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1. 发明授权

US11795135B2 Prostacyclin compounds, compositions and methods of use thereof 有权
公开(公告)号：US11795135B2
公开(公告)日：2023-10-24
申请号：US17186658
申请日：2021-02-26
申请人： Insmed Incorporated
发明人： Vladimir Malinin , Walter Perkins , Franziska Leifer , Donna Konicek , Zhili Li , Adam Plaunt
IPC分类号： C07C69/734 , C07C69/712 , A61K47/60 , A61K47/54 , C07C69/736 , C07C69/753 , C07C235/22 , C07C235/20 , A61K31/165 , A61K31/216 , A61K31/225 , A61K47/06 , A61K9/00 , A61P9/12 , A61P11/00 , A61K9/10 , A61K9/14 , A61K9/51 , A61K47/14 , A61K47/24 , A61K47/28 , A61K47/34 , A61M15/00 , A61M16/14
CPC分类号： C07C69/734 , A61K9/0019 , A61K9/0043 , A61K9/0053 , A61K9/0073 , A61K9/0075 , A61K9/0078 , A61K9/10 , A61K9/14 , A61K9/51 , A61K31/165 , A61K31/216 , A61K31/225 , A61K47/06 , A61K47/14 , A61K47/24 , A61K47/28 , A61K47/34 , A61K47/543 , A61K47/544 , A61K47/60 , A61M15/009 , A61M15/0085 , A61M16/14 , A61P9/12 , A61P11/00 , C07C69/712 , C07C69/736 , C07C69/753 , C07C235/20 , C07C235/22 , A61M2202/064 , C07C2601/18 , C07C2603/14
摘要： Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C5-C18 alkyl, branched C5-C18 alkyl, linear C2-C18 alkenyl, branched C3-C18 alkenyl, aryl, aryl-C1-C18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

2. 发明申请

US20190337888A1 METHODS OF MANUFACTURING TREPROSTINIL AND TREPROSTINIL DERIVATIVE PRODRUGS 审中-公开
公开(公告)号：US20190337888A1
公开(公告)日：2019-11-07
申请号：US16417958
申请日：2019-05-21
申请人： Insmed Incorporated
发明人： Vladimir Malinin , Walter Perkins , Franziska Leifer , Donna M. Konicek , Zhili Li , Adam Plaunt
IPC分类号： C07C231/02 , C07C67/08
摘要： Methods for making prodrugs of trepreostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C5-C18 alkyl, branched C5-C18 alkyl, linear C2-C18 alkenyl, branched C3-C18 alkenyl, aryl, aryl-C1-C18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide). The linkage, in one embodiment, is via an amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. The compounds provided herein can be used to treat pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension.

3. 发明申请

US20170320813A1 METHODS OF MANUFACTURING TREPROSTINIL AND TREPROSTINIL DERIVATIVE PRODRUGS 审中-公开
公开(公告)号：US20170320813A1
公开(公告)日：2017-11-09
申请号：US15527811
申请日：2015-11-18
申请人： Insmed Incorporated
发明人： Vladimir Malinin , Walter Perkins , Franziska Leifer , Donna M. Konicek , Zhili Li , Adam Plaunt
IPC分类号： C07C231/02 , C07C67/08 , C07C2601/18 , C07C2602/24
CPC分类号： C07C231/02 , C07C67/08 , C07C2601/18 , C07C2602/24 , C07C235/06 , C07C235/12 , C07C235/14 , C07C69/712
摘要： Methods for making prodrugs of trepreostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C5-C18 alkyl, branched C5-C18 alkyl, linear C2-C18 alkenyl, branched C3-C18 alkenyl, aryl, aryl-C1-C18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide). The linkage, in one embodiment, is via an amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. The compounds provided herein can be used to treat pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension.

