FI107927B - Förfarande för framställning av polyetylen-proteinkonjugater - Google Patents

Förfarande för framställning av polyetylen-proteinkonjugater Download PDF

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Publication number
FI107927B
FI107927B FI921267A FI921267A FI107927B FI 107927 B FI107927 B FI 107927B FI 921267 A FI921267 A FI 921267A FI 921267 A FI921267 A FI 921267A FI 107927 B FI107927 B FI 107927B
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Prior art keywords
protein
oxy
peg
sru
conjugate
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FI921267A
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English (en)
Finnish (fi)
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FI921267A0 (fi
FI921267A (fi
Inventor
John Hakimi
Perry Rosen
Patricia Kilian
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Hoffmann La Roche
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • A61P37/02—Immunomodulators
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/964—Chemistry: molecular biology and microbiology including enzyme-ligand conjugate production, e.g. reducing rate of nonproductive linkage
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/81—Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
    • Y10S530/812—Peptides or proteins is immobilized on, or in, an organic carrier
    • Y10S530/815—Carrier is a synthetic polymer
    • Y10S530/816—Attached to the carrier via a bridging agent

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Polyethers (AREA)
  • Vending Machines For Individual Products (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)

Claims (12)

1. Förfarande för framställning av ett fysio-logiskt aktivt proteinkonjugat med formeln 5 rf-CXCHgCHaO^-CHssCHa-Fp^ ^NHj-protein S R3 J m 10 där R1 är lägre alkyl med 1-6 kolatomer; R2 är -0- eller -NH-; R3 är =N-R4, =S eller =0; R4 är lägre Ci_6-alkyl eller cylkoalkyl; m och n är heltal > 1 som valts sä att 15 konjugatet har atminstone en del av det icke-konjugerade proteinets biologiska aktivitet; och där proteinet är interleukin-1, interleukin-lra, interferon-α eller interleukin 2, förutsatt att när R2 är -0- sä är R3 inte =N-R4 och att när R2 är -O- och R3 är =0 sä är proteinet 20 inte interleukin-2, kännetecknat av att nägon av de ♦# aktiverade föreningarna, vilkas allmänna formler är ·· ·· följande: • · * f » I • · · • a • · · • · · • a *:··: 25 n‘A R1(XCH2CH20)5- CH2CH2 C=N—R4 • · • · · *" ** /V ‘ Π-B R10(CH2CH20)-0—C —iKjJ SO • * .···. 30 „5 ·"" , Vi : *·· II-C R 0(CH2CH20)-CH2CH2-NH — C —0—JJ • * H T o • · « · · ; 35 π-d =c=s « ·· • a 107927 II-E R'CKCH2CiiOVCH2(M2-NH—C-Ο-ζΧ^ S 5 Ι^ϊ Π-F R’CKCH^OX.-CHjCHz-O-C-O-'s-n^ I O 10 il-G ^CXCH^OVCH2CH2- O— C—0-% S där R1, R4 och R5 har sarana betydelse som ovan och n är vilket heltal som heist mellan 1 och 1000, fas att reagera 15 med proteinets fria aminogrupp eller dess salt och proteinkonjugatet isoleras frän reaktionsblandningen.
2. Förfarande enligt patentkrav 1, kännetecknat av att m och n väljs sä att pegyleringsrestens eller -resternas molekylvikt per 20 proteinmolekyl är 300-30 000 dalton.
3. Förfarande enligt patentkrav 1 eller 2, • , kännetecknat av att m är 1 eller 2. • · I
"···' 4. Förfarande enligt nägot av patentkraven 1-3, *.**: kännetecknat av att ett proteinkonjugat med formeln T! 25 :M Γ H H :T: , N N--protein (I-A) R -OfCHjCHjO) -CHjCH{ ¥ ....: ” “ • · " m .···. 30 *Γ framställs, där R1, R4, m, n och proteinet har samma »· : *·· betydelse som i patentkrav 1.
5. Förfarande enligt nägot av patentkraven 1-3, ; *·, kännetecknat av att ett proteinkonjugat med formeln • t · ··« « . . 35 • · · • ·· • · 107927 hT rf^OH1CH^VCH»PH!rON.M'-prot.lI. (I_B) S ]- 5 framställs, där R1, m, n och proteinet har samma betydelse som i patentkrav 1.
6. Förfarande enligt nägot av patentkraven 1-3, kännetecknat av att ett proteinkonjugat med formeln r H I N ^NH-- protein R1 -0(CH2CH20\l-CH2CHf C II (I-C) O m 15 framstails, där R1, m, n och proteinet har samma betydelse som i patentkrav 1.
7. Förfarande enligt nägot av patentkraven 1-3, kännetecknat av att ett proteinkonjugat med formeln
20 N NH — protein R1-0-(CH2CH20) -CH2CHf c λ*. " ft m {I-D) • · · • ·· • · : ** 25 framställs, där R1, m, n och proteinet har samma betydelse • · ·.*·· som i patentkrav 1.
: 8. Förfarande enligt nägot av patentkraven 1-3, kännetecknat av att ett proteinkonjugat med formeln • · .···. 30 Γ ··** *NH- — protein j\ Fr-0-(CH2CH20) -ch2ch/ η : ·* n „ (i-E) ··· II :: n m • * « · « • · · ··· · - .·, · 35 framställs, där R , m, n och proteinet har samma betydelse • ·· som i patentkrav 1. 107927
9. Förfarande enligt nägot av patentkraven 1-8, kännetecknat av att R1 är CH3.
10. Förfarande enligt patentkrav 1, känne tecknat av att ett proteinkonjugat med formeln 5 H N NH— interferon —·<Χ y \,y H3C-0(CH2CH20VCH2CH/ c o 10 framställs, där n är cirka 112.
11. Förfarande enligt patentkrav 1, känne tecknat av att ett proteinkonjugat med formeln 15 O NH— interferon— 0c. H3C-0-<CH2CH20) -CHzCH/' c n il o 20 framställs, där n är cirka 112.
12. Förfarande enligt patentkrav 10 eller 11, • · ·« *. kännetecknat av att interferon-α är interferon-α A. 44* * · · ·«# • · • · ft • »« • · ♦ ···· • · * • # 9*9 • ·· • · *44 4 9 4 4*4 • • · ··· • 4 4 4 *·· • 44 • · * ·♦ ft ··· • · • · 4*4 4 9 * 4 9 4 4 4 4 944 4 4 9 9*4 9 *9 4 4
FI921267A 1991-03-25 1992-03-24 Förfarande för framställning av polyetylen-proteinkonjugater FI107927B (sv)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US67400191A 1991-03-25 1991-03-25
US67400191 1991-03-25
US76700091 1991-09-27
US07/767,000 US5595732A (en) 1991-03-25 1991-09-27 Polyethylene-protein conjugates

