公开(公告)号：WO2004060967A1

公开(公告)日：2004-07-22

申请号：PCT/US2003/041706

申请日：2003-12-31

Applicant: NEKTAR THERAPEUTICS AL, CORPORATION ,  BENTLEY, Michael, D. ,  FANG, Zhihao

Inventor： BENTLEY, Michael, D. ,  FANG, Zhihao

IPC: C08G65/334

CPC classification number: C08G65/3342 ,  A61K47/60 ,  A61L24/0031 ,  A61L24/046 ,  C08G65/329 ,  C08J3/24 ,  C08J2300/14 ,  C08J2381/00 ,  C08L2203/02 ,  C08L81/08

Abstract: The present invention provides both crosslinked polymer compositions capable of forming hydrogels upon exposure to an aqueous environment and thiosulfonate hydrogel-forming components. The thiosulfonate hydrogel-forming components of the invention are preferably multi-arm thiosulfonate polymer derivatives that form a crosslinked polymer composition when exposed to a base without requiring the presence of a second cross-linking reagent, redox catalyst, or radiation. Methods for forming hydrogel compositions, as well as methods for using the hydrogels, are also provided.

Abstract translation: 本发明提供了两种能够在暴露于水性环境中形成水凝胶的交联聚合物组合物和形成硫代磺酸盐的水凝胶组分。 本发明的硫代磺酸盐水凝胶形成组分优选为在不需要存在第二交联剂，氧化还原催化剂或辐射的情况下暴露于碱而形成交联聚合物组合物的多臂硫代磺酸盐聚合物衍生物。 还提供了形成水凝胶组合物的方法以及使用水凝胶的方法。

公开(公告)号：WO2002059179A3

公开(公告)日：2002-08-01

申请号：PCT/US2001/049081

申请日：2001-12-18

Applicant: SHEARWATER CORPORATION ,  KOZLOWSKI, Antoni ,  SHEN, Xioaming ,  BENTLEY, Michael, David ,  FANG, Zhihao

Inventor： KOZLOWSKI, Antoni ,  SHEN, Xioaming ,  BENTLEY, Michael, David ,  FANG, Zhihao

IPC: C08G65/329

Abstract: High molecular weight derivatives of activated poly(ethylene glycol) and the like polymers are prepared in high purity by conjugating a large PEG molecule to a small PEG molecule. Most of the reaction steps can be accomplished on the more readily purified small molecule to avoid laborious purification of the high molecular weight derivatives.

公开(公告)号：WO2010048184A3

公开(公告)日：2010-04-29

申请号：PCT/US2009/061327

申请日：2009-10-20

Applicant: BAXTER INTERNATIONAL INC. ,  BAXTER HEALTHCARE S.A. ,  NEKTAR THERAPEUTICS ,  VARADI, Katalin ,  SCHRENK, Gerald ,  ROTTENSTEINER, Hanspeter ,  TURECEK, Peter ,  WEBER, Alfred ,  ANDERLE, Heinz ,  CULBERTSON, Sean, M. ,  FANG, Zhihao ,  ZAPPE, Harold ,  ZHANG, Ping ,  BOSSARD, Mary, J.

Inventor： VARADI, Katalin ,  SCHRENK, Gerald ,  ROTTENSTEINER, Hanspeter ,  TURECEK, Peter ,  WEBER, Alfred ,  ANDERLE, Heinz ,  CULBERTSON, Sean, M. ,  FANG, Zhihao ,  ZAPPE, Harold ,  ZHANG, Ping ,  BOSSARD, Mary, J.

IPC: G01N33/542 ,  G01N33/58 ,  G01N33/68 ,  G01N33/86

Abstract: The invention relates to the development of in vitro assay systems that force the release of a water-soluble polymer, such as polyethylene glycol (PEG) and polysialic acid (PSA), from proteins modified with a reversibly-linked water-soluble polymer. The invention includes methods for analyzing the release of the water- soluble polymer and measuring regained protein activity. The invention further includes methods appropriate for the quality control of proteins modified with releasable water-soluble polymers, including polymers like PEG and PSA.

公开(公告)号：WO2009043027A3

公开(公告)日：2009-06-25

申请号：PCT/US2008078159

申请日：2008-09-29

Applicant: SERINA THERAPEUTICS INC ,  HARRIS J MILTON ,  BENTLEY MICHAEL DAVID ,  YOON KUNSANG ,  FANG ZHIHAO

Inventor： HARRIS J MILTON ,  BENTLEY MICHAEL DAVID ,  YOON KUNSANG ,  FANG ZHIHAO

IPC: C07D263/10 ,  C08G73/00 ,  C08L79/04

CPC classification number: C07D263/12 ,  A61K47/59 ,  A61K47/64 ,  C08G73/0233 ,  C08L79/02

Abstract: The present disclosure provides novel POZ-2 derivatives, methods for synthesizing POZ-2 derivatives and intermediates useful in such methods. In one embodiment, the POZ-2 derivative comprises two linear POZ chains of the present disclosure linked directly or indirectly to a branching moiety that contains a functional group for linking the POZ-2 derivative to the target molecule. Target molecule-POZ-2 conjugates are also described. In certain embodiment, the POZ-2 derivatives have low polydispersity values and a decreased amount of impurities produced by unwanted side reactions, such as, but not limited to, chain transfer.

