ZA200307792B - Expression technology for proteins containing a hybrid isotype antibody moioety. - Google Patents
Expression technology for proteins containing a hybrid isotype antibody moioety. Download PDFInfo
- Publication number
- ZA200307792B ZA200307792B ZA200307792A ZA200307792A ZA200307792B ZA 200307792 B ZA200307792 B ZA 200307792B ZA 200307792 A ZA200307792 A ZA 200307792A ZA 200307792 A ZA200307792 A ZA 200307792A ZA 200307792 B ZA200307792 B ZA 200307792B
- Authority
- ZA
- South Africa
- Prior art keywords
- fusion protein
- protein
- antibody
- domain
- hinge
- Prior art date
Links
- 108090000623 proteins and genes Proteins 0.000 title claims description 183
- 102000004169 proteins and genes Human genes 0.000 title claims description 178
- 238000005516 engineering process Methods 0.000 title description 7
- 108020001507 fusion proteins Proteins 0.000 claims description 263
- 102000037865 fusion proteins Human genes 0.000 claims description 263
- 235000018102 proteins Nutrition 0.000 claims description 157
- 108060003951 Immunoglobulin Proteins 0.000 claims description 48
- 235000018417 cysteine Nutrition 0.000 claims description 48
- 102000018358 immunoglobulin Human genes 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 34
- 150000007523 nucleic acids Chemical class 0.000 claims description 19
- 102000009109 Fc receptors Human genes 0.000 claims description 18
- 108010087819 Fc receptors Proteins 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 108020004707 nucleic acids Proteins 0.000 claims description 15
- 102000039446 nucleic acids Human genes 0.000 claims description 15
- 239000000427 antigen Substances 0.000 claims description 14
- 102000036639 antigens Human genes 0.000 claims description 14
- 108091007433 antigens Proteins 0.000 claims description 14
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 229940105423 erythropoietin Drugs 0.000 claims description 9
- 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 claims description 9
- 102000003951 Erythropoietin Human genes 0.000 claims description 8
- 108090000394 Erythropoietin Proteins 0.000 claims description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 7
- 229920001184 polypeptide Polymers 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 238000010353 genetic engineering Methods 0.000 claims description 3
- 230000002068 genetic effect Effects 0.000 claims 2
- POFWRMVFWIJXHP-UHFFFAOYSA-N n-benzyl-9-(oxan-2-yl)purin-6-amine Chemical compound C=1C=CC=CC=1CNC(C=1N=C2)=NC=NC=1N2C1CCCCO1 POFWRMVFWIJXHP-UHFFFAOYSA-N 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 66
- 239000012634 fragment Substances 0.000 description 50
- 230000000875 corresponding effect Effects 0.000 description 39
- 239000013612 plasmid Substances 0.000 description 37
- 108020004414 DNA Proteins 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 30
- 230000006870 function Effects 0.000 description 28
- 230000004927 fusion Effects 0.000 description 27
- 229940039781 leptin Drugs 0.000 description 27
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 26
- 239000012636 effector Substances 0.000 description 24
- 235000001014 amino acid Nutrition 0.000 description 21
- 230000035772 mutation Effects 0.000 description 21
- 108091005804 Peptidases Proteins 0.000 description 19
- 239000004365 Protease Substances 0.000 description 19
- 150000001945 cysteines Chemical class 0.000 description 19
- 229940024606 amino acid Drugs 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 18
- 210000004962 mammalian cell Anatomy 0.000 description 18
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 18
- 239000013613 expression plasmid Substances 0.000 description 17
- 239000013604 expression vector Substances 0.000 description 16
- 210000002966 serum Anatomy 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 16
- 108010002350 Interleukin-2 Proteins 0.000 description 15
- 102000000588 Interleukin-2 Human genes 0.000 description 15
- 238000006467 substitution reaction Methods 0.000 description 14
- 238000010276 construction Methods 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 230000014616 translation Effects 0.000 description 13
- 102000004127 Cytokines Human genes 0.000 description 12
- 108090000695 Cytokines Proteins 0.000 description 12
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 238000013519 translation Methods 0.000 description 12
- 241000894007 species Species 0.000 description 11
- 108010065805 Interleukin-12 Proteins 0.000 description 10
- 102000013462 Interleukin-12 Human genes 0.000 description 10
- 102000016267 Leptin Human genes 0.000 description 10
- 108010092277 Leptin Proteins 0.000 description 10
- 210000003527 eukaryotic cell Anatomy 0.000 description 10
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 9
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 9
- 108010076504 Protein Sorting Signals Proteins 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 230000013595 glycosylation Effects 0.000 description 9
- 238000006206 glycosylation reaction Methods 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000000178 monomer Substances 0.000 description 9
- 235000004400 serine Nutrition 0.000 description 9
- 229960001153 serine Drugs 0.000 description 9
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 9
- 108020004705 Codon Proteins 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 8
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 8
- 238000004220 aggregation Methods 0.000 description 8
- 125000003275 alpha amino acid group Chemical group 0.000 description 8
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 8
- 238000012512 characterization method Methods 0.000 description 8
- 239000012228 culture supernatant Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical group 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 8
- 238000006384 oligomerization reaction Methods 0.000 description 8
- 108700019828 Hinge Exons Proteins 0.000 description 7
- 102000035195 Peptidases Human genes 0.000 description 7
- 230000002776 aggregation Effects 0.000 description 7
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 7
- 230000006334 disulfide bridging Effects 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 229940127130 immunocytokine Drugs 0.000 description 7
- 230000002441 reversible effect Effects 0.000 description 7
- 238000001542 size-exclusion chromatography Methods 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 102000014914 Carrier Proteins Human genes 0.000 description 6
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 6
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 6
- 108091008324 binding proteins Proteins 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 210000004899 c-terminal region Anatomy 0.000 description 6
