SI2307458T1 - Humanizacija kunčjih protiteles z uporabo univerzalnega protitelesnega ogrodja - Google Patents
Humanizacija kunčjih protiteles z uporabo univerzalnega protitelesnega ogrodja Download PDFInfo
- Publication number
- SI2307458T1 SI2307458T1 SI200931857T SI200931857T SI2307458T1 SI 2307458 T1 SI2307458 T1 SI 2307458T1 SI 200931857 T SI200931857 T SI 200931857T SI 200931857 T SI200931857 T SI 200931857T SI 2307458 T1 SI2307458 T1 SI 2307458T1
- Authority
- SI
- Slovenia
- Prior art keywords
- seq
- framework
- antigen
- threonine
- binding polypeptide
- Prior art date
Links
Classifications
-
- 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
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- 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
- A61K47/51—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 non-active ingredient being a modifying agent
- A61K47/68—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 non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—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 non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6875—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 non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody being a hybrid immunoglobulin
- A61K47/6877—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 non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody being a hybrid immunoglobulin the antibody being an immunoglobulin containing regions, domains or residues from different species
-
- 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
-
- 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
-
- 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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
- C07K16/464—Igs containing CDR-residues from one specie grafted between FR-residues from another
- C07K16/465—Igs containing CDR-residues from one specie grafted between FR-residues from another with additional modified FR-residues
-
- 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
-
- 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
- C07K2317/54—F(ab')2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
-
- 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
- C07K2317/50—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
- C07K2317/567—Framework region [FR]
-
- 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
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
Landscapes
- 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)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Claims (46)
- Humanizacija kunčjih protiteles z uporabo univerzalnega protitelesnega ogrodja Patentni zahtevki1. Akceptorsko ogrodje za transplantacijo CDR-jev lagomorfov, ki obsega ogrodje humane variabilne težke verige, ki ima vsaj 95-odstotno enakost s SEQ ID NO: 4 in ki obsega treonin (T) na položaju 24, alanin (A) ali glicin (G) na položaju 56, treonin (T) na položaju 84, valin (V) na položaju 89 in arginin (R) na položaju 108 (številčenje AHo).
- 2. Akceptorsko ogrodje po zahtevku 1, kjer je ogrodje variabilne težke verige izbrano iz skupine, ki jo sestavljata SEQ ID NO: 4 in SEQ ID NO: 6.
- 3. Akceptorsko ogrodje po katerem koli od prejšnjih zahtevkov, ki nadalje obsega ogrodje variabilne lahke verige, ki ima vsaj 85-odstotno enakost s SEQ ID NO: 2.
- 4. Akceptorsko ogrodje po zahtevku 3, ki obsega treonin (T) na položaju 87 ogrodja variabilne lahke verige (številčenje AHo).
- 5. Akceptorsko ogrodje po zahtevku 3, ki nadalje obsega CDR1, CDR2 in CDR3 lahke verige od antigen vezavnega polipeptida lagomorfnega donorja.
- 6. Akceptorsko ogrodje po katerem koli od prejšnjih zahtevkov, kjer sta ogrodje variabilne težke verige in ogrodje variabilne lahke verige vezana preko povezovalca s SEQ ID NO: 8.
- 7. Akceptorsko ogrodje po katerem koli od prejšnjih zahtevkov, ki obsega ogrodje, ki ima vsaj 70-odstotno enakost s SEQ ID NO: 3, SEQ ID NO: 5 ali SEQ ID NO: 7.
- 8. Akceptorsko ogrodje humane ali humanizirane variabilne težke verige za transplantacijo CDR-jev, ki obsega vsaj štiri aminokisline iz skupine, ki jo sestavljajo treonin (T) na položaju 24, valin (V) na položaju 25, alanin (A) ali glicin (G) na položaju 56, lizin (K) na položaju 82, treonin (T) na položaju 84, valin (V) na položaju 89 in arginin (R) na položaju 108 (številčenje AHo), kjer ima akceptorsko ogrodje vsaj 95-odstotno enakost s SEQ ID NO: 4.
- 9. Akceptorsko ogrodje po katerem koli od prejšnjih zahtevkov, kjer je bila aminokislina na položaju 12, 103 in/ali 144 (številčenje AHo) subtituirana s hidrofilno aminokislino.
- 10. Akceptorsko ogrodje po zahtevku 9, ki ima: (a) serin (S) na položaju 12, (b) serin (S) ali treonin (T) na položaju 103 in/ali (c) serin (S) ali treonin (T) na položaju 144 (številčenje AHo) v ogrodju variabilne težke verige.
- 11. Akceptorsko ogrodje po katerem koli od prejšnjih zahtevkov, ki ima glutaminsko kislino (E) na položaju 1, valin (V) na položaju 3, levcin (L) na položaju 4, serin (S) na položaju 10, arginin (R) na položaju 47, serin (S) na položaju 57, fenilalanin (F) na položaju 91 in/ali valin (V) na položaju 103 v ogrodju variabilne lahke verige (številčenje AHo).
