜多肽的合成的方法和组合物。本发明通过逐步化学选择性化学连接未受保护的肽区段，其中至少一个肽片段嵌入脂质基质中，制备嵌入脂质基质内的预折叠膜多肽。可以使用适用于未保护肽段连接的任何化学选择性反应化学物质。合适的脂质基质包括脂质体，胶束，细胞膜片和光学各向同性立体脂质相基质。根据本发明的方法和组合物合成的预先折叠的合成和半合成膜多肽还允许位点特异性引入一个或多个可检测部分，例如发色团，其可以在合成期间方便地引入。本发明的方法和组合物具有多种用途。例如，它们可用于测定配体结合膜多肽和包含受体的结构域，因此对于结构/功能研究，药物筛选/选择/设计和诊断等（包括高通量应用）非常有用。本发明的方法和组合物特别适用于以前不可接近的膜多肽的FRET分析。

4. 发明申请

WO2004105685A2 DISPLACEABLE LINKER SOLID PHASE CHEMICAL LIGATION 审中-公开
标题翻译：可拆卸连接器固体相化学发光
公开(公告)号：WO2004105685A2
公开(公告)日：2004-12-09
申请号：PCT/US2004015435
申请日：2004-05-17
申请人： GRYPHON THERAPEUTICS INC , LOW DONALD , HU YING , BOTTI PAOLO
发明人： LOW DONALD , HU YING , BOTTI PAOLO
IPC分类号： A61K20060101 , C07K1/04 , C07K1/107 , C08B37/00 , C08F2/00 , A61K
CPC分类号： C07K1/042 , C07K1/1072
摘要： The invention is directed to methods and compositions for aqueous-compatible solid phase chemical ligation. The methods and compositions of the invention involve the chemical ligation of first and second polymers, where the first polymer is attached to a support through a displaceable linker. The displaceable linker can be cleaved or otherwise displaced under aqueous conditions compatible with subsequent removal of the ligation product from the solid support. The methods and compositions of the invention are particularly useful for ligation of peptides and polypeptides on a solid support. The ligation system of the invention is applicable to a wide variety of molecules, and thus can be exploited to generate ligated polymers including peptides, polypeptides and other amino acid containing polymers.
摘要翻译：本发明涉及用于水相容性固相化学连接的方法和组合物。本发明的方法和组合物涉及第一和第二聚合物的化学连接，其中第一聚合物通过位移连接体连接到载体上。在与固体支持物随后除去连接产物相容的水性条件下，可置换接头可以被切割或以其它方式置换。本发明的方法和组合物特别可用于在固体支持物上连接肽和多肽。本发明的连接系统可应用于各种各样的分子，因此可用于产生连接的聚合物，包括肽，多肽和其它含氨基酸的聚合物。

5. 发明专利

JP2008150393A Extended native chemical ligation 审中-公开
标题翻译：扩展的原料化学品
公开(公告)号：JP2008150393A
公开(公告)日：2008-07-03
申请号：JP2008025907
申请日：2008-02-06
申请人： Gryphon Therapeutics Inc , グリフォンセラピューティクス,インコーポレーテッド
发明人： BOTTI PAOLO , BRADBURNE JAMES A , KENT STEPHEN B H , LOW DONALD W
IPC分类号： C07K5/00 , C07K5/04 , A61K38/00 , C07K1/04 , C07K1/06 , C07K1/08 , C07K1/10 , C07K5/06 , C07K5/068 , C07K5/078 , C07K5/087 , C07K7/00 , C07K7/04 , C07K7/06 , C07K14/00 , C07K14/505 , C07K14/80
CPC分类号： C07K14/80 , C07K5/06026 , C07K5/06086 , C07K5/06147 , C07K5/0812 , C07K7/06
摘要： PROBLEM TO BE SOLVED: To provide native chemical ligation with a peptide-amide bond. SOLUTION: Provided is an N-substituted amide compound expressed by formula I: J1-C(O)-N(C1(R1)-C2-SH)-J2, or formula II: J1-C(O)-N(C1(R1)-C2(R2)-C3(R3)-SH)-J2, wherein J1 and J2 express each individually a peptide having ≥1 arbitrarily protected amino acid side chains, R1, R2 and R3 express each individually H or an electron donating group complexed with C1 through a covalent bond, C2 and C3 express each carbon, with the proviso that at least one of R1, R2 or R3 comprises the electron donating group complexed with C1. COPYRIGHT: (C)2008,JPO&INPIT
摘要翻译：待解决的问题：提供天然化学连接与肽 - 酰胺键。解决方案：提供由式I表示的N-取代的酰胺化合物：J1-C（O）-N（C1（R1）-C2-SH）-J2或式II：J1-C（O） N（C1（R1）-C2（R2）-C3（R3）-SH）-J2，其中J1和J2分别表示具有≥1任意保护的氨基酸侧链的肽，R1，R2和R3各自表示H 或通过共价键与C1配合的给电子基团，C2和C3表示每个碳，条件是R1，R2或R3中的至少一个包含与C1络合的给电子基团。版权所有（C）2008，JPO＆INPIT