- 102000044890 human EPO Human genes 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 235000013930 proline Nutrition 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 238000003146 transient transfection Methods 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- 102000001301 EGF receptor Human genes 0.000 description 5
- 108060006698 EGF receptor Proteins 0.000 description 5
- 108700024394 Exon Proteins 0.000 description 5
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 5
- -1 IL- 10 Proteins 0.000 description 5
- 102100029571 Immunoglobulin J chain Human genes 0.000 description 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 5
- 229920002684 Sepharose Polymers 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 229940072221 immunoglobulins Drugs 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229960002429 proline Drugs 0.000 description 5
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 238000012795 verification Methods 0.000 description 5
- 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 4
- 108091026890 Coding region Proteins 0.000 description 4
- 108091006020 Fc-tagged proteins Proteins 0.000 description 4
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 4
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 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 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 229960003767 alanine Drugs 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000001502 gel electrophoresis Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 229960003646 lysine Drugs 0.000 description 4
- 235000018977 lysine Nutrition 0.000 description 4
- 229960000485 methotrexate Drugs 0.000 description 4
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000037432 silent mutation Effects 0.000 description 4
- 108020005098 Anticodon Proteins 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 108090001008 Avidin Proteins 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 description 3
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 3
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 3
- 108091092195 Intron Proteins 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102000018697 Membrane Proteins Human genes 0.000 description 3
- 108010052285 Membrane Proteins Proteins 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 108020004566 Transfer RNA Proteins 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000003636 conditioned culture medium Substances 0.000 description 3
- 150000001944 cysteine derivatives Chemical class 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 238000001638 lipofection Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000011987 methylation Effects 0.000 description 3
- 238000007069 methylation reaction Methods 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000012723 sample buffer Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 102000003390 tumor necrosis factor Human genes 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 238000012800 visualization Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 2
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 2
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 2
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 2
- 108010008165 Etanercept Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 108010001160 IgY Proteins 0.000 description 2
- 108010017515 Interleukin-12 Receptors Proteins 0.000 description 2
- 102000004560 Interleukin-12 Receptors Human genes 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 238000006664 bond formation reaction Methods 0.000 description 2
- 108091092356 cellular DNA Proteins 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 229940073621 enbrel Drugs 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 229960002743 glutamine Drugs 0.000 description 2
- 235000004554 glutamine Nutrition 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 102000005861 leptin receptors Human genes 0.000 description 2
- 108010019813 leptin receptors Proteins 0.000 description 2
- 229960003136 leucine Drugs 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 235000008521 threonine Nutrition 0.000 description 2
- 108700008509 tucotuzumab celmoleukin Proteins 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101150111062 C gene Proteins 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 101000972324 Cynodon dactylon Leaf protein Proteins 0.000 description 1
- 102100038493 Cytokine receptor-like factor 1 Human genes 0.000 description 1
- 101710194728 Cytokine receptor-like factor 1 Proteins 0.000 description 1
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 108010092408 Eosinophil Peroxidase Proteins 0.000 description 1
- 102100031939 Erythropoietin Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010038486 Interleukin-4 Receptors Proteins 0.000 description 1
- 102000010787 Interleukin-4 Receptors Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 102220555409 Wnt inhibitory factor 1_H32G_mutation Human genes 0.000 description 1
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 1
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 102000002467 interleukin receptors Human genes 0.000 description 1
- 108010093036 interleukin receptors Proteins 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 108010027445 interleukin-22 receptor Proteins 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000012510 peptide mapping method Methods 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 238000009163 protein therapy Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 108010061338 ranpirnase Proteins 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 102200046443 rs9014 Human genes 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 238000012868 site-directed mutagenesis technique Methods 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 150000003588 threonines Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- 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
-
- 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
- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US27409601P | 2001-03-07 | 2001-03-07 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200307792B true ZA200307792B (en) | 2004-07-06 |
Family
ID=23046749
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200307792A ZA200307792B (en) | 2001-03-07 | 2003-10-06 | Expression technology for proteins containing a hybrid isotype antibody moioety. |
Country Status (17)
Country | Link |
---|---|
US (2) | US7148321B2 (fr) |
EP (1) | EP1366067B1 (fr) |
JP (1) | JP4234438B2 (fr) |
KR (2) | KR20090010127A (fr) |
CN (1) | CN1330664C (fr) |
AU (1) | AU2002248571B2 (fr) |
BR (1) | BR0207854A (fr) |
CA (1) | CA2440221C (fr) |
DK (1) | DK1366067T3 (fr) |
ES (1) | ES2393733T3 (fr) |
HU (1) | HUP0303428A2 (fr) |
MX (1) | MXPA03008031A (fr) |
PL (1) | PL206701B1 (fr) |
PT (1) | PT1366067E (fr) |
RU (1) | RU2003129528A (fr) |
