HRP20120139T1 - Kimerna i humanizirana monoklonska protutijela protiv interleukina 13 - Google Patents
Kimerna i humanizirana monoklonska protutijela protiv interleukina 13 Download PDFInfo
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- HRP20120139T1 HRP20120139T1 HR20120139T HRP20120139T HRP20120139T1 HR P20120139 T1 HRP20120139 T1 HR P20120139T1 HR 20120139 T HR20120139 T HR 20120139T HR P20120139 T HRP20120139 T HR P20120139T HR P20120139 T1 HRP20120139 T1 HR P20120139T1
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- 102000003816 Interleukin-13 Human genes 0.000 title 1
- 108090000176 Interleukin-13 Proteins 0.000 title 1
- 239000012634 fragment Substances 0.000 claims abstract 11
- 230000001225 therapeutic effect Effects 0.000 claims abstract 11
- 239000000427 antigen Substances 0.000 claims abstract 10
- 102000036639 antigens Human genes 0.000 claims abstract 10
- 108091007433 antigens Proteins 0.000 claims abstract 10
- 230000003993 interaction Effects 0.000 claims abstract 2
- 208000006673 asthma Diseases 0.000 claims 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 20
- 201000010099 disease Diseases 0.000 claims 12
- 210000004027 cell Anatomy 0.000 claims 11
- 208000035475 disorder Diseases 0.000 claims 8
- 150000003431 steroids Chemical class 0.000 claims 8
- 102000040430 polynucleotide Human genes 0.000 claims 6
- 108091033319 polynucleotide Proteins 0.000 claims 6
- 239000002157 polynucleotide Substances 0.000 claims 6
- 208000009657 Aspirin-Induced Asthma Diseases 0.000 claims 4
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 4
- 208000011231 Crohn disease Diseases 0.000 claims 4
- 206010012438 Dermatitis atopic Diseases 0.000 claims 4
- 201000003066 Diffuse Scleroderma Diseases 0.000 claims 4
- 208000017604 Hodgkin disease Diseases 0.000 claims 4
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 4
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims 4
- 108090000978 Interleukin-4 Proteins 0.000 claims 4
- 208000004554 Leishmaniasis Diseases 0.000 claims 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 4
- 206010039085 Rhinitis allergic Diseases 0.000 claims 4
- 201000009594 Systemic Scleroderma Diseases 0.000 claims 4
- 206010042953 Systemic sclerosis Diseases 0.000 claims 4
- 201000009961 allergic asthma Diseases 0.000 claims 4
- 201000010105 allergic rhinitis Diseases 0.000 claims 4
- 201000008937 atopic dermatitis Diseases 0.000 claims 4
- 208000029771 childhood onset asthma Diseases 0.000 claims 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 4
- 208000019425 cirrhosis of liver Diseases 0.000 claims 4
- 230000001419 dependent effect Effects 0.000 claims 4
- 230000003176 fibrotic effect Effects 0.000 claims 4
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 208000024696 nocturnal asthma Diseases 0.000 claims 4
- 229950011485 pascolizumab Drugs 0.000 claims 4
- 230000022983 regulation of cell cycle Effects 0.000 claims 4
- 201000004409 schistosomiasis Diseases 0.000 claims 4
- 208000024815 Granulomatous liver disease Diseases 0.000 claims 3
- 231100000843 hepatic granuloma Toxicity 0.000 claims 3
- 208000017694 hepatic granuloma Diseases 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 2
- 239000001963 growth medium Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 206010018691 Granuloma Diseases 0.000 claims 1
- 241000288906 Primates Species 0.000 claims 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims 1
- 230000024203 complement activation Effects 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 238000010494 dissociation reaction Methods 0.000 claims 1
- 230000005593 dissociations Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 239000004017 serum-free culture medium Substances 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
- A61P33/12—Schistosomicides
-
- 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
-
- 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
-
- 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
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- 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
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- 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
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- 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]
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- 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
Terapijsko protutijelo, ili njegov antigenski vežući fragment, naznačeno time što specifično veže hIL-13 i inhibira međudjelovanje između hIL-13 i hIL-13R, te sadrži sljedeći CDRH3: SEQ ID NO:3. Patent sadrži još 44 patentna zahtjeva.
