ZA200305384B - Silenced anti-CD28 antibodies and use thereof. - Google Patents
Silenced anti-CD28 antibodies and use thereof. Download PDFInfo
- Publication number
- ZA200305384B ZA200305384B ZA200305384A ZA200305384A ZA200305384B ZA 200305384 B ZA200305384 B ZA 200305384B ZA 200305384 A ZA200305384 A ZA 200305384A ZA 200305384 A ZA200305384 A ZA 200305384A ZA 200305384 B ZA200305384 B ZA 200305384B
- Authority
- ZA
- South Africa
- Prior art keywords
- antibody
- seq
- cells
- composition
- substance
- Prior art date
Links
- 210000004027 cell Anatomy 0.000 claims description 148
- 238000000034 method Methods 0.000 claims description 64
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 37
- 239000013604 expression vector Substances 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 24
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 22
- 108091033319 polynucleotide Proteins 0.000 claims description 17
- 102000040430 polynucleotide Human genes 0.000 claims description 17
- 239000002157 polynucleotide Substances 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 15
- 239000013598 vector Substances 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 10
- 206010052779 Transplant rejections Diseases 0.000 claims description 9
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 8
- 239000003018 immunosuppressive agent Substances 0.000 claims description 8
- 230000001939 inductive effect Effects 0.000 claims description 8
- 238000012258 culturing Methods 0.000 claims description 7
- 230000001506 immunosuppresive effect Effects 0.000 claims description 7
- 210000000056 organ Anatomy 0.000 claims description 7
- 206010062016 Immunosuppression Diseases 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 2
- 230000001861 immunosuppressant effect Effects 0.000 claims 7
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 56
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 56
- 108090000623 proteins and genes Proteins 0.000 description 51
- 241000699666 Mus <mouse, genus> Species 0.000 description 47
- 230000027455 binding Effects 0.000 description 33
- 238000002474 experimental method Methods 0.000 description 27
- 235000018102 proteins Nutrition 0.000 description 26
- 102000004169 proteins and genes Human genes 0.000 description 26
- 108700024394 Exon Proteins 0.000 description 19
- 238000000684 flow cytometry Methods 0.000 description 17
- 238000002965 ELISA Methods 0.000 description 16
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 16
- 238000003752 polymerase chain reaction Methods 0.000 description 16
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 15
- 241000283707 Capra Species 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000012634 fragment Substances 0.000 description 14
- 210000004408 hybridoma Anatomy 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 241000699800 Cricetinae Species 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 239000002299 complementary DNA Substances 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 10
- 230000002297 mitogenic effect Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 241000283074 Equus asinus Species 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 238000002054 transplantation Methods 0.000 description 9
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 8
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 8
- 229940045513 CTLA4 antagonist Drugs 0.000 description 8
- 108020004635 Complementary DNA Proteins 0.000 description 8
- 241001529936 Murinae Species 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 239000000427 antigen Substances 0.000 description 8
- 238000010367 cloning Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000012163 sequencing technique Methods 0.000 description 8
- 238000003146 transient transfection Methods 0.000 description 8
- 108010076504 Protein Sorting Signals Proteins 0.000 description 7
- 210000000612 antigen-presenting cell Anatomy 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 102000010910 CD28 Antigens Human genes 0.000 description 6
- 108010062433 CD28 Antigens Proteins 0.000 description 6
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000001052 transient effect Effects 0.000 description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 108010087819 Fc receptors Proteins 0.000 description 5
