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1. 发明授权

US08940801B2 Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation 有权
标题翻译：异双功能聚（乙二醇）衍生物及其制备方法
公开(公告)号：US08940801B2
公开(公告)日：2015-01-27
申请号：US12620011
申请日：2009-11-17
申请人： Michael D. Bentley , J. Milton Harris , Antoni Kozlowski
发明人： Michael D. Bentley , J. Milton Harris , Antoni Kozlowski
IPC分类号： C08G65/332 , C08G65/329 , C07C41/01
CPC分类号： C08G65/3322 , C08G65/329
摘要： This invention provides a method related to the preparation of derivatives of poly(ethylene glycol), wherein the method comprises increasing the pH of an aqueous composition comprising a poly(ethylene glycol) bearing a —O—(CH2)n—CO2R3 functional group to result in an aqueous composition comprising a poly(ethylene glycol) bearing a —O—(CH2)n—CO2H functional group, wherein R3 is alkyl and (n) in each instance is 1-6.
摘要翻译：本发明提供了与制备聚（乙二醇）衍生物有关的方法，其中该方法包括将含有-O-（CH 2）n -CO 2 R 3官能团的聚（乙二醇）的含水组合物的pH提高到得到包含含有-O-（CH 2）n -CO 2 H官能团的聚（乙二醇）的水性组合物，其中R 3是烷基，（n）各自为1-6。

2. 发明授权

US08796248B2 Oligomer-corticosteroid conjugates 有权
标题翻译：低聚物 - 皮质类固醇共轭物
公开(公告)号：US08796248B2
公开(公告)日：2014-08-05
申请号：US12680877
申请日：2008-10-03
申请人： Wen Zhang , Jennifer Riggs-Sauthier , J. Milton Harris , Michael D. Bentley
发明人： Wen Zhang , Jennifer Riggs-Sauthier , J. Milton Harris , Michael D. Bentley
IPC分类号： A61K31/573 , C07J41/00 , C07J5/00 , A61P25/08
CPC分类号： A61K31/573 , A61K47/48215 , A61K47/60 , C07J41/0005
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.
摘要翻译：本发明提供通过共价连接水溶性寡聚物进行化学修饰的皮质类固醇。当与多种施用途径中的任何一种施用时，本发明的化合物与未附着于水溶性低聚物的皮质类固醇的生物膜交联率相比表现出降低的生物膜交叉率。

3. 发明授权

US08633277B2 Methods for forming polymer-drug conjugates 有权
标题翻译：形成聚合物 - 药物共轭物的方法
公开(公告)号：US08633277B2
公开(公告)日：2014-01-21
申请号：US13043438
申请日：2011-03-08
申请人： J. Milton Harris , Antoni Kozlowski , Samuel P. McManus , Michael D. Bentley , Stephen A. Charles
发明人： J. Milton Harris , Antoni Kozlowski , Samuel P. McManus , Michael D. Bentley , Stephen A. Charles
IPC分类号： A61K47/48 , C08G63/91 , A61K31/74 , A61K45/00 , A61K38/21
CPC分类号： A61K47/60 , A61K31/357 , A61K31/4025 , A61K31/52 , A61K38/11 , A61K38/1816 , A61K38/193 , A61K38/212 , A61K38/215 , A61K38/24 , A61K38/27 , A61K38/37 , C08G65/329 , C08G65/33337 , C08G65/33344
摘要： Methods for preparing polymer-drug conjugates are provided. The disclosed methods involve polymeric reagents comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. Related methods, compositions, preparations, and so forth are also provided.
摘要翻译：提供了制备聚合物 - 药物偶联物的方法。所公开的方法涉及包含以特定顺序排列的原子部分的聚合物试剂，其中该部分位于水溶性聚合物和反应性基团之间。还提供了相关方法，组合物，制剂等。

4. 发明申请

US20120123055A1 Multifunctional Forms of Polyoxazoline Copolymers and Drug Compositions Comprising the Same 有权
标题翻译：多官能团形式的聚恶唑啉共聚物和药物组合物组成
公开(公告)号：US20120123055A1
公开(公告)日：2012-05-17
申请号：US13356552
申请日：2012-01-23
申请人： Kunsang Yoon , Michael David Bentley , J. Milton Harris , Zhihao Fang , Tacey Viegas
发明人： Kunsang Yoon , Michael David Bentley , J. Milton Harris , Zhihao Fang , Tacey Viegas
IPC分类号： C08G73/02
CPC分类号： A61K47/48207 , A61K38/09 , A61K47/59 , C08G73/0233
摘要： The present disclosure provides copolymers of 2-substituted-2-oxazolines possessing two or three reactive functional groups which are also chemically orthogonal. The copolymers described may be random copolymers, block copolymers or a mixture of random and block copolymer configurations. Furthermore, the present disclosure provides novel methods for synthesizing the above polymers and for conjugating to molecules such as targeting, diagnostic and therapeutic agents.
摘要翻译：本公开提供了具有两个或三个也是化学正交的反应性官能团的2-取代-2-恶唑啉的共聚物。所述共聚物可以是无规共聚物，嵌段共聚物或无规嵌段共聚物构型的混合物。此外，本公开提供了用于合成上述聚合物并用于与靶标，诊断和治疗剂等分子缀合的新方法。

