DE3249568A1 - Glykoverwandtes antigen, verfahren zu dessen herstellung und dessen verwendung zur bekaempfung von krebs - Google Patents
Glykoverwandtes antigen, verfahren zu dessen herstellung und dessen verwendung zur bekaempfung von krebsInfo
- Publication number
- DE3249568A1 DE3249568A1 DE19823249568 DE3249568A DE3249568A1 DE 3249568 A1 DE3249568 A1 DE 3249568A1 DE 19823249568 DE19823249568 DE 19823249568 DE 3249568 A DE3249568 A DE 3249568A DE 3249568 A1 DE3249568 A1 DE 3249568A1
- Authority
- DE
- Germany
- Prior art keywords
- gra
- lectin
- cancer
- cells
- related antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 101
- 201000011510 cancer Diseases 0.000 title claims abstract description 91
- 239000000427 antigen Substances 0.000 title claims abstract description 21
- 102000036639 antigens Human genes 0.000 title claims abstract description 21
- 108091007433 antigens Proteins 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims description 38
- 238000002360 preparation method Methods 0.000 title claims description 14
- 230000008569 process Effects 0.000 title claims description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 title abstract 6
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 title abstract 3
- 210000004027 cell Anatomy 0.000 claims abstract description 170
- 108090001090 Lectins Proteins 0.000 claims abstract description 49
- 102000004856 Lectins Human genes 0.000 claims abstract description 49
- 239000002523 lectin Substances 0.000 claims abstract description 49
- 210000000170 cell membrane Anatomy 0.000 claims abstract description 21
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical group CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims abstract description 19
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229930182830 galactose Natural products 0.000 claims abstract description 18
- 238000000265 homogenisation Methods 0.000 claims abstract description 4
- 108010046016 Peanut Agglutinin Proteins 0.000 claims description 12
- 239000002246 antineoplastic agent Substances 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 4
- 230000027455 binding Effects 0.000 claims description 4
- 238000005063 solubilization Methods 0.000 claims description 3
- 230000007928 solubilization Effects 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 2
- 101710186708 Agglutinin Proteins 0.000 claims 2
- 101710146024 Horcolin Proteins 0.000 claims 2
- 244000112675 Lablab purpureus Species 0.000 claims 2
- 101710189395 Lectin Proteins 0.000 claims 2
- 101710179758 Mannose-specific lectin Proteins 0.000 claims 2
- 101710150763 Mannose-specific lectin 1 Proteins 0.000 claims 2
- 101710150745 Mannose-specific lectin 2 Proteins 0.000 claims 2
- 239000000910 agglutinin Substances 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 208000033763 Familial hyperaldosteronism type I Diseases 0.000 description 209
- 201000011266 glucocorticoid-remediable aldosteronism Diseases 0.000 description 209
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 41
- 210000004698 lymphocyte Anatomy 0.000 description 35
- 241000699670 Mus sp. Species 0.000 description 30
- 238000012360 testing method Methods 0.000 description 23
- 239000000872 buffer Substances 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 21
- 239000002609 medium Substances 0.000 description 20
- 239000011780 sodium chloride Substances 0.000 description 20
- 241000699666 Mus <mouse, genus> Species 0.000 description 19
- 239000012980 RPMI-1640 medium Substances 0.000 description 17
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 16
- 208000005718 Stomach Neoplasms Diseases 0.000 description 16
- 239000012894 fetal calf serum Substances 0.000 description 16
- 206010017758 gastric cancer Diseases 0.000 description 16
- 201000011549 stomach cancer Diseases 0.000 description 16
- 239000001963 growth medium Substances 0.000 description 15
- 239000012636 effector Substances 0.000 description 14
- 210000004989 spleen cell Anatomy 0.000 description 14
- 230000003013 cytotoxicity Effects 0.000 description 13
- 231100000135 cytotoxicity Toxicity 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 229920002684 Sepharose Polymers 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 238000000926 separation method Methods 0.000 description 12
- 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 11
- 108010002350 Interleukin-2 Proteins 0.000 description 11
