公开(公告)号：US20120226022A1

公开(公告)日：2012-09-06

申请号：US13474548

申请日：2012-05-17

Applicant: Antoni Kozlowski ,  Remy F. Gross, III ,  Samuel P. McManus

Inventor： Antoni Kozlowski ,  Remy F. Gross, III ,  Samuel P. McManus

IPC: C07D207/404 ,  C07D207/416 ,  C07K17/02

CPC classification number: C08G65/33396 ,  A61K47/48215 ,  A61K47/60 ,  C08G65/33337 ,  C08L63/10 ,  C08L2203/02

Abstract: The present invention is directed to conjugates of hydrolytically stabilized maleimide-functionalized water soluble polymers and to methods for making and utilizing such polymers and their precursors.

Abstract translation: 本发明涉及水解稳定的马来酰亚胺官能化水溶性聚合物的共轭物，以及制备和利用这些聚合物及其前体的方法。

公开(公告)号：US08217123B2

公开(公告)日：2012-07-10

申请号：US12943740

申请日：2010-11-10

Applicant: Antoni Kozlowski ,  Samuel P. McManus

Inventor： Antoni Kozlowski ,  Samuel P. McManus

IPC: C08G75/00 ,  C08F283/00 ,  C08L81/00 ,  A61K31/415

CPC classification number: A61K47/48215 ,  A61K31/415 ,  A61K47/60 ,  C07C323/12 ,  C07D213/70 ,  C07D213/71

Abstract: Disclosed are water soluble polymeric reagents comprising the structure POLY-[Y—S—W]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 25, and S—W is a thiol, protected thiol, or thiol-reactive derivative. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are conjugates of such polymeric reagents with pharmaceutically relevant molecules, and methods of their formation and use.

Abstract translation: 公开了包含结构POLY- [Y-S-W] x的水溶性聚合物试剂，其中POLY是水溶性聚合物; Y为烃类间隔基，x为1〜25，S-W为硫醇，被保护的硫醇或硫醇活性衍生物。 优选地，水溶性聚合物是PEG聚合物。 还公开了这些聚合物试剂与药学上相关的分子的缀合物，以及它们的形成和用途的方法。

公开(公告)号：US07977427B2

公开(公告)日：2011-07-12

申请号：US12756905

申请日：2010-04-08

Applicant: Antoni Kozlowski

Inventor： Antoni Kozlowski

IPC: C08G63/48 ,  C08F8/30 ,  C08F16/06 ,  C08F116/06 ,  C08F216/06 ,  C08C19/00

CPC classification number: A61K47/58 ,  A61K31/7088 ,  A61K47/60 ,  A61K47/6901 ,  C08G63/91 ,  C08G65/48

Abstract: The invention provides a method comprising the steps of (i) reacting a water-soluble and non-peptidic polymer having two or more terminal hydroxyl groups with di(1-benzotriazolyl)carbonate to form a water-soluble and non-peptidic polymer having two or more 1-benzotriazolylcarbonate ester groups; and (ii) reacting the water-soluble and non-peptidic polymer having two or more 1-benzotriazolylcarbonate ester groups with a water-soluble and non-peptidic polymer having three or more primary amino groups under conditions effective to form a cross-linked polymer composition.

Abstract translation: 本发明提供了一种方法，其包括以下步骤：（i）使具有两个或多个末端羟基的水溶性和非肽类聚合物与二（1-苯并三唑基）碳酸酯反应，形成具有两个 或更多的1-苯并三唑基碳酸酯基团; 和（ii）在有效形成交联聚合物的条件下使具有两个或多个1-苯并三唑基碳酸酯基团的水溶性和非肽类聚合物与具有三个或更多个伯氨基的水溶性和非肽性聚合物反应 组成。

公开(公告)号：US07838595B2

公开(公告)日：2010-11-23

申请号：US12361427

申请日：2009-01-28

Applicant: Antoni Kozlowski

Inventor： Antoni Kozlowski

IPC: C08G63/48 ,  C08G63/91 ,  C08G10/00 ,  C08G12/00

CPC classification number: A61K47/48215 ,  A61K47/60 ,  C07C43/315 ,  C07C45/30 ,  C07C47/198 ,  C08G65/2603 ,  C08G65/329 ,  C08L2203/02 ,  C07C47/14

Abstract: The present invention is directed to alkanal derivatives of water-soluble polymers such as poly(ethylene glycol), their corresponding hydrates and acetals, and to methods for preparing and using such polymer alkanals. The polymer alkanals of the invention are prepared in high purity and exhibit storage stability.