- 102000009109 Fc receptors Human genes 0.000 description 5
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 229960002685 biotin Drugs 0.000 description 5
- 239000011616 biotin Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000013613 expression plasmid Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 201000000050 myeloid neoplasm Diseases 0.000 description 5
- 230000009871 nonspecific binding Effects 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000012679 serum free medium Substances 0.000 description 5
- 230000003393 splenic effect Effects 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 241000282693 Cercopithecidae Species 0.000 description 4
- 241000699679 Cricetulus migratorius Species 0.000 description 4
- 108091008874 T cell receptors Proteins 0.000 description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 238000001042 affinity chromatography Methods 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000010353 genetic engineering Methods 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 210000003292 kidney cell Anatomy 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 238000003153 stable transfection Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 102100032937 CD40 ligand Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000005094 computer simulation Methods 0.000 description 3
- 230000000139 costimulatory effect Effects 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 101150106093 gpt gene Proteins 0.000 description 3
- 230000008105 immune reaction Effects 0.000 description 3
- 230000006058 immune tolerance Effects 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 230000016784 immunoglobulin production Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 230000000263 nonmitogenic effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 239000001103 potassium chloride Substances 0.000 description 3
- 235000011164 potassium chloride Nutrition 0.000 description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 description 3
- 235000011009 potassium phosphates Nutrition 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000001742 protein purification Methods 0.000 description 3
- 239000012460 protein solution Substances 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- 238000011735 C3H mouse Methods 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102000003712 Complement factor B Human genes 0.000 description 2
- 108090000056 Complement factor B Proteins 0.000 description 2
- 108010017826 DNA Polymerase I Proteins 0.000 description 2
- 102000004594 DNA Polymerase I Human genes 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 2
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 241000699673 Mesocricetus auratus Species 0.000 description 2
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 102000008212 P-Selectin Human genes 0.000 description 2
- 108010035766 P-Selectin Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 108090000919 Pyroglutamyl-Peptidase I Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 108010029180 Sialic Acid Binding Ig-like Lectin 3 Proteins 0.000 description 2
- 102000001555 Sialic Acid Binding Ig-like Lectin 3 Human genes 0.000 description 2
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
- 108010027570 Xanthine phosphoribosyltransferase Proteins 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000012997 ficoll-paque Substances 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
- 239000011544 gradient gel Substances 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101000852101 Bombyx mori DNA topoisomerase 2 Proteins 0.000 description 1
- 108700031361 Brachyury Proteins 0.000 description 1
- 102000004497 CCR2 Receptors Human genes 0.000 description 1
- 108010017312 CCR2 Receptors Proteins 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 108090000270 Ficain Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 102100026973 Heat shock protein 75 kDa, mitochondrial Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 101000966481 Mus musculus Dihydrofolate reductase Proteins 0.000 description 1
