WO2000067788A2 - Use of soluble costimulatory molecules to enhance immune responses - Google Patents
Use of soluble costimulatory molecules to enhance immune responses Download PDFInfo
- Publication number
- WO2000067788A2 WO2000067788A2 PCT/US2000/012435 US0012435W WO0067788A2 WO 2000067788 A2 WO2000067788 A2 WO 2000067788A2 US 0012435 W US0012435 W US 0012435W WO 0067788 A2 WO0067788 A2 WO 0067788A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antigen
- molecule
- cells
- peptide
- cell
- Prior art date
Links
- 230000000139 costimulatory effect Effects 0.000 title claims abstract description 84
- 230000028993 immune response Effects 0.000 title claims abstract description 56
- 239000000427 antigen Substances 0.000 claims abstract description 107
- 108091007433 antigens Proteins 0.000 claims abstract description 107
- 102000036639 antigens Human genes 0.000 claims abstract description 107
- 238000000034 method Methods 0.000 claims abstract description 95
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 49
- 230000002708 enhancing effect Effects 0.000 claims abstract description 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 278
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 158
- 229920001184 polypeptide Polymers 0.000 claims description 100
- 206010028980 Neoplasm Diseases 0.000 claims description 89
- 108090000623 proteins and genes Proteins 0.000 claims description 64
- 102000004169 proteins and genes Human genes 0.000 claims description 53
- 235000018102 proteins Nutrition 0.000 claims description 52
- 239000000203 mixture Substances 0.000 claims description 37
- 239000002671 adjuvant Substances 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 230000027455 binding Effects 0.000 claims description 19
- 108060003951 Immunoglobulin Proteins 0.000 claims description 16
- 102000018358 immunoglobulin Human genes 0.000 claims description 16
- 230000005867 T cell response Effects 0.000 claims description 15
- 239000012634 fragment Substances 0.000 claims description 15
- 201000011510 cancer Diseases 0.000 claims description 10
- 230000003612 virological effect Effects 0.000 claims description 10
- 230000024932 T cell mediated immunity Effects 0.000 claims description 7
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- 230000028996 humoral immune response Effects 0.000 claims description 5
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 108010087819 Fc receptors Proteins 0.000 claims description 4
- 102000009109 Fc receptors Human genes 0.000 claims description 4
- 206010039491 Sarcoma Diseases 0.000 claims description 4
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 201000001531 bladder carcinoma Diseases 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 4
- 208000010570 urinary bladder carcinoma Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 201000006512 mast cell neoplasm Diseases 0.000 claims description 3
- 208000006971 mastocytoma Diseases 0.000 claims description 3
- 244000045947 parasite Species 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 208000015347 renal cell adenocarcinoma Diseases 0.000 claims description 2
- 238000002649 immunization Methods 0.000 abstract description 65
- 230000003053 immunization Effects 0.000 abstract description 63
- 102000005738 B7 Antigens Human genes 0.000 abstract description 32
- 108010045634 B7 Antigens Proteins 0.000 abstract description 30
- 230000001225 therapeutic effect Effects 0.000 abstract description 24
- 230000000069 prophylactic effect Effects 0.000 abstract description 7
- 239000012678 infectious agent Substances 0.000 abstract description 3
- 241000699670 Mus sp. Species 0.000 description 104
- 210000004027 cell Anatomy 0.000 description 100
- 230000004044 response Effects 0.000 description 85
- 210000001744 T-lymphocyte Anatomy 0.000 description 56
- 230000000694 effects Effects 0.000 description 43
- 108020004414 DNA Proteins 0.000 description 32
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 28
- 102000004127 Cytokines Human genes 0.000 description 27
- 108090000695 Cytokines Proteins 0.000 description 27
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 27
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 27
- 235000001014 amino acid Nutrition 0.000 description 27