4. 发明申请

US20170049739A1 PROSTACYCLIN COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF 审中-公开
标题翻译：前体化合物，组合物及其使用方法
公开(公告)号：US20170049739A1
公开(公告)日：2017-02-23
申请号：US15031604
申请日：2014-10-24
申请人： INSMED INCORPORATED
发明人： Adam Plaunt , Walter Perkins , Franziska Leifer , Donna M. Konicek , Zhili Li , Vladimir Malinin
IPC分类号： A61K31/225 , A61K9/00
CPC分类号： C07C69/734 , A61K9/0019 , A61K9/0043 , A61K9/0053 , A61K9/0073 , A61K9/0075 , A61K9/0078 , A61K9/10 , A61K9/14 , A61K9/51 , A61K31/165 , A61K31/216 , A61K31/225 , A61K47/06 , A61K47/14 , A61K47/24 , A61K47/28 , A61K47/34 , A61K47/543 , A61K47/544 , A61K47/60 , A61M15/0085 , A61M15/009 , A61M16/14 , A61M2202/064 , A61P9/12 , A61P11/00 , C07C69/712 , C07C69/736 , C07C69/753 , C07C235/20 , C07C235/22 , C07C2601/18 , C07C2603/14
摘要： Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C5-C18 alkyl, branched C5-C18 alkyl, linear C2-C18 alkenyl, branched C3-C18 alkenyl, aryl, aryl-C1-C18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.
摘要翻译：前列环素化合物和包含其的组合物在本文中提供。具体地说，包括与直链C 5 -C 18烷基，支链C 5 -C 18烷基，直链C 2 -C 18烯基，支链C 3 -C 18烯基，芳基，芳基-C 1 -C 18烷基或氨基酸或肽（共价连接）共价连接的曲前列素的前列环素化合物例如二肽，三肽，四肽）。在一个实施方案中，连接是经由氨基甲酸酯，酰胺或酯键。本文提供的前列环素化合物还可包括至少一个被至少一个氘原子取代的氢原子。还提供了治疗肺动脉高压（例如肺动脉高压）和肺动脉高压的方法。

5. 发明申请

US20150272880A1 SYSTEMS FOR TREATING PULMONARY INFECTIONS 审中-公开
标题翻译：用于治疗肺部感染的系统
公开(公告)号：US20150272880A1
公开(公告)日：2015-10-01
申请号：US14430179
申请日：2013-05-21
申请人： INSMED INCORPORATED
发明人： Dominique Seidel , Philipp Holzmann , Harald Schulz , Michael Hahn , Walter Perkins , Vladimir Malinin , Xingong Li , Brian Miller
IPC分类号： A61K9/00 , A61M11/00 , A61M11/02 , A61K31/7036 , A61K9/127
CPC分类号： A61K31/7036 , A61K9/0078 , A61K9/127 , A61K9/1271 , A61M11/005 , A61M11/02
摘要： Provided herein are systems for treating a subject with a pulmonary infection, for example, a nontuberculous mycobacterial pulmonary infection, a Burkholderia pulmonary infection, a pulmonary infection associated with bronchiectasis, or a Pseudomonas pulmonary infection. The system includes a pharmaceutical formulation comprising a liposomal aminoglycoside dispersion, and the lipid component of the liposomes consist essentially of electrically neutral lipids. The system also includes a nebulizer which generates an aerosol of the pharmaceutical formulation at a rate greater than about 0.53 gram per minute. The aerosol is delivered to the subject via inhalation for the treatment of the pulmonary infection.
摘要翻译：本文提供用于治疗患有肺部感染的受试者的系统，例如非结核性分枝杆菌肺部感染，伯克霍尔德氏病肺感染，与支气管扩张相关的肺部感染或肺炎假单胞菌感染。该系统包括包含脂质体氨基糖苷分散体的药物制剂，脂质体的脂质组分基本上由电中性脂质组成。该系统还包括雾化器，其以大于约0.53克/分钟的速率产生药物制剂的气溶胶。通过吸入将气溶胶输送给受试者用于治疗肺部感染。

6. 发明申请

US20140314835A1 SUSTAINED RELEASE OF ANTIINFECTIVES 有权
标题翻译：持续释放抗生素
公开(公告)号：US20140314835A1
公开(公告)日：2014-10-23
申请号：US14319018
申请日：2014-06-30
申请人： INSMED INCORPORATED
发明人： Lawrence T. Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
IPC分类号： A61K47/28 , A61K9/127 , A61K45/06 , A61K31/7036
CPC分类号： A61K47/28 , A61K9/0078 , A61K9/127 , A61K9/1277 , A61K31/407 , A61K31/4709 , A61K31/496 , A61K31/545 , A61K31/7036 , A61K31/704 , A61K45/06 , Y02A50/473
摘要： Provided are lipid antiinfective formulations substantially free of anionic lipids with a lipid to antiinfective ratio is about 1:1 to about 4:1, and a mean average diameter of less than about 1 μm. Also provided is a method of preparing a lipid antiinfective formulation comprising an infusion process. Also provided are lipid antiinfective formulations wherein the lipid to drug ratio is about 1:1 or less, about 0.75:1 or less, or about 0.50:1 or less prepared by an in line fusion process. The present invention also relates to a method of treating a patient with a pulmonary infection comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention. The present invention also relates to a method of treating a patient for cystic fibrosis comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention.
摘要翻译：提供基本上不含阴离子脂质的脂质抗感染制剂，其脂质与抗感染比为约1:1至约4:1，平均平均直径小于约1μm。还提供了制备包含输注方法的脂质抗感染制剂的方法。还提供了脂质抗感染制剂，其中通过在线融合方法制备的脂质与药物的比例为约1:1或更低，约0.75:1或更低，或约0.50:1或更低。本发明还涉及治疗患有肺部感染的患者的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染药物。本发明还涉及一种治疗患者囊性纤维化的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染制剂。

