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LV10201B - Target specific antibody-superantigen conjugates and their preparation - Google Patents

Target specific antibody-superantigen conjugates and their preparation Download PDF

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Publication number
LV10201B
LV10201B LVP-93-1362A LV931362A LV10201B LV 10201 B LV10201 B LV 10201B LV 931362 A LV931362 A LV 931362A LV 10201 B LV10201 B LV 10201B
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LV
Latvia
Prior art keywords
antibody
group
conjugate
superantigen
sea
Prior art date
Application number
LVP-93-1362A
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English (en)
Other versions
LV10201A (lv
Inventor
Kalland Terje
Hedlund Gunnar
Dohlsten Mikael
Lando Peter
Akerblom Eva
Original Assignee
Kabi Pharmacia Ab
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.)
Filing date
Publication date
Priority claimed from SE9002484A external-priority patent/SE9002484L/xx
Priority claimed from SE9002479A external-priority patent/SE9002479D0/xx
Application filed by Kabi Pharmacia Ab filed Critical Kabi Pharmacia Ab
Publication of LV10201A publication Critical patent/LV10201A/lv
Publication of LV10201B publication Critical patent/LV10201B/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/385—Haptens or antigens, bound to carriers
    • 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
    • A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • A61K47/6829—Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A
    • 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
    • A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6068—Other bacterial proteins, e.g. OMP
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/62—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier
    • A61K2039/627—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier characterised by the linker

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Toxicology (AREA)
  • Microbiology (AREA)
  • Virology (AREA)
  • Mycology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Claims (22)

