HRP20170595T1 - Mutanti fc protutijela koji su otporni na aktivnu proteazu - Google Patents
Mutanti fc protutijela koji su otporni na aktivnu proteazu Download PDFInfo
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- HRP20170595T1 HRP20170595T1 HRP20170595TT HRP20170595T HRP20170595T1 HR P20170595 T1 HRP20170595 T1 HR P20170595T1 HR P20170595T T HRP20170595T T HR P20170595TT HR P20170595 T HRP20170595 T HR P20170595T HR P20170595 T1 HRP20170595 T1 HR P20170595T1
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- 108091005804 Peptidases Proteins 0.000 title claims 4
- 239000004365 Protease Substances 0.000 title claims 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 title 1
- 201000010099 disease Diseases 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 230000015556 catabolic process Effects 0.000 claims 5
- 210000004027 cell Anatomy 0.000 claims 5
- 238000006731 degradation reaction Methods 0.000 claims 5
- 238000006467 substitution reaction Methods 0.000 claims 5
- 238000002372 labelling Methods 0.000 claims 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims 4
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 claims 3
- 102100030417 Matrilysin Human genes 0.000 claims 3
- 108090000855 Matrilysin Proteins 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 102000035195 Peptidases Human genes 0.000 claims 3
- 102100030416 Stromelysin-1 Human genes 0.000 claims 3
- 101710108790 Stromelysin-1 Proteins 0.000 claims 3
- 230000004540 complement-dependent cytotoxicity Effects 0.000 claims 3
- LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 claims 2
- 108010032595 Antibody Binding Sites Proteins 0.000 claims 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims 2
- 108090000617 Cathepsin G Proteins 0.000 claims 2
- 102000004173 Cathepsin G Human genes 0.000 claims 2
- 102000004190 Enzymes Human genes 0.000 claims 2
- 108090000790 Enzymes Proteins 0.000 claims 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims 2
- 101001106413 Homo sapiens Macrophage-stimulating protein receptor Proteins 0.000 claims 2
- 102000009490 IgG Receptors Human genes 0.000 claims 2
- 108010073807 IgG Receptors Proteins 0.000 claims 2
- 102100027998 Macrophage metalloelastase Human genes 0.000 claims 2
- 101710187853 Macrophage metalloelastase Proteins 0.000 claims 2
- 102100021435 Macrophage-stimulating protein receptor Human genes 0.000 claims 2
- 102000057297 Pepsin A Human genes 0.000 claims 2
- 108090000284 Pepsin A Proteins 0.000 claims 2
- 102000002262 Thromboplastin Human genes 0.000 claims 2
- 108010000499 Thromboplastin Proteins 0.000 claims 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 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
- 239000008280 blood Substances 0.000 claims 2
- 210000004369 blood Anatomy 0.000 claims 2
- 230000000295 complement effect Effects 0.000 claims 2
- 229940088598 enzyme Drugs 0.000 claims 2
- 210000005087 mononuclear cell Anatomy 0.000 claims 2
- 229940111202 pepsin Drugs 0.000 claims 2
- 210000004881 tumor cell Anatomy 0.000 claims 2
- 230000002792 vascular Effects 0.000 claims 2
- 102100027995 Collagenase 3 Human genes 0.000 claims 1
- 108050005238 Collagenase 3 Proteins 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 claims 1
- 108090000695 Cytokines Proteins 0.000 claims 1
- 108091006020 Fc-tagged proteins Proteins 0.000 claims 1
- 108010051815 Glutamyl endopeptidase Proteins 0.000 claims 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 claims 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 claims 1
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 102100022338 Integrin alpha-M Human genes 0.000 claims 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 claims 1
- 101710160107 Outer membrane protein A Proteins 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 claims 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims 1
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 claims 1
- 230000006037 cell lysis Effects 0.000 claims 1
- 230000012292 cell migration Effects 0.000 claims 1
- 230000004663 cell proliferation Effects 0.000 claims 1
- 230000009089 cytolysis Effects 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 239000012636 effector Substances 0.000 claims 1
- 230000003176 fibrotic effect Effects 0.000 claims 1
- 229940088597 hormone Drugs 0.000 claims 1
- 239000005556 hormone Substances 0.000 claims 1
- 210000002865 immune cell Anatomy 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- 229940072221 immunoglobulins Drugs 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000000977 initiatory effect Effects 0.000 claims 1
- 230000003211 malignant effect Effects 0.000 claims 1