WO (1) | WO2002072605A2 (fr) |
ZA (1) | ZA200307792B (fr) |
Families Citing this family (159)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69824039T2 (de) * | 1997-12-08 | 2005-08-18 | Lexigen Pharmaceuticals Corp., Lexington | Heterodimäre fusionsproteine zur verwendung für gezielte immuntherapie und allgemeine immunerregung |
US20030105294A1 (en) * | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
WO1999052562A2 (fr) * | 1998-04-15 | 1999-10-21 | Lexigen Pharmaceuticals Corp. | Co-administration d'un inhibiteur de l'angiogenese pour renforcer la reponse immunitaire a mediation de proteine de fusion d'une cytokine d'anticorps |
JP2003530070A (ja) * | 1999-05-19 | 2003-10-14 | レキシジェン ファーマシューティカルズ コーポレイション | Fc融合タンパク質としてのインターフェロン−αタンパク質の発現および搬出 |
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 |
SK782002A3 (en) | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
US6617135B1 (en) * | 1999-08-09 | 2003-09-09 | Emd Lexigen Research Center Corp. | Multiple cytokine protein complexes |
US20050202538A1 (en) * | 1999-11-12 | 2005-09-15 | Merck Patent Gmbh | Fc-erythropoietin fusion protein with improved pharmacokinetics |
WO2001058957A2 (fr) * | 2000-02-11 | 2001-08-16 | Lexigen Pharmaceuticals Corp. | Amelioration de la demi-vie circulante de proteines de fusion a base d'anticorps |
MXPA02012734A (es) * | 2000-06-29 | 2003-04-25 | Merck Patent Gmbh | Mejoramiento de las respuestas inmunes mediadas por la proteina de fusion anticuerpo-citocina, mediante tratamiento combinado con agentes mejoradores de la captacion de inmunocitocina. |
DE10045591A1 (de) | 2000-09-15 | 2002-04-04 | Klaus Pfizenmaier | Ortsspezifische, antikörpervermittelte Aktivierung proapoptotischer Zytokine - AMAIZe (Antibody-Mediated Apoptosis Inducing Zytokine) |
US20030133939A1 (en) * | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
US7829084B2 (en) | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
US7754208B2 (en) * | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
MXPA03008031A (es) | 2001-03-07 | 2003-12-04 | Merck Patent Gmbh | Tecnologia de expresion para proteinas que contienen porcion de anticuerpo isotipo hibrida. |
US6992174B2 (en) | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
CN100503639C (zh) | 2001-05-03 | 2009-06-24 | 默克专利有限公司 | 重组肿瘤特异性抗体及其应用 |
WO2003048334A2 (fr) * | 2001-12-04 | 2003-06-12 | Merck Patent Gmbh | Immunocytokines a selectivite modulee |
ATE471946T1 (de) * | 2002-12-17 | 2010-07-15 | Merck Patent Gmbh | Humanisierter antikörper (h14.18) des maus antikörpers 14.18, der gd2 bindet und seine fusion mit il-2 |
US7754209B2 (en) | 2003-07-26 | 2010-07-13 | Trubion Pharmaceuticals | Binding constructs and methods for use thereof |
US20050069521A1 (en) * | 2003-08-28 | 2005-03-31 | Emd Lexigen Research Center Corp. | Enhancing the circulating half-life of interleukin-2 proteins |
JP2008502317A (ja) * | 2003-12-30 | 2008-01-31 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | Il−7融合タンパク質 |
WO2005063808A1 (fr) * | 2003-12-31 | 2005-07-14 | Merck Patent Gmbh | Proteine hybride fc-erythropoietine a pharmacocinetique amelioree |
AU2005203962C1 (en) | 2004-01-05 | 2012-11-08 | Antisoma Research Limited | Interleukin-12 targeted to oncofoetal fibronectin |
AU2005206277B2 (en) * | 2004-01-22 | 2011-06-23 | Merck Patent Gmbh | Anti-cancer antibodies with reduced complement fixation |
US7670595B2 (en) * | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
EP1769000B1 (fr) * | 2004-07-16 | 2014-12-24 | Amgen Research (Munich) GmbH | Polypeptides a expression amelioree |
ES2342964T3 (es) | 2004-12-09 | 2010-07-20 | Merck Patent Gmbh | Variantes de la interleucina-7 con inmunogenicidad reducida. |
EP1870459B1 (fr) | 2005-03-31 | 2016-06-29 | Chugai Seiyaku Kabushiki Kaisha | Procede pour la production de polypeptide au moyen de la regulation d'un ensemble |
EP2298815B1 (fr) | 2005-07-25 | 2015-03-11 | Emergent Product Development Seattle, LLC | Reduction de lymphocytes B au moyen de molecules de liaison specifique de CD37 et specifique de CD20 |
US20070041979A1 (en) * | 2005-08-19 | 2007-02-22 | Raju T S | Proteolysis resistant antibody preparations |
US20070104689A1 (en) * | 2005-09-27 | 2007-05-10 | Merck Patent Gmbh | Compositions and methods for treating tumors presenting survivin antigens |
WO2007067828A2 (fr) * | 2005-10-24 | 2007-06-14 | Centocor, Inc. | Mimétiques et polypeptides de glp-2, compositions, méthodes et utilisations |
ATE550353T1 (de) | 2005-12-30 | 2012-04-15 | Merck Patent Gmbh | Die bindung von mit il-6ralpha komplexiertem il-6 an gp130 verhindernde anti-il-6-antikörper |
ATE555125T1 (de) | 2005-12-30 | 2012-05-15 | Merck Patent Gmbh | Interleukin-12p40-varianten mit verbesserter stabilität |
ATE509954T1 (de) | 2005-12-30 | 2011-06-15 | Merck Patent Gmbh | Anti-cd19-antikörper mit reduzierter immunogenität |
US7625564B2 (en) | 2006-01-27 | 2009-12-01 | Novagen Holding Corporation | Recombinant human EPO-Fc fusion proteins with prolonged half-life and enhanced erythropoietic activity in vivo |
EP1991577A2 (fr) | 2006-01-31 | 2008-11-19 | Parkinson, John F. | Modulation de l'activite mdl-1 pour le traitement de maladies inflammatoires |
PL2008460T3 (pl) * | 2006-03-30 | 2017-10-31 | Lg Electronics Inc | Sposób i urządzenie do dekodowania/kodowania sygnału wideo |
DK2006381T3 (en) | 2006-03-31 | 2016-02-22 | Chugai Pharmaceutical Co Ltd | PROCEDURE FOR REGULATING ANTIBODIES BLOOD PHARMACOKINETICS |
DK2009101T3 (en) | 2006-03-31 | 2018-01-15 | Chugai Pharmaceutical Co Ltd | Antibody modification method for purification of a bispecific antibody |
KR101571027B1 (ko) | 2006-06-12 | 2015-11-23 | 이머전트 프로덕트 디벨롭먼트 시애틀, 엘엘씨 | 효과기 기능을 갖는 단일쇄 다가 결합 단백질 |
WO2008003473A2 (fr) * | 2006-07-06 | 2008-01-10 | Merck Patent Gmbh | Compositions et procédés destinés à améliorer l'efficacité de réponses immunitaires à médiation par il-2 |
US20100209385A1 (en) * | 2007-03-30 | 2010-08-19 | Mark Anthony Febbraio | Treatment of obesity |
BRPI0811857A2 (pt) * | 2007-05-14 | 2014-10-21 | Biogen Idec Inc | Regiões fc (scfc) de cadeia simples, polipeptídeos de aglutinação que as compreendem e métodos relacionados. |
JP5168538B2 (ja) * | 2007-05-24 | 2013-03-21 | アボットジャパン株式会社 | 抗体−抗体コンジュゲートと抗体測定系診断薬への応用 |
PL2185589T3 (pl) * | 2007-06-01 | 2016-09-30 | Środki wiążące receptor regionu stałego Fc immunoglobuliny | |
AU2013263716B2 (en) * | 2007-06-01 | 2016-01-07 | Gliknik Inc | Immunoglobulin constant region FC receptor binding agents |
US8222016B2 (en) | 2007-06-29 | 2012-07-17 | Daiichi Sankyo Company, Limited | Recombinant C-terminal α-amidating enzyme derivative |
US20090148447A1 (en) * | 2007-07-06 | 2009-06-11 | Trubion Pharmaceuticals, Inc. | Binding Peptides Having a C-terminally Disposed Specific Binding Domain |
