HRP20210240T1 - Vezujući proteini slični protutijelu s dvostrukom varijabilnom regijom koji imaju unakrsno orjentiranu vezujuću regiju - Google Patents
Vezujući proteini slični protutijelu s dvostrukom varijabilnom regijom koji imaju unakrsno orjentiranu vezujuću regiju Download PDFInfo
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- HRP20210240T1 HRP20210240T1 HRP20210240TT HRP20210240T HRP20210240T1 HR P20210240 T1 HRP20210240 T1 HR P20210240T1 HR P20210240T T HRP20210240T T HR P20210240TT HR P20210240 T HRP20210240 T HR P20210240T HR P20210240 T1 HRP20210240 T1 HR P20210240T1
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Classifications
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- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
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- A61P37/00—Drugs for immunological or allergic disorders
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- C07K—PEPTIDES
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- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C07K16/241—Tumor Necrosis Factors
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- C07K16/244—Interleukins [IL]
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- C—CHEMISTRY; METALLURGY
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- C07K16/244—Interleukins [IL]
- C07K16/245—IL-1
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
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- C07K16/244—Interleukins [IL]
- C07K16/247—IL-4
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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- C—CHEMISTRY; METALLURGY
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K16/46—Hybrid immunoglobulins
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C—CHEMISTRY; METALLURGY
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- C07K2317/00—Immunoglobulins specific features
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- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
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- C07K2317/55—Fab or Fab'
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Claims (16)
1. Vezujući protein sličan protutijelu koji sadrži četiri polipeptidna lanca koji tvore četiri mjesta za vezanje antigena koja su sposobna specifično vezati jedan ili više antigenskih ciljeva, naznačen time što dva polipeptidna lanca imaju strukturu predstavljenu formulom:
VL1-L1-VL2-L2-CL[I]
i dva polipeptidna lanca imaju strukturu predstavljenu formulom:
VH2-L3-VH1-L4-CH1-Fc [II]
pri čemu:
VL1 je prva varijabilna domena lakog lanca imunoglobulina;
VL2 je druga varijabilna domena lakog lanca imunoglobulina;
VH1 je prva varijabilna domena teškog lanca imunoglobulina;
VH2 je druga varijabilna domena teškog lanca imunoglobulina;
CL je konstantna domena lakog lanca imunoglobulina;
CH1 je konstantna domena teškog lanca imunoglobulina CH1;
Fc je zglobna regija imunoglobulina i CH2, CH3 konstantne domene teškog lanca imunoglobulina; i
L1, L2, L3, i L4 su aminokiselinske poveznice; pri čemu
duljina od L4 je najmanje dvostruka duljina od L2; i
duljina od L3 je najmanje dvostruka duljina od L1;
i pri čemu poveznice osiguravaju dovoljnu pokretljivost za uparivanje VL1 i VH1, i za uparivanje VL2 i VH2, i polipeptidi s formulom I i polipeptidi s formulom II tvore unakrsni par laki lanac-teški lanac.
2. Vezujući protein sličan protutijelu koji sadrži dva polipeptidna lanca koji tvore dva mjesta za vezanje antigena koja su sposobna specifično vezati jedan ili više antigenskih ciljeva, naznačen time što prvi polipeptidni lanac ima strukturu predstavljenu formulom:
VL1-L1-VL2-L2-CL[I]
i drugi polipeptidni lanac ima strukturu predstavljenu formulom:
VH2-L3-VH1-L4-CH1[II]
pri čemu:
VL1 je prva varijabilna domena lakog lanca imunoglobulina;
VL2 je druga varijabilna domena lakog lanca imunoglobulina;
VH1 je prva varijabilna domena teškog lanca imunoglobulina;
VH2 je druga varijabilna domena teškog lanca imunoglobulina;
CL je konstantna domena lakog lanca imunoglobulina;
CH1 je konstantna domena teškog lanca imunoglobulina CH1; i
L1, L2, L3, i L4 su aminokiselinske poveznice; pri čemu
duljina od L4 je najmanje dvostruka duljina od L2; i
duljina od L3 je najmanje dvostruka duljina od L1;
i pri čemu poveznice osiguravaju dovoljnu pokretljivost za uparivanje VL1 i VH1, i za uparivanje VL2 i VH2, i prvi i drugi polipeptidi tvore unakrsni par laki lanac-teški lanac.