- 238000011282 treatment Methods 0.000 description 27
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 26
- 125000003275 alpha amino acid group Chemical group 0.000 description 26
- 241000700605 Viruses Species 0.000 description 25
- 150000001413 amino acids Chemical class 0.000 description 24
- 238000002474 experimental method Methods 0.000 description 23
- 241000699666 Mus <mouse, genus> Species 0.000 description 22
- 230000009089 cytolysis Effects 0.000 description 22
- 229940037003 alum Drugs 0.000 description 21
- 108020001507 fusion proteins Proteins 0.000 description 21
- 150000007523 nucleic acids Chemical class 0.000 description 21
- 102000037865 fusion proteins Human genes 0.000 description 20
- 102000039446 nucleic acids Human genes 0.000 description 20
- 108020004707 nucleic acids Proteins 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 20
- 238000000338 in vitro Methods 0.000 description 19
- 230000001965 increasing effect Effects 0.000 description 19
- 108010074328 Interferon-gamma Proteins 0.000 description 17
- 238000003556 assay Methods 0.000 description 17
- 238000002347 injection Methods 0.000 description 17
- 239000007924 injection Substances 0.000 description 17
- 102100037850 Interferon gamma Human genes 0.000 description 14
- 230000014509 gene expression Effects 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- 230000004940 costimulation Effects 0.000 description 13
- 230000009696 proliferative response Effects 0.000 description 13
- 230000004083 survival effect Effects 0.000 description 13
- 238000002255 vaccination Methods 0.000 description 13
- 229960005486 vaccine Drugs 0.000 description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 239000013604 expression vector Substances 0.000 description 12
- 210000002865 immune cell Anatomy 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 239000003446 ligand Substances 0.000 description 12
- 230000001404 mediated effect Effects 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 230000004614 tumor growth Effects 0.000 description 12
- 241001529936 Murinae Species 0.000 description 11
- 230000004913 activation Effects 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 230000036039 immunity Effects 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 125000003729 nucleotide group Chemical group 0.000 description 11
- 230000035755 proliferation Effects 0.000 description 11
- -1 ICOS Proteins 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 230000004927 fusion Effects 0.000 description 10
- 210000001165 lymph node Anatomy 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 102000000588 Interleukin-2 Human genes 0.000 description 9
- 108010002350 Interleukin-2 Proteins 0.000 description 9
- 108091008874 T cell receptors Proteins 0.000 description 9
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 9
- 230000000259 anti-tumor effect Effects 0.000 description 9
- 239000012707 chemical precursor Substances 0.000 description 9
- 239000002299 complementary DNA Substances 0.000 description 9
- 230000001419 dependent effect Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- 238000003752 polymerase chain reaction Methods 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 210000003719 b-lymphocyte Anatomy 0.000 description 8
- 230000001413 cellular effect Effects 0.000 description 8
- 230000000875 corresponding effect Effects 0.000 description 8
- 239000000839 emulsion Substances 0.000 description 8
- 239000000816 peptidomimetic Substances 0.000 description 8
- 210000004988 splenocyte Anatomy 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 239000013598 vector Substances 0.000 description 8
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 7
- 125000000539 amino acid group Chemical group 0.000 description 7
- 210000000612 antigen-presenting cell Anatomy 0.000 description 7
- 230000036755 cellular response Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 102100026445 A-kinase anchor protein 17A Human genes 0.000 description 6
- 238000011740 C57BL/6 mouse Methods 0.000 description 6
- 238000011765 DBA/2 mouse Methods 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 101000718019 Homo sapiens A-kinase anchor protein 17A Proteins 0.000 description 6
- 102000011931 Nucleoproteins Human genes 0.000 description 6