BRPI0814465B1 (pt) * | 2007-07-26 | 2021-11-23 | Novagen Holding Corporation | Proteína de fusão, dímero, método para produzir uma proteína de fusão, linhagem de célula, usos de uma proteína de fusão e de uma composição farmacêutica e composição farmacêutica |
MX2010002683A (es) | 2007-09-14 | 2010-03-26 | Amgen Inc | Poblaciones de anticuerpos homogeneos. |
SG193868A1 (en) | 2007-09-26 | 2013-10-30 | Chugai Pharmaceutical Co Ltd | Modified antibody constant region |
HUE029635T2 (en) | 2007-09-26 | 2017-03-28 | Chugai Pharmaceutical Co Ltd | A method for modifying an isoelectric point of an antibody by amino acid substitution in CDR |
KR101643005B1 (ko) | 2007-12-05 | 2016-07-28 | 추가이 세이야쿠 가부시키가이샤 | 항nr10 항체 및 그의 이용 |
US8454960B2 (en) * | 2008-01-03 | 2013-06-04 | The Scripps Research Institute | Multispecific antibody targeting and multivalency through modular recognition domains |
US8557242B2 (en) * | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | ERBB2 antibodies comprising modular recognition domains |
GEP20156390B (en) * | 2008-01-03 | 2015-11-10 | Scripps Research Inst | Antibody targeting through a modular recognition domain |
US8574577B2 (en) * | 2008-01-03 | 2013-11-05 | The Scripps Research Institute | VEGF antibodies comprising modular recognition domains |
US8557243B2 (en) * | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | EFGR antibodies comprising modular recognition domains |
WO2009126944A1 (fr) | 2008-04-11 | 2009-10-15 | Trubion Pharmaceuticals, Inc. | Produits d’immunothérapie de cd37 et combinaison avec un produit chimiothérapique bifonctionnel de celui-ci |
TWI440469B (zh) | 2008-09-26 | 2014-06-11 | Chugai Pharmaceutical Co Ltd | Improved antibody molecules |
JP5717624B2 (ja) * | 2009-03-19 | 2015-05-13 | 中外製薬株式会社 | 抗体定常領域改変体 |
TWI682995B (zh) | 2009-03-19 | 2020-01-21 | 日商中外製藥股份有限公司 | 抗體恆定區域改變體 |
EP2421896A1 (fr) * | 2009-04-22 | 2012-02-29 | Merck Patent GmbH | Protéines de fusion à des anticorps avec des sites de liaison à fcrn modifiés |
MA33405B1 (fr) | 2009-05-15 | 2012-07-03 | Chugai Pharmaceutical Co Ltd | Anticorps anti-axl |
WO2011037158A1 (fr) | 2009-09-24 | 2011-03-31 | 中外製薬株式会社 | Régions constantes modifiées d'un anticorps |
WO2011059684A1 (fr) * | 2009-10-29 | 2011-05-19 | Centocor Ortho Biotech Inc. | Variantes de glycosylation des anticorps |
DK2496691T3 (en) * | 2009-11-02 | 2017-06-06 | Univ Washington | THERAPEUTIC NUCLEASE COMPOSITIONS AND PROCEDURES |
WO2011064758A2 (fr) * | 2009-11-30 | 2011-06-03 | Pfizer Limited | Protéine de fusion |
WO2011108714A1 (fr) | 2010-03-04 | 2011-09-09 | 中外製薬株式会社 | Variante de région constante d'anticorps |
CN101870735B (zh) * | 2010-06-02 | 2013-06-12 | 北京精益泰翔技术发展有限公司 | 一种新型高糖基化促红细胞生成素免疫融合蛋白 |
US20120100166A1 (en) | 2010-07-15 | 2012-04-26 | Zyngenia, Inc. | Ang-2 Binding Complexes and Uses Thereof |
PL2598533T3 (pl) | 2010-07-28 | 2019-07-31 | Gliknik Inc. | Białka fuzyjne naturalnych fragmentów białka ludzkiego do tworzenia uporządkowanych multimeryzowanych kompozycji Fc immunoglobulin |
KR101333958B1 (ko) | 2010-10-20 | 2013-11-27 | 주식회사 한독 | 인간 인터루킨-1 수용체 길항제-하이브리드 Fc 융합단백질 |
EP3144320B9 (fr) * | 2011-04-13 | 2018-08-22 | Bristol-Myers Squibb Company | Protéines de fusion fc comprenant de nouveaux lieurs et arrangements |
EP3449933A1 (fr) | 2011-04-29 | 2019-03-06 | University of Washington | Compositions à base de nucléase thérapeutique et procédés associés |
CA2837169C (fr) | 2011-05-24 | 2021-11-09 | Zyngenia, Inc. | Complexes multispecifiques contenant un peptide de liaison de l'angiopoietin-2 et utilisations connexes |
EP3626739A1 (fr) | 2011-06-24 | 2020-03-25 | Stephen D. Gillies | Protéines de fusion d'immunoglobuline à chaîne légère et leurs procédés d'utilisation |
EP2537933A1 (fr) | 2011-06-24 | 2012-12-26 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Immunocytokines basées sur le domaine IL-15 et IL-15Ralpha sushi |
CA2843158A1 (fr) * | 2011-08-26 | 2013-03-07 | Merrimack Pharmaceuticals, Inc. | Anticorps bispecifiques a fc en tandem |
CA2849765C (fr) * | 2011-09-26 | 2021-10-19 | Jn Biosciences Llc | Regions constantes hybrides |
US9382319B2 (en) | 2011-09-26 | 2016-07-05 | Jn Biosciences Llc | Hybrid constant regions |
AU2013211824B2 (en) * | 2012-01-27 | 2017-06-01 | Gliknik Inc. | Fusion proteins comprising IgG2 hinge domains |
WO2013156054A1 (fr) * | 2012-04-16 | 2013-10-24 | Universität Stuttgart | Domaine 2 de chaîne lourde d'igm et d'ige en tant que modules d'homodimérisation à liaison covalente pour la génération de protéines de fusion à double spécificité |
KR102177252B1 (ko) | 2012-04-23 | 2020-11-10 | 가부시키가이샤 에스 앤드 케이 바이오파마 | 락토페린 융합 단백질 및 그의 제조방법 |
EP2708556B1 (fr) | 2012-09-12 | 2018-11-07 | Samsung Electronics Co., Ltd | Composition pharmaceutique à utiliser dans une thérapie combinée pour la prévention ou le traitement des maladies induites par c-met ou le facteur d'angiogénèse |
AU2014227638A1 (en) | 2013-03-15 | 2015-09-17 | Merck Patent Gmbh | Tetravalent bispecific antibodies |
BR112015023752B1 (pt) | 2013-03-15 | 2023-11-14 | Zyngenia, Inc. | Domínio de reconhecimento modular (mrd), complexo compreendendo mrd e cetuximabe, usos do complexo para inibir a angiogênese e tratar câncer e composição farmacêutica compreendendo o dito complexo |
KR20150145260A (ko) | 2013-04-19 | 2015-12-29 | 싸이튠 파마 | 감소된 혈관 누출 증후근에 대한 사이토카인 유도체 치료 |
US20150038682A1 (en) * | 2013-08-02 | 2015-02-05 | Jn Biosciences Llc | Antibodies or fusion proteins multimerized via homomultimerizing peptide |
SI3702373T1 (sl) | 2013-09-13 | 2022-11-30 | Beigene Switzerland Gmbh | Protitelesa proti PD-1 in njihova uporaba kot terapevtiki in diagnostiki |
CA2925256C (fr) | 2013-09-27 | 2023-08-15 | Chugai Seiyaku Kabushiki Kaisha | Procede de production d'un heteromultimere polypeptidique |
DK3063275T3 (da) | 2013-10-31 | 2019-11-25 | Resolve Therapeutics Llc | Terapeutiske nuklease-albumin-fusioner og fremgangsmåder |
US9717715B2 (en) | 2013-11-15 | 2017-08-01 | Samsung Electronics Co., Ltd. | Method of combination therapy using an anti-C-Met antibody |
HUE054873T2 (hu) | 2014-02-10 | 2021-10-28 | Merck Patent Gmbh | Célzott TGF-béta-gátlás |
EP2915569A1 (fr) | 2014-03-03 | 2015-09-09 | Cytune Pharma | Procédé de purification de conjugués à base Il -15/IL-15Ralpha |
GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
EP3114143B1 (fr) | 2014-03-05 | 2020-07-08 | UCB Biopharma SRL | Protéines fc multimères |
KR20230155600A (ko) * | 2014-04-03 | 2023-11-10 | 아이쥐엠 바이오사이언스 인코포레이티드 | 변형된 j-사슬 |
SG10201808825XA (en) | 2014-04-10 | 2018-11-29 | Seattle Childrens Hospital Dba Seattle Childrens Res Inst | Defined composition gene modified t-cell products |
BR112016027845A2 (pt) * | 2014-05-29 | 2017-10-31 | Medimmune Llc | proteínas de fusão de ox40l e usos das mesmas |
KR102003754B1 (ko) | 2014-07-03 | 2019-07-25 | 베이진 엘티디 | Pd-l1 항체와 이를 이용한 치료 및 진단 |
US10428146B2 (en) | 2014-07-22 | 2019-10-01 | Cb Therapeutics, Inc. | Anti PD-1 antibodies |
