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HRP20161030T1 - Protutijelu slični vezivni proteini s dvostrukom promjenjivom regijom koji imaju prijelaznu orjentaciju vezivne regije - Google Patents

Protutijelu slični vezivni proteini s dvostrukom promjenjivom regijom koji imaju prijelaznu orjentaciju vezivne regije Download PDF

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HRP20161030T1
HRP20161030T1 HRP20161030TT HRP20161030T HRP20161030T1 HR P20161030 T1 HRP20161030 T1 HR P20161030T1 HR P20161030T T HRP20161030T T HR P20161030TT HR P20161030 T HRP20161030 T HR P20161030T HR P20161030 T1 HRP20161030 T1 HR P20161030T1
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amino acid
acid residues
immunoglobulin
length
heavy chain
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HRP20161030TT
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Nicolas Baurin
Christian Beil
Carsten Corvey
Christian Lange
Danxi Li
Vincent Mikol
Anke Steinmetz
Ercole Rao
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Sanofi
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Claims (16)

1. Protutijelu sličan vezivni protein koji sadrži četiri polipeptidna lanca koji tvore četiri mjesta vezanja antigena, pri čemu dva polipeptidna lanca imaju strukturu predstavljenu s formulom: [image] i dva polipeptidna lanca imaju strukturu predstavljenu s formulom: [image] pri čemu: VL1 je varijabilna domena prvog lakog imunoglobulinskog lanca; VL2 je varijabilna domena drugog lakog imunoglobulinskog lanca; VH1 je varijabilna domena prvog teškog imunoglobulinskog lanca; VH2 je varijabilna domena drugog teškog imunoglobulinskog lanca; CL je konstantna domena lakog imunoglobulinskog lanca; CH1 je imunoglobulinska CH1 konstantna domena teškog lanca; Fc je imunoglobulinska zglobna regija i CH2, CH3 imunoglobulinska konstantna domena teških lanaca; i L1, L2, L3, i L4 su amino kiselinske poveznice; pri čemu: L1 je duljine 3 do 12 ostataka amino kiseline; L2 je duljine 3 do 14 ostataka amino kiseline; L3 je duljine 1 do 8 ostataka amino kiseline; i L4 je duljine 1 do 3 ostataka amino kiseline; i pri čemu polipeptidi s formulom I i polipeptidi s formulom II tvore prijelazni par laki lanac-teški lanac.
2. Protutijelu sličan vezivni protein koji sadrži dva polipeptidna lanca koji tvore dva mjesta vezivanja antigena, pri čemu prvi polipeptidni lanac ima strukturu predstavljenu s formulom: [image] i drugi polipeptidni lanac ima strukturu predstavljenu s formulom: [image] pri čemu: VL1 je varijabilna domena prvog lakog imunoglobulinskog lanca; VL2 je varijabilna domena drugog lakog imunoglobulinskog lanca; VH1 je varijabilna domena prvog teškog imunoglobulinskog lanca; VH2 je varijabilna domena drugog teškog imunoglobulinskog lanca; CL je konstantna domena lakog imunoglobulinskog lanca; CH1 je imunoglobulinska CH1 konstantna domena teškog lanca; i L1, L2, L3, i L4 su amino kiselinske poveznice; pri čemu: L1 je duljine 3 do 12 ostataka amino kiseline; L2 je duljine 3 do 14 ostataka amino kiseline; L3 je duljine 1 do 8 ostataka amino kiseline; i L4 je duljine 1 do 3 ostatka amino kiseline; i pri čemu prvi i drugi polipeptidi tvore prijelazni par laki lanac-teški lanac.
3. Protutijelu sličan vezivni protein prema bilo kojem zahtjevu 1 ili 2, pri čemu: L1 je duljine 5 do 10 ostataka amino kiseline; L2 je duljine 5 do 8 ostataka amino kiseline; L3 je duljine 1 do 5 ostataka amino kiseline; i L4 je duljine 1 do 2 ostatka amino kiseline.
4. Protutijelu sličan vezivni protein prema bilo kojem zahtjevu 1 ili 2, pri čemu: L1 je duljine 7 ostataka amino kiseline; L2 je duljine 5 ostataka amino kiseline; L3 je duljine 1 ostatak amino kiseline; i L4 je duljine 2 ostatka amino kiseline.
5. Protutijelu sličan vezivni protein koji sadrži četiri polipeptidna lanca koji tvore četiri mjesta vezanja antigena, pri čemu dva polipeptidna lanca imaju strukturu predstavljenu s formulom: [image] i dva polipeptidna lanca imaju strukturu predstavljenu s formulom: [image] pri čemu: VL1 je varijabilna domena prvog lakog imunoglobulinskog lanca; VL2 je varijabilna domena drugog lakog imunoglobulinskog lanca; VH1 je varijabilna domena prvog teškog imunoglobulinskog lanca; VH2 je varijabilna domena drugog teškog imunoglobulinskog lanca; CL je konstantna domena lakog imunoglobulinskog lanca; CH1 je imunoglobulinska CH1 konstantna domena teškog lanca; Fc je imunoglobulinska zglobna regija i CH2, CH3 imunoglobulinska konstantna domena teških lanaca; i L1, L2, L3, i L4 su amino kiselinske poveznice; pri čemu: L1 je duljine 1 do 3 ostatka amino kiseline; L2 je duljine 1 do 4 ostatka amino kiseline; L3 je duljine 2 do 15 ostataka amino kiseline; i L4 je duljine 2 do 15 ostataka amino kiseline; i pri čemu polipeptidi s formulom I i polipeptidi s formulom II tvore prijelazni par laki lanac-teški lanac.
