HRP20211119T1 - POSTUPCI I PRIPRAVCI ZA DOSTAVU mRNA KODIRANIH PROTUTIJELA - Google Patents
POSTUPCI I PRIPRAVCI ZA DOSTAVU mRNA KODIRANIH PROTUTIJELA Download PDFInfo
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- HRP20211119T1 HRP20211119T1 HRP20211119TT HRP20211119T HRP20211119T1 HR P20211119 T1 HRP20211119 T1 HR P20211119T1 HR P20211119T T HRP20211119T T HR P20211119TT HR P20211119 T HRP20211119 T HR P20211119T HR P20211119 T1 HRP20211119 T1 HR P20211119T1
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- Croatia
- Prior art keywords
- uracil
- methyl
- use according
- modified
- antibody
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- 108020004999 messenger RNA Proteins 0.000 title claims 12
- 239000000203 mixture Substances 0.000 title claims 4
- 239000002502 liposome Substances 0.000 claims 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims 4
- 150000002632 lipids Chemical class 0.000 claims 3
- 125000003729 nucleotide group Chemical group 0.000 claims 3
- HPZMWTNATZPBIH-UHFFFAOYSA-N 1-methyladenine Chemical compound CN1C=NC2=NC=NC2=C1N HPZMWTNATZPBIH-UHFFFAOYSA-N 0.000 claims 2
- RFLVMTUMFYRZCB-UHFFFAOYSA-N 1-methylguanine Chemical compound O=C1N(C)C(N)=NC2=C1N=CN2 RFLVMTUMFYRZCB-UHFFFAOYSA-N 0.000 claims 2
- YSAJFXWTVFGPAX-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetic acid Chemical compound OC(=O)COC1=CNC(=O)NC1=O YSAJFXWTVFGPAX-UHFFFAOYSA-N 0.000 claims 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 claims 2
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims 2
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 claims 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 claims 2
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims 2
- 229930010555 Inosine Natural products 0.000 claims 2
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims 2
- HYVABZIGRDEKCD-UHFFFAOYSA-N N(6)-dimethylallyladenine Chemical compound CC(C)=CCNC1=NC=NC2=C1N=CN2 HYVABZIGRDEKCD-UHFFFAOYSA-N 0.000 claims 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims 2
- -1 cationic lipid Chemical class 0.000 claims 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims 2
- 229960003786 inosine Drugs 0.000 claims 2
- 239000002773 nucleotide Substances 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 108020003175 receptors Proteins 0.000 claims 2
- 102000005962 receptors Human genes 0.000 claims 2
- 229940035893 uracil Drugs 0.000 claims 2
- SATCOUWSAZBIJO-UHFFFAOYSA-N 1-methyladenine Natural products N=C1N(C)C=NC2=C1NC=N2 SATCOUWSAZBIJO-UHFFFAOYSA-N 0.000 claims 1
- WJNGQIYEQLPJMN-IOSLPCCCSA-N 1-methylinosine Chemical compound C1=NC=2C(=O)N(C)C=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WJNGQIYEQLPJMN-IOSLPCCCSA-N 0.000 claims 1
- SGAKLDIYNFXTCK-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)methylamino]acetic acid Chemical compound OC(=O)CNCC1=CNC(=O)NC1=O SGAKLDIYNFXTCK-UHFFFAOYSA-N 0.000 claims 1
- SVBOROZXXYRWJL-UHFFFAOYSA-N 2-[(4-oxo-2-sulfanylidene-1h-pyrimidin-5-yl)methylamino]acetic acid Chemical compound OC(=O)CNCC1=CNC(=S)NC1=O SVBOROZXXYRWJL-UHFFFAOYSA-N 0.000 claims 1
- JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 claims 1
- XMSMHKMPBNTBOD-UHFFFAOYSA-N 2-dimethylamino-6-hydroxypurine Chemical compound N1C(N(C)C)=NC(=O)C2=C1N=CN2 XMSMHKMPBNTBOD-UHFFFAOYSA-N 0.000 claims 1
- SMADWRYCYBUIKH-UHFFFAOYSA-N 2-methyl-7h-purin-6-amine Chemical compound CC1=NC(N)=C2NC=NC2=N1 SMADWRYCYBUIKH-UHFFFAOYSA-N 0.000 claims 1
- KOLPWZCZXAMXKS-UHFFFAOYSA-N 3-methylcytosine Chemical compound CN1C(N)=CC=NC1=O KOLPWZCZXAMXKS-UHFFFAOYSA-N 0.000 claims 1
- GJAKJCICANKRFD-UHFFFAOYSA-N 4-acetyl-4-amino-1,3-dihydropyrimidin-2-one Chemical compound CC(=O)C1(N)NC(=O)NC=C1 GJAKJCICANKRFD-UHFFFAOYSA-N 0.000 claims 1
- MQJSSLBGAQJNER-UHFFFAOYSA-N 5-(methylaminomethyl)-1h-pyrimidine-2,4-dione Chemical compound CNCC1=CNC(=O)NC1=O MQJSSLBGAQJNER-UHFFFAOYSA-N 0.000 claims 1
- WPYRHVXCOQLYLY-UHFFFAOYSA-N 5-[(methoxyamino)methyl]-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CONCC1=CNC(=S)NC1=O WPYRHVXCOQLYLY-UHFFFAOYSA-N 0.000 claims 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 claims 1
- KELXHQACBIUYSE-UHFFFAOYSA-N 5-methoxy-1h-pyrimidine-2,4-dione Chemical compound COC1=CNC(=O)NC1=O KELXHQACBIUYSE-UHFFFAOYSA-N 0.000 claims 1
- ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 claims 1
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 claims 1