7. 发明申请

US20210388028A1 GLYCOPEPTIDE DERIVATIVE COMPOUNDS AND USES THEREOF 有权
公开(公告)号：US20210388028A1
公开(公告)日：2021-12-16
申请号：US17295370
申请日：2019-11-20
申请人： INSMED INCORPORATED
发明人： Donna Konicek , Adam Plaunt , Vladimir Malinin , Walter Perkins , Ryan Heckler
IPC分类号： C07K9/00
摘要： Provided herein are compounds, compositions and methods for the treatment of Gram positive bacterial infections. The infection in some embodiments, is a pulmonary infection. The method for treating the bacterial infection, comprises in one embodiment, administering to a patient in need thereof, a composition comprising an effective amount of a compound a glycopeptide derivative of Formula (I) or (II), or a pharmaceutically acceptable salt of Formula (I) or (II). The bacterial infection can comprise intracellular bacteria, planktonic bacteria and/or bacteria present in a biofilm.

8. 发明授权

US11071769B2 Lipo-glycopeptide cleavable derivatives and uses thereof 有权
公开(公告)号：US11071769B2
公开(公告)日：2021-07-27
申请号：US16615214
申请日：2018-05-22
申请人： Insmed Incorporated
发明人： Ryan Heckler , Donna Konicek , Adam Plaunt , Vladimir Malinin , Walter Perkins
IPC分类号： A61K38/14 , A61P31/04 , A61K9/00
摘要： The present invention provides certain lipo-glycopeptide cleavable derivatives and methods for using the same for the treatment of bacterial infections, for example, pulmonary bacterial infections. The LGPC derivatives include a cleavable moiety that in certain embodiments, is designed to allow for cellular uptake and/or a more rapid clearance of the glycopeptide metabolite (i.e., the cleaved glycopeptide) from the site of administration (e.g., the lung) as compared to the uncleaved LGPC.

9. 发明授权

US09255064B2 Prostacyclin compounds, compositions and methods of use thereof 有权
公开(公告)号：US09255064B2
公开(公告)日：2016-02-09
申请号：US14641104
申请日：2015-03-06
申请人： Insmed Incorporated
发明人： Vladimir Malinin , Walter Perkins , Franziska Leifer , Donna Konicek , Zhili Li , Adam Plaunt
IPC分类号： C07C235/22 , C07C69/736 , C07C69/753 , C07C235/20 , C07C69/712
CPC分类号： A61K31/225 , A61K9/0075 , A61K9/0078 , A61K31/165 , A61K31/216 , A61K47/06 , A61K47/543 , A61K47/544 , A61K47/60 , C07C69/712 , C07C69/736 , C07C69/753 , C07C235/20 , C07C235/22 , C07C2601/18 , C07C2603/14
摘要： Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C5-C18 alkyl, branched C5-C18 alkyl, linear C2-C18 alkenyl, branched C3-C18 alkenyl, aryl, aryl-C1-C18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

10. 发明授权

US11458098B2 Dry powder compositions of treprostinil prodrugs and methods of use thereof 有权
公开(公告)号：US11458098B2
公开(公告)日：2022-10-04
申请号：US16860428
申请日：2020-04-28
申请人： Insmed Incorporated
发明人： Ju Du , Adam Plaunt , Vladimir Malinin
IPC分类号： A61K9/14 , A61K31/216 , A61K31/198
摘要： The present disclosure provides a dry powder composition of treprostinil prodrugs and a method of treating pulmonary hypertension (e.g., pulmonary arterial hypertension), portopulmonary hypertension, or pulmonary fibrosis in a patient in need thereof. The dry powder composition includes (a) from about 0.1 wt % to about 3 wt % of a compound of Formula (I): or an enantiomer, diastereomer, or a pharmaceutically acceptable salt thereof, (b) from about 0.01 wt % to about 3 wt % of DSPE-PEG2000, (c) from about 10 wt % to about 50 wt % of leucine, and the balance being (d) a sugar selected from the group consisting of trehalose and mannitol. The entirety of (a), (b), (c), and (d) is 100 wt %, and R1 is tetradecyl, pentadecyl, hexadecyl, heptadecyl, or octadecyl. The method includes administering an effective amount of the dry powder composition to the lungs of the patient by inhalation via a dry powder inhaler. In certain compositions and methods provided herein, R1 is hexadecyl, e.g., linear hexadecyl.

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