- 239000011159 matrix material Substances 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 238000013508 migration Methods 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 230000017854 proteolysis Effects 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
Classifications
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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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
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- 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
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- 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
-
- 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
- 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
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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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
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
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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
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
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- 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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- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
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- C07K2317/53—Hinge
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- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/72—Increased effector function due to an Fc-modification
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- 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
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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- 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
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
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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
- C07K2317/92—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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Claims (12)
1. Modificirana molekula koja sadrži Fc koji je otporan na proteolitičku degradaciju u usporedbi s divljim tipom IgG1 molekule koja sadrži Fc, koja obuhvaća Fc domenu protutijela s mutiranom IgG1 konstantnom regijom u kojoj je sekvenca E233-L234-L235-G236 ljudskog IgG1 zamijenjena s P233-V234-A235 s G236 koji je izbrisan, kako se definira prema EU numeraciji, te nadalje obuhvaća jednu ili više supstitucija iz divljeg tipa ljudske IgG1 sekvence odabrane između S239D/1332E; K326A/E333A; E333A/K334A; H268F/S324T/1332E; F243L/R292P/Y300L; S239D/H268F/S324T/1332E; S267E/H268F/S324T/1332E; K326A/1332E/E333A; S239D/K326A/E333A; S267E/1332E; i G237X/S239D/1332E, gdje je X A, D, P, Q ili S, kako se definira prema EU obilježavanju.
2. Molekula koja sadrži Fc prema zahtjevu 1, naznačena time da molekula koja sadrži Fc obuhvaća supstitucije S239D/K326A/E333A iz divljeg tipa ljudske IgG1 sekvence, kako se definira prema EU obilježavanju.
3. Molekula koja sadrži Fc prema zahtjevu 1, naznačena time da je molekula koji sadrži Fc:
i. otporna na degradaciju proteazom koja može cjepati IgG1 molekulu između ostataka 222-237 kako se definira prema EU obilježavanju, proizvoljno gdje je molekula koja sadrži Fc otporna na degradaciju MMP-3, MMP-7, MMP-12, MMP-13, katepsinom G, pepsinom, enzimom koji degradira imunoglobuline iz Strep. Pyrongenes (IdeS), ili glutamil endopeptidazom I iz Staph. aureus (GluV8), u usporedbi s divljim tipom IgG1, gdje je molekula koja sadrži Fc otporna na degradaciju s jednim ili više MMP-3, MMP-7, IdeS, ili GluV8 u usporedbi s divljim tipom IgG1;
ii. sposobna pokrenuti ADCP koji se mjeri u prisutnosti CD14 pos i/ili CD11b pos mononuklearnih stanica krvi, pri čemu molekula sadrži sekvencu koja je odabrana iz skupine SEQ ID NO: 8, 10-15, i 18-20, proizvoljno s dodatnim I332E kako se definira prema EU sustavu obilježavanja.
iii. sposobna pokrenuti ADCC koji se mjeri u prisutnosti mononuklearnih stanica krvi, proizvoljno pri čemu molekula koja sadrži Fc obuhvaća:
a) dodatnu supstituciju I332E kako se definira prema EU sustavu obilježavanja; ili
b) sekvencu koja se bira iz skupine SEQ ID NO: 8 i 10-12, i 15, 18-20;
iv. sposobna pokrenuti citotoksičnost koja ovisi od komplementa (CDC) koji se meri lizom stanica u prisutnosti komplementa, proizvoljno pri čemu molekula koja sadrži Fc obuhvaća sekvencu koja se bira iz skupine SEQ ID NO: 13, 14, i 18-20;
v. sposobna vezati se za Fcγ receptor s usporedivim ili većim afinitetom nego za Fc domenu IgG2 divljeg tipa; ili
vi. sposobna vezati se za Fcγ receptor s usporedivim ili većim afinitetom nego za Fc domenu IgG1 divljeg tipa.