- 108010061100 Nucleoproteins Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000006052 T cell proliferation Effects 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 238000005755 formation reaction Methods 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 210000004962 mammalian cell Anatomy 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 5
- 102100034980 ICOS ligand Human genes 0.000 description 5
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 5
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 5
- 102000000743 Interleukin-5 Human genes 0.000 description 5
- 108010002616 Interleukin-5 Proteins 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 230000002163 immunogen Effects 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 230000002516 postimmunization Effects 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 230000002269 spontaneous effect Effects 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 230000006023 anti-tumor response Effects 0.000 description 4
- 230000000890 antigenic effect Effects 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 230000016396 cytokine production Effects 0.000 description 4
- 239000002612 dispersion medium Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 231100000518 lethal Toxicity 0.000 description 4
- 230000001665 lethal effect Effects 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 102000054765 polymorphisms of proteins Human genes 0.000 description 4
- 210000004986 primary T-cell Anatomy 0.000 description 4
- 230000009257 reactivity Effects 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 210000004989 spleen cell Anatomy 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000011191 terminal modification Methods 0.000 description 4
- 229940030325 tumor cell vaccine Drugs 0.000 description 4
- 238000010600 3H thymidine incorporation assay Methods 0.000 description 3
- 229940045513 CTLA4 antagonist Drugs 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102000013462 Interleukin-12 Human genes 0.000 description 3
- 108010065805 Interleukin-12 Proteins 0.000 description 3
- 102000003816 Interleukin-13 Human genes 0.000 description 3
- 108090000176 Interleukin-13 Proteins 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 102000043131 MHC class II family Human genes 0.000 description 3
- 108091054438 MHC class II family Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 230000009435 amidation Effects 0.000 description 3
- 238000007112 amidation reaction Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000002788 anti-peptide Effects 0.000 description 3
- 229940121375 antifungal agent Drugs 0.000 description 3
- 239000003429 antifungal agent Substances 0.000 description 3
- 230000003190 augmentative effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 210000002443 helper t lymphocyte Anatomy 0.000 description 3
- 239000007951 isotonicity adjuster Substances 0.000 description 3
- 230000021633 leukocyte mediated immunity Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 210000004976 peripheral blood cell Anatomy 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000004481 post-translational protein modification Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000002708 random mutagenesis Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000000284 resting effect Effects 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 239000012646 vaccine adjuvant Substances 0.000 description 3
- 229940124931 vaccine adjuvant Drugs 0.000 description 3
- 230000005730 ADP ribosylation Effects 0.000 description 2
- 238000012935 Averaging Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 150000008574 D-amino acids Chemical class 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101710093458 ICOS ligand Proteins 0.000 description 2
- 241001500351 Influenzavirus A Species 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 108010028921 Lipopeptides Proteins 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 239000003070 absorption delaying agent Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 229940030156 cell vaccine Drugs 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000000562 conjugate Substances 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 230000006251 gamma-carboxylation Effects 0.000 description 2