- 102000000588 Interleukin-2 Human genes 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 206010006187 Breast cancer Diseases 0.000 description 10
- 208000026310 Breast neoplasm Diseases 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 239000013504 Triton X-100 Substances 0.000 description 8
- 229920004890 Triton X-100 Polymers 0.000 description 8
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 8
- 239000002504 physiological saline solution Substances 0.000 description 8
- 210000000952 spleen Anatomy 0.000 description 8
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 7
- 238000001042 affinity chromatography Methods 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 108010039433 dolichos biflorus agglutinin Proteins 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 208000011691 Burkitt lymphomas Diseases 0.000 description 5
- 239000012981 Hank's balanced salt solution Substances 0.000 description 5
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 5
- 206010029260 Neuroblastoma Diseases 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 5
- 230000002147 killing effect Effects 0.000 description 5
- 201000005202 lung cancer Diseases 0.000 description 5
- 208000020816 lung neoplasm Diseases 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 206010005003 Bladder cancer Diseases 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 229920005654 Sephadex Polymers 0.000 description 4
- 239000012507 Sephadex™ Substances 0.000 description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 4
- 238000001502 gel electrophoresis Methods 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 201000005112 urinary bladder cancer Diseases 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- -1 bromoacetyl Chemical group 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 210000005104 human peripheral blood lymphocyte Anatomy 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 229960004857 mitomycin Drugs 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000001235 sensitizing effect Effects 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- 101000934342 Mus musculus T-cell surface glycoprotein CD5 Proteins 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 208000000389 T-cell leukemia Diseases 0.000 description 2
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000002308 calcification Effects 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000004040 coloring Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000013256 coordination polymer Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 108010065337 fluorescein isothiocyanate-peanut agglutinin Proteins 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229920001542 oligosaccharide Chemical group 0.000 description 2
- 150000002482 oligosaccharides Chemical group 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 108010086652 phytohemagglutinin-P Proteins 0.000 description 2
- 230000007505 plaque formation Effects 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 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
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical group N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 102000007563 Galectins Human genes 0.000 description 1
- 108010046569 Galectins Proteins 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- VLHUSFYMPUDOEL-WZTVWXICSA-N Iothalamate meglumine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC(=O)C1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I VLHUSFYMPUDOEL-WZTVWXICSA-N 0.000 description 1
- 241001507252 Japanese monkeys Species 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000009097 Phosphorylases Human genes 0.000 description 1
- 108010073135 Phosphorylases Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 101150052863 THY1 gene Proteins 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 235000005770 birds nest Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000005880 cancer cell killing Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000000853 cresyl group Chemical group C1(=CC=C(C=C1)C)* 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 1
- UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- HBNYJWAFDZLWRS-UHFFFAOYSA-N ethyl isothiocyanate Chemical compound CCN=C=S HBNYJWAFDZLWRS-UHFFFAOYSA-N 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000013016 learning Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- HFZNPKDYLSOGBE-SCEMAYBHSA-N nrc-12 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(C)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C1=CC=C(O)C=C1 HFZNPKDYLSOGBE-SCEMAYBHSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- OQUKIQWCVTZJAF-UHFFFAOYSA-N phenol;sulfuric acid Chemical compound OS(O)(=O)=O.OC1=CC=CC=C1 OQUKIQWCVTZJAF-UHFFFAOYSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 229940116357 potassium thiocyanate Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 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
- 230000009696 proliferative response Effects 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 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
- 238000013207 serial dilution Methods 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 235000005765 wild carrot Nutrition 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP56156413A JPS5857318A (ja) | 1981-10-01 | 1981-10-01 | 癌細胞障害性リンパ球の製造法 |
JP15641481A JPS5857321A (ja) | 1981-10-01 | 1981-10-01 | 抗癌剤 |
JP56158473A JPS5859923A (ja) | 1981-10-05 | 1981-10-05 | 抗癌剤 |
JP56158472A JPS5859922A (ja) | 1981-10-05 | 1981-10-05 | 癌細胞障害性リンパ球 |
JP57111168A JPS591420A (ja) | 1982-06-28 | 1982-06-28 | 糖鎖関連抗原およびその製造法 |
Publications (2)
Publication Number | Publication Date |
---|---|
DE3249568A1 true DE3249568A1 (de) | 1985-02-07 |
DE3249568C2 DE3249568C2 (fi) | 1987-10-01 |
Family
ID=27526479
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19823249568 Granted DE3249568A1 (de) | 1981-10-01 | 1982-09-30 | Glykoverwandtes antigen, verfahren zu dessen herstellung und dessen verwendung zur bekaempfung von krebs |
DE19823236298 Granted DE3236298A1 (de) | 1981-10-01 | 1982-09-30 | Krebszellen bekaempfende lymphocyten, verfahren zu deren herstellung und anti-krebsmittel, welche die lymphocyten enthalten |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19823236298 Granted DE3236298A1 (de) | 1981-10-01 | 1982-09-30 | Krebszellen bekaempfende lymphocyten, verfahren zu deren herstellung und anti-krebsmittel, welche die lymphocyten enthalten |
Country Status (19)
Country | Link |
---|---|
AR (1) | AR230731A1 (fi) |
AT (2) | AT382080B (fi) |
AU (1) | AU554858B2 (fi) |
BE (1) | BE893704A (fi) |
CA (1) | CA1195269A (fi) |
CH (2) | CH655660B (fi) |
DD (2) | DD209577A5 (fi) |
DE (2) | DE3249568A1 (fi) |
DK (1) | DK292182A (fi) |
FI (1) | FI77157C (fi) |
FR (1) | FR2513882B1 (fi) |
IL (1) | IL66270A (fi) |
IT (1) | IT1189305B (fi) |
MX (1) | MX7437E (fi) |
NL (1) | NL8202638A (fi) |
NO (1) | NO161601C (fi) |
NZ (1) | NZ201112A (fi) |
PT (1) | PT75148B (fi) |
SE (1) | SE8204058L (fi) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60214737A (ja) * | 1984-04-06 | 1985-10-28 | Nippon Koutai Kenkyusho:Kk | 糖鎖関連抗原の製造法 |
EP0334300A1 (en) * | 1988-03-21 | 1989-09-27 | Neorx Corporation | The use of monoclonal antibodies and conjugates thereof as signals to direct sensitized effector cells to tumor sites |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1193378A (en) * | 1967-04-11 | 1970-05-28 | Rand Dev Corp | Cancer Antigen Complexes |
DE1943699A1 (de) * | 1969-08-28 | 1971-03-04 | Stiftung Onophrio | Heilmittel mit proliferationshemmender Wirkung und Verfahren zur Herstellung dieses Heilmittels |
YU34005B (en) * | 1970-02-24 | 1978-10-31 | Podvinec Srecko | Process for obtaining bovine lymphatic gland extract |
US4371515A (en) * | 1978-12-26 | 1983-02-01 | E-Y Laboratories, Inc. | Method for forming an isolated lectin-immunological conjugate |
-
1982
- 1982-06-29 DK DK292182A patent/DK292182A/da not_active Application Discontinuation
- 1982-06-29 NZ NZ201112A patent/NZ201112A/en unknown
- 1982-06-29 PT PT75148A patent/PT75148B/pt not_active IP Right Cessation
- 1982-06-29 NO NO822215A patent/NO161601C/no unknown
- 1982-06-29 FI FI822325A patent/FI77157C/fi not_active IP Right Cessation
- 1982-06-30 AU AU85458/82A patent/AU554858B2/en not_active Ceased
- 1982-06-30 BE BE0/208493A patent/BE893704A/fr not_active IP Right Cessation
- 1982-06-30 AR AR289864A patent/AR230731A1/es active
- 1982-06-30 MX MX8210163U patent/MX7437E/es unknown
- 1982-06-30 CH CH398882A patent/CH655660B/de unknown
- 1982-06-30 FR FR8211489A patent/FR2513882B1/fr not_active Expired
- 1982-06-30 SE SE8204058A patent/SE8204058L/xx not_active Application Discontinuation
- 1982-06-30 DD DD82241290A patent/DD209577A5/de not_active IP Right Cessation
