RU2008122710A - Антагонисты нейропилина - Google Patents
Антагонисты нейропилина Download PDFInfo
- Publication number
- RU2008122710A RU2008122710A RU2008122710/13A RU2008122710A RU2008122710A RU 2008122710 A RU2008122710 A RU 2008122710A RU 2008122710/13 A RU2008122710/13 A RU 2008122710/13A RU 2008122710 A RU2008122710 A RU 2008122710A RU 2008122710 A RU2008122710 A RU 2008122710A
- Authority
- RU
- Russia
- Prior art keywords
- seq
- antibody
- nrp1
- antibody according
- variable region
- Prior art date
Links
- 102000002111 Neuropilin Human genes 0.000 title claims abstract 5
- 108050009450 Neuropilin Proteins 0.000 title claims abstract 5
- 239000005557 antagonist Substances 0.000 title claims 3
- 102000004207 Neuropilin-1 Human genes 0.000 claims abstract 24
- 108090000772 Neuropilin-1 Proteins 0.000 claims abstract 24
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims abstract 11
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract 11
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract 11
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 6
- 230000000903 blocking effect Effects 0.000 claims abstract 4
- 230000003993 interaction Effects 0.000 claims abstract 4
- 230000001404 mediated effect Effects 0.000 claims abstract 4
- 108050003978 Semaphorin Proteins 0.000 claims abstract 2
- 102000014105 Semaphorin Human genes 0.000 claims abstract 2
- 230000033115 angiogenesis Effects 0.000 claims abstract 2
- 230000004071 biological effect Effects 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 3
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims 2
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 2
- 239000004037 angiogenesis inhibitor Substances 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 229940127089 cytotoxic agent Drugs 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims 2
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims 2
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims 2
- 229960000241 vandetanib Drugs 0.000 claims 2
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 claims 2
- BRVFNEZMTRVUGW-QFIPXVFZSA-N (2s)-2-[6-[(3-methyl-1-oxo-4h-benzo[f]quinazolin-9-yl)methylamino]-3-oxo-1h-isoindol-2-yl]pentanedioic acid Chemical compound C1=C2C(=O)N([C@@H](CCC(O)=O)C(O)=O)CC2=CC(NCC2=CC=C3C=CC4=C(C3=C2)C(=O)N=C(N4)C)=C1 BRVFNEZMTRVUGW-QFIPXVFZSA-N 0.000 claims 1
- YABJJWZLRMPFSI-UHFFFAOYSA-N 1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolamine Chemical compound N=1C2=CC(OC=3C=C(N=CC=3)C=3NC(=CN=3)C(F)(F)F)=CC=C2N(C)C=1NC1=CC=C(C(F)(F)F)C=C1 YABJJWZLRMPFSI-UHFFFAOYSA-N 0.000 claims 1
- XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 claims 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 101000577540 Homo sapiens Neuropilin-1 Proteins 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 206010027406 Mesothelioma Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 241001529936 Murinae Species 0.000 claims 1
- CXQHYVUVSFXTMY-UHFFFAOYSA-N N1'-[3-fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC(C(=C1)F)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 CXQHYVUVSFXTMY-UHFFFAOYSA-N 0.000 claims 1
- 229960005557 OSI-7904 Drugs 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 claims 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- -1 SER-701 Chemical compound 0.000 claims 1
- 230000000118 anti-neoplastic effect Effects 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 claims 1
- 229960000397 bevacizumab Drugs 0.000 claims 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims 1
- 229960002412 cediranib Drugs 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 229960001433 erlotinib Drugs 0.000 claims 1
- 229960002584 gefitinib Drugs 0.000 claims 1
- 229940080856 gleevec Drugs 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 102000050920 human NRP1 Human genes 0.000 claims 1
- 229960002411 imatinib Drugs 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 229960004891 lapatinib Drugs 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- BMGQWWVMWDBQGC-IIFHNQTCSA-N midostaurin Chemical compound CN([C@H]1[C@H]([C@]2(C)O[C@@H](N3C4=CC=CC=C4C4=C5C(=O)NCC5=C5C6=CC=CC=C6N2C5=C43)C1)OC)C(=O)C1=CC=CC=C1 BMGQWWVMWDBQGC-IIFHNQTCSA-N 0.000 claims 1
- 229950010895 midostaurin Drugs 0.000 claims 1
- RAHBGWKEPAQNFF-UHFFFAOYSA-N motesanib Chemical compound C=1C=C2C(C)(C)CNC2=CC=1NC(=O)C1=CC=CN=C1NCC1=CC=NC=C1 RAHBGWKEPAQNFF-UHFFFAOYSA-N 0.000 claims 1
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 229960003876 ranibizumab Drugs 0.000 claims 1
- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 claims 1
- 229960001796 sunitinib Drugs 0.000 claims 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims 1
- 229940034785 sutent Drugs 0.000 claims 1
