ZA200705146B - Conjugates of insulin-like growth factor-1 (IGF-1) and poly(ethylene glycol) - Google Patents

Conjugates of insulin-like growth factor-1 (IGF-1) and poly(ethylene glycol) Download PDF

Info

Publication number: ZA200705146B
Authority: ZA; South Africa
Prior art keywords: igf; variant; amino acid; peg; lysine
Prior art date: 2004-12-22

Application number

ZA200705146A

Other languages

English (en)

Inventor

Amrein Beat

Lang Kurt

Regula Jorg

Hesse Friederike

Lanzendoerfer Martin

Foser Stefan

Metzger Friedrich

Schaubmar Andreas

Kuenkele Klaus-Peter

Original Assignee

Hoffmann La Roche

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.)

2004-12-22

Filing date

2007-06-21

Publication date

2008-06-25

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34927913&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ZA200705146(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2007-06-21 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2008-06-25 Publication of ZA200705146B publication Critical patent/ZA200705146B/en

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- 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
- C07K14/475—Growth factors; Growth regulators
- 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
- C07K14/575—Hormones
- C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes

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Animal Behavior & Ethology (AREA)
Biochemistry (AREA)
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Proteomics, Peptides & Aminoacids (AREA)
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ZA200705146A 2004-12-22 2007-06-21 Conjugates of insulin-like growth factor-1 (IGF-1) and poly(ethylene glycol) ZA200705146B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP04030415A EP1674113A1 (fr)	2004-12-22	2004-12-22	Conjugués de l'IGF-1 et du poly(éthylène glycol)

Publications (1)

Publication Number	Publication Date
ZA200705146B true ZA200705146B (en)	2008-06-25

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Application Number	Title	Priority Date	Filing Date
ZA200705146A ZA200705146B (en)	2004-12-22	2007-06-21	Conjugates of insulin-like growth factor-1 (IGF-1) and poly(ethylene glycol)

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Country	Link
US (5)	US20060154865A1 (fr)
EP (2)	EP1674113A1 (fr)
JP (1)	JP4954896B2 (fr)
KR (3)	KR20090010138A (fr)
CN (1)	CN101123991B (fr)
AR (1)	AR052842A1 (fr)
AU (1)	AU2005318387B2 (fr)
BR (1)	BRPI0515857A (fr)
CA (1)	CA2592006C (fr)
CR (1)	CR9177A (fr)
EA (1)	EA011284B1 (fr)
IL (1)	IL183966A (fr)
MA (1)	MA29107B1 (fr)
MX (1)	MX2007007479A (fr)
NO (1)	NO20073103L (fr)
NZ (1)	NZ555840A (fr)