- 12. Akceptorsko ogrodje po zahtevku 11, ki nadalje obsega ostanke donorskega ogrodja, vključene v antigensko vezavo.
- 13. Akceptorsko ogrodje po katerem koli od prejšnjih zahtevkov, ki nadalje obsega glicin (G) na položaju 141 variabilne težke verige (številčenje AHo).
- 14. Uporaba akceptorskega ogrodja po katerem koli od zahtevkov 1-13 za transplantacijo CDR-jev lagomorfov.
- 15. Antigen vezavni polipeptid, ki obsega akceptorsko ogrodje po katerem koli od zahtevkov 1-13.
- 16. Antigen vezavni polipeptid po zahtevku 15, ki je protitelo scFv.
- 17. Antigen vezavni polipeptid po katerem koli od zahtevkov 15-16, ki nadalje obsega eno ali več vezanih molekul, zlasti terapevtsko sredstvo, kot na primer citotoksično sredstvo, citokin, kemokin, rastni faktor ali drugo signalno molekulo, kontrastno sredstvo ali drugi protein, zlasti transkripcij ski aktivator ali DNA-vezavno domeno.
- 18. Antigen vezavni polipeptid po katerem koli od zahtevkov 15-17 za uporabo v diagnostičnih aplikacijah, terapevtskih aplikacijah, tarčni validaciji ali genski terapiji.
- 19. Nukleinska kislina, zlasti izolirana nukleinska kislina, ki kodira akceptorsko ogrodje po katerem koli od zahtevkov 1-13 ali antigen vezavni polipeptid po katerem koli od zahtevkov 15-17.
- 20. Vektor, ki obsega nukleinsko kislino po zahtevku 19.
- 21. Gostiteljska celica, ki obsega vektor po zahtevku 20.
- 22. Nukleinska kislina po zahtevku 19 ali vektor po zahtevku 20 za uporabo v genski terapiji.
- 23. Sestavek, ki obsega akceptorsko ogrodje po katerem koli od zahtevkov 1-13, antigen vezavni polipeptid po katerem koli od zahtevkov 15-17, nukleinsko kislino po zahtevku 19 ali vektor po zahtevku 20.
- 24. Postopek za humaniziranje kunčjega antigen vezavnega polipeptida, pri čemer kunčji antigen vezavni polipeptid obsega sekvence CDR1, CDR2 in CDR3 težke verige in/ali sekvence CDR1, CDR2 in CDR3 lahke verige, pri čemer postopek obsega: (i) transplantacijo vsaj enega CDR težke verige iz skupine, ki jo sestavljajo sekvence CDR HI, CDR H2 in CDR H3, v ogrodje humane variabilne težke verige, ki ima vsaj 95-odstotno enakost s SEQ ID NO: 4, ki nadalje obsega vsaj šest aminokislin iz skupine, ki jo sestavljajo treonin (T) na položaju 24, valin (V) na položaju 25, alanin (A) ali glicin (G) na položaju 56, lizin (K) na položaju 82, treonin (T) na položaju 84, valin (V) na položaju 89 in arginin (R) na položaju 108 (številčenje AHo), in (ii) transplantacijo vsaj enega CDR lahke verige iz skupine, ki jo sestavljajo sekvence CDR Ll, CDR L2 in CDR L3, v ogrodje humane variabilne lahke verige, kjer ima ogrodje humane variabilne lahke verige vsaj 85-odstotno enakost s SEQ ID NO: 2.
- 25. Postopek po zahtevku 24, kjer: (i) ogrodje humane variabilne težke verige obsega ogrodno aminokislinsko sekvenco od SEQ ID NO: 1, SEQ ID NO: 4 ali SEQ ID NO: 6; in (ii) ogrodje humane variabilne lahke verige obsega ogrodno aminokislinsko sekvenco od SEQ ID NO: 2 ali SEQ ID NO: 9.
- 26. Postopek po zahtevku 24 ali 25, ki nadalje obsega substituiranje ogrodnih ostankov z ogrodnimi ostanki kunčjega antigen vezavnega polipeptida, ki je vključen v antigensko vezavo. 2Ί. Postopek po katerem koli od zahtevkov 24-26, ki nadalje obsega stopnjo substituiranja ogrodnega ostanka akceptorskega ogrodja variabilne težke verige s substitucijo na vsaj enem od težkoverižnih aminopoložajev 12, 103 in 144 (številčenje AHo), zlasti s substituiranjem s hidrofilno aminokislino, prednostno s substitucijo, izbrano iz skupine, ki jo sestavljajo: (a) serin (S) na položaju 12, (b) treonin (T) na položaju 103 in (c) treonin (T) na položaju 144.