Description
SPISAK SLJEDOVA
[0358]
SEQ.I.D.NO:1
FYIKDTYMH
SEQ.I.D.NO:2
TIDPANGNTKYVPKFQG
SEQ.I.D.NO:3
SIYDDYHYDDYYAMDY
SEQ.I.D.NO:4
RSSQNIVHINGNTYLE
SEQ.I.D.NO:5
KISDRFS
SEQ.I.D.NO:6
FQGSHVPWT
SEQ.I.D.NO:7
EIQLQQSVAELVRPGASVRLSCTASGFYIKDTYMHWVIQRPEQGLEWIGTIDPANGNTKYVPKFQGKATITADTSSNTAYLRLSSLTSEDTAIYYCARSIYDDYHYDDYYAMDYWGQGTSVTVSS
SEQ.I.D.NO:8
DVLMTQTPLSLPVSLGDQASISCRSSQNIVHINGNTYLEWYLQKPGQSPKLLIYKISDRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIK
SEQ.I.D.NO:9
GPVPPSTALRELIEELVNITQNQKAPLCNGSMVWSINLTAGMYCAALESLINVSGCSAIEKTQRMLSGFCPHKVSAGQFSSLHVRDTKIEVAQFVKDLLLHLKKLFREGRFN
SEQ.I.D.NO:10
GGCCCTGTGCCTCCCTCTACAGCCCTCAGGGAGCTCATTGAGGAGCTGGTCAACATCACCCAGAACCAGAAGGCTCCGCTCTGCAATGGCAGCATGGTATGGAGCATCAACCTGACAGCTGGCATGTACTGTGCAGCCCTGGAATCCCTGATCAACGTGTCAGGCTGCAGTGCCATCGAGAAGACCCAGAGGATGCTGAGCGGATTCTGCCCGCACAAGGTCTCAGCTGGGCAGTTTTCCAGCTTGCATGTCCGAGACACCAAAATCGAGGTGGCCCAGTTTGTAAAGGACCTGCTCTTACATTTAAAGAAACTTTTTCGCGAGGGACGGTTCAACTGA
SEQ.I.D.NO:11
QVQLVQSGAEVKKPGSSVKVSCKASGFYIKDTYMHWVRQAPGQGLEWMGTIDPANGNTKYVPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSIYDDYHYDDYYAMDYWGQGTLVTVSS
SEQ.I.D.NO:12
QVQLVQSGAEVKKPGSSVKVSCKASGFYIKDTYMHWVIQAPGQGLEWMGTIDPANGNTKYVPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSIYDDYHYDDYYAMDYWGQGTLVTVSS
SEQ.I.D.NO:13
QVQLVQSGAEVKKPGSSVKVSCKASGFYIKDTYMHWVIQAPGQGLEWMGTIDPANGNTKYVPKFQGRVTITADTSTSTAYMELSSLRSEDTAVYYCARSIYDDYHYDDYYAMDYWGQGTLVTVSS
SEQ.I.D.NO:14
QVQLVQSGAEVKKPGSSVRVSCKASGFYIKDTYMHWVIQAPGQGLEWMGTIDPANGNTKYVPKFQGRVTITADTSTSTAYMRLSSLRSEDTAVYYCARSIYDDYHYDDYYAMDYWGQGTLVTVSS
SEQ.I.D.NO:15
DIVMTQSPLSLPVTPGEPASISCRSSQNIVHINGNTYLEWYLQKPGQSPRLLIYKISDRFSGVPDRFSGSGSGTDFTLKISRVEADDVGIYYCFQGSHVPWTFGQGTKLEIK
SEQ.I.D.NO:16
DIVMTQSPLSLPVTPGEPASISCRSSQNIVHINGNTYLEWYLQKPGQSPRLLIYKISDRFSGVPDRFSGSGSGTDFTLKISRVEADDVGVYYCFQGSHVPWTFGQGTKLEIK
SEQ.I.D.NO:17
MGWSCIILFLVATATGVHS
SEQ.I.D.NO:18
QVQLVQSGAEVKKPGSSVKVSCKASGFYIKDTYMHWVRQAPGQGLEWMGTIDPANGNTKYVPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSIYDDYHYDDYYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
SEQ.I.D.NO:19
QVQLVQSGAEVKKPGSSVKVSCKASGFYIKDTYMHWVIQAPGQGLEWMGTIDPANGNTKYVPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSIYDDYHYDDYYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
SEQ.I.D.NO:20
QVQLVQSGAEVKKPGSSVKVSCKASGFYIKDTYMHWVIQAPGQGLEWMGTIDPANGNTKYVPKFQGRVTITADTSTSTAYMELSSLRSEDTAVYYCARSIYDDYHYDDYYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
SEQ.I.D.NO:21
QVQLVQSGAEVKKPGSSVRVSCKASGFYIKDTYMHWVIQAPGQGLEWMGTIDPANGNTKYVPKFQGRVTITADTSTSTAYMRLSSLRSEDTAVYYCARSIYDDYHYDDYYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
SEQ.I.D.NO:22
DIVMTQSPLSLPVTPGEPASISCRSSQNIVHINGNTYLEWYLQKPGQSPRLLIYKISDRFSGVPDRFSGSGSGTDFTLKISRVEADDVGIYYCFQGSHVPWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ.I.D.NO:23
DIVMTQSPLSLPVTPGEPASISCRSSQNIVHINGNTYLEWYLQKPGQSPRLLIYKISDRFSGVPDRFSGSGSGTDFTLKISRVEADDVGVYYCFQGSHVPWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ.I.D.NO:24
GAAATTCAGCTGCAGCAGTCTGTGGCAGAACTTGTGAGGCCAGGGGCCTCAGTCAGGTTGTCCTGCACAGCTTCTGGCTTCTACATTAAAGACACCTATATGCACTGGGTGATTCAGAGGCCTGAACAGGGCCTGGAGTGGATTGGAACGATTGATCCTGCGAATGGTAATACTAAATATGTCCCGAAGTTCCAGGGCAAGGCCACTATAACTGCAGACACATCCTCCAACACAGCCTACCTGCGGCTCAGCAGCCTGACATCTGAGGACACTGCCATCTATTACTGTGCTAGAAGCATCTATGATGATTACCACTACGACGATTACTATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCA
SEQ.I.D.NO:25
GATGTTTTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCAGATCTAGTCAGAACATTGTACATATTAATGGAAACACCTATTTAGAATGGTACCTTCAGAAACCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAATTTCCGACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACGCTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTACTGCTTTCAAGGTTCACATGTTCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA
SEQ.I.D.NO:26
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGATTCTACATTAAAGACACCTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAACGATTGATCCTGCGAATGGTAATACTAAATATGTCCCGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAAGCATCTATGATGATTACCACTACGACGATTACTATGCTATGGACTACTGGGGCCAAGGGACACTAGTCACAGTCTCCTCA
SEQ.I.D.NO:27
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGATTCTACATTAAAGACACCTATATGCACTGGGTGATACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAACGATTGATCCTGCGAATGGTAATACTAAATATGTCCCGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAAGCATCTATGATGATTACCACTACGACGATTACTATGCTATGGACTACTGGGGCCAAGGGACACTAGTCACAGTCTCCTCA
SEQ.I.D.NO:28
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGATTCTACATTAAAGACACCTATATGCACTGGGTGATACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAACGATTGATCCTGCGAATGGTAATACTAAATATGTCCCGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACACATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAAGCATCTATGATGATTACCACTACGACGATTACTATGCTATGGACTACTGGGGCCAAGGGACACTAGTCACAGTCTCCTCA
SEQ.I.D.NO:29
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAGGGTCTCCTGCAAGGCTTCTGGATTCTACATTAAAGACACCTATATGCACTGGGTGATACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAACGATTGATCCTGCGAATGGTAATACTAAATATGTCCCGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACACATCCACGAGCACAGCCTACATGAGGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAAGCATCTATGATGATTACCACTACGACGATTACTATGCTATGGACTACTGGGGCCAAGGGACACTAGTCACAGTCTCCTCA
SEQ.I.D.NO:30
GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGATCTAGTCAGAACATTGTACATATTAATGGAAACACCTATTTAGAATGGTACCTGCAGAAGCCAGGGCAGTCTCCACGGCTCTTGATCTATAAAATTTCCGACCGATTTTCTGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACATTGAAAATCAGCAGAGTGGAGGCTGACGATGTTGGAATTTATTACTGCTTTCAAGGTTCACATGTTCCGTGGACGTTTGGCCAGGGGACCAAGCTGGAGATCAAG
SEQ.I.D.NO:31
GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGATCTAGTCAGAACATTGTACATATTAATGGAAACACCTATTTAGAATGGTACCTGCAGAAGCCAGGGCAGTCTCCACGGCTCTTGATCTATAAAATTTCCGACCGATTTTCTGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACATTGAAAATCAGCAGAGTGGAGGCTGACGATGTTGGAGTTTATTACTGCTTTCAAGGTTCACATGTTCCGTGGACGTTTGGCCAGGGGACCAAGCTGGAGATCAAG
SEQ.I.D.NO:32
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGATTCTACATTAAAGACACCTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAACGATTGATCCTGCGAATGGTAATACTAAATATGTCCCGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAAGCATCTATGATGATTACCACTACGACGATTACTATGCTATGGACTACTGGGGCCAAGGGACACTAGTCACAGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA
SEQ.I.D.NO:33