- 229940044627 gamma-interferon Drugs 0.000 description 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 229940028885 interleukin-4 Drugs 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 235000005772 leucine Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 235000018977 lysine Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 238000000302 molecular modelling Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000002515 oligonucleotide synthesis Methods 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 2
- 239000002644 phorbol ester Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 238000010561 standard procedure Methods 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
- 230000019635 sulfation Effects 0.000 description 2
- 238000005670 sulfation reaction Methods 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 241000712461 unidentified influenza virus Species 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- 150000005207 1,3-dihydroxybenzenes Chemical class 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- 101150098072 20 gene Proteins 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 102000015404 Amino Acid Receptors Human genes 0.000 description 1
- 108010025177 Amino Acid Receptors Proteins 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102000004858 Growth differentiation factor-9 Human genes 0.000 description 1
- 108090001086 Growth differentiation factor-9 Proteins 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000000646 Interleukin-3 Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102000000704 Interleukin-7 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 235000019766 L-Lysine Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-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
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108091005461 Nucleic proteins Chemical group 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 101710126321 Pancreatic trypsin inhibitor Proteins 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
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710118538 Protease Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 238000000692 Student's t-test Methods 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
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 1
- 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 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 230000003091 anti-genotoxic effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000010516 arginylation Effects 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000006161 blood agar Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 108091008034 costimulatory receptors Proteins 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000005860 defense response to virus Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000012645 endogenous antigen Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 229960005051 fluostigmine Drugs 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 150000003278 haem Chemical group 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000005931 immune cell recruitment Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000012623 in vivo measurement Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 229940076264 interleukin-3 Drugs 0.000 description 1
- 229940100602 interleukin-5 Drugs 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 229940100994 interleukin-7 Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000007498 myristoylation Effects 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000863 peptide conjugate Substances 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 208000016021 phenotype Diseases 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000013823 prenylation Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 239000003725 proteoliposome Substances 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 229940043131 pyroglutamate Drugs 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229940108519 trasylol Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/145—Orthomyxoviridae, e.g. influenza virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5152—Tumor cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55516—Proteins; Peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Virology (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL14610600A IL146106A0 (en) | 1999-05-06 | 2000-05-05 | Use of soluble costimulatory molecules to enhance immune responses |