6. 发明专利

JP2007269799A Pseudo native chemical ligation 审中-公开
标题翻译： PSEUDO原料化学品
公开(公告)号：JP2007269799A
公开(公告)日：2007-10-18
申请号：JP2007125104
申请日：2007-05-09
申请人： Gryphon Therapeutics Inc , グリフォンセラピューティクス,インコーポレーテッド
发明人： HUNTER CHRISTIE L , BOTTI PAOLO , BRADBURNE JAMES A , CHEN SHIAH-YUN , CRESSMAN SONYA , KENT STEPHEN B H , KOCHENDOERFER GERD G , LOW DONALD W
IPC分类号： A61K38/00 , C07K14/47 , A61K38/02 , A61K38/22 , A61K47/34 , A61K47/42 , A61K47/48 , A61P7/00 , A61P7/06 , A61P9/10 , A61P11/02 , A61P11/06 , A61P17/00 , A61P19/02 , A61P29/00 , A61P31/12 , A61P37/00 , A61P37/06 , A61P37/08 , A61P43/00 , C07K1/00 , C07K1/06 , C07K14/505 , C07K14/52 , C07K17/08 , C07K19/00
CPC分类号： C07K14/505 , A61K38/00
摘要： PROBLEM TO BE SOLVED: To provide a method and a composition for extending the technique of native chemical ligation of a wider range of peptides, polypeptides, other polymers and other molecules via an amide bond. SOLUTION: The synthetic protein contains a pseudo amino acid residue the side chain of which has the formula: -S-Raa [wherein, Raa is selected from the group consisting of pseudo Asp, pseudo Gln, pseudo Asn, pseudo Ser, pseudo Thr, pseudo Lys, pseudo Arg, pseudo Met, pseudo Phe, pseudo Tyr, pseudo phospho-tyr, pseudo Dopa pseudo Gla, pseudo His, pseudo Trp, pseudo Leu, pseudo Val, pseudo Ile, pseudo N-(ethyl)trifluoroacetamide, pseudo SBF and pseudo methyl-SBF in table I (not shown)]. COPYRIGHT: (C)2008,JPO&INPIT
摘要翻译：待解决的问题：提供一种方法和组合物，用于通过酰胺键扩展更广泛范围的肽，多肽，其它聚合物和其它分子的天然化学连接技术。解决方案：合成蛋白质包含其侧链具有下式的假氨基酸残基：-S-Raa [其中，Raa选自伪Asp，伪Gln，伪Asn，伪Ser，假Thr，假Lys，假Arg，假Met，伪Phe，假Tyr，伪磷酸三酯，伪Dopa伪Gla，伪His，伪Trp，假Leu，假Val，假Ile，假N-（乙基）三氟乙酰胺，伪SBF和假甲基-SFF（表1中未示出）]。版权所有（C）2008，JPO＆INPIT

