AU2012307157B2 - Neutralising antibodies to the major exotoxins TcdA and TcdB of Clostridium difficile - Google Patents
Neutralising antibodies to the major exotoxins TcdA and TcdB of Clostridium difficile Download PDFInfo
- Publication number
- AU2012307157B2 AU2012307157B2 AU2012307157A AU2012307157A AU2012307157B2 AU 2012307157 B2 AU2012307157 B2 AU 2012307157B2 AU 2012307157 A AU2012307157 A AU 2012307157A AU 2012307157 A AU2012307157 A AU 2012307157A AU 2012307157 B2 AU2012307157 B2 AU 2012307157B2
- Authority
- AU
- Australia
- Prior art keywords
- seq
- cdr
- sequence given
- antibody
- heavy chain
- 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.)
- Expired - Fee Related
Links
- 230000003472 neutralizing effect Effects 0.000 title claims abstract description 26
- 239000002095 exotoxin Substances 0.000 title abstract description 5
- 231100000776 exotoxin Toxicity 0.000 title abstract description 5
- 241000193163 Clostridioides difficile Species 0.000 title description 32
- 239000003053 toxin Substances 0.000 claims description 114
- 231100000765 toxin Toxicity 0.000 claims description 113
- 239000000203 mixture Substances 0.000 claims description 102
- 238000000034 method Methods 0.000 claims description 58
- 239000000427 antigen Substances 0.000 claims description 45
- 102000036639 antigens Human genes 0.000 claims description 45
- 108091007433 antigens Proteins 0.000 claims description 45
- 208000015181 infectious disease Diseases 0.000 claims description 43
- 238000003556 assay Methods 0.000 claims description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims description 29
- 208000037384 Clostridium Infections Diseases 0.000 claims description 20
- 206010009657 Clostridium difficile colitis Diseases 0.000 claims description 19
- 206010012735 Diarrhoea Diseases 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 206010054236 Clostridium difficile infection Diseases 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 11
- 108010059993 Vancomycin Proteins 0.000 claims description 8
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 claims description 8
- 229960003165 vancomycin Drugs 0.000 claims description 8
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 4
- ZVGNESXIJDCBKN-WUIGKKEISA-N R-Tiacumicin B Natural products O([C@@H]1[C@@H](C)O[C@H]([C@H]([C@H]1O)OC)OCC1=CC=CC[C@H](O)C(C)=C[C@@H]([C@H](C(C)=CC(C)=CC[C@H](OC1=O)[C@@H](C)O)O[C@H]1[C@H]([C@@H](O)[C@H](OC(=O)C(C)C)C(C)(C)O1)O)CC)C(=O)C1=C(O)C(Cl)=C(O)C(Cl)=C1CC ZVGNESXIJDCBKN-WUIGKKEISA-N 0.000 claims description 3
- ZVGNESXIJDCBKN-UUEYKCAUSA-N fidaxomicin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@H]([C@H]1O)OC)OCC\1=C/C=C/C[C@H](O)/C(C)=C/[C@@H]([C@H](/C(C)=C/C(/C)=C/C[C@H](OC/1=O)[C@@H](C)O)O[C@H]1[C@H]([C@@H](O)[C@H](OC(=O)C(C)C)C(C)(C)O1)O)CC)C(=O)C1=C(O)C(Cl)=C(O)C(Cl)=C1CC ZVGNESXIJDCBKN-UUEYKCAUSA-N 0.000 claims description 3
- 229960000628 fidaxomicin Drugs 0.000 claims description 3
- 229960002227 clindamycin Drugs 0.000 claims description 2
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims description 2
- 230000000977 initiatory effect Effects 0.000 claims description 2
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 2
- 229960000282 metronidazole Drugs 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000009795 derivation Methods 0.000 abstract 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 288
- 108700012359 toxins Proteins 0.000 description 112
- 230000027455 binding Effects 0.000 description 71
- 230000001147 anti-toxic effect Effects 0.000 description 54
- 238000006386 neutralization reaction Methods 0.000 description 50
- 210000004027 cell Anatomy 0.000 description 41
- 239000012634 fragment Substances 0.000 description 36
- 108091033319 polynucleotide Proteins 0.000 description 34
- 102000040430 polynucleotide Human genes 0.000 description 34
- 239000002157 polynucleotide Substances 0.000 description 34
- 241000699800 Cricetinae Species 0.000 description 32
- 241000282414 Homo sapiens Species 0.000 description 31
- 108090000765 processed proteins & peptides Proteins 0.000 description 31
- 238000009472 formulation Methods 0.000 description 28
- -1 IL-Ιβ Proteins 0.000 description 26
- 230000036515 potency Effects 0.000 description 26
- 102000004196 processed proteins & peptides Human genes 0.000 description 25
- 241001465754 Metazoa Species 0.000 description 24
- 210000001035 gastrointestinal tract Anatomy 0.000 description 24
- 230000000694 effects Effects 0.000 description 23
