公开(公告)号：US20100210505A1

公开(公告)日：2010-08-19

申请号：US12086687

申请日：2006-12-18

申请人： Mary J. Bossard ,  Zhihao Fang ,  Tacey X. Viegas ,  Stewart A. Thompson ,  Mei-chang Kuo

发明人： Mary J. Bossard ,  Zhihao Fang ,  Tacey X. Viegas ,  Stewart A. Thompson ,  Mei-chang Kuo

IPC分类号： A61K38/22 ,  C07K14/575 ,  A61K38/28 ,  A61P3/10

CPC分类号： C07K17/08 ,  A61K47/60 ,  C07K14/605

摘要： Conjugates of a GLP-I moiety may be covalently attached to one or more water-soluble polymers. For instance, a GLP-I polymer conjugate may include a GLP-I moiety releasably attached at its N-terminus to a water-soluble polymer. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached to a water-soluble polymer, wherein the GLP-I moiety possesses an N-methyl substituent. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached at a polymer attachment site to a water-soluble polymer, wherein the GLP-I moiety is glycosylated at a site separate from the polymer attachment site.

摘要翻译： GLP-1部分的缀合物可以共价连接到一种或多种水溶性聚合物上。 例如，GLP-1聚合物缀合物可以包括其N-末端可释放地连接到水溶性聚合物上的GLP-1部分。 GLP-1聚合物缀合物可以包括与水溶性聚合物共价连接的GLP-1部分，其中GLP-1部分具有N-甲基取代基。 GLP-1聚合物缀合物可以包括在聚合物附着位点共价连接到水溶性聚合物上的GLP-1部分，其中GLP-1部分在与聚合物附着部位分开的位置被糖基化。

公开(公告)号：US20230113413A1

公开(公告)日：2023-04-13

申请号：US17818687

申请日：2022-08-09

申请人： Nektar Therapeutics

发明人： J. Milton Harris ,  Antoni Kozlowski ,  Samuel P. McManus ,  Michael D. Bentley ,  Stephen A. Charles

IPC分类号： A61K47/60 ,  A61K31/52 ,  A61K38/095 ,  C08G65/329 ,  C08G65/333 ,  A61K31/357 ,  A61K31/4025 ,  A61K38/18 ,  A61K38/19 ,  A61K38/21 ,  A61K38/24 ,  A61K38/27 ,  A61K38/37

摘要： Polymeric reagents are provided comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.

公开(公告)号：US11464788B2

公开(公告)日：2022-10-11

申请号：US15788626

申请日：2017-10-19

申请人： Nektar Therapeutics

发明人： Wen Zhang ,  Jennifer Riggs-Sauthier ,  J. Milton Harris ,  Michael D. Bentley

IPC分类号： A61K31/573 ,  C07J41/00 ,  A61K47/60 ,  A61K47/59

摘要： The invention provides corticosteroids that are chemically modified by covalent attachment of a water-soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits a reduced biological membrane crossing rate as compared to the biological membrane crossing rate of the corticosteroid not attached to the water-soluble oligomer.

公开(公告)号：US11446385B2

公开(公告)日：2022-09-20

申请号：US16841669

申请日：2020-04-06

申请人： Nektar Therapeutics

发明人： J. Milton Harris ,  Antoni Kozlowski ,  Samuel P. McManus ,  Michael D. Bentley ,  Stephen A. Charles

IPC分类号： A61K47/60 ,  A61K31/52 ,  A61K38/095 ,  C08G65/329 ,  C08G65/333 ,  A61K31/357 ,  A61K31/4025 ,  A61K38/18 ,  A61K38/19 ,  A61K38/21 ,  A61K38/24 ,  A61K38/27 ,  A61K38/37

摘要： Polymeric reagents are provided comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.

