EP0608212A1 - Verfahren zur behandlung viraler infektionen - Google Patents
Verfahren zur behandlung viraler infektionenInfo
- Publication number
- EP0608212A1 EP0608212A1 EP91915297A EP91915297A EP0608212A1 EP 0608212 A1 EP0608212 A1 EP 0608212A1 EP 91915297 A EP91915297 A EP 91915297A EP 91915297 A EP91915297 A EP 91915297A EP 0608212 A1 EP0608212 A1 EP 0608212A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- tnf
- ligand
- residues
- binds
- binding
- 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.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims abstract description 37
- 208000036142 Viral infection Diseases 0.000 title claims abstract description 27
- 230000009385 viral infection Effects 0.000 title claims abstract description 26
- 239000003446 ligand Substances 0.000 claims abstract description 126
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims abstract description 78
- 241000124008 Mammalia Species 0.000 claims abstract description 25
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 72
- 230000027455 binding Effects 0.000 claims description 70
- 230000000694 effects Effects 0.000 claims description 58
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 52
- 102000005962 receptors Human genes 0.000 claims description 39
- 108020003175 receptors Proteins 0.000 claims description 39
- 102000057041 human TNF Human genes 0.000 claims description 35
- 230000006698 induction Effects 0.000 claims description 32
- 210000002889 endothelial cell Anatomy 0.000 claims description 18
- 150000001413 amino acids Chemical class 0.000 claims description 15
- 230000000840 anti-viral effect Effects 0.000 claims description 15
- 102000008070 Interferon-gamma Human genes 0.000 claims description 13
- 108010074328 Interferon-gamma Proteins 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 13
- 230000003511 endothelial effect Effects 0.000 claims description 13
- 229940044627 gamma-interferon Drugs 0.000 claims description 13
- 231100000135 cytotoxicity Toxicity 0.000 claims description 12
- 230000003013 cytotoxicity Effects 0.000 claims description 12
- 102000009123 Fibrin Human genes 0.000 claims description 10
- 108010073385 Fibrin Proteins 0.000 claims description 10
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 10
- 229950003499 fibrin Drugs 0.000 claims description 10
- 230000002947 procoagulating effect Effects 0.000 claims description 10
- 230000008021 deposition Effects 0.000 claims description 9
- 239000012634 fragment Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 238000011260 co-administration Methods 0.000 claims description 5
- 108010002350 Interleukin-2 Proteins 0.000 claims description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims description 3
- 229960004150 aciclovir Drugs 0.000 claims description 3
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 101800000194 Growth hormone-binding protein Proteins 0.000 claims description 2
- 102400001066 Growth hormone-binding protein Human genes 0.000 claims description 2
- 239000003443 antiviral agent Substances 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 230000000259 anti-tumor effect Effects 0.000 abstract description 6
- 230000004071 biological effect Effects 0.000 abstract description 4
- 206010054094 Tumour necrosis Diseases 0.000 abstract 1
- 102000009270 Tumour necrosis factor alpha Human genes 0.000 description 264
- 108050000101 Tumour necrosis factor alpha Proteins 0.000 description 264
- 210000004027 cell Anatomy 0.000 description 49
- 241000699670 Mus sp. Species 0.000 description 23
- 241000700605 Viruses Species 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 10
- 238000010790 dilution Methods 0.000 description 9
- 239000012895 dilution Substances 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 108010044091 Globulins Proteins 0.000 description 8
- 102000006395 Globulins Human genes 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 230000031915 positive regulation of coagulation Effects 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 7
- 210000001672 ovary Anatomy 0.000 description 7
- 206010003445 Ascites Diseases 0.000 description 6
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 6
- 230000002788 anti-peptide Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 201000001441 melanoma Diseases 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 239000012981 Hank's balanced salt solution Substances 0.000 description 5
- 241001494479 Pecora Species 0.000 description 5
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 206010040070 Septic Shock Diseases 0.000 description 4
- 206010044248 Toxic shock syndrome Diseases 0.000 description 4
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 4
- 206010046865 Vaccinia virus infection Diseases 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 101150030901 mab-21 gene Proteins 0.000 description 4
- 238000011275 oncology therapy Methods 0.000 description 4
- 239000003805 procoagulant Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000009257 reactivity Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 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 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 208000007089 vaccinia Diseases 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 3
- 206010005003 Bladder cancer Diseases 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 102000008946 Fibrinogen Human genes 0.000 description 3
- 108010049003 Fibrinogen Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 201000001531 bladder carcinoma Diseases 0.000 description 3
- 108010006025 bovine growth hormone Proteins 0.000 description 3
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 244000309466 calf Species 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000035602 clotting Effects 0.000 description 3
- 229940012952 fibrinogen Drugs 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 229940092253 ovalbumin Drugs 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 3
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 238000011725 BALB/c mouse Methods 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- AZLASBBHHSLQDB-GUBZILKMSA-N Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(C)C AZLASBBHHSLQDB-GUBZILKMSA-N 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 210000002403 aortic endothelial cell Anatomy 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- -1 dounorubicin Chemical compound 0.000 description 2
