HRP20200415T1 - Anti-ceacam5 protutijela i njihova uporaba - Google Patents
Anti-ceacam5 protutijela i njihova uporaba Download PDFInfo
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- HRP20200415T1 HRP20200415T1 HRP20200415TT HRP20200415T HRP20200415T1 HR P20200415 T1 HRP20200415 T1 HR P20200415T1 HR P20200415T T HRP20200415T T HR P20200415TT HR P20200415 T HRP20200415 T HR P20200415T HR P20200415 T1 HRP20200415 T1 HR P20200415T1
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- immunoconjugate
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- 229940127121 immunoconjugate Drugs 0.000 claims 18
- 238000000034 method Methods 0.000 claims 7
- 239000003795 chemical substances by application Substances 0.000 claims 5
- -1 4-methyl-4-mercapto-1-oxopentyl Chemical group 0.000 claims 4
- 230000002401 inhibitory effect Effects 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 239000003053 toxin Substances 0.000 claims 3
- 231100000765 toxin Toxicity 0.000 claims 3
- 108700012359 toxins Proteins 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 229940127089 cytotoxic agent Drugs 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 206010017758 gastric cancer Diseases 0.000 claims 2
- ANZJBCHSOXCCRQ-FKUXLPTCSA-N mertansine Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCS)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 ANZJBCHSOXCCRQ-FKUXLPTCSA-N 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 229920001184 polypeptide Polymers 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims 2
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- UQVNRKBFAXNOGA-OHLDGCSVSA-N (Z)-tomaymycin Chemical compound CO[C@H]1NC2=CC(O)=C(OC)C=C2C(=O)N2C\C(=C/C)C[C@@H]12 UQVNRKBFAXNOGA-OHLDGCSVSA-N 0.000 claims 1
- FUHCFUVCWLZEDQ-UHFFFAOYSA-N 1-(2,5-dioxopyrrolidin-1-yl)oxy-1-oxo-4-(pyridin-2-yldisulfanyl)butane-2-sulfonic acid Chemical compound O=C1CCC(=O)N1OC(=O)C(S(=O)(=O)O)CCSSC1=CC=CC=N1 FUHCFUVCWLZEDQ-UHFFFAOYSA-N 0.000 claims 1
- NNPUPCNWEHWRPW-UHFFFAOYSA-N 4-(pyridin-2-yldisulfanyl)-2-sulfobutanoic acid Chemical compound OC(=O)C(S(O)(=O)=O)CCSSC1=CC=CC=N1 NNPUPCNWEHWRPW-UHFFFAOYSA-N 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 239000012624 DNA alkylating agent Substances 0.000 claims 1
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 229940123237 Taxane Drugs 0.000 claims 1
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 claims 1
- 241000863480 Vinca Species 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 229940088710 antibiotic agent Drugs 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 239000012736 aqueous medium Substances 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 108010044540 auristatin Proteins 0.000 claims 1
- 238000004587 chromatography analysis Methods 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical class C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H]2[C@H](O2)C=2C=CC=CC=2)C/C=C/C(=O)N1 PSNOPSMXOBPNNV-VVCTWANISA-N 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims 1
- 231100000433 cytotoxic Toxicity 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 230000001472 cytotoxic effect Effects 0.000 claims 1
- 238000011026 diafiltration Methods 0.000 claims 1
- AMRJKAQTDDKMCE-UHFFFAOYSA-N dolastatin Chemical class CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)C)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 AMRJKAQTDDKMCE-UHFFFAOYSA-N 0.000 claims 1
- 229940088598 enzyme Drugs 0.000 claims 1
- 230000009036 growth inhibition Effects 0.000 claims 1
- 239000003966 growth inhibitor Substances 0.000 claims 1
- 239000001963 growth medium Substances 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- YACHGFWEQXFSBS-RJXCBBHPSA-N leptomycin Chemical class OC(=O)/C=C(C)/C[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)/C=C(\C)/C=C/C[C@@H](C)\C=C(/CC)\C=C\[C@@H]1OC(=O)C=C[C@@H]1C YACHGFWEQXFSBS-RJXCBBHPSA-N 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 239000000651 prodrug Substances 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- YUOCYTRGANSSRY-UHFFFAOYSA-N pyrrolo[2,3-i][1,2]benzodiazepine Chemical class C1=CN=NC2=C3C=CN=C3C=CC2=C1 YUOCYTRGANSSRY-UHFFFAOYSA-N 0.000 claims 1