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGATTCTACATTAAAGACACCTATATGCACTGGGTGATACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAACGATTGATCCTGCGAATGGTAATACTAAATATGTCCCGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAAGCATCTATGATGATTACCACTACGACGATTACTATGCTATGGACTACTGGGGCCAAGGGACACTAGTCACAGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA
SEQ.I.D.NO:34
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGATTCTACATTAAAGACACCTATATGCACTGGGTGATACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAACGATTGATCCTGCGAATGGTAATACTAAATATGTCCCGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACACATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAAGCATCTATGATGATTACCACTACGACGATTACTATGCTATGGACTACTGGGGCCAAGGGACACTAGTCACAGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA
SEQ.I.D.NO:35
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAGGGTCTCCTGCAAGGCTTCTGGATTCTACATTAAAGACACCTATATGCACTGGGTGATACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAACGATTGATCCTGCGAATGGTAATACTAAATATGTCCCGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACACATCCACGAGCACAGCCTACATGAGGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAAGCATCTATGATGATTACCACTACGACGATTACTATGCTATGGACTACTGGGGCCAAGGGACACTAGTCACAGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA
SEQ.I.D.NO:36
GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGATCTAGTCAGAACATTGTACATATTAATGGAAACACCTATTTAGAATGGTACCTGCAGAAGCCAGGGCAGTCTCCACGGCTCTTGATCTATAAAATTTCCGACCGATTTTCTGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACATTGAAAATCAGCAGAGTGGAGGCTGACGATGTTGGAATTTATTACTGCTTTCAAGGTTCACATGTTCCGTGGACGTTTGGCCAGGGGACCAAGCTGGAGATCAAGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGACAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG
SEQ.I.D.NO:37
GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGATCTAGTCAGAACATTGTACATATTAATGGAAACACCTATTTAGAATGGTACCTGCAGAAGCCAGGGCAGTCTCCACGGCTCTTGATCTATAAAATTTCCGACCGATTTTCTGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACATTGAAAATCAGCAGAGTGGAGGCTGACGATGTTGGAGTTTATTACTGCTTTCAAGGTTCACATGTTCCGTGGACGTTTGGCCAGGGGACCAAGCTGGAGATCAAGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGACAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG
SEQ.I.D.NO:38
SGSGPSTALRELIEELVNIT
SEQ.I.D.NO:39
SGSGLRELIEELVNITQNQK
SEQ.I.D.NO:40
SGSGIEELVNITQNQKAPLC
SEQ.I.D.NO:41
SGSGVNITQNQKAPLCNGSM
SEQ.I.D.NO:42
SGSGQNQKAPLCNGSMVWSI
SEQ.I.D.NO:43
SGSGAPLCNGSMVWSINLTA
SEQ.I.D.NO:44
SGSGNGSMVWSINLTAGMYC
SEQ.I.D.NO:45
SGSGVWSINLTAGMYCAALE
SEQ.I.D.NO:46
SGSGNLTAGMYCAALESLIN
SEQ.I.D.NO:47
SGSGGMYCAALESLINVSGC
SEQ.I.D.NO:48
SGSGAALESLINVSGCSAIE
SEQ.I.D.NO:49
SGSGSLINVSGCSAIEKTQR
SEQ.I.D.NO:50
SGSGVSGCSAIEKTQRMLSG
SEQ.I.D.NO:51
SGSGSAIEKTQRMLSGFCPH
SEQ.I.D.NO:52
SGSGKTQRMLSGFCPHKVSA
SEQ.I.D.NO:53
SGSGMLSGFCPHKVSAGQFS
SEQ.I.D.NO:54
SGSGFCPHKVSAGQFSSLHV
SEQ.I.D.NO:55
SGSGKVSAGQFSSLHVRDTK
SEQ.I.D.NO:56
SGSGGQFSSLHVRDTKIEVA
SEQ.I.D.NO:57
SGSGSLHVRDTKIEVAQFVK
SEQ.I.D.NO:58
SGSGRDTKIEVAQFVKDLLL
SEQ.I.D.NO:59
SGSGIEVAQFVKDLLLHLKK
SEQ.I.D.NO:60
SGSGQFVKDLLLHLKKLFRE
SEQ.I.D.NO:61
SGSGDLLLHLKKLFREGRFN
SEQ.I.D.NO:62
SGSGPSTALKELIEELVNIT
SEQ.I.D.NO:63
SGSGLKELIEELVNITQNQK
SEQ.I.D.NO:64
SGSGNGSMVWSINLTAGVYC
SEQ.I.D.NO:65
SGSGVWSINLTAGVYCAALE