Abstract translation: 本发明涉及水溶性聚合物如聚（乙二醇），它们相应的水合物和缩醛的链烷醛衍生物，以及制备和使用这种聚合物链烷醛的方法。 本发明的聚合物链烷可以高纯度制备并显示储存稳定性。

公开(公告)号：US07834138B2

公开(公告)日：2010-11-16

申请号：US11402350

申请日：2006-04-11

Applicant: Antoni Kozlowski ,  Xiaoming Shen ,  Michael D. Bentley ,  Zhihao Fang ,  Tony L. Sander

Inventor： Antoni Kozlowski ,  Xiaoming Shen ,  Michael D. Bentley ,  Zhihao Fang ,  Tony L. Sander

IPC: C08F6/00

CPC classification number: C08G65/329 ,  A61K47/56 ,  A61K47/60 ,  Y10S530/815

Abstract: Segmented water soluble polymers, containing a higher molecular weight segment linked to a lower molecular weight segment, are described. In one embodiment, the polymer segments are poly(ethylene glycol) segments. The segmented polymers are functionalized and are useful for conjugation to various moieties such as pharmacologically active substances. Also described are conjugates of such polymers and methods of their preparation.

Abstract translation: 描述了含有与较低分子量链段连接的较高分子量链段的分段水溶性聚合物。 在一个实施方案中，聚合物链段是聚（乙二醇）链段。 分段的聚合物被官能化并且可用于与各种部分缀合，例如药理学活性物质。 还描述了这些聚合物的共轭物及其制备方法。

公开(公告)号：US20100063328A1

公开(公告)日：2010-03-11

申请号：US12620011

申请日：2009-11-17

Applicant: Michael D. Bentley ,  J. Milton Harris ,  Antoni Kozlowski

Inventor： Michael D. Bentley ,  J. Milton Harris ,  Antoni Kozlowski

IPC: C07C41/01

CPC classification number: C08G65/3322 ,  C08G65/329

Abstract: This invention provides a method related to the preparation of derivatives of poly(ethylene glycol).

Abstract translation: 本发明提供了与制备聚（乙二醇）衍生物有关的方法。

公开(公告)号：US20100010158A1

公开(公告)日：2010-01-14

申请号：US12224201

申请日：2007-02-21

Applicant: Samuel P. McManus ,  Antoni Kozlowski

Inventor： Samuel P. McManus ,  Antoni Kozlowski

IPC: C08G63/91

CPC classification number: A61K47/48215 ,  A61K47/60

Abstract: The present invention provides, among other things, segmented, degradable polymeric reagents suitable for reaction with biologically active agents to form conjugates, the polymeric reagents comprising one or more polymer chains divided or separated by one or more degradable linkages into polymer segments having a molecular weight suitable for renal clearance. The polymeric reagents can have a substantially linear structure, a branched structure, or a multiarm structure. Each structure includes one or more linkages capable of degradation in vivo.

Abstract translation: 本发明尤其提供了适用于与生物活性剂反应以形成共轭物的分段的可降解聚合物试剂，所述聚合物试剂包含一个或多个由一个或多个可降解键分隔或分隔成聚合物链段的聚合物链，其具有分子量 适合肾清除。 聚合物试剂可以具有基本上线性的结构，分支结构或多臂结构。 每个结构包括能够在体内降解的一种或多种键。