CN118388646A (zh) | 2014-08-05 | 2024-07-26 | 中美冠科生物技术(太仓)有限公司 | 抗pd-l1抗体 |
EP3482766B1 (fr) | 2014-08-11 | 2020-05-20 | Delinia, Inc. | Variantes il-2 modifiées d'activation sélective de lymphocytes t régulateurs pour le traitement de maladies auto-immunes |
CN107250157B (zh) | 2014-11-21 | 2021-06-29 | 百时美施贵宝公司 | 包含修饰的重链恒定区的抗体 |
SG11201703192SA (en) | 2014-11-21 | 2017-05-30 | Bristol Myers Squibb Co | Antibodies against cd73 and uses thereof |
KR20160101702A (ko) * | 2015-02-17 | 2016-08-25 | 한미약품 주식회사 | 지속형 인슐린 또는 이의 아날로그 결합체 |
CN107249637A (zh) | 2015-02-27 | 2017-10-13 | 中外制药株式会社 | 用于治疗il‑6相关疾病的组合物 |
EP3279216A4 (fr) | 2015-04-01 | 2019-06-19 | Chugai Seiyaku Kabushiki Kaisha | Procédé pour la production d'un hétéro-oligomère polypeptidique |
BR112017022658A2 (pt) * | 2015-04-22 | 2018-07-17 | Alivegen Usa Inc | proteína isolada, molécula de ácido nucleico isolada, vetor recombinante, célula hospedeira, método de produção de uma proteína actriib híbrida, composição farmacêutica, métodos de tratamentos de distúrbios relacionados à miostatina ou relacionados à ativina a, de doença de desgaste dos músculos, de doença cardiovascular, de distúrbios metabólicos, de células cancerígenas, de doença renal, de doença inflamatória/autoimune, de uma doença de fibrose, de anemia, da dor, da condição de envelhecimento, de distúrbios ósseos, de um desgaste dos músculos ou distúrbio metabólico ou fibrótico ou inflamatório ou relacionado à ativina em indivíduos, e, método de indução do crescimento das células-tronco para o reparo de tecido ou regeneração do órgão em um indivíduo |
US10280449B2 (en) * | 2015-06-29 | 2019-05-07 | The Regents Of The University Of California | Methods of producing nucleic acid libraries and compositions and kits for practicing same |
US11458167B2 (en) | 2015-08-07 | 2022-10-04 | Seattle Children's Hospital | Bispecific CAR T-cells for solid tumor targeting |
SG10202002577XA (en) | 2015-09-21 | 2020-04-29 | Aptevo Res & Development Llc | Cd3 binding polypeptides |
WO2017059387A1 (fr) | 2015-09-30 | 2017-04-06 | Igm Biosciences, Inc. | Molécules de liaison à chaîne j modifiée |
AU2016329197B2 (en) | 2015-09-30 | 2021-01-21 | Igm Biosciences, Inc. | Binding molecules with modified J-chain |
US20180271998A1 (en) | 2015-12-04 | 2018-09-27 | Merrimack Pharmaceuticals, Inc. | Disulfide-stabilized fabs |
EP3398965A4 (fr) | 2015-12-28 | 2019-09-18 | Chugai Seiyaku Kabushiki Kaisha | Procédé pour favoriser l'efficacité de purification d'un polypeptide contenant une région fc |
US20170204154A1 (en) | 2016-01-20 | 2017-07-20 | Delinia, Inc. | Molecules that selectively activate regulatory t cells for the treatment of autoimmune diseases |
US11034775B2 (en) | 2016-06-07 | 2021-06-15 | Gliknik Inc. | Cysteine-optimized stradomers |
US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
HRP20240603T1 (hr) | 2016-07-01 | 2024-07-19 | Resolve Therapeutics, Llc | Optimizirane fuzije binukleaze i postupci njihove upotrebe |
NZ749997A (en) | 2016-07-05 | 2022-11-25 | Beigene Ltd | Combination of a pd-l antagonist and a raf inhibitor for treating cancer |
RU2019106663A (ru) | 2016-08-12 | 2020-09-14 | Мерк Патент Гмбх | Комбинированная терапия рака |
ES2971881T3 (es) | 2016-08-19 | 2024-06-10 | Beigene Switzerland Gmbh | Combinación de zanubrutinib con un anticuerpo anti-cd20 o anti-pd-1 para su uso en el tratamiento del cáncer |
SG10201607778XA (en) | 2016-09-16 | 2018-04-27 | Chugai Pharmaceutical Co Ltd | Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use |
WO2018079702A1 (fr) | 2016-10-28 | 2018-05-03 | 株式会社Nrlファーマ | Protéine de fusion lactoferrine/albumine et son procédé de production |
EP3534947A1 (fr) | 2016-11-03 | 2019-09-11 | Kymab Limited | Anticorps, combinaisons comprenant des anticorps, biomarqueurs, utilisations et procédés |
CN110167957A (zh) | 2016-11-08 | 2019-08-23 | 德里尼亚公司 | 用于治疗自身免疫疾病的il-2变体 |
US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
WO2018107082A1 (fr) | 2016-12-09 | 2018-06-14 | Gliknik Inc. | Méthodes de traitement de troubles inflammatoires avec des composés fc multivalents |
AU2017371179B2 (en) | 2016-12-09 | 2022-07-14 | Gliknik Inc. | Manufacturing optimization of GL-2045, a multimerizing stradomer |
US11408005B2 (en) | 2016-12-12 | 2022-08-09 | Seattle Children's Hospital | Chimeric transcription factor variants with augmented sensitivity to drug ligand induction of transgene expression in mammalian cells |
EP3573989A4 (fr) | 2017-01-25 | 2020-11-18 | Beigene, Ltd. | Formes cristallines de (s) -7- (1- (but-2-ynoyl) pipéridin-4-yl) -2- (4-phénoxyphényl) -4, 5, 6, 7-tétrahy dropyrazolo [1, 5-a]pyrimidine-3-carboxamide, préparation et utilisations associées |
US11851486B2 (en) | 2017-05-02 | 2023-12-26 | National Center Of Neurology And Psychiatry | Method for predicting and evaluating therapeutic effect in diseases related to IL-6 and neutrophils |
WO2018215936A1 (fr) | 2017-05-24 | 2018-11-29 | Novartis Ag | Protéines greffées d'anticorps-cytokine et procédés d'utilisation dans le traitement du cancer |
TW201906866A (zh) | 2017-06-26 | 2019-02-16 | 英屬開曼群島商百濟神州有限公司 | 酸性鞘磷脂酶缺乏症患者中異常骨狀況的治療 |
IL271837B2 (en) * | 2017-07-07 | 2024-01-01 | Hanmi Pharm Ind Co Ltd | A new medical fusion protein with an enzyme and its uses |
CN111801334B (zh) | 2017-11-29 | 2023-06-09 | 百济神州瑞士有限责任公司 | 使用包含btk抑制剂的组合治疗惰性或侵袭性b-细胞淋巴瘤 |
MX2020006322A (es) | 2017-12-19 | 2020-09-18 | Xencor Inc | Proteinas de fusion il-2 fc modificadas. |
CA3093468A1 (fr) | 2018-03-09 | 2019-09-12 | Agenus Inc. | Anticorps anti-cd73 et leurs procedes d'utilisation |
CA3093729A1 (fr) | 2018-03-15 | 2019-09-19 | Chugai Seiyaku Kabushiki Kaisha | Anticorps diriges contre le virus de la dengue presentant une reactivite croisee au virus zika et procedes d'utilisation |
JP2021535746A (ja) * | 2018-09-05 | 2021-12-23 | エルジー・ケム・リミテッド | O−グリコシル化可能なポリペプチド領域を含む融合ポリペプチド |
US11358999B2 (en) | 2018-10-03 | 2022-06-14 | Xencor, Inc. | IL-12 heterodimeric Fc-fusion proteins |
CN113301961A (zh) | 2018-11-01 | 2021-08-24 | 默克专利有限公司 | 给予抗tim-3抗体的方法 |
WO2020093023A1 (fr) | 2018-11-01 | 2020-05-07 | Merck Patent Gmbh | Anticorps anti-tim-3 |
WO2020127369A1 (fr) | 2018-12-21 | 2020-06-25 | Ose Immunotherapeutics | Molécule bifonctionnelle dirigée contre le pd-1 humain |
EP3898676A1 (fr) | 2018-12-21 | 2021-10-27 | OSE Immunotherapeutics | Molécule bifonctionnelle anti-pd-1/sirpa |
BR112021012037A2 (pt) | 2018-12-21 | 2021-11-03 | Ose Immunotherapeutics | Molécula anti-pd-1/il-7 bifuncional |
CA3122526C (fr) | 2018-12-21 | 2023-01-03 | Ose Immunotherapeutics | Anticorps anti-pd-1 anti-humain humanise |
WO2020165374A1 (fr) | 2019-02-14 | 2020-08-20 | Ose Immunotherapeutics | Molécule bifonctionnelle comprenant il-15ra |
US12006345B2 (en) | 2019-02-21 | 2024-06-11 | Xencor, Inc. | Untargeted and targeted IL-10 Fc-fusion proteins |
AU2020279112A1 (en) | 2019-05-17 | 2021-12-02 | Xencor, Inc. | IL-7-Fc-fusion proteins |