- 28. Postopek po katerem koli od zahtevkov 24-27, ki nadalje obsega substituiranje ogrodnega ostanka akceptorskega ogrodja variabilne lahke verige s substitucijo za povečanje stabilnosti na vsaj enem od položajev 1, 3, 4, 10, 47, 57, 91 in 103 variabilne regije lahke verige po sistemu številčenje AHo, zlasti s substitucijo, izbrano iz skupine, ki jo sestavljajo (a) glutaminska kislina (E) na položaju 1, (b) valin (V) na položaju 3, (c) levcin (L) na položaju 4, (d) serin (S) na položaju 10, (e) arginin (R) na položaju 47, (e) serin (S) na položaju 57, (f) fenilalanin (F) na položaju 91 in (g) valin (V) na položaju 103.
- 29. Antigen vezavni polipeptid, humaniziran po postopku po katerem koli od zahtevkov 24-28.
- 30. Antigen vezavni polipeptid po zahtevku 29, kjer je tarčni antigen VEGF ali TNFa.
- 31. Postopek po katerem koli od zahtevkov 24-28, kjer postopek nadalje obsega identifikacijo donorskih CDR-jev protitelesne variabilne domene, ustvarjene s celicami B po stopnjah: a) inkubiranje kunčjih celic B s tarčnim antigenom; b) izbiranje tistih celic B, ki se vežejo na tarčni antigen, in c) identificiranje CDR-jev protitelesne variabilne domene, ustvarjene s celicami B.
- 32. Postopek po zahtevku 31, kjer so celice B izolirane iz kunca, kije bil imuniziran proti tarčnemu antigenu, prednostno z DNA-vakcinacij o.
- 33. Postopek po katerem koli od zahtevkov 31 ali 32, kjer so celice B in tarčni antigen različno obarvani in je sopojavnost obeh barv pozitivno izbrana s sortiranjem posameznih celic, kije osnovano na pretočni citometriji.
- 34. Postopek po katerem koli od zahtevkov 31-33, kjer je tarčni antigen topen protein.
- 35. Postopek po katerem koli od zahtevkov 31-33, kjer je tarčni antigen eksprimiran na površini celice, zlasti kjer je tarčni antigen transmembranski protein, zlasti protein, ki se razteza čez več membran.
- 36. Postopek po zahtevku 35, kjer je tarčni antigen obarvan indirektno z barvanjem celice, ki eksprimira tarčni antigen, z intracelulamo fluorescenčno barvo.
- 37. Postopek po katerem koli od zahtevkov 31-36, kjer so celice B obarvane z enim ali več označenimi protitelesi, ki so specifična za površinske markerje celic B.
- 38. Postopek po katerem koli od zahtevkov 31-37, kjer so celice B obarvane z označenimi protitelesi proti IgG.
- 39. Postopek po zahtevku 38, kjer so celice B obarvane z označenimi protitelesi proti IgG in z drugače označenimi protitelesi proti IgM.
- 40. Postopek po zahtevku 39, kjer so celice B, ki so bile obarvane z označenimi protitelesi proti IgM, negativno izbrane.
- 41. Postopek po katerem koli od zahtevkov 31-40, ki nadalje obsega stopnjo kultiviranja celic B, izbranih v stopnji b) po zahtevku 31, tako da se ustvarjena protitelesa izločijo v medij kulture, zlasti v prisotnosti pomočniške celične linije.
- 42. Postopek po zahtevku 41, ki nadalje obsega stopnjo preizkušanja izločenih protiteles za specifično vezavo na tarčni antigen.
- 43. Postopek po zahtevku 42, kjer so CDR-ji navedenih protiteles pomnoženi, zlasti z uporabo RT-PCR, in transplantirani v akceptorsko ogrodje, da se ustvari antigen vezavni polipeptid, ki ga nato preizkusimo za specifično vezavo na tarčni antigen.
- 44. Uporaba akceptorskega ogrodja humane variabilne težke verige, ki obsega sekvenco, ki ima vsaj 95-odstotno enakost s SEQ ID NO: 4, ki nadalje obsega vsaj šest aminokislin iz skupine, ki jo sestavljajo treonin (T) na položaju 24, valin (V) na položaju 25, alanin (A) ali glicin (G) na položaju 56, lizin (K) na položaju 82, treonin (T) na položaju 84, valin (V) na položaju 89 in arginin (R) na položaju 108 (številčenje AHo), in akceptorskega ogrodja humane variabilne lahke verige ki obsega sekvenco, ki ima vsaj 85-odstotno enakost s SEQ ID NO: 2, za transplantacijo kunčjih CDR-jev.
- 45. Uporaba po zahtevku 44, kjer ogrodje obsega SEQ ID NO: 1 in SEQ ID NO: 2, obe vezani preko povezovalca, ki ima SEQ ID NO: 8.
- 46. Farmacevtski sestavek, ki obsega antigen vezavni polipeptid po katerem koli od prejšnjih zahtevkov, formuliran za topično, peroralno, nazalno, intracerebrospinalno, rektalno ali parenteralno dajanje.
- 47. Formulacija, ki obsega akceptorsko ogrodje po katerem koli od zahtevkov 1-13 ali antigen vezavni polipeptid po zahtevku 29 ali 30, za uporabo kot zdravilo, označena s tem, daje treba dati sestavek intramuskulamo, intraperitonealno, intracerebrospinalno, subkutano, intraartikulamo, intrasinovialno, intratekalno, peroralno, topično ali z inhalacijo.