TN (1)	TNSN07237A1 (fr)
TW (3)	TW200635604A (fr)
UA (1)	UA93666C2 (fr)
WO (1)	WO2006066891A2 (fr)
ZA (1)	ZA200705146B (fr)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1674113A1 (fr)	2004-12-22	2006-06-28	F. Hoffmann-La Roche Ag	Conjugués de l'IGF-1 et du poly(éthylène glycol)
KR101459789B1 (ko)	2006-06-09	2014-11-07	노파르티스 아게	안정화된 인슐린-유사 성장 인자 폴리펩티드
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.
JP5173018B2 (ja) *	2008-04-03	2013-03-27	エフ．ホフマン−ラロシュアーゲー	神経筋障害の処置のためのｐｅｇ化ｉｇｆ−ｉ変異体の使用
JP2012513477A (ja) *	2008-12-23	2012-06-14	ソークインスティチュートフォーバイオロジカルスタディーズ	神経変性疾患の治療方法
WO2011011072A2 (fr)	2009-07-22	2011-01-27	Ipsen Pharma S.A.S.	Analogues au facteur-1 de croissance insulinomimétique (igf-1) présentant une substitution d'acide aminé en position 59
WO2011041376A1 (fr) *	2009-09-30	2011-04-07	Prolong Pharmaceuticals	Facteur modifié de stimulation des colonies de granulocytes (g-csf)
US20110152188A1 (en)	2009-12-23	2011-06-23	Hanns-Christian Mahler	Pharmaceutical compositions of igf/i proteins
CA2786340C (fr) *	2010-02-11	2017-08-22	F. Hoffmann-La Roche Ag	Conjugues de l'igf-i et du poly(ethylene glycol)
CN101831067A (zh) *	2010-05-31	2010-09-15	王二新	聚乙二醇脂类缀合物及其在制备药物中的应用
WO2014004467A1 (fr) *	2012-06-25	2014-01-03	The Brigham And Women's Hospital, Inc.	Thérapie sélective des cartilages
PL2935320T3 (pl)	2012-12-18	2020-03-31	Novartis Ag	Stabilizowane polipeptydy insulinopodobnego czynnika wzrostu
US20160271265A1 (en)	2013-10-02	2016-09-22	Novartis Ag	Insulin-like growth factor mimetics for use in therapy
UY35874A (es)	2013-12-12	2015-07-31	Novartis Ag	Un proceso para la preparación de una composición de proteínas pegiladas
AU2016321298A1 (en) *	2015-09-09	2018-03-29	The Trustees Of Columbia University In The City Of New York	Reduction of ER-MAM localized APP-C99 and methods of treating Alzheimer's Disease
KR200481741Y1 (ko)	2016-02-22	2016-11-04	강진범	차량의 방향지시등에 연동하여 특수 인식 영역에 led 반사광을 형성하기 위한 노면 광조사 장치
CN109072242A (zh)	2016-02-23	2018-12-21	科罗拉多州立大学董事会法人团体	用于治疗神经损伤的基于肽的方法
RU2711111C1 (ru) *	2018-09-05	2020-01-15	Илья Владимирович Духовлинов	Гибридный белок igf-1-long для лечения инсульта, нуклеиновая кислота, вектор, клетка, фармацевтическая композиция, способ лечения
EP3911668A1 (fr)	2019-01-18	2021-11-24	The Regents of the University of Colorado, a body corporate	Peptides antimicrobiens alpha-hélicoïdaux amphipathiques pour le traitement d'infections par des agents pathogènes à gram-négatif
US12222354B2 (en)	2021-03-19	2025-02-11	Quest Diagnostics Investments Llc	Identification and quantitation of insulin-like growth factor-I variants by mass spectrometry
CN120731069A (zh) *	2022-12-22	2025-09-30	凯沃利生物科学公司	用于治疗睑板腺功能障碍的组合物和方法

