HRP20170658T1 - Molekula bispecifičnog protutijela - Google Patents
Molekula bispecifičnog protutijela Download PDFInfo
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- HRP20170658T1 HRP20170658T1 HRP20170658TT HRP20170658T HRP20170658T1 HR P20170658 T1 HRP20170658 T1 HR P20170658T1 HR P20170658T T HRP20170658T T HR P20170658TT HR P20170658 T HRP20170658 T HR P20170658T HR P20170658 T1 HRP20170658 T1 HR P20170658T1
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- antibody molecule
- fab fragment
- amino acid
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- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims 18
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims 18
- 235000001014 amino acid Nutrition 0.000 claims 12
- 150000001413 amino acids Chemical class 0.000 claims 12
- 239000000427 antigen Substances 0.000 claims 11
- 108091007433 antigens Proteins 0.000 claims 11
- 102000036639 antigens Human genes 0.000 claims 11
- 230000037430 deletion Effects 0.000 claims 11
- 238000012217 deletion Methods 0.000 claims 11
- 206010028980 Neoplasm Diseases 0.000 claims 8
- 239000012634 fragment Substances 0.000 claims 8
- 108091008874 T cell receptors Proteins 0.000 claims 7
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims 7
- 238000006467 substitution reaction Methods 0.000 claims 7
- 102000039446 nucleic acids Human genes 0.000 claims 5
- 108020004707 nucleic acids Proteins 0.000 claims 5
- 150000007523 nucleic acids Chemical class 0.000 claims 5
- -1 (CD115) Proteins 0.000 claims 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims 4
- 210000004027 cell Anatomy 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 229920001184 polypeptide Polymers 0.000 claims 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- 102100028757 Chondroitin sulfate proteoglycan 4 Human genes 0.000 claims 3
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims 3
- 125000000539 amino acid group Chemical group 0.000 claims 3
- 108700012439 CA9 Proteins 0.000 claims 2
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 claims 2
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 claims 2
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 claims 2
- 108010087819 Fc receptors Proteins 0.000 claims 2
- 102000009109 Fc receptors Human genes 0.000 claims 2
- 101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 claims 2
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims 2
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 claims 2
- 101000610551 Homo sapiens Prominin-1 Proteins 0.000 claims 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims 2
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 claims 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims 2
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims 2
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 claims 2
- 102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 claims 2
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims 2
- 102100040120 Prominin-1 Human genes 0.000 claims 2
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 claims 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims 2
- 210000001744 T-lymphocyte Anatomy 0.000 claims 2
- 101150056647 TNFRSF4 gene Proteins 0.000 claims 2
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 claims 2
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 claims 2
- 210000000822 natural killer cell Anatomy 0.000 claims 2
- 230000002062 proliferating effect Effects 0.000 claims 2
- 102000005962 receptors Human genes 0.000 claims 2
- 108020003175 receptors Proteins 0.000 claims 2
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 claims 1
- 108010058905 CD44v6 antigen Proteins 0.000 claims 1
- 102100035350 CUB domain-containing protein 1 Human genes 0.000 claims 1
- 102100032768 Complement receptor type 2 Human genes 0.000 claims 1
- 101100481408 Danio rerio tie2 gene Proteins 0.000 claims 1
- 102100030438 Derlin-1 Human genes 0.000 claims 1
- 101710178882 Derlin-1 Proteins 0.000 claims 1
- 102100037241 Endoglin Human genes 0.000 claims 1
- 108010036395 Endoglin Proteins 0.000 claims 1
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims 1
- 101710181403 Frizzled Proteins 0.000 claims 1
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims 1
- 102000006354 HLA-DR Antigens Human genes 0.000 claims 1
- 108010058597 HLA-DR Antigens Proteins 0.000 claims 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims 1
- 101000980814 Homo sapiens CAMPATH-1 antigen Proteins 0.000 claims 1
- 101000737742 Homo sapiens CUB domain-containing protein 1 Proteins 0.000 claims 1
- 101000941929 Homo sapiens Complement receptor type 2 Proteins 0.000 claims 1
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims 1
- 101100396742 Homo sapiens IL3RA gene Proteins 0.000 claims 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 claims 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 claims 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims 1
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 claims 1
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 claims 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims 1
- 101001126417 Homo sapiens Platelet-derived growth factor receptor alpha Proteins 0.000 claims 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 claims 1
- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 claims 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims 1
- 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 claims 1
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 claims 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 claims 1
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 claims 1
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 claims 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 claims 1
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 claims 1
- 101100346932 Mus musculus Muc1 gene Proteins 0.000 claims 1
- 101100481410 Mus musculus Tek gene Proteins 0.000 claims 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims 1
- 102000003729 Neprilysin Human genes 0.000 claims 1
- 108090000028 Neprilysin Proteins 0.000 claims 1
- 102100021768 Phosphoserine aminotransferase Human genes 0.000 claims 1
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 claims 1
- 101710148465 Platelet-derived growth factor receptor alpha Proteins 0.000 claims 1
- 102100036735 Prostate stem cell antigen Human genes 0.000 claims 1
- 108010072866 Prostate-Specific Antigen Proteins 0.000 claims 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 claims 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 claims 1
- 101001039269 Rattus norvegicus Glycine N-methyltransferase Proteins 0.000 claims 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims 1
- 102100038126 Tenascin Human genes 0.000 claims 1
- 108010008125 Tenascin Proteins 0.000 claims 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 108010039524 chondroitin sulfate proteoglycan 4 Proteins 0.000 claims 1
- 235000018417 cysteine Nutrition 0.000 claims 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 1
- 108010087914 epidermal growth factor receptor VIII Proteins 0.000 claims 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 1
- 210000002744 extracellular matrix Anatomy 0.000 claims 1
- 210000002950 fibroblast Anatomy 0.000 claims 1
- 108010003374 fms-Like Tyrosine Kinase 3 Proteins 0.000 claims 1
- 210000005095 gastrointestinal system Anatomy 0.000 claims 1
- 230000009033 hematopoietic malignancy Effects 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 201000008806 mesenchymal cell neoplasm Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 230000035772 mutation Effects 0.000 claims 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 101150047061 tag-72 gene Proteins 0.000 claims 1
- 210000004291 uterus Anatomy 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 210000005166 vasculature Anatomy 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- C07K16/2803—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
-
- 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
- C07K16/2803—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
- C07K16/2809—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 against the T-cell receptor (TcR)-CD3 complex
-
- 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
- C07K16/2803—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
- C07K16/2818—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 against CD28 or CD152
-
- 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
- C07K16/2803—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
- C07K16/283—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 against Fc-receptors, e.g. CD16, CD32, CD64
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—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 cytokines, lymphokines, interferons
-
- 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
- C07K16/3015—Breast
-
- 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
- C07K16/3053—Skin, nerves, brain
-
- 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
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/522—CH1 domain
-
- C—CHEMISTRY; METALLURGY
- 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
- C07K2317/524—CH2 domain
-
- C—CHEMISTRY; METALLURGY
- 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
- C07K2317/526—CH3 domain
-
- 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
- C07K2317/60—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
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Claims (15)
1. Rekombinantna bispecifična molekula protutijela, naznačena time što je čine fragment Fab koji sadrži prvo mjesto vezanja za prvi antigen, jednolančani fragment Fv koji sadrži drugo mjesto vezanja za drugi antigen i imunoglobulinska domena CH2, gdje fragment Fab dodatno sadrži područje zgloba, gdje su fragment Fab i jednolančani fragment Fv povezani preko domene CH2, gdje najmanje jedan aminokiselinski ostatak u domeni CH2 sposoban za vezanje na receptore za Fc nedostaje ili je mutiran, te gdje dodatno aminokiselinski ostaci na položajima u slijedu 226 i 229 (položaji u slijedu numerirani su prema EU-indeksu) nedostaju ili su mutirani, gdje najmanje jedan aminokiselinski ostatak u području zgloba ili u domeni CH2 sposoban za vezanje na receptore za Fc nedostaje ili je mutiran, te se bira iz skupine koju čine položaj 228, 230, 231, 232, 233, 234, 235, 236, 237, 238, 265, 297, 327, te 330 u slijedu (položaji u slijedu numerirani su prema EU-indeksu).