4. Molekula koja sadrži Fc, prema bilo kojem od patentnih zahtjeva 1-3, naznačena time da je molekula koja sadrži Fc protutijelo ili Fc fuzijski protein, proizvoljno gdje se protutijelo veže za antigen na tumorskoj stanici, tumorskoj matrici, ili vaskularnom sustavu tumora, na primjer pri čemu se protutijelo veže za jedan od CD20, ErbB1, ErbB2, ErbB3, VEGF, RON, i tkivni faktor.
5. Molekula koja sadrži Fc prema patentnom zahtjevu 1 ili zahtjevu 2, naznačena time da sekvenca Fc domene ima barem 90 % identičnosti s divljim tipom ljudskog IgG1 od ostatka 214 do oko ostatka 340 prema EU sustavu obilježavanja.
6. Izolirana vezujuća molekula koja je rekombinantni polipeptid koji obuhvaća: (i) vezujuću domenu koja može vezati ciljanu molekulu koja je na stanici ili koja je vezana za stanicu, te (ii) Fc regiju IgG1, pri čemu ostatci 214 do 238 kako je definirano prema EU sustavu obilježavanja, sadrže sekvencu koja se bira iz SEQ ID NO: 4 i 5, s G236 koji je izbrisan; naznačena time da vezujuća molekula može vezati ciljanu molekulu na ciljanoj stanici i da molekula proizvodi lizu koja je ovisna od komplementa koji se može izmjeriti, ili stanično posredovano ubijanje ciljnih stanica u prisutnosti potrebnog efektorskog staničnog tipa.
7. Vezujuća molekula prema patentnom zahtjevu 6 naznačena time da:
i. Fc domena nadalje sadrži jednu ili više supstitucija iz sekvence divljeg tipa ljudskog IgG1 koje se biraju iz S239D/I332E; K326A/E333A; E333A/K334A; H268F/S324T/I332E; F243L/R292P/Y300L; S239D/H268F/S324T/I332E; S267E/H268F/S324T/I332E; K326A/I332E/E333A; S239D/K326A/E333A;S267E/I332E; i G237X/S239D/I332E, gdje X je A, D, P, Q ili S, kako se definira EU sustavom obilježavanja;
ii. Fc domena je otporna na degradaciju proteazom koja se može cijepati IgG1 molekula između ostataka 222-237, koji su definirani EU sustavom obilježavanja, proizvoljno pri čemu je molekula koja sadrži Fc otporna na degradaciju MMP-3, MMP-7, MMP-12, MMP-13, katepsinom G, pepsinom, IdeS, ili GluV8 u usporedbi s divljim tipom IgG1 ; ili
iii. vezujuću domenu koja se bira iz domene koja sadrži paratop protutijela; enzim; hormon; receptor; citokin; površinski antigen imunosne stanice; adhezijsku molekulu.
8. Vezujuća molekula prema patentnom zahtjevu 7 (iii), naznačena time da molekula obuhvaća dvije ili više domena za ciljno vezanje i izražava aviditet.
9. Vezujuća molekula prema patentnom zahtjevu 8, naznačena time da vezujuća molekula obuhvaća paratop protutijela koje se veže za antigen na tumorskoj stanici ili vaskularnom sustavu tumora.
10. Vezujuća molekula prema patentnom zahtjevu 9, naznačena time da se vezujuća molekula veže za jedan od CD20, ErbB1, ErbB2, ErbB3, VEGF, RON i tkivni faktor.
11. Farmaceutski pripravak naznačen time da sadrži molekulu prema bilo kojom od zahtjeva 1-10.
12. Farmaceutski pripravak prema patentnom zahtjevu 11 za uporabu u postupku liječenja bolesti koje su naznačene nepoželjnom proliferacijom ili migracijom stanica, pri čemu je bolest maligna bolest, fibrozna bolest, ili bolest koja je naznačena nepoželjnom angiogenezom.