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ207842A (en)	1983-04-25	1988-02-12	Chiron Corp	Production of human insulin-like growth factor (igf) using cdna
IL71991A (en)	1983-06-06	1994-05-30	Genentech Inc	Preparation of human FGI and FGE in their processed form through recombinant AND tranology in prokaryotes
US4904584A (en)	1987-12-23	1990-02-27	Genetics Institute, Inc.	Site-specific homogeneous modification of polypeptides
ATE116335T1 (de) *	1987-12-24	1995-01-15	Gropep Pty Ltd	Peptid-analoge vom insulinähnlichen wachstums- faktor 1 (igf-1) oder faktor 2 (igf-2).
DK0400472T3 (da)	1989-05-27	1996-05-13	Sumitomo Pharma	Fremgangsmåde til fremstilling af polyethylenglycolderivater og modificeret protein
DE3924705A1 (de)	1989-07-26	1991-01-31	Boehringer Mannheim Gmbh	Heterobifunktionelle verbindungen
US5681814A (en)	1990-06-07	1997-10-28	Genentech, Inc.	Formulated IGF-I Composition
JP3051145B2 (ja)	1990-08-28	2000-06-12	住友製薬株式会社	新規なポリエチレングリコール誘導体修飾ペプチド
US5861373A (en) *	1991-08-01	1999-01-19	Genentech, Inc	IGF-1 to improve the neural condition
EP0597033B1 (fr)	1991-08-01	1997-04-09	Genentech, Inc.	Igf-1 utilise pour ameliorer l'etat pathologique du systeme nerveux
EP0679095A1 (fr) *	1992-11-25	1995-11-02	Amgen Boulder Inc.	Facteur de croissance insulinoide modifie
WO1995032003A1 (fr) *	1994-05-24	1995-11-30	Amgen Boulder Inc.	Facteurs de croissance proches de l'insuline modifies
US5824784A (en)	1994-10-12	1998-10-20	Amgen Inc.	N-terminally chemically modified protein compositions and methods
US5932462A (en) *	1995-01-10	1999-08-03	Shearwater Polymers, Inc.	Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
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
JP2001511162A (ja) *	1997-02-06	2001-08-07	ノボノルディスクアクティーゼルスカブ	付加され、そして／又は除去された付着基を有するポリペプチド−ポリマー結合体
US6767892B1 (en)	1997-11-07	2004-07-27	Chrion Corporation	Compositions providing for increased IGF-I solubility
US7067485B2 (en)	1997-11-07	2006-06-27	Chiron Corporation	IGF-I composition and its use
WO1999055362A1 (fr)	1998-04-29	1999-11-04	Genentech, Inc.	Formulations de igf-i sechees par pulverisation
US6436897B2 (en)	1998-06-01	2002-08-20	Celtrix Pharmaceuticals, Inc.	Pharmaceutical formulations for IGF/IGFBP
US6451986B1 (en)	1998-06-22	2002-09-17	Immunex Corporation	Site specific protein modification
AU762351B2 (en) *	1999-01-06	2003-06-26	Genentech Inc.	Insulin-like growth factor (IGF) I mutant variants
JP2002535967A (ja) *	1999-01-06	2002-10-29	ジェネンテック・インコーポレーテッド	インシュリン様成長因子（ｉｇｆ）ｉ変異体
AU763039B2 (en)	1999-04-08	2003-07-10	Genentech Inc.	Composition based on oppositely-charged polypeptides
US7431921B2 (en)	1999-08-27	2008-10-07	Maxygen Aps	Interferon beta-like molecules
AU6687000A (en) *	1999-08-27	2001-03-26	Maxygen Aps	New interferon beta-like molecules
US20040014652A1 (en) *	2000-06-01	2004-01-22	Andre Trouet	Tumor activated prodrug compounds and methods of making and using the same
EP1286700A2 (fr) *	2000-06-01	2003-03-05	Universite Catholique De Louvain	Composes de promedicaments a activation tumorale et procedes de fabrication et d'utilisation de ces derniers
US20020082215A1 (en)	2000-10-13	2002-06-27	Chiron Corporation	Method for treating ischemic events affecting the central nervous system
GEP20084487B (en) *	2002-12-26	2008-09-25	Mountain View Pharmaceuticals	Polymer conjugates of cytokines, chemokines, growth factors, polypeptide hormones and antagonists thereof
EP1674113A1 (fr)	2004-12-22	2006-06-28	F. Hoffmann-La Roche Ag	Conjugués de l'IGF-1 et du poly(éthylène glycol)
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.
JP5173018B2 (ja)	2008-04-03	2013-03-27	エフ．ホフマン−ラロシュアーゲー	神経筋障害の処置のためのｐｅｇ化ｉｇｆ−ｉ変異体の使用