Abstract translation: 本公开提供了新的POZ-2衍生物，用于合成POZ-2衍生物的方法和用于这些方法的中间体。 在一个实施方案中，POZ-2衍生物包含直接或间接连接至含有用于将POZ-2衍生物连接至靶分子的官能团的支化部分的本发明的两条线性POZ链。 还描述了靶分子-POZ-2缀合物。 在某些实施方案中，POZ-2衍生物具有低多分散性值和由不希望的副反应产生的杂质的量降低，例如但不限于链转移。

公开(公告)号：WO2008082669A3

公开(公告)日：2009-04-09

申请号：PCT/US2007026522

申请日：2007-12-27

Applicant: NEKTAR THERAPEUTICS AL CORP ,  BAXTER INT ,  BAXTER HEALTHCARE SA ,  BOSSARD MARY J ,  STEPHENSON GAYLE ,  FANG ZHIHAO ,  ZAPPE HAROLD ,  MITCHELL STACY ,  ZHANG PING ,  SCHEIFLINGER FRITZ ,  TURECEK PETER ,  SIEKMANN JUERGEN ,  VARADI KATALIN ,  GRITSCH HERBERT

Inventor： BOSSARD MARY J ,  STEPHENSON GAYLE ,  FANG ZHIHAO ,  ZAPPE HAROLD ,  MITCHELL STACY ,  ZHANG PING ,  SCHEIFLINGER FRITZ ,  TURECEK PETER ,  SIEKMANN JUERGEN ,  VARADI KATALIN ,  GRITSCH HERBERT

IPC: A61K47/48 ,  A61P7/00

CPC classification number: C07K14/755 ,  A61K47/60

Abstract: The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.

Abstract translation: 本发明提供了von Willebrand因子 - 聚合物共轭物和因子VIII-聚合物缀合物，其各自具有可释放的连接。 还提供了制备缀合物的方法，用于施用缀合物的方法。

公开(公告)号：WO2008106186A3

公开(公告)日：2008-10-23

申请号：PCT/US2008002626

申请日：2008-02-28

Applicant: SERINA THERAPEUTICS INC ,  HARRIS J MILTON ,  BENTLEY MICHAEL DAVID ,  YOON KUNSANG ,  FANG ZHIHAO ,  VERONESE FRANCESCO MARIA

Inventor： HARRIS J MILTON ,  BENTLEY MICHAEL DAVID ,  YOON KUNSANG ,  FANG ZHIHAO ,  VERONESE FRANCESCO MARIA

IPC: A01N47/00

CPC classification number: A61K31/787 ,  A61K47/60 ,  C07D207/452 ,  C07D207/46 ,  C07D401/12 ,  C08G73/0233 ,  C08L79/02

Abstract: The present disclosure provides terminally activated monofunctional POZ derivatives having a range of functional active groups allowing conjugation of the monofunctional POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed terminally activated monofunctional POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives.

Abstract translation: 本公开提供了具有一系列官能活性基团的末端活化的单官能POZ衍生物，其允许单官能POZ衍生物在宽范围的反应条件下与各种目标分子缀合以产生水解稳定的靶分子-POZ缀合物。 此外，本公开提供了公开的末端活化的单官能POZ衍生物和使用所公开的末端活化的单官能POZ衍生物产生的水解稳定的靶分子-POZ缀合物的合成新方法。

公开(公告)号：WO2008106186A2

公开(公告)日：2008-09-04

申请号：PCT/US2008/002626

申请日：2008-02-28

Applicant: SERINA THERAPEUTICS, INC. ,  HARRIS, J., Milton ,  BENTLEY, Michael, David ,  YOON, Kunsang ,  FANG, Zhihao ,  VERONESE, Francesco, Maria

Inventor： HARRIS, J., Milton ,  BENTLEY, Michael, David ,  YOON, Kunsang ,  FANG, Zhihao ,  VERONESE, Francesco, Maria

IPC: A61K31/787

CPC classification number: A61K31/787 ,  A61K47/60 ,  C07D207/452 ,  C07D207/46 ,  C07D401/12 ,  C08G73/0233 ,  C08L79/02

Abstract: The present disclosure provides terminally activated monofunctional POZ derivatives having a range of functional active groups allowing conjugation of the monofunctional POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed terminally activated monofunctional POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives.