- 101100370002 Mus musculus Tnfsf14 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 101710204707 Transforming growth factor-beta receptor-associated protein 1 Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 241000133063 Trixis Species 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003172 anti-dna Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- POTUGHMKJGOKRI-UHFFFAOYSA-N ficin Chemical compound FI=CI=N POTUGHMKJGOKRI-UHFFFAOYSA-N 0.000 description 1
- 235000019836 ficin Nutrition 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- -1 glycine Chemical class 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 102000053391 human F Human genes 0.000 description 1
- 108700031895 human F Proteins 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940046781 other immunosuppressants in atc Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 229940072288 prograf Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012772 sequence design Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 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
-
- 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
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Transplantation (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25515500P | 2000-12-14 | 2000-12-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200305384B true ZA200305384B (en) | 2004-10-11 |
Family
ID=22967074
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200305384A ZA200305384B (en) | 2000-12-14 | 2003-07-11 | Silenced anti-CD28 antibodies and use thereof. |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP1341553A4 (es) |
| JP (1) | JP2004515243A (es) |
| KR (1) | KR20040020866A (es) |
| CN (1) | CN1272345C (es) |
| AR (1) | AR031924A1 (es) |
| AU (2) | AU2002226086C1 (es) |
| BR (1) | BR0116686A (es) |
| CA (1) | CA2432736A1 (es) |
| CZ (1) | CZ20031909A3 (es) |
| HU (1) | HUP0400697A3 (es) |
| IL (1) | IL156262A0 (es) |
| MX (1) | MXPA03005327A (es) |
| NO (1) | NO20032542L (es) |
| NZ (1) | NZ526569A (es) |
| PL (1) | PL363239A1 (es) |
| RU (1) | RU2261723C2 (es) |
| WO (1) | WO2002047721A1 (es) |
| ZA (1) | ZA200305384B (es) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080095774A1 (en) * | 2001-02-16 | 2008-04-24 | Wyeth | Agents and Methods for Specifically Blocking CD28-Mediated Signaling |
| US7531168B2 (en) | 2001-02-16 | 2009-05-12 | Genetics Institute Llc | Method for downmodulating immune response in type I diabetes |
| BRPI0611901A2 (pt) | 2005-06-14 | 2012-08-28 | Amgen, Inc | composição, liofilizado, kit, e, processo para preparar uma composição |
| FR2951176A1 (fr) * | 2009-10-09 | 2011-04-15 | Tcl Pharma | Ligands monovalents du recepteur cd28 humain |
| US8785604B2 (en) * | 2010-02-18 | 2014-07-22 | Effimune | Anti-CD28 humanized antibodies |
| CN114917185B (zh) | 2016-10-21 | 2023-11-14 | 美国安进公司 | 药物配制品及其制备方法 |
| WO2019241730A2 (en) | 2018-06-15 | 2019-12-19 | Flagship Pioneering Innovations V, Inc. | Increasing immune activity through modulation of postcellular signaling factors |
| US20220153845A1 (en) * | 2019-03-14 | 2022-05-19 | Biond Biologics Ltd. | A method for immunosuppression |
| MA55805A (fr) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V Inc | Métodes de modulation de l'activité immunitaire |
| EP4076434A1 (en) | 2019-12-17 | 2022-10-26 | Flagship Pioneering Innovations V, Inc. | Combination anti-cancer therapies with inducers of iron-dependent cellular disassembly |
| US20230355804A1 (en) | 2020-06-29 | 2023-11-09 | Flagship Pioneering Innovations V, Inc. | Viruses engineered to promote thanotransmission and their use in treating cancer |
| MX2023001962A (es) | 2020-08-19 | 2023-04-26 | Xencor Inc | Composiciones anti-cd28. |
| WO2022212784A1 (en) | 2021-03-31 | 2022-10-06 | Flagship Pioneering Innovations V, Inc. | Thanotransmission polypeptides and their use in treating cancer |
| CA3224374A1 (en) | 2021-06-29 | 2023-01-05 | Flagship Pioneering Innovations V, Inc. | Immune cells engineered to promote thanotransmission and uses thereof |
| WO2024040195A1 (en) | 2022-08-17 | 2024-02-22 | Capstan Therapeutics, Inc. | Conditioning for in vivo immune cell engineering |
| WO2024077191A1 (en) | 2022-10-05 | 2024-04-11 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additionalpolypeptides and their use in treating cancer |
| WO2024148336A1 (en) * | 2023-01-06 | 2024-07-11 | Igm Biosciences, Inc. | T cell costimulatory multimeric binding molecules and uses thereof |
