ZA200105932B - GCSF conjugates. - Google Patents
GCSF conjugates. Download PDFInfo
- Publication number
- ZA200105932B ZA200105932B ZA200105932A ZA200105932A ZA200105932B ZA 200105932 B ZA200105932 B ZA 200105932B ZA 200105932 A ZA200105932 A ZA 200105932A ZA 200105932 A ZA200105932 A ZA 200105932A ZA 200105932 B ZA200105932 B ZA 200105932B
- Authority
- ZA
- South Africa
- Prior art keywords
- conjugates
- conjugate
- gcsf
- peg
- mutein
- Prior art date
Links
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Classifications
-
- 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
- A61K47/00—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
- A61K47/50—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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
- Polyethers (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11791799P | 1999-01-29 | 1999-01-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200105932B true ZA200105932B (en) | 2002-10-18 |
Family
ID=22375505
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200105932A ZA200105932B (en) | 1999-01-29 | 2001-07-18 | GCSF conjugates. |
Country Status (26)
Country | Link |
---|---|
US (4) | US20030130193A1 (pt) |
EP (1) | EP1157037B1 (pt) |
JP (1) | JP2002540065A (pt) |
KR (1) | KR100689212B1 (pt) |
CN (1) | CN1376164A (pt) |
AT (1) | ATE246202T1 (pt) |
AU (1) | AU2618500A (pt) |
BG (1) | BG65213B1 (pt) |
BR (1) | BR0007781A (pt) |
CA (1) | CA2361766C (pt) |
CZ (1) | CZ300546B6 (pt) |
DE (1) | DE60004172T2 (pt) |
DK (1) | DK1157037T3 (pt) |
EA (2) | EA004685B1 (pt) |
ES (1) | ES2204509T3 (pt) |
HK (1) | HK1049673A1 (pt) |
HU (1) | HU228488B1 (pt) |
IL (1) | IL144361A0 (pt) |
MX (1) | MXPA01007609A (pt) |
NO (1) | NO331787B1 (pt) |
NZ (1) | NZ513113A (pt) |
PT (1) | PT1157037E (pt) |
RS (1) | RS50928B (pt) |
SK (1) | SK286898B6 (pt) |
WO (1) | WO2000044785A1 (pt) |
ZA (1) | ZA200105932B (pt) |
Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1376164A (zh) * | 1999-01-29 | 2002-10-23 | 霍夫曼-拉罗奇有限公司 | Gcsf缀合物 |
US6646110B2 (en) | 2000-01-10 | 2003-11-11 | Maxygen Holdings Ltd. | G-CSF polypeptides and conjugates |
US6831158B2 (en) | 2000-01-10 | 2004-12-14 | Maxygen Holdings Ltd. | G-CSF conjugates |
US6555660B2 (en) | 2000-01-10 | 2003-04-29 | Maxygen Holdings Ltd. | G-CSF conjugates |
JP5170931B2 (ja) | 2000-10-16 | 2013-03-27 | 中外製薬株式会社 | Peg修飾エリスロポエチン |
DK2279753T3 (en) * | 2001-10-10 | 2015-11-23 | Novo Nordisk As | The conversion of peptides and glycokonjugering |
US7214660B2 (en) | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
US7173003B2 (en) | 2001-10-10 | 2007-02-06 | Neose Technologies, Inc. | Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF |
IL161251A0 (en) * | 2001-10-10 | 2004-09-27 | Neose Technologies Inc | Remodeling and glycoconjugation of peptides |
BR0214451A (pt) * | 2001-11-20 | 2006-05-30 | Pharmacia Corp | conjugados do hormÈnio do crescimento humano quimicamente modificado |
CN100337689C (zh) * | 2002-07-24 | 2007-09-19 | 弗·哈夫曼-拉罗切有限公司 | 聚亚烷基二醇酸加合物 |
US7695723B2 (en) | 2002-12-31 | 2010-04-13 | Sygnis Bioscience Gmbh & Co. Kg | Methods of treating neurological conditions with hematopoietic growth factors |
US7785601B2 (en) | 2002-12-31 | 2010-08-31 | Sygnis Bioscience Gmbh & Co. Kg | Methods of treating neurological conditions with hematopoietic growth factors |
MXPA05010773A (es) | 2003-04-09 | 2005-12-12 | Neose Technologies Inc | Metodos de glicopegilacion y proteinas/peptidos producidos por los metodos. |
WO2005012484A2 (en) | 2003-07-25 | 2005-02-10 | Neose Technologies, Inc. | Antibody-toxin conjugates |
EP1667706A4 (en) * | 2003-08-22 | 2009-06-24 | Queensland Inst Med Res | G-CSF DERIVATIVE FOR INDUCING IMMUNOLOGICAL TOLERANCE |
US20080305992A1 (en) | 2003-11-24 | 2008-12-11 | Neose Technologies, Inc. | Glycopegylated erythropoietin |
JP5948627B2 (ja) | 2004-10-29 | 2016-07-20 | レイショファーム ゲーエムベーハー | 線維芽細胞成長因子(fgf)のリモデリングと糖質ペグ化 |
