DK2953977T3 - Immunimagografimiddel til anvendelse ved antistof-lægemiddel-konjugatterapi - Google Patents

Immunimagografimiddel til anvendelse ved antistof-lægemiddel-konjugatterapi Download PDF

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Publication number
DK2953977T3
DK2953977T3 DK14717073.2T DK14717073T DK2953977T3 DK 2953977 T3 DK2953977 T3 DK 2953977T3 DK 14717073 T DK14717073 T DK 14717073T DK 2953977 T3 DK2953977 T3 DK 2953977T3
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antibody
binding protein
immunoglobulin
ser
gly
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DK14717073.2T
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English (en)
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Jochen Kruip
Susanta K Sarkar
Mathias Gebauer
Christian Lange
Ingo Focken
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Sanofi Sa
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3076Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties
    • C07K16/3092Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties against tumour-associated mucins
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35Valency
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/626Diabody or triabody
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/64Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/20Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/52Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Peptides Or Proteins (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Physics & Mathematics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Optics & Photonics (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)

Claims (15)

1. Antistoflignende bindingsprotein, der specifikt binder den tumorassocierede MUCl-syaloglycotop CA6, der er kendetegnet ved, at det antistoflignende bindingsprotein omfatter to polypeptider med strukturer som vist ved formlerne [I] og [II] nedenfor: Vli-Li-VL2-Cl [I] Vh1-Ij2-Vh2-Ch1 [II] hvor: Vli er et variabelt domæne af let kæde af immunoglobulin, der er afledt fra DS6-antistoffet; Vl2 er et variabelt domæne af let kæde af immunoglobulin, der er afledt fra DS6-antistoffet; Vhi er et variabelt domæne af tung kæde af immunoglobulin, der er afledt fra DS6-antistoffet; Vh2 er et variabelt domæne af tung kæde af immunoglobulin, der er afledt fra DS6-antistoffet; Cl er et konstant domæne af let kæde af immunoglobulin, såsom et humant IGKC konstant domæne af let kæde af immunoglobulin; Chi er et immunoglobulin Chi konstant domæne af tung kæde, såsom et humant immunoglobulin Chi konstant domæne af tung kæde af; Li og L2 er aminosyrelinkere; og hvor polypeptiderne med formel [I] og polypeptiderne med formel [II] danner et bivalent monospecifikt tandem- immunoglobulin-antistoflignende bindingsprotein, hvor polypeptidet med formel [I] omfatter en sekvens, der er mindst 80 % identisk med SEQ ID NO: 1, og polypeptidet med formel [II] omfatter en sekvens, der er mindst 80 % identisk med SEQ ID NO: 7.
2. Antistoflignende bindingsprotein ifølge krav 1, hvor Vli og Vl2 er defineret ved sekvensen SEQ ID NO: 2; og VHi og VH2 er defineret ved sekvensen SEQ ID NO: 8.
3. Antistoflignende bindingsprotein ifølge krav 1 eller krav 2, hvor Li er GGGGS eller GGGGSGGGGS (SEQ ID NO: 3).
4. Antistoflignende bindingsprotein ifølge et hvilket som helst af kravene 1 til 3, hvor L2 er GGGGS eller GGGGSGGGGS (SEQ ID NO: 3).
5. Antistoflignende bindingsprotein ifølge et hvilket som helst af kravene 1 til 4, hvor polypeptidet med formel [I] omfatter aminosyresekvensen SEQ ID NO: 1.
6. Antistoflignende bindingsprotein ifølge et hvilket som helst af kravene 1 til 5, hvor polypeptidet med formel [II] omfatter aminosyresekvensen SEQ ID NO: 7.
7. Antistoflignende bindingsprotein ifølge et hvilket som helst af kravene 1 til 6, der yderligere omfatter mindst ét radioaktivt mærke, imagografimiddel, terapeutisk middel eller diagnostisk middel.
8. Antistoflignende bindingsprotein ifølge krav 7, hvor det radioaktive mærke, imagografimidlet, det terapeutiske middel eller det diagnostiske middel er 110In, i:L1In, 177Lu, 18F, 52Fe, 62Cu, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 89Zr, 94Tc, 94Tc, 99mTc, 120I, i23i, 124I, 125I, 131I, 154“158Gd, 32P, nC, 13N, 150, 186Re, 188Re, 51Mn, 52mMn, 55Co, 72As, 75Br, 76Br, 82mRb eller 83Sr.
9. Antistoflignende bindingsprotein ifølge krav 7 eller 8, hvor det radioaktive mærke, imagografimidlet, det terapeutiske middel eller det diagnostiske middel omfatter et eller flere midler til en imagografiplatform valgt fra gruppen, der består af MR-scanning (MRI); positronemissionstomografi (PET); enkeltfotonemissionstomografi (SPECT); optisk imagografi, computertomografi (CT); ultralyd, røntgen og fotoakustisk imagografi.
10. Isoleret nukleinsyremolekyle, der koder for polypeptiderne med formel [I] og [II] af det antistoflignende bindingsprotein ifølge et hvilket som helst af kravene 1 til 6.
11. Isoleret nukleinsyremolekyle ifølge krav 10, hvor nukleinsyremolekylet omfatter nukleotidsekvensen ifølge SEQ ID NO: 5 eller SEQ ID NO: 10.
12. Ekspressionsvektor, der omfatter nukleinsyremolekylet ifølge krav 10 eller 11.
13. Isoleret værtscelle, der omfatter nukleinsyremolekylet ifølge krav 10 eller 11 eller ekspressionsvektoren ifølge krav 12.
14. Fremgangsmåde til fremstilling af et antistoflignende bindingsprotein, der specifikt binder den tumorassocierede MUCl-syaloglycotop CA6, som omfatter ekspression i en celle af et eller flere nukleinsyremolekyler, der koder for polypeptider med strukturer som vist ved formlerne [I] og [II] nedenfor: Vli-Li-VL2-Cl [I] Vhi-L2-Vh2-Chi [II] hvor: Vli er et variabelt domæne af let kæde af immunoglobulin, der er afledt fra DS6-antistoffet; Vl2 er et variabelt domæne af let kæde af immunoglobulin, der er afledt fra DS6-antistoffet; Vhi er et variabelt domæne af tung kæde af immunoglobulin, der er afledt fra DS6-antistoffet; Vh2 er et variabelt domæne af tung kæde af immunoglobulin, der er afledt fra DS6-antistoffet; Cl er et konstant domæne af let kæde af immunoglobulin, såsom et humant IGKC konstant domæne af let kæde af immunoglobulin; Chi er et immunoglobulin Chi konstant domæne af tung kæde, såsom et humant immunoglobulin Chi konstant domæne af tung kæde; Li og L2 er aminosyrelinkere; hvor polypeptiderne med formel [I] og polypeptiderne med formel [II] danner et bivalent monospecifikt tandem-immunoglobulin-antistoflignende bindingsprotein; og hvor polypeptidet med formel [I] omfatter en sekvens, der er mindst 80 % identisk med SEQ ID NO: 1, og polypeptidet med formel [II] omfatter en sekvens, der er mindst 80 % identisk med SEQ ID NO: 7.
15. Fremgangsmåde ifølge krav 14, hvor Vli og Vl2 er defineret ved sekvensen SEQ ID NO: 2; og Vhi og Vh2 er defineret ved sekvensen SEQ ID NO: 8.
DK14717073.2T 2013-02-05 2014-02-05 Immunimagografimiddel til anvendelse ved antistof-lægemiddel-konjugatterapi DK2953977T3 (da)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361761190P 2013-02-05 2013-02-05
EP14305082 2014-01-21
PCT/IB2014/000279 WO2014122529A1 (en) 2013-02-05 2014-02-05 Immuno imaging agent for use with antibody-drug conjugate therapy