  1. IZGUDROJUMA FORMULA 1. Šķīstošs antivielas Jconjugāts, kas satur antivielu un superantigēnu.
  2. 2. Šķīstošs_antivielas Jconjūgāts pēc punkta 1, kas atšķiras ar to, ka: (1) minētā antiviela ir specifiska pret tās mērķa šūnas virsmu, kura saistīta ar saslimšanu, un (2) minēto superantigēnu pazīst T-šūnas un tas aktivē citotoksiskās T- šūnas (CTŠ), pie kam tas sevišķi sadarbojas ar T-šūnas receptūra kompleksa elementiem, piemēram, ar T-šūnas receptora variab-lā apgabala beta-ķēdi.
  3. 3. Konjugāts pēc punkta 1 vai 2, kas atšķiras ar to, ka mērķa šūna saistīta ar slimību no grupas: vēzis, autoimūnās saslimšanas, parazītu invāzijā, infekcijas, piemēram, vīrusu infekcija, sēnīšu infekcija un mikrobu infekcija, pie kam antiviela ir specifiski vērsta pret antigēno determinanti, kas atrodas uz minētās mērķa šūnas. ki vērsta pret antigeno determinanti, kas atrodas uz minētās mērķa šūnas.
  4. 4. Ķonjugāts pēc punkta 2 vai 3, kas atšķiras ar to, ka saslimšana ir vēzis, un antiviela vērsta pret antigēno determinanti (epitopu), kura atrodas uz audzēja šūnas, piemēram, resnās zarnas vēža šūnas.
  5. 5. pēc punkta 4, kas atšķiras ar to, ka antiviela ir specifiski vērsta pret epitopu C242.
  6. 6. Pēc Punkta 4, kas atšķiras ar to, ka antiviela specifiski vērsta pret epitopu olbaltumvielā, kurš pieder saimei CA-733, sevišķi, pret epitopu C215.
  7. 7. Konjugēts pēc punkta 1-6, kas atšķiras ar to, ka ar vienu antivielu konjugēti vismaz 1-5, vēlams 1-3 superantigēni.
  8. 8. Konjugēts pēc punkta 1-7, kas atšķiras ar to, ka par antivielu izmanto monoklonālo antivielu.
  9. 9. Konjugēts pēc punkta 1-8, kas atšķiras ar to, ka lieto bakteriālas izcelsmes superantigēnu, vēlams no stafilokoku en-terotoksīnu grupas.
  10. 10. Konjugēts pēc punkta 1-9, kas atšķiras ar to, ka par superantigenu pielieto SEA.
  11. 11. P®c 1-10, kas atšķiras ar to, ka superantigēns un antiviela saistīti ar kovalentu organisko saitīti -B-, kurā, vēlams, ietilpst vismaz viena amīda grupa un kura, vēlams, ir hidrofīla un minētās saitītes garums ir vismaz 6 atomi.
  12. 12. ĶSīļiHgāts pēc punkta 11, kas atšķiras ar to, ka saitīte -B- ir ar sekojošu struktūru: -S RCONHCH-CHL(0CHoCHo) 0(CH_) C0Y- (I) r 22 2 2 n 2m kur: r ir 1 vai 2; R ir alkilēngrupa, kas satur 1-4 oglekļa atomus; n ir vesels skaitlis no 1 līdz 20; m ir 1 vai 2; Y ir -NH-.-NHNH- vai -NHNCH-.
  13. 13. Konjugāts pēc punkta 1-11, kas atšķiras ar to, ka tas pielietojams tādu mērķa šūnu lizēšanai, uz kuru virsmas ir struktūras, pret kurām vērsta konjugēta antiviela.
  14. 14. 5ē2®E?i®2Ē roērķa šūnas lizēšanai, kas atšķiras ar to, ka mērķa šūnas kontaktē ar efektīvi lizējošu šķīstošu antivielas konjugēta, kurš satur ar superantigēnu saistītu antivielu, daudzumu, pie kam antiviela ir specifiska pret mērķa šūnu, un minēto superantigēnu pazīst T-šūnas un tas spēj aktivēt citotoksiskās T-šūnas (CTŠ).
  15. 15. Paņēmiens lizēšanai pēc punkta 14, kas atšķiras ar to, ka antiviela, superantigēns un tos savienojošā saitīte atbilst punktos 1-13 dotajām definīcijām.
  16. 16. EāSiūiiĒīīĒ konjugēta iegūšanai, kas atšķiras ar to, ka antivielu un/vai superantigēnu savieno vismaz caur vienu struktūras elementu, kas ņemts no (a) ogļhidrātu struktūrām, un (b) funkcionālajām grupām: tiolu grupām, disulfīdu grupām, karboksilgrupām un aminogrupām, un pēc tam izdala iegūto konjugētu no vides.
  17. 17. Paņēmiens konjugēta iegūšanai pēc punkta 16, kas atšķiras ar to, ka savienošanu veic caur superantigēna un/vai antivielas aminogrupu.
  18. 18. konjugēta iegūšanai pēc punkta 17, kas atšķiras ar to, ka savienošana ietver sekojošus posmus: (1) antivielas vai superantigēna reakcija ar organisku reaģentu, kurš satur grupu, kura spēj reaģēt ar tiola grupu, un grupu, kura spēj reaģēt ar aminogrupu, iegūstot antivielu vai superantigēnu, kam pievienota grupa, kas spēj reaģēt ar tiola grupu; un (2) pārējas superantigēna un antivielas daļas reakcoja ar organisko reaģentu, kurš satur tiola grupu vai aizsargātu tiola grupu vai arī grupu, kas spēj reaģēt ar aminogrupu, veidojot superantigēnu vai antivielu, kam pievienota tiola grupa vai aizsargāta tiola grupa; un (3) produktu, kuri iegūti attiecīgi posmos (2) un (3), savstarpēja reakcija, veidojot konjugātu, kurā superantigēns saistīts ar antivielu ar disulfīda vai tioētera grupas palīdzību.
  19. 19. Paņēmiens konjugāta iegūšanai pēc punkta 18, kas atšķiras ar to, ka aģents, kurš spēj reaģēt ar aminogru-pu un satur grupu, kura var reaģēt ar tiola grupu, ir alfa-halogenēts acetilhalogenīds, un savienojums, kurš satur tiola grupu vai aizsargātu tiola grupu, ir bifunkcionāls savienošanas reaģents ar formulu (II) Z.RCONHCHCH„(OCH,CH_) 0(CH_) Z\ 1 22 22n 2 m 1 kur: m ir 1 vai 2; n ir vesels skaitlis no 1 līdz 20; ir ar -SH grupu reaģēt spējīga elektrofīla grupa, tiola grupa (-SH) vai aizsargāta tiola grupa (piemēram, AcS-), ar tādu noteikumu, ka tiola grupa un hidroksilgrupa nevar būt saistītas ar vienu un to pašu oglekļa atomu grupā R, un Zļ ir aktivēta karboksilgrupa.
  20. 20. Paņēmiens konjugēta iegūšanai pēc punkta 16 - 19, kas atšķiras ar to, ka minētie superantigēns un antiviela ir attiecīgi definēti kā punktos 2 - 10.
  21. 21. Konjugāta pēc punktiem 1-12 pielietojums ārstniecības preparāta iegūšanai zīdītāju, ieskaitot cilvēkus, ārstēšanai no tādām slimībām ,kā vēzis, autoimūnās saslimšanas, parazītu invāzija, infekcijas, piemēram, vīrusu infekcija, sēnīšu infekcija un mikrobu infekcija, ievadot minētajā zīdītājā tādu daudzumu konjugāta, kas pietiekošs ar ārstējamo saslimšanu saistīto mērķa šūnu lizešanal.
  22. 22. Konjugāta pēc punkta 1-12 pielietojums tāda ārstnieciskā satāva pagatavošanai, kas paredzēts vēža, autoimūno saslimšanu, parazītu invāzijas, infekciju, piemēram, vīrusu infekcijas, sēnīšu infekcijas un mikrobu infekcijas, ārstēšanai.
LVP-93-1362A 1990-07-20 1993-12-22 Target specific antibody-superantigen conjugates and their preparation LV10201B (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SE9002484A SE9002484L (sv) 1990-07-20 1990-07-20 Nya substituerade polyetrar
SE9002479A SE9002479D0 (sv) 1990-07-20 1990-07-20 Antibody conjugates
PCT/SE1991/000496 WO1992001470A1 (en) 1990-07-20 1991-07-16 Target specific antibody-superantigen conjugates and their preparation