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US7569708P | 2008-06-25 | 2008-06-25 | |
US7569208P | 2008-06-25 | 2008-06-25 | |
US15504109P | 2009-02-24 | 2009-02-24 | |
US15510509P | 2009-02-24 | 2009-02-24 | |
CH8322009 | 2009-06-02 | ||
PCT/CH2009/000222 WO2009155726A2 (en) | 2008-06-25 | 2009-06-25 | Humanization of rabbit antibodies using a universal antibody framework |
EP09768695.0A EP2307458B1 (en) | 2008-06-25 | 2009-06-25 | Humanization of rabbit antibodies using a universal antibody framework |
Publications (1)
Publication Number | Publication Date |
---|---|
SI2307458T1 true SI2307458T1 (sl) | 2018-08-31 |
Family
ID=43414179
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SI200932039T SI2752428T1 (sl) | 2008-06-25 | 2009-06-25 | Humaniziranje zajčjih protiteles z uporabo univerzalnega ogrodja protitelesa |
SI200931857T SI2307458T1 (sl) | 2008-06-25 | 2009-06-25 | Humanizacija kunčjih protiteles z uporabo univerzalnega protitelesnega ogrodja |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SI200932039T SI2752428T1 (sl) | 2008-06-25 | 2009-06-25 | Humaniziranje zajčjih protiteles z uporabo univerzalnega ogrodja protitelesa |
Country Status (16)
Country | Link |
---|---|
US (5) | US8293235B2 (sl) |
EP (3) | EP3628686B1 (sl) |
JP (1) | JP5856480B2 (sl) |
KR (4) | KR101956059B1 (sl) |
CN (3) | CN107090035A (sl) |
AU (4) | AU2009264567B2 (sl) |
BR (1) | BRPI0914663A2 (sl) |
DK (3) | DK3628686T3 (sl) |
ES (1) | ES2677003T3 (sl) |
HU (1) | HUE038432T2 (sl) |
MX (1) | MX345395B (sl) |
PL (2) | PL2307458T3 (sl) |
RU (1) | RU2635186C2 (sl) |
SI (2) | SI2752428T1 (sl) |
TR (1) | TR201808591T4 (sl) |
WO (1) | WO2009155726A2 (sl) |
Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2719400C (en) * | 2008-03-26 | 2017-11-14 | Epitomics, Inc. | Anti-vegf antibody |
AU2009264564B2 (en) | 2008-06-25 | 2014-05-08 | Novartis Ag | Stable and soluble antibodies inhibiting TNFalpha |
ES2677003T3 (es) | 2008-06-25 | 2018-07-27 | Esbatech, An Alcon Biomedical Research Unit Llc | Humanización de anticuerpos de conejo utilizando un marco universal de anticuerpos |
KR102095257B1 (ko) | 2008-06-25 | 2020-04-01 | 노바르티스 아게 | Vegf를 억제하는 안정하고 가용성인 항체 |
US8697074B2 (en) * | 2008-07-10 | 2014-04-15 | Esbatech, An Alcon Biomedical Research Unit Llc | Methods and compositions for enhanced delivery of macromolecules |
CN102239181A (zh) | 2009-02-24 | 2011-11-09 | 艾斯巴技术,爱尔康生物医药研究装置有限责任公司 | 用于鉴定细胞表面抗原的免疫结合剂的方法 |
US8399625B1 (en) | 2009-06-25 | 2013-03-19 | ESBATech, an Alcon Biomedical Research Unit, LLC | Acceptor framework for CDR grafting |
AU2010335950B2 (en) * | 2009-12-23 | 2014-08-21 | Novartis Ag | Method for decreasing immunogenicity |
AU2014262201B2 (en) * | 2009-12-23 | 2016-09-15 | Novartis Ag | Method for decreasing immunogenicity |
UA107490C2 (uk) | 2010-04-07 | 2015-01-12 | Еббві Інк. | TNF-α-ЗВ'ЯЗУВАЛЬНИЙ БІЛОК |
AR083495A1 (es) | 2010-10-22 | 2013-02-27 | Esbatech Alcon Biomed Res Unit | Anticuerpos estables y solubles |
ES2687245T3 (es) | 2011-10-20 | 2018-10-24 | Esbatech - A Novartis Company Llc | Anticuerpo estable de unión a antígenos múltiples |
KR102069394B1 (ko) * | 2011-11-23 | 2020-01-22 | 에프. 호프만-라 로슈 아게 | Cd40l 발현 포유류 세포 및 그의 용도 |
CA2888583C (en) | 2012-11-05 | 2022-03-29 | Delenex Therapeutics Ag | Binding members to il-1 beta |
ES2895848T3 (es) | 2012-12-17 | 2022-02-22 | Cell Medica Inc | Anticuerpos contra IL-1 beta |
WO2014124677A1 (en) * | 2013-02-15 | 2014-08-21 | Esbatech - A Novartis Company Llc | Acceptor framework for cdr grafting |
AU2013379444A1 (en) * | 2013-02-20 | 2015-06-11 | Esbatech - A Novartis Company Llc | Acceptor framework for CDR grafting |
CN113943366A (zh) | 2013-06-26 | 2022-01-18 | 努玛医疗技术有限公司 | 新型抗体框架 |
TWI738632B (zh) | 2014-11-07 | 2021-09-11 | 瑞士商諾華公司 | 穩定的含有高濃度抗vegf抗體之蛋白質溶液調配物 |
