AU6048294A - Modified insulin-like growth factors - Google Patents

Modified insulin-like growth factors

Info

Publication number: AU6048294A
Authority: AU; Australia
Prior art keywords: igf; mutein; peg; conjugate; free cysteine
Prior art date: 1992-11-25
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

AU60482/94A

Other languages

English (en)

Inventor

George N. Cox

Martin J McDermott

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Amgen Boulder Inc

Original Assignee

Amgen Boulder Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-11-25

Filing date

1993-11-24

Publication date

1994-06-22

1993-11-24 Application filed by Amgen Boulder Inc filed Critical Amgen Boulder Inc

1994-06-22 Publication of AU6048294A publication Critical patent/AU6048294A/en

Status Abandoned legal-status Critical Current

Links

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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
- A—HUMAN NECESSITIES
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- 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
- 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

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
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Pharmacology & Pharmacy (AREA)
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Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
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Endocrinology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Medicinal Preparation (AREA)

AU60482/94A 1992-11-25 1993-11-24 Modified insulin-like growth factors Abandoned AU6048294A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US98051992A	1992-11-25	1992-11-25
US980519		1992-11-25
PCT/US1993/011458 WO1994012219A2 (en)	1992-11-25	1993-11-24	Modified insulin-like growth factors

Publications (1)

Publication Number	Publication Date
AU6048294A true AU6048294A (en)	1994-06-22

Family

ID=25527621

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU60482/94A Abandoned AU6048294A (en)	1992-11-25	1993-11-24	Modified insulin-like growth factors

Country Status (6)

Country	Link
EP (1)	EP0679095A1 (de)
JP (1)	JPH08506095A (de)
KR (1)	KR950703999A (de)
AU (1)	AU6048294A (de)
CA (1)	CA2149048A1 (de)
WO (1)	WO1994012219A2 (de)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5166322A (en) *	1989-04-21	1992-11-24	Genetics Institute	Cysteine added variants of interleukin-3 and chemical modifications thereof
WO1995032003A1 (en) *	1994-05-24	1995-11-30	Amgen Boulder Inc.	Modified insulin-like growth factors
US5824784A (en)	1994-10-12	1998-10-20	Amgen Inc.	N-terminally chemically modified protein compositions and methods
US7122636B1 (en)	1997-02-21	2006-10-17	Genentech, Inc.	Antibody fragment-polymer conjugates and uses of same
US6870033B1 (en)	1997-02-21	2005-03-22	Genentech, Inc.	Antibody fragment-polymer conjugates and humanized anti-IL-8 monoclonal antibodies
US20080076706A1 (en)	1997-07-14	2008-03-27	Bolder Biotechnology, Inc.	Derivatives of Growth Hormone and Related Proteins, and Methods of Use Thereof
US6753165B1 (en)	1999-01-14	2004-06-22	Bolder Biotechnology, Inc.	Methods for making proteins containing free cysteine residues
US7495087B2 (en)	1997-07-14	2009-02-24	Bolder Biotechnology, Inc.	Cysteine muteins in the C-D loop of human interleukin-11
US7153943B2 (en)	1997-07-14	2006-12-26	Bolder Biotechnology, Inc.	Derivatives of growth hormone and related proteins, and methods of use thereof
ES2297889T3 (es)	1997-07-14	2008-05-01	Bolder Biotechnology, Inc.	Derivados de hormona de crecimiento y proteinas relacionadas.
US7270809B2 (en)	1997-07-14	2007-09-18	Bolder Biotechnology, Inc.	Cysteine variants of alpha interferon-2
US7005504B2 (en)	1998-01-22	2006-02-28	Genentech, Inc.	Antibody fragment-peg conjugates
US6458355B1 (en)	1998-01-22	2002-10-01	Genentech, Inc.	Methods of treating inflammatory disease with anti-IL-8 antibody fragment-polymer conjugates
US6468532B1 (en)	1998-01-22	2002-10-22	Genentech, Inc.	Methods of treating inflammatory diseases with anti-IL-8 antibody fragment-polymer conjugates
AU3548999A (en)	1998-04-03	1999-10-25	Chiron Corporation	Use of igfi for treating articular cartilage disorders
US8288126B2 (en)	1999-01-14	2012-10-16	Bolder Biotechnology, Inc.	Methods for making proteins containing free cysteine residues
CA2359345A1 (en)	1999-01-14	2000-07-20	Bolder Biotechnology, Inc.	Methods for making proteins containing free cysteine residues
DE60022336T2 (de)	1999-04-02	2006-06-22	Ajinomoto Co., Inc.	Vefahren zur herstellung von peptiduntereinheiten aus polymer-proteinen
US6309633B1 (en) *	1999-06-19	2001-10-30	Nobex Corporation	Amphiphilic drug-oligomer conjugates with hydroyzable lipophile components and methods for making and using the same
IL152804A0 (en) *	2000-05-16	2003-06-24	Bolder Biotechnology Inc	Methods for refolding proteins containing free cysteine residues
EP1501866A4 (de)	2001-10-02	2006-02-08	Genentech Inc	Varianten des liganden apo-2 und verwendungen davon
EP2500032A1 (de)	2002-06-24	2012-09-19	Genentech, Inc.	APO-2-Liganden-/Trailvarianten und Verwendungen dafür
US20060228331A1 (en)	2003-10-10	2006-10-12	Novo Nordisk A/S	IL-21 Derivatives and variants
EP1674113A1 (de) *	2004-12-22	2006-06-28	F. Hoffmann-La Roche Ag	Konjugate von insulinähnlichem Wachstumfaktor-1 und Poly(Ethylenglykol)
ES2553160T3 (es) *	2005-06-17	2015-12-04	Novo Nordisk Health Care Ag	Reducción y derivatización selectivas de proteínas Factor VII transformadas por ingeniería que comprenden al menos una cisteína no nativa
WO2007041614A2 (en)	2005-10-03	2007-04-12	Bolder Biotechnology, Inc.	Long acting vegf inhibitors and methods of use
JP4958975B2 (ja)	2006-08-31	2012-06-20	エフ．ホフマン−ラロシュアーゲー	インスリン様増殖因子ｉの製造方法
CL2007002502A1 (es)	2006-08-31	2008-05-30	Hoffmann La Roche	Variantes del factor de crecimiento similar a insulina-1 humano (igf-1) pegilados en lisina; metodo de produccion; proteina de fusion que la comprende; y su uso para tratar la enfermedad de alzheimer.
JP2010507382A (ja)	2006-10-26	2010-03-11	ノヴォノルディスクアクティーゼルスカブ	Ｉｌ−２１変異体
WO2008076933A2 (en)	2006-12-14	2008-06-26	Bolder Biotechnology, Inc.	Long acting proteins and peptides and methods of making and using the same
CA2786340C (en) *	2010-02-11	2017-08-22	F. Hoffmann-La Roche Ag	Igf-i poly (ethylene glycol) conjugates
SG11201601044XA (en)	2013-08-12	2016-03-30	Genentech Inc	Compositions and method for treating complement-associated conditions
AU2015253042A1 (en)	2014-05-01	2016-10-20	Genentech, Inc.	Anti-factor D antibody variants and uses thereof
US10407510B2 (en)	2015-10-30	2019-09-10	Genentech, Inc.	Anti-factor D antibodies and conjugates
EP3368090A1 (de)	2015-10-30	2018-09-05	H. Hoffnabb-La Roche Ag	Anti-faktor-d-antikörpervarianten-konjugate und verwendungen davon
AU2021242249A1 (en)	2020-03-24	2022-08-18	Genentech, Inc.	Tie2-binding agents and methods of use

