HRP20150444T1 - Trovalentna, bispecifiäśna protutijela - Google Patents
Trovalentna, bispecifiäśna protutijela Download PDFInfo
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- HRP20150444T1 HRP20150444T1 HRP20150444TT HRP20150444T HRP20150444T1 HR P20150444 T1 HRP20150444 T1 HR P20150444T1 HR P20150444T T HRP20150444T T HR P20150444TT HR P20150444 T HRP20150444 T HR P20150444T HR P20150444 T1 HRP20150444 T1 HR P20150444T1
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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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
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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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- 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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- 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
-
- 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
-
- 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
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (11)
1. Trovalentno, bispecifično protutijelo, naznačeno time, da obuhvaća
a) protutijelo u punoj duljini, koje se specifično veže na prvi antigen i sastoji se od dva jaka lanca protutijela i dva slaba lanca protutijela;
b) polipeptid koji se sastoji od sljedećih:
ba) varijabilna domena jakog lanca protutijela (VH); ili
bb) varijabilna domena jakog lanca protutijela (VH) i konstantna domena 1 protutijela (CH1), pri čemu je navedeni polipeptid staljen s N-završetkom od VH-domene preko peptidne poveznice na C-završetak od jednog između dva jaka lanca od navedenog protutijela pune duljine;
c) polipetid koji se sastoji od sljedećih:
ca) varijabilna domena slabog lanca protutijela (VL); ili
cb) varijabilna domena slabog lanca protutijela (VL) i konstantna domena 1 slabog lanca protutijela (CL), pri čemu je navedeni polipeptid staljen s N-završetkom od VL-domene preko peptidne poveznice na C-završetak od preostalog između dva jaka lanca od nevedenog protutijela pune duljine;
i pritom varijabilna domena jakog lanca protutijela (VH) od polipeptida pod točkom b) i varijabilna domena slabog lanca protutijela (VL) od polipeptida pod točkom c), zajedno tvore mjesto vezanja antigena, gdje se specifično vežu na drugi antigen.
2. Trovalentno, bispecifično protutijelo prema zahtjevu 1, naznačeno time, da se CH3-domena od jednog jakog lanca i CH3-domena od drugog jakog lanca, sastaju na sučelju koje obuhvaća originalno sučelje između CH3-domena od protutijela;
pri čemu se navedeno sučelje mijenja u svrhu pokretanja tvorbe trovalentnog, bispecifičnog protutijela, gdje je ta promjena naznačena time, da se
i) mijenja CH3-domena od jednog jakog lanca,
tako da se unutar originalnog sučelja CH3-domena od jednog jakog lanca koji se sastaje s originalnim sučeljem od CH3-domene od drugog jakog lanca unutar trovalentnog, bispecifičnog protutijela,
zamjenjuje aminokiselinski ostatak s aminokiselinskim ostatkom koji ima veći volumen bočnog lanca, čime se generira izbočenje unutar sučelja od CH3-domene od jednog jakog lanca, koje se može pozicionirati u šupljini unutar sučelja od CH3-domene od drugog jakog lanca,
i
ii) mijenja CH3-domena od drugog jakog lanca,
tako da se unutar originalnog sučelja od druge CH3-domene koja se sastaje s originalnim sučeljem od prve CH3-domene unutar trovalentnog, bispecifičnog protutijela,
zamjenjuje aminokiselinski ostatak s aminokiselinskim ostatkom koji ima manji volumen bočnog lanca, čime se generira šupljina unutar sučelja od druge CH3-domene, u kojoj se može pozicionirati izbočenje unutar sučelja od prve CH3-domene.
3. Trovalentno, bispecifično protutijelo prema zahtjevu 1, naznačeno time, da se
i) navedeni aminokiselinski ostatak koji ima veći volumen bočnog lanca, odabire iz skupine koju čine arginin (R), fenilalanin (F), tirozin (Y), triptofan (W); i
ii) navedeni aminokiselinski ostatak koji ima manji volumen bočnog lanca, odabire iz skupine koju čine alanin (A), serin (S), treonin (T), valin (V).
4. Trovalentno, bispecifično protutijelo prema zahtjevima 2 ili 3, naznačeno time, da se obje CH3-domene dalje mijenjaju pomoću uvođenja cisteina (C) kao aminokiseline, na odgovarajućim pozicijama od svake CH3-domene, tako da se može stvoriti disulfidni most između obje CH3-domene.