EP3026060A1 (en) | 2014-11-26 | 2016-06-01 | Miltenyi Biotec GmbH | Humanized antibody or fragment thereof specific for CD45R0 |
WO2016168755A1 (en) | 2015-04-17 | 2016-10-20 | Distributed Bio, Inc. | Method for mass humanization of non-human antibodies |
US11685773B2 (en) | 2015-04-30 | 2023-06-27 | Abcheck S.R.O. | Method for mass humanization of rabbit antibodies |
ES2903408T3 (es) | 2016-02-25 | 2022-04-01 | Cell Medica Switzerland Ag | Miembros de unión para PD-L1 |
WO2017158084A1 (en) | 2016-03-17 | 2017-09-21 | Numab Innovation Ag | ANTI-TNFα-ANTIBODIES AND FUNCTIONAL FRAGMENTS THEREOF |
CA3011500A1 (en) | 2016-03-17 | 2017-09-21 | Numab Innovation Ag | Anti-tnfalpha-antibodies and functional fragments thereof |
EP3219726B1 (en) | 2016-03-17 | 2020-12-02 | Tillotts Pharma AG | Anti-tnf alpha-antibodies and functional fragments thereof |
CN109153718B (zh) | 2016-03-17 | 2022-02-08 | 努玛治疗有限公司 | 抗TNFα抗体及其功能片段 |
EP3219727B1 (en) | 2016-03-17 | 2020-12-16 | Tillotts Pharma AG | Anti-tnf alpha-antibodies and functional fragments thereof |
EP3409688A1 (en) | 2017-05-31 | 2018-12-05 | Tillotts Pharma Ag | Topical treatment of inflammatory bowel disease using anti-tnf-alpha antibodies and fragments thereof |
EP3456739A1 (en) | 2017-09-19 | 2019-03-20 | Tillotts Pharma Ag | Use of anti-tnfalpha antibodies for treating wounds |
EP3459529A1 (en) | 2017-09-20 | 2019-03-27 | Tillotts Pharma Ag | Preparation of sustained release solid dosage forms comprising antibodies by spray drying |
ES2938609T3 (es) | 2017-09-20 | 2023-04-13 | Tillotts Pharma Ag | Preparación de formas farmacéuticas sólidas que comprenden anticuerpos mediante estratificación de solución/suspensión |
EP3459968A1 (en) | 2017-09-20 | 2019-03-27 | Numab Innovation AG | Novel stable antibody variable domain framework combinations |
ES2938608T3 (es) | 2017-09-20 | 2023-04-13 | Tillotts Pharma Ag | Método para preparar una forma farmacéutica sólida que comprende anticuerpos mediante granulación en húmedo, extrusión y esferonización |
WO2019233984A1 (en) * | 2018-06-08 | 2019-12-12 | Ventana Medical Systems, Inc. | Universal or normalized antibody frameworks for improved functionality and manufacturability |
WO2020114616A1 (en) | 2018-12-07 | 2020-06-11 | Tillotts Pharma Ag | Topical treatment of immune checkpoint inhibitor induced diarrhoea, colitis or enterocolitis using antibodies and fragments thereof |
CA3119241A1 (en) | 2018-12-18 | 2020-06-25 | Novartis Ag | Protein solution formulation containing high concentration of an anti-vegf antibody |
SG11202107995SA (en) | 2019-01-31 | 2021-08-30 | Numab Therapeutics AG | Multispecific antibodies having specificity for tnfa and il-17a, antibodies targeting il-17a, and methods of use thereof |
WO2022171771A1 (en) | 2021-02-12 | 2022-08-18 | Boehringer Ingelheim International Gmbh | Complement c3 antigen binding proteins |
EP4304725A1 (en) | 2021-03-09 | 2024-01-17 | CDR-Life AG | Rabbit-derived antigen binding protein nucleic acid libraries |
EP4304726A1 (en) | 2021-03-09 | 2024-01-17 | CDR-Life AG | Mage-a4 peptide-mhc antigen binding proteins |
KR20240116828A (ko) | 2021-12-14 | 2024-07-30 | 씨디알-라이프 아게 | 이중 mhc-표적화 t 세포 관여자 |
WO2024056758A1 (en) | 2022-09-14 | 2024-03-21 | Cdr-Life Ag | Mage-a4 peptide dual t cell engagers |
WO2024114906A1 (en) | 2022-11-30 | 2024-06-06 | Mabylon Ag | Antibodies against apoptosis-associated speck-like protein containing a card (asc) and uses thereof |
Family Cites Families (72)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4704362A (en) | 1977-11-08 | 1987-11-03 | Genentech, Inc. | Recombinant cloning vehicle microbial polypeptide expression |
GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
US4881175A (en) | 1986-09-02 | 1989-11-14 | Genex Corporation | Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides |
US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