- UXXQOJXBIDBUAC-UHFFFAOYSA-N tandutinib Chemical compound COC1=CC2=C(N3CCN(CC3)C(=O)NC=3C=CC(OC(C)C)=CC=3)N=CN=C2C=C1OCCCN1CCCCC1 UXXQOJXBIDBUAC-UHFFFAOYSA-N 0.000 claims 1
- 229940120982 tarceva Drugs 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 claims 1
- 229940099039 velcade Drugs 0.000 claims 1
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
- 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
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A61K31/33—Heterocyclic compounds
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
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- A61K31/69—Boron compounds
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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
- 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
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- 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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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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- 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
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- A—HUMAN NECESSITIES
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- A61P35/04—Antineoplastic agents specific for metastasis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
- C07K16/28—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
- C07K16/3023—Lung
-
- 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
- C07K2317/70—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
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Endocrinology (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
1. Антитело к нейропилину-1 (NRP1), которое обладает способностью ингибировать по меньшей мере один вид биологической активности, опосредуемый нейропилином (NRP). ! 2. Антитело по п.1, которое обладает способностью ингибировать взаимодействие NRP1 с семафорином. ! 3. Антитело по п.1, которое обладает способностью ингибировать взаимодействие NRP1 с сосудистым эндотелиальным фактором роста (VEGF). ! 4. Антитело по п.1, которое связывается с NRP1 в а1а2-домене и блокирует связывание NRP1 с семафорином, не блокируя при этом связывание NRP1 с VEGF. ! 5. Антитело по п.4, которое обладает способностью ингибировать опосредуемый NRP1 ангиогенез. ! 6. Антитело по п.4, которое включает вариабельную область легкой цепи, содержащую следующие аминокислотные последовательности гипервариабельных участков (CDR): CDRL1 (RASQSISSYLA; SEQ ID NO:123), CDRL2 (GASSRAS; SEQ ID NO:124) и CDRL3 (QQYMSVPIT; SEQ ID NO:125). ! 7. Антитело по п.6, которое включает последовательность вариабельной области легкой цепи, представленную в SEQ ID NO:3. ! 8. Антитело по п.4, которое включает вариабельную область тяжелой цепи, содержащую следующие аминокислотные последовательности CDR: CDRH1 (GFSFSSEPIS; SEQ ID NO:126), CDRH2 (SSITGKNGYTYYADSVKG; SEQ ID NO:127) и CDRH3 (WGKKVYGMDV; SEQ ID NO:128). ! 9. Антитело по п.8, которое содержит последовательность вариабельной области тяжелой цепи, представленную в SEQ ID NO:4. ! 10. Антитело по п.4, представляющее собой антитело YW64.3, которое содержит последовательность вариабельной области легкой цепи, представленную в SEQ ID NO:3, и последовательность вариабельной области тяжелой цепи, представленную в SEQ ID NO:4. ! 11. Антитело по п.1, которое связывается с NRP1 в b1b2-домене и блокирует связывание NRP1 с VEGF, не блокируя при этом связывание NRP1 с семафорином. ! 12. Антитело по п
Claims (30)
1. Антитело к нейропилину-1 (NRP1), которое обладает способностью ингибировать по меньшей мере один вид биологической активности, опосредуемый нейропилином (NRP).
2. Антитело по п.1, которое обладает способностью ингибировать взаимодействие NRP1 с семафорином.
3. Антитело по п.1, которое обладает способностью ингибировать взаимодействие NRP1 с сосудистым эндотелиальным фактором роста (VEGF).
4. Антитело по п.1, которое связывается с NRP1 в а1а2-домене и блокирует связывание NRP1 с семафорином, не блокируя при этом связывание NRP1 с VEGF.
5. Антитело по п.4, которое обладает способностью ингибировать опосредуемый NRP1 ангиогенез.
6. Антитело по п.4, которое включает вариабельную область легкой цепи, содержащую следующие аминокислотные последовательности гипервариабельных участков (CDR): CDRL1 (RASQSISSYLA; SEQ ID NO:123), CDRL2 (GASSRAS; SEQ ID NO:124) и CDRL3 (QQYMSVPIT; SEQ ID NO:125).
7. Антитело по п.6, которое включает последовательность вариабельной области легкой цепи, представленную в SEQ ID NO:3.
8. Антитело по п.4, которое включает вариабельную область тяжелой цепи, содержащую следующие аминокислотные последовательности CDR: CDRH1 (GFSFSSEPIS; SEQ ID NO:126), CDRH2 (SSITGKNGYTYYADSVKG; SEQ ID NO:127) и CDRH3 (WGKKVYGMDV; SEQ ID NO:128).