Abstract translation: 本公开提供具有一定功能活性基团的末端活化的单官能POZ衍生物，其允许在宽范围的反应条件下使单官能POZ衍生物与多种靶分子缀合以产生水解稳定的靶分子-POZ缀合物。 此外，本公开提供了所公开的末端活化单官能POZ衍生物和使用所公开的末端活化单官能POZ衍生物产生的水解稳定的靶分子-POZ共轭物的合成新方法。

公开(公告)号：WO2008082669A2

公开(公告)日：2008-07-10

申请号：PCT/US2007/026522

申请日：2007-12-27

Applicant: NEKTAR THERAPEUTICS AL, CORPORATION ,  BAXTER INTERNATIONAL INC. ,  BAXTER HEALTHCARE SA ,  BOSSARD, Mary, J. ,  STEPHENSON, Gayle ,  FANG, Zhihao ,  ZAPPE, Harold ,  MITCHELL, Stacy ,  ZHANG, Ping ,  SCHEIFLINGER, Fritz ,  TURECEK, Peter ,  SIEKMANN, Juergen ,  VARADI, Katalin ,  GRITSCH, Herbert

Inventor： BOSSARD, Mary, J. ,  STEPHENSON, Gayle ,  FANG, Zhihao ,  ZAPPE, Harold ,  MITCHELL, Stacy ,  ZHANG, Ping ,  SCHEIFLINGER, Fritz ,  TURECEK, Peter ,  SIEKMANN, Juergen ,  VARADI, Katalin ,  GRITSCH, Herbert

IPC: A61K47/48 ,  A61P7/00

CPC classification number: C07K14/755 ,  A61K47/60

Abstract: The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.

Abstract translation: 本发明提供了von Willebrand因子 - 聚合物共轭物和因子VIII-聚合物缀合物，其各自具有可释放的连接。 还提供了制备缀合物的方法，用于施用缀合物的方法。

公开(公告)号：WO03031581A3

公开(公告)日：2003-10-16

申请号：PCT/US0232219

申请日：2002-10-09

Applicant: SHEARWATER CORP ,  ROBERTS MICHAEL JAMES ,  FANG ZHIHAO

Inventor： ROBERTS MICHAEL JAMES ,  FANG ZHIHAO

IPC: C07K1/113 ,  A61K47/48 ,  C07K14/555 ,  C08G65/334 ,  A61K31/74

CPC classification number: C07K1/13 ,  A61K47/60

Abstract: The invention provides reagents and methods for conjugating a polymer specifically to the PROPORTIONAL -amine of a polypeptide. The invention provides monofunctional, bifunctional, and multifunctional PEGs and related polymers having a terminal thioester moiety capable of specifically conjugating to the PROPORTIONAL -amine of a polypeptide having a cysteine or histidine residue at the N-terminus. The invention provides reactive thioester-terminated PEG polymers that have suitable reactivity with an N-terminal cysteine or histidine residue of a polypeptide to produce an amide bond between the PEG molecule and the polypeptide.

Abstract translation: 本发明提供用于将聚合物特异性缀合于多肽的比例胺的试剂和方法。 本发明提供了具有能够在N末端具有半胱氨酸或组氨酸残基的多肽的比例胺结合的末端硫酯部分的单功能，双功能和多官能PEG以及相关聚合物。 本发明提供了具有与多肽的N-末端半胱氨酸或组氨酸残基的合适反应性的反应性硫酯封端的PEG聚合物，以在PEG分子和多肽之间产生酰胺键。

公开(公告)号：WO2010048184A2

公开(公告)日：2010-04-29

申请号：PCT/US2009061327

申请日：2009-10-20

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  NEKTAR THERAPEUTICS ,  VARADI KATALIN ,  SCHRENK GERALD ,  ROTTENSTEINER HANSPETER ,  TURECEK PETER ,  WEBER ALFRED ,  ANDERLE HEINZ ,  CULBERTSON SEAN M ,  FANG ZHIHAO ,  ZAPPE HAROLD ,  ZHANG PING ,  BOSSARD MARY J

Inventor： VARADI KATALIN ,  SCHRENK GERALD ,  ROTTENSTEINER HANSPETER ,  TURECEK PETER ,  WEBER ALFRED ,  ANDERLE HEINZ ,  CULBERTSON SEAN M ,  FANG ZHIHAO ,  ZAPPE HAROLD ,  ZHANG PING ,  BOSSARD MARY J

IPC: G01N33/542 ,  G01N33/58 ,  G01N33/68 ,  G01N33/86

CPC classification number: G01N33/68 ,  G01N33/542 ,  G01N33/582 ,  G01N33/86 ,  G01N2333/76

Abstract: The invention relates to the development of in vitro assay systems that force the release of a water-soluble polymer, such as polyethylene glycol (PEG) and polysialic acid (PSA), from proteins modified with a reversibly-linked water-soluble polymer. The invention includes methods for analyzing the release of the water- soluble polymer and measuring regained protein activity. The invention further includes methods appropriate for the quality control of proteins modified with releasable water-soluble polymers, including polymers like PEG and PSA.

Abstract translation: 本发明涉及从用可逆连接的水溶性聚合物改性的蛋白质强制释放水溶性聚合物如聚乙二醇（PEG）和聚唾液酸（PSA）的体外测定系统的开发。 本发明包括分析水溶性聚合物的释放并测量重新获得的蛋白质活性的方法。 本发明还包括适用于用可释放水溶性聚合物（包括聚合物如PEG和PSA）改性的蛋白质的质量控制的方法。