- 230000002285 radioactive effect Effects 0.000 claims 1
- 150000003384 small molecules Chemical class 0.000 claims 1
- 238000000108 ultra-filtration Methods 0.000 claims 1
Classifications
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- 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
- C07K16/30—Immunoglobulins [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
- C07K16/3007—Carcino-embryonic Antigens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
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- 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
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- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
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- 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
- A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
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- A—HUMAN NECESSITIES
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- 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
- A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6853—Carcino-embryonic antigens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
- C07K16/464—Igs containing CDR-residues from one specie grafted between FR-residues from another
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57473—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving carcinoembryonic antigen, i.e. CEA
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
Claims (22)
1. Protutijelo koje sadrži teški lanac i laki lanac naznačeno time što varijabilna domena teškog lanca sadrži sekvencu SEQ ID NO: 5, ili sekvencu koja je najmanje 85% identična s njom, CDR1-H od sekvence SEQ ID NO:7, CDR2-H od sekvence SEQ ID NO:8, i CDR3-H od sekvence SEQ ID NO:9, te varijabilna domena lakog lanca sadrži sekvencu SEQ ID NO: 29, ili sekvencu koja je najmanje 85% identična s njom, CDR1-L od sekvence SEQ ID NO:10, CDR2-L od sekvence NTR i CDR3-L od sekvence SEQ ID NO:12.
2. Protutijelo prema patentnom zahtjevu 1 naznačeno time što varijabilna domena teškog lanca sadrži sekvencu SEQ ID NO: 5, ili sekvencu koja je najmanje 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% ili 99% identična s njom.
3. Protutijelo prema patentnom zahtjevu 1 naznačeno time što varijabilna domena lakog lanca sadrži sekvencu SEQ ID NO: 29, ili sekvencu koja je najmanje 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% ili 99% identična s njom.
4. Protutijelo prema patentnom zahtjevu 1 naznačeno time što protutijelo sadrži teški lanac koji sadrži sekvencu SEQ ID NO:87, ili sekvencu koja je najmanje 85% identična s njom, te laki lanac koji sadrži sekvencu SEQ ID NO:88, ili sekvencu koja je najmanje 85% identična s njom.
5. Izolirana nukleinska kiselina naznačena time što sadrži sekvencu koja kodira protutijelo prema bilo kojem od patentnih zahtjeva 1 do 4.
6. Stanica domaćin naznačena time što je transformirana nukleinskom kiselinom prema patentnom zahtjevu 5.
7. Imunokonjugat naznačen time što sadrži protutijelo prema bilo kojem od patentnih zahtjeva 1 do 4 konjugirano ili vezano na najmanje jedno sredstvo za inhibiciju rasta.
8. Imunokonjugat prema patentnom zahtjevu 7, naznačen time što je navedeno sredstvo za inhibiciju rasta citotoksično sredstvo ili radioaktivni izotop.
9. Imunokonjugat prema patentnom zahtjevu 7 ili 8, naznačen time što je navedeno sredstvo za inhibiciju rasta odabrano iz skupine koju čine kemoterapeutska sredstva, enzimi, antibiotici, i toksini kao što su toksini malih molekula ili enzimatski aktivni toksini, taksoidi, vinka, taksani, majtanzinoid ili analozi majtanzinoida, tomamicin ili derivati pirolobenzodiazepina, derivati kriptoficina, derivati leptomicina, analozi auristatina ili dolastatina, predlijekovi, inhibitori topoizomeraze II, DNA alkilirajuća sredstva, anti-tubulinska sredstva, te analozi CC-1065 ili CC-1065.
10. Imunokonjugat prema bilo kojem od patentnih zahtjeva 7 do 9, naznačen time što je navedeno sredstvo za inhibiciju rasta (N2'-deacetil-N2'-(3-merkapto-1-oksopropil)-majtanzin) DM1 ili N2'-deacetil-N-2'(4-metil-4-merkapto-1-oksopentil)-majtanzin (DM4).
