CN1382158A - 多细胞因子-抗体复合物 - Google Patents
多细胞因子-抗体复合物 Download PDFInfo
- Publication number
- CN1382158A CN1382158A CN00813726A CN00813726A CN1382158A CN 1382158 A CN1382158 A CN 1382158A CN 00813726 A CN00813726 A CN 00813726A CN 00813726 A CN00813726 A CN 00813726A CN 1382158 A CN1382158 A CN 1382158A
- Authority
- CN
- China
- Prior art keywords
- fusion rotein
- cytokine
- mouse
- cell
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 108090000695 Cytokines Proteins 0.000 claims abstract description 313
- 102000004127 Cytokines Human genes 0.000 claims abstract description 312
- 238000000034 method Methods 0.000 claims abstract description 68
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 42
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 39
- 108060003951 Immunoglobulin Proteins 0.000 claims abstract description 29
- 102000018358 immunoglobulin Human genes 0.000 claims abstract description 29
- 230000008685 targeting Effects 0.000 claims abstract description 5
- 230000004927 fusion Effects 0.000 claims description 332
- 210000004027 cell Anatomy 0.000 claims description 162
- 206010028980 Neoplasm Diseases 0.000 claims description 158
- 108010002350 Interleukin-2 Proteins 0.000 claims description 82
- 108090000623 proteins and genes Proteins 0.000 claims description 77
- 230000000694 effects Effects 0.000 claims description 71
- 239000000203 mixture Substances 0.000 claims description 71
- 102000004169 proteins and genes Human genes 0.000 claims description 65
- 238000011282 treatment Methods 0.000 claims description 58
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 52
- 102000019034 Chemokines Human genes 0.000 claims description 49
- 108010012236 Chemokines Proteins 0.000 claims description 49
- 108090000978 Interleukin-4 Proteins 0.000 claims description 38
- 102000036639 antigens Human genes 0.000 claims description 35
- 108091007433 antigens Proteins 0.000 claims description 35
- 201000011510 cancer Diseases 0.000 claims description 35
- 108020004707 nucleic acids Proteins 0.000 claims description 35
- 102000039446 nucleic acids Human genes 0.000 claims description 35
- 150000007523 nucleic acids Chemical class 0.000 claims description 35
- 239000000427 antigen Substances 0.000 claims description 34
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 31
- 229920001184 polypeptide Polymers 0.000 claims description 30
- 230000014509 gene expression Effects 0.000 claims description 29
- 239000000833 heterodimer Substances 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 241000124008 Mammalia Species 0.000 claims description 18
- 239000000539 dimer Substances 0.000 claims description 10
- 108010065805 Interleukin-12 Proteins 0.000 claims description 9
- 102000013462 Interleukin-12 Human genes 0.000 claims description 9
- 230000009466 transformation Effects 0.000 claims description 9
- 210000004899 c-terminal region Anatomy 0.000 claims description 7
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 5
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 claims description 4
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 4
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 4
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 4
- 238000001727 in vivo Methods 0.000 claims description 4
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 3
- 210000005260 human cell Anatomy 0.000 claims 1
- 102000007474 Multiprotein Complexes Human genes 0.000 abstract description 4
- 108010085220 Multiprotein Complexes Proteins 0.000 abstract description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 142
- 102000000588 Interleukin-2 Human genes 0.000 description 77
- 108020004414 DNA Proteins 0.000 description 59
- 235000018102 proteins Nutrition 0.000 description 58
- 108090000663 Annexin A1 Proteins 0.000 description 43
- 102100030698 Interleukin-12 subunit alpha Human genes 0.000 description 43
- 241000282414 Homo sapiens Species 0.000 description 42
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 description 41
- 102000004388 Interleukin-4 Human genes 0.000 description 36
- 241001529936 Murinae Species 0.000 description 30
- 238000007920 subcutaneous administration Methods 0.000 description 28
- 238000002347 injection Methods 0.000 description 27
- 239000007924 injection Substances 0.000 description 27
- 210000002966 serum Anatomy 0.000 description 25
- 229940104230 thymidine Drugs 0.000 description 25
- 102100037850 Interferon gamma Human genes 0.000 description 23
- 108010074328 Interferon-gamma Proteins 0.000 description 23
- 238000002474 experimental method Methods 0.000 description 23
- 238000012360 testing method Methods 0.000 description 22
- 210000004881 tumor cell Anatomy 0.000 description 21
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 20
- 238000011740 C57BL/6 mouse Methods 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 18
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 17
- SOEGEPHNZOISMT-BYPYZUCNSA-N Gly-Ser-Gly Chemical compound NCC(=O)N[C@@H](CO)C(=O)NCC(O)=O SOEGEPHNZOISMT-BYPYZUCNSA-N 0.000 description 17
- 239000012634 fragment Substances 0.000 description 17
- 210000002751 lymph Anatomy 0.000 description 17
- 108091026890 Coding region Proteins 0.000 description 16
- 238000010276 construction Methods 0.000 description 16
- 230000004071 biological effect Effects 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 14
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 14
- 238000010254 subcutaneous injection Methods 0.000 description 14
- 239000007929 subcutaneous injection Substances 0.000 description 14
- 230000000295 complement effect Effects 0.000 description 13
- 239000002299 complementary DNA Substances 0.000 description 13
- 108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 101001043827 Mus musculus Interleukin-2 Proteins 0.000 description 12
- 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 12
- 239000002671 adjuvant Substances 0.000 description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 11
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- 210000002865 immune cell Anatomy 0.000 description 11
- 210000004072 lung Anatomy 0.000 description 11
- 108020001775 protein parts Proteins 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- 229960005486 vaccine Drugs 0.000 description 11
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 10
- 101001090482 Mus musculus Glutathione S-transferase LANCL1 Proteins 0.000 description 10
- 108091081024 Start codon Proteins 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 201000005202 lung cancer Diseases 0.000 description 10
- 208000020816 lung neoplasm Diseases 0.000 description 10
- 230000002441 reversible effect Effects 0.000 description 10
- 230000014621 translational initiation Effects 0.000 description 10
- 230000036039 immunity Effects 0.000 description 9
- 108020004705 Codon Proteins 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 8
- 101000920667 Homo sapiens Epithelial cell adhesion molecule Proteins 0.000 description 8
- 108090001007 Interleukin-8 Proteins 0.000 description 8
- 101000959737 Mus musculus Annexin A1 Proteins 0.000 description 8
- 101000583937 Mus musculus CDK-activating kinase assembly factor MAT1 Proteins 0.000 description 8
- 101001038345 Mus musculus GTP cyclohydrolase 1 feedback regulatory protein Proteins 0.000 description 8
- 101000808124 Mus musculus Uroplakin-3b Proteins 0.000 description 8
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 8
- 238000012408 PCR amplification Methods 0.000 description 8
- 238000011579 SCID mouse model Methods 0.000 description 8
- 230000000890 antigenic effect Effects 0.000 description 8
- 239000010432 diamond Substances 0.000 description 8
- 238000006471 dimerization reaction Methods 0.000 description 8
- 239000000178 monomer Substances 0.000 description 8