SEQ.I.D.NO:66
SGSGNLTAGVYCAALESLIN
SEQ.I.D.NO:67
SGSGGVYCAALESLINVSGC
SEQ.I.D.NO:68
SGSGVSGCSAIEKTQRMLNG
SEQ.I.D.NO:69
SGSGSAIEKTQRMLNGFCPH
SEQ.I.D.NO:70
SGSGKTQRMLNGFCPHKVSA
SEQ.I.D.NO:71
SGSGMLNGFCPHKVSAGQFS
SEQ.I.D.NO:72
SGSGFCPHKVSAGQFSSLRV
SEQ.I.D.NO:73
SGSGKVSAGQFSSLRVRDTK
SEQ.I.D.NO:74
SGSGGQFSSLRVRDTKIEVA
SEQ.I.D.NO:75
SGSGSLRVRDTKIEVAQFVK
SEQ.I.D.NO:76
SGSGRDTKIEVAQFVKDLLV
SEQ.I.D.NO:77
SGSGIEVAQFVKDLLVHLKK
SEQ.I.D.NO:78
SGSGQFVKDLLVHLKKLFRE
SEQ.I.D.NO:79
SGSGDLLVHLKKLFREGQFN
SEQ.I.D.NO:80
QFVKDLLLHLKKLFRE
SEQ.I.D.NO:81
DLLLHLKKLFREGRFN
SEQ.I.D.NO:82
QFVKDLLVHLKKLFRE
SEQ.I.D.NO:83
DLLVHLKKLFREGQFN
SEQ.I.D.NO:84
DLLLHLKKLFRE
SEQ.I.D.NO:85
DLLVHLKKLFRE
SEQ.I.D.NO:86
GATGAAGCTTGCCACCATGAAATGCAGCTGGGTCATC
SEQ.I.D.NO:87
GATGGACTAGTGTTCCTTGACCCCAGTA
SEQ.I.D.NO:88
GATGAAGCTTGCCACCATGAAGTTGCCTGTTAGGCTG
SEQ.I.D.NO:89
GATGCGTACGTTTGATTTCCAGCTTGGTGCC
SEQ.I.D.NO:90
SPVPPSTALKELIEELVNITQNQKAPLCNGSMVWSINLTAGVYCAALESLINVSGCSAIEKTQRMLNGFCPHKVSAGQFSSLRVRDTKIEVAQFVKDLLVHLKKLFREGQPN
SEQ.I.D.NO:91
AGCCCTGTGCCTCCCTCTACAGCCCTCAAGGAGCTCATTGAGGAGCTGGTCAACATCACCCAGAACCAGAAGGCCCCGCTCTGCAATGGCAGCATGGTGTGGAGCATCAACCTGACAGCTGGCGTGTACTGTGCAGCCCTGGAATCCCTGATCAACGTGTCAGGCTGCAGTGCCATCGAGAAGACCCAGAGGATGCTGAACGGATTCTGCCCGCACAAGGTCTCAGCTGGGCAGTTTTCCAGCTTGCGTGTCCGAGACACCAAAATCGAGGTGGCCCAGTTTGTAAAGGACCTGCTCGTACATTTAAAGAAACTTTTTCGCGAGGGACAGTTCAACTGA
SEQ.I.D.NO:92
QVQLVQSGAEVKKPGSSVKVSCKASGFYIKDTYMHWVRQAPGQGLEWMGTIDPANGNTKYVPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSIYDDYHYDDYYAMDYWGQGTLVTVSSG
SEQ.I.D.NO:93
DIVMTQSPLSLPVTPGEPASISCRSSQNIVHINGNTYLEWYLQKPGQSPRLLIYKISDRFSGVPDRFSGSGSGTDFTLKISRVEADDVGIYYCFQGSHVPWTFGQGTKLEIK
SEQ.I.D.NO:94
SGSGKDLLLHLKKLFREG
SEQ.I.D.NO:95
SGSGDLLLHLKKLFREG
SEQ.I.D.NO:96
SGSGLLLHLKKLFREG
SEQ.I.D.NO:97
SGSGLLHLKKLFREG
SEQ.I.D.NO:98
SGSGLHLKKLFREG
SEQ.I.D.NO:99
SGSGHLKKLFREG
SEQ.I.D.NO:100
SGSGLKKLFREG
SEQ.I.D.NO:101
SGSGKKLFREG
SEQ.I.D.NO:102
SGSGKLFREG
SEQ.I.D.NO:103
SGSGLFREG
SEQ.I.D.NO:104
SGSGFREG
SEQ.I.D.NO:105
SGSGKDLLLHLKKLFRE
SEQ.I.D.NO:106
SGSGKDLLLHLKKLFR
SEQ.I.D.NO:107
SGSGKDLLLHLKKLF
SEQ.I.D.NO:108
SGSGKDLLLHLKKL
SEQ.I.D.NO:109
SGSGKDLLLHLKK
SEQ.I.D.NO:110
SGSGKDLLLHLK
SEQ.I.D.NO:111
SGSGKDLLLHL
SEQ.I.D.NO:112
SGSGKDLLLH
SEQ.I.D.NO:113
SGSGKDLLL
SEQ.I.D.NO:114
SGSGKDLL
SEQ.I.D.NO:115
SGSGKDLLVHLKKLFREG
SEQ.I.D.NO:116
SGSGDLLVHLKKLFREG
SEQ.I.D.NO:117
SGSGLLVHLKKLFREG
SEQ.I.D.NO:118
SGSGLVHLKKLFREG
SEQ.I.D.NO:119
SGSGVHLKKLFREG
SEQ.I.D.NO:120
SGSGKDLLVHLKKLFRE
SEQ.I.D.NO:121
SGSGKDLLVHLKKLFR
SEQ.I.D.NO:122
SGSGKDLLVHLKKLF
SEQ.I.D.NO:123
SGSGKDLLVHLKKL
SEQ.I.D.NO:124
SGSGKDLLVHLKK
SEQ.I.D.NO:125
SGSGKDLLVHLK
SEQ.I.D.NO:126
SGSGKDLLVHL
SEQ.I.D.NO:127
SGSGKDLLVH
SEQ.I.D.NO:128
SGSGKDLLV
SEQ.I.D.NO:129
QFVKDLLLHLKKLFREGRFN
SEQ.I.D.NO:130
QFVKDLLLHAKKLFREGRFN
SEQ.I.D.NO:131
QFVKDLLLHLAKLFREGRFN
SEQ.I.D.NO:132
QFVKDLLLHLKALFREGRFN
SEQ.I.D.NO:133
QFVKDLLLHLKKAFREGRFN
SEQ.I.D.NO:134
QFVKDLLLHLKKLAREGRFN
SEQ.I.D.NO:135
QFVKDLLLHLKKLFAEGRFN
SEQ.I.D.NO:136
QFVKDLLLHLKKLFRAGRFN
Claims (45)
1. Terapijsko protutijelo, ili njegov antigenski vežući fragment, naznačeno time što specifično veže hIL-13 i inhibira međudjelovanje između hIL-13 i hIL-13R, te sadrži sljedeći CDRH3:
SEQ ID NO:3.