CN115916233A (zh) | 2019-10-03 | 2023-04-04 | Xencor股份有限公司 | 靶向IL-12异源二聚体Fc融合蛋白 |
BR112023026352A2 (pt) * | 2021-06-17 | 2024-03-05 | Fapon Biotech Inc | Imunoglobulina quimérica |
US20230190799A1 (en) * | 2021-07-21 | 2023-06-22 | City Of Hope | Chimeric antigen receptor t cells targeting cea and anti-cea-il2 immunocytokines for cancer therapy |
WO2023076927A1 (fr) * | 2021-10-27 | 2023-05-04 | Anwita Biosciences, Inc. | Protéines de fusion d'il-2, compositions pharmaceutiques et applications thérapeutiques |
CN115028726B (zh) * | 2022-03-31 | 2024-01-09 | 浙江特瑞思药业股份有限公司 | 一种抗pd-1纳米抗体及其应用 |
Family Cites Families (190)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US193570A (en) * | 1877-07-24 | Improvement in washing-boards | ||
US192222A (en) * | 1877-06-19 | Improvement in watches | ||
US44423A (en) * | 1864-09-27 | Improved screw for music-stools | ||
US53539A (en) * | 1866-03-27 | Improvement in revolving fire-arms | ||
US147311A (en) * | 1874-02-10 | Improvement in electric telegraphs | ||
US12789A (en) * | 1855-05-01 | Office | ||
US105294A (en) * | 1870-07-12 | Erasmus w | ||
US166877A (en) * | 1875-08-17 | Improvement in electric lights | ||
US49227A (en) * | 1865-08-08 | Improvement in construction of railway trains and cars | ||
US3529A (en) * | 1844-04-10 | yvolfe | ||
US81664A (en) * | 1868-09-01 | Island | ||
US4196265A (en) | 1977-06-15 | 1980-04-01 | The Wistar Institute | Method of producing antibodies |
US4522811A (en) * | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
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 |
US4703008A (en) | 1983-12-13 | 1987-10-27 | Kiren-Amgen, Inc. | DNA sequences encoding erythropoietin |
NZ210501A (en) | 1983-12-13 | 1991-08-27 | Kirin Amgen Inc | Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence |
US5082658A (en) * | 1984-01-16 | 1992-01-21 | Genentech, Inc. | Gamma interferon-interleukin-2 synergism |
EP0158198A1 (fr) | 1984-03-29 | 1985-10-16 | Takeda Chemical Industries, Ltd. | ADN et son utilisation |
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 |
US4667016A (en) * | 1985-06-20 | 1987-05-19 | Kirin-Amgen, Inc. | Erythropoietin purification |
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 (fr) | 1986-03-14 | 1988-03-09 | Toray Industries, Inc. | Interféron conjugué et sa préparation à partir d'un gène recombinant |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
DK173067B1 (da) | 1986-06-27 | 1999-12-13 | Univ Washington | Humant erythropoietin-gen, fremgangsmåde til ekspression deraf i transficerede cellelinier, de transficerede cellelinier sa |
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 |
JP3101690B2 (ja) | 1987-03-18 | 2000-10-23 | エス・ビィ・2・インコーポレイテッド | 変性抗体の、または変性抗体に関する改良 |
AU612370B2 (en) | 1987-05-21 | 1991-07-11 | Micromet Ag | Targeted multifunctional proteins |
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 |
ES2073394T3 (es) | 1987-06-10 | 1995-08-16 | Dana Farber Cancer Inst Inc | Constructos de anticuerpos bifuncionales y su utilizacion para destruir selectivamente las poblaciones celulares. |
US5064646A (en) | 1988-08-02 | 1991-11-12 | The University Of Maryland | Novel infectious bursal disease virus |
ES2054753T3 (es) | 1987-09-02 | 1994-08-16 | Ciba Geigy Ag | Conjugados de citoquinas con inmunoglobulinas. |
US5677425A (en) * | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
GB8720833D0 (en) * | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
CA1338518C (fr) | 1987-09-23 | 1996-08-13 | Joyce M. Zarling | Heteroconjugues d'anticorps pour tuer les cellules infectees par le vih |
NZ226414A (en) | 1987-10-02 | 1992-07-28 | Genentech Inc | Cd4 peptide adhesion variants and their preparation and use |
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 |
WO1989006692A1 (fr) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Procede de traitement de cellules tumorales par inhibition de la fonction receptrice du facteur de croissance |
CA1341588C (fr) | 1988-01-26 | 2009-01-06 | Michel Revel | Ifn-beta2/i1-6, humain, sa purification et ses utilisations |
US5120525A (en) | 1988-03-29 | 1992-06-09 | Immunomedics, Inc. | Radiolabeled antibody cytotoxic therapy of cancer |
US4975369A (en) | 1988-04-21 | 1990-12-04 | Eli Lilly And Company | Recombinant and chimeric KS1/4 antibodies directed against a human adenocarcinoma antigen |
IT1217724B (it) | 1988-05-26 | 1990-03-30 | Ist Naz Ric Sul Cancro | Anticorpo monoclonale specifico per una sequenza di fibronettina espressa in cellule trasformate ibridoma secernente tale anticorpo e impiego dell'anticorpo monoclonale per la diagnosi di tumori |
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 |
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 |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
IE63847B1 (en) | 1989-05-05 | 1995-06-14 | Res Dev Foundation | A novel antibody delivery system for biological response modifiers |
US6291158B1 (en) | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for tapping the immunological repertoire |
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 |
EP0406857B1 (fr) | 1989-07-07 | 1995-05-24 | Takeda Chemical Industries, Ltd. | Protéines et leur production |
US5073627A (en) | 1989-08-22 | 1991-12-17 | Immunex Corporation | Fusion proteins comprising GM-CSF and IL-3 |
ATE228566T1 (de) * | 1989-09-20 | 2002-12-15 | Abbott Lab | Verfahren zur herstellung von fusionsproteinen |
US5856298A (en) | 1989-10-13 | 1999-01-05 | Amgen Inc. | Erythropoietin isoforms |
KR100263845B1 (ko) | 1989-10-13 | 2000-08-16 | 스튜어트 엘.왓트 | 에리트로포이에틴 동형체와 그의 제조방법 및 그를 포함하는제약학적 조성물 |
DK0790255T3 (da) | 1989-12-22 | 2007-11-26 | Hoffmann La Roche | Monoklonale antistoffer som er rettet mod den cytotoksiske lymfocytmodningsfaktor |
US5314995A (en) | 1990-01-22 | 1994-05-24 | Oncogen | Therapeutic interleukin-2-antibody based fusion proteins |
EP0517754A1 (fr) * | 1990-03-02 | 1992-12-16 | Repligen Corporation | Constructions d'anticorps ayant une affinite de liaison amelioree |
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 |
US5770429A (en) * | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5650150A (en) | 1990-11-09 | 1997-07-22 | Gillies; Stephen D. | Recombinant antibody cytokine fusion proteins |
US5709859A (en) | 1991-01-24 | 1998-01-20 | Bristol-Myers Squibb Company | Mixed specificity fusion proteins |
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 |
DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
DE69227693T2 (de) | 1991-08-30 | 1999-07-22 | Fred Hutchinson Cancer Research Center, Seattle, Wash. | Hybride cytokine |
US20020037558A1 (en) | 1991-10-23 | 2002-03-28 | Kin-Ming Lo | E.coli produced immunoglobulin constructs |
US5277375A (en) * | 1991-12-04 | 1994-01-11 | The Procter & Gamble Company | Spindle for use with compressed core wound paper products |