JP2000616813A JP2002544170A (en) | 1999-05-06 | 2000-05-05 | Use of soluble costimulatory molecules to enhance immune response |
CA002373256A CA2373256A1 (en) | 1999-05-06 | 2000-05-05 | Use of soluble costimulatory molecules to enhance immune responses |
KR1020017014170A KR20020001865A (en) | 1999-05-06 | 2000-05-05 | Use of soluble costimulatory molecules to enhance immune responses |
AU48257/00A AU4825700A (en) | 1999-05-06 | 2000-05-05 | Use of soluble costimulatory molecules to enhance immune responses |
BR0010711-5A BR0010711A (en) | 1999-05-06 | 2000-05-05 | Use of soluble co-stimulatory molecules to enhance immune responses |
EP00930437A EP1181053A2 (en) | 1999-05-06 | 2000-05-05 | Use of soluble costimulatory molecules to enhance immune responses |
PL36091500A PL360915A1 (en) | 1999-05-06 | 2000-05-05 | Use of soluble costimulatory molecules to enhance immune responses |
NO20015396A NO20015396L (en) | 1999-05-06 | 2001-11-05 | Use of soluble costimulatory molecules to enhance immune responses |
HK02102335.8A HK1041810A1 (en) | 1999-05-06 | 2002-03-26 | Use of soluble costimulatory molecules to enhance immune responses |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13294499P | 1999-05-06 | 1999-05-06 | |
US60/132,944 | 1999-05-06 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2000067788A2 true WO2000067788A2 (en) | 2000-11-16 |
WO2000067788A3 WO2000067788A3 (en) | 2001-04-05 |
Family
ID=22456295
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/012435 WO2000067788A2 (en) | 1999-05-06 | 2000-05-05 | Use of soluble costimulatory molecules to enhance immune responses |
Country Status (15)
Country | Link |
---|---|
EP (1) | EP1181053A2 (en) |
JP (1) | JP2002544170A (en) |
KR (1) | KR20020001865A (en) |
CN (1) | CN1377279A (en) |
AU (1) | AU4825700A (en) |
BR (1) | BR0010711A (en) |
CA (1) | CA2373256A1 (en) |
CZ (1) | CZ20013964A3 (en) |
HK (1) | HK1041810A1 (en) |
HU (1) | HUP0201222A3 (en) |
IL (1) | IL146106A0 (en) |
NO (1) | NO20015396L (en) |
PL (1) | PL360915A1 (en) |
WO (1) | WO2000067788A2 (en) |
ZA (1) | ZA200109376B (en) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6803039B2 (en) | 2000-05-18 | 2004-10-12 | Japan Tobacco Inc. | Human monoclonal antibody against a costimulatory signal transduction molecule AILIM |
US7030225B1 (en) | 1997-02-27 | 2006-04-18 | Japan Tobacco, Inc. | Antibodies to JTT-1 protein, cells secreting such antibodies, and methods of making such antibodies |
US7045615B2 (en) | 1997-02-27 | 2006-05-16 | Japan Tobacco, Inc. | Nucleic acids encoding JTT-1 protein |
WO2007067682A2 (en) * | 2005-12-08 | 2007-06-14 | University Of Louisville Research Foundation, Inc. | In vivo cell surface engineering |
US7438905B2 (en) | 2001-03-01 | 2008-10-21 | Japan Tobacco, Inc. | Methods of suppressing, treating, or preventing graft rejection with an antibody or a portion thereof that binds to AILIM |
US7465445B2 (en) | 1999-08-30 | 2008-12-16 | Japan Tobacco Inc. | Methods of preventing or treating graft versus host reaction by administering an antibody or portion thereof that binds to AILIM |
US7465444B2 (en) | 2001-03-27 | 2008-12-16 | Japan Tobacco, Inc. | Methods of suppressing or treating an inflammatory bowel disease by administering an antibody or portion thereof that binds to AILIM |
US7745215B2 (en) | 2005-12-08 | 2010-06-29 | University Of Louisville Research Foundation, Inc. | Methods and compositions for expanding T regulatory cells |
US9511151B2 (en) | 2010-11-12 | 2016-12-06 | Uti Limited Partnership | Compositions and methods for the prevention and treatment of cancer |
US10080808B2 (en) | 2012-10-11 | 2018-09-25 | Uti Limited Partnership | Methods and compositions for treating multiple sclerosis and related disorders |
US10124045B2 (en) | 2013-11-04 | 2018-11-13 | Uti Limited Partnership | Methods and compositions for sustained immunotherapy |
US10485882B2 (en) | 2015-05-06 | 2019-11-26 | Uti Limited Partnership | Nanoparticle compositions for sustained therapy |