- 230000002062 proliferating effect Effects 0.000 description 8
- 238000001890 transfection Methods 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 238000011144 upstream manufacturing Methods 0.000 description 8
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 7
- 101001002703 Mus musculus Interleukin-4 Proteins 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 239000002975 chemoattractant Substances 0.000 description 7
- 238000001415 gene therapy Methods 0.000 description 7
- 231100000652 hormesis Toxicity 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- 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 6
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 6
- 206010009944 Colon cancer Diseases 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000004471 Glycine Substances 0.000 description 6
- 102000003812 Interleukin-15 Human genes 0.000 description 6
- 108090000172 Interleukin-15 Proteins 0.000 description 6
- 101000746372 Mus musculus Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 6
- 230000004663 cell proliferation Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 210000004443 dendritic cell Anatomy 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 230000001939 inductive effect Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 230000004936 stimulating effect Effects 0.000 description 6
- 230000004614 tumor growth Effects 0.000 description 6
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 5
- 108020005098 Anticodon Proteins 0.000 description 5
- 108020004566 Transfer RNA Proteins 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000001900 immune effect Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 125000003607 serino group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 108091033380 Coding strand Proteins 0.000 description 4
- 102100023688 Eotaxin Human genes 0.000 description 4
- 101710139422 Eotaxin Proteins 0.000 description 4
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 4
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 4
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 4
- 108010047761 Interferon-alpha Proteins 0.000 description 4
- 102000006992 Interferon-alpha Human genes 0.000 description 4
- 102000003816 Interleukin-13 Human genes 0.000 description 4
- 108090000176 Interleukin-13 Proteins 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 239000013613 expression plasmid Substances 0.000 description 4
- 230000002349 favourable effect Effects 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 230000006054 immunological memory Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000009385 viral infection Effects 0.000 description 4
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 3
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 102000009109 Fc receptors Human genes 0.000 description 3
- 108010087819 Fc receptors Proteins 0.000 description 3
- WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 108010047620 Phytohemagglutinins Proteins 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 102000002067 Protein Subunits Human genes 0.000 description 3
- 108010001267 Protein Subunits Proteins 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 201000010989 colorectal carcinoma Diseases 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000008034 disappearance Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000710 homodimer Substances 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 229940100601 interleukin-6 Drugs 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 229960004452 methionine Drugs 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 244000045947 parasite Species 0.000 description 3
- 230000001885 phytohemagglutinin Effects 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000004062 sedimentation Methods 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000003151 transfection method Methods 0.000 description 3
- 230000010474 transient expression Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- HBOMLICNUCNMMY-KJFJCRTCSA-N 1-[(4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1C1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-KJFJCRTCSA-N 0.000 description 2
- BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 2
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 2
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 2
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 2
- 241000222122 Candida albicans Species 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 108010055166 Chemokine CCL5 Proteins 0.000 description 2
- 108010055124 Chemokine CCL7 Proteins 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 108010062580 Concanavalin A Proteins 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 241000222732 Leishmania major Species 0.000 description 2
- 241000186779 Listeria monocytogenes Species 0.000 description 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 101100393516 Mus musculus Gca gene Proteins 0.000 description 2
- DXTOOBDIIAJZBJ-BQBZGAKWSA-N Pro-Gly-Ser Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(O)=O DXTOOBDIIAJZBJ-BQBZGAKWSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 241000242680 Schistosoma mansoni Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 108020005038 Terminator Codon Proteins 0.000 description 2
- 241000223997 Toxoplasma gondii Species 0.000 description 2
- 229940037003 alum Drugs 0.000 description 2
- RASZIXQTZOARSV-BDPUVYQTSA-N astacin Chemical compound CC=1C(=O)C(=O)CC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)C(=O)CC1(C)C RASZIXQTZOARSV-BDPUVYQTSA-N 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000005482 chemotactic factor Substances 0.000 description 2
- 238000005352 clarification Methods 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000013016 damping Methods 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 108010033706 glycylserine Proteins 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 210000005007 innate immune system Anatomy 0.000 description 2
- -1 interferon- Proteins 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 210000004279 orbit Anatomy 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000012846 protein folding Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical group CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 102000034498 Astacin Human genes 0.000 description 1
- 108090000658 Astacin Proteins 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102100023703 C-C motif chemokine 15 Human genes 0.000 description 1
- 102100034871 C-C motif chemokine 8 Human genes 0.000 description 1
- 101710155833 C-C motif chemokine 8 Proteins 0.000 description 1
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078239 Chemokine CX3CL1 Proteins 0.000 description 1
- 102000016951 Chemokine CXCL2 Human genes 0.000 description 1
- 108010014414 Chemokine CXCL2 Proteins 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 235000016795 Cola Nutrition 0.000 description 1
- 244000228088 Cola acuminata Species 0.000 description 1
- 235000011824 Cola pachycarpa Nutrition 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- 238000007399 DNA isolation Methods 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- FMKGDHLSXFDSOU-BDPUVYQTSA-N Dienon-Astacin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)C(=O)C(=CC1(C)C)O)C=CC=C(/C)C=CC2=C(C)C(=O)C(=CC2(C)C)O FMKGDHLSXFDSOU-BDPUVYQTSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- IRJWAYCXIYUHQE-WHFBIAKZSA-N Gly-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)CN IRJWAYCXIYUHQE-WHFBIAKZSA-N 0.000 description 1
- 208000012766 Growth delay Diseases 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 101000978376 Homo sapiens C-C motif chemokine 15 Proteins 0.000 description 1
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 1