6. Protutijelu sličan vezivni protein koji sadrži dva polipeptidna lanca koji tvore dva mjesta vezivanja antigena, pri čemu prvi polipeptidni lanac ima strukturu predstavljenu s formulom: [image] i drugi polipeptidni lanac ima strukturu predstavljenu s formulom: [image] pri čemu: VL1 je varijabilna domena prvog lakog imunoglobulinskog lanca; VL2 je varijabilna domena drugog lakog imunoglobulinskog lanca; VH1 je varijabilna domena prvog teškog imunoglobulinskog lanca; VH2 je varijabilna domena drugog teškog imunoglobulinskog lanca; CL je konstantna domena lakog imunoglobulinskog lanca; CH1 je imunoglobulinska CH1 konstantna domena teškog lanca; i L1, L2, L3, i L4 su amino kiselinske poveznice; pri čemu: L1 je duljine 1 do 3 ostatka amino kiseline; L2 je duljine 1 do 4 ostatka amino kiseline; L3 je duljine 2 do 15 ostataka amino kiseline; i L4 je duljine 2 do 15 ostataka amino kiseline; i pri čemu prvi i drugi polipeptidi tvore prijelazni par laki lanac-teški lanac.
7. Protutijelu sličan vezivni protein prema bilo kojem zahtjevu 5 ili 6, naznačen time da: L1 je duljine 1 do 2 ostatka amino kiseline; L2 je duljine 1 do 2 ostatka amino kiseline; L3 je duljine 4 do 12 ostataka amino kiseline; i L4 je duljine 2 do 12 ostataka amino kiseline.
8. Protutijelu sličan vezivni protein prema bilo kojem zahtjevu 5 ili 6, naznačen time da: L1 je duljine 1 ostatak amino kiseline; L2 je duljine 2 ostatka amino kiseline; L3 je duljine 7 ostataka amino kiseline; i L4 je duljine 5 ostataka amino kiseline.
9. Protutijelu sličan vezivni protein prema bilo kojem od zahtjeva 1, 2, 5 ili 6, naznačen time da vezivni peptid može specifično vezati jedan ili više antigenskih ciljeva, pri čemu, poželjno, jedan ili više antigenskih ciljeva se bira iz skupine koju čine B7.1, B7.2, BAFF, BlyS, C3, C5, CCL11 (eotaksin), CCL15 (MIP-ld), CCL17 (TARC), CCL19 (MIP-3b), CCL2 (MCP-1), CCL20 (MIP-3a), CCL21 (MIP-2), SLC, CCL24 (MPIF-2/eotaxin-2), CCL25 (TECK), CCL26 (eotaxin-3), CCL3 (MIP-la), CCL4 (MIP-lb), CCL5 (RANTES), CCL7 (MCP-3), CCL8 (mcp-2), CD3, CD19, CD20, CD24, CD40, CD40L, CD80, CD86, CDH1 (E-kadherin), Kitinaza, CSF1 (M-CSF), CSF2 (GM-CSF), CSF3 (GCSF), CTLA4, CX3CL1 (SCYD1), CXCL12 (SDF1), CXCL13, EGFR, FCER1A, FCER2, HER2, IGF1R, IL-1, IL-12, IL13, IL15, IL17, IL18, IL1A, IL1B, IL1F10, IL1β, IL2, IL4, IL6, IL7, IL8, IL9, IL12/23, IL22, IL23, IL25, IL27, IL35, ITGB4 (b 4 integrin), LEP (leptin), MHC razred II, TLR2, TLR4, TLR5, TNF, TNFα, TNFSF4 (OX40 ligand), TNFSF5 (CD40 ligand), Toll-slični receptori, TREM1, TSLP, TWEAK, XCR1 (GPR5/CCXCR1), DNGR-1(CLEC91), i HMGB1.
10. Protutijelu sličan vezivni protein prema bilo kojem od zahtjeva 1, 2, 5 ili 6, naznačen time da vezivni peptid je bispecifičan i može vezati dva različita antigenska cilja, pri čemu, poželjno, dva različita antigenska cilja se biraju iz skupine koju čine IL4 i IL13, IGF1R i HER2, IGF1R i EGFR, EGFR i HER2, BK i IL13, PDL-1 i CTLA-4, CTLA4 i MHC razred II, IL-12 i IL-18, IL-1α i IL-1β, TNFα i IL12/23, TNFα i IL-12p40, TNFα i IL1β, TNFα i IL-23, i IL17 i IL23.
11. Protutijelu sličan vezivni protein prema bilo kojem od zahtjeva 1, 2, 5 ili 6, naznačen time da vezivni peptid može inhibirati funkciju jednog ili više antigenskih ciljeva.
12. Protutijelu sličan vezivni protein prema bilo kojem od zahtjeva 1, 2, 5 ili 6, naznačen time da barem jedna od poveznica odabrana iz skupine koju čine L1, L2, L3, i L4 sadrži barem jedan cisteinski ostatak.
13. Izolirana molekula nukleinske kiseline naznačena time da sadrži nukleotidnu sekvencu koja kodira protutijelu sličan vezivni peptid prema bilo kojem od zahtjeva 1, 2, 5 ili 6.
14. Ekspresijski vektor naznačen time da sadrži molekulu nukleinske kiseline prema zahtjevu13.
15. Izolirana stanica domaćin naznačena time da sadrži molekulu nukleinske kiseline prema zahtjevu 13 ili ekspresijski vektor prema zahtjevu 14, pri čemu, poželjno, stanica domaćin je stanica sisavca ili stanica insekta.
16. Farmaceutski pripravak naznačen time da sadrži farmaceutski prihvatljiv nosač i terapeutski učinkovitu količinu protutijelu sličnog vezivnog peptida prema bilo kojem od zahtjeva 1, 2, 5 ili 6.
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