Publications (3)

Publication Number Publication Date
FI921267A0 FI921267A0 (fi) 1992-03-24
FI921267A FI921267A (fi) 1992-09-26
FI107927B true FI107927B (sv) 2001-10-31

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ID=27101069

Family Applications (2)

Application Number Title Priority Date Filing Date
FI921267A FI107927B (sv) 1991-03-25 1992-03-24 Förfarande för framställning av polyetylen-proteinkonjugater
FI20011554A FI20011554A (sv) 1991-03-25 2001-07-17 Polyetylen-proteinkonjugater

Family Applications After (1)

Application Number Title Priority Date Filing Date
FI20011554A FI20011554A (sv) 1991-03-25 2001-07-17 Polyetylen-proteinkonjugater

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US (7) US5595732A (sv)
EP (1) EP0510356B1 (sv)
JP (1) JP2637010B2 (sv)
KR (1) KR920018079A (sv)
CN (2) CN1038035C (sv)
AT (1) ATE176159T1 (sv)
AU (2) AU657311B2 (sv)
BG (1) BG60800B2 (sv)
BR (1) BR9201015A (sv)
CA (1) CA2063886C (sv)
CS (1) CS87192A3 (sv)
CY (1) CY2169B1 (sv)
DE (1) DE69228269T2 (sv)
DK (1) DK0510356T3 (sv)
EE (1) EE9400356A (sv)
ES (1) ES2128329T3 (sv)
FI (2) FI107927B (sv)
GR (1) GR3030049T3 (sv)
HU (2) HUT60512A (sv)
IE (1) IE920936A1 (sv)
IL (1) IL101348A0 (sv)
IS (1) IS3824A (sv)
MW (1) MW1892A1 (sv)
MX (1) MX9201298A (sv)
MY (1) MY131095A (sv)
NO (1) NO921142L (sv)
NZ (2) NZ242084A (sv)
OA (1) OA09760A (sv)
RO (1) RO109543B1 (sv)
SI (1) SI9210294A (sv)
ZA (1) ZA922110B (sv)
ZW (1) ZW4392A1 (sv)

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