公开(公告)号：US20100004428A1

公开(公告)日：2010-01-07

申请号：US12560339

申请日：2009-09-15

Applicant: Antoni Kozlowski ,  Samuel P. McManus

Inventor： Antoni Kozlowski ,  Samuel P. McManus

IPC: C07K14/555 ,  C07D207/46 ,  C07C205/06 ,  C07D249/18 ,  C07D233/54 ,  C07K14/715 ,  C07K14/505 ,  C07K14/61

CPC classification number: C08F8/14 ,  C08G65/3322

Abstract: The invention provides methods for preparing polymers bearing a terminal propionic acid. The method involves first reacting a water soluble and non-peptidic polymer comprising at least one hydroxyl group with a tertiary alkyl acrylate in the presence of a catalyst to form a propionic acid ester of the polymer, wherein the polymer has a weight average molecular weight of at least about 10,000 Da; and then treating the propionic acid ester of the polymer with a strong acid to form a propionic acid of the polymer.

Abstract translation: 本发明提供了制备具有末端丙酸的聚合物的方法。 该方法包括首先使包含至少一个羟基的水溶性和非肽聚合物与丙烯酸叔烷基酯在催化剂存在下反应以形成聚合物的丙酸酯，其中聚合物的重均分子量为 至少约10,000Da; 然后用强酸处理聚合物的丙酸酯，形成聚合物的丙酸。

公开(公告)号：US20090215910A1

公开(公告)日：2009-08-27

申请号：US12433874

申请日：2009-04-30

Applicant: Antoni Kozlowski

Inventor： Antoni Kozlowski

IPC: A61K47/14 ,  C07D249/18

CPC classification number: A61K47/58 ,  A61K31/7088 ,  A61K47/60 ,  A61K47/6901 ,  C08G63/91 ,  C08G65/48

Abstract: The invention provides a method for preparing a 1-benzotriazolylcarbonate ester of a water-soluble and non-peptidic polymer by reacting a terminal hydroxyl group of a water-soluble and non-peptidic polymer with di(1-benzotriazolyl)carbonate in the presence of an amine base and an organic solvent. The polymer backbone can be poly(ethylene glycol). The 1-benzotriazolylcarbonate ester can then be reacted directly with a biologically active agent to form a biologically active polymer conjugate or reacted with an amino acid, such as lysine, to form an amino acid derivative.

Abstract translation: 本发明提供了通过使水溶性和非肽类聚合物的末端羟基与二（1-苯并三唑基）碳酸酯在存在下进行反应制备水溶性和非肽类聚合物的1-苯并三唑基碳酸酯的方法。 胺基和有机溶剂。 聚合物主链可以是聚（乙二醇）。 然后可以将1-苯并三唑基碳酸酯酯与生物活性剂直接反应以形成生物活性聚合物缀合物或与氨基酸如赖氨酸反应以形成氨基酸衍生物。

公开(公告)号：US20080227872A1

公开(公告)日：2008-09-18

申请号：US12150136

申请日：2008-04-25

Applicant: Antoni Kozlowski

Inventor： Antoni Kozlowski

IPC: A61K47/48

CPC classification number: A61K47/58 ,  A61K31/7088 ,  A61K47/60 ,  A61K47/6901 ,  C08G63/91 ,  C08G65/48

Abstract: The invention provides a method for preparing a 1-benzotriazolylcarbonate ester of a water-soluble and non-peptidic polymer by reacting a terminal hydroxyl group of a water-soluble and non-peptidic polymer with di(1-benzotriazolyl)carbonate in the presence of an amine base and an organic solvent. The polymer backbone can be poly(ethylene glycol). The 1-benzotriazolylcarbonate ester can then be reacted directly with a biologically active agent to form a biologically active polymer conjugate or reacted with an amino acid, such as lysine, to form an amino acid derivative.

Abstract translation: 本发明提供了通过使水溶性和非肽类聚合物的末端羟基与二（1-苯并三唑基）碳酸酯在存在下进行反应制备水溶性和非肽类聚合物的1-苯并三唑基碳酸酯的方法。 胺基和有机溶剂。 聚合物主链可以是聚（乙二醇）。 然后可以将1-苯并三唑基碳酸酯酯与生物活性剂直接反应以形成生物活性聚合物缀合物或与氨基酸如赖氨酸反应以形成氨基酸衍生物。