- CKOMXBHMKXXTNW-UHFFFAOYSA-N 6-methyladenine Chemical compound CNC1=NC=NC2=C1N=CN2 CKOMXBHMKXXTNW-UHFFFAOYSA-N 0.000 claims 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims 1
- 229930024421 Adenine Natural products 0.000 claims 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims 1
- 101000719121 Arabidopsis thaliana Protein MEI2-like 1 Proteins 0.000 claims 1
- 102100028043 Fibroblast growth factor 3 Human genes 0.000 claims 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 claims 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims 1
- 101001043352 Homo sapiens Lysyl oxidase homolog 2 Proteins 0.000 claims 1
- 101000857677 Homo sapiens Runt-related transcription factor 1 Proteins 0.000 claims 1
- 108050002021 Integrator complex subunit 2 Proteins 0.000 claims 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 claims 1
- 102100031413 L-dopachrome tautomerase Human genes 0.000 claims 1
- 101710093778 L-dopachrome tautomerase Proteins 0.000 claims 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 claims 1
- 102100021948 Lysyl oxidase homolog 2 Human genes 0.000 claims 1
- SGSSKEDGVONRGC-UHFFFAOYSA-N N(2)-methylguanine Chemical compound O=C1NC(NC)=NC2=C1N=CN2 SGSSKEDGVONRGC-UHFFFAOYSA-N 0.000 claims 1
- 102100023606 Retinoic acid receptor alpha Human genes 0.000 claims 1
- 102100025373 Runt-related transcription factor 1 Human genes 0.000 claims 1
- 101710173694 Short transient receptor potential channel 2 Proteins 0.000 claims 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims 1
- 108091036066 Three prime untranslated region Proteins 0.000 claims 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 229960000643 adenine Drugs 0.000 claims 1
- 230000002494 anti-cea effect Effects 0.000 claims 1
- 235000012000 cholesterol Nutrition 0.000 claims 1
- 229940104302 cytosine Drugs 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 claims 1
- 229960002949 fluorouracil Drugs 0.000 claims 1
- 102000006495 integrins Human genes 0.000 claims 1
- 108010044426 integrins Proteins 0.000 claims 1
- DJLUSNAYRNFVSM-UHFFFAOYSA-N methyl 2-(2,4-dioxo-1h-pyrimidin-5-yl)acetate Chemical compound COC(=O)CC1=CNC(=O)NC1=O DJLUSNAYRNFVSM-UHFFFAOYSA-N 0.000 claims 1
- 150000004702 methyl esters Chemical class 0.000 claims 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims 1
- XJVXMWNLQRTRGH-UHFFFAOYSA-N n-(3-methylbut-3-enyl)-2-methylsulfanyl-7h-purin-6-amine Chemical compound CSC1=NC(NCCC(C)=C)=C2NC=NC2=N1 XJVXMWNLQRTRGH-UHFFFAOYSA-N 0.000 claims 1
- 230000007935 neutral effect Effects 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 claims 1
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 1
- 150000008298 phosphoramidates Chemical class 0.000 claims 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108091008726 retinoic acid receptors α Proteins 0.000 claims 1
- 235000000346 sugar Nutrition 0.000 claims 1
- 150000008163 sugars Chemical class 0.000 claims 1
- 229940113082 thymine Drugs 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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
-
- 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
- A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6911—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
- A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- C—CHEMISTRY; METALLURGY
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
Claims (8)
1. Pripravak, naznačen time, da sadrži prvu mRNA koja kodira teški lanac protutijela i drugu mRNA koja kodira laki lanac protutijela pri molarnom omjeru u rasponu od 2:1 do 1:2, za uporabu u liječenju pacijenta, pri čemu prva mRNA i druga mRNA (i) svaka sadrži 5' cap strukturu, 3' poli-A rep, 5' netranslatiranu regiju i 3' netranslatiranu regiju i (ii) one su enkapsulirane u liposomima koji sadrže kationski lipid, neutralni lipid, lipid na bazi kolesterola, i PEG-modificirani lipid i imaju dimenziju koja nije veća od 150 nm, gdje su prva mRNA koja kodira teški lanac i druga mRNA koja kodira laki lanac, enkapsulirane u istom liposomu, pri čemu je protutijelo tetramer i svaki tetramer je sastavljen od dva identična para polipeptidnih lanaca, od kojih svaki par posjeduje jedan laki lanac od otprilike 25 kD i jedan teški lanac od otprilike 50-70 kD, i time, da se pripravak daje pacijentu intravenozno i protutijelo se sustavno distribuira u pacijentu.
