HRP20190486T1 - Konjugirani spojevi koji sadrže cisteinska protutijela dobivena inženjeringom - Google Patents
Konjugirani spojevi koji sadrže cisteinska protutijela dobivena inženjeringom Download PDFInfo
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- HRP20190486T1 HRP20190486T1 HRP20190486TT HRP20190486T HRP20190486T1 HR P20190486 T1 HRP20190486 T1 HR P20190486T1 HR P20190486T T HRP20190486T T HR P20190486TT HR P20190486 T HRP20190486 T HR P20190486T HR P20190486 T1 HRP20190486 T1 HR P20190486T1
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- Prior art keywords
- compound according
- amino acid
- conjugated compound
- cysteine
- antibody
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- 150000001875 compounds Chemical class 0.000 title claims 16
- 235000018417 cysteine Nutrition 0.000 claims 16
- 235000001014 amino acid Nutrition 0.000 claims 14
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 14
- -1 cysteine amino acid Chemical class 0.000 claims 6
- 108091006020 Fc-tagged proteins Proteins 0.000 claims 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims 5
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 239000012634 fragment Substances 0.000 claims 3
- 238000006467 substitution reaction Methods 0.000 claims 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 239000000427 antigen Substances 0.000 claims 2
- 102000036639 antigens Human genes 0.000 claims 2
- 108091007433 antigens Proteins 0.000 claims 2
- 150000001945 cysteines Chemical class 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- YUOCYTRGANSSRY-UHFFFAOYSA-N pyrrolo[2,3-i][1,2]benzodiazepine Chemical compound C1=CN=NC2=C3C=CN=C3C=CC2=C1 YUOCYTRGANSSRY-UHFFFAOYSA-N 0.000 claims 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 1
- 239000004475 Arginine Substances 0.000 claims 1
- 102000019034 Chemokines Human genes 0.000 claims 1
- 108010012236 Chemokines Proteins 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 claims 1
- 108090000695 Cytokines Proteins 0.000 claims 1
- 108020004414 DNA Proteins 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 239000004606 Fillers/Extenders Substances 0.000 claims 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 1
- 108700011259 MicroRNAs Proteins 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- 108091093037 Peptide nucleic acid Proteins 0.000 claims 1
- 108091030071 RNAI Proteins 0.000 claims 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 1
- 108020004459 Small interfering RNA Proteins 0.000 claims 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 1
- 239000004037 angiogenesis inhibitor Substances 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 1
- 108010044540 auristatin Proteins 0.000 claims 1
- 229960002685 biotin Drugs 0.000 claims 1
- 235000020958 biotin Nutrition 0.000 claims 1
- 239000011616 biotin Substances 0.000 claims 1
- 150000001720 carbohydrates Chemical class 0.000 claims 1
- 239000002738 chelating agent Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000021615 conjugation Effects 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 239000007850 fluorescent dye Substances 0.000 claims 1
- 230000009368 gene silencing by RNA Effects 0.000 claims 1
- 235000013922 glutamic acid Nutrition 0.000 claims 1
- 239000004220 glutamic acid Substances 0.000 claims 1
- 239000003102 growth factor Substances 0.000 claims 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 1
- 239000005556 hormone Substances 0.000 claims 1
- 229940088597 hormone Drugs 0.000 claims 1
- 239000003667 hormone antagonist Substances 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 229940121354 immunomodulator Drugs 0.000 claims 1
- 230000002584 immunomodulator Effects 0.000 claims 1
- 238000003780 insertion Methods 0.000 claims 1
- 230000037431 insertion Effects 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 239000002679 microRNA Substances 0.000 claims 1
- 230000000861 pro-apoptotic effect Effects 0.000 claims 1
- 210000002966 serum Anatomy 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 102000003390 tumor necrosis factor Human genes 0.000 claims 1
- 239000004474 valine Substances 0.000 claims 1
- 238000012800 visualization Methods 0.000 claims 1
Classifications
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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
- 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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- A61K47/50—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
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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
- A61K47/6801—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
- A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
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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
- 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
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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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
- 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
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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
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P35/00—Antineoplastic agents
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- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
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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
- C07K2317/52—Constant or Fc region; Isotype
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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
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
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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
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/526—CH3 domain
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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
- C07K2317/71—Decreased effector function due to an Fc-modification
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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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- 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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- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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Claims (15)
1. Konjugirani spoj koji sadrži cisteinsko protutijelo dobiveno inženjeringom ili Fc fuzijski protein i najmanje jedan heterologni ostatak, naznačen time što:
(i) Fc domena protutijela ili Fc fuzijski protein obuhvaća umetanje cistein aminokiseline između položaja 239 i 240, pri čemu je numeriranje položaja aminokiseline prema EU indeksu kako je navedeno u Kabatu; i
(ii) pri čemu je najmanje jedan heterologni ostatak konjugiran na cistein aminokiselinu koja je umetnuta između položaja 239 i 240.