11. Imunokonjugat prema bilo kojem od patentnih zahtjeva 7 do 10, naznačen time što je protutijelo kovalentno vezano preko cijepajućeg ili ne-cijepajućeg linkera na najmanje jedno sredstvo za inhibiciju rasta.
12. Imunokonjugat prema patentnom zahtjevu 11, naznačen time što je navedeni linker odabran iz skupine koju čine N-sukcinimidil piridilditiobutirat (SPDB), 4-(piridin-2-ildisulfanil)-2-sulfo-maslačna kiselina (sulfo-SPDB), i sukcinimidil (N-maleimidometil) cikloheksan-1-karboksilat (SMCC).
13. Imunokonjugat prema bilo kojem od patentnih zahtjeva 7 do 11 naznačen time što je protutijelo kovalentno vezano putem N-sukcinimidil piridilditiobutirata (SPDB) na N2'-deacetil-N-2'(4-metil-4-merkapto-1-oksopentil)-majtanzin (DM4).
14. Imunokonjugat prema bilo kojem od patentnih zahtjeva 7 do 13 naznačen time što protutijelo sadrži teški lanac koji sadrži sekvencu SEQ ID NO:87 i laki lanac koji sadrži sekvencu SEQ ID NO:88 i kovalentno je vezano putem N-sukcinimidil piridilditiobutirata (SPDB) na N2'-deacetil-N-2'(4-metil-4-merkapto-1-oksopentil)-majtanzin (DM4).
15. Farmaceutski pripravak naznačen time što sadrži protutijelo prema bilo kojem od patentnih zahtjeva 1 do 4 ili imunokonjugat prema bilo kojem od patentnih zahtjeva 7 do 14, te farmaceutski prihvatljiv nosač.
16. Protutijelo prema bilo kojem od patentnih zahtjeva 1 do 4, ili imunokonjugat prema bilo kojem od patentnih zahtjeva 7 do 14, ili farmaceutski pripravak prema patentnom zahtjevu 15, naznačen time što je za uporabu za liječenje raka.
17. Protutijelo ili imunokonjugat prema patentnom zahtjevu 16 naznačen time što rak je rak debelog crijeva, želuca, gastrični rak ili rak pluća.
18. Postupak za proizvodnju protutijela prema bilo kojem od patentnih zahtjeva 1 do 4, koji postupak obuhvaća korake koji se sastoje od: (i) kultiviranja transformirane stanice domaćina prema patentnom zahtjevu 6; (ii) eksprimiranje navedenog protutijela ili polipeptida; i (iii) izdvajanje eksprimiranog protutijela ili polipeptida.
19. Postupak prema patentnom zahtjevu 18 naznačen time što je navedeno protutijelo prikladno odvojeno iz medija za kultiviranje konvencionalnim postupcima pročišćavanja imunoglobulina.
20. Postupak za proizvodnju imunokonjugata ili imunokonjugat prema bilo kojem od patentnih zahtjeva 7 do 14 naznačen time što sadrži korake (i) dovođenje u kontakt po izboru puferirane vodene otopine protutijela prema bilo kojem od patentnih zahtjeva 1 do 4 s otopinama poveznice i citotoksičnog spoja, i (ii) zatim izborno odvajanje konjugata koji je nastao u (i) iz nereagiranog protutijela.
21. Postupak za proizvodnju imunokonjugata ili imunokonjugat prema patentnom zahtjevu 20 naznačen time što se nakon koraka (i) ili (ii), otopina koja sadrži konjugat može podvrgnuti dodatnom koraku (iii) kromatografije, ultrafiltracije i/ili diafiltracije.
22. Postupak za pripremu farmaceutskog pripravka koji sadrži protutijelo prema bilo kojem od patentnih zahtjeva 1 do 4 ili dobivenog postupkom prema patentnim zahtjevima 18 ili 19, ili imunokonjugat prema bilo kojem od patentnih zahtjeva 7 do 14 ili dobivenog postupkom prema patentnim zahtjevima 20 ili 21, naznačen time što je učinkovita količina navedenog protutijela ili navedenog imunokonjugata otopljena ili dispergirana u farmaceutski prihvatljivom nosaču ili vodenom mediju.
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