2. Terapijsko protutijelo, ili njegov antigenski vežući fragment, u skladu s patentni zahtjev 1, naznačeno time što sadrži sljedeće CDR-ove:
CDRH1: SEQ ID NO:1,
CDRH2: SEQ ID NO:2,
CDRH3: SEQ ID NO:3,
CDRL1: SEQ ID NO:4,
CDRL2: SEQ ID NO:5 i
CDRL3: SEQ ID NO:6.
3. Terapijsko protutijelo, ili antigenski vežući fragment, u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačeno time što je navedeno protutijelo intaktno protutijelo.
4. Terapijsko protutijelo, ili antigenski vežući fragment, u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, naznačen time što je navedeno protutijelo štakorsko, mišje, primatsko ili ljudsko protutijelo.
5. Mišje protutijelo u skladu s patentnim zahtjevom 4, naznačeno time što sadrži VH domenu sa SEQ ID NO:7 i VL domenu sa SEQ ID NO:8.
6. Terapijsko protutijelo u skladu s patentnim zahtjevom 4, naznačeno time što je navedeno protutijelo humanizirano ili kimerno protutijelo.
7. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži VH domenu sa SEQ ID NO:11 i VL domenu sa SEQ ID NO:15.
8. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži VH domenu sa SEQ ID NO:12 i VL domenu sa SEQ ID NO:15.
9. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži VH domenu sa SEQ ID NO:13 i VL domenu sa SEQ ID NO:15.
10. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži VH domenu sa SEQ ID NO:14 i VL domenu sa SEQ ID NO:15.
11. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži VH domenu sa SEQ ID NO:11 i VL domenu sa SEQ ID NO:16.
12. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži VH domenu sa SEQ ID NO:12 i VL domenu sa SEQ ID NO:16.
13. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži VH domenu sa SEQ ID NO:13 i VL domenu sa SEQ ID NO:16.
14. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži VH domenu sa SEQ ID NO:14 i VL domenu sa SEQ ID NO:16.
15. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 6 do 14, naznačeno time što navedeno protutijelo sadrži ljudsko konstantno područje.
16. Protutijelo u skladu s patentnim zahtjevom 15, naznačeno time što navedeno protutijelo sadrži konstantno područje IgG izotipa.
17. Protutijelo u skladu s patentnim zahtjevom 16, naznačeno time što je navedeno protutijelo IgG1 ili IgG4.
18. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži teški lanac sa SEQ ID NO:18 i laki lanac sa SEQ ID NO:22.
19. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži teški lanac sa SEQ ID NO:19 i laki lanac sa SEQ ID NO:22.
20. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži teški lanac sa SEQ ID NO:20 i laki lanac sa SEQ ID NO:22.
21. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži teški lanac sa SEQ ID NO:21 i laki lanac sa SEQ ID NO:22.
22. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži teški lanac sa SEQ ID NO:18 i laki lanac sa SEQ ID NO:23.
23. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži teški lanac sa SEQ ID NO:19 i laki lanac sa SEQ ID NO:23.
24. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži teški lanac sa SEQ ID NO:20 i laki lanac sa SEQ ID NO:23.
25. Humanizirano protutijelo u skladu s patentnim zahtjevom 6, naznačeno time što sadrži teški lanac sa SEQ ID NO:21 i laki lanac sa SEQ ID NO:23.
26. Antigenski vežući fragment u skladu s bilo kojim od patentnih zahtjeva 1-4, naznačen time što je navedeni fragment Fab, Fab', F(ab')2, Fv, diatrijelo, triatrijelo, tetratrijelo, miniprotutijelo, minitrijelo, izolirani VH, izolirani VL.
27. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 6 do 25, naznačeno time što sadrži mutirano Fc područje, tako da navedeno protutijelo pokazuje smanjeni ADCC i/ili aktiviranje komplementa.