EP1858543B1 (en) | 2005-01-10 | 2013-11-27 | BioGeneriX AG | Glycopegylated granulocyte colony stimulating factor |
US20060174362A1 (en) * | 2005-02-01 | 2006-08-03 | Origen Therapeutics, Inc. | Long-term culture of avian primordial germ cells (PGCs) |
EP2386571B1 (en) | 2005-04-08 | 2016-06-01 | ratiopharm GmbH | Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants |
CN101193658B (zh) | 2005-06-01 | 2011-08-31 | 马克西根控股公司 | 聚乙二醇化g-csf多肽及其产生方法 |
KR101304157B1 (ko) | 2005-06-16 | 2013-09-06 | 넥타르 테라퓨틱스 | 분해가능한 결합을 갖는 컨주게이트 및 이러한 컨주게이트제조에 유용한 고분자 시약 |
JP2009503111A (ja) * | 2005-08-04 | 2009-01-29 | ネクター セラピューティックス エイエル,コーポレイション | G−csf部分および重合体の複合体 |
US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
JP2007112924A (ja) * | 2005-10-21 | 2007-05-10 | National Institute For Materials Science | 高分子架橋剤及びこの架橋剤を用いたリポソーム又は細胞の架橋体 |
WO2007056191A2 (en) | 2005-11-03 | 2007-05-18 | Neose Technologies, Inc. | Nucleotide sugar purification using membranes |
CN101002943B (zh) * | 2006-01-17 | 2012-02-01 | 中国科学院过程工程研究所 | 支链peg-gcsf和peg-gmcsf结合物及其制备方法 |
US9187532B2 (en) | 2006-07-21 | 2015-11-17 | Novo Nordisk A/S | Glycosylation of peptides via O-linked glycosylation sequences |
ITMI20061624A1 (it) | 2006-08-11 | 2008-02-12 | Bioker Srl | Mono-coniugati sito-specifici di g-csf |
JP2010505874A (ja) | 2006-10-03 | 2010-02-25 | ノヴォ ノルディスク アー/エス | ポリペプチドコンジュゲートの精製方法 |
US20100316631A1 (en) * | 2006-10-19 | 2010-12-16 | The Uab Research Foundation | Water Soluble Curcumin-Based Compounds |
KR101079993B1 (ko) * | 2006-11-17 | 2011-11-04 | 동아제약주식회사 | 폴리에틸렌글리콜 과립구 콜로니 자극인자 접합체 |
JP2008125952A (ja) * | 2006-11-24 | 2008-06-05 | National Institute For Materials Science | 複合架橋体 |
CN101245109B (zh) * | 2007-02-12 | 2011-12-14 | 杭州九源基因工程有限公司 | 一种聚乙二醇单修饰的重组人粒细胞集落刺激因子突变体及其制备方法 |
KR20150064246A (ko) | 2007-04-03 | 2015-06-10 | 바이오제너릭스 게엠베하 | 글리코페길화 g―csf를 이용하는 치료 방법 |
CA2690611C (en) | 2007-06-12 | 2015-12-08 | Novo Nordisk A/S | Improved process for the production of nucleotide sugars |
CL2008002053A1 (es) | 2007-07-17 | 2009-05-22 | Hoffmann La Roche | Metodo para la purificacion de una eritropoyetina monopeguilada (epompeg) que consiste en proporcionar una solucion que contiene eritropoyetina mono, poli y no peguilada y hacerla pasar por dos pasos de cromatografia de intercambio cationico y metodo para producir epo mpeg que incluye metodo de purificacion. |
AR067536A1 (es) | 2007-07-17 | 2009-10-14 | Hoffmann La Roche | Metodo para obtener una eritropoyetina mono-pegilada en una forma sustancialmente homogenea |
CN101352573B (zh) * | 2007-07-27 | 2011-02-09 | 杭州九源基因工程有限公司 | 聚乙二醇单修饰的重组人集落细胞刺激因子赖氨酸缺陷体 |
US8629104B2 (en) | 2008-02-18 | 2014-01-14 | Jiangsu Hengrui Medicine Co. Ltd. | G-CSF and water-soluble polymer conjugate |
WO2009108806A1 (en) | 2008-02-27 | 2009-09-03 | Novo Nordisk A/S | Conjugated factor viii molecules |
RU2409669C9 (ru) | 2008-08-18 | 2012-05-27 | ООО "Саентифик Фьючер Менеджмент" ("Scientific Future Management", "SFM") | Способ иммобилизации биологически активного вещества (бав) на носитель (варианты) и конъюгат бав-носитель, полученный данными способами |
ES2435272T3 (es) | 2008-09-23 | 2013-12-17 | F. Hoffmann-La Roche Ag | Purificación de la eritropoyetina |
MX339559B (es) | 2010-02-11 | 2016-05-31 | Hoffmann La Roche | Conjugados de igf-i poli(etilenglicol). |
RU2566267C2 (ru) | 2010-09-14 | 2015-10-20 | Ф. Хоффманн-Ля Рош Аг | Способ очистки пегилированного эритропоэтина |
US8889630B2 (en) | 2011-12-23 | 2014-11-18 | Carlos Lopez | Method for hair regrowth using Granulocyte-Colony Stimulating Factor |
CA3027143A1 (en) | 2016-07-15 | 2018-01-18 | F. Hoffmann-La Roche Ag | Method for purifying pegylated erythropoietin |
JP7046173B2 (ja) | 2017-10-11 | 2022-04-01 | エランコ・ユーエス・インコーポレイテッド | ブタg-csf変異体とその使用 |
HRP20220041T1 (hr) | 2017-12-29 | 2022-04-15 | F. Hoffmann - La Roche Ag | Postupak za dobivanje pegiliranog proteinskog pripravka |