9. Антитело по п.8, которое содержит последовательность вариабельной области тяжелой цепи, представленную в SEQ ID NO:4.
10. Антитело по п.4, представляющее собой антитело YW64.3, которое содержит последовательность вариабельной области легкой цепи, представленную в SEQ ID NO:3, и последовательность вариабельной области тяжелой цепи, представленную в SEQ ID NO:4.
11. Антитело по п.1, которое связывается с NRP1 в b1b2-домене и блокирует связывание NRP1 с VEGF, не блокируя при этом связывание NRP1 с семафорином.
12. Антитело по п.11, которое включает вариабельную область легкой цепи, содержащую следующие аминокислотные последовательности CDR: CDRL1 (RASQYFSSYLA; SEQ ID NO:129), CDRL2 (GASSRAS; SEQ ID NO:130) и CDRL3 (QQYLGSPPT; SEQ ID NO:131).
13. Антитело по п.12, которое содержит последовательность вариабельной области легкой цепи, представленную в SEQ ID NO:5.
14. Антитело по п.11, которое включает вариабельную область тяжелой цепи, содержащую следующие аминокислотные последовательности CDR: CDRH1 (GFTFSSYAMS; SEQ ID NO:132), CDRH2 (SQISPAGGYTNYADSVKG; SEQ ID NO:133) и CDRH3 (ELPYYRMSKVMDV; SEQ ID NO:134).
15. Антитело по п.14, которое содержит последовательность вариабельной области тяжелой цепи, представленную в SEQ ID NO:6.
16. Антитело по п.11, представляющее собой антитело YW107.4.87, которое содержит последовательность вариабельной области легкой цепи, представленную в SEQ ID NO:5, и последовательность вариабельной области тяжелой цепи, представленную в SEQ ID NO:6.
17. Антитело по п.1, где антитело обладает способностью связываться как с мышиным NRP1, так и с человеческим NRP1.
18. Антитело по п.1, где антитело представляет собой моноклональное антитело.
19. Антитело по п.1, где антитело представляет собой биспецифическое антитело.
20. Антитело по п.1, где антитело представляет собой синтетическое антитело.
21. Применение антитела к NRP1 по п.1 для приготовления лекарственного средства, предназначенного для лечения или предупреждения нарушения, ассоциированного с патологическим ангиогенезом у млекопитающего.
22. Применение по п.21, где нарушение представляет собой рак.
23. Применение по п.22, где рак выбран из группы, включающей рак молочной железы, колоректальный рак, немелкоклеточный рак легкого, не-ходжкинскую лимфому (NHL), почечный рак, рак предстательной железы, рак печени, рак головы и шеи, меланому, рак яичника, мезотелиому и множественную миелому.
24. Применение по п.23, где лечение включает также применение второго терапевтического агента.
25. Применение по п.24, где второй терапевтический агент представляет собой агент, выбранный из группы, включающей антиангиогенный агент, антинеопластическую композицию, химиотерапевтический агент и цитотоксический агент.
26. Применение по п.25, в котором антиангиогенный агент представляет собой антагонист VEGF.
27. Применение по п.26, в котором антагонист VEGF представляет собой антитело к hVEGF.
28. Применение по п.27, в котором антитело к hVEGF обладает способностью связываться с тем же эпитопом VEGF, что и антитело А4.6.1.
29. Применение по п.28, в котором антитело к hVEGF представляет собой бевасизумаб или ранибизумаб.
30. Применение по п.24, в котором второй терапевтический агент представляет собой ингибитор тирозинкиназного рецептора, выбранный из группы, включающей ваталаниб (PTK787), эрлотиниб (TARCEVA®), OSI-7904, ZD6474 (ZACTIMA®), ZD6126 (ANG453), ZD1839, сунитиниб (SUTENT®), семаксаниб (SU5416), AMG706, AG013736, иматиниб (GLEEVEC®), MLN-518, СЕР-701, РКС-412, лапатиниб (GSK572016), VELCADE®, AZD2171, сорафениб (NEXAVAR®), XL880 и CHIR-265.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73479805P | 2005-11-08 | 2005-11-08 | |
| US60/734,798 | 2005-11-08 | ||
| US82056106P | 2006-07-27 | 2006-07-27 | |
| US60/820,561 | 2006-07-27 |
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| Publication Number | Publication Date |
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| RU2008122710A true RU2008122710A (ru) | 2009-12-20 |
| RU2425842C2 RU2425842C2 (ru) | 2011-08-10 |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2008122710/10A RU2425842C2 (ru) | 2005-11-08 | 2006-11-08 | Антагонисты нейропилина |
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