3. Vezujući protein sličan protutijelu prema bilo kojem od patentnih zahtjeva 1-2, naznačen time što je jedan ili više antigenskih ciljeva odabran iz skupine koja se sastoji od B7.1, B7.2, BAFF, BlyS, C3, C5, CCL11 (eotaksin), CCL15 (MIP-1d), 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-1a), CCL4 (MIP-1b), CCL5 (RANTES), CCL7 (MCP-3), CCL8 (mcp-2), CD3, CD19, CD20, CD24, CD40, CD40L, CD80, CD86, CDH1 (E-kadherin), Hitinaze, 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, ILIA, 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-like receptori, TREM1, TSLP, TWEAK, XCR1 (GPR5/CCXCR1), DNGR-1(CLEC91), i HMGB1.
4. Vezujući protein sličan protutijelu prema bilo kojem od patentnih zahtjeva 1-3, naznačen time što je vezujući protein bispecifičan i sposoban vezati dva različita antigenska cilja, po mogućnosti IL-4 i IL-13.
5. Vezujući protein sličan protutijelu prema bilo kojem od patentnih zahtjeva 1-4, naznačen time što su dva različita antigenska cilja odabrana iz skupine koja sadrži 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.
6. Vezujući protein sličan protutijelu prema bilo kojem od patentnih zahtjeva 1-5, naznačen time što je vezujući protein sposoban inhibirati funkciju jednog ili više antigenskih ciljeva.
7. Vezujući protein sličan protutijelu prema bilo kojem od patentnih zahtjeva 1-6, naznačen time što najmanje jedna od poveznica odabrana iz skupine koja se sastoji od L1, L2, L3, i L4 sadrži najmanje jedan cisteinski ostatak.
8. Izolirana molekula nukleinske kiseline naznačena time što sadrži nukleotidnu sekvencu koja kodira vezujući protein sličan protutijelu prema bilo kojem od patentnih zahtjeva 1-7.
9. Ekspresijski vektor naznačen time što sadrži molekulu nukleinske kiseline prema zahtjevu 8.
10. Izolirana stanica domaćina koja sadrži sadrži molekulu nukleinske kiseline prema zahtjevu 8 ili ekspresijski vektor prema zahtjevu 9, naznačena time što je stanica domaćina poželjno stanica sisavca ili stanica insekta.
11. Farmaceutski pripravak naznačen time što sadrži farmaceutski prihvatljiv nosač i terapeutski učinkovitu količinu vezujućeg proteina sličnog protutijelu prema bilo kojem od patentnih zahtjeva 1-7.
12. Postupak za proizvodnju vezujućeg proteina sličnog protutijelu prema bilo kojem od patentnih zahtjeva 1, i 3 do 7, naznačen time što obuhvaća ekspresiju u stanici jedne ili više molekula nukleinske kiseline koje kodiraju polipeptide koji imaju strukture predstavljene formulama [I] i [II] ispod:
VL1-L1-VL2-L2-CL[I]
VH2-L3-VH1-L4-CH1-Fc [II]
pri čemu:
VL1 je prva varijabilna domena lakog lanca imunoglobulina;
VL2 je druga varijabilna domena lakog lanca imunoglobulina;
VH1 je prva varijabilna domena teškog lanca imunoglobulina;
VH2 je druga varijabilna domena teškog lanca imunoglobulina;
CL je konstantna domena lakog lanca imunoglobulina;
CH1 je konstantna domena teškog lanca imunoglobulina CH1;
Fc je zglobna regija imunoglobulina i CH2, CH3 konstantne domene teškog lanca imunoglobulina; i
L1, L2, L3, i L4 su aminokiselinske poveznice;
pri čemu duljina od L4 je najmanje dvostruka duljina od L2; i
pri čemu duljina od L3 je najmanje dvostruka duljina od L1;
i pri čemu poveznice osiguravaju dovoljnu pokretljivost za uparivanje VL1 i VH1, i za uparivanje VL2 i VH2, i polipeptidi s formulom I i polipeptidi s formulom II tvore unakrsni par laki lanac-teški lanac.
