公开(公告)号：US10039737B2

公开(公告)日：2018-08-07

申请号：US15296414

申请日：2016-10-18

Applicant: Nektar Therapeutics

Inventor： Antoni Kozlowski ,  Samuel P. McManus ,  Jennifer Riggs-Sauthier ,  Xiaoming Shen ,  Wen Zhang

IPC: A61K31/337 ,  A61K38/00 ,  A61K31/785 ,  C08G79/08 ,  A61K47/48 ,  A61K31/4745 ,  C08G65/332 ,  C08G65/333

Abstract: Among other aspects, provided herein are multi-armed polymer conjugates comprising an alkanoate-linker, compositions comprising such conjugates, and related methods of making and administering the same. Methods of treatment employing such conjugates and related uses are also provided. The conjugates are prepared with high drug loading efficiencies.

公开(公告)号：US20170121459A1

公开(公告)日：2017-05-04

申请号：US15408037

申请日：2017-01-17

Applicant: Nektar Therapeutics

Inventor： Sean M. Culbertson ,  Xiaoming Shen ,  Antoni Kozlowski ,  Samuel P. McManus

IPC: C08G65/332 ,  C08G65/333

CPC classification number: C08G65/2606 ,  A61K38/00 ,  A61K47/60 ,  C07K1/003 ,  C07K17/08 ,  C08G65/26 ,  C08G65/2609 ,  C08G65/331 ,  C08G65/3315 ,  C08G65/3318 ,  C08G65/3326 ,  C08G65/33306 ,  C08G65/33313 ,  C08G65/33317 ,  C08G65/33327 ,  C08L71/02

Abstract: Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

公开(公告)号：US09579392B2

公开(公告)日：2017-02-28

申请号：US14951035

申请日：2015-11-24

Applicant: Nektar Therapeutics

Inventor： Sean M. Culbertson ,  Xiaoming Shen ,  Antoni Kozlowski ,  Samuel P. McManus

IPC: A61K47/48 ,  C08L71/02 ,  C08G65/26 ,  C07K1/00 ,  C07K17/08 ,  C08G65/331 ,  C08G65/333 ,  A61K38/16 ,  A61K38/28 ,  A61K38/47

CPC classification number: C08G65/2606 ,  A61K38/00 ,  A61K47/60 ,  C07K1/003 ,  C07K17/08 ,  C08G65/26 ,  C08G65/2609 ,  C08G65/331 ,  C08G65/3315 ,  C08G65/3318 ,  C08G65/3326 ,  C08G65/33306 ,  C08G65/33313 ,  C08G65/33317 ,  C08G65/33327 ,  C08L71/02

Abstract: Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

Abstract translation: 本文提供的是聚合α-羟基醛或α-羟基酮试剂，其可以与含胺化合物结合以在单步反应中形成稳定的共轭物。 在选择的实施方案中，聚合物试剂本身包含内部质子抽提（碱性）官能团，以促进更有效的反应。 如果需要，取代基通过接头适当地定位，以使基团定位以进行质子抽提，优选在提取的原子和α-碳上的氢原子之间提供4-或5-键的间隔。 还提供了使用试剂和试剂的稳定的，溶解的缀合物与生物活性化合物的方法。 在优选的实施方案中，试剂或缀合物的聚合物组分是聚乙二醇。

公开(公告)号：US20160144046A1

公开(公告)日：2016-05-26

申请号：US14951035

申请日：2015-11-24

Applicant: Nektar Therapeutics

Inventor： Sean M. Culbertson ,  Xiaoming Shen ,  Antoni Kozlowski ,  Samuel P. McManus

IPC: A61K47/48 ,  A61K38/28 ,  A61K38/47 ,  A61K38/16

CPC classification number: C08G65/2606 ,  A61K38/00 ,  A61K47/60 ,  C07K1/003 ,  C07K17/08 ,  C08G65/26 ,  C08G65/2609 ,  C08G65/331 ,  C08G65/3315 ,  C08G65/3318 ,  C08G65/3326 ,  C08G65/33306 ,  C08G65/33313 ,  C08G65/33317 ,  C08G65/33327 ,  C08L71/02

Abstract: Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

Abstract translation: 本文提供的是聚合α-羟基醛或α-羟基酮试剂，其可以与含胺化合物结合以在单步反应中形成稳定的共轭物。 在选择的实施方案中，聚合物试剂本身包含内部质子抽提（碱性）官能团，以促进更有效的反应。 如果需要，取代基通过接头适当地定位，以使基团定位以进行质子抽提，优选在提取的原子和α-碳上的氢原子之间提供4-或5-键的间隔。 还提供了使用试剂和试剂的稳定的，溶解的缀合物与生物活性化合物的方法。 在优选的实施方案中，试剂或缀合物的聚合物组分是聚乙二醇。

公开(公告)号：US09173951B2

公开(公告)日：2015-11-03

申请号：US14167271

申请日：2014-01-29

Applicant: NEKTAR THERAPEUTICS

Inventor： Antoni Kozlowski ,  Samuel P. McManus ,  Xiaoming Shen

IPC: A61K38/10 ,  A61K38/16 ,  A61K38/28 ,  A61K47/48

CPC classification number: A61K47/48215 ,  A61K38/10 ,  A61K38/16 ,  A61K38/28 ,  A61K47/60 ,  A61K47/61

Abstract: Provided herein are water-soluble carbohydrate polymers which are monoderivatized at their reducing terminus, such that the carbohydrate polymers can be selectively conjugated at a single location. Also provided are methods of preparation and conjugation of the monoderivatized carbohydrate polymers.

