CN107949565A - 聚乙二醇化粒细胞集落刺激因子(gcsf) - Google Patents
聚乙二醇化粒细胞集落刺激因子(gcsf) Download PDFInfo
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- CN107949565A CN107949565A CN201680047209.0A CN201680047209A CN107949565A CN 107949565 A CN107949565 A CN 107949565A CN 201680047209 A CN201680047209 A CN 201680047209A CN 107949565 A CN107949565 A CN 107949565A
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
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- Veterinary Medicine (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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- Diabetes (AREA)
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- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US201562174373P | 2015-06-11 | 2015-06-11 | |
| US62/174373 | 2015-06-11 | ||
| US201562184042P | 2015-06-24 | 2015-06-24 | |
| US62/184042 | 2015-06-24 | ||
| PCT/US2016/037278 WO2016201448A2 (en) | 2015-06-11 | 2016-06-13 | Pegylated granulocyte colony stimulating factor (gcsf) |
Publications (1)
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| CN107949565A true CN107949565A (zh) | 2018-04-20 |
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| MX2022011630A (es) * | 2020-03-20 | 2022-12-02 | Amgen Inc | Determinación del extremo n libre del pegfilgrastim utilizando una proteasa ácida. |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1897812A (zh) * | 2003-12-03 | 2007-01-17 | 尼奥斯技术有限公司 | 糖聚乙二醇化的粒细胞集落刺激因子 |
| CN101193658A (zh) * | 2005-06-01 | 2008-06-04 | 马克西根控股公司 | 聚乙二醇化g-csf多肽及其产生方法 |
| CN101328213A (zh) * | 2001-07-11 | 2008-12-24 | 马克西根控股公司 | G-csf偶联物 |
| CN101602801A (zh) * | 2008-06-13 | 2009-12-16 | 杭州九源基因工程有限公司 | 聚乙二醇单修饰的重组人粒细胞集落刺激因子突变体 |
| CN104109235A (zh) * | 2014-05-30 | 2014-10-22 | 厦门赛诺邦格生物科技有限公司 | 一种具有氮原子支化中心的单一官能化聚乙二醇、制备方法及其生物相关物质 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020177688A1 (en) * | 1988-12-22 | 2002-11-28 | Kirin-Amgen, Inc., | Chemically-modified G-CSF |
| US6565841B1 (en) * | 1991-03-15 | 2003-05-20 | Amgen, Inc. | Pulmonary administration of granulocyte colony stimulating factor |
| AU1676992A (en) * | 1991-03-18 | 1992-10-21 | Enzon, Inc. | Hydrazine containing conjugates of polypeptides and glycopolypeptides with polymers |
| US5581476A (en) * | 1993-01-28 | 1996-12-03 | Amgen Inc. | Computer-based methods and articles of manufacture for preparing G-CSF analogs |
| US5981709A (en) * | 1997-12-19 | 1999-11-09 | Enzon, Inc. | α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same |
| US6646110B2 (en) * | 2000-01-10 | 2003-11-11 | Maxygen Holdings Ltd. | G-CSF polypeptides and conjugates |
| WO2003006501A2 (en) * | 2001-07-11 | 2003-01-23 | Maxygen Holdings, Ltd. | G-csf conjugates |
| US7144978B2 (en) * | 2002-01-15 | 2006-12-05 | Pan Asia Bio Co., Ltd. | Multidrop tree branching functional polyethylene glycol, methods of preparing and using same |
| ES2536710T3 (es) * | 2002-03-25 | 2015-05-27 | Arimed Inc. | Nuevo uso terapéutico de LPC, ligandos agonistas específicos para el receptor G2A |
| US7892745B2 (en) * | 2003-04-24 | 2011-02-22 | Xdx, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
| CA2617064A1 (en) * | 2005-08-04 | 2007-02-15 | Nektar Therapeutics Al, Corporation | Conjugates of a g-csf moiety and a polymer |
| CU23556A1 (es) * | 2005-11-30 | 2010-07-20 | Ct Ingenieria Genetica Biotech | Estructura polimérica semejante a dendrímero para la obtención de conjugados de interés farmacéutico |
| US20110104100A1 (en) * | 2007-10-04 | 2011-05-05 | Medistem Laboratories, Inc. | Compositions and methods of stem cell therapy for autism |
| TW201138831A (en) * | 2009-09-30 | 2011-11-16 | Prolong Pharmaceuticals Inc | Modified granulocyte colony stimulating factor (G-CSF) |
| WO2011075606A2 (en) * | 2009-12-18 | 2011-06-23 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
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2016
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- 2016-06-13 WO PCT/US2016/037278 patent/WO2016201448A2/en not_active Ceased
- 2016-06-13 CA CA2988988A patent/CA2988988A1/en not_active Abandoned
- 2016-06-13 AU AU2016277147A patent/AU2016277147A1/en not_active Abandoned
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2017
- 2017-12-07 IL IL256167A patent/IL256167A/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101328213A (zh) * | 2001-07-11 | 2008-12-24 | 马克西根控股公司 | G-csf偶联物 |
| CN1897812A (zh) * | 2003-12-03 | 2007-01-17 | 尼奥斯技术有限公司 | 糖聚乙二醇化的粒细胞集落刺激因子 |
| CN101193658A (zh) * | 2005-06-01 | 2008-06-04 | 马克西根控股公司 | 聚乙二醇化g-csf多肽及其产生方法 |
| CN101602801A (zh) * | 2008-06-13 | 2009-12-16 | 杭州九源基因工程有限公司 | 聚乙二醇单修饰的重组人粒细胞集落刺激因子突变体 |
| CN104109235A (zh) * | 2014-05-30 | 2014-10-22 | 厦门赛诺邦格生物科技有限公司 | 一种具有氮原子支化中心的单一官能化聚乙二醇、制备方法及其生物相关物质 |
Non-Patent Citations (1)
| Title |
|---|
| PARVEEN S, SAHOO S K: "《Nanomedicine:Clinical Applications of Polyethylene Glycol Conjugated Proteins and Drugs》", 《CLINICAL PHARMACOKINETICS》 * |
Also Published As
| Publication number | Publication date |
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| JP2018519359A (ja) | 2018-07-19 |
| EP3307757A4 (en) | 2019-03-13 |
| CA2988988A1 (en) | 2016-12-15 |
| WO2016201448A3 (en) | 2017-02-09 |
| AU2016277147A1 (en) | 2018-01-18 |
| US20160361426A1 (en) | 2016-12-15 |
| EP3307757A2 (en) | 2018-04-18 |
| IL256167A (en) | 2018-04-30 |
| RU2018100425A3 (enExample) | 2019-11-21 |
| KR20180017104A (ko) | 2018-02-20 |
| RU2018100425A (ru) | 2019-07-15 |
| WO2016201448A2 (en) | 2016-12-15 |
| MX2017016103A (es) | 2018-05-22 |
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