HRP20200812T1 - Protutijela protiv teihonske kiseline staničnog zida i konjugati - Google Patents
Protutijela protiv teihonske kiseline staničnog zida i konjugati Download PDFInfo
- Publication number
- HRP20200812T1 HRP20200812T1 HRP20200812TT HRP20200812T HRP20200812T1 HR P20200812 T1 HRP20200812 T1 HR P20200812T1 HR P20200812T T HRP20200812T T HR P20200812TT HR P20200812 T HRP20200812 T HR P20200812T HR P20200812 T1 HRP20200812 T1 HR P20200812T1
- Authority
- HR
- Croatia
- Prior art keywords
- antibody
- conjugate compound
- compound according
- antibiotic conjugate
- antibiotic
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims 53
- 125000003275 alpha amino acid group Chemical group 0.000 claims 19
- 125000005647 linker group Chemical group 0.000 claims 18
- 108090000765 processed proteins & peptides Proteins 0.000 claims 17
- 238000000034 method Methods 0.000 claims 9
- 239000002253 acid Substances 0.000 claims 6
- 230000003115 biocidal effect Effects 0.000 claims 6
- 241000191967 Staphylococcus aureus Species 0.000 claims 5
- 210000004027 cell Anatomy 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 229940124597 therapeutic agent Drugs 0.000 claims 4
- 239000003242 anti bacterial agent Substances 0.000 claims 3
- ALBODLTZUXKBGZ-JUUVMNCLSA-N (2s)-2-amino-3-phenylpropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CC1=CC=CC=C1 ALBODLTZUXKBGZ-JUUVMNCLSA-N 0.000 claims 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
- 125000000539 amino acid group Chemical group 0.000 claims 2
- 230000001580 bacterial effect Effects 0.000 claims 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims 2
- 210000002421 cell wall Anatomy 0.000 claims 2
- 229960002173 citrulline Drugs 0.000 claims 2
- 235000018417 cysteine Nutrition 0.000 claims 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 2
- PZFAZQUREQIODZ-LJQANCHMSA-N dvf0pr037d Chemical compound C1CCOC(C=N2)=C1C=C2CNC(CC1)CCN1C[C@H]1N2C(=O)C=NC(C=CC3=O)=C2N3C1 PZFAZQUREQIODZ-LJQANCHMSA-N 0.000 claims 2
- -1 glidant Substances 0.000 claims 2
- 208000015181 infectious disease Diseases 0.000 claims 2
- AGGWFDNPHKLBBV-YUMQZZPRSA-N (2s)-2-[[(2s)-2-amino-3-methylbutanoyl]amino]-5-(carbamoylamino)pentanoic acid Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=O AGGWFDNPHKLBBV-YUMQZZPRSA-N 0.000 claims 1
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims 1
- NLEPLDKPYLYCSY-UHFFFAOYSA-N 2-fluoroquinoline Chemical compound C1=CC=CC2=NC(F)=CC=C21 NLEPLDKPYLYCSY-UHFFFAOYSA-N 0.000 claims 1
- MPORYQCGWFQFLA-ONPDANIMSA-N 7-[(7s)-7-amino-5-azaspiro[2.4]heptan-5-yl]-8-chloro-6-fluoro-1-[(1r,2s)-2-fluorocyclopropyl]-4-oxoquinoline-3-carboxylic acid;trihydrate Chemical compound O.O.O.C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1.C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 MPORYQCGWFQFLA-ONPDANIMSA-N 0.000 claims 1
- 239000004475 Arginine Substances 0.000 claims 1
- 241000894006 Bacteria Species 0.000 claims 1
- 108090000712 Cathepsin B Proteins 0.000 claims 1
- 108010069514 Cyclic Peptides Proteins 0.000 claims 1
- 102000001189 Cyclic Peptides Human genes 0.000 claims 1
- 108010013198 Daptomycin Proteins 0.000 claims 1
- 108010016626 Dipeptides Proteins 0.000 claims 1
- 239000004471 Glycine Substances 0.000 claims 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 claims 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 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
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
- 239000004472 Lysine Substances 0.000 claims 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 claims 1
- YJQPYGGHQPGBLI-UHFFFAOYSA-N Novobiocin Natural products O1C(C)(C)C(OC)C(OC(N)=O)C(O)C1OC1=CC=C(C(O)=C(NC(=O)C=2C=C(CC=C(C)C)C(O)=CC=2)C(=O)O2)C2=C1C YJQPYGGHQPGBLI-UHFFFAOYSA-N 0.000 claims 1
- 108091005804 Peptidases Proteins 0.000 claims 1