7. 发明专利

JP2007302668A Polymer-modified synthetic proteins 审中-公开
标题翻译：聚合物改性合成蛋白
公开(公告)号：JP2007302668A
公开(公告)日：2007-11-22
申请号：JP2007125101
申请日：2007-05-09
申请人： Gryphon Therapeutics Inc , グリフォンセラピューティクス,インコーポレーテッド
发明人： KOCHENDOERFER GERD G , BOTTI PAOLO , BRADBURNE JAMES A , CHEN SHIAH-YUN , CRESSMAN SONYA , HUNTER CHRISTIE L , KENT STEPHEN B H , LOW DONALD W , WILKEN JILL G
IPC分类号： A61K38/00 , C07K14/52 , A61K38/02 , A61K38/21 , A61K38/22 , A61K45/00 , A61K47/34 , A61K47/42 , A61K47/48 , A61P7/00 , A61P7/06 , A61P9/10 , A61P11/02 , A61P11/06 , A61P17/00 , A61P17/02 , A61P19/02 , A61P29/00 , A61P31/12 , A61P37/06 , A61P37/08 , A61P43/00 , C07K1/00 , C07K1/06 , C07K14/00 , C07K14/47 , C07K14/505 , C07K17/08 , C07K19/00 , C08G81/00
CPC分类号： C07K14/505 , A61K38/00
摘要： PROBLEM TO BE SOLVED: To provide a method for forming a bioactive protein utilizable for formation of a polymer enabling polymer modification, different from a recombinant DNA method, and to provide the polymer preferably usable therefor. SOLUTION: The polymer-modified synthetic bioactive protein, a pharmaceutical composition containing the protein, and the methods for producing and using them are provided. The polymer-modified synthetic bioactive protein is formed by chemical synthesis, and is different from a biologically produced protein. Concretely, the composition contains the separated synthetic polymer-modified bioactive protein of the formula: "protein"-n (U-B)s-"polymer". (wherein, U is a chemical group covalently bonding to one to six side chains of one or more amino acids of one or more non-overlapping peptide segments; B is a branching core having three or more arms; and "polymer" is a water-soluble polyamide polymer). COPYRIGHT: (C)2008,JPO&INPIT
摘要翻译：待解决的问题：提供一种用于形成可用于形成聚合物修饰的聚合物的生物活性蛋白质的方法，不同于重组DNA方法，并提供优选可用的聚合物。解决方案：提供了聚合物改性的合成生物活性蛋白，含有蛋白质的药物组合物及其制备和使用方法。聚合物改性的合成生物活性蛋白质是通过化学合成形成的，不同于生物产生的蛋白质。具体地，该组合物含有分子式为：“蛋白质”-n（U-B）s-“聚合物”的合成聚合物改性的生物活性蛋白质。（其中U是与一个或多个非重叠肽段的一个或多个氨基酸的一至六个侧链共价结合的化学基团; B是具有三个或更多个臂的分支核心;“聚合物”是水 - 可溶性聚酰胺聚合物）。版权所有（C）2008，JPO＆INPIT

8. 发明公开

EP1315511A4 SYNTHETIC ERYTHROPOIESIS STIMULATING PROTEINS 审中-公开
标题翻译：合成红细胞生成刺激蛋白
公开(公告)号：EP1315511A4
公开(公告)日：2005-10-19
申请号：EP01957133
申请日：2001-07-12
申请人： GRYPHON THERAPEUTICS INC
发明人： KOCHENDOERFER GERD , BOTTI PAOLO , BRADBURNE JAMES A , CHEN SHIAH-YUN , CRESSMAN SONYA , HUNTER CHRISTIE L , KENT STEPHEN B H , LOW DONALD W
IPC分类号： A61K38/00 , A61K38/02 , A61K38/22 , A61K47/34 , A61K47/42 , A61K47/48 , A61P7/00 , A61P7/06 , A61P9/10 , A61P11/02 , A61P11/06 , A61P17/00 , A61P19/02 , A61P29/00 , A61P31/12 , A61P37/06 , A61P37/08 , A61P43/00 , C07K1/00 , C07K1/06 , C07K14/47 , C07K14/505 , C07K14/52 , C07K17/08 , C07K19/00
CPC分类号： C07K14/505 , A61K38/00