- 238000000338 in vitro Methods 0.000 description 22
- 239000012636 effector Substances 0.000 description 21
- 229920001223 polyethylene glycol Polymers 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 21
- 229920000642 polymer Polymers 0.000 description 20
- 229940024606 amino acid Drugs 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 230000006378 damage Effects 0.000 description 17
- 235000018102 proteins Nutrition 0.000 description 17
- 238000011282 treatment Methods 0.000 description 17
- 101710084578 Short neurotoxin 1 Proteins 0.000 description 15
- 101710182532 Toxin a Proteins 0.000 description 15
- 230000003308 immunostimulating effect Effects 0.000 description 15
- 239000002953 phosphate buffered saline Substances 0.000 description 15
- 239000002671 adjuvant Substances 0.000 description 14
- 230000002776 aggregation Effects 0.000 description 14
- 238000004220 aggregation Methods 0.000 description 14
- 229920001184 polypeptide Polymers 0.000 description 14
- 230000034994 death Effects 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 13
- 210000001578 tight junction Anatomy 0.000 description 13
- 229960005486 vaccine Drugs 0.000 description 13
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 12
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 101710182223 Toxin B Proteins 0.000 description 11
- 125000003275 alpha amino acid group Chemical group 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 230000002265 prevention Effects 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 102000037865 fusion proteins Human genes 0.000 description 10
- 108020001507 fusion proteins Proteins 0.000 description 10
- 239000000872 buffer Substances 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 238000013019 agitation Methods 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 8
- 210000003719 b-lymphocyte Anatomy 0.000 description 8
- 238000011321 prophylaxis Methods 0.000 description 8
- 229930182490 saponin Natural products 0.000 description 8
- 150000007949 saponins Chemical class 0.000 description 8
- 235000017709 saponins Nutrition 0.000 description 8
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 108010088751 Albumins Proteins 0.000 description 7
- 102000009027 Albumins Human genes 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- 108091034117 Oligonucleotide Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 238000002649 immunization Methods 0.000 description 7
- 229960001438 immunostimulant agent Drugs 0.000 description 7
- 239000003022 immunostimulating agent Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 208000003100 Pseudomembranous Enterocolitis Diseases 0.000 description 6
- 206010037128 Pseudomembranous colitis Diseases 0.000 description 6
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 6
- 108010090804 Streptavidin Proteins 0.000 description 6
- 230000001154 acute effect Effects 0.000 description 6
- 210000001072 colon Anatomy 0.000 description 6
- 230000003053 immunization Effects 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 6
- 229960000907 methylthioninium chloride Drugs 0.000 description 6
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000001681 protective effect Effects 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 108060003951 Immunoglobulin Proteins 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 229940037003 alum Drugs 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000005034 decoration Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 230000002163 immunogen Effects 0.000 description 5
- 102000018358 immunoglobulin Human genes 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 238000007912 intraperitoneal administration Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000001717 pathogenic effect Effects 0.000 description 5
- 238000003260 vortexing Methods 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
- 239000004743 Polypropylene Substances 0.000 description 4
- 241001415846 Procellariidae Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 206010009887 colitis Diseases 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 229930186900 holotoxin Natural products 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 229920001427 mPEG Polymers 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 238000010839 reverse transcription Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 108020001568 subdomains Proteins 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- 201000002516 toxic megacolon Diseases 0.000 description 4