HRP20220388T1 (hr) | 2017-12-29 | 2022-05-27 | F. Hoffmann - La Roche Ag | Postupak za dobivanje pegiliranog proteinskog pripravka |
KR102523239B1 (ko) | 2017-12-29 | 2023-04-18 | 에프. 호프만-라 로슈 아게 | 페길화 단백질 조성물을 제공하기 위한 방법 |
TW202241922A (zh) * | 2020-12-23 | 2022-11-01 | 愛爾蘭商爵士製藥愛爾蘭有限公司 | 純化電荷遮蔽的融合蛋白質之方法 |
Family Cites Families (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1609546A (en) * | 1925-11-19 | 1926-12-07 | Petroleum Rectifying Co | Process of separating water from emulsions |
US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US4002531A (en) * | 1976-01-22 | 1977-01-11 | Pierce Chemical Company | Modifying enzymes with polyethylene glycol and product produced thereby |
US6936694B1 (en) * | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
DE3380726D1 (en) * | 1982-06-24 | 1989-11-23 | Japan Chem Res | Long-acting composition |
US4514497B1 (en) * | 1983-12-30 | 1998-02-24 | Novagene Inc | Modified live pseudorabies viruses |
JPS61227526A (ja) * | 1984-07-25 | 1986-10-09 | Chugai Pharmaceut Co Ltd | 新規なコロニー刺激因子 |
US5532341A (en) * | 1985-03-28 | 1996-07-02 | Sloan-Kettering Institute For Cancer Research | Human pluripotent hematopoietic colony stimulating factor |
US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
US4810643A (en) * | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
US4791192A (en) * | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
US4894226A (en) * | 1986-11-14 | 1990-01-16 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polyproline conjugation |
US5194592A (en) * | 1986-12-23 | 1993-03-16 | Kyowa Hakko Kogyo Co. Ltd. | Monoclonal antibodies to novel polypeptide derivatives of human granulocyte colony stimulating factor |
US5362853A (en) * | 1986-12-23 | 1994-11-08 | Kyowa Hakko Kogyo Co., Ltd. | Polypeptide derivatives of human granulocyte colony stimulating factor |
US5214132A (en) * | 1986-12-23 | 1993-05-25 | Kyowa Hakko Kogyo Co., Ltd. | Polypeptide derivatives of human granulocyte colony stimulating factor |
US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
US4847325A (en) * | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
CA1340810C (en) * | 1988-03-31 | 1999-11-02 | Motoo Yamasaki | Polypeptide derivatives of human granulocyte colony stimulating factor |
US5218092A (en) * | 1988-09-29 | 1993-06-08 | Kyowa Hakko Kogyo Co., Ltd. | Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains |
US5349052A (en) * | 1988-10-20 | 1994-09-20 | Royal Free Hospital School Of Medicine | Process for fractionating polyethylene glycol (PEG)-protein adducts and an adduct for PEG and granulocyte-macrophage colony stimulating factor |
US6166183A (en) * | 1992-11-30 | 2000-12-26 | Kirin-Amgen, Inc. | Chemically-modified G-CSF |
ATE135370T1 (de) * | 1988-12-22 | 1996-03-15 | Kirin Amgen Inc | Chemisch modifizierte granulocytenkolonie erregender faktor |
US5166322A (en) * | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
US5372808A (en) * | 1990-10-17 | 1994-12-13 | Amgen Inc. | Methods and compositions for the treatment of diseases with consensus interferon while reducing side effect |
US5252714A (en) * | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
US5281698A (en) * | 1991-07-23 | 1994-01-25 | Cetus Oncology Corporation | Preparation of an activated polymer ester for protein conjugation |
US5382657A (en) * | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
US5581476A (en) * | 1993-01-28 | 1996-12-03 | Amgen Inc. | Computer-based methods and articles of manufacture for preparing G-CSF analogs |
US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
JP3708151B2 (ja) * | 1994-12-15 | 2005-10-19 | 協和醗酵工業株式会社 | Peg化したヒト顆粒球コロニー刺激因子の定量法 |
US5672662A (en) * | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
KR0176625B1 (ko) * | 1996-11-05 | 1999-04-01 | 삼성전자주식회사 | 적외선 물체검출장치 |
CN1376164A (zh) * | 1999-01-29 | 2002-10-23 | 霍夫曼-拉罗奇有限公司 | Gcsf缀合物 |
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