公开(公告)号：US20220081512A1

公开(公告)日：2022-03-17

申请号：US17538885

申请日：2021-11-30

申请人： Nektar Therapeutics

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

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

摘要： 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：US11241415B2

公开(公告)日：2022-02-08

申请号：US16412096

申请日：2019-05-14

申请人： Nektar Therapeutics

发明人： Franco J. Duarte ,  Neel K. Anand ,  Wen Zhang ,  Pankaj Sharma ,  Devendrapratap Singh

IPC分类号： A61K31/4025 ,  C07D213/71 ,  C07D231/18 ,  C07D333/34 ,  C07D239/60 ,  C07D261/10 ,  C07D207/12 ,  C07D207/14 ,  C07D295/13 ,  C07D295/135 ,  C07D207/04

摘要： Compounds and pharmaceutically acceptable salts and solvates thereof are described. The compounds relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology and organic chemistry.

公开(公告)号：US11129794B2

公开(公告)日：2021-09-28

申请号：US16020773

申请日：2018-06-27

申请人： Nektar Therapeutics

发明人： C. Simone Jude-Fishburn ,  David Lechuga-Ballesteros ,  Tacey X. Viegas ,  Mei-Chang Kuo ,  Hema Gursahani ,  Chester Leach ,  Yuan Song

IPC分类号： A61K9/00 ,  A61K47/60 ,  A61K31/167 ,  A61K31/485 ,  C07C41/24

摘要： Methods of modifying the rate of systemic absorption of a drug administered to a subject by a pulmonary route, the method comprising covalently conjugating a hydrophilic polymer to a drug, wherein the drug has a half-life of elimination from the lung of less than about 180 minutes, to form a drug-polymer conjugate, wherein the drug-polymer conjugate has a net hydrophilic character and a weight average molecular weight of from about 50 to about 20,000 Daltons, and wherein the half-life of elimination from the lung of the drug-polymer conjugate is at least about 1.5-fold greater than the half-life of elimination from the lung of the drug, wherein the half-life of elimination from the lung is measured by bronchioalveolar lavage followed by assaying residual lung material.

公开(公告)号：US11111335B2

公开(公告)日：2021-09-07

申请号：US16000561

申请日：2018-06-05

申请人： Nektar Therapeutics

发明人： J. Milton Harris ,  Antoni Kozlowski ,  Lihong Guo

IPC分类号： C08G65/332 ,  C08G63/91 ,  C08G65/334 ,  A61K31/765 ,  C08F251/00 ,  C08F261/04 ,  C08F265/00 ,  C08F271/00 ,  C08F283/06 ,  C08F289/00 ,  C08F291/00 ,  C08G65/30

摘要： Methods for preparing water soluble, non-peptidic polymers carrying carboxyl functional groups, particularly carboxylic acid functionalized poly(ethylene glycol) (PEG) polymers are disclosed, as are the products of these methods. In general, an ester reagent R(C═O)OR′, wherein R′ is a tertiary group and R comprises a functional group X, is reacted with a water soluble, non-peptidic polymer POLY-Y, where Y is a functional group which reacts with X to form a covalent bond, to form a tertiary ester of the polymer, which is then treated with a strong base in aqueous solution, to form a carboxylate salt of the polymer. Typically, this carboxylate salt is then treated with an inorganic acid in aqueous solution, to convert the carboxylate salt to a carboxylic acid, thereby forming a carboxylic acid functionalized polymer.

公开(公告)号：US20210130546A1

公开(公告)日：2021-05-06

申请号：US17144870

申请日：2021-01-08

申请人： Nektar Therapeutics

发明人： Antoni Kozlowski ,  Jon McKannan ,  Samuel P. McManus

IPC分类号： C08G65/333 ,  A61K47/60 ,  C08G65/329 ,  C08G65/332 ,  C08L71/02 ,  C07B47/00 ,  C08G65/48

摘要： Methods for preparing active carbonate esters of water-soluble polymers are provided. Also provided are other methods related to the active carbonate esters of water-soluble polymers, as well as corresponding compositions.

公开(公告)号：US20210023186A1

公开(公告)日：2021-01-28

申请号：US17063654

申请日：2020-10-05

申请人： Nektar Therapeutics

发明人： Mary J. Bossard ,  Gayle Stephenson-Phillips

IPC分类号： A61K38/48 ,  A61K47/60 ,  C12N9/64 ,  C12N9/96

摘要： Conjugates of a Factor IX moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided (among other things) are compositions comprising the conjugates, methods of making the conjugates, and methods of administering to a patient compositions comprising the conjugates.