- 239000004365 Protease Substances 0.000 claims 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
- 108010053950 Teicoplanin Proteins 0.000 claims 1
- 239000004098 Tetracycline Substances 0.000 claims 1
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 claims 1
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 claims 1
- WPVFJKSGQUFQAP-GKAPJAKFSA-N Valcyte Chemical group N1C(N)=NC(=O)C2=C1N(COC(CO)COC(=O)[C@@H](N)C(C)C)C=N2 WPVFJKSGQUFQAP-GKAPJAKFSA-N 0.000 claims 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 1
- 108010059993 Vancomycin Proteins 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 235000004279 alanine Nutrition 0.000 claims 1
- 150000001412 amines Chemical group 0.000 claims 1
- 229940126575 aminoglycoside Drugs 0.000 claims 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims 1
- 229960000723 ampicillin Drugs 0.000 claims 1
- 235000009697 arginine Nutrition 0.000 claims 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 1
- 239000012752 auxiliary agent Substances 0.000 claims 1
- 229960004099 azithromycin Drugs 0.000 claims 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims 1
- DDTDNCYHLGRFBM-YZEKDTGTSA-N chembl2367892 Chemical compound CC(=O)N[C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@H]1O[C@@H]([C@H]1C(N[C@@H](C2=CC(O)=CC(O[C@@H]3[C@H]([C@H](O)[C@H](O)[C@@H](CO)O3)O)=C2C=2C(O)=CC=C(C=2)[C@@H](NC(=O)[C@@H]2NC(=O)[C@@H]3C=4C=C(O)C=C(C=4)OC=4C(O)=CC=C(C=4)[C@@H](N)C(=O)N[C@H](CC=4C=C(Cl)C(O5)=CC=4)C(=O)N3)C(=O)N1)C(O)=O)=O)C(C=C1Cl)=CC=C1OC1=C(O[C@H]3[C@H]([C@@H](O)[C@H](O)[C@H](CO)O3)NC(C)=O)C5=CC2=C1 DDTDNCYHLGRFBM-YZEKDTGTSA-N 0.000 claims 1
- 235000013477 citrulline Nutrition 0.000 claims 1
- 229960002227 clindamycin Drugs 0.000 claims 1
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims 1
- 230000021615 conjugation Effects 0.000 claims 1
- 229960002488 dalbavancin Drugs 0.000 claims 1
- 108700009376 dalbavancin Proteins 0.000 claims 1
- DOAKLVKFURWEDJ-QCMAZARJSA-N daptomycin Chemical compound C([C@H]1C(=O)O[C@H](C)[C@@H](C(NCC(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@H](CO)C(=O)N[C@H](C(=O)N1)[C@H](C)CC(O)=O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CCCCCCCCC)C(=O)C1=CC=CC=C1N DOAKLVKFURWEDJ-QCMAZARJSA-N 0.000 claims 1
- 229960005484 daptomycin Drugs 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- AVAACINZEOAHHE-VFZPANTDSA-N doripenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](CNS(N)(=O)=O)C1 AVAACINZEOAHHE-VFZPANTDSA-N 0.000 claims 1
- 229960000895 doripenem Drugs 0.000 claims 1
- 229960004679 doxorubicin Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229940124307 fluoroquinolone Drugs 0.000 claims 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 1
- 229960005277 gemcitabine Drugs 0.000 claims 1
- 229950010739 gepotidacin Drugs 0.000 claims 1
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 claims 1
- 229960002182 imipenem Drugs 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 claims 1
- 235000018977 lysine Nutrition 0.000 claims 1
- 239000003120 macrolide antibiotic agent Substances 0.000 claims 1
- 229940041033 macrolides Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229960002950 novobiocin Drugs 0.000 claims 1
- YJQPYGGHQPGBLI-KGSXXDOSSA-N novobiocin Chemical compound O1C(C)(C)[C@H](OC)[C@@H](OC(N)=O)[C@@H](O)[C@@H]1OC1=CC=C(C(O)=C(NC(=O)C=2C=C(CC=C(C)C)C(O)=CC=2)C(=O)O2)C2=C1C YJQPYGGHQPGBLI-KGSXXDOSSA-N 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 235000008729 phenylalanine Nutrition 0.000 claims 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 1
- 229950009965 radezolid Drugs 0.000 claims 1
- BTTNOGHPGJANSW-IBGZPJMESA-N radezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C1=CC=C(C=2C=CC(CNCC=3NN=NC=3)=CC=2)C(F)=C1 BTTNOGHPGJANSW-IBGZPJMESA-N 0.000 claims 1