- MZZYGYNZAOVRTG-UHFFFAOYSA-N 2-hydroxy-n-(1h-1,2,4-triazol-5-yl)benzamide Chemical compound OC1=CC=CC=C1C(=O)NC1=NC=NN1 MZZYGYNZAOVRTG-UHFFFAOYSA-N 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 208000003322 Coinfection Diseases 0.000 description 3
- 206010011409 Cross infection Diseases 0.000 description 3
- 206010061819 Disease recurrence Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 3
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
- BACYUWVYYTXETD-UHFFFAOYSA-N N-Lauroylsarcosine Chemical compound CCCCCCCCCCCC(=O)N(C)CC(O)=O BACYUWVYYTXETD-UHFFFAOYSA-N 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 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 3
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 3
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 3
- 159000000013 aluminium salts Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000004534 cecum Anatomy 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 239000013553 cell monolayer Substances 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 230000002939 deleterious effect Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000009931 harmful effect Effects 0.000 description 3
- 238000013537 high throughput screening Methods 0.000 description 3
- 238000001114 immunoprecipitation Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 231100000518 lethal Toxicity 0.000 description 3
- 230000001665 lethal effect Effects 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 229940053128 nerve growth factor Drugs 0.000 description 3
- 238000010899 nucleation Methods 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 239000012521 purified sample Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000007423 screening assay Methods 0.000 description 3
- 239000002356 single layer Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 230000007888 toxin activity Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 2
- 150000003923 2,5-pyrrolediones Chemical group 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 206010000060 Abdominal distension Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 206010063045 Effusion Diseases 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 101000658622 Homo sapiens Testis-specific Y-encoded-like protein 2 Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000699673 Mesocricetus auratus Species 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010029803 Nosocomial infection Diseases 0.000 description 2
- 108091081548 Palindromic sequence Proteins 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 208000035415 Reinfection Diseases 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 102100034917 Testis-specific Y-encoded-like protein 2 Human genes 0.000 description 2
- 102000000591 Tight Junction Proteins Human genes 0.000 description 2
- 108010002321 Tight Junction Proteins Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- FHICGHSMIPIAPL-HDYAAECPSA-N [2-[3-[6-[3-[(5R,6aS,6bR,12aR)-10-[6-[2-[2-[4,5-dihydroxy-3-(3,4,5-trihydroxyoxan-2-yl)oxyoxan-2-yl]ethoxy]ethyl]-3,4,5-trihydroxyoxan-2-yl]oxy-5-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]peroxypropyl]-5-[[5-[8-[3,5-dihydroxy-4-(3,4,5-trihydroxyoxan-2-yl)oxyoxan-2-yl]octoxy]-3,4-dihydroxy-6-methyloxan-2-yl]methoxy]-3,4-dihydroxyoxan-2-yl]propoxymethyl]-5-hydroxy-3-[(6S)-6-hydroxy-2,6-dimethylocta-2,7-dienoyl]oxy-6-methyloxan-4-yl] (2E,6S)-6-hydroxy-2-(hydroxymethyl)-6-methylocta-2,7-dienoate Chemical compound C=C[C@@](C)(O)CCC=C(C)C(=O)OC1C(OC(=O)C(\CO)=C\CC[C@](C)(O)C=C)C(O)C(C)OC1COCCCC1C(O)C(O)C(OCC2C(C(O)C(OCCCCCCCCC3C(C(OC4C(C(O)C(O)CO4)O)C(O)CO3)O)C(C)O2)O)C(CCCOOC(=O)C23C(CC(C)(C)CC2)C=2[C@@]([C@]4(C)CCC5C(C)(C)C(OC6C(C(O)C(O)C(CCOCCC7C(C(O)C(O)CO7)OC7C(C(O)C(O)CO7)O)O6)O)CC[C@]5(C)C4CC=2)(C)C[C@H]3O)O1 FHICGHSMIPIAPL-HDYAAECPSA-N 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000012382 advanced drug delivery Methods 0.000 description 2
- 230000009824 affinity maturation Effects 0.000 description 2
- 229910000329 aluminium sulfate Inorganic materials 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 208000024330 bloating Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000012656 cationic ring opening polymerization Methods 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000001010 compromised effect Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000011461 current therapy Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 230000003503 early effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000013020 final formulation Substances 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229960002885 histidine Drugs 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000002429 large intestine Anatomy 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 235000003715 nutritional status Nutrition 0.000 description 2