13. Postupak za proizvodnju vezujućeg proteina sličnog protutijelu prema bilo kojem od patentnih zahtjeva 2 do 7, naznačen time što obuhvaća ekspresiju u stanici jedne ili više molekula nukleinske kiseline koje kodiraju polipeptide koji imaju strukture predstavljene formulama [I] i [II] ispod:
VL1-L1-VL2-L2-CL[I]
VH2-L3-VH1-L4-CH1[II]
pri čemu:
VL1 je prva varijabilna domena lakog lanca imunoglobulina;
VL2 je druga varijabilna domena lakog lanca imunoglobulina;
VH1 je prva varijabilna domena teškog lanca imunoglobulina;
VH2 je druga varijabilna domena teškog lanca imunoglobulina;
CL je konstantna domena lakog lanca imunoglobulina;
CH1 je konstantna domena teškog lanca imunoglobulina CH1; i
L1, L2, L3, i L4 su aminokiselinske poveznice;
pri čemu duljina od L4 je najmanje dvostruka duljina od L2; i
pri čemu duljina od L3 je najmanje dvostruka duljina od L1;
i pri čemu poveznice osiguravaju dovoljnu pokretljivost za uparivanje VL1 i VH1, i za uparivanje VL2 i VH2, i polipeptid s formulom I i polipeptid s formulom II tvore unakrsni par laki lanac-teški lanac.
14. Postupak za proizvodnju vezujućeg proteina sličnog protutijelu koji sadrži četiri polipeptidna lanca koji tvore četiri mjesta za vezanje antigena, naznačen time što obuhvaća:
(a) identificiranje varijabilne domene prvog protutijela koja veže prvi ciljni antigen i varijabilne domene drugog protutijela koje veže drugi ciljni antigen, od kojih svaka sadrži VL, i VH;
(b) dodjeljivanje lakog lanca kao lanca predloška;
(c) dodjeljivanje VL varijabilne domene prvog protutijela i varijabilne domene drugog protutijela kaoVL1;
(d) dodjeljivanje VL2, VH1, i VH2 prema formulama [I] i [II] ispod:
VL1-L1-VL2-L2-CL[I]
VH1-L3-VH1-L4-CH1-Fc [II]
(e) određivanje maksimalne i minimalne duljine za L1, L2, L3, i L4;
(f) generiranje polipeptidnih struktura s formulama I i II;
(g) odabir polipeptidnih struktura s formulama I i II koje vežu prvi ciljni antigen i drugi ciljni antigen kada se kombiniraju da tvore vezujući protein sličan protutijelu;
pri čemu:
VL1 je prva varijabilna domena lakog lanca imunoglobulina;
VL2 je druga varijabilna domena lakog lanca imunoglobulina;
VH1 je prva varijabilna domena teškog lanca imunoglobulina;
VH2 je druga varijabilna domena teškog lanca imunoglobulina;
CL je konstantna domena lakog lanca imunoglobulina;
CH1 je konstantna domena teškog lanca imunoglobulina CH1;
Fc je zglobna regija imunoglobulina i CH2, CH3 konstantne domene teškog lanca imunoglobulina; i
L1, L2, L3, i L4 su aminokiselinske poveznice;
pri čemu duljina od L4 je najmanje dvostruka duljina od L2; i
pri čemu duljina od L3 je najmanje dvostruka duljina od L1;
i pri čemu poveznice osiguravaju dovoljnu pokretljivost za uparivanje VL1 i VH1, i za uparivanje VL2 i VH2, i polipeptidi s formulom I i polipeptidi s formulom II tvore unakrsni par laki lanac-teški lanac.