Abstract translation: 本文提供的水溶性碳水化合物聚合物在其还原性末端被单体化，使得碳水化合物聚合物可以在单个位置选择性缀合。 还提供了单分解碳水化合物聚合物的制备和缀合的方法。

公开(公告)号：US08895759B2

公开(公告)日：2014-11-25

申请号：US14153783

申请日：2014-01-13

Applicant: Nektar Therapeutics

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

IPC: C07D207/46 ,  C07D403/12 ,  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.

公开(公告)号：US20140329994A1

公开(公告)日：2014-11-06

申请号：US14334223

申请日：2014-07-17

Applicant: NEKTAR THERAPEUTICS

Inventor： Michael D. Bentley ,  Xuan Zhao ,  Xiaoming Shen ,  William D. Battle, III

IPC: C07K17/08

CPC classification number: C08G65/48 ,  A61K47/60 ,  A61K47/6901 ,  C07K17/08 ,  C08G65/329 ,  C08G65/3322 ,  C08L2203/02 ,  C12N9/96

Abstract: The present invention is directed to branched reactive water-soluble polymers comprising at least two polymer arms, such as poly(ethylene glycol), attached to a central aliphatic hydrocarbon core molecule through heteroatom linkages. The branched polymers bear at least one functional group for reacting with a biologically active agent to form a biologically active conjugate. The functional group of the branched polymer can be directly attached to the aliphatic hydrocarbon core or via an intervening linkage, such as a heteroatom, -alkylene-, —O-alkylene-O—, -alkylene-O-alkylene-, -aryl-O—, —O-aryl-, (—O-alkylene-)m, or (-alkylene-O—)m linkage, wherein m is 1-10.

Abstract translation: 本发明涉及包含通过杂原子键连接到中心脂族烃核心分子的至少两个聚合物臂（例如聚（乙二醇））的支链反应性水溶性聚合物。 支链聚合物具有至少一个用于与生物活性剂反应以形成生物活性缀合物的官能团。 支链聚合物的官能团可以直接连接到脂族烃核心上或通过插入键如杂原子， - 亚烷基 - ， - - 亚烷基-O-， - 亚烷基-O-亚烷基 - ， - 芳基 - O-，-O-芳基 - ，（ - - 亚烷基 - ）m或（ - 亚烷基-O-）m键，其中m为1-10。

公开(公告)号：US11672776B2

公开(公告)日：2023-06-13

申请号：US16026979

申请日：2018-07-03

Applicant: Nektar Therapeutics

Inventor： Antoni Kozlowski ,  Samuel P. McManus ,  Jennifer Riggs-Sauthier ,  Xiaoming Shen ,  Wen Zhang

IPC: A61K31/337 ,  A61K38/00 ,  A61K31/785 ,  C08G79/08 ,  A61K47/60 ,  A61K31/4745 ,  C08G65/332 ,  C08G65/333

CPC classification number: A61K31/337 ,  A61K31/4745 ,  A61K31/785 ,  A61K38/00 ,  A61K47/60 ,  C08G65/3328 ,  C08G65/33344 ,  C08G79/08

Abstract: Among other aspects, provided herein are multi-armed polymer conjugates comprising an alkanoate-linker, compositions comprising such conjugates, and related methods of making and administering the same. Methods of treatment employing such conjugates and related uses are also provided. The conjugates are prepared with high drug loading efficiencies.

公开(公告)号：US11406618B2

公开(公告)日：2022-08-09

申请号：US16243914

申请日：2019-01-09

Applicant: Nektar Therapeutics

Inventor： Antoni Kozlowski ,  Sean M. Culbertson ,  Xiaoming Shen ,  Samuel P. McManus ,  Mark A. Wilson

IPC: A61K31/404 ,  A61K47/60 ,  A61P35/00

Abstract: The invention relates to (among other things) polymer-des-ethyl sunitinib conjugates and related compounds. A compound of the invention, when administered by any of a number of administration routes, exhibits advantages over des-ethyl sunitinib in unconjugated form.

公开(公告)号：US10759906B2

公开(公告)日：2020-09-01

申请号：US15867524

申请日：2018-01-10

Applicant: Nektar Therapeutics

Inventor： Sean M. Culbertson ,  Xiaoming Shen ,  Antoni Kozlowski ,  Samuel P. McManus

IPC: C08G65/26 ,  C08L71/02 ,  C07K1/00 ,  C07K17/08 ,  C08G65/331 ,  A61K47/60 ,  C08G65/333 ,  C08G65/332 ,  A61K38/00

Abstract: Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.