5. 发明申请

US20120041155A1 Method of Preparing Carboxylic Acid Functionalized Polymers 审中-公开
标题翻译：羧酸官能化聚合物的制备方法
公开(公告)号：US20120041155A1
公开(公告)日：2012-02-16
申请号：US13279134
申请日：2011-10-21
申请人： J. Milton Harris , Antoni Kozlowski , Lihong Guo
发明人： J. Milton Harris , Antoni Kozlowski , Lihong Guo
IPC分类号： C08L71/02
CPC分类号： C08G63/91 , A61K31/765 , C08F251/00 , C08F261/04 , C08F265/00 , C08F271/00 , C08F283/06 , C08F289/00 , C08F291/00 , C08G65/30 , C08G65/332 , C08G65/3322 , C08G65/3346
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.
摘要翻译：公开了用于制备携带羧基官能团的水溶性非肽聚合物，特别是羧酸官能化聚（乙二醇）（PEG）聚合物的方法，以及这些方法的产物。通常，其中R'是叔基，R包含官能团X的酯试剂R（C = O）OR'与水溶性非肽聚合物POLY-Y反应，其中Y是官能团基团与X反应形成共价键，形成聚合物的叔酯，然后用强碱在水溶液中处理，形成聚合物的羧酸盐。通常，该羧酸盐然后用水溶液中的无机酸处理，以将羧酸盐转化为羧酸，从而形成羧酸官能化聚合物。

6. 发明授权

US08110651B2 Multifunctional forms of polyoxazoline copolymers and drug compositions comprising the same 有权
标题翻译：多官能形式的聚恶唑啉共聚物和包含它们的药物组合物
公开(公告)号：US08110651B2
公开(公告)日：2012-02-07
申请号：US12744472
申请日：2009-01-12
申请人： Kunsang Yoon , J. Milton Harris , Michael David Bentley
发明人： Kunsang Yoon , J. Milton Harris , Michael David Bentley
IPC分类号： C08G73/06 , C08G75/02 , C08G69/00
CPC分类号： C08G73/0233 , C08G73/028
摘要： The present disclosure provides copolymers of 2-substituted-2-oxazolines possessing two or three reactive functional groups which are also chemically orthogonal. The copolymers described may be random copolymers, block copolymers or a mixture of random and block copolymer configurations. Furthermore, the present disclosure provides novel methods for synthesizing the above polymers and for conjugating to molecules such as targeting, diagnostic and therapeutic agents.
摘要翻译：本公开提供了具有两个或三个也是化学正交的反应性官能团的2-取代-2-恶唑啉的共聚物。所述共聚物可以是无规共聚物，嵌段共聚物或无规嵌段共聚物构型的混合物。此外，本公开提供了用于合成上述聚合物并用于与靶标，诊断和治疗剂等分子缀合的新方法。

7. 发明申请

US20110178242A1 Methods for Forming Polymer-Drug Conjugates 有权
标题翻译：形成聚合物 - 药物缀合物的方法
公开(公告)号：US20110178242A1
公开(公告)日：2011-07-21
申请号：US13043438
申请日：2011-03-08
申请人： J. Milton Harris , Antoni Kozlowski , Samuel P. McManus , Michael D. Bentley , Stephen A. Charles
发明人： J. Milton Harris , Antoni Kozlowski , Samuel P. McManus , Michael D. Bentley , Stephen A. Charles
IPC分类号： C08G65/48
CPC分类号： A61K47/60 , A61K31/357 , A61K31/4025 , A61K31/52 , A61K38/11 , A61K38/1816 , A61K38/193 , A61K38/212 , A61K38/215 , A61K38/24 , A61K38/27 , A61K38/37 , C08G65/329 , C08G65/33337 , C08G65/33344
摘要： Methods for preparing polymer-drug conjugates are provided. The disclosed methods involve polymeric reagents comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. Related methods, compositions, preparations, and so forth are also provided.
摘要翻译：提供了制备聚合物 - 药物偶联物的方法。所公开的方法涉及包含以特定顺序排列的原子部分的聚合物试剂，其中该部分位于水溶性聚合物和反应性基团之间。还提供了相关方法，组合物，制剂等。