EP0279582A3 (en) | 1987-02-17 | 1989-10-18 | Pharming B.V. | Dna sequences to target proteins to the mammary gland for efficient secretion |
US5013653A (en) | 1987-03-20 | 1991-05-07 | Creative Biomolecules, Inc. | Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage |
WO1988009344A1 (en) | 1987-05-21 | 1988-12-01 | Creative Biomolecules, Inc. | Targeted multifunctional proteins |
US5132405A (en) | 1987-05-21 | 1992-07-21 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
US5633076A (en) | 1989-12-01 | 1997-05-27 | Pharming Bv | Method of producing a transgenic bovine or transgenic bovine embryo |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
ES2206447T3 (es) | 1991-06-14 | 2004-05-16 | Genentech, Inc. | Anticuerpo humanizado para heregulina. |
WO1994009817A1 (en) | 1992-11-04 | 1994-05-11 | City Of Hope | Novel antibody construct |
US5804187A (en) | 1992-11-16 | 1998-09-08 | Cancer Research Fund Of Contra Costa | Modified antibodies with human milk fat globule specificity |
US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
CA2267620A1 (en) * | 1996-07-16 | 1998-01-22 | Andreas Pluckthun | Immunoglobulin superfamily domains and fragments with increased solubility |
US6905668B1 (en) | 1998-09-25 | 2005-06-14 | Tokyo Gas Company Limited | Diagnostic agents for pancreatic exocrine function |
AU1097301A (en) * | 1999-10-22 | 2001-05-08 | Scripps Research Institute, The | Humanization of non-human, mammalian antibodies |
US7258986B2 (en) | 1999-12-28 | 2007-08-21 | Esbatech Ag | Intrabodies with defined framework that is stable in a reducing environment and applications thereof |
GB0013810D0 (en) | 2000-06-06 | 2000-07-26 | Celltech Chiroscience Ltd | Biological products |
WO2002002781A1 (en) | 2000-06-30 | 2002-01-10 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | Heterodimeric fusion proteins |
UA81743C2 (uk) | 2000-08-07 | 2008-02-11 | Центокор, Инк. | МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ |
PT1354034E (pt) * | 2000-11-30 | 2008-02-28 | Medarex Inc | Roedores transgénicos transcromossómicos para produção de anticorpos humanos |
EP1361893B1 (en) | 2001-02-19 | 2012-10-24 | Merck Patent GmbH | Modified anti-egfr antibodies with reduced immunogenicity |
GB0110029D0 (en) * | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
AU2003217912A1 (en) * | 2002-03-01 | 2003-09-16 | Xencor | Antibody optimization |
NZ536412A (en) * | 2002-05-22 | 2008-10-31 | Esbatech Ag | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
US20040086979A1 (en) * | 2002-08-15 | 2004-05-06 | Dongxiao Zhang | Humanized rabbit antibodies |
AU2003298112A1 (en) * | 2002-11-13 | 2004-06-03 | Micromet Ag | Method for identifying antigen specific b cells |
DE10314412A1 (de) | 2003-03-28 | 2004-10-14 | Genovac Ag | Genetische Immunisierung mit multiplen Expressionskonstrukten zur Herstellung von monoklonalen Antikörpern |
WO2004108721A1 (en) | 2003-04-01 | 2004-12-16 | Sun Pharmaceutical Industries Limited | Process for the preparation of 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl] methyl]-2,4-thiazolidinedione |
US20050048578A1 (en) * | 2003-06-26 | 2005-03-03 | Epitomics, Inc. | Methods of screening for monoclonal antibodies with desirable activity |
KR101206206B1 (ko) | 2003-07-22 | 2012-11-29 | 크루셀 홀란드 비.브이. | 사스-코로나바이러스에 대한 결합분자 및 그것의 용도 |
AU2003259718A1 (en) * | 2003-08-07 | 2005-03-07 | Epitomics, Inc. | Methods for humanizing rabbit monoclonal antibodies |
AU2004280333A1 (en) | 2003-08-22 | 2005-04-21 | Medimmune, Llc | Humanization of antibodies |
US7569708B2 (en) | 2003-11-20 | 2009-08-04 | Mitsubishi Gas Chemical Company, Inc. | Liquid cyclohexane-tricarboxylic acid anhydride |
US7431927B2 (en) * | 2005-03-24 | 2008-10-07 | Epitomics, Inc. | TNFα-neutralizing antibodies |
RS52861B (en) | 2005-06-07 | 2013-12-31 | Esbatech - A Novartis Company Llc | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNF (ALPHA) |