2004
- 2004-12-22 EP EP04030415A patent/EP1674113A1/fr not_active Withdrawn
2005
- 2005-12-20 US US11/313,101 patent/US20060154865A1/en not_active Abandoned
- 2005-12-21 CN CN2005800485069A patent/CN101123991B/zh not_active Expired - Fee Related
- 2005-12-21 EA EA200701234A patent/EA011284B1/ru not_active IP Right Cessation
- 2005-12-21 BR BRPI0515857-5A patent/BRPI0515857A/pt not_active Application Discontinuation
- 2005-12-21 TW TW094145672A patent/TW200635604A/zh unknown
- 2005-12-21 EP EP05849990.6A patent/EP1830889B1/fr not_active Expired - Lifetime
- 2005-12-21 WO PCT/EP2005/013756 patent/WO2006066891A2/fr not_active Ceased
- 2005-12-21 TW TW097145363A patent/TW200914041A/zh unknown
- 2005-12-21 TW TW098120879A patent/TW200940085A/zh unknown
- 2005-12-21 KR KR1020097000308A patent/KR20090010138A/ko not_active Withdrawn
- 2005-12-21 JP JP2007547330A patent/JP4954896B2/ja not_active Expired - Fee Related
- 2005-12-21 AU AU2005318387A patent/AU2005318387B2/en not_active Ceased
- 2005-12-21 NZ NZ555840A patent/NZ555840A/en not_active IP Right Cessation
- 2005-12-21 UA UAA200708134A patent/UA93666C2/ru unknown
- 2005-12-21 KR KR1020077016867A patent/KR100915278B1/ko not_active Expired - Fee Related
- 2005-12-21 MX MX2007007479A patent/MX2007007479A/es active IP Right Grant
- 2005-12-21 CA CA2592006A patent/CA2592006C/fr not_active Expired - Fee Related
- 2005-12-21 KR KR1020097014300A patent/KR101106860B1/ko not_active Expired - Fee Related
- 2005-12-22 AR ARP050105473A patent/AR052842A1/es not_active Application Discontinuation
2007
- 2007-06-12 CR CR9177A patent/CR9177A/es not_active Application Discontinuation
- 2007-06-14 IL IL183966A patent/IL183966A/en not_active IP Right Cessation
- 2007-06-18 NO NO20073103A patent/NO20073103L/no not_active Application Discontinuation
- 2007-06-21 TN TNP2007000237A patent/TNSN07237A1/fr unknown
- 2007-06-21 MA MA30023A patent/MA29107B1/fr unknown
- 2007-06-21 ZA ZA200705146A patent/ZA200705146B/en unknown
2010
- 2010-06-02 US US12/791,904 patent/US20110009317A1/en not_active Abandoned
2012
- 2012-07-18 US US13/551,648 patent/US20120322732A1/en not_active Abandoned
2013
- 2013-03-18 US US13/845,179 patent/US20130217623A1/en not_active Abandoned
2014
- 2014-09-10 US US14/482,703 patent/US9724425B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2592006A1 (fr)	2006-06-29
KR20090010138A (ko)	2009-01-28
KR20090089457A (ko)	2009-08-21
US9724425B2 (en)	2017-08-08
AR052842A1 (es)	2007-04-04
JP2008524296A (ja)	2008-07-10
BRPI0515857A (pt)	2008-08-12
TNSN07237A1 (fr)	2008-11-21
US20060154865A1 (en)	2006-07-13
NZ555840A (en)	2010-02-26
IL183966A0 (en)	2007-10-31
MX2007007479A (es)	2007-07-20
TW200940085A (en)	2009-10-01
NO20073103L (no)	2007-09-19
UA93666C2 (en)	2011-03-10
MA29107B1 (fr)	2007-12-03
CA2592006C (fr)	2015-01-27
US20130217623A1 (en)	2013-08-22
WO2006066891A2 (fr)	2006-06-29
EA200701234A1 (ru)	2007-12-28
EP1674113A1 (fr)	2006-06-28
CN101123991A (zh)	2008-02-13
IL183966A (en)	2012-01-31
KR101106860B1 (ko)	2012-01-19
CN101123991B (zh)	2011-03-16
EP1830889A2 (fr)	2007-09-12
KR100915278B1 (ko)	2009-09-03
US20110009317A1 (en)	2011-01-13
EP1830889B1 (fr)	2017-05-17
CR9177A (es)	2007-11-23
EA011284B1 (ru)	2009-02-27
AU2005318387B2 (en)	2011-07-21
WO2006066891A3 (fr)	2007-05-31
AU2005318387A1 (en)	2006-06-29
JP4954896B2 (ja)	2012-06-20
US20120322732A1 (en)	2012-12-20
KR20070088809A (ko)	2007-08-29
TW200635604A (en)	2006-10-16
US20150099699A1 (en)	2015-04-09
TW200914041A (en)	2009-04-01

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US9724425B2 (en)	2017-08-08	Conjugates of insulin-like growth factor-1 and poly(ethylene glycol)
EP2358749B1 (fr)	2018-07-18	Mutants fgf21 et leurs utilisations
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JP5173018B2 (ja)	2013-03-27	神経筋障害の処置のためのｐｅｇ化ｉｇｆ−ｉ変異体の使用
AU2017246404A1 (en)	2018-11-01	Conjugated C1 esterase inhibitor and uses thereof
HK1117055A (en)	2009-01-09	Conjugates of insulin-like growth factor-1 and poly(ethylene glycol)
KR20160095133A (ko)	2016-08-10	Peg화 단백질의 조성물을 제조하는 방법
CN101277715A (zh)	2008-10-01	神经变性疾病的治疗
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