US10988516B2 (en) | 2012-03-26 | 2021-04-27 | Uti Limited Partnership | Methods and compositions for treating inflammation |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007005583A1 (en) * | 2005-06-30 | 2007-01-11 | Eisai Co., Ltd. | Compounds for preparing immunological adjuvant |
CA2843274A1 (en) | 2011-07-29 | 2013-02-07 | Selecta Biosciences, Inc. | Synthetic nanocarriers that generate humoral and cytotoxic t lymphocyte (ctl) immune responses |
US20150056232A1 (en) * | 2012-04-02 | 2015-02-26 | The Arizona Board Of Regents For And On Behalf Of Arizona State University | Recombinant bacterium for induction of cellular immune response |
CN110743006B (en) * | 2019-11-22 | 2020-08-25 | 北京启辰生生物科技有限公司 | Composition for synergistically relieving immune cell failure and application |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000006605A2 (en) * | 1998-07-28 | 2000-02-10 | Micromet Ag | Heterominibodies |
-
2000
- 2000-05-05 EP EP00930437A patent/EP1181053A2/en not_active Withdrawn
- 2000-05-05 JP JP2000616813A patent/JP2002544170A/en not_active Withdrawn
- 2000-05-05 AU AU48257/00A patent/AU4825700A/en not_active Abandoned
- 2000-05-05 CA CA002373256A patent/CA2373256A1/en not_active Abandoned
- 2000-05-05 WO PCT/US2000/012435 patent/WO2000067788A2/en not_active Application Discontinuation
- 2000-05-05 CZ CZ20013964A patent/CZ20013964A3/en unknown
- 2000-05-05 CN CN00810038A patent/CN1377279A/en active Pending
- 2000-05-05 IL IL14610600A patent/IL146106A0/en unknown
- 2000-05-05 KR KR1020017014170A patent/KR20020001865A/en not_active Application Discontinuation
- 2000-05-05 HU HU0201222A patent/HUP0201222A3/en unknown
- 2000-05-05 BR BR0010711-5A patent/BR0010711A/en not_active Application Discontinuation
- 2000-05-05 PL PL36091500A patent/PL360915A1/en not_active Application Discontinuation
-
2001
- 2001-11-05 NO NO20015396A patent/NO20015396L/en not_active Application Discontinuation
- 2001-11-14 ZA ZA200109376A patent/ZA200109376B/en unknown
-
2002
- 2002-03-26 HK HK02102335.8A patent/HK1041810A1/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000006605A2 (en) * | 1998-07-28 | 2000-02-10 | Micromet Ag | Heterominibodies |
Non-Patent Citations (4)
Title |
---|
CHEN AOSHUANG ET AL: "Non-glycosylated human B7-1(CD80) retains the capacity to bind its counter-receptors." FEBS LETTERS, vol. 428, no. 3, 29 May 1998 (1998-05-29), pages 127-134, XP002154489 ISSN: 0014-5793 * |
MORO MONICA ET AL: "Induction of therapeutic T-cell immunity by tumor targeting with soluble recombinant B7-immunoglobulin costimulatory molecules." CANCER RESEARCH, vol. 59, no. 11, 1 June 1999 (1999-06-01), pages 2650-2656, XP002154490 ISSN: 0008-5472 * |
RAO JAY B ET AL: "IL-12 is an effective adjuvant to recombinant vaccinia virus-based tumor vaccines: Enhancement by simultaneous B7-1 expression." JOURNAL OF IMMUNOLOGY, vol. 156, no. 9, 1996, pages 3357-3365, XP002154488 ISSN: 0022-1767 * |
RENNERT PAUL ET AL: "The IgV domain of human B7-2 (CD86) is sufficient to co-stimulate T lymphocytes and induce cytokine secretion." INTERNATIONAL IMMUNOLOGY, vol. 9, no. 6, 1997, pages 805-813, XP000971089 ISSN: 0953-8178 * |
Cited By (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7247612B2 (en) | 1997-02-27 | 2007-07-24 | Japan Tobacco Inc. | Methods of treating an inflammatory disease with a JJT-1 polypeptide |
US7294473B2 (en) | 1997-02-27 | 2007-11-13 | Japan Tobacco Inc. | Methods of identifying substances that interact with JTT-1 protein |
US7045615B2 (en) | 1997-02-27 | 2006-05-16 | Japan Tobacco, Inc. | Nucleic acids encoding JTT-1 protein |
US7112655B1 (en) | 1997-02-27 | 2006-09-26 | Japan Tobacco, Inc. | JTT-1 protein and methods of inhibiting lymphocyte activation |
US8389690B2 (en) | 1997-02-27 | 2013-03-05 | Japan Tobacco Inc. | Antibodies to JTT-1 protein and cells secreting such antibodies |
US7196175B2 (en) | 1997-02-27 | 2007-03-27 | Japan Tobacco Inc. | Antibodies to JTT-1 protein and cells secreting such antibodies |
US7217792B2 (en) | 1997-02-27 | 2007-05-15 | Japan Tobacco Inc. | JTT-1 protein and methods of inhibiting lymphocyte activation |
US7932358B2 (en) | 1997-02-27 | 2011-04-26 | Japan Tobacco Inc. | Antibodies to JTT-1 protein and cells secreting such antibodies |
US7030225B1 (en) | 1997-02-27 | 2006-04-18 | Japan Tobacco, Inc. | Antibodies to JTT-1 protein, cells secreting such antibodies, and methods of making such antibodies |
