DK2026842T3 - N-terminalmodificeret PEG-TRAIL, fremgangsmåde til fremstilling og anvendelser deraf - Google Patents

N-terminalmodificeret PEG-TRAIL, fremgangsmåde til fremstilling og anvendelser deraf Download PDF

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DK2026842T3
DK2026842T3 DK07746877.5T DK07746877T DK2026842T3 DK 2026842 T3 DK2026842 T3 DK 2026842T3 DK 07746877 T DK07746877 T DK 07746877T DK 2026842 T3 DK2026842 T3 DK 2026842T3
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trail
peg
terminal modified
conjugate
modified peg
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DK07746877.5T
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Kang Choon Lee
Sung Kwon Lee
Su Young Chae
Yu Seok Youn
Won Bae Kim
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Theraly Pharmaceuticals Inc
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    • 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
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/191—Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • C07K14/525—Tumour necrosis factor [TNF]
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
    • B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
    • B01D15/361—Ion-exchange
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • C—CHEMISTRY; METALLURGY
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    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/73—Fusion polypeptide containing domain for protein-protein interaction containing coiled-coiled motif (leucine zippers)
    • G—PHYSICS
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    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/96—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation using ion-exchange

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  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (16)

1. N-terminal-modificeret PEG (polyethylenglycol)-TRAIL-(tumornekrose-faktor-relateret apoptose-inducerende ligand)-konjugat omfattende: en trimerisk TRAIL omfattende zipper-aminosyremotiver, der fremmer trimer-dannelse ved N-terminalerne deraf; og en PEG, hvor PEG'en er bundet til N-terminalen af en monomer af den trimeriske TRAIL.
2. N-terminal-modificeret PEG-TRAIL-konjugat ifølge krav 1, hvor PEG'en har en lige eller forgrenet form.
3. N-terminal-modificeret PEG-TRAIL-konjugat ifølge krav 1, hvor PEG'en er mindst en udvalgt fra gruppen bestående af methoxypolyethylenglycolsucci-nimidylpropionat, methoxypolyethylenglycol-N-hydroxysuccinimid, methoxy-polyethylenglycolaldehyd, methoxypolyethylenglycolmaleimid og multiforgre-net polyethylenglycol, fortrinsvis methoxypolyethylenglycolaldehyd.
4. N-terminal-modificeret PEG-TRAIL-konjugat ifølge krav 1, hvor PEG'en har en molekylvægt på mellem 1.000 og 100.000, såsom mellem 1.000 og 40.000, fortrinsvis mellem 5.000 og 40.000.
5. N-terminal-modificeret PEG-TRAIL-konjugat ifølge krav 1, hvor TRAIL'en er tilvejebragt i en nativ eller genmodificeret (rekombinant) form.
6. N-terminal-modificeret PEG-TRAIL-konjugat ifølge krav 1, hvor TRAIL'en er human TRAIL, med en aminosyresekvens med en længde på 281 aminosyrer.
7. N-terminal-modificeret PEG-TRAIL-konjugat ifølge krav 1, hvor TRAIL'en har en aminosyresekvens fra arginin-114 til glycin-281 af TRAIL-formen med fuld længde (1-281).
8. N-terminal-modificeret PEG-TRAIL-konjugat ifølge krav 1, hvor zipper-aminosyremotivet er en isoleucin-zipper.
9. Fremgangsmåde til fremstilling af det N-terminal-modificerede PEG-TRAIL-konjugat ifølge krav 1, omfattende at reagere en N-terminal amin af en trimerisk TRAIL omfattende zipper-aminosyremotiverne ved N-terminalerne deraf med en aldehydgruppe af en PEG i nærvær af et reduceringsmiddel.
10. Fremgangsmåde ifølge krav 9, hvor PEG'en og TRAIL'en reagerer i et molforhold (PEG/TRAIL) på 2 til 10, fortrinsvis 5 til 7,5.
11. Fremgangsmåde ifølge krav 9, hvor zipper-aminosyremotivet er en isoleucin-zipper.
12. Fremgangsmåde ifølge krav 9, hvor reduceringsmidlet er NaCNBH3 eller NaBH4.
13. Anvendelse af det N-terminal-modificerede PEG-TRAIL-konjugat ifølge krav 1 ved fremstillingen af et medikament til forebyggelse eller behandling af cancer, fortrinsvis en hvilken som helst udvalgt fra gruppen bestående af tarmkarcinom, gliom, lungekarcinom, prostatakarcinom, hjernetumor og multipelt myelom.
14. N-terminal-modificeret PEG-TRAIL-konjugat ifølge krav 1 til anvendelse ved forebyggelse eller behandling af cancer, fortrinsvis en hvilken som helst udvalgt fra gruppen bestående af tarmkcarcinom, gliom, lungekarcinom, prostatakarcinom, hjernetumor og multipelt myelom.
15. Anvendelse af det N-terminal-modificerede PEG-TRAIL-konjugat ifølge krav 1 ved fremstilling af et medikament til forebyggelse eller behandling af en autoimmun sygdom, fortrinsvis en hvilken som helst udvalgt fra gruppen bestående af eksperimentel autoimmun encephalomyelitis, rheumatoid arthritis og type I diabetes.
16. N-terminal-modificeret PEG-TRAIL-konjugat ifølge krav 1 til anvendelse ved forebyggelse eller behandling af en autoimmun sygdom, fortrinsvis en hvilken som helst udvalgt fra gruppen bestående af eksperimentel autoimmun encephalomyelitis, rheumatoid arthritis og type I diabetes.
DK07746877.5T 2006-06-12 2007-06-12 N-terminalmodificeret PEG-TRAIL, fremgangsmåde til fremstilling og anvendelser deraf DK2026842T3 (da)