8. 发明申请

US20100267895A1 Hydrolytically Degradable Polymers and Hydrogels Made Therefrom 有权
标题翻译：水解降解聚合物和水凝胶
公开(公告)号：US20100267895A1
公开(公告)日：2010-10-21
申请号：US12826664
申请日：2010-06-29
申请人： J. Milton Harris , Michael David Bentley , Xuan Zhao , Xiaoming Shen
发明人： J. Milton Harris , Michael David Bentley , Xuan Zhao , Xiaoming Shen
IPC分类号： A61K47/48
CPC分类号： C08G64/0208 , C08G64/0216 , C08G64/183
摘要： Conjugates between a protein and a water soluble polymer comprising multiple degradable carbonate linkages are provided.
摘要翻译：提供蛋白质和包含多个可降解碳酸酯键的水溶性聚合物之间的缀合物。

9. 发明授权

US07655747B2 Soluble, degradable poly(ethylene glycol) derivatives for controllable release of bound molecules into solution 有权
标题翻译：可溶性，可降解的聚（乙二醇）衍生物，用于将结合分子可控地释放到溶液中
公开(公告)号：US07655747B2
公开(公告)日：2010-02-02
申请号：US11051728
申请日：2005-02-04
申请人： J. Milton Harris
发明人： J. Milton Harris
IPC分类号： A61K31/74 , A61K31/765
CPC分类号： C08G65/33396 , A61K47/60 , C08G65/33317
摘要： PEG and related polymer derivatives having weak, hydrolytically unstable linkages near the reactive end of the polymer are provided for conjugation to drugs, including proteins, enzymes, small molecules, and others. These derivatives provide a sufficient circulation period for a drug-PEG conjugate, followed by hydrolytic breakdown of the conjugate and release of the bound molecule. In some cases, drugs that demonstrate reduced activity when permanently coupled to PEG maintain a therapeutically suitable activity when coupled to a degradable PEG in accordance with the invention. The PEG derivatives of the invention can be used to impart improved water solubility, increased size, a slower rate of kidney clearance, and reduced immunogenicity to a conjugate formed by attachment thereto. Controlled hydrolytic release of the bound molecule into an aqueous environment can then enhance the drug's delivery profile by providing a delivery system which employs such polymers and utilizes the teachings provided herein.
摘要翻译：提供在聚合物的反应性末端附近具有弱的水解不稳定键的PEG和相关的聚合物衍生物用于与药物（包括蛋白质，酶，小分子等）共轭。这些衍生物为药物-PEG缀合物提供足够的循环周期，随后结合物的水解分解和结合分子的释放。在一些情况下，当与PEG永久偶联时表现出降低的活性的药物在与根据本发明的可降解的PEG偶联时，保持治疗上合适的活性。本发明的PEG衍生物可用于赋予改善的水溶性，增加的尺寸，较慢的肾清除速率，以及降低对通过其附着形成的缀合物的免疫原性。然后通过提供使用这种聚合物并利用本文提供的教导的递送系统，将结合的分子控制的水解释放到水性环境中可以增强药物的递送分布。

10. 发明授权

US07030278B2 Polyethylene(Glycol) derivatives with proximal reactive groups 有权
标题翻译：具有近端反应性基团的聚乙烯（乙二醇）衍生物
公开(公告)号：US07030278B2
公开(公告)日：2006-04-18
申请号：US10668456
申请日：2003-09-23
申请人： J. Milton Harris , Antoni Kozlowski
发明人： J. Milton Harris , Antoni Kozlowski
IPC分类号： C07C49/00 , C07C49/21 , C07C49/105 , C07C49/385 , C07C49/587
CPC分类号： C08G65/33396 , A61K47/60 , C08G65/329 , C08G65/33313 , C08G65/33337 , Y10S530/816
摘要： An activated, substantially water soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated poly(ethylene glycol) and the biologically active agent.
摘要翻译：提供活化的基本上水溶性的聚（乙二醇），其具有直链或支链的聚（乙二醇）主链和至少一个通过水解稳定键连接至主链的末端，其中末端是支链的且具有近端反应性基团。自由活性基团能够与生物活性剂如蛋白质或肽中的活性部分反应，从而在活化的聚（乙二醇）与生物活性剂之间形成共轭物。

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