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 1
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 1
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 1
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 1
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 1
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 1
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 1
- 101000773122 Homo sapiens Thioredoxin domain-containing protein 5 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102100029571 Immunoglobulin J chain Human genes 0.000 description 1
- 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 102000014154 Interleukin-12 Subunit p35 Human genes 0.000 description 1
- 108010011301 Interleukin-12 Subunit p35 Proteins 0.000 description 1
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 1
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 1
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 102100023487 Lens fiber major intrinsic protein Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- XGDCYUQSFDQISZ-BQBZGAKWSA-N Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(O)=O XGDCYUQSFDQISZ-BQBZGAKWSA-N 0.000 description 1
- JIHDFWWRYHSAQB-GUBZILKMSA-N Leu-Ser-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O JIHDFWWRYHSAQB-GUBZILKMSA-N 0.000 description 1
- 102100035304 Lymphotactin Human genes 0.000 description 1
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 1
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108010047660 Mitochondrial intermediate peptidase Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 102000004211 Platelet factor 4 Human genes 0.000 description 1
- 108090000778 Platelet factor 4 Proteins 0.000 description 1
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 1
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 1
- 102100029812 Protein S100-A12 Human genes 0.000 description 1
- 101710110949 Protein S100-A12 Proteins 0.000 description 1
- UIGMAMGZOJVTDN-WHFBIAKZSA-N Ser-Gly-Ser Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O UIGMAMGZOJVTDN-WHFBIAKZSA-N 0.000 description 1
- 108010088160 Staphylococcal Protein A Proteins 0.000 description 1
- 108010039445 Stem Cell Factor Proteins 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108700007696 Tetrahydrofolate Dehydrogenase Proteins 0.000 description 1
- 102100030269 Thioredoxin domain-containing protein 5 Human genes 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 235000003676 astacin Nutrition 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000011262 co‐therapy Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000000222 eosinocyte Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000001357 hemopoietic progenitor cell Anatomy 0.000 description 1
- 102000046157 human CSF2 Human genes 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 108700027921 interferon tau Proteins 0.000 description 1
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 108010019677 lymphotactin Proteins 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 101800000857 p40 protein Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000011049 pearl Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019633 pungent taste Nutrition 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2013—IL-2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/208—IL-12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6813—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin the drug being a peptidic cytokine, e.g. an interleukin or interferon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5434—IL-12
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/55—IL-2
-
- 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]
- C07K16/245—IL-1
-
- 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]
- C07K16/247—IL-4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3076—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties
- C07K16/3084—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties against tumour-associated gangliosides
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- 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
- C07K2317/74—Inducing cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/027—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a retrovirus
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims (53)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14792499P | 1999-08-09 | 1999-08-09 | |
US60/147,924 | 1999-08-09 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1382158A true CN1382158A (zh) | 2002-11-27 |
CN1235911C CN1235911C (zh) | 2006-01-11 |
Family
ID=22523478
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB008137269A Expired - Fee Related CN1235911C (zh) | 1999-08-09 | 2000-08-09 | 多细胞因子-抗体复合物 |
Country Status (20)
Country | Link |
---|---|
US (3) | US6617135B1 (zh) |
EP (1) | EP1200479B1 (zh) |
JP (2) | JP4793971B2 (zh) |
KR (1) | KR100827757B1 (zh) |
CN (1) | CN1235911C (zh) |
AT (1) | ATE316982T1 (zh) |
AU (1) | AU778611B2 (zh) |
BR (1) | BR0013231A (zh) |
CA (1) | CA2380331C (zh) |
DE (1) | DE60025832T2 (zh) |
DK (1) | DK1200479T3 (zh) |
ES (1) | ES2256027T3 (zh) |
HU (1) | HUP0202442A3 (zh) |
MX (1) | MXPA02001417A (zh) |
NO (1) | NO20020641L (zh) |
PL (1) | PL202058B1 (zh) |
RU (1) | RU2263118C2 (zh) |
SK (1) | SK1842002A3 (zh) |
WO (1) | WO2001010912A1 (zh) |
ZA (1) | ZA200200789B (zh) |
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102221607A (zh) * | 2011-03-29 | 2011-10-19 | 浙江大学医学院附属第一医院 | 一种抗体组合物及其应用 |
WO2014085947A1 (zh) * | 2012-12-05 | 2014-06-12 | Chiou Shiow-Her | 趋化素-细胞素融合蛋白和其应用 |
CN104136457A (zh) * | 2011-11-08 | 2014-11-05 | Umc乌德勒支控股有限公司 | 包括白细胞介素10和白细胞介素4的融合蛋白 |
TWI487713B (zh) * | 2011-12-06 | 2015-06-11 | Nat Univ Chung Hsing | 趨化素-細胞素融合蛋白和其應用 |
CN105658669A (zh) * | 2013-07-19 | 2016-06-08 | 弗拉芒区生物技术研究所 | 细胞因子拮抗剂的靶向 |
CN105705641A (zh) * | 2013-07-18 | 2016-06-22 | 弗拉芒区生物技术研究所 | 涉及具有强烈降低的受体结合亲和力的细胞因子的融合因子 |
CN109824786A (zh) * | 2019-03-01 | 2019-05-31 | 王仁喜 | hIL-12p35-Fc融合蛋白、编码基因、重组载体、宿主细胞及应用 |
CN110546168A (zh) * | 2016-09-27 | 2019-12-06 | 埃皮辛特瑞柯斯公司 | 免疫调节性融合蛋白 |
CN111107868A (zh) * | 2017-05-24 | 2020-05-05 | 诺华股份有限公司 | 抗体细胞因子移植蛋白及使用方法 |
CN111303296A (zh) * | 2019-12-16 | 2020-06-19 | 启辰生生物科技(珠海)有限公司 | 双功能融合多肽、细胞和药物组合物及应用 |
CN111848811A (zh) * | 2019-04-27 | 2020-10-30 | 张晋宇 | 一种蛋白质异二聚体及其用途 |
WO2020221135A1 (zh) * | 2019-04-28 | 2020-11-05 | 张晋宇 | 一种蛋白质分子及其用途 |
WO2020259536A1 (zh) * | 2019-06-24 | 2020-12-30 | 南京金斯瑞生物科技有限公司 | 单克隆抗体-细胞因子融合蛋白二聚体及其应用 |
CN112513276A (zh) * | 2018-07-30 | 2021-03-16 | 张晋宇 | 蛋白质异二聚体及其用途 |
CN112566650A (zh) * | 2018-06-21 | 2021-03-26 | 沙塔克实验室有限公司 | 异二聚体蛋白及其用途 |
US11312757B2 (en) | 2019-04-19 | 2022-04-26 | Synerkine Pharma B.V. | Fusion protein comprising IL13 |
CN114466657A (zh) * | 2019-07-25 | 2022-05-10 | 芝加哥大学 | 包括蛋白酶激活治疗剂的组合物和方法 |
CN114945586A (zh) * | 2020-01-21 | 2022-08-26 | 张晋宇 | 一种药物组合物及其用途 |
WO2023011575A1 (zh) * | 2021-08-04 | 2023-02-09 | 清华大学 | 一种靶向并杀伤病原体和/或肿瘤细胞的多功能融合蛋白药物 |
US11834492B2 (en) | 2017-09-27 | 2023-12-05 | Epicentrx, Inc. | Human IL-10 receptor alpha fusion proteins |
Families Citing this family (123)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1489100B1 (en) | 1997-12-08 | 2016-06-15 | Merck Patent GmbH | Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation |
US20030105294A1 (en) * | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
AU758860B2 (en) * | 1998-04-15 | 2003-04-03 | Merck Patent Gmbh | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with angiogenesis inhibitor |
US7666400B2 (en) * | 2005-04-06 | 2010-02-23 | Ibc Pharmaceuticals, Inc. | PEGylation by the dock and lock (DNL) technique |
US7550143B2 (en) | 2005-04-06 | 2009-06-23 | Ibc Pharmaceuticals, Inc. | Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses |
CA2372400C (en) * | 1999-05-19 | 2010-04-27 | Lexigen Pharmaceuticals Corp. | Expression and export of interferon-alpha proteins as fc fusion proteins |
SK782002A3 (en) * | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
US7067110B1 (en) | 1999-07-21 | 2006-06-27 | Emd Lexigen Research Center Corp. | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
CN1235911C (zh) * | 1999-08-09 | 2006-01-11 | 利思进药品公司 | 多细胞因子-抗体复合物 |
US20050202538A1 (en) * | 1999-11-12 | 2005-09-15 | Merck Patent Gmbh | Fc-erythropoietin fusion protein with improved pharmacokinetics |
DE19963859A1 (de) * | 1999-12-30 | 2001-07-12 | Apotech Res & Dev Ltd | Bi- oder Oligomer eines Di-, Tri-, Quattro- oder Pentamers von rekombinanten Fusionsproteinen |
ATE336514T1 (de) * | 2000-02-11 | 2006-09-15 | Merck Patent Gmbh | Steigerung der zirkulierenden halbwertzeit von auf antikörpern basierenden fusionsproteinen |
EP1294401B1 (en) * | 2000-06-29 | 2007-08-01 | EMD Lexigen Research Center Corp. | Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents |
US20030049689A1 (en) * | 2000-12-14 | 2003-03-13 | Cynthia Edwards | Multifunctional polypeptides |
KR20090010127A (ko) * | 2001-03-07 | 2009-01-28 | 메르크 파텐트 게엠베하 | 하이브리드 이소타입 항체 부분구조를 포함하는 단백질을 위한 발현 기술 |
US6992174B2 (en) * | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
PL205352B1 (pl) * | 2001-05-03 | 2010-04-30 | Merck Patent Gmbh | Rekombinowane przeciwciało specyficzne dla nowotworu |
RU2312677C9 (ru) * | 2001-12-04 | 2008-03-27 | Мерк Патент Гмбх | Иммуноцитокины с модулированной селективностью |
US7736657B2 (en) | 2002-02-10 | 2010-06-15 | Apoxis S.A. | Fusion constructs containing active sections on TNF ligands |
US7736652B2 (en) * | 2002-03-21 | 2010-06-15 | The Regents Of The University Of California | Antibody fusion proteins: effective adjuvants of protein vaccination |
US20070003514A1 (en) * | 2002-04-05 | 2007-01-04 | The Regents Of The University Of California | Mono-and bi-functional antibody conjugates as effective adjuvants of protein vaccination |
AU2003243415A1 (en) * | 2002-06-07 | 2003-12-22 | Zymogenetics, Inc. | Use of il-21 in cancer and other therapeutic applications |
US7906118B2 (en) * | 2005-04-06 | 2011-03-15 | Ibc Pharmaceuticals, Inc. | Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technology |
PL211180B1 (pl) * | 2002-12-17 | 2012-04-30 | Merck Patent Gmbh | Białko fuzyjne typu przeciwciało-IL2, wektor zawierający sekwencję kwasów nukleinowych kodujących takie białko, kompozycja farmaceutyczna zawierająca takie białko fuzyjne oraz jego zastosowania do wytwarzania leków |
WO2004069272A2 (en) * | 2003-02-05 | 2004-08-19 | Movecare Ltd | Adjuvant combination for use in the immunization of a mamal comprising il2 and il12 |
TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
WO2005007121A2 (en) | 2003-07-18 | 2005-01-27 | Massachusetts Institute Of Technology | Mutant interleukin-2(il-2) polypeptides |
US7534585B2 (en) * | 2003-07-21 | 2009-05-19 | Transgene S.A. | Multifunctional cytokines |
DE602004031341D1 (de) | 2003-07-21 | 2011-03-24 | Transgene Sa | Multifunktionelle cytokine |
US20050069521A1 (en) * | 2003-08-28 | 2005-03-31 | Emd Lexigen Research Center Corp. | Enhancing the circulating half-life of interleukin-2 proteins |
AR046594A1 (es) * | 2003-10-16 | 2005-12-14 | Applied Research Systems | Usos terapeuticos de variantes de quemoquina |
AU2004309050B2 (en) | 2003-12-30 | 2010-10-14 | Merck Patent Gmbh | IL-7 fusion proteins |
BRPI0417916A (pt) * | 2003-12-31 | 2007-04-10 | Merck Patent Gmbh | proteìna de fusão de fc-eritropoietina com farmacocinética melhorada |
PT1706428E (pt) * | 2004-01-22 | 2009-12-29 | Merck Patent Gmbh | Anticorpos anticancerígenos com fixação de complemento reduzida |
US20110020273A1 (en) * | 2005-04-06 | 2011-01-27 | Ibc Pharmaceuticals, Inc. | Bispecific Immunocytokine Dock-and-Lock (DNL) Complexes and Therapeutic Use Thereof |
US20110064754A1 (en) * | 2005-03-03 | 2011-03-17 | Center For Molecular Medicine And Immunology | Immunoconjugates Comprising Poxvirus-Derived Peptides and Antibodies Against Antigen-Presenting Cells for Subunit-Based Poxvirus Vaccines |
US9481878B2 (en) | 2004-02-13 | 2016-11-01 | Immunomedics, Inc. | Compositions and methods of use of immunotoxins comprising ranpirnase (Rap) show potent cytotoxic activity |
US8551480B2 (en) | 2004-02-13 | 2013-10-08 | Immunomedics, Inc. | Compositions and methods of use of immunotoxins comprising ranpirnase (Rap) show potent cytotoxic activity |
US8034352B2 (en) | 2005-04-06 | 2011-10-11 | Ibc Pharmaceuticals, Inc. | Tetrameric cytokines with improved biological activity |
US8435539B2 (en) * | 2004-02-13 | 2013-05-07 | Immunomedics, Inc. | Delivery system for cytotoxic drugs by bispecific antibody pretargeting |
US8491914B2 (en) | 2004-02-13 | 2013-07-23 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (DNL) complexes for delivery of interference RNA |
US8562988B2 (en) * | 2005-10-19 | 2013-10-22 | Ibc Pharmaceuticals, Inc. | Strategies for improved cancer vaccines |
US8652484B2 (en) | 2004-02-13 | 2014-02-18 | Immunomedics, Inc. | Delivery system for cytotoxic drugs by bispecific antibody pretargeting |
US8003111B2 (en) * | 2005-04-06 | 2011-08-23 | Ibc Pharmaceuticals, Inc. | Dimeric alpha interferon pegylated site-specifically shows enhanced and prolonged efficacy in vivo |
US7670595B2 (en) * | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
WO2005021578A2 (en) * | 2004-08-25 | 2005-03-10 | Amprotein Corporation | A novel chimeric polypeptide and use thereof |
DE602005020837D1 (de) * | 2004-12-09 | 2010-06-02 | Merck Patent Gmbh | Il-7-varianten mit reduzierter immunogenität |
US20090136505A1 (en) | 2005-02-23 | 2009-05-28 | Johanna Bentz | Intranasal Administration of Active Agents to the Central Nervous System |
AU2006217027A1 (en) * | 2005-02-23 | 2006-08-31 | Alza Corporation | Intranasal administration of active agents to the central nervous system |
US8481041B2 (en) | 2005-04-06 | 2013-07-09 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (DNL) constructs for human immunodeficiency virus (HIV) therapy |
US8475794B2 (en) | 2005-04-06 | 2013-07-02 | Ibc Pharmaceuticals, Inc. | Combination therapy with anti-CD74 antibodies provides enhanced toxicity to malignancies, Autoimmune disease and other diseases |
US9931413B2 (en) | 2005-04-06 | 2018-04-03 | Ibc Pharmaceuticals, Inc. | Tetrameric cytokines with improved biological activity |
US9623115B2 (en) | 2005-04-06 | 2017-04-18 | Ibc Pharmaceuticals, Inc. | Dock-and-Lock (DNL) Complexes for Disease Therapy |
US8349332B2 (en) | 2005-04-06 | 2013-01-08 | Ibc Pharmaceuticals, Inc. | Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseases |
US8158129B2 (en) | 2005-04-06 | 2012-04-17 | Ibc Pharmaceuticals, Inc. | Dimeric alpha interferon PEGylated site-specifically shows enhanced and prolonged efficacy in vivo |
US20070104689A1 (en) * | 2005-09-27 | 2007-05-10 | Merck Patent Gmbh | Compositions and methods for treating tumors presenting survivin antigens |
AU2006332155B2 (en) | 2005-12-30 | 2013-01-10 | Cancer Research Technology Limited | Anti-CD19 antibodies with reduced immunogenicity |
ATE555125T1 (de) | 2005-12-30 | 2012-05-15 | Merck Patent Gmbh | Interleukin-12p40-varianten mit verbesserter stabilität |
AU2009233925B2 (en) * | 2006-12-05 | 2014-03-13 | Ibc Pharmaceuticals, Inc. | Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technology |
EP2839743A1 (en) | 2007-01-16 | 2015-02-25 | Abbvie Inc. | Methods for treating psoriasis |
KR101629702B1 (ko) * | 2007-02-12 | 2016-06-13 | 체에스엘 베링 게엠베하 | 카잘-형 세린 프로테아제 억제제의 치료학적 적용 |
US8906356B2 (en) * | 2007-11-05 | 2014-12-09 | Massachusetts Institute Of Technology | Mutant interleukin-2 (IL-2) polypeptides |
JP2011515404A (ja) * | 2008-03-18 | 2011-05-19 | アボット・ラボラトリーズ | 乾癬を治療するための方法 |
ES2797126T3 (es) * | 2008-05-30 | 2020-12-01 | Xbiotech Inc | Usos de anticuerpos IL-1 alfa |