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5206344A (en) *	1985-06-26	1993-04-27	Cetus Oncology Corporation	Interleukin-2 muteins and polymer conjugation thereof
DK0458064T3 (da) *	1990-05-04	1998-04-27	American Cyanamid Co	Stabilisering af somatotropiner ved modificering af cysteinrester

1993
- 1993-11-24 EP EP94907044A patent/EP0679095A1/de not_active Withdrawn
- 1993-11-24 AU AU60482/94A patent/AU6048294A/en not_active Abandoned
- 1993-11-24 JP JP6513381A patent/JPH08506095A/ja active Pending
- 1993-11-24 CA CA002149048A patent/CA2149048A1/en not_active Abandoned
- 1993-11-24 WO PCT/US1993/011458 patent/WO1994012219A2/en not_active Ceased
- 1993-11-24 KR KR1019950702108A patent/KR950703999A/ko not_active Withdrawn

Also Published As

Publication number	Publication date
EP0679095A1 (de)	1995-11-02
KR950703999A (ko)	1995-11-17
CA2149048A1 (en)	1994-06-09
WO1994012219A2 (en)	1994-06-09
JPH08506095A (ja)	1996-07-02
WO1994012219A3 (en)	1994-07-21

Publication	Publication Date	Title
AU6048294A (en)	1994-06-22	Modified insulin-like growth factors
WO1995032003A1 (en)	1995-11-30	Modified insulin-like growth factors
JP4949844B2 (ja)	2012-06-13	エリスロポエチン受容体に結合する新規ペプチド
US6703480B1 (en)	2004-03-09	Peptide dimers as agonists of the erythropoientin (EPO) receptor, and associated methods of synthesis and use
US6420339B1 (en)	2002-07-16	Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility
JP2007530441A (ja)	2007-11-01	エリスロポエチン受容体に結合する新規ペプチド
JP5961730B2 (ja)	2016-08-02	修飾されたエリスロポエチン
JPH06228199A (ja)	1994-08-16	血液脳関門通過可能なペプチド結合体
JPH08301899A (ja)	1996-11-19	Ｉｇｆ−１スーパーアゴニスト
WO1996033216A1 (en)	1996-10-24	Truncated igf-i
WO1993019084A1 (en)	1993-09-30	Refolding and purification of insulin-like growth factor i
EA009289B1 (ru)	2007-12-28	ЛЕЧЕНИЕ ХРОНИЧЕСКОЙ ВОСПАЛИТЕЛЬНОЙ ДЕМИЕЛИНИЗИРУЮЩЕЙ ПОЛИНЕВРОПАТИИ С ИСПОЛЬЗОВАНИЕМ β-ИНТЕРФЕРОНА
KR19990022716A (ko)	1999-03-25	골 자극 인자
JP2007523840A (ja)	2007-08-23	ケラチノサイト増殖因子アゴニストおよびカストリン化合物を組み合わせた使用
AU6093794A (en)	1994-08-15	Wound healing composition
US20090042802A1 (en)	2009-02-12	Compounds and peptides that bind the kgf receptor
RU2119800C1 (ru)	1998-10-10	Аналог пептида фактора гормона роста (фгр), способ стимулирования секреции гормона роста и композиция для стимулирования секреции
JP2008519858A (ja)	2008-06-12	エリスロポエチンレセプターに結合する新規ペプチド
US20090088374A1 (en)	2009-04-02	Novel use
WO2004005335A2 (en)	2004-01-15	Multimerised growth hormone fusion proteins
JPH03180192A (ja)	1991-08-06	遺伝子組換えによるヒトプロＴＧＦ―β１の製造
US20090137465A1 (en)	2009-05-28	Novel use