2. Molekula protutijela u skladu s patentnim zahtjevom 1, naznačena time što se
a) bilo prvo mjesto vezanja ili drugo mjesto vezanja veže na antigen povezan s tumorom; gdje
(i) antigen povezan s tumorom se po mogućnosti nalazi na vaskulaturi tumora; i/ili
(ii) antigen povezan s tumorom je po mogućnosti površinski antigen ili antigen izvanstaničnog matriksa; i/ili
(iii) antigen povezan s tumorom se po mogućnosti bira iz skupine koju čine CD10, CD19, CD20, CD21, CD22, CD25, CD30, CD33, CD34, CD37, CD44v6, CD45, CDw52, Fms-u slična tirozinska kinaza 3 (FLT-3, CD135), c-Kit (CD117), CSF1R, (CD115), CD133, PDGFR-α (CD140a), PDGFR-β (CD140b), kondroitin-sulfatni proteoglikan 4 (CSPG4, kondroitin-sulfatni proteoglikan povezan s melanomom), Muc-1, EGFR, de2-7-EGFR, EGFRvIII, folatno vežući protein, Her2neu, Her3, PSMA, PSCA, PSA, TAG-72, HLA-DR, IGFR, CD133, IL3R, protein koji aktivira fibroblaste (FAP), karboanhidraza IX (MN/CA IX), karcinoembrionalni antigen (CEA), EpCAM, CDCP1, Derlin1, Tenascin, kovrčavi 1-10, vaskularni antigeni VEGFR2 (KDR/FLK1), VEGFR3 (FLT4, CD309), endoglin, CLEC14, Tem1-8, te Tie2; i/ili
b) bilo prvo mjesto vezanja ili drugo mjesto vezanja po mogućnosti veže na receptorsku molekulu specifičnu za T-stanice ili stanice NK (prirodni ubojice), gdje je receptorska molekula specifična za T-stanice ili stanice NK po mogućnosti jedan od CD3, T-staničnog receptora (TCR), CD28, CD16, NKG2D, Ox40, 4-1 BB, CD2, CD5 i CD95, gdje je TCR po mogućnosti TCR (α/β) ili TCR (γ/δ).
3. Molekula protutijela u skladu s patentnim zahtjevom 1 ili 2, naznačena time što
(i) fragment Fab je povezan s domenom CH2 preko teškoolančanih domena CH1 i VH fragmenta Fab ili preko lakolančanih domena CL i VL fragmenta Fab, gdje se teškolančane domene fragmenta Fab ili lakolančane domene fragmenta Fab po mogućnosti nalaze na N-kraju polipeptidnog lanca, gdje je domena CH2 po mogućnosti povezana s fragmentom scFv preko varijabilne domene lakog lanca (domene VL) fragmenta scFv koji sadrži drugo mjesto vezanja ili preko varijabilne domene teškog lanca (domene VH) fragmenta scFv koji sadrži drugo mjesto vezanja; ili
(ii) fragment Fab koji sadrži prvo mjesto vezanja za prvi antigen po mogućnosti se sastoji od domene VL konjugirane s domenom CH1 i domene VH konjugirane s domenom CL, gdje je domena CH1 fragmenta Fab po mogućnosti konjugirana s domenom CH2, i/ili gdje se lanac VL-CH1 fragmenta Fab po mogućnosti nalazi na N-kraju polipeptidnog lanca.
4. Molekula protutijela u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što je fragment Fab povezan s domenom CH2 preko teškolančanih domena CH1 i VH fragmenta Fab.
5. Molekula protutijela u skladu s patentnim zahtjevom 4, naznačena time što se teškolančane domene fragmenta Fab nalaze na N-kraju polipeptidnog lanca.
6. Molekula protutijela u skladu s patentnim zahtjevom 5, naznačena time što je domena CH2 povezana s fragmentom scFv preko varijabilne domene lakog lanca (domene VL) fragmenta scFv koji sadrži drugo mjesto vezanja.
7. Molekula protutijela u skladu s patentnim zahtjevom 5, naznačena time što je domena CH2 povezana s fragmentom scFv preko varijabilne domene teškog lanca (domene VH) fragmenta scFv koji sadrži drugo mjesto vezanja.
8. Molekula protutijela u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što
a) fragment Fab sadrži područje zgloba; i/ili
b) prvo mjesto vezanja se veže na površinski antigen povezan s tumorom, a drugo mjesto vezanja se veže na jedan od CD3, T-staničnog receptora (TCR), CD28, CD16, NKG2D, Ox40, 4-1 BB, CD2, CD5 i CD95.
9. Molekula protutijela u skladu s patentnim zahtjevom 1, naznačena time što je cistein na jednom ili oba položaja 226 i 229 koji nedostaju ili su mutirani zamijenjen različitom aminokiselinom (položaji u slijedu numerirani su prema EU-indeksu).