CA2734265C (en) * | 2008-08-20 | 2017-12-19 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (dnl) vaccines for cancer therapy |
EP2752427A1 (en) * | 2009-02-24 | 2014-07-09 | Alexion Pharmaceuticals, Inc. | Antibodies containing therapeutic TPO/EPO mimetic peptides |
EA201171259A1 (ru) * | 2009-04-22 | 2012-05-30 | Мерк Патент Гмбх | Антительные гибридные белки с модифицированными сайтами связывания fcrn |
CN107252484A (zh) * | 2010-08-23 | 2017-10-17 | 埃克斯生物科技公司 | 对肿瘤疾病的治疗 |
EP2655409A4 (en) | 2010-12-22 | 2015-07-01 | Univ Leland Stanford Junior | SUPERAGONISTS AND ANTAGONISTS OF INTERLEUKIN-2 |
JP2014517690A (ja) * | 2011-05-09 | 2014-07-24 | ミネルバ バイオテクノロジーズ コーポレーション | 遺伝子操作した成長因子変異体 |
EP2723380B1 (en) * | 2011-06-24 | 2019-08-21 | Stephen D. Gillies | Light chain immunoglobulin fusion proteins and methods of use thereof |
CN104470535A (zh) * | 2012-03-29 | 2015-03-25 | 阿尔托生物科学有限公司 | 用于治疗肿瘤的方法 |
JP6357467B2 (ja) | 2012-04-30 | 2018-07-11 | バイオコン・リミテッド | 標的化された/免疫調節性融合タンパク質およびそれを作製するための方法 |
US9657076B2 (en) | 2012-10-23 | 2017-05-23 | Emory University | GM-CSF and IL-4 conjugates, compositions, and methods related thereto |
AU2014257906A1 (en) * | 2013-04-26 | 2015-12-10 | Philogen S.P.A. | IL4 conjugated to antibodies against extracellular matrix components |
CN105722860A (zh) | 2013-09-24 | 2016-06-29 | 梅迪塞纳医疗股份有限公司 | 白介素-2融合蛋白及其应用 |
CA2927543C (en) | 2013-10-15 | 2021-07-20 | The California Institute For Biomedical Research | Peptidic chimeric antigen receptor t cell switches and uses thereof |
CA2931299C (en) * | 2013-11-20 | 2024-03-05 | Regeneron Pharmaceuticals, Inc. | Aplnr modulators and uses thereof |
GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
EP3134102B1 (en) | 2014-04-24 | 2019-07-03 | The Board of Trustees of The Leland Stanford Junior University | Superagonists, partial agonists and antagonists of interleukin-2 |
HUE047806T2 (hu) * | 2014-08-29 | 2020-05-28 | Hoffmann La Roche | Kombinációs kezelés tumort célzó IL-2-variáns immuncitokinekkel és humán PD-L1 elleni antitestekkel |
CN105543279A (zh) * | 2014-10-30 | 2016-05-04 | 常州卡斯比生物科技有限公司 | 一种防治辐射线损伤、肿瘤治疗的IL-12/Fc融合蛋白的制备方法及其药剂 |
CN104403004B (zh) | 2014-11-24 | 2017-10-13 | 苏州丁孚靶点生物技术有限公司 | 抗体‑干扰素异二聚体的制备和用途 |
WO2016154621A1 (en) | 2015-03-26 | 2016-09-29 | The California Institute For Biomedical Research | SWITCHABLE NON-scFv CHIMERIC RECEPTORS, SWITCHES, AND USES THEREOF |
WO2016168773A2 (en) | 2015-04-15 | 2016-10-20 | The California Institute For Biomedical Research | Optimized pne-based chimeric receptor t cell switches and uses thereof |
TWI617319B (zh) * | 2015-09-01 | 2018-03-11 | 免疫功坊股份有限公司 | 用以治療病理性血栓的融合蛋白 |
US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
CA3031955A1 (en) * | 2016-07-29 | 2018-02-01 | Juno Therapeutics, Inc. | Immunomodulatory polypeptides and related compositions and methods |
BR112019007288A2 (pt) | 2016-10-14 | 2019-07-09 | Xencor Inc | proteína heterodimérica biespecífica, composições de ácido nucleico e de vetor de expressão, vetor de expressão, célula hospedeira, e, métodos para produzir proteína heterodimérica biespecífica e para tratar câncer em um paciente |
KR102613430B1 (ko) | 2016-10-19 | 2023-12-18 | 더 스크립스 리서치 인스티튜트 | 인간화된 표적화 모이어티 및/또는 최적화된 키메라 항원 수용체-상호작용 도메인을 갖는 키메라 항원 수용체 효과기 세포 스위치 및 이의 용도 |
US11779604B2 (en) | 2016-11-03 | 2023-10-10 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses and methods |
WO2018144999A1 (en) * | 2017-02-06 | 2018-08-09 | Orionis Biosciences, Inc. | Targeted engineered interferon and uses thereof |
CN108623693B (zh) * | 2017-03-20 | 2022-03-25 | 徐寒梅 | 一种融合蛋白及其制备方法和其在制备治疗眼科疾病、抗炎、抗肿瘤药物中的应用 |
CN108686202A (zh) * | 2017-04-06 | 2018-10-23 | 张晋宇 | 肿瘤免疫疗法 |
MX2019014023A (es) | 2017-05-24 | 2020-02-17 | Novartis Ag | Proteinas de anticuerpo injertadas con citocina y metodos de uso en el tratamiento del cancer. |
AU2018287317B2 (en) | 2017-06-19 | 2024-06-20 | Medicenna Therapeutics Inc. | Uses and methods for IL-2 superagonists, agonists, and fusions thereof |
EP3675892A4 (en) | 2017-07-03 | 2021-10-06 | Torque Therapeutics, Inc. | IMMUNOSTIMULATORY FUSION MOLECULES AND THEIR USES |
CA3044097A1 (en) * | 2017-11-10 | 2019-05-16 | I-Mab | Fusion proteins containing cd47 antibodies and cytokines |
WO2019104092A1 (en) | 2017-11-21 | 2019-05-31 | The Board Of Trustees Of The Leland Stanford Junior University | Partial agonists of interleukin-2 |
AU2018390418B2 (en) | 2017-12-19 | 2023-12-21 | Xencor, Inc. | Engineered IL-2 Fc fusion proteins |
EP3743438A4 (en) * | 2018-01-24 | 2022-02-23 | Beijing Percans Oncology Co. Ltd. | CYTOKI FUSION PROTEINS |
CA3097593A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Pd-1 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and pd-1 antigen binding domains and uses thereof |
WO2019204655A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains |
CU24554B1 (es) * | 2018-05-07 | 2021-11-04 | Ct Inmunologia Molecular | Proteínas de fusión compuestas por una muteína de interleucina 2 e interferón tipo 1 |
CN118108857A (zh) | 2018-06-01 | 2024-05-31 | 利兰斯坦福初级大学董事会 | 免疫细胞靶向性构建体 |
MA53822A (fr) * | 2018-10-03 | 2021-08-11 | Xencor Inc | Protéines de fusion fc hétérodimères d'il -12 |
PE20211055A1 (es) | 2018-10-12 | 2021-06-07 | Xencor Inc | Proteinas de fusion il-15 / il-15 ralpha f c dirigidas a pd-1 y usos en terapias de combinacion de las mismas |
US20220054611A1 (en) * | 2018-12-17 | 2022-02-24 | Immune Design Corp. | Pathogen-associated molecular pattern molecules and rna immunogenic compositions and methods of using the compositions for treating cancer |
CN113438961A (zh) | 2018-12-20 | 2021-09-24 | Xencor股份有限公司 | 含有IL-15/IL-15Rα和NKG2D抗原结合结构域的靶向异二聚体Fc融合蛋白 |
KR102524247B1 (ko) * | 2018-12-21 | 2023-04-21 | 가톨릭대학교 산학협력단 | p40-EBI3의 복합체 및 이의 용도 |
CN112210014B (zh) * | 2019-07-12 | 2022-10-11 | 北京科诺科服生物科技有限公司 | 一种用于治疗动物肿瘤的融合蛋白及组合物 |
US11851466B2 (en) | 2019-10-03 | 2023-12-26 | Xencor, Inc. | Targeted IL-12 heterodimeric Fc-fusion proteins |
TW202128757A (zh) | 2019-10-11 | 2021-08-01 | 美商建南德克公司 | 具有改善之特性的 PD-1 標靶 IL-15/IL-15Rα FC 融合蛋白 |
CN115315273A (zh) | 2020-01-14 | 2022-11-08 | 辛德凯因股份有限公司 | Il-2直向同源物及其使用方法 |
MX2022008771A (es) | 2020-01-14 | 2022-10-07 | Synthekine Inc | Metodos y composiciones de muteinas de il2 sesgadas. |
AU2020459746A1 (en) * | 2020-07-20 | 2023-03-16 | Deka Biosciences, Inc. | Dual cytokine fusion proteins comprising IL-10 |
KR20230065259A (ko) | 2020-08-05 | 2023-05-11 | 신테카인, 인크. | Il10 수용체 결합 분자 및 사용 방법 |
WO2022032040A1 (en) | 2020-08-05 | 2022-02-10 | Synthekine, Inc. | Il2rb/il2rg synthetic cytokines |
US20230399371A1 (en) * | 2020-10-29 | 2023-12-14 | Proviva Therapeutics (Hong Kong) Limited | Il-12 compositions and methods of use thereof |
AU2021410089A1 (en) * | 2020-12-23 | 2023-08-10 | Immunowake Inc. | Immunocytokines and uses thereof |
EP4370139A2 (en) | 2021-07-14 | 2024-05-22 | Synthekine, Inc. | Methods and compositions for use in cell therapy of neoplastic disease |
AU2022369312A1 (en) | 2021-10-20 | 2024-05-02 | Synthekine, Inc. | Heterodimeric fc cytokines and uses thereof |
CN118695868A (zh) * | 2021-12-16 | 2024-09-24 | 德卡生物科学公司 | 包含il-10的双细胞因子融合蛋白与过继细胞疗法或双特异性t细胞衔接器用于治疗癌症 |
Family Cites Families (149)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4196265A (en) | 1977-06-15 | 1980-04-01 | The Wistar Institute | Method of producing antibodies |
US4469797A (en) | 1982-09-23 | 1984-09-04 | Miles Laboratories, Inc. | Digoxigenin immunogens, antibodies, labeled conjugates, and related derivatives |
US4737462A (en) | 1982-10-19 | 1988-04-12 | Cetus Corporation | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of interferon-β |
US4966843A (en) | 1982-11-01 | 1990-10-30 | Cetus Corporation | Expression of interferon genes in Chinese hamster ovary cells |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