EP2135881B1 (en) * | 2005-06-20 | 2011-09-07 | Genentech, Inc. | Antibodies binding to the tumour associated antigen TAT10772 for the diagnosis and treatment of tumor |
US7429487B2 (en) | 2005-07-05 | 2008-09-30 | Epitomics, Inc. | Fusion partner for production of monoclonal rabbit antibodies |
GB0520436D0 (en) | 2005-10-07 | 2005-11-16 | Photobiotics Ltd | Biological materials and uses thereof |
CA2625222A1 (en) | 2005-10-11 | 2007-04-19 | Domantis Limited | Antibody polypeptide library screening and selected antibody polypeptides |
UA92504C2 (en) | 2005-10-12 | 2010-11-10 | Эли Лилли Энд Компани | Anti-myostatin monoclonal antibody |
CN101443361B (zh) * | 2006-04-28 | 2015-08-19 | 德勒尼克斯治疗股份公司 | 与受体酪氨酸激酶alk的胞外域结合的抗体 |
EP1918302A3 (en) * | 2006-05-18 | 2009-11-18 | AvantGen, Inc. | Methods for the identification and the isolation of epitope specific antibodies |
CN103030696B (zh) | 2006-05-30 | 2016-09-28 | 健泰科生物技术公司 | 抗体和免疫偶联物及其用途 |
WO2008004834A1 (en) * | 2006-07-06 | 2008-01-10 | Isu Abxis Co., Ltd | Humanized monoclonal antibody highly binding to epidermal growth factor receptor, egf receptor |
ES2603399T3 (es) * | 2006-07-10 | 2017-02-27 | Esbatech, An Alcon Biomedical Research Unit Llc | Anticuerpos scFv que atraviesan capas epiteliales y/o endoteliales |
US7552970B2 (en) | 2006-07-11 | 2009-06-30 | La-Z-Boy Incorporated | Furniture mechanism with tilt cam for multiple position tilt |
RU2009137582A (ru) | 2007-03-12 | 2011-04-20 | Эсбатек Аг (Ch) | Инженерия и оптимизация одноцепочечных антител на основе последовательности |
AU2008232409C1 (en) * | 2007-03-22 | 2013-12-05 | Biogen Ma Inc. | Binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind CD154 and uses thereof |
WO2008144757A1 (en) | 2007-05-21 | 2008-11-27 | Alder Biopharmaceuticals, Inc. | Novel rabbit antibody humanization methods and humanized rabbit antibodies |
CN111253484A (zh) | 2007-06-25 | 2020-06-09 | 艾斯巴技术-诺华有限责任公司 | 修饰抗体的方法和具有改善的功能性质的修饰抗体 |
AU2008267733B2 (en) | 2007-06-25 | 2013-11-14 | Esbatech, An Alcon Biomedical Research Unit Llc | Sequence based engineering and optimization of single chain antibodies |
AU2009264564B2 (en) * | 2008-06-25 | 2014-05-08 | Novartis Ag | Stable and soluble antibodies inhibiting TNFalpha |
KR102095257B1 (ko) * | 2008-06-25 | 2020-04-01 | 노바르티스 아게 | Vegf를 억제하는 안정하고 가용성인 항체 |
ES2677003T3 (es) * | 2008-06-25 | 2018-07-27 | Esbatech, An Alcon Biomedical Research Unit Llc | Humanización de anticuerpos de conejo utilizando un marco universal de anticuerpos |
AU2009264566B2 (en) | 2008-06-25 | 2014-05-08 | Novartis Ag | Solubility optimization of immunobinders |
CN102239181A (zh) * | 2009-02-24 | 2011-11-09 | 艾斯巴技术,爱尔康生物医药研究装置有限责任公司 | 用于鉴定细胞表面抗原的免疫结合剂的方法 |
AU2010335950B2 (en) * | 2009-12-23 | 2014-08-21 | Novartis Ag | Method for decreasing immunogenicity |
AR083495A1 (es) * | 2010-10-22 | 2013-02-27 | Esbatech Alcon Biomed Res Unit | Anticuerpos estables y solubles |
EP2760855B1 (en) * | 2011-09-30 | 2017-03-15 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds as well as their use in treating type-2 diabetes |
TWI738632B (zh) * | 2014-11-07 | 2021-09-11 | 瑞士商諾華公司 | 穩定的含有高濃度抗vegf抗體之蛋白質溶液調配物 |
US20210017266A1 (en) | 2018-03-16 | 2021-01-21 | Novartis Ag | Methods for treating ocular diseases |
CA3119241A1 (en) | 2018-12-18 | 2020-06-25 | Novartis Ag | Protein solution formulation containing high concentration of an anti-vegf antibody |
-
2009
- 2009-06-25 ES ES09768695.0T patent/ES2677003T3/es active Active
- 2009-06-25 MX MX2013004869A patent/MX345395B/es unknown
- 2009-06-25 US US13/000,309 patent/US8293235B2/en active Active
- 2009-06-25 EP EP19208570.2A patent/EP3628686B1/en active Active
- 2009-06-25 BR BRPI0914663A patent/BRPI0914663A2/pt not_active Application Discontinuation