- STZYTFJPGGDRJD-NHUWBDDWSA-N retapamulin Chemical compound C([C@H]([C@@]1(C)[C@@H](C[C@@](C)(C=C)[C@@H](O)[C@@H]2C)OC(=O)CS[C@@H]3C[C@H]4CC[C@H](N4C)C3)C)C[C@]32[C@H]1C(=O)CC3 STZYTFJPGGDRJD-NHUWBDDWSA-N 0.000 claims 1
- 229960002771 retapamulin Drugs 0.000 claims 1
- 229960003177 sitafloxacin Drugs 0.000 claims 1
- 125000006850 spacer group Chemical group 0.000 claims 1
- 229960001608 teicoplanin Drugs 0.000 claims 1
- 229960002180 tetracycline Drugs 0.000 claims 1
- 229930101283 tetracycline Natural products 0.000 claims 1
- 235000019364 tetracycline Nutrition 0.000 claims 1
- 150000003522 tetracyclines Chemical class 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 229960003500 triclosan Drugs 0.000 claims 1
- 229940010343 valcyte Drugs 0.000 claims 1
- 235000014393 valine Nutrition 0.000 claims 1
- 239000004474 valine Substances 0.000 claims 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 claims 1
- 229960003165 vancomycin Drugs 0.000 claims 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 claims 1
- KGPGQDLTDHGEGT-JCIKCJKQSA-N zeven Chemical compound C=1C([C@@H]2C(=O)N[C@H](C(N[C@H](C3=CC(O)=C4)C(=O)NCCCN(C)C)=O)[C@H](O)C5=CC=C(C(=C5)Cl)OC=5C=C6C=C(C=5O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@H](O5)C(O)=O)NC(=O)CCCCCCCCC(C)C)OC5=CC=C(C=C5)C[C@@H]5C(=O)N[C@H](C(N[C@H]6C(=O)N2)=O)C=2C(Cl)=C(O)C=C(C=2)OC=2C(O)=CC=C(C=2)[C@H](C(N5)=O)NC)=CC=C(O)C=1C3=C4O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O KGPGQDLTDHGEGT-JCIKCJKQSA-N 0.000 claims 1
- 150000003952 β-lactams Chemical class 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
- C07K16/1271—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Micrococcaceae (F), e.g. Staphylococcus
-
- 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
- A61K47/6807—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
- A61K47/6809—Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
-
- 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
- A61K47/6835—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
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
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Claims (52)
1. Spoj konjugata protutijelo-antibiotik, naznačen time, da obuhvaća monoklonsko protutijelo protiv teihonske kiseline staničnog zida (anti-WTA-engl. anti-wall teichoic acid), pri čemu se to monoklonsko protutijelo protiv teihonske kiseline veže na Staphylococcus aureus, i kovalentno je vezano na antibiotik iz rifamicin-vrste putem peptidnog povezivača (L) koji se može cijepati kroz S. aureus-endopeptidazu ili S. aureus-cisteinsku proteazu, gdje je spoj konjugata protutijelo-antibiotik odabran od sljedećih formula:
[image]
gdje
R5 je neovisno odabran od H i C1-C12-alkila; i
n iznosi 0 ili 1; i
[image]
gdje
R3 je neovisno odabran od H i C1-C12-alkila; i
n iznosi 1 ili 2;
pri čemu R je H, C1-C12-alkil ili C(O)CH3;
L je peptidni povezivač koji ima sljedeću formulu:
-Str-Pep-Y-
gdje je Str jedinica za produljenje; Pep je peptid od dva do 12 aminokiselinskih ostataka, i Y je jedinica za držanje razmaka;
Ab je monoklonsko protutijelo protiv teihonske kiseline staničnog zida; i
p je cijeli broj od 1 do 8;
pri čemu VL od anti-WTA monoklonskog protutijela, obuhvaća sljedeće: CDR L1 koje sadrži sekvencu KSSQSIFRTSRNKNLLN (identifikacijskog broja sekvence 99), CDR L2 koje sadrži sekvencu WASTRKS (identifikacijskog broja sekvence 100) i CDR L3 koje sadrži sekvencu QQYFSPPYT (identifikacijskog broja sekvence 101); dok VH od anti-WTA monoklonskog protutijela, obuhvaća sljedeće: CDR H1 koje sadrži sekvencu SFWMH (identifikacijskog broja sekvence 102), CDR H2 koje sadrži sekvencu FTNNEGTTTAYADSVRG (identifikacijskog broja sekvence 103) i CDR H3 koje sadrži sekvencu GEGGLDD (identifikacijskog broja sekvence 118) ili GDGGLDD (identifikacijskog broja sekvence 104).
2. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da protutijelo obuhvaća VL koji sadrži aminokiselinsku sekvencu identifikacijskog broja 119.
3. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, da protutijelo obuhvaća VH koji sadrži aminokiselinsku sekvencu identifikacijskog broja 156.
4. Spoj konjugata protutijelo-antibiotik prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time, da protutijelo obuhvaća VL i VH, pri čemu VL sadrži sekvencu identifikacijskog broja 119, dok VH sadrži sekvencu identifikacijskog broja 156.
5. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da protutijelo obuhvaća laki lanac (LC) gdje LC sadrži aminokiselinsku sekvencu identifikacijskog broja 121, i teški lanac (HC) gdje HC sadrži aminokiselinsku sekvencu identifikacijskog broja sekvence 146, 147, 157 ili 124.
6. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da protutijelo obuhvaća laki lanac (LC) gdje LC sadrži aminokiselinsku sekvencu identifikacijskog broja 123, i teški lanac (HC) gdje HC sadrži aminokiselinsku sekvencu identifikacijskog broja sekvence 146, 147, 157 ili 124.
7. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da protutijelo obuhvaća laki lanac (LC) gdje LC sadrži aminokiselinsku sekvencu identifikacijskog broja 145, i teški lanac (HC) gdje HC sadrži aminokiselinsku sekvencu identifikacijskog broja sekvence 146, 147, 157 ili 124.
8. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, da protutijelo obuhvaća VH koji sadrži aminokiselinsku sekvencu identifikacijskog broja sekvence 120.
9. Spoj konjugata protutijelo-antibiotik prema bilo kojem od patentnih zahtjeva 1, 2 ili 8, naznačen time, da protutijelo obuhvaća VL i VH, pri čemu VL sadrži sekvencu identifikacijskog broja 119, dok VH sadrži sekvencu identifikacijskog broja 120.
10. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da protutijelo obuhvaća laki lanac (LC) gdje LC sadrži aminokiselinsku sekvencu identifikacijskog broja 121, i teški lanac (HC) gdje HC sadrži aminokiselinsku sekvencu identifikacijskog broja 146.
11. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da protutijelo obuhvaća laki lanac (LC) gdje LC sadrži aminokiselinsku sekvencu identifikacijskog broja 123, i teški lanac (HC) gdje HC sadrži aminokiselinsku sekvencu identifikacijskog broja 147.
12. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da protutijelo obuhvaća laki lanac (LC) gdje LC sadrži aminokiselinsku sekvencu identifikacijskog broja 145, i teški lanac (HC) gdje HC sadrži aminokiselinsku sekvencu identifikacijskog broja 157.
13. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da protutijelo obuhvaća laki lanac (LC) gdje LC sadrži aminokiselinsku sekvencu identifikacijskog broja 145, i teški lanac (HC) gdje HC sadrži aminokiselinsku sekvencu identifikacijskog broja 147.
14. Spoj konjugata protutijelo-antibiotik prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da antibiotik rifamicin-vrste obuhvaća kvaternarni amin koji je priključen na peptidni povezivač.
15. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 14, naznačen time, da je peptidni povezivač priključen na cistein ili cistein modificiran inženjeringom od anti-WTA protutijela.
16. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da peptidni povezivač je stafopain-B-povezivač ili stafopain-A-povezivač koji se može cijepati.
17. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 16, naznačen time, da peptidni povezivač je povezivač koji se može cijepati od ljudske proteaze katepsin B.
18. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 17, naznačen time, da peptidni povezivač je val-cit dipeptidni povezivač.
19. Spoj konjugata protutijelo-antibiotik prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da p iznosi od 2 do 4.
20. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da ima sljedeću formulu:
[image]
21. Spoj konjugata protutijelo-antibiotik prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da Str ima sljedeću formulu:
[image]
u kojoj je R6 odabran iz skupine koju čine: Ci-Cio-alkilen-, -C3-C8-karbociklo, -O-(C1-C8-alkil)-, -arilen-, -C1-C10-alkilen-arilen-, -arilen-Ci-C10-alkilen-, -C1-C10-alkilen-(C3-C8-karbociklo)-, -(C3-C8-karbociklo)-Ci-Cio-alkilen-, -C3-C8-heterociklo-, -C1-C10-alkilen-(C3-C8-heterociklo)-, -(C3-C8-heterociklo)-C1-C10-alkilen-, -(CH2CH2O)r- i –(CH2CH2O)r-CH2; dok r je cijeli broj u rasponu od 1 do 10.
22. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 21, naznačen time, da R6 je –(CH2)5-.
23. Spoj konjugata protutijelo-antibiotik prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da Pep obuhvaća dva ili 12 aminokiselinskih ostataka koji su neovisno odabrani od sljedećih: glicin, alanin, fenilalanin, lizin, arginin, valin i citrulin.
24. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 23, naznačen time, da je Pep odabran od valin-citrulina (val-cit, vc); fenilalanin-lizina (fk); i valin-citrulin-fenilalanina (val-cit-phe).
25. Spoj konjugata protutijelo-antibiotik prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da Y obuhvaća para-aminobenzil ili para-aminobenziloksikarbonil.
26. Spoj konjugata protutijelo-antibiotik prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da je L peptidni povezivač koji ima sljedeću formulu:
[image]
u kojoj su AA1 i AA2 neovisno odabrani iz aminokiselinskog bočnog lanca.
27. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 26, naznačen time, da je aminokiselinski bočni lanac neovisno odabran od sljedećih: H, -CH3, –CH2(C6H5), -CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, -CHCH(CH3)CH3 i -CH2CH2CH2NHC(O)NH2.
28. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 26, naznačen time, da je L peptidni povezivač koji ima sljedeću formulu:
[image]
29. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 26, naznačen time, da je L peptidni povezivač koji ima sljedeću formulu:
[image]
30. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 29, naznačen time, da je L peptidni povezivač koji ima sljedeću formulu:
[image]
31. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 26, naznačen time, da je L peptidni povezivač koji ima sljedeću formulu:
[image]
32. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 31, naznačen time, da je L peptidni povezivač koji ima sljedeću formulu:
[image]
33. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 26, naznačen time, da je L peptidni povezivač koji ima sljedeću formulu:
[image]
34. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 33, naznačen time, da je L peptidni povezivač koji ima sljedeću formulu:
[image]
35. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 26, naznačen time, da je L peptidni povezivač koji ima sljedeću formulu:
[image]
u kojoj R7 je neovisno odabran od H i C1-C12-alkila.
36. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 26, naznačen time, da ima sljedeću formulu:
[image]
37. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 36, naznačen time, da ima sljedeću formulu:
[image]
38. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 26, naznačen time, da ima sljedeću formulu:
[image]
39. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 38, naznačen time, da ima sljedeću formulu:
[image]
40. Spoj konjugata protutijelo-antibiotik prema patentnom zahtjevu 1, naznačen time, da ima sljedeću formulu:
[image]
gdje Ab je monoklonsko protutijelo protiv teihonske kiseline staničnog zida (anti-WTA), koje se veže na Staphylococcus aureus, pri čemu VL od monoklonskog protutijela protiv teihonske kiseline staničnog zida (anti-WTA), obuhvaća sljedeće: CDR L1 koje sadrži sekvencu KSSQSIFRTSRNKNLLN (identifikacijskog broja sekvence 99), CDR L2 koje sadrži sekvencu WASTRKS (identifikacijskog broja sekvence 100) i CDR L3 koje sadrži sekvencu QQYFSPPYT (identifikacijskog broja sekvence 101); te VH od anti-WTA monoklonskog protutijela, obuhvaća sljedeće: CDR H1 koje sadrži sekvencu SFWMH (identifikacijskog broja sekvence 102), CDR H2 koje sadrži sekvencu FTNNEGTTTAYADSVRG (identifikacijskog broja sekvence 103) i CDR H3 koje sadrži sekvencu GEGGLDD (identifikacijskog broja sekvence 118); i
p je cijeli broj od 1 do 8.