5. Trovalentno, bispecifično protutijelo prema bilo kojem od zahtjeva 2 do 4, naznačeno time, da CH3-domena pod točkom i) sadrži mutaciju T366W; i CH3-domena pod točkom ii) sadrži mutacije: T366S, L368A, Y407V.
6. Trovalentno, bispecifično protutijelo prema zahtjevu 4, naznačeno time, da CH3-domena pod točkom i) sadrži mutacije: Y349C, T366W; i CH3-domena pod točkom ii) sadrži mutacije: S354C, T366S, L368A, Y407V.
7. Trovalentno, bispecifično protutijelo prema bilo kojem od zahtjeva 1 do 6, naznačeno time, da su varijabilna domena jakog lanca protutijela (VH) od polipeptida pod točkom b) i varijabilna domena slabog lanca od protutijela (VL) od polipeptida pod točkom c), povezane i stabilizirane preko međulanca disulfidnog mosta pomoću uvođenja disulfidne veze između sljedećih pozicija:
i) pozicija 44 varijabilne domene jakog lanca prema poziciji 100 varijabilne domene slabog lanca,
ii) pozicija 105 varijabilne domene jakog lanca prema poziciji 43 varijabilne domene slabog lanca, ili
iii) pozicija 101 varijabilne domene jakog lanca prema poziciji 100 varijabilne domene slabog lanca.
8. Trovalentno, bispecifično protutijelo prema zahtjevu 7, naznačeno time, da su varijabilna domena jakog lanca protutijela (VH) od polipeptida pod točkom b) i varijabilna domena slabog lanca od protutijela (VL) od polipeptida pod točkom c), povezane i stabilizirane preko međulanca disulfidnog mosta pomoću uvođenja disulfidne veze između sljedećih pozicija:
i) pozicija 44 varijabilne domene jakog lanca prema poziciji 100 varijabilne domene slabog lanca.
9. Trovalentno, bispecifično protutijelo prema zahtjevu 6, naznačeno time, da su peptidne poveznice pod točkama b) i c), identični peptidi s duljinom između 25 i 50 aminokiselina.
10. Farmaceutski sastav, naznačen time, da obuhvaća trovalentno, bispecifično protutijelo prema zahtjevima od 1 do 9.
11. Nukleinska kiselina, naznačena time, da kodira trovalentno, bispecifično protutijelo prema zahtjevima od 1 do 9.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09005108 | 2009-04-07 | ||
| EP10712365.5A EP2417156B1 (en) | 2009-04-07 | 2010-04-01 | Trivalent, bispecific antibodies |
| PCT/EP2010/002122 WO2010115589A1 (en) | 2009-04-07 | 2010-04-01 | Trivalent, bispecific antibodies |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20150444T1 true HRP20150444T1 (hr) | 2015-05-22 |
Family
ID=40942481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20150444TT HRP20150444T1 (hr) | 2009-04-07 | 2010-04-01 | Trovalentna, bispecifiäśna protutijela |
Country Status (20)
| Country | Link |
|---|---|
| US (4) | US20100256340A1 (hr) |
| EP (1) | EP2417156B1 (hr) |
| JP (2) | JP5616428B2 (hr) |
| KR (1) | KR101456326B1 (hr) |
| CN (1) | CN102369214B (hr) |
| AR (1) | AR076193A1 (hr) |
| AU (1) | AU2010234031B2 (hr) |
| CA (1) | CA2757931C (hr) |
| CY (1) | CY1116376T1 (hr) |
| DK (1) | DK2417156T3 (hr) |
| ES (1) | ES2537100T3 (hr) |
| HR (1) | HRP20150444T1 (hr) |
| IL (1) | IL214884A (hr) |
| MX (1) | MX2011010168A (hr) |
| PL (1) | PL2417156T3 (hr) |
| PT (1) | PT2417156E (hr) |
| SG (1) | SG175077A1 (hr) |
| SI (1) | SI2417156T1 (hr) |
| TW (1) | TW201039850A (hr) |
| WO (1) | WO2010115589A1 (hr) |
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| EP3674317B1 (en) | 2009-03-19 | 2024-12-11 | Chugai Seiyaku Kabushiki Kaisha | Antibody constant region variant |
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