2. Konjugirani spoj prema zahtjevu 1 naznačen time što nadalje sadrži jedan ili više cisteina dobivenih inženjeringom na 241, 243, 251, 253, 258, 264, 269, 271, 272, 274, 280, 281, 285, 288, 291, 293, 294, 296, 301, 307, 309, 311, 318, 329, 340, 341, 345, 357, 385, 386, 387, 401, 402, 411, 417, 433, 435, ili 439 pri čemu je numeriranje položaja aminokiseline prema EU indeksu kako je navedeno u Kabatu.
3. Konjugirani spoj prema zahtjevu 2, naznačen time što je inženjeringom dobivena cisteinska aminokiselina odabrana od supstitucija cisteinske aminokiseline na položajima aminokiselina 241, 243, 251, 253, 258, 264, 271, 285, 288, 291, 296, 301, 307, 309, 311, 329, 385, 387, 433, ili 435, i njihovih kombinacija.
4. Konjugirani spoj prema zahtjevu 2, naznačen time što je inženjeringom dobivena cisteinska aminokiselina odabrana od supstitucija cisteinske aminokiseline na položajima aminokiselina 258, ili 435, i njihovih kombinacija.
5. Konjugirani spoj prema bilo kojem od zahtjeva 1 do 4, naznačen time što sadrži:
Cistein (C) umetnut između Serina (S) koji se nalazi na položaju 239 i Valina (V) koji se nalazi na položaju 240; i
(a) Cistein (C) koji zamjenjuje glutaminsku kiselinu (E) koja se nalazi na položaju 258;
(b) Cistein (C) koji zamjenjuje histidin (H) koji se nalazi na položaju 435;
(c) Cistein (C) koji zamjenjuje arginin (R) koji se nalazi na položaju 435; ili
(d) njihovu kombinaciju,
pri čemu je numeriranje položaja aminokiseline prema EU indeksu kako je navedeno u Kabatu.
6. Konjugirani spoj prema bilo kojem od zahtjeva 1 do 5, naznačen time što Fc domena nadalje sadrži najmanje jedan cisteinski ostatak dobiven inženjeringom odabran od cisteinskih aminokiselinskih supstitucija na položajima aminokiselina 239, 248, 254, 273, 279, 282, 284, 286, 287, 289, 297, 298, 312, 324, 326, 330, 335, 337, 339, 350, 355, 356, 359, 360, 361, 375, 383, 384, 389, 398, 400, 413, 415, 418, 422, 440, 441, 442, 443 i 446.
7. Konjugirani spoj prema bilo kojem od zahtjeva 1 do 6, naznačen time što je svaki od heterolognih ostataka konjugiran na cistein dobiven inženjeringom.
8. Konjugirani spoj prema bilo kojem od zahtjeva 1 do 7, naznačen time što Fc domena protutijela ili Fc fuzijski protein je ljudska IgG Fc domena, proizvoljno odabrana iz skupine koja se sastoji od IgG Fc domene od IgG1, IgG2, IgG3, ili IgG4.
9. Konjugirani spoj prema bilo kojem od zahtjeva 1 do 8, naznačen time što Fc fuzijski protein odabrana iz skupine koja se sastoji od domenu koja veže antigen sele odabranu iz skupine koju čine: (a) scFv; (b) diatijelo; (c) Fd fragment; (d) Fv fragment; (e) F(ab')2 fragment; i (f) F(ab) fragment.