KR850004274A (ko) | 1983-12-13 | 1985-07-11 | 원본미기재 | 에리트로포이에틴의 제조방법 |
NZ210501A (en) | 1983-12-13 | 1991-08-27 | Kirin Amgen Inc | Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence |
US4703008A (en) | 1983-12-13 | 1987-10-27 | Kiren-Amgen, Inc. | DNA sequences encoding erythropoietin |
US5082658A (en) | 1984-01-16 | 1992-01-21 | Genentech, Inc. | Gamma interferon-interleukin-2 synergism |
EP0158198A1 (en) | 1984-03-29 | 1985-10-16 | Takeda Chemical Industries, Ltd. | DNA and use thereof |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
US4690915A (en) | 1985-08-08 | 1987-09-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adoptive immunotherapy as a treatment modality in humans |
US5679543A (en) | 1985-08-29 | 1997-10-21 | Genencor International, Inc. | DNA sequences, vectors and fusion polypeptides to increase secretion of desired polypeptides from filamentous fungi |
US5643565A (en) | 1985-09-20 | 1997-07-01 | Chiron Corporation | Human IL-2 as a vaccine adjuvant |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US4935233A (en) | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
US5359035A (en) | 1985-12-21 | 1994-10-25 | Hoechst Aktiengesellschaft | Bifunctional proteins including interleukin-2 (IL-2) and granuloctyte macrophage colony stimulating factor (GM-CSF) |
DE3712985A1 (de) | 1987-04-16 | 1988-11-03 | Hoechst Ag | Bifunktionelle proteine |
EP0237019A3 (en) | 1986-03-14 | 1988-03-09 | Toray Industries, Inc. | Interferon conjugate and production thereof using recombinant gene |
JPS63267278A (ja) | 1986-03-14 | 1988-11-04 | Toray Ind Inc | インタ−フエロン結合体を暗号化する塩基配列 |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
DK173067B1 (da) | 1986-06-27 | 1999-12-13 | Univ Washington | Humant erythropoietin-gen, fremgangsmåde til ekspression deraf i transficerede cellelinier, de transficerede cellelinier sa |
US4954617A (en) | 1986-07-07 | 1990-09-04 | Trustees Of Dartmouth College | Monoclonal antibodies to FC receptors for immunoglobulin G on human mononuclear phagocytes |
US4894227A (en) | 1986-08-01 | 1990-01-16 | Cetus Corporation | Composition of immunotoxins with interleukin-2 |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US5508031A (en) | 1986-11-21 | 1996-04-16 | Cetus Oncology Corporation | Method for treating biological damage using a free-radial scavenger and interleukin-2 |
US4732683A (en) | 1986-12-02 | 1988-03-22 | Biospectrum, Inc. | Purification method for alpha interferon |
US5019368A (en) | 1989-02-23 | 1991-05-28 | Cancer Biologics, Inc. | Detection of necrotic malignant tissue and associated therapy |
DE3883899T3 (de) | 1987-03-18 | 1999-04-22 | Sb2, Inc., Danville, Calif. | Geänderte antikörper. |
DE3856559T2 (de) | 1987-05-21 | 2004-04-29 | Micromet Ag | Multifunktionelle Proteine mit vorbestimmter Zielsetzung |
US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
ATE122238T1 (de) | 1987-06-10 | 1995-05-15 | Dana Farber Cancer Inst Inc | Bifunktionelle antikörperkonstruktionen und verfahren zur selektiven tötung von zellbeständen. |
ES2054753T3 (es) | 1987-09-02 | 1994-08-16 | Ciba Geigy Ag | Conjugados de citoquinas con inmunoglobulinas. |
CA1338518C (en) | 1987-09-23 | 1996-08-13 | Joyce M. Zarling | Antibody heteroconjugates for the killing of hiv-infected cells |
PT88641B (pt) | 1987-10-02 | 1993-04-30 | Genentech Inc | Metodo para a preparacao de uma variante de adesao |
AU2635088A (en) | 1987-12-04 | 1989-06-08 | Du Pont Merck Pharmaceutical Company, The | Immobilized interleukin 2 and interleukin 2 containing a carboxyl-terminal extension |
JP3040121B2 (ja) | 1988-01-12 | 2000-05-08 | ジェネンテク,インコーポレイテッド | 増殖因子レセプターの機能を阻害することにより腫瘍細胞を処置する方法 |
CA1341588C (en) | 1988-01-26 | 2009-01-06 | Michel Revel | Human ifn-beta2/i1-6, its purification and use |
US5120525A (en) | 1988-03-29 | 1992-06-09 | Immunomedics, Inc. | Radiolabeled antibody cytotoxic therapy of cancer |
DE3812605A1 (de) | 1988-04-15 | 1990-06-07 | Leskovar Peter Dipl Ing Dr Hab | Immunregulative stoffe und stoffgemische zur aktiven beeinflussung des krankheitsverlaufes |
IE62463B1 (en) | 1988-07-07 | 1995-02-08 | Res Dev Foundation | Immunoconjugates for cancer diagnosis and therapy |
US5601819A (en) | 1988-08-11 | 1997-02-11 | The General Hospital Corporation | Bispecific antibodies for selective immune regulation and for selective immune cell binding |
IL91933A (en) | 1988-10-11 | 1994-12-29 | Univ Southern California | Their immuno-bracelet and isophiles which are beneficial in increasing vascular permeability or blood supply to tumor or otherwise damaged tissue |
US5457038A (en) | 1988-11-10 | 1995-10-10 | Genetics Institute, Inc. | Natural killer stimulatory factor |
US5242824A (en) | 1988-12-22 | 1993-09-07 | Oncogen | Monoclonal antibody to human carcinomas |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
ZA902949B (en) | 1989-05-05 | 1992-02-26 | Res Dev Foundation | A novel antibody delivery system for biological response modifiers |
US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
WO1991000360A1 (en) | 1989-06-29 | 1991-01-10 | Medarex, Inc. | Bispecific reagents for aids therapy |
DE69019609T2 (de) | 1989-07-07 | 1995-11-30 | Takeda Chemical Industries Ltd | Proteine und deren Herstellung. |
US5073627A (en) | 1989-08-22 | 1991-12-17 | Immunex Corporation | Fusion proteins comprising GM-CSF and IL-3 |
CA2066612C (en) | 1989-09-20 | 1998-12-08 | Stephen D. Gillies | Method of producing fusion proteins |
US5856298A (en) | 1989-10-13 | 1999-01-05 | Amgen Inc. | Erythropoietin isoforms |
EP0790255B1 (en) | 1989-12-22 | 2007-08-08 | F. Hoffmann-La Roche Ag | Monoclonal antibodies directed to the cytotoxic lymphocyte maturation factor |
US5314995A (en) | 1990-01-22 | 1994-05-24 | Oncogen | Therapeutic interleukin-2-antibody based fusion proteins |
WO1991013166A1 (en) | 1990-03-02 | 1991-09-05 | Abbott Biotech, Inc. | Antibody constructs with enhanced binding affinity |
JP3319594B2 (ja) | 1990-03-20 | 2002-09-03 | ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨーク | 定常領域の代わりに受容体結合性リガンドを有するキメラ抗体 |
US5349053A (en) | 1990-06-01 | 1994-09-20 | Protein Design Labs, Inc. | Chimeric ligand/immunoglobulin molecules and their uses |
US7253264B1 (en) | 1990-06-28 | 2007-08-07 | Sanofi-Arentideutschland GmbH | Immunoglobulin fusion proteins, their production and use |
CA2082804A1 (en) | 1990-07-27 | 1992-01-28 | Theodore Maione | Methods and compositions for treatment of angiogenic diseases |
WO1992004455A1 (en) | 1990-08-29 | 1992-03-19 | Genetics Institute, Inc. | Multidomain hematopoiesis stimulators |
US5650150A (en) * | 1990-11-09 | 1997-07-22 | Gillies; Stephen D. | Recombinant antibody cytokine fusion proteins |
EP0556328A4 (en) | 1990-11-09 | 1994-06-08 | Abbott Lab | Bridging antibody fusion constructs |
DK0574395T3 (da) * | 1990-11-09 | 2002-10-07 | Stephen D Gillies | Cytokin-immunkonjugater |
US5709859A (en) | 1991-01-24 | 1998-01-20 | Bristol-Myers Squibb Company | Mixed specificity fusion proteins |
GB9105245D0 (en) | 1991-03-12 | 1991-04-24 | Lynxvale Ltd | Binding molecules |
US6072039A (en) | 1991-04-19 | 2000-06-06 | Rohm And Haas Company | Hybrid polypeptide comparing a biotinylated avidin binding polypeptide fused to a polypeptide of interest |
US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
WO1993003157A1 (en) | 1991-07-29 | 1993-02-18 | Dana Farber Cancer Institute | Plasmids for the rapid preparation of modified proteins |
ATE173763T1 (de) | 1991-08-30 | 1998-12-15 | Hutchinson Fred Cancer Res | Hybride cytokine |
US20020037558A1 (en) | 1991-10-23 | 2002-03-28 | Kin-Ming Lo | E.coli produced immunoglobulin constructs |
US5376367A (en) | 1991-11-22 | 1994-12-27 | Immunex Corporation | Fusion proteins comprising MGF and IL-3 |
US6627615B1 (en) | 1991-12-17 | 2003-09-30 | The Regents Of The University Of California | Methods and compositions for in vivo gene therapy |