41. Farmaceutski pripravak, naznačen time, da sadrži spoj konjugata protutijelo-antibiotik u skladu s bilo kojim od prethodnih zahtjeva, i farmaceutski prihvatljiv nosač, klizno sredstvo, razrjeđivač ili pomoćno sredstvo.
42. Postupak za proizvodnju spoja konjugata protutijelo-antibiotik u skladu s bilo kojim od zahtjeva 1 do 40, naznačen time, da obuhvaća konjugiranje antibiotika rifamicin-vrste na monoklonsko WTA-protutijelo.
43. Spoj konjugata protutijelo-antibiotik prema bilo kojem od patentnih zahtjeva 1 do 40, naznačen time, da je za terapeutsku uporabu.
44. Spoj konjugata protutijelo-antibiotik prema bilo kojem od patentnih zahtjeva 1 do 40, naznačen time, da se upotrebljava u postupku liječenja bakterijske infekcije kod pacijenta, pri čemu ta bakterijska infekcija je infekcija bakterijom Staphylococcus aureus.
45. Spoj konjugata protutijelo-antibiotik za uporabu u postupku prema patentnom zahtjevu 44, naznačen time, da se kod pacijenta pomoću liječenja smanjuje količina bakterija.
46. Spoj konjugata protutijelo-antibiotik prema bilo kojem od patentnih zahtjeva 1 do 40, naznačen time, da se upotrebljava u postupku smanjivanja broja unutarstaničnih bakterijskih stanica Staphylococcus aureus u stanicama domaćina kod pacijenta koji ima infekciju bakterijom Staphylococcus aureus, a da se pritom ne smanjuje broj stanica domaćina.
47. Spoj konjugata protutijelo-antibiotik za uporabu u postupku prema patentnom zahtjevu 46, naznačen time, da se smanjuje broj izdržljivih bakterijskih stanica.
48. Spoj konjugata protutijelo-antibiotik za uporabu u postupku prema bilo kojem od patentnih zahtjeva 44 do 47, naznačen time, da se radi o pacijentu koji je čovjek.
49. Spoj konjugata protutijelo-antibiotik za uporabu u postupku prema bilo kojem od patentnih zahtjeva 44 do 48, naznačen time, da nadalje obuhvaća primjenu drugog terapeutskog sredstva.
50. Spoj konjugata protutijelo-antibiotik za uporabu u postupku prema patentnom zahtjevu 49, naznačen time, da se kod drugog terapeutskog sredstva radi o antibiotiku.
51. Spoj konjugata protutijelo-antibiotik za uporabu u postupku prema patentnom zahtjevu 50, naznačen time, da drugo terapeutsko sredstvo je antibiotik odabran iz strukturnog razreda koji se sastoji od (i) aminoglikozida; (ii) betalaktama; (iii) makrolida/cikličkih peptida; (iv) tetraciklina; (v) fluorokinolina/fluorokinolona; i (vi) oksazolidinona.
52. Spoj konjugata protutijelo-antibiotik za uporabu u postupku prema patentnom zahtjevu 50, naznačen time, da drugo terapeutsko sredstvo je antibiotik odabran iz skupine koja se sastoji od klindamicina, novobiocina, retapamulina, daptomicina, GSK-2140944 (gepotidacina) koji ima sljedeću strukturu:
[image]
CG-400549 koji ima sljedeću strukturu:
[image]
sitafloksacina, teikoplanina, triklosana, naftiridona, radezolida, doksorubicina, ampicilina, vankomicina, imipenema, doripenema, gemcitabina, dalbavancina i azitromicina.
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