Publications (2)

Publication Number Publication Date
LV10201A LV10201A (lv) 1994-10-20
LV10201B true LV10201B (en) 1995-08-20

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Family Applications (1)

Application Number Title Priority Date Filing Date
LVP-93-1362A LV10201B (en) 1990-07-20 1993-12-22 Target specific antibody-superantigen conjugates and their preparation

Country Status (16)

Country Link
EP (1) EP0610179B1 (lv)
JP (1) JP3334130B2 (lv)
KR (1) KR100189024B1 (lv)
AT (1) ATE144145T1 (lv)
AU (1) AU656906B2 (lv)
CA (1) CA2087164C (lv)
DE (1) DE69122777T2 (lv)
DK (1) DK0610179T3 (lv)
ES (1) ES2094231T3 (lv)
GR (1) GR3022202T3 (lv)
HK (1) HK1007955A1 (lv)
HU (1) HU218603B (lv)
LV (1) LV10201B (lv)
NO (1) NO312816B1 (lv)
RU (1) RU2125889C1 (lv)
WO (1) WO1992001470A1 (lv)

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US6004554A (en) * 1992-03-05 1999-12-21 Board Of Regents, The University Of Texas System Methods for targeting the vasculature of solid tumors
US6749853B1 (en) 1992-03-05 2004-06-15 Board Of Regents, The University Of Texas System Combined methods and compositions for coagulation and tumor treatment
US5965132A (en) 1992-03-05 1999-10-12 Board Of Regents, The University Of Texas System Methods and compositions for targeting the vasculature of solid tumors
EP0659438A1 (en) * 1993-12-23 1995-06-28 Boehringer Mannheim Gmbh Conjugates consisting of peptidic T cell antigens and cell binding groups, and their use for therapy
GB9326574D0 (en) * 1993-12-31 1994-03-02 King S College London Dry power inhalers
SE9402430L (sv) * 1994-07-11 1996-01-12 Pharmacia Ab Konjugat mellan modifierat superantigen och en målsökande förening samt användning av konjugaten
JP3871713B2 (ja) * 1995-05-10 2007-01-24 協和醗酵工業株式会社 新規毒素複合体
SE9601245D0 (sv) 1996-03-29 1996-03-29 Pharmacia Ab Chimeric superantigens and their use
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AU750414B2 (en) 1998-07-13 2002-07-18 Board Of Regents, The University Of Texas System Cancer treatment methods using therapeutic conjugates that bind to aminophospholipids
US6818213B1 (en) 1998-07-13 2004-11-16 Board Of Regents, The University Of Texas System Cancer treatment compositions comprising therapeutic conjugates that bind to aminophospholipids
US8025873B2 (en) 2002-06-20 2011-09-27 Paladin Labs, Inc. Chimeric antigens for eliciting an immune response
US8029803B2 (en) 2002-06-20 2011-10-04 Paladin Labs, Inc. Chimeric antigens for eliciting an immune response
US8007805B2 (en) 2003-08-08 2011-08-30 Paladin Labs, Inc. Chimeric antigens for breaking host tolerance to foreign antigens

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Also Published As

Publication number Publication date
EP0610179A1 (en) 1994-08-17
DK0610179T3 (da) 1997-03-24
DE69122777T2 (de) 1997-04-10
LV10201A (lv) 1994-10-20
HUT67502A (en) 1995-04-28
WO1992001470A1 (en) 1992-02-06
EP0610179B1 (en) 1996-10-16
JP3334130B2 (ja) 2002-10-15
AU8294191A (en) 1992-02-18
HU9300148D0 (en) 1993-04-28
NO930174D0 (no) 1993-01-19
CA2087164C (en) 2002-11-26
JPH05508856A (ja) 1993-12-09
HK1007955A1 (en) 1999-04-30
DE69122777D1 (de) 1996-11-21
GR3022202T3 (en) 1997-03-31
NO930174L (no) 1993-01-19
ATE144145T1 (de) 1996-11-15
NO312816B1 (no) 2002-07-08
KR100189024B1 (ko) 1999-06-01
CA2087164A1 (en) 1992-01-21
AU656906B2 (en) 1995-02-23
RU2125889C1 (ru) 1999-02-10
HU218603B (hu) 2000-10-28
ES2094231T3 (es) 1997-01-16

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