ATE260971T1 (de) | 1992-04-01 | 2004-03-15 | Univ Rockefeller | Verfahren zur in vitro kultivierung dendritischer vorläuferzellen und deren verwendung zur immunogen herstellung |
IL105914A0 (en) | 1992-06-04 | 1993-10-20 | Univ California | Methods and compositions for in vivo gene therapy |
DE69332485T2 (de) | 1992-08-11 | 2003-11-13 | The President And Fellows Of Harvard College, Cambridge | Immunmodulierende peptide |
DE4228839A1 (de) | 1992-08-29 | 1994-03-03 | Behringwerke Ag | Verfahren zum Nachweis und zur Bestimmung von Mediatoren |
PT668777E (pt) | 1992-11-05 | 2007-01-31 | Sloan Kettering Inst Cancer | Antigenio de membrana especifico para a prostata |
US5738849A (en) | 1992-11-24 | 1998-04-14 | G. D. Searle & Co. | Interleukin-3 (IL-3) variant fusion proteins, their recombinant production, and therapeutic compositions comprising them |
US5543297A (en) | 1992-12-22 | 1996-08-06 | Merck Frosst Canada, Inc. | Human cyclooxygenase-2 cDNA and assays for evaluating cyclooxygenase-2 activity |
CN1074243A (zh) | 1993-02-06 | 1993-07-14 | 北京中化生物技术研究所 | 白介素6-白介素2融合蛋白及其制法和用途 |
US6096331A (en) | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
US5759551A (en) | 1993-04-27 | 1998-06-02 | United Biomedical, Inc. | Immunogenic LHRH peptide constructs and synthetic universal immune stimulators for vaccines |
BR9406490A (pt) | 1993-04-29 | 1996-03-05 | Abbott Lab | Análogo de eritropoietina humana,DNA de filamento duplo,vetor de expressão célula de mamiferos em cultura composição farmaceutica segundo e terceiro análogo de eritropoietina humana e processos para fabricar um segundo análogo de eritropoietina e para usar um segundo análogo |
US5554512A (en) | 1993-05-24 | 1996-09-10 | Immunex Corporation | Ligands for flt3 receptors |
CA2125763C (en) | 1993-07-02 | 2007-08-28 | Maurice Kent Gately | P40 homodimer of interleukin-12 |
GB9316989D0 (en) | 1993-08-16 | 1993-09-29 | Lynxvale Ltd | Binding molecules |
CA2182498A1 (en) | 1994-02-01 | 1995-08-10 | William J. Larochelle | Fusion proteins that include antibody and nonantibody portions |
WO1995028427A1 (en) | 1994-04-15 | 1995-10-26 | Imclone Systems Incorporated | Chimeric interleukin-3/mutein interleukin-6 lymphokine |
US5837682A (en) | 1996-03-08 | 1998-11-17 | The Children's Medical Center Corporation | Angiostatin fragments and method of use |
JP3880064B2 (ja) | 1994-04-26 | 2007-02-14 | ザ チルドレンズ メディカル センター コーポレイション | アンジオスタチンおよび血管形成の抑制におけるその使用 |
US5639725A (en) | 1994-04-26 | 1997-06-17 | Children's Hospital Medical Center Corp. | Angiostatin protein |
US6429199B1 (en) | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
US5541087A (en) | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
ES2167391T3 (es) | 1994-09-16 | 2002-05-16 | Merck Patent Gmbh | Inmunoconjugados ii. |
US6086875A (en) | 1995-01-17 | 2000-07-11 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of immunogens |
US6485726B1 (en) * | 1995-01-17 | 2002-11-26 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of therapeutics |
US5691309A (en) | 1995-01-31 | 1997-11-25 | Eli Lilly And Company | Anti-obesity proteins |
US5552524A (en) | 1995-01-31 | 1996-09-03 | Eli Lilly And Company | Anti-obesity proteins |
US5891680A (en) | 1995-02-08 | 1999-04-06 | Whitehead Institute For Biomedical Research | Bioactive fusion proteins comprising the p35 and p40 subunits of IL-12 |
ATE271606T1 (de) | 1995-03-10 | 2004-08-15 | Genentech Inc | Die aktivierung von rezeptoren durch gas6 |
US5719266A (en) | 1995-03-17 | 1998-02-17 | Eli Lilly And Company | Anti-obesity proteins |
KR19990028388A (ko) | 1995-06-30 | 1999-04-15 | 피터 지. 스트링거 | 당뇨병 치료 방법 |
US6406689B1 (en) | 1995-10-03 | 2002-06-18 | Frank W. Falkenberg | Compositions and methods for treatment of tumors and metastatic diseases |
US5854205A (en) | 1995-10-23 | 1998-12-29 | The Children's Medical Center Corporation | Therapeutic antiangiogenic compositions and methods |
US5723125A (en) | 1995-12-28 | 1998-03-03 | Tanox Biosystems, Inc. | Hybrid with interferon-alpha and an immunoglobulin Fc linked through a non-immunogenic peptide |
US6080409A (en) | 1995-12-28 | 2000-06-27 | Dendreon Corporation | Immunostimulatory method |
US6750334B1 (en) | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
EP0914453A1 (en) * | 1996-05-20 | 1999-05-12 | Schering Corporation | HUMAN INTERLEUKIN-1j AND ANTAGONISTS THEREOF |
CA2205757C (en) | 1996-05-30 | 2006-01-24 | F. Hoffmann-La Roche Ag | Pyridazinone derivatives and their use as inhibitors of prostaglandin g/h synthase i and ii(cox i and ii) |
US5922685A (en) | 1996-06-05 | 1999-07-13 | Powderject Vaccines, Inc. | IL-12 gene therapy of tumors |
ES2176574T3 (es) | 1996-09-03 | 2002-12-01 | Gsf Forschungszentrum Umwelt | Utilizacion de anticuerpos bi y triespecificos para la induccion de inmunidad tumoral. |
US5994104A (en) | 1996-11-08 | 1999-11-30 | Royal Free Hospital School Of Medicine | Interleukin-12 fusion protein |
US6100387A (en) | 1997-02-28 | 2000-08-08 | Genetics Institute, Inc. | Chimeric polypeptides containing chemokine domains |
US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
JP2001521520A (ja) | 1997-04-11 | 2001-11-06 | ジー.ディー.サール アンド カンパニー | 抗α▲下v▼β▲下3▼インテグリン抗体アンタゴニスト |
EP1489100B1 (en) * | 1997-12-08 | 2016-06-15 | Merck Patent GmbH | Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation |
JP2002501031A (ja) * | 1998-01-23 | 2002-01-15 | ジェネティックス・インスチチュート・インコーポレーテッド | ウイルスおよび寄生体感染ならびに癌の治療のために細胞性免疫を促進するためのil−11の使用方法 |
US20030105294A1 (en) * | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
AU758860B2 (en) * | 1998-04-15 | 2003-04-03 | Merck Patent Gmbh | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with angiogenesis inhibitor |
BR9909677A (pt) * | 1998-04-17 | 2000-12-19 | Lexigen Pharm Corp | Intensificação de respostas imunológicas, mediadas por proteìna de fusão anticorpo-citocina, através de co-administração com inibidor de prostaglandinas |
WO1999054484A1 (en) | 1998-04-20 | 1999-10-28 | The Regents Of The University Of California | Modified immunoglobulin molecules and methods for use thereof |
US6620382B1 (en) | 1998-05-22 | 2003-09-16 | Biopheresis Technologies, Llc. | Method and compositions for treatment of cancers |
ES2342239T3 (es) * | 1998-08-25 | 2010-07-02 | Merck Patent Gmbh | Expresion y exportacion de angiostatina y de endostatina como inmunofusinas. |
US6646113B1 (en) | 1998-09-17 | 2003-11-11 | The Trustees Of The University Of Pennsylvania | Nucleic acid molecule encoding human survival of motor neuron-interacting protein 1 (SIP1) deletion mutants |
US6335176B1 (en) | 1998-10-16 | 2002-01-01 | Pharmacopeia, Inc. | Incorporation of phosphorylation sites |
KR20020007287A (ko) * | 1999-01-07 | 2002-01-26 | 추후보정 | Fc 융합 단백질로서 항-비만 단백질의 발현 및 이출 |
MXPA01011250A (es) | 1999-05-06 | 2002-08-12 | Univ Wake Forest | Composiciones y metodos para identificar antigenos que producen una respuesta inmune. |
US6348192B1 (en) | 1999-05-11 | 2002-02-19 | Bayer Corporation | Interleukin-2 mutein expressed from mammalian cells |
CA2372400C (en) * | 1999-05-19 | 2010-04-27 | Lexigen Pharmaceuticals Corp. | Expression and export of interferon-alpha proteins as fc fusion proteins |
CZ299516B6 (cs) | 1999-07-02 | 2008-08-20 | F. Hoffmann-La Roche Ag | Konjugát erythropoetinového glykoproteinu, zpusobjeho výroby a použití a farmaceutická kompozice sjeho obsahem |
JO2291B1 (en) | 1999-07-02 | 2005-09-12 | اف . هوفمان لاروش ايه جي | Erythropoietin derivatives |
CN1235911C (zh) * | 1999-08-09 | 2006-01-11 | 利思进药品公司 | 多细胞因子-抗体复合物 |
ES2269361T3 (es) * | 2000-02-24 | 2007-04-01 | Philogen S.P.A. | Composiciones y metodos para tratamiento de la angiogenesis en lesiones patologicas. |
US6586398B1 (en) | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