9. 发明申请

WO2008037484A3 FORMULATIONS COMPRISING CYCLIC COMPOUNDS 审中-公开
标题翻译：包含环化合物的制剂
公开(公告)号：WO2008037484A3
公开(公告)日：2008-12-18
申请号：PCT/EP2007008442
申请日：2007-09-27
申请人： BOTTI PAOLO
发明人： BOTTI PAOLO
IPC分类号： A61K47/22 , A61K31/365 , A61K47/14 , C07D323/00
CPC分类号： C07D323/00 , A61K47/22 , A61K47/6949 , B82Y5/00
摘要： This invention relates to the use of a cyclic compound of formula (I), wherein A, B independently in each occurrence is alkane-i,j-diyl having k carbon atoms, i and independently j being less than or equal k and k being selected from 1 to 10, wherein said alkane-i,j-diyl (i) may comprise one or more double bonds; (ii) is optionally substituted; and/or (iii) comprises a cycle, wherein the total number of cycles being cyclic sugars in said compound is selected from 0 to 4 and is less than p (n+m); X,Y independently in each occurrence is a biocompatible functional group comprising at least one oxygen atom or two sulphur atoms; n, m independently of each other are selected from 0 to 20; p is selected from 1 to 10; n+m is equal or greater than 1; and p.(n+m) is selected from 3 to 30; wherein said compound is capable of forming a complex with a protonated primary and/or protonated secondary amino group and/or a protonated guanidinium group for the manufacture of a pharmaceutical or diagnostic composition further comprising a pharmaceutically or diagnostically active agent, said active agent comprising one or more protonated primary and/or protonated secondary amino groups and/or a protonated guanidinium groups, wherein (a) transmembrane and/or transmucosal delivery; (b) solubility in non-aqueous solvents; and/or (c) stability of said active agent are improved.
摘要翻译：本发明涉及式（I）环状化合物的用途，其中A，B在每种情况下独立地为具有k个碳原子的链烷-ε，j-二基，i和独立地j小于或等于k且k为选自1至10，其中所述烷烃-i，j-二基（i）可以包含一个或多个双键; （ii）任选被取代; 和/或（iii）包括一个循环，其中所述化合物中循环糖的总循环次数选自0至4且小于p（n + m）;和/或（iii）包含循环。 X，Y在每种情况下独立地为包含至少一个氧原子或两个硫原子的生物相容性官能团; n，m彼此独立地选自0至20; p选自1至10; n + m等于或大于1; 并且p（n + m）选自3至30; 其中所述化合物能够与质子化的伯氨基和/或质子化的仲氨基和/或质子化的胍基形成复合物用于制备还包含药学或诊断活性剂的药物或诊断组合物，所述活性剂包含一种或质子化的主要和/或质子化的仲氨基和/或质子化的胍基，其中（a）跨膜和/或透粘膜递送; （b）在非水溶剂中的溶解度; 和/或（c）所述活性剂的稳定性得到改善。

10. 发明公开

EP1631597A4 DISPLACEABLE LINKER SOLID PHASE CHEMICAL LIGATION 审中-公开
标题翻译：化学固相结扎互换LEFT
公开(公告)号：EP1631597A4
公开(公告)日：2007-07-11
申请号：EP04752449
申请日：2004-05-17
申请人： GRYPHON THERAPEUTICS INC
发明人： LOW DONALD , HU YING , BOTTI PAOLO
IPC分类号： C08F2/00 , A61K20060101 , C07K1/04 , C07K1/107 , C08B37/00
CPC分类号： C07K1/042 , C07K1/1072
摘要： The invention is directed to methods and compositions for aqueous-compatible solid phase chemical ligation. The methods and compositions of the invention involve the chemical ligation of first and second polymers, where the first polymer is attached to a support through a displaceable linker. The displaceable linker can be cleaved or otherwise displaced under aqueous conditions compatible with subsequent removal of the ligation product from the solid support. The methods and compositions of the invention are particularly useful for ligation of peptides and polypeptides on a solid support. The ligation system of the invention is applicable to a wide variety of molecules, and thus can be exploited to generate ligated polymers including peptides, polypeptides and other amino acid containing polymers.

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