2. Pripravak za uporabu prema patentnom zahtjevu 1, naznačen time, da su prva mRNA i druga mRNA u molarnom omjeru od 1:1.
3. Pripravak za uporabu prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da su liposomi veličine koja nije veća od oko 100 nm ili 75 nm.
4. Pripravak za uporabu prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da su liposomi veličine u rasponu od 10 nm - 100 nm.
5. Pripravak za uporabu prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da su obje mRNA (i) modificirane u svrhu ojačanja stabilnosti, pri čemu su obje mRNA modificirane tako da uključuju nukleozidne analoge, kemijski ili biološki modificirane baze, interkalirane baze, modificirane fosfatne skupine i/ili modificirane šećere, ili (ii) kemijski nemodificirane.
6. Pripravak za uporabu prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da se obje mRNA sintetiziraju iz (i) prirodnih nukleotida adenina (A), gvanina (G), timina (T), citozina (C), i uracila (D), ili modificiranih nukleotidnih analoga odabranih iz skupine koju čine 1-metiladenin, 2-metiladenin, 2-metiltio-N-6-izopentenil-adenin, N-6-metil-adenin, N-6- izopentenil-adenin, 2-tio-citozin, 3-metil-citozin, 4-acetil-citozin, 5-metil-citozin, 2,6-diaminopurin, 1-metil-gvanin, 2-metil-gvanin, 2,2-dimetil-gvanin, 7-metilgvanin, inozin, 1-metil-inozin, pseudouracil (5-uracil), dihidro-uracil, 2-tio- uracil, 4-tiouracil, 5-karboksimetilaminometil-2-tio-uracil, 5-(karboksihidroksimetil-uracil, 5-fluorouracil, 5-bromo-uracil, 5-karboksimetilaminometil-uracil, 5-metil-2-tio-uracil, 5-metiluracil, N-uracil-5- oksioctena kiselina metil ester, 5-metilaminometil-uracil, 5-metoksiaminometil-2- tio-uracil, 5-metoksikarbonilmetil-uracil, 5-metoksi-uracil, uracil-5-oksioctena kiselina metil ester, uracil-5-oksioctena kiselina (v), 1-metil-pseudouracil, kveozin,β-D-manozil-kveozin, vibutoksozin, i fosforamidati, fosforotioati, peptidni nukleotidi, metilfosfonati, 7-deazagvanozin, 5-metilcitozin i inozin.
7. Pripravak za uporabu prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da protutijelo jest IgG.
8. Pripravak za uporabu prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da se protutijelo bira iz skupine koju čine anti-CCL2, anti-lizil oksidazi nalik-2 (LOXL2), anti-Flt-1, anti-TNF -α, anti-interleukin-2Rα receptor (CD25), anti TGFp, anti-B-stanični aktivacijski faktor, anti-alfa-4 integrin, anti- BAGE, anti-β-katenin/m, anti Bcr-abl, anti-C5, anti-CA125, anti-CAMEL, anti- CAP-1, anti-CASP-8, anti-CD4, anti-CD19, anti-CD20, anti-CD22, anti-CD25, anti-CDC27/m, anti-CD30, anti-CD33, anti-CD52, anti-CD56, anti-CD80, anti- CDK4/m, anti-CEA, anti-CT, anti-CTL4, anti-Cyp-B, anti-DAM, anti-EGFR, anti- ErbB3, anti-ELF2M, anti-EMMPRIN, anti-EpCam, anti-ETV6-AML1, anti-HER2, anti-G250, anti-GAGE, anti-GnT-V, anti-Gp100, anti-HAGE, anti-HER-2/neu, anti-HLA-A*0201-R170I, anti-IGF-IR, anti-IL-2R, anti-IL-5, anti-MC1R, anti- miosin/m, anti-MUC1, anti-MUM-1, -2, -3, anti-proteinaza-3, anti-p190 minorni bcr-abl, anti-Pml/RARα, anti-PRAMS, anti-PSA, anti-PSM, anti-PSMA, anti- RAGE, anti-RANKL, anti RUI ili RU2, anti-SAGE, anti-SART-1 ili anti-SART-3, anti-survivin, anti-TEL/AML1, anti-TPI/m, anti-TRP-1, anti-TRP-2, anti-TRP- 2/INT2, anti-VEGF i anti-VEGF receptor.
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PCT/US2014/027717 WO2014152774A1 (en) | 2013-03-14 | 2014-03-14 | Methods and compositions for delivering mrna coded antibodies |
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