- 1982-06-30 NL NL8202638A patent/NL8202638A/nl not_active Application Discontinuation
- 1982-06-30 DD DD82261475A patent/DD221917A5/de not_active IP Right Cessation
- 1982-06-30 CH CH551284A patent/CH655661B/de unknown
- 1982-06-30 IT IT48724/82A patent/IT1189305B/it active
- 1982-07-08 IL IL66270A patent/IL66270A/xx unknown
- 1982-09-30 DE DE19823249568 patent/DE3249568A1/de active Granted
- 1982-09-30 DE DE19823236298 patent/DE3236298A1/de active Granted
- 1982-10-01 AT AT0363782A patent/AT382080B/de not_active IP Right Cessation
- 1982-10-01 CA CA000412670A patent/CA1195269A/en not_active Expired
-
1985
- 1985-12-09 AT AT0354585A patent/AT390002B/de not_active IP Right Cessation
Non-Patent Citations (9)
Title |
---|
Biochem.Biophys.Res.Comm., 62, 144, 1975, 89, 448-455, 1979, 96, 1547-1553, 1980 * |
Biochemistry, 13, 196-204, 1974 * |
Br.J.Exp.Pathol., 27, 228-236, 1946 * |
Carbohydrate Research, 51, 107-118, 1976 * |
Cell, 18, 183-191, 1979 * |
J.B.C., 250, 8518-8523, 1975 * |
J.Biochem., 89, 473-481, 1981 * |
Proc.Nat.Acad.Sci., 75, 2215-2219, 1978 * |
Z.Immunitätsforsch., 138, 423-433, 1966 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE3833319C2 (fi) | ||
DE69125735T2 (de) | Verfahren zur Aktivierung der zytolytischen Wirkung von Lymphozyten unter Verwendung von anti-CD28-Antikörper | |
US6051613A (en) | Nitrogen monoxide production suppressor | |
WO1997017084A1 (de) | Medikament, insbesondere zur modulation der immunantwort bei der bekämpfung von viren, tumoren, bakterien und parasiten | |
DE69725317T2 (de) | Implantierbare agarose-kollagenkügelchen enthaltende zellen, die ein diffusionsfähiges biologisches produkt bilden und ihre verwendung | |
DE3812605A1 (de) | Immunregulative stoffe und stoffgemische zur aktiven beeinflussung des krankheitsverlaufes | |
DE69014543T2 (de) | Multivalentes immunogen lmi. | |
PT1289535E (pt) | Entidades apoptóticas para utilização no tratamento de desordens neurodegenerativas e de outras desordens neurológicas | |
GB2106935A (en) | Cancer cell-combatting lymphocytes process, for the production thereof, and anticancer agents containing said lymphocytes | |
DE60022499T2 (de) | Neue therapeutische verwendung eines eine virale ansteckung modulierendes protein zur verhinderung von abstossung von fremdtransplantaten | |
DE3249568A1 (de) | Glykoverwandtes antigen, verfahren zu dessen herstellung und dessen verwendung zur bekaempfung von krebs | |
DE69429657T2 (de) | Verwendung von modifizierten tall-104 zellen zur behandlung von krebs und viralen krankheiten | |
Alexander et al. | Stimulants of cellular proliferation in wounds | |
CH643459A5 (de) | Mikrobielles zellwandgeruest mit adjuvans- und antitumorwirkung enthaltende, verfestigte pharmazeutische zubereitung und ihre herstellung. | |
DE69527640T2 (de) | Zusammensetzungen die gemischte transferrine als wirkstoff für induktion von immunotoleranz gegen antigen enthalten | |
DE3782996T2 (de) | Zellmembranproteine, zubereitungen, die sie enthalten und verfahren zu ihrer herstellung. | |
EP0019167B1 (de) | Arzneipräparat zur Behandlung von Carcinomen und Verfahren zu dessen Herstellung | |
Garcia-Giralt et al. | Extraction From Bovine Spleen of Immunosuppressant With No Activity on Hematopoietic Spleen Colony Formation ¹ | |
DE69433472T2 (de) | Recognin-vakzine | |
Bolton | On the production of a specific gastrotoxic serum.—Preliminary communication. | |
DE69430188T2 (de) | Behandlung von hiv-infektionen mittels huminsäure | |
CA1201988A (en) | Cancer cell-combatting lymphocytes, process for the production thereof and anticancer agents containing said lymphocytes | |
KR880001758B1 (ko) | 암세포에 대항하는 임파구의 제조방법 | |
US4877616A (en) | Process for preparing xerosin II and xerosin III, improved biological response modifiers | |
DE102018113041A1 (de) | Implantierbares pharmazeutisches Erzeugnis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AC | Divided out of |
Ref country code: DE Ref document number: 3236298 Format of ref document f/p: P |
|
OP8 | Request for examination as to paragraph 44 patent law | ||
AC | Divided out of |
Ref country code: DE Ref document number: 3236298 Format of ref document f/p: P |
|
AC | Divided out of |
Ref country code: DE Ref document number: 3236298 Format of ref document f/p: P |
|
D2 | Grant after examination | ||
8364 | No opposition during term of opposition | ||
8339 | Ceased/non-payment of the annual fee |