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EP (1) EP2953977B1 (da)
JP (1) JP6605331B2 (da)
KR (1) KR20150113197A (da)
CN (1) CN105229034B (da)
AU (1) AU2014213687B2 (da)
CA (1) CA2900154A1 (da)
DK (1) DK2953977T3 (da)
ES (1) ES2657053T3 (da)
HU (1) HUE037909T2 (da)
LT (1) LT2953977T (da)
MX (1) MX2015010145A (da)
PL (1) PL2953977T3 (da)
PT (1) PT2953977T (da)
RU (1) RU2015137858A (da)
SG (2) SG11201506054XA (da)
SI (1) SI2953977T1 (da)
WO (1) WO2014122529A1 (da)

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WO2016202457A1 (en) * 2015-06-15 2016-12-22 Numab Ag Hetero-dimeric multi-specific antibody format
CN110124057B (zh) * 2019-06-06 2022-04-19 天津医科大学总医院 一种包含谷氨酰胺修饰的环糊精的抗肿瘤药物或药物载体

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CA2410551A1 (en) * 2000-06-30 2002-01-10 Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw (Vib) Heterodimeric fusion proteins
JP2007503202A (ja) 2003-07-21 2007-02-22 イミュノジェン・インコーポレーテッド Ca6抗原特異的な細胞毒性コンジュゲートおよびその使用方法
EP1917034A4 (en) * 2005-08-22 2009-04-29 Immunogen Inc CA6 ANTIGEN-SPECIFIC CYTOTOXIC CONJUGATE AND METHOD OF ITS APPLICATION
GB0822001D0 (en) * 2008-12-02 2009-01-07 Glaxosmithkline Biolog Sa Vaccine
BR112012004710A2 (pt) * 2009-09-01 2016-08-16 Abbott Lab imunoglobulinas de domínio variável duplo e uso das mesmas
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CN105229034B (zh) 2019-12-10
SI2953977T1 (en) 2018-02-28
JP2016509606A (ja) 2016-03-31
ES2657053T3 (es) 2018-03-01
CN105229034A (zh) 2016-01-06
AU2014213687A1 (en) 2015-08-20
LT2953977T (lt) 2018-02-12
EP2953977A1 (en) 2015-12-16
SG10201707391QA (en) 2017-10-30
AU2014213687B2 (en) 2018-12-06
MX2015010145A (es) 2016-05-31
CA2900154A1 (en) 2014-08-14
RU2015137858A (ru) 2017-03-13
PL2953977T3 (pl) 2018-04-30
HUE037909T2 (hu) 2018-09-28
PT2953977T (pt) 2018-01-29
EP2953977B1 (en) 2017-10-25
WO2014122529A1 (en) 2014-08-14
JP6605331B2 (ja) 2019-11-13
KR20150113197A (ko) 2015-10-07
SG11201506054XA (en) 2015-08-28

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