公开(公告)号：US20110021761A1

公开(公告)日：2011-01-27

申请号：US12898687

申请日：2010-10-05

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: C07K14/00 ,  C07C309/64 ,  C07C271/06 ,  C07D207/40 ,  C07C223/02 ,  C07C229/02

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：US07829074B2

公开(公告)日：2010-11-09

申请号：US10398845

申请日：2001-10-18

Applicant: Michael J. Roberts ,  Antoni Kozlowski

Inventor： Michael J. Roberts ,  Antoni Kozlowski

IPC: A61K47/48 ,  A61K9/00 ,  A61K38/16

CPC classification number: A61K47/18 ,  A61K31/715 ,  A61K47/24 ,  A61K47/60 ,  C08G65/329 ,  C08G65/3353 ,  C08L2203/02

Abstract: Isolatable, hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are provided. The polymeric structure includes a linear or branched water-soluble and non-peptidic polymer backbone, such as a PEG backbone, having at least two termini, a first terminus being covalently bonded to a hydroxyapatite-targeting moiety, such as a bisphosphonate, and a second terminus covalently bonded to a chemically reactive group, wherein said chemically reactive group is protected or unprotected. Methods of preparing and using hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are also provided.

Abstract translation: 提供可分离的羟基磷灰石靶向聚合物结构及其生物活性缀合物。 聚合物结构包括直链或支链的水溶性和非肽聚合物主链，例如具有至少两个末端的PEG主链，第一个末端与羟基磷灰石靶向部分如二膦酸共价键合，和 第二末端共价键合到化学反应基团，其中所述化学反应基团被保护或未被保护。 还提供了制备和使用羟基磷灰石靶向聚合物结构及其生物活性缀合物的方法。

公开(公告)号：US20100197806A1

公开(公告)日：2010-08-05

申请号：US12756905

申请日：2010-04-08

Applicant: Antoni Kozlowski

Inventor： Antoni Kozlowski

IPC: A61K47/34 ,  C08L69/00 ,  C07D249/18 ,  A61P43/00

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：US07569214B2

公开(公告)日：2009-08-04

申请号：US10659735

申请日：2003-09-09

Applicant: Antoni Kozlowski

Inventor： Antoni Kozlowski

IPC: A61K31/74 ,  A61K47/48

CPC classification number: C07D493/08 ,  A61K9/1611 ,  A61K9/1617 ,  A61K9/1623 ,  A61K9/1635 ,  A61K9/1652 ,  A61K9/209 ,  A61K31/74 ,  C08G65/002 ,  C08G65/331 ,  C08G65/332 ,  C08G65/33317 ,  C08G2650/42 ,  C08L2203/02

Abstract: A method is provided for preparing water-soluble polymer derivatives bearing a terminal carboxylic acid or ester thereof. The method involves the hydrolyzing an ortho ester of a water-soluble polymer so as provide the corresponding acid. In addition, the invention provides water-soluble polymers bearing a terminal carboxylic acid or ester thereof, intermediates and reagents useful in carrying out the method, as well as gels, pharmaceutical formulations, conjugates related to the described water-soluble polymer derivatives.

Abstract translation: 提供了一种制备带有末端羧酸或其酯的水溶性聚合物衍生物的方法。 该方法包括水解水溶性聚合物的原酸酯以提供相应的酸。 此外，本发明提供了带有末端羧酸或其酯的水溶性聚合物，可用于实施该方法的中间体和试剂，以及与所述水溶性聚合物衍生物相关的凝胶，药物制剂，缀合物。

公开(公告)号：US20070166277A1

公开(公告)日：2007-07-19

申请号：US11714322

申请日：2007-03-06

Applicant: Samuel McManus ,  Antoni Kozlowski ,  Xiaoming Shen ,  Daniel Cook

Inventor： Samuel McManus ,  Antoni Kozlowski ,  Xiaoming Shen ,  Daniel Cook

IPC: A61K31/74

CPC classification number: A61K47/48215 ,  A61K47/60 ,  C08G65/329 ,  C08G65/331 ,  C08G65/3344 ,  C08L2203/02

Abstract: Polymeric reagents comprising a polymer attached, either directly or through one or more atoms, to a ketone or a related functional group such as ketone hydrate, thione, monothiohydrate, dithiohydrate, hemiketal, monothiohemiketal, dithiohemiketal, ketal, or dithioketal are provided. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.

Abstract translation: 提供了包含直接或通过一个或多个原子连接到酮或相关官能团例如酮水合物，硫酮，一硫代水合物，二硫代水合物，半缩酮，单硫代缩酮，二硫代葡萄糖酮，缩酮或二硫缩酮的聚合试剂。 聚合物试剂尤其可用于形成聚合物 - 活性剂缀合物。 还提供了相关方法，组合物，制剂等。

公开(公告)号：US20060264578A1

公开(公告)日：2006-11-23

申请号：US11492133

申请日：2006-07-24

Applicant: Antoni Kozlowski

Inventor： Antoni Kozlowski

IPC: C08F297/02

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.

公开(公告)号：US20060194940A1

公开(公告)日：2006-08-31

申请号：US11375698

申请日：2006-03-13

Applicant: Antoni Kozlowski

Inventor： Antoni Kozlowski

IPC: C08G2/00

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.

公开(公告)号：US20050176922A1

公开(公告)日：2005-08-11

申请号：US11004631

申请日：2004-12-03

Applicant: Samuel McManus ,  Antoni Kozlowski ,  Tracy Hutchison ,  Brian Bray ,  Xiaoming Shen

Inventor： Samuel McManus ,  Antoni Kozlowski ,  Tracy Hutchison ,  Brian Bray ,  Xiaoming Shen

IPC: A61K47/48 ,  C08G65/333 ,  C08G69/08

CPC classification number: C07D403/12 ,  A61K47/60 ,  C08G65/33337 ,  C08G69/08

Abstract: Methods for forming maleimide functionalized polymers are provided. In one such embodiment, a maleimide functionalized polymer is prepared in a method that includes a step of carrying out a reverse Diels-Alder reaction. Intermediates useful in the methods, as well as methods for preparing the intermediates, are also provided. Also provided are polymeric reagents, methods of using polymeric reagents, compounds and conjugates.

Abstract translation: 提供了形成马来酰亚胺官能化聚合物的方法。 在一个这样的实施方案中，马来酰亚胺官能化聚合物在包括进行反向Diels-Alder反应的步骤的方法中制备。 还提供了可用于该方法的中间体以及制备中间体的方法。 还提供了聚合物试剂，使用聚合物试剂，化合物和共轭物的方法。

公开(公告)号：US20050171291A1

公开(公告)日：2005-08-04

申请号：US11040142

申请日：2005-01-21

Applicant: Antoni Kozlowski ,  Samuel McManus

Inventor： Antoni Kozlowski ,  Samuel McManus

IPC: C07C67/31 ,  C08F8/12 ,  C08F8/14 ,  C08F232/00 ,  C08G65/332

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：US06710125B2

公开(公告)日：2004-03-23

申请号：US10068371

申请日：2002-02-06

Applicant: Antoni Kozlowski

Inventor： Antoni Kozlowski

IPC: C08F1606

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。