14. Vezujuća molekula prema zahtjevu 6, naznačena time da je za upotrabu u postupku liječenja bolesti naznačne time, da su infekcije prokariotskih organizama.
15. Vezujuća molekula za uporabu prema zahtjevu 14, naznačena time da je Fc otporan na prokariotsku proteazu i sposoban za CDC.
16. Vezujuća molekula za uporabu prema zahtjevu 14, naznačena time da vezujuća molekula sadrži sekvencu koja se bira iz skupine SEQ ID NO: 13, 14, i 18-20.
17. Vezujuća molekula prema bilo kojem patentnom zahtjevu 6-10, farmaceutski pripravak prema zahtjevu 11, farmaceutski pripravak za uporabu prema zahtjevu 12, vezujuća molekula za uporabu prema zahtjevu 14 ili zahtjevu 15, naznačena time da molekula koja sadrži Fc ili vezujuća molekula sadrži supstitucije, kako je definirano EU sustavom obilježavanja, iz sekvence ljudskog IgG1 divljeg tipa.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201061426619P | 2010-12-23 | 2010-12-23 | |
| US201161540882P | 2011-09-29 | 2011-09-29 | |
| PCT/US2011/065174 WO2012087746A1 (en) | 2010-12-23 | 2011-12-15 | Active protease-resistant antibody fc mutants |
| EP11851794.5A EP2654780B1 (en) | 2010-12-23 | 2011-12-15 | Active protease-resistant antibody fc mutants |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20170595T1 true HRP20170595T1 (hr) | 2017-06-16 |
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| US10781246B2 (en) | 2015-06-05 | 2020-09-22 | New York University | Compositions and methods for anti-staphylococcal biologic agents |
| ES2846024T7 (es) * | 2015-07-24 | 2023-06-22 | Gliknik Inc | Proteínas de fusión de fragmentos de proteína humana para crear composiciones de Fc de inmunoglobulina multimerizada de forma ordenada con unión al complemento aumentada |
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| EP3365448A1 (en) * | 2015-10-23 | 2018-08-29 | Apogenix AG | Single-chain cd137-receptor agonist proteins |
| EP3912681A1 (en) | 2016-03-14 | 2021-11-24 | Orega Biotech | Anti-cd39 antibodies |
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| DK3484514T3 (da) * | 2016-05-23 | 2024-01-29 | Momenta Pharmaceuticals Inc | Compositions and methods related to engineered fc constructs |
| US20190263918A1 (en) * | 2016-06-08 | 2019-08-29 | Shanghai Jiao Tong University School Of Medicine | Sequence of antibody heavy chain constant region for enhancing agonistic antibody activity |
| GB2552473A (en) * | 2016-07-21 | 2018-01-31 | Evox Therapeutics Ltd | Surface decoration of extracellular vesicles |
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| JP7308150B2 (ja) | 2017-03-16 | 2023-07-13 | イナート・ファルマ・ソシエテ・アノニム | 癌を処置するための組成物及び方法 |
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| AU2018266847A1 (en) * | 2017-05-10 | 2019-11-28 | Albajuna Therapeutics, S.L. | Fc-fusion protein derivatives with high dual HIV antiviral and immunomodulatory activity |
| LT3456736T (lt) | 2017-09-19 | 2021-06-10 | Tillotts Pharma Ag | Antikūnų variantai |
| CN112334486A (zh) | 2018-06-18 | 2021-02-05 | 先天制药公司 | 用于治疗癌症的组合物和方法 |
| CA3110513A1 (en) | 2018-08-31 | 2020-03-05 | Regeneron Pharmaceuticals, Inc. | Dosing strategy that mitigates cytokine release syndrome for cd3/c20 bispecific antibodies |
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- 2011-12-15 ES ES11851794.5T patent/ES2623912T3/es active Active
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- 2011-12-15 BR BR112013018317A patent/BR112013018317A2/pt not_active Application Discontinuation
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