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Application Number Priority Date Filing Date Title
KR1020060052702A KR100886783B1 (ko) 2006-06-12 2006-06-12 N-말단이 수식된 peg-trail 결합체, 이의 제조방법 및 이의 용도
PCT/KR2007/002825 WO2007145457A1 (en) 2006-06-12 2007-06-12 N-terminal modified peg-trail, method for preparing and uses thereof

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US (2) US9321825B2 (da)
EP (1) EP2026842B1 (da)
KR (1) KR100886783B1 (da)
DK (1) DK2026842T3 (da)
ES (1) ES2610576T3 (da)
WO (1) WO2007145457A1 (da)

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KR100886783B1 (ko) 2006-06-12 2009-03-04 성균관대학교산학협력단 N-말단이 수식된 peg-trail 결합체, 이의 제조방법 및 이의 용도
AU2009303304A1 (en) * 2008-10-10 2010-04-15 Anaphore, Inc. Polypeptides that bind TRAIL-RI and TRAIL-R2
US11299528B2 (en) 2014-03-11 2022-04-12 D&D Pharmatech Inc. Long acting TRAIL receptor agonists for treatment of autoimmune diseases
KR20150133576A (ko) * 2014-05-20 2015-11-30 삼성전자주식회사 화학적 개질된 표적화 단백질 및 그의 이용
WO2016074033A1 (en) * 2014-11-13 2016-05-19 The Heart Research Institute Ltd Tumour necrosis factor (tnf)-related apoptosis-inducing ligand (trail): compositions and methods for treating wound healing
CN108601819B (zh) 2015-12-17 2022-03-15 约翰霍普金斯大学 用死亡受体激动剂改善系统性硬化症
KR102508650B1 (ko) 2016-04-07 2023-03-13 더 존스 홉킨스 유니버시티 사멸 수용체 작용제로써 췌장암 및 통증을 치료하기 위한 조성물 및 방법
US11767353B2 (en) * 2020-06-05 2023-09-26 Theraly Fibrosis, Inc. Trail compositions with reduced immunogenicity

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KR100886783B1 (ko) 2006-06-12 2009-03-04 성균관대학교산학협력단 N-말단이 수식된 peg-trail 결합체, 이의 제조방법 및 이의 용도
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US20130101553A1 (en) 2011-04-18 2013-04-25 The Regents Of The University Of California Inducing inactivation of fibrogenic myofibroblasts

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KR20070118492A (ko) 2007-12-17
US20090203599A1 (en) 2009-08-13
KR100886783B1 (ko) 2009-03-04
EP2026842B1 (en) 2016-10-12
EP2026842A4 (en) 2011-05-18
US9321825B2 (en) 2016-04-26
EP2026842A1 (en) 2009-02-25
US10046059B2 (en) 2018-08-14
US20160279253A1 (en) 2016-09-29
ES2610576T3 (es) 2017-04-28
WO2007145457A1 (en) 2007-12-21

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