15. Postupak za proizvodnju vezujućeg proteina sličnog protutijelu koji sadrži četiri polipeptidna lanca koji tvore četiri mjesta za vezanje antigena, naznačen time što obuhvaća:
(a) identificiranje varijabilne domene prvog protutijela koja veže prvi ciljni antigen i varijabilne domene drugog protutijela koje veže drugi ciljni antigen, od kojih svaka sadrži VL, i VH;
(b) dodjeljivanje lakog lanca kao lanca predloška;
(c) dodjeljivanje VL varijabilne domene prvog protutijela i varijabilne domene drugog protutijela kaoVL1;
(d) dodjeljivanje VL2, VH1, i VH2 prema formulama [I] i [II] ispod:
VL1-L1-VL2-L2-CL[I]
VH1-L3-VH1-L4-CH1[II]
(e) određivanje maksimalne i minimalne duljine za L1, L2, L3, i L4;
(f) generiranje polipeptidnih struktura s formulama I i II;
(g) odabir polipeptidnih struktura s formulama I i II koje vežu prvi ciljni antigen i drugi ciljni antigen kada se kombiniraju da tvore vezujući protein sličan protutijelu;
pri čemu:
VL1 je prva varijabilna domena lakog lanca imunoglobulina;
VL2 je druga varijabilna domena lakog lanca imunoglobulina;
VH1 je prva varijabilna domena teškog lanca imunoglobulina;
VH2 je druga varijabilna domena teškog lanca imunoglobulina;
CL je konstantna domena lakog lanca imunoglobulina;
CH1 je konstantna domena teškog lanca imunoglobulina CH1; i
L1, L2, L3, i L4 su aminokiselinske poveznice;
pri čemu duljina od L4 je najmanje dvostruka duljina od L2; i
pri čemu duljina od L3 je najmanje dvostruka duljina od L1;
i pri čemu poveznice osiguravaju dovoljnu pokretljivost za uparivanje VL1 i VH1, i za uparivanje VL2 i VH2, i polipeptidi s formulom I i polipeptidi s formulom II tvore unakrsni par laki lanac-teški lanac.
16. Postupak prema patentnom zahtjevu 14 ili 15, naznačen time što su prva varijabilna domena protutijela i druga varijabilna domena protutijela, iste.
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| US201161468276P | 2011-03-28 | 2011-03-28 | |
| FR1160311 | 2011-11-14 | ||
| EP16205057.9A EP3199547B1 (en) | 2011-03-28 | 2012-03-28 | Dual variable region antibody-like binding proteins having cross-over binding region orientation |
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| KR (1) | KR102240802B1 (hr) |
| CL (1) | CL2013002763A1 (hr) |
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| LT (1) | LT3199547T (hr) |
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| US5989830A (en) * | 1995-10-16 | 1999-11-23 | Unilever Patent Holdings Bv | Bifunctional or bivalent antibody fragment analogue |
| CN107226864A (zh) * | 2007-06-21 | 2017-10-03 | 宏观基因有限公司 | 共价双抗体及其用途 |
| EP2050764A1 (en) * | 2007-10-15 | 2009-04-22 | sanofi-aventis | Novel polyvalent bispecific antibody format and uses thereof |
| UY32808A (es) * | 2009-07-29 | 2011-02-28 | Abbott Lab | Inmunoglobulinas como dominio variable dual y usos de las mismas |
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| Publication number | Publication date |
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| IL274870B1 (en) | 2023-01-01 |
| KR102240802B1 (ko) | 2021-04-16 |
| IL249369B (en) | 2019-11-28 |
| IL274870A (en) | 2020-07-30 |
| PH12018501305A1 (en) | 2020-01-27 |
| MX366923B (es) | 2019-07-31 |
| ES2859906T3 (es) | 2021-10-04 |
| KR20190049902A (ko) | 2019-05-09 |
| PT3199547T (pt) | 2021-02-02 |
| IL274876A (en) | 2020-07-30 |
| MX2019009016A (es) | 2019-09-10 |
| RU2019122155A (ru) | 2020-03-16 |
| IL274870B2 (en) | 2023-05-01 |
| HUE053139T2 (hu) | 2021-06-28 |
| LT3199547T (lt) | 2021-02-25 |
| CL2013002763A1 (es) | 2014-03-07 |
| IL249369A0 (en) | 2017-02-28 |
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