- 239000007764 o/w emulsion Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000007918 pathogenicity Effects 0.000 description 2
- 229920001281 polyalkylene Polymers 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229940068977 polysorbate 20 Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000009738 saturating Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 229920001059 synthetic polymer Polymers 0.000 description 2
- 238000002849 thermal shift Methods 0.000 description 2
- 239000012929 tonicity agent Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 108010000239 Aequorin Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 102000012936 Angiostatins Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 102000005367 Carboxypeptidases Human genes 0.000 description 1
- 108010006303 Carboxypeptidases Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 108700022831 Clostridium difficile toxB Proteins 0.000 description 1
- 208000037041 Community-Acquired Infections Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102400001047 Endostatin Human genes 0.000 description 1
- 108010079505 Endostatins Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 101000635852 Equus caballus Myoglobin Proteins 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004195 Isomerases Human genes 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 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
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 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 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 239000012515 MabSelect SuRe Substances 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 241001092142 Molina Species 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241001644525 Nastus productus Species 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
- 241001454523 Quillaja saponaria Species 0.000 description 1
- 235000009001 Quillaja saponaria Nutrition 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102000018594 Tumour necrosis factor Human genes 0.000 description 1
- 108050007852 Tumour necrosis factor Proteins 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- UFUVLHLTWXBHGZ-MGZQPHGTSA-N [(2r,3r,4s,5r,6r)-6-[(1s,2s)-2-chloro-1-[[(2s,4r)-1-methyl-4-propylpyrrolidine-2-carbonyl]amino]propyl]-4,5-dihydroxy-2-methylsulfanyloxan-3-yl] dihydrogen phosphate Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](OP(O)(O)=O)[C@@H](SC)O1 UFUVLHLTWXBHGZ-MGZQPHGTSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000009692 acute damage Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 150000003978 alpha-halocarboxylic acids Chemical class 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 238000011190 asparagine deamidation Methods 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 210000004082 barrier epithelial cell Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- JCXGWMGPZLAOME-RNFDNDRNSA-N bismuth-213 Chemical compound [213Bi] JCXGWMGPZLAOME-RNFDNDRNSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 238000007623 carbamidomethylation reaction Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 231100000762 chronic effect Toxicity 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 229960002291 clindamycin phosphate Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 230000009146 cooperative binding Effects 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 150000001944 cysteine derivatives Chemical class 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000000804 electron spin resonance spectroscopy Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 208000010227 enterocolitis Diseases 0.000 description 1
- 230000002242 enterotoxic effect Effects 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000004890 epithelial barrier function Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 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 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 210000005205 gut mucosa Anatomy 0.000 description 1