- 108010076046 endothelial cell procoagulant activity Proteins 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 210000003501 vero cell Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- 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
- VUCNQOPCYRJCGQ-UHFFFAOYSA-N 2-[4-(hydroxymethyl)phenoxy]acetic acid Chemical compound OCC1=CC=C(OCC(O)=O)C=C1 VUCNQOPCYRJCGQ-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 241000867607 Chlorocebus sabaeus Species 0.000 description 1
- 101800004419 Cleaved form Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 101000764535 Homo sapiens Lymphotoxin-alpha Proteins 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 1
- 102100022119 Lipoprotein lipase Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 206010027260 Meningitis viral Diseases 0.000 description 1
- 101000648740 Mus musculus Tumor necrosis factor Proteins 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 241001467552 Mycobacterium bovis BCG Species 0.000 description 1
- 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 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 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
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 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
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 108091007231 endothelial receptors Proteins 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 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
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 229940106780 human fibrinogen Drugs 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 101150091368 mab-20 gene Proteins 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- IOPLHGOSNCJOOO-UHFFFAOYSA-N methyl 3,4-diaminobenzoate Chemical compound COC(=O)C1=CC=C(N)C(N)=C1 IOPLHGOSNCJOOO-UHFFFAOYSA-N 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 230000002071 myeloproliferative effect Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 206010038464 renal hypertension Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- ZERULLAPCVRMCO-UHFFFAOYSA-N sulfure de di n-propyle Natural products CCCSCCC ZERULLAPCVRMCO-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 201000010044 viral meningitis Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/525—Tumour necrosis factor [TNF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPK197690 | 1990-08-27 | ||
| AU1976/90 | 1990-08-27 | ||
| PCT/AU1991/000400 WO1992003145A1 (en) | 1990-08-27 | 1991-08-27 | Method of treating viral infection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0608212A4 EP0608212A4 (de) | 1993-10-20 |
| EP0608212A1 true EP0608212A1 (de) | 1994-08-03 |
Family
ID=3774922
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP91915297A Ceased EP0608212A1 (de) | 1990-08-27 | 1991-08-27 | Verfahren zur behandlung viraler infektionen |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0608212A1 (de) |
| JP (1) | JPH06500323A (de) |
| CA (1) | CA2090401A1 (de) |
| WO (1) | WO1992003145A1 (de) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6375928B1 (en) * | 1990-03-12 | 2002-04-23 | Peptech Limited | Neutrophil stimulating peptides |
| US5587457A (en) * | 1990-03-12 | 1996-12-24 | Peptide Technology Limited | Neutrophil stimulating peptides |
| IT1254315B (it) * | 1992-03-27 | 1995-09-14 | Mini Ricerca Scient Tecnolog | Anticorpi monoclonali anti-idiotipici diretti contro anticorpi anti-tnf. |
| ATE172880T1 (de) * | 1992-08-28 | 1998-11-15 | Bayer Ag | Verwendung von monoklonalen anti-tnf-antikörpern für die behandlung von bakteriellen meningitiden |
| US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
| CA2868614A1 (en) | 2001-06-08 | 2002-12-08 | Abbott Laboratories (Bermuda) Ltd. | Methods of administering anti-tnf.alpha. antibodies |
| US20030206898A1 (en) | 2002-04-26 | 2003-11-06 | Steven Fischkoff | Use of anti-TNFalpha antibodies and another drug |
| US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
| MY150740A (en) | 2002-10-24 | 2014-02-28 | Abbvie Biotechnology Ltd | Low dose methods for treating disorders in which tnf? activity is detrimental |
| AU2003298816C1 (en) | 2002-12-02 | 2010-12-16 | Amgen Fremont, Inc. | Antibodies directed to Tumor Necrosis Factor and uses thereof |
| DK2376101T3 (en) | 2008-12-29 | 2016-01-18 | Trevena Inc | BETA-arrestin effectors AND COMPOSITIONS AND METHODS FOR USE THEREOF |
| NZ627995A (en) | 2012-01-31 | 2016-12-23 | Trevena Inc | ß-arrestin effectors and compositions and methods of use thereof |
| AU2015213777A1 (en) | 2014-02-07 | 2016-09-22 | Trevena, Inc. | Crystalline and amorphous forms of a beta-arrestin effector |
| CN106456698B (zh) | 2014-05-19 | 2022-05-17 | 特维娜有限公司 | β-抑制蛋白效应物的合成 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03503840A (ja) * | 1988-01-15 | 1991-08-29 | セントコアー，インコーポレーテッド | 異種連結抗体およびその治療的使用 |
| AU4182289A (en) * | 1988-08-19 | 1990-03-23 | Celltech Limited | Pharmaceutical products for anti-neoplastic therapy |
| GB8905400D0 (en) * | 1989-03-09 | 1989-04-19 | Jonker Margreet | Medicaments |
| GB8921123D0 (en) * | 1989-09-19 | 1989-11-08 | Millar Ann B | Treatment of ards |
-
1991
- 1991-08-27 JP JP3514178A patent/JPH06500323A/ja active Pending
- 1991-08-27 EP EP91915297A patent/EP0608212A1/de not_active Ceased
- 1991-08-27 CA CA002090401A patent/CA2090401A1/en not_active Abandoned
- 1991-08-27 WO PCT/AU1991/000400 patent/WO1992003145A1/en not_active Application Discontinuation
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9203145A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH06500323A (ja) | 1994-01-13 |
| WO1992003145A1 (en) | 1992-03-05 |
| CA2090401A1 (en) | 1992-02-28 |
| EP0608212A4 (de) | 1993-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU640400B2 (en) | Tumour necrosis factor binding ligands | |
| US6593458B1 (en) | Tumor necrosis factor peptide binding antibodies | |
| US6451983B2 (en) | Tumor necrosis factor antibodies | |
| US7544782B2 (en) | Tumour necrosis factor binding ligands | |
| EP0608212A1 (de) | Verfahren zur behandlung viraler infektionen | |
| AU654501B2 (en) | Method of treating viral infection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19930325 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): CH DE DK FR GB IT LI SE |
|
| 17Q | First examination report despatched |
Effective date: 19960111 |
|
| GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED |
|
| 18R | Application refused |
Effective date: 19970726 |