10. Molekula protutijela u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što sadrži najmanje jednu mutaciju, koju se bira iz skupine koju čine delecija aminokiseline 228, delecija aminokiseline 229, delecija aminokiseline 230, delecija aminokiseline 231, delecija aminokiseline 232, delecija aminokiseline 233, zamjena Glu233→Pro, zamjena Leu234→Val, delecija aminokiseline 234, zamjena Leu235→Ala, delecija aminokiseline 235, delecija aminokiseline 236, delecija aminokiseline 237, delecija aminokiseline 238, zamjena Asp265→Gly, zamjena Asn297→Gln, zamjena Ala327→Gln, te zamjena Ala330→Ser (položaji u slijedu numerirani su prema EU-indeksu).
11. Molekula protutijela u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što je fragment Fab povezan s domenom CH2 preko teškolančane domene fragmenta Fab ili preko lakolančane domene fragmenta Fab, gdje se teškolančane domene fragmenta Fab po mogućnosti nalaze na N-kraju polipeptidnog lanca.
12. Farmaceutski pripravak, naznačen time što sadrži molekulu protutijela u skladu s bilo kojim od prethodnih patentnih zahtjeva.
13. Molekula protutijela u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačena time što je namijenjena upotrebi u liječenju bolesti, gdje je bolest po mogućnosti proliferativna bolest, gdje se proliferativnu bolest po mogućnosti bira iz skupine koju čine hemopoetske zloćudne novotvorine, poput akutnih i kroničnih mijeloidnih i limfatičnih leukemija, kao i limfomi, čvrstih tumora, poput tumora gastrointestinalnog sustava, pluća, bubreg, prostate, dojke, mozga, jajnika, maternice, mezenhimnih tumora i melanoma.
14. Molekula, vektor ili stanica domaćin, naznačeni time što su molekula nukleinske kiseline koja kodira molekulu protutijela u skladu s bilo kojim od patentnih zahtjeva 1 do 11, ili vektor koji sadrži navedenu molekulu nukleinske kiseline, ili stanica domaćin koja sadrži navedenu molekulu nukleinske kiseline ili navedeni vektor.
15. Postupak proizvodnje molekule protutijela u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačen time što se sastoji u ekspresiji nukleinska kiselina koja kodira molekulu protutijela u uvjetima koji omogućuju ekspresiju nukleinske kiseline, gdje se molekula protutijela po mogućnosti eksprimira u stanici domaćinu ili sustavu bez stanica.
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US201161577327P | 2011-12-19 | 2011-12-19 | |
PCT/EP2012/072364 WO2013092001A1 (en) | 2011-12-19 | 2012-11-12 | Bispecific antibody molecule |
EP12798623.0A EP2794658B1 (en) | 2011-12-19 | 2012-11-12 | Bispecific antibody molecule |
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US (2) | US9718893B2 (hr) |
EP (1) | EP2794658B1 (hr) |
JP (1) | JP6441079B2 (hr) |
CN (1) | CN104203981A (hr) |
BR (1) | BR112014015018A2 (hr) |
CA (1) | CA2859767C (hr) |
DK (1) | DK2794658T3 (hr) |
EA (1) | EA201400709A1 (hr) |
ES (1) | ES2628075T3 (hr) |
HR (1) | HRP20170658T1 (hr) |
HU (1) | HUE033245T2 (hr) |
LT (1) | LT2794658T (hr) |
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- 2012-11-12 JP JP2014547791A patent/JP6441079B2/ja active Active
- 2012-11-12 EP EP12798623.0A patent/EP2794658B1/en active Active
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- 2012-11-12 HU HUE12798623A patent/HUE033245T2/hu unknown
- 2012-11-12 EA EA201400709A patent/EA201400709A1/ru unknown
- 2012-11-12 SI SI201230939A patent/SI2794658T1/sl unknown
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US20180057608A1 (en) | 2018-03-01 |
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CN104203981A (zh) | 2014-12-10 |
CA2859767C (en) | 2018-09-11 |
EP2794658A1 (en) | 2014-10-29 |
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JP2015502373A (ja) | 2015-01-22 |
SI2794658T1 (sl) | 2017-05-31 |
ES2628075T3 (es) | 2017-08-01 |
HUE033245T2 (hu) | 2017-11-28 |
CA2859767A1 (en) | 2013-06-27 |
DK2794658T3 (en) | 2017-06-19 |
JP6441079B2 (ja) | 2018-12-19 |
US9718893B2 (en) | 2017-08-01 |
BR112014015018A2 (pt) | 2020-10-27 |
EA201400709A1 (ru) | 2016-08-31 |
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