US7279560B2 (en) | 1997-02-27 | 2007-10-09 | Japan Tobacco Inc. | Antibody fragments to JTT-1 protein and cells secreting such antibody fragments |
US7226909B2 (en) | 1997-02-27 | 2007-06-05 | Japan Tobacco Inc. | Methods of inhibiting transmission of a costimulatory signal of lymphocytes |
US7259147B2 (en) | 1997-02-27 | 2007-08-21 | Japan Tobacco Inc. | Methods of treating multiple sclerosis with a JTT-1 polypeptide |
US7465445B2 (en) | 1999-08-30 | 2008-12-16 | Japan Tobacco Inc. | Methods of preventing or treating graft versus host reaction by administering an antibody or portion thereof that binds to AILIM |
US7998478B2 (en) | 1999-08-30 | 2011-08-16 | Japan Tobacco, Inc. | Pharmaceutical composition for treating immune diseases |
US7988965B2 (en) | 2000-05-18 | 2011-08-02 | Japan Tobacco, Inc. | Methods of treating systemic lupus erythematosus with an antibody against costimulatory signal transduction molecule ailim |
US6803039B2 (en) | 2000-05-18 | 2004-10-12 | Japan Tobacco Inc. | Human monoclonal antibody against a costimulatory signal transduction molecule AILIM |
US7166283B2 (en) | 2000-05-18 | 2007-01-23 | Japan Tobacco Inc. | Methods of treating an inflammatory disorder and prohibiting proliferation, cytokine production, and signal transduction with antibody against costimulatory signal transduction molecule AILIM |
US7438905B2 (en) | 2001-03-01 | 2008-10-21 | Japan Tobacco, Inc. | Methods of suppressing, treating, or preventing graft rejection with an antibody or a portion thereof that binds to AILIM |
US8052972B2 (en) | 2001-03-27 | 2011-11-08 | Japan Tobacco, Inc. | Remedies for inflammatory bowel diseases |
US7465444B2 (en) | 2001-03-27 | 2008-12-16 | Japan Tobacco, Inc. | Methods of suppressing or treating an inflammatory bowel disease by administering an antibody or portion thereof that binds to AILIM |
WO2007067681A2 (en) * | 2005-12-08 | 2007-06-14 | University Of Louisville Research Foundation, Inc. | Immunostimulatory compositions and methods |
US7598345B2 (en) | 2005-12-08 | 2009-10-06 | University Of Louisville Research Foundation, Inc. | Immunostimulatory compositions and methods |
WO2007067681A3 (en) * | 2005-12-08 | 2008-01-03 | Univ Louisville Res Found | Immunostimulatory compositions and methods |
US8017582B2 (en) | 2005-12-08 | 2011-09-13 | University Of Louisville Research Foundation, Inc. | Immunostimulatory compositions and methods |
WO2007067682A3 (en) * | 2005-12-08 | 2007-11-15 | Univ Louisville Res Found | In vivo cell surface engineering |
WO2007067682A2 (en) * | 2005-12-08 | 2007-06-14 | University Of Louisville Research Foundation, Inc. | In vivo cell surface engineering |
US9079976B2 (en) | 2005-12-08 | 2015-07-14 | University Of Louisville Research Foundation, Inc. | Immunostimulatory compositions and methods |
US7745215B2 (en) | 2005-12-08 | 2010-06-29 | University Of Louisville Research Foundation, Inc. | Methods and compositions for expanding T regulatory cells |
US9511151B2 (en) | 2010-11-12 | 2016-12-06 | Uti Limited Partnership | Compositions and methods for the prevention and treatment of cancer |
US11000596B2 (en) | 2010-11-12 | 2021-05-11 | UTI Limited Parttiership | Compositions and methods for the prevention and treatment of cancer |
US10172955B2 (en) | 2010-11-12 | 2019-01-08 | Uti Limited Partnership | Compositions and methods for the prevention and treatment of cancer |
US10988516B2 (en) | 2012-03-26 | 2021-04-27 | Uti Limited Partnership | Methods and compositions for treating inflammation |
US10080808B2 (en) | 2012-10-11 | 2018-09-25 | Uti Limited Partnership | Methods and compositions for treating multiple sclerosis and related disorders |
US10905773B2 (en) | 2012-10-11 | 2021-02-02 | Uti Limited Partnership | Methods and compositions for treating multiple sclerosis and related disorders |
US10124045B2 (en) | 2013-11-04 | 2018-11-13 | Uti Limited Partnership | Methods and compositions for sustained immunotherapy |
US11338024B2 (en) | 2013-11-04 | 2022-05-24 | Uti Limited Partnership | Methods and compositions for sustained immunotherapy |
US10485882B2 (en) | 2015-05-06 | 2019-11-26 | Uti Limited Partnership | Nanoparticle compositions for sustained therapy |
Also Published As
Publication number | Publication date |