| WO2024151687A1 (en) | 2023-01-09 | 2024-07-18 | Flagship Pioneering Innovations V, Inc. | Genetic switches and their use in treating cancer |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6641809B1 (en) * | 1990-03-26 | 2003-11-04 | Bristol-Myers Squibb Company | Method of regulating cellular processes mediated by B7 and CD28 |
-
2001
- 2001-12-14 AU AU2002226086A patent/AU2002226086C1/en not_active Ceased
- 2001-12-14 NZ NZ526569A patent/NZ526569A/en unknown
- 2001-12-14 MX MXPA03005327A patent/MXPA03005327A/es unknown
- 2001-12-14 RU RU2003121231/15A patent/RU2261723C2/ru not_active IP Right Cessation
- 2001-12-14 EP EP01995504A patent/EP1341553A4/en not_active Withdrawn
- 2001-12-14 PL PL01363239A patent/PL363239A1/xx not_active Application Discontinuation
- 2001-12-14 AR ARP010105828A patent/AR031924A1/es unknown
- 2001-12-14 KR KR10-2003-7007798A patent/KR20040020866A/ko not_active Application Discontinuation
- 2001-12-14 AU AU2608602A patent/AU2608602A/xx active Pending
- 2001-12-14 CA CA002432736A patent/CA2432736A1/en not_active Abandoned
- 2001-12-14 CN CNB018226361A patent/CN1272345C/zh not_active Expired - Fee Related
- 2001-12-14 HU HU0400697A patent/HUP0400697A3/hu unknown
- 2001-12-14 CZ CZ20031909A patent/CZ20031909A3/cs unknown
- 2001-12-14 JP JP2002549291A patent/JP2004515243A/ja not_active Withdrawn
- 2001-12-14 IL IL15626201A patent/IL156262A0/xx unknown
- 2001-12-14 WO PCT/US2001/047955 patent/WO2002047721A1/en not_active Application Discontinuation
- 2001-12-14 BR BR0116686-7A patent/BR0116686A/pt not_active IP Right Cessation
-
2003
- 2003-06-05 NO NO20032542A patent/NO20032542L/no not_active Application Discontinuation
- 2003-07-11 ZA ZA200305384A patent/ZA200305384B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0400697A3 (en) | 2007-05-02 |
| NO20032542L (no) | 2003-08-07 |
| CZ20031909A3 (cs) | 2003-11-12 |
| KR20040020866A (ko) | 2004-03-09 |
| RU2261723C2 (ru) | 2005-10-10 |
| EP1341553A1 (en) | 2003-09-10 |
| BR0116686A (pt) | 2003-12-30 |
| WO2002047721A1 (en) | 2002-06-20 |
| AU2608602A (en) | 2002-06-24 |
| MXPA03005327A (es) | 2004-12-03 |
| CA2432736A1 (en) | 2002-06-20 |
| AU2002226086C1 (en) | 2006-03-09 |
| PL363239A1 (en) | 2004-11-15 |
| CN1489473A (zh) | 2004-04-14 |
| HUP0400697A2 (hu) | 2004-06-28 |
| NO20032542D0 (no) | 2003-06-05 |
| EP1341553A4 (en) | 2004-07-28 |
| NZ526569A (en) | 2005-07-29 |
| AU2002226086B2 (en) | 2005-08-25 |
| JP2004515243A (ja) | 2004-05-27 |
| RU2003121231A (ru) | 2005-02-10 |
| IL156262A0 (en) | 2004-01-04 |
| CN1272345C (zh) | 2006-08-30 |
| AR031924A1 (es) | 2003-10-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2244720C2 (ru) | Антитело igg с аффинностью связывания в отношении антигенного комплекса cd3, рекомбинантные нуклеиновые кислоты, кодирующие легкую и тяжелую цепи антитела, способ получения системы, способ получения антитела, способ лечения пациента | |
| AU2002226086B2 (en) | Silensed anti-CD28 antibodies and use thereof | |
| EP0966485B1 (en) | MUTATED NONACTIVATING IgG2 DOMAINS AND ANTI-CD3 ANTIBODIES INCORPORATING THE SAME | |
| KR100191152B1 (ko) | Cd4 특이적 재조합 항체 | |
| AU751064B2 (en) | Antibodies against human CD40 | |
| US6887673B2 (en) | Humanized antibodies against human 4-1BB | |
| CA2212750C (en) | Humanized antibodies against cd3 | |
| JP4804357B2 (ja) | 改変抗ｃｄ５２抗体 | |
| RU2630656C2 (ru) | АНТИТЕЛА ПРОТИВ αβTCR | |
| AU2002226086A1 (en) | Silensed anti-CD28 antibodies and use thereof | |
| US5951983A (en) | Methods of inhibiting T cell mediated immune responses with humanized LO-CD2A-specific antibodies | |
| KR20050111748A (ko) | 면역억제 특성을 가진 인간화 항-ｃｄ4 항체 | |
| EP2583980A1 (en) | Antibodies directed against the alpha chain of IL7 receptor - their use for the preparation of drug candidates | |
| JP4448906B2 (ja) | Ｃｄ４特異的抗体ｔｒｘ１およびその使用 | |
| TW201726716A (zh) | 抗體－細胞激素植入組合物及用於免疫調節的方法 | |
| AU754185B2 (en) | LO-CD2a antibody and uses thereof for inhibiting T cell activation and proliferation | |
| KR20070036138A (ko) | 영장류에서 관용 유발을 위한 항-ｃｄ４ 항체를 사용하는최적화 용량 결정 | |
| MXPA01008098A (es) | Inmunoglobulina humanizada reactiva con moleculas b7 y metodo de tratamiento con el mismo. | |
| CN102369219A (zh) | 针对人tweak的抗体及其应用 | |
| US20040116675A1 (en) | Silenced anti-cd28 antibodies and use thereof | |
| GB2376467A (en) | TRX1 Antibodies | |
| JP7278623B2 (ja) | 抗ｃｄ２７抗体およびその使用 |