- 2009-06-25 DK DK19208570.2T patent/DK3628686T3/da active
- 2009-06-25 WO PCT/CH2009/000222 patent/WO2009155726A2/en active Application Filing
- 2009-06-25 EP EP14162664.8A patent/EP2752428B8/en active Active
- 2009-06-25 AU AU2009264567A patent/AU2009264567B2/en active Active
- 2009-06-25 DK DK09768695.0T patent/DK2307458T3/en active
- 2009-06-25 DK DK14162664.8T patent/DK2752428T3/da active
- 2009-06-25 JP JP2011515051A patent/JP5856480B2/ja active Active
- 2009-06-25 PL PL09768695T patent/PL2307458T3/pl unknown
- 2009-06-25 TR TR2018/08591T patent/TR201808591T4/tr unknown
- 2009-06-25 CN CN201710186530.3A patent/CN107090035A/zh active Pending
- 2009-06-25 CN CN201410191675.9A patent/CN104004094B/zh active Active
- 2009-06-25 KR KR1020167003710A patent/KR101956059B1/ko active IP Right Grant
- 2009-06-25 SI SI200932039T patent/SI2752428T1/sl unknown
- 2009-06-25 KR KR1020117001962A patent/KR101834797B1/ko active IP Right Grant
- 2009-06-25 SI SI200931857T patent/SI2307458T1/sl unknown
- 2009-06-25 PL PL14162664T patent/PL2752428T3/pl unknown
- 2009-06-25 KR KR1020187021025A patent/KR102007492B1/ko active Protection Beyond IP Right Term
- 2009-06-25 HU HUE09768695A patent/HUE038432T2/hu unknown
- 2009-06-25 KR KR1020167018056A patent/KR101882352B1/ko active IP Right Grant
- 2009-06-25 EP EP09768695.0A patent/EP2307458B1/en active Active
- 2009-06-25 CN CN2009801243120A patent/CN102164958A/zh active Pending
-
2012
- 2012-09-14 US US13/616,214 patent/US8937162B2/en active Active
-
2014
- 2014-02-12 US US14/179,141 patent/US9593161B2/en active Active
- 2014-07-11 AU AU2014203813A patent/AU2014203813B2/en active Active
-
2015
- 2015-12-10 US US14/965,488 patent/US10087244B2/en active Active
-
2016
- 2016-02-02 RU RU2016103262A patent/RU2635186C2/ru active
- 2016-02-18 AU AU2016201023A patent/AU2016201023B2/en active Active
-
2017
- 2017-12-18 US US15/844,984 patent/US11858981B2/en active Active
-
2018
- 2018-01-25 AU AU2018200640A patent/AU2018200640B2/en active Active
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
SI2307458T1 (sl) | Humanizacija kunčjih protiteles z uporabo univerzalnega protitelesnega ogrodja | |
ES2837134T3 (es) | Constructos de anticuerpos para CD70 y CD3 | |
US12059474B2 (en) | Methods for selecting antibodies that specifically bind glycosylated immune checkpoint proteins | |
ES2943147T3 (es) | Construcciones de anticuerpos para FLT3 y CD3 | |
RU2666915C2 (ru) | Антитела к интерлейкину-1альфа и способы применения | |
JP6515101B2 (ja) | Gitr抗原結合タンパク質 | |
US11739157B2 (en) | IL2Rbeta/common gamma chain antibodies | |
HRP20192160T1 (hr) | Vezujući proteini serumskog albumina | |
JP2021520788A (ja) | Dll3に対するキメラ受容体及びその使用方法 | |
KR20210138574A (ko) | Dll3 표적화 키메라 항원 수용체 및 결합제 | |
SI2840892T1 (sl) | Živali razen človeka s spremenjenimi zaporedji težke verige imunoglobulina | |
RU2018104703A (ru) | Опухолеспецифичное антитело против egfr и его применение | |
CY1112876T1 (el) | Πρωτεϊνες συνδεσης ειδικες για παρομοιους με ινσουλινη παραγοντες αναπτυξης και χρησεις αυτων | |
ES2633965T3 (es) | Uso terapéutico de ligando específico en enfermedades asociadas a MSRV | |
CN111630067B (zh) | 针对muc17和cd3的双特异性抗体构建体 | |
ES2960835T3 (es) | Moléculas de unión a antígeno y métodos de uso de las mismas | |
IL273196B1 (en) | Claudin 6 antibodies and methods of cancer treatment | |
US20220073619A1 (en) | Btn3a binding proteins and uses thereof | |
RU2014102617A (ru) | Выявление аффинно-зрелых человеческих антител | |
JP2021530233A (ja) | Steap1に対するキメラ受容体及びその使用方法 | |
CN112243381A (zh) | 抗bcma car抗体、缀合物和使用方法 | |
US11117936B2 (en) | Affinity-enhanced monomeric streptavidin chimeric antigen receptor (CAR) | |
EP2641915A1 (en) | Antibodies to the chemokine receptor XCR1 | |
JP2023506262A (ja) | 抗bcma car抗体、コンジュゲートおよび使用方法 | |
US20200172615A1 (en) | Novel method for producing antibodies |