10. Konjugirani spoj prema bilo kojem od zahtjeva 1 do 8, naznačen time što protutijelo je a monoklonsko protutijelo, bispecifično protutijelo, multispecifično protutijelo, kimerno protutijelo, ljudsko protutijelo, ili humanizirano protutijelo.
11. Konjugirani spoj prema bilo kojem od zahtjeva 1 do 10, naznačen time što najmanje jedan heterologni ostatak je toksin, lijek, radionuklid, imunomodulator, citokin, limfokin, kemokin, faktor rasta, faktor nekroze tumora, hormon, antagonist hormona, enzim, oligonukleotid, DNA, RNA, siRNA, RNAi, mikroRNA, peptidna nukleinska kiselina, fotoaktivno terapijsko sredstvo, anti-angiogeno sredstvo, pro-apoptotičko sredstvo, ne-prirodna amino kiselina, peptid, lipid, ugljikohidrat, skeletna molekula, fluorescentna oznaka, vizualizacijski peptid, biotin, produživač poluživota u serumu, oznaka za hvatanje, sredstvo za keliranje, kruta podloga, ili njihova kombinacija, te pri čemu se konjugacija nalazi na jednom od cisteina dobivenih inženjeringom.
12. Konjugirani spoj prema zahtjevu 11, naznačen time što je lijek auristatin, tubulizin, a pirolobenzodiazepin (PBD) ili majtanzinoid.
13. Konjugirani spoj prema bilo kojem od zahtjeva 1 do 12, naznačen time što se cisteinsko protutijelo dobiveno inženjeringom ili Fc fuzijski protein veže na najmanje jednu metu.
14. Konjugirani spoj prema zahtjevu 13, naznačen time što je meta tumorski antigen i heterologni dio je antitumorsko sredstvo.
15. Konjugirani spoj prema bilo kojem od zahtjeva 1 do 14 naznačen time što je za uporabu u terapiji.
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EP15777039.7A EP3129406B1 (en) | 2014-04-11 | 2015-04-10 | Conjugated compounds comprising cysteine-engineered antibodies |
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EP (1) | EP3129406B1 (hr) |
JP (1) | JP6685924B2 (hr) |
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CA (1) | CA2944784A1 (hr) |
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DK (1) | DK3129406T3 (hr) |
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HU (1) | HUE041976T2 (hr) |
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SI (1) | SI3129406T1 (hr) |
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US10046056B2 (en) | 2014-02-21 | 2018-08-14 | École Polytechnique Fédérale De Lausanne (Epfl) | Glycotargeting therapeutics |
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AU2015243380A1 (en) | 2016-11-10 |
US20180169255A1 (en) | 2018-06-21 |
SI3129406T1 (sl) | 2019-04-30 |
TR201903526T4 (tr) | 2019-03-21 |
CY1122155T1 (el) | 2020-11-25 |
JP2017512486A (ja) | 2017-05-25 |
CN106459205A (zh) | 2017-02-22 |
RS58440B1 (sr) | 2019-04-30 |
CA2944784A1 (en) | 2015-10-15 |
AU2015243380B2 (en) | 2020-05-14 |
RU2016144146A (ru) | 2018-05-11 |
PT3129406T (pt) | 2019-04-24 |
HUE041976T2 (hu) | 2019-06-28 |
LT3129406T (lt) | 2019-04-10 |
WO2015157595A1 (en) | 2015-10-15 |
EP3129406B1 (en) | 2019-01-09 |
RU2016144146A3 (hr) | 2018-12-14 |
DK3129406T3 (en) | 2019-04-01 |
PL3129406T3 (pl) | 2019-07-31 |
ES2719584T3 (es) | 2019-07-11 |
EP3129406A4 (en) | 2017-12-06 |
JP6685924B2 (ja) | 2020-04-22 |
CN106459205B (zh) | 2021-04-09 |
US10744204B2 (en) | 2020-08-18 |
EP3129406A1 (en) | 2017-02-15 |
BR112016023436A2 (pt) | 2017-10-17 |
RU2711485C2 (ru) | 2020-01-17 |
US20210069341A1 (en) | 2021-03-11 |
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