US6627615B1 (en) | 1991-12-17 | 2003-09-30 | The Regents Of The University Of California | Methods and compositions for in vivo gene therapy |
CA2133409C (fr) | 1992-04-01 | 2011-05-24 | Ralph M. Steinman | Methode de proliferation in vitro de precurseurs de cellules dendritiques et facon d'utiliser lesdits precurseurs pour produire des immunogenes |
DK0615451T3 (da) * | 1992-05-26 | 2006-04-24 | Immunex Corp | Hidtil ukendt cytokin der binder til CD30 |
EP0646178A1 (fr) | 1992-06-04 | 1995-04-05 | The Regents Of The University Of California | Cassette d'expression avec des regious regulatrices fonctionnelles chez le mammifere hote |
US5614184A (en) * | 1992-07-28 | 1997-03-25 | New England Deaconess Hospital | Recombinant human erythropoietin mutants and therapeutic methods employing them |
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 |
CA2126967A1 (fr) | 1992-11-04 | 1994-05-11 | Anna M. Wu | Nouvelle construction d'anticorps |
EP1757694A3 (fr) | 1992-11-05 | 2008-02-27 | Sloan Kettering Institute For Cancer Research | Antigene de membrane spécifique à la prostate |
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 |
US6096331A (en) | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
CN1079830C (zh) * | 1993-04-20 | 2002-02-27 | 索利斯治疗学公司 | 对受胞内传染原感染的个体进行治疗的方法和物质 |
US5759551A (en) | 1993-04-27 | 1998-06-02 | United Biomedical, Inc. | Immunogenic LHRH peptide constructs and synthetic universal immune stimulators for vaccines |
HUT73876A (en) | 1993-04-29 | 1996-10-28 | Abbott Lab | Erythropoietin analog compositions and methods |
US5554512A (en) | 1993-05-24 | 1996-09-10 | Immunex Corporation | Ligands for flt3 receptors |
CA2125763C (fr) | 1993-07-02 | 2007-08-28 | Maurice Kent Gately | Homodimere p40 de l'interleukine-12 |
US5609876A (en) * | 1993-08-09 | 1997-03-11 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Peptide vaccines and associated methods for protection against feline leukemia virus |
IL192290A0 (en) | 1993-08-17 | 2008-12-29 | Kirin Amgen Inc | Erythropoietin analogs |
US5639725A (en) | 1994-04-26 | 1997-06-17 | Children's Hospital Medical Center Corp. | Angiostatin protein |
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 |
CU22615A1 (es) * | 1994-06-30 | 2000-02-10 | Centro Inmunologia Molecular | Procedimiento de obtención de anticuerpos monoclonales murinos menos inmunogénicos. anticuerpos monoclonales obtenidos |
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 |
US5888773A (en) * | 1994-08-17 | 1999-03-30 | The United States Of America As Represented By The Department Of Health And Human Services | Method of producing single-chain Fv molecules |
US5541087A (en) | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
EP0706799B1 (fr) | 1994-09-16 | 2001-11-14 | MERCK PATENT GmbH | Immunoconjugués |
JP3429578B2 (ja) * | 1994-10-31 | 2003-07-22 | オリンパス光学工業株式会社 | 小型リアフォーカスズームレンズ |
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 |
US5552524A (en) | 1995-01-31 | 1996-09-03 | Eli Lilly And Company | Anti-obesity proteins |
US5691309A (en) | 1995-01-31 | 1997-11-25 | 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 |
JP3342873B2 (ja) | 1995-03-10 | 2002-11-11 | ジェネンテク・インコーポレイテッド | gas6による受容体活性化 |
US5719266A (en) | 1995-03-17 | 1998-02-17 | Eli Lilly And Company | Anti-obesity proteins |
US6281010B1 (en) * | 1995-06-05 | 2001-08-28 | The Trustees Of The University Of Pennsylvania | Adenovirus gene therapy vehicle and cell line |
EP0836479A2 (fr) | 1995-06-30 | 1998-04-22 | Eli Lilly And Company | Procedes pour le traitement du diabete |
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 |
US6620413B1 (en) * | 1995-12-27 | 2003-09-16 | Genentech, Inc. | OB protein-polymer chimeras |
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 |
CN1136197C (zh) | 1996-05-30 | 2004-01-28 | 霍夫曼-拉罗奇有限公司 | 新的哒嗪酮衍生物 |
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 |
DE69808609T2 (de) | 1997-04-11 | 2003-06-12 | G.D. Searle & Co., Chicago | Antagonistische anti-avb3 integrin antikörper |
AU8182298A (en) * | 1997-07-10 | 1999-02-08 | Beth Israel Deaconess Medical Center | Recombinant erythropoietin / immunoglobulin fusion proteins |
DE69824039T2 (de) * | 1997-12-08 | 2005-08-18 | Lexigen Pharmaceuticals Corp., Lexington | Heterodimäre fusionsproteine zur verwendung für gezielte immuntherapie und allgemeine immunerregung |
US20030105294A1 (en) | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
HUP0100813A3 (en) * | 1998-02-25 | 2003-08-28 | Lexigen Pharmaceuticals Corp L | Enhancing the circulating half-life of antibody-based fusion proteins |
WO1999052562A2 (fr) | 1998-04-15 | 1999-10-21 | Lexigen Pharmaceuticals Corp. | Co-administration d'un inhibiteur de l'angiogenese pour renforcer la reponse immunitaire a mediation de proteine de fusion d'une cytokine d'anticorps |
CN1305387A (zh) * | 1998-04-17 | 2001-07-25 | 利思进药品公司 | 通过共同给予前列腺素抑制剂增强抗体-细胞因子融合蛋白介导的免疫应答 |
US6284536B1 (en) * | 1998-04-20 | 2001-09-04 | The Regents Of The University Of California | Modified immunoglobin molecules and methods for use thereof |
AU751823B2 (en) | 1998-05-14 | 2002-08-29 | Merck Patent Gmbh | Fused protein |
US6620382B1 (en) | 1998-05-22 | 2003-09-16 | Biopheresis Technologies, Llc. | Method and compositions for treatment of cancers |
JP2002522063A (ja) * | 1998-08-17 | 2002-07-23 | アブジェニックス インコーポレイテッド | 増加した血清半減期を有する改変された分子の生成 |
CN101386651A (zh) | 1998-08-25 | 2009-03-18 | 默克专利股份公司 | 表达以及分泌制管张素和内皮抑制素的免疫融合物 |
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 |
KR100922809B1 (ko) | 1999-05-06 | 2009-10-21 | 웨이크 포리스트 유니버시티 | 면역 반응을 유발하는 항원을 동정하기 위한 조성물과 방법 |
US6348192B1 (en) | 1999-05-11 | 2002-02-19 | Bayer Corporation | Interleukin-2 mutein expressed from mammalian cells |
JP2003530070A (ja) * | 1999-05-19 | 2003-10-14 | レキシジェン ファーマシューティカルズ コーポレイション | Fc融合タンパク質としてのインターフェロン−αタンパク質の発現および搬出 |
JO2291B1 (en) | 1999-07-02 | 2005-09-12 | اف . هوفمان لاروش ايه جي | Erythropoietin derivatives |
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 |
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 |
SK782002A3 (en) | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
DE60037896D1 (de) * | 1999-07-29 | 2008-03-13 | Medarex Inc | Menschliche antikörper gegen her2/neu |
US6617135B1 (en) | 1999-08-09 | 2003-09-09 | Emd Lexigen Research Center Corp. | Multiple cytokine protein complexes |
AU2154401A (en) * | 1999-11-12 | 2001-05-30 | Merck Patent Gmbh | Erythropoietin forms with improved properties |
US20050202538A1 (en) | 1999-11-12 | 2005-09-15 | Merck Patent Gmbh | Fc-erythropoietin fusion protein with improved pharmacokinetics |
WO2001058957A2 (fr) * | 2000-02-11 | 2001-08-16 | Lexigen Pharmaceuticals Corp. | Amelioration de la demi-vie circulante de proteines de fusion a base d'anticorps |
ATE333900T1 (de) * | 2000-02-24 | 2006-08-15 | Philogen Spa | Zusamensetzungen und verfahren zur behandlung von angiogenese in pathologischen schädigungen |