- 238000011553 hamster model Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 229940042743 immune sera Drugs 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 230000003960 inflammatory cascade Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- ZTLGJPIZUOVDMT-UHFFFAOYSA-N n,n-dichlorotriazin-4-amine Chemical compound ClN(Cl)C1=CC=NN=N1 ZTLGJPIZUOVDMT-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 230000002126 nonhaemolytic effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002859 polyalkenylene Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 235000013930 proline Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 230000000601 reactogenic effect Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 125000006853 reporter group Chemical group 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 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
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000028070 sporulation Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000010421 standard material Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 229960005314 suramin Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
- C07K16/1282—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Clostridium (G)
-
- 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
- A61K39/40—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum bacterial
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P31/04—Antibacterial agents
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/91091—Glycosyltransferases (2.4)
- G01N2333/91097—Hexosyltransferases (general) (2.4.1)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Mycology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161535532P | 2011-09-16 | 2011-09-16 | |
| US61/535,532 | 2011-09-16 | ||
| US201261638731P | 2012-04-26 | 2012-04-26 | |
| US61/638,731 | 2012-04-26 | ||
| PCT/GB2012/052222 WO2013038156A1 (en) | 2011-09-16 | 2012-09-10 | Neutralising antibodies to the major exotoxins tcda and tcdb of clostridium difficile |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2012307157A1 AU2012307157A1 (en) | 2014-04-24 |
| AU2012307157B2 true AU2012307157B2 (en) | 2017-08-03 |
Family
ID=46881094
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2012307157A Expired - Fee Related AU2012307157B2 (en) | 2011-09-16 | 2012-09-10 | Neutralising antibodies to the major exotoxins TcdA and TcdB of Clostridium difficile |
Country Status (30)
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108424449A (zh) * | 2011-09-16 | 2018-08-21 | Ucb医药有限公司 | 针对艰难梭菌的主要外毒素TcdA和TcdB的中和抗体 |
| AU2013352034B2 (en) * | 2012-11-28 | 2018-08-02 | Emergent Biosolutions Canada Inc. | Antibodies against Clostridium difficile |
| EP2988778A4 (en) * | 2013-04-22 | 2016-12-14 | Board Of Regents Of The Univ Of Oklahoma | CLOSTRIDIUM DIFFICILE IMPREGENT AND METHOD OF USE |
| CA2939969A1 (en) | 2014-02-18 | 2015-08-27 | The Hospital For Sick Children | Compositions and methods for treating or preventing clostridium infection |
| US9717711B2 (en) | 2014-06-16 | 2017-08-01 | The Lauridsen Group | Methods and compositions for treating Clostridium difficile associated disease |
| WO2016178773A1 (en) * | 2015-04-06 | 2016-11-10 | Saureus, Inc. | System and method for detecting clostridium difficile toxins |
| WO2016168392A1 (en) * | 2015-04-15 | 2016-10-20 | Medimmune, Llc | Methods for treating clostridium difficile infection and associated disease |
| MY193078A (en) | 2015-06-24 | 2022-09-26 | Hoffmann La Roche | Anti-transferrin receptor antibodies with tailored affinity |
| EP3344276B1 (en) | 2015-09-03 | 2020-04-22 | The Board of Regents of the University of Oklahoma | Peptide inhibitors of clostridium difficile tcdb toxin |
| CN108137697A (zh) | 2015-10-02 | 2018-06-08 | 豪夫迈·罗氏有限公司 | 双特异性抗人cd20/人转铁蛋白受体抗体及使用方法 |
| AR106189A1 (es) | 2015-10-02 | 2017-12-20 | Hoffmann La Roche | ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO |
| USD864160S1 (en) | 2016-12-06 | 2019-10-22 | Samsung Electronics Co., Ltd. | Audio device |
| US12071666B2 (en) * | 2016-12-14 | 2024-08-27 | Merck Sharp & Dohme Llc | Human genetic markers associated with response to treatments that target clostridium difficile toxin B |
| CN110607314B (zh) * | 2019-10-31 | 2022-09-23 | 四川农业大学 | 一种TcdB RBD基因、重组RBD蛋白和应用 |
| CN111763263A (zh) * | 2020-07-09 | 2020-10-13 | 宁夏医科大学 | 一种艰难梭菌抗原及多克隆抗体的制备方法和检测试剂盒 |
| CN112500484B (zh) * | 2021-01-29 | 2021-06-08 | 迈杰转化医学研究(苏州)有限公司 | 一种抗trop2抗体及其应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006121422A2 (en) * | 2004-02-06 | 2006-11-16 | University Of Massachusetts | Antibodies against clostridium difficile toxins and uses thereof |