EP1285072A2 (en) * | 2000-05-12 | 2003-02-26 | Neose Technologies, Inc. | In vitro fucosylation recombinant glycopeptides |
EP1294401B1 (en) * | 2000-06-29 | 2007-08-01 | EMD Lexigen Research Center Corp. | Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents |
CA2435037A1 (en) * | 2001-01-18 | 2002-07-25 | Silke Schumacher | Bifunctional fusion proteins with glucocerebrosidase activity |
CN100522242C (zh) * | 2001-02-19 | 2009-08-05 | 默克专利有限公司 | 具有降低的免疫原性的人工蛋白质 |
ATE400030T1 (de) * | 2001-02-19 | 2008-07-15 | Merck Patent Gmbh | Methode zur identifizierung von t-zellepitopen und deren anwendung zur herstellung von molekülen mit reduzierter immunogenität |
KR20090010127A (ko) * | 2001-03-07 | 2009-01-28 | 메르크 파텐트 게엠베하 | 하이브리드 이소타입 항체 부분구조를 포함하는 단백질을 위한 발현 기술 |
US6992174B2 (en) * | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
PL205352B1 (pl) * | 2001-05-03 | 2010-04-30 | Merck Patent Gmbh | Rekombinowane przeciwciało specyficzne dla nowotworu |
RU2312677C9 (ru) * | 2001-12-04 | 2008-03-27 | Мерк Патент Гмбх | Иммуноцитокины с модулированной селективностью |
-
2000
- 2000-08-09 CN CNB008137269A patent/CN1235911C/zh not_active Expired - Fee Related
- 2000-08-09 PL PL353348A patent/PL202058B1/pl unknown
- 2000-08-09 AT AT00953896T patent/ATE316982T1/de active
- 2000-08-09 RU RU2002106234/04A patent/RU2263118C2/ru not_active IP Right Cessation
- 2000-08-09 BR BR0013231-4A patent/BR0013231A/pt active Search and Examination
- 2000-08-09 EP EP00953896A patent/EP1200479B1/en not_active Expired - Lifetime
- 2000-08-09 KR KR1020027001705A patent/KR100827757B1/ko not_active IP Right Cessation
- 2000-08-09 DK DK00953896T patent/DK1200479T3/da active
- 2000-08-09 US US09/634,368 patent/US6617135B1/en not_active Expired - Lifetime
- 2000-08-09 SK SK184-2002A patent/SK1842002A3/sk not_active Application Discontinuation
- 2000-08-09 MX MXPA02001417A patent/MXPA02001417A/es active IP Right Grant
- 2000-08-09 AU AU66268/00A patent/AU778611B2/en not_active Ceased
- 2000-08-09 HU HU0202442A patent/HUP0202442A3/hu unknown
- 2000-08-09 DE DE60025832T patent/DE60025832T2/de not_active Expired - Lifetime
- 2000-08-09 JP JP2001515719A patent/JP4793971B2/ja not_active Expired - Fee Related
- 2000-08-09 CA CA2380331A patent/CA2380331C/en not_active Expired - Fee Related
- 2000-08-09 WO PCT/US2000/021715 patent/WO2001010912A1/en active IP Right Grant
- 2000-08-09 ES ES00953896T patent/ES2256027T3/es not_active Expired - Lifetime
-
2002
- 2002-01-29 ZA ZA200200789A patent/ZA200200789B/xx unknown
- 2002-02-08 NO NO20020641A patent/NO20020641L/no not_active Application Discontinuation
-
2003
- 2003-06-24 US US10/603,064 patent/US7141651B2/en not_active Expired - Fee Related
-
2006
- 2006-11-20 US US11/603,278 patent/US7582288B2/en not_active Expired - Fee Related
-
2010
- 2010-11-08 JP JP2010250341A patent/JP2011067211A/ja not_active Withdrawn
Cited By (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102221607A (zh) * | 2011-03-29 | 2011-10-19 | 浙江大学医学院附属第一医院 | 一种抗体组合物及其应用 |
CN102221607B (zh) * | 2011-03-29 | 2013-10-02 | 浙江大学医学院附属第一医院 | 一种抗体组合物及其应用 |
CN104136457A (zh) * | 2011-11-08 | 2014-11-05 | Umc乌德勒支控股有限公司 | 包括白细胞介素10和白细胞介素4的融合蛋白 |
CN108129574A (zh) * | 2011-11-08 | 2018-06-08 | Umc乌德勒支控股有限公司 | 包括白细胞介素10和白细胞介素4的融合蛋白 |
US10981964B2 (en) | 2011-11-08 | 2021-04-20 | Synerkine Pharma B.V. | Fusion protein comprising IL-4 and IL-10 |
US10851143B2 (en) | 2011-11-08 | 2020-12-01 | Synerkine Pharma B.V. | Methods of treatment with a fusion protein comprising IL-4 and IL-10 |
TWI487713B (zh) * | 2011-12-06 | 2015-06-11 | Nat Univ Chung Hsing | 趨化素-細胞素融合蛋白和其應用 |
WO2014085947A1 (zh) * | 2012-12-05 | 2014-06-12 | Chiou Shiow-Her | 趋化素-细胞素融合蛋白和其应用 |
CN104968686A (zh) * | 2012-12-05 | 2015-10-07 | 邱绣河 | 趋化素-细胞素融合蛋白和其应用 |
CN104968686B (zh) * | 2012-12-05 | 2020-02-04 | 薛富盛 | 趋化素-细胞素融合蛋白和其应用 |
CN105705641A (zh) * | 2013-07-18 | 2016-06-22 | 弗拉芒区生物技术研究所 | 涉及具有强烈降低的受体结合亲和力的细胞因子的融合因子 |
CN105658669A (zh) * | 2013-07-19 | 2016-06-08 | 弗拉芒区生物技术研究所 | 细胞因子拮抗剂的靶向 |
US12054530B2 (en) | 2016-09-27 | 2024-08-06 | Epicentrx, Inc. | Immunomodulatory fusion proteins |
CN110546168A (zh) * | 2016-09-27 | 2019-12-06 | 埃皮辛特瑞柯斯公司 | 免疫调节性融合蛋白 |
CN110546168B (zh) * | 2016-09-27 | 2024-03-15 | 埃皮辛特瑞柯斯公司 | 免疫调节性融合蛋白 |
CN111107868A (zh) * | 2017-05-24 | 2020-05-05 | 诺华股份有限公司 | 抗体细胞因子移植蛋白及使用方法 |
US11834492B2 (en) | 2017-09-27 | 2023-12-05 | Epicentrx, Inc. | Human IL-10 receptor alpha fusion proteins |
CN112566650A (zh) * | 2018-06-21 | 2021-03-26 | 沙塔克实验室有限公司 | 异二聚体蛋白及其用途 |
CN112513276A (zh) * | 2018-07-30 | 2021-03-16 | 张晋宇 | 蛋白质异二聚体及其用途 |
CN112513276B (zh) * | 2018-07-30 | 2024-03-15 | 张晋宇 | 蛋白质异二聚体及其用途 |
CN109824786A (zh) * | 2019-03-01 | 2019-05-31 | 王仁喜 | hIL-12p35-Fc融合蛋白、编码基因、重组载体、宿主细胞及应用 |
US11312757B2 (en) | 2019-04-19 | 2022-04-26 | Synerkine Pharma B.V. | Fusion protein comprising IL13 |
CN111848811B (zh) * | 2019-04-27 | 2024-10-01 | 张晋宇 | 一种蛋白质异二聚体及其用途 |
CN111848811A (zh) * | 2019-04-27 | 2020-10-30 | 张晋宇 | 一种蛋白质异二聚体及其用途 |
WO2020221136A1 (zh) * | 2019-04-27 | 2020-11-05 | 张晋宇 | 一种蛋白质异二聚体及其用途 |
WO2020221135A1 (zh) * | 2019-04-28 | 2020-11-05 | 张晋宇 | 一种蛋白质分子及其用途 |
CN114008082A (zh) * | 2019-06-24 | 2022-02-01 | 南京金斯瑞生物科技有限公司 | 单克隆抗体-细胞因子融合蛋白二聚体及其应用 |
WO2020259536A1 (zh) * | 2019-06-24 | 2020-12-30 | 南京金斯瑞生物科技有限公司 | 单克隆抗体-细胞因子融合蛋白二聚体及其应用 |
CN114466657A (zh) * | 2019-07-25 | 2022-05-10 | 芝加哥大学 | 包括蛋白酶激活治疗剂的组合物和方法 |
CN111303296A (zh) * | 2019-12-16 | 2020-06-19 | 启辰生生物科技(珠海)有限公司 | 双功能融合多肽、细胞和药物组合物及应用 |
CN114945586A (zh) * | 2020-01-21 | 2022-08-26 | 张晋宇 | 一种药物组合物及其用途 |
WO2023011575A1 (zh) * | 2021-08-04 | 2023-02-09 | 清华大学 | 一种靶向并杀伤病原体和/或肿瘤细胞的多功能融合蛋白药物 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1382158A (zh) | 多细胞因子-抗体复合物 | |
FI121571B (fi) | Interleukiini-15-antagonisteja | |
CA2034741C (en) | Therapeutic antibody based fusion proteins | |
CN1464790A (zh) | T细胞受体融合物及共轭物以及其使用方法 | |
CN1304427C (zh) | 抑制血管新生的融合蛋白质及其用途 | |
FI119733B (fi) | Menetelmiä sellaisten rekombinantti -IL4-vasta-aineiden valmistamiseksi jotka ovat käyttökelpoisia IL-4-välitteisten häiriötilojen hoidossa | |
CN1443199A (zh) | 人mcp-1的抗体 | |
CN1399556A (zh) | April受体(bcma)及其用途 | |
JP2022513265A (ja) | ヒトインターロイキン2の変異体またはその誘導体 | |
CN1898262A (zh) | Il-7融合蛋白 | |
CN102177178A (zh) | 抗il-12/il-23抗体 | |
CN1395581A (zh) | 抗人IL-1β抗体 | |
CN1751122A (zh) | 具有改进特性的干扰素α突变蛋白的融合蛋白 | |
US7491500B2 (en) | Mammalian cytokine; related reagents | |
CN1946740A (zh) | 抗人腱生蛋白单克隆抗体 | |
KR100479790B1 (ko) | G - c s f 수용체의 항진 항체 및 이를 스크리닝하는 방법 | |
CN110205296B (zh) | 具有Fc突变体的抗体与效应细胞的组合、用途和制法 | |
CN1230223A (zh) | 高亲和性白细胞介素-4突变蛋白质 | |
CN1245533A (zh) | 哺乳动物趋化因子 | |
CN1299833A (zh) | 抗人血管内皮生长因子单链抗体及其制备方法 | |
CN108409861A (zh) | 一种双特异性抗体及其应用 | |
KR101572912B1 (ko) | 돼지 cd7 유전자 및 이를 이용한 cd7 융합 이뮤노글로불린 | |
CN1687119A (zh) | 表皮生长因子受体靶向短肽与力达霉素构成的抗肿瘤基因工程融合蛋白 | |
JP2000502995A (ja) | Bリンパ球による抗体放出を刺激する組成物および方法 | |
CN1169835C (zh) | 人b淋巴细胞刺激因子突变体及其构建方法和编码基因 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: MERCK PATENT GMBH Free format text: FORMER OWNER: EMD LISIJIN RESEARCH CENTRE CO.,LTD. Effective date: 20080725 |
|
C41 | Transfer of patent application or patent right or utility model | ||
C56 | Change in the name or address of the patentee |
Owner name: EMD LISIJIN RESEARCH CENTRE CO.,LTD. Free format text: FORMER NAME OR ADDRESS: PHARMACEUTICAL COMPANY |
|
CP03 | Change of name, title or address |
Address after: Massachusetts Patentee after: EMD in Leith Research Center Co.,Ltd. Address before: Massachusetts Patentee before: LEXIGEN PHARMACEUTICALS Corp. |
|
TR01 | Transfer of patent right |
Effective date of registration: 20080725 Address after: Darmstadt Patentee after: MERCK PATENT GmbH Address before: Massachusetts Patentee before: EMD in Leith Research Center Co.,Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20060111 Termination date: 20180809 |
|
CF01 | Termination of patent right due to non-payment of annual fee |