US6586398B1 (en) | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
WO2001088117A2 (fr) | 2000-05-12 | 2001-11-22 | Neose Technologies, Inc. | Modification in vitro de motifs de glycosylation de glycopeptides recombines |
MXPA02012734A (es) | 2000-06-29 | 2003-04-25 | Merck Patent Gmbh | Mejoramiento de las respuestas inmunes mediadas por la proteina de fusion anticuerpo-citocina, mediante tratamiento combinado con agentes mejoradores de la captacion de inmunocitocina. |
US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
US20040043457A1 (en) * | 2001-01-18 | 2004-03-04 | Silke Schumacher | Bifunctional fusion proteins with glucocerebrosidase activity |
WO2002069232A2 (fr) | 2001-02-19 | 2002-09-06 | Merck Patent Gmbh | Procede d'identification d'epitopes de lymphocytes t et utilisation dans la preparation de molecules a immunogenicite reduite |
AU2002233340B2 (en) * | 2001-02-19 | 2008-05-22 | Merck Patent Gmbh | Artificial fusion proteins with reduced immunogenicity |
MXPA03008031A (es) | 2001-03-07 | 2003-12-04 | Merck Patent Gmbh | Tecnologia de expresion para proteinas que contienen porcion de anticuerpo isotipo hibrida. |
US6992174B2 (en) * | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
CN100503639C (zh) | 2001-05-03 | 2009-06-24 | 默克专利有限公司 | 重组肿瘤特异性抗体及其应用 |
WO2003048334A2 (fr) * | 2001-12-04 | 2003-06-12 | Merck Patent Gmbh | Immunocytokines a selectivite modulee |
ATE471946T1 (de) * | 2002-12-17 | 2010-07-15 | Merck Patent Gmbh | Humanisierter antikörper (h14.18) des maus antikörpers 14.18, der gd2 bindet und seine fusion mit il-2 |
US20050069521A1 (en) * | 2003-08-28 | 2005-03-31 | Emd Lexigen Research Center Corp. | Enhancing the circulating half-life of interleukin-2 proteins |
JP2008502317A (ja) * | 2003-12-30 | 2008-01-31 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | Il−7融合タンパク質 |
WO2005063808A1 (fr) | 2003-12-31 | 2005-07-14 | Merck Patent Gmbh | Proteine hybride fc-erythropoietine a pharmacocinetique amelioree |
AU2005206277B2 (en) | 2004-01-22 | 2011-06-23 | Merck Patent Gmbh | Anti-cancer antibodies with reduced complement fixation |
US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
ES2342964T3 (es) * | 2004-12-09 | 2010-07-20 | Merck Patent Gmbh | Variantes de la interleucina-7 con inmunogenicidad reducida. |
US20070104689A1 (en) * | 2005-09-27 | 2007-05-10 | Merck Patent Gmbh | Compositions and methods for treating tumors presenting survivin antigens |
ATE509954T1 (de) | 2005-12-30 | 2011-06-15 | Merck Patent Gmbh | Anti-cd19-antikörper mit reduzierter immunogenität |
ATE555125T1 (de) | 2005-12-30 | 2012-05-15 | Merck Patent Gmbh | Interleukin-12p40-varianten mit verbesserter stabilität |
ATE550353T1 (de) | 2005-12-30 | 2012-04-15 | Merck Patent Gmbh | Die bindung von mit il-6ralpha komplexiertem il-6 an gp130 verhindernde anti-il-6-antikörper |
JP5474531B2 (ja) | 2006-03-24 | 2014-04-16 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 操作されたヘテロ二量体タンパク質ドメイン |
WO2008003473A2 (fr) * | 2006-07-06 | 2008-01-10 | Merck Patent Gmbh | Compositions et procédés destinés à améliorer l'efficacité de réponses immunitaires à médiation par il-2 |
-
2002
- 2002-03-07 MX MXPA03008031A patent/MXPA03008031A/es active IP Right Grant
- 2002-03-07 KR KR1020087032161A patent/KR20090010127A/ko not_active Application Discontinuation
- 2002-03-07 AU AU2002248571A patent/AU2002248571B2/en not_active Ceased
- 2002-03-07 RU RU2003129528/13A patent/RU2003129528A/ru unknown
- 2002-03-07 WO PCT/US2002/007011 patent/WO2002072605A2/fr active Application Filing
- 2002-03-07 KR KR1020037011719A patent/KR100900176B1/ko not_active IP Right Cessation
- 2002-03-07 JP JP2002571518A patent/JP4234438B2/ja not_active Expired - Fee Related
- 2002-03-07 US US10/093,958 patent/US7148321B2/en not_active Expired - Lifetime
- 2002-03-07 PL PL366981A patent/PL206701B1/pl unknown
- 2002-03-07 CN CNB028060644A patent/CN1330664C/zh not_active Expired - Fee Related
- 2002-03-07 CA CA2440221A patent/CA2440221C/fr not_active Expired - Fee Related
- 2002-03-07 PT PT02717581T patent/PT1366067E/pt unknown
- 2002-03-07 ES ES02717581T patent/ES2393733T3/es not_active Expired - Lifetime
- 2002-03-07 HU HU0303428A patent/HUP0303428A2/hu unknown
- 2002-03-07 EP EP02717581A patent/EP1366067B1/fr not_active Expired - Lifetime
- 2002-03-07 BR BR0207854-6A patent/BR0207854A/pt not_active IP Right Cessation
- 2002-03-07 DK DK02717581.9T patent/DK1366067T3/da active
-
2003
- 2003-10-06 ZA ZA200307792A patent/ZA200307792B/en unknown
-
2006
- 2006-07-19 US US11/489,653 patent/US8066994B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CA2440221C (fr) | 2013-02-05 |
CN1509293A (zh) | 2004-06-30 |
RU2003129528A (ru) | 2005-04-10 |
HUP0303428A2 (hu) | 2004-01-28 |
DK1366067T3 (da) | 2012-10-22 |
US20060263856A1 (en) | 2006-11-23 |
KR100900176B1 (ko) | 2009-06-02 |
MXPA03008031A (es) | 2003-12-04 |
AU2002248571B2 (en) | 2007-01-18 |
EP1366067A2 (fr) | 2003-12-03 |
KR20030092015A (ko) | 2003-12-03 |
EP1366067B1 (fr) | 2012-09-26 |
PL206701B1 (pl) | 2010-09-30 |
CA2440221A1 (fr) | 2002-09-19 |
WO2002072605A2 (fr) | 2002-09-19 |
PL366981A1 (en) | 2005-02-07 |
BR0207854A (pt) | 2004-08-24 |
ES2393733T3 (es) | 2012-12-27 |
PT1366067E (pt) | 2012-11-29 |
CN1330664C (zh) | 2007-08-08 |
US7148321B2 (en) | 2006-12-12 |
KR20090010127A (ko) | 2009-01-28 |
US8066994B2 (en) | 2011-11-29 |
JP2004525630A (ja) | 2004-08-26 |
US20030044423A1 (en) | 2003-03-06 |
EP1366067A4 (fr) | 2005-07-20 |
JP4234438B2 (ja) | 2009-03-04 |
WO2002072605A3 (fr) | 2002-11-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2002248571B2 (en) | Expression technology for proteins containing a hybrid isotype antibody moiety | |
AU2002248571A1 (en) | Expression technology for proteins containing a hybrid isotype antibody moiety | |
JP5572665B2 (ja) | 抗体ベース融合タンパク質の循環系内半減期の増強 | |
AU758240B2 (en) | Enhancing the circulating half-life of antibody-based fusion proteins | |
CA2919076C (fr) | Stabilisation de polypeptides contenant une fc | |
CA2572015C (fr) | Proteines de fusion fc-interferon-beta | |
JP2018162253A (ja) | 遺伝子操作された免疫グロブリン重鎖−軽鎖対およびその使用 | |
US20060194952A1 (en) | Enhancing the circulating half-life of antibody-based fusion proteins | |
US8637637B2 (en) | Fc fusion proteins of human growth hormone | |
CA2759333A1 (fr) | Proteines de fusion a des anticorps avec des sites de liaison a fcrn modifies | |
EP2951284B1 (fr) | Transformé de levure recombinée et procédé de préparation de fragment fc d'immunoglobuline faisant appel à celui-ci | |
AU2001243148B2 (en) | Enhancing the circulating half-life of antibody-based fusion proteins | |
JP2024539432A (ja) | インターロイキン15を有効成分とする融合タンパク質構築物およびその使用 | |
AU2001243148A1 (en) | Enhancing the circulating half-life of antibody-based fusion proteins | |
MXPA00008312A (es) | Metodos para mejorar la vida media en circulacion de proteinas de fusion a base de anticuerpo |