28. Rekombinantno transformirana ili transficirana stanica-domaćin, naznačena time što sadrži prvi i drugi vektor, gdje navedeni prvi vektor sadrži polinukleotid koji kodira teški lanac protutijela u skladu s bilo kojim od prethodnih patentnih zahtjeva, a navedeni drugi vektor sadrži polinukleotid koji kodira laki lanac protutijela u skladu s bilo kojim od prethodnih patentnih zahtjeva.
29. Stanica-domaćin u skladu s patentnim zahtjevom 28, naznačena time što prvi vektor sadrži polinukleotid sa SEQ ID NO:7, a drugi vektor sadrži polinukleotid sa SEQ ID NO:8.
30. Stanica-domaćin u skladu s patentnim zahtjevom 29, naznačena time što prvi vektor sadrži polinukleotid kojeg se bira iz skupine koju čine SEQ ID NO: 26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, a drugi vektor sadrži polinukleotid kojeg se bira iz skupine koju čine SEQ ID NO: 15, SEQ ID NO:16, SEQ ID NO:36, SEQ ID NO:37.
31. Stanica-domaćin u skladu s bilo kojim od patentnih zahtjeva 28 do 30, naznačena time što je navedena stanica eukariotska.
32. Stanica-domaćin u skladu s patentnim zahtjevom 31, naznačena time što je navedena stanica sisavačka.
33. Stanica-domaćin u skladu s patentnim zahtjevom 31, naznačena time što je navedena stanica CHO ili NS0.
34. Postupak proizvodnje terapijskog protutijela u skladu s bilo kojim od patentnih zahtjeva 1 do 27, naznačen time što navedeni postupak uključuje korak uzgoja u kulturi stanice-domaćina u skladu s bilo od patentnih zahtjeva 28 do 33 u mediju za kulturu koji ne sadrži serum.
35. Postupak u skladu s patentnim zahtjevom 34, naznačen time što navedeno protutijelo navedena stanica-domaćin izlučuje u navedeni medij za kulturu.
36. Postupak u skladu s patentnim zahtjevom 35, naznačen time što se navedeno protutijelo dodatno pročišćuje do najmanje 95% ili više u odnosu na navedeno protutijelo koje sadrži medij za kulturu.
37. Farmaceutski pripravak, naznačen time što sadrži terapijsko protutijelo, ili njegov antigenski vežući fragment, u skladu s bilo kojim od patentnih zahtjeva 1 do 27 i farmaceutski prihvatljivu podlogu.
38. Terapijsko protutijelo, ili njegov antigenski vežući fragment, u skladu s bilo kojim od patentnih zahtjeva 1 do 27, naznačeno time što je namijenjeno liječenju bolesti ili poremećaja koje se bira iz skupine koju čine: alergijska astma, teška astma, teško izlječiva astma, krhka astma, noćna astma, premenstrualna astma, astma otporna na steroide, astma ovisna o steroidima, astma uzrokovana aspirinom, astma s početkom u odrasloj dobi, astma s početkom u dječjoj dobi, atopični dermatitis, alergijski rinitis, Crohnova bolest, COPD, fibrotične bolesti ili poremećaji, poput idiopatske plućne fibroze, progresivne sistemne skleroze, jetrene fibroze, jetrenih granuloma, shistosomijaza, lišmanijaza, bolesti regulacije staničnog ciklusa, poput Hodgkinove bolesti, B-stanica kronična limfocitni leukemia.
39. Upotreba terapijsko protutijelo, ili njegov antigenski vežući fragment, u skladu s bilo kojim od patentnih zahtjeva 1 do 27, naznačena time što su navedeno protutijelo ili njegov antigenski vežući fragment namijenjeni proizvodnji medikamenta za liječenje bolesti ili poremećaja koje se bira iz skupine koju čine: alergijska astma, teška astma, teško izlječiva astma, krhka astma, noćna astma, premenstrualna astma, astma otporna na steroide, astma ovisna o steroidima, astma uzrokovana aspirinom, astma s početkom u odrasloj dobi, astma s početkom u dječjoj dobi, atopični dermatitis, alergijski rinitis, Crohnova bolest, COPD, fibrotične bolesti ili poremećaji, poput idiopatske plućne fibroze, progresivne sistemne skleroze, jetrene fibroze, jetrenih granuloma, shistosomijaza, lišmanijaza, bolesti regulacije staničnog ciklusa, poput Hodgkinove bolesti, kronične limfocitne leukemije B-stanica.
40. Terapijsko protutijelo u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačeno time što se specifično veže na hIL-13 i konstanta disocijacije koff mu je u rasponu od 1,4 × 10–4 do 8,22 × 10–5 s–1.
41. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1 do 27 i monoklonsko protutijelo protiv IL-4, poput paskolizumaba, naznačena time što su namijenjena liječenju bolesti ili poremećaja koje se bira iz skupine koju čine: alergijska astma, teška astma, teško izlječiva astma, krhka astma, noćna astma, premenstrualna astma, astma otporna na steroide, astma ovisna o steroidima, astma uzrokovana aspirinom, astma s početkom u odrasloj dobi, astma s početkom u dječjoj dobi, atopični dermatitis, alergijski rinitis, Crohnova bolest, COPD, fibrotične bolesti ili poremećaji, poput idiopatske plućne fibroze, progresivne sistemne skleroze, jetrene fibroze, jetrenih granuloma, shistosomijaza, lišmanijaza, bolesti regulacije staničnog ciklusa, poput Hodgkinove bolesti, kronične limfocitne leukemije B-stanica.