Family Cites Families (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4436727A (en) | 1982-05-26 | 1984-03-13 | Ribi Immunochem Research, Inc. | Refined detoxified endotoxin product |
| US4741900A (en) | 1982-11-16 | 1988-05-03 | Cytogen Corporation | Antibody-metal ion complexes |
| GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
| DK336987D0 (da) | 1987-07-01 | 1987-07-01 | Novo Industri As | Immobiliseringsmetode |
| US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
| CA1331443C (en) | 1987-05-29 | 1994-08-16 | Charlotte A. Kensil | Saponin adjuvant |
| GB8719042D0 (en) | 1987-08-12 | 1987-09-16 | Parker D | Conjugate compounds |
| GB8720833D0 (en) | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
| US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| GB8907617D0 (en) | 1989-04-05 | 1989-05-17 | Celltech Ltd | Drug delivery system |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| EP0468520A3 (en) | 1990-07-27 | 1992-07-01 | Mitsui Toatsu Chemicals, Inc. | Immunostimulatory remedies containing palindromic dna sequences |
| WO1992002551A1 (en) | 1990-08-02 | 1992-02-20 | B.R. Centre Limited | Methods for the production of proteins with a desired function |
| GB9112536D0 (en) | 1991-06-11 | 1991-07-31 | Celltech Ltd | Chemical compounds |
| GB9113120D0 (en) | 1991-06-18 | 1991-08-07 | Kodak Ltd | Photographic processing apparatus |
| GB9120467D0 (en) | 1991-09-26 | 1991-11-06 | Celltech Ltd | Anti-hmfg antibodies and process for their production |
| JP3723231B2 (ja) | 1991-12-23 | 2005-12-07 | ディミナコ アクチェンゲゼルシャフト | アジュバント |
| CA2138997C (en) | 1992-06-25 | 2003-06-03 | Jean-Paul Prieels | Vaccine composition containing adjuvants |
| EP0812593B8 (en) | 1993-03-23 | 2010-11-10 | SmithKline Beecham Biologicals S.A. | Vaccine compositions containing 3-0 deacylated monophosphoryl lipid a |
| CN1055093C (zh) | 1993-11-17 | 2000-08-02 | 实验室奥姆公司 | 葡糖胺二糖类、其制备方法和用途、以及含有这些二糖的药物组合物 |
| GB9326253D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
| FR2716640B1 (fr) | 1994-02-28 | 1996-05-03 | Procedes Machines Speciales | Dispositif de centrage et de blocage d'une pièce en vue de son rodage à l'aide d'un rodoir à expansion. |
| EP1167378B1 (en) | 1994-07-15 | 2011-05-11 | University of Iowa Research Foundation | Immunomodulatory oligonucleotides |
| AUPM873294A0 (en) | 1994-10-12 | 1994-11-03 | Csl Limited | Saponin preparations and use thereof in iscoms |
| UA56132C2 (uk) | 1995-04-25 | 2003-05-15 | Смітклайн Бічем Байолоджікалс С.А. | Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини |
| GB9620795D0 (en) | 1996-10-05 | 1996-11-20 | Smithkline Beecham Plc | Vaccines |
| ES2241042T3 (es) | 1996-10-11 | 2005-10-16 | The Regents Of The University Of California | Conjugados de polinucleotido inmunoestimulador/ molecula inmunomoduladora. |
| US5980898A (en) | 1996-11-14 | 1999-11-09 | The United States Of America As Represented By The U.S. Army Medical Research & Material Command | Adjuvant for transcutaneous immunization |
| GB9625640D0 (en) | 1996-12-10 | 1997-01-29 | Celltech Therapeutics Ltd | Biological products |
| GB9711990D0 (en) | 1997-06-11 | 1997-08-06 | Smithkline Beecham Biolog | Vaccine |
| US6645495B1 (en) | 1997-08-29 | 2003-11-11 | Antigenics, Inc. | Compositions of saponin adjuvants and excipients |
| EP1279401B1 (en) | 1997-09-05 | 2008-01-09 | GlaxoSmithKline Biologicals S.A. | Oil in water emulsions containing saponins |
| GB9718901D0 (en) | 1997-09-05 | 1997-11-12 | Smithkline Beecham Biolog | Vaccine |
| GB9812545D0 (en) | 1998-06-10 | 1998-08-05 | Celltech Therapeutics Ltd | Biological products |
| US6908963B2 (en) | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
| WO2004041857A2 (en) * | 2002-06-17 | 2004-05-21 | Ballard Jimmy D | Mutant of clostridium difficile toxin b and methods of use |
| PT1567117E (pt) * | 2002-11-26 | 2012-05-09 | Univ Chicago | Prevenção e tratamento de distúrbios epiteliais mediados por micróbios |
| CA2507004A1 (en) | 2002-12-03 | 2004-06-17 | Celltech R & D Limited | Assay for identifying antibody producing cells |
| GB0312481D0 (en) | 2003-05-30 | 2003-07-09 | Celltech R&D Ltd | Antibodies |
| GB0315457D0 (en) | 2003-07-01 | 2003-08-06 | Celltech R&D Ltd | Biological products |
| GB0315450D0 (en) | 2003-07-01 | 2003-08-06 | Celltech R&D Ltd | Biological products |
| CA2527020A1 (en) | 2003-07-01 | 2005-01-13 | Celltech R & D Limited | Modified antibody fab fragments |
| GB0411186D0 (en) | 2004-05-19 