---|---|
IL146106A0 (en) | 2002-07-25 |
JP2002544170A (en) | 2002-12-24 |
KR20020001865A (en) | 2002-01-09 |
HUP0201222A3 (en) | 2004-07-28 |
CN1377279A (en) | 2002-10-30 |
PL360915A1 (en) | 2004-09-20 |
CA2373256A1 (en) | 2000-11-16 |
EP1181053A2 (en) | 2002-02-27 |
HK1041810A1 (en) | 2002-07-26 |
CZ20013964A3 (en) | 2002-06-12 |
AU4825700A (en) | 2000-11-21 |
ZA200109376B (en) | 2003-03-13 |
BR0010711A (en) | 2002-02-13 |
NO20015396D0 (en) | 2001-11-05 |
WO2000067788A3 (en) | 2001-04-05 |
NO20015396L (en) | 2002-01-02 |
HUP0201222A2 (en) | 2002-08-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Corr et al. | Costimulation provided by DNA immunization enhances antitumor immunity. | |
KR100689739B1 (en) | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens | |
AU765822B2 (en) | CD40 binding molecules and CTL peptides for treating tumors | |
CA2480162C (en) | Induction of anti-tumor ctl immunity through in vivo triggering of 4-1bb and/or cd40 | |
WO2000067788A2 (en) | Use of soluble costimulatory molecules to enhance immune responses | |
EP1086224B1 (en) | B2 microglobulin fusion proteins and high affinity variants | |
SK3062001A3 (en) | Method for down-regulating osteoprotegerin ligand activity | |
US20210283242A1 (en) | Immune-mediated coronavirus treatments | |
TW514530B (en) | Tumor vaccines and methods for their production | |
KR20200142600A (en) | Combinations of modalities for the treatment of diabetes | |
Facciabene et al. | Vectors encoding carcinoembryonic antigen fused to the B subunit of heat-labile enterotoxin elicit antigen-specific immune responses and antitumor effects | |
KR20070068398A (en) | Combination of a recombinant mycobacterium and a biologically active agent as a vaccine | |
US7011833B1 (en) | Enhancing immune responses with B7-1 or B7-2 in the absence of a crosslinking agent | |
US20040091492A1 (en) | Beta2 microglobulin fusion proteins and high affinity variants | |
JP5901084B2 (en) | Peptide adjuvant | |
KR20210010873A (en) | Artificial indiscriminate T helper cell epitope facilitating targeted antibody production with a limited T cell inflammatory response | |
MXPA01011130A (en) | Use of soluble costimulatory molecules to enhance immune responses | |
US20050255106A1 (en) | Induction of anti-tumor ctl immunity through in vivo triggering of 4-1bb and/or cd40 | |
BERGER et al. | o. 3 Vaccination strategy to treat persistent viral infections | |
EP1284751A1 (en) | Compositions and methods for induction of active autoimmunity | |
WO2006089251A2 (en) | SYNERGISTIC EFFECT OF TGF-β BLOCKADE AND IMMUNOGENIC AGENTS ON TUMORS |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
AK | Designated states |
Kind code of ref document: A3 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2001/011130 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: PV2001-3964 Country of ref document: CZ |
|
ENP | Entry into the national phase |
Ref document number: 2373256 Country of ref document: CA Ref country code: CA Ref document number: 2373256 Kind code of ref document: A Format of ref document f/p: F |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 616813 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020017014170 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 515410 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2001/09376 Country of ref document: ZA Ref document number: 200109376 Country of ref document: ZA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 48257/00 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2000930437 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 008100381 Country of ref document: CN |
|
WWP | Wipo information: published in national office |
Ref document number: 1020017014170 Country of ref document: KR |
|
WWP | Wipo information: published in national office |
Ref document number: 2000930437 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: PV2001-3964 Country of ref document: CZ |
|
WWR | Wipo information: refused in national office |
Ref document number: PV2001-3964 Country of ref document: CZ |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2000930437 Country of ref document: EP |
|
WWR | Wipo information: refused in national office |
Ref document number: 1020017014170 Country of ref document: KR |