42. Upotreba protutijela u skladu s bilo kojim od patentnih zahtjeva 1 do 27 i monoklonskog protutijela protiv IL-4, poput paskolizumaba, naznačena time što su navedeno protutijelo i navedeno monoklonsko protutijelo namijenjena proizvodnji medikamenta za liječenje bolesti ili poremećaja koje se bira iz skupine koju čine: alergijska astma, teška astma, teško izlječiva astma, krhka astma, noćna astma, premenstrualna astma, astma otporna na steroide, astma ovisna o steroidima, astma uzrokovana aspirinom, astma s početkom u odrasloj dobi, astma s početkom u dječjoj dobi, atopični dermatitis, alergijski rinitis, Crohnova bolest, COPD, fibrotične bolesti ili poremećaji, poput idiopatske plućne fibroze, progresivne sistemne skleroze, jetrene fibroze, jetrenih granuloma, shistosomijaza, lišmanijaza, bolesti regulacije staničnog ciklusa, poput Hodgkinove bolesti, kronične limfocitne leukemije B-stanica.
43. Upotreba u skladu s patentnim zahtjevom 41 ili 42, naznačena time što se monoklonsko protutijelo protiv IL-4 primijenjuje istodobno, uzastopno ili odvojeno od protutijela u skladu s bilo kojim od patentnih zahtjeva 1 do 27.
44. Upotreba u skladu s patentnim zahtjevom 41 do 43, naznačena time što je protutijelo protiv IL-4 paskolizumab.
45. Farmaceutski pripravak, naznačen time što sadrži prvo protutijelo u skladu s bilo kojim od patentnih zahtjeva 1 do 27 i drugo protutijelo, gdje je navedeno drugo protutijelo protutijelo protiv IL-4, poput paskolizumaba, i farmaceutski prihvatljivu podlogu.
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| PCT/GB2005/002581 WO2006003407A2 (en) | 2004-07-01 | 2005-06-30 | Chimeric and humanised monoclonal antibodies against inteleukin- 13 |
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2005
- 2005-06-29 TW TW094121993A patent/TWI307630B/zh not_active IP Right Cessation
- 2005-06-30 AU AU2005259025A patent/AU2005259025B2/en not_active Ceased
- 2005-06-30 EP EP11181891.0A patent/EP2436697B1/en not_active Revoked
- 2005-06-30 EP EP05757024A patent/EP1802658B1/en active Active
- 2005-06-30 PE PE2005000762A patent/PE20060376A1/es not_active Application Discontinuation
- 2005-06-30 PT PT05757024T patent/PT1802658E/pt unknown
- 2005-06-30 RU RU2007103826/10A patent/RU2404192C2/ru not_active IP Right Cessation
- 2005-06-30 WO PCT/GB2005/002581 patent/WO2006003407A2/en active Application Filing
- 2005-06-30 US US11/570,736 patent/US7807788B2/en not_active Expired - Fee Related
- 2005-06-30 PL PL05757024T patent/PL1802658T3/pl unknown
- 2005-06-30 AR ARP050102731A patent/AR049565A1/es unknown
- 2005-06-30 DK DK05757024.4T patent/DK1802658T3/da active
- 2005-06-30 ES ES05757024T patent/ES2378173T3/es active Active
- 2005-06-30 BR BRPI0512826-9A patent/BRPI0512826A/pt not_active IP Right Cessation
- 2005-06-30 AT AT05757024T patent/ATE535545T1/de active
- 2005-06-30 KR KR1020077002166A patent/KR20070034609A/ko active IP Right Grant
- 2005-06-30 CA CA002571799A patent/CA2571799A1/en not_active Abandoned
- 2005-06-30 NZ NZ552063A patent/NZ552063A/en not_active IP Right Cessation
- 2005-06-30 SI SI200531473T patent/SI1802658T1/sl unknown
- 2005-06-30 ES ES11181891.0T patent/ES2456897T3/es active Active
- 2005-06-30 JP JP2007518695A patent/JP5102616B2/ja not_active Expired - Fee Related
- 2005-06-30 MX MX2007000026A patent/MX2007000026A/es active IP Right Grant
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2006
- 2006-12-18 IL IL180152A patent/IL180152A0/en unknown
- 2006-12-29 MA MA29577A patent/MA28726B1/fr unknown
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2007
- 2007-01-11 NO NO20070189A patent/NO20070189L/no not_active Application Discontinuation
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2010
- 2010-08-24 US US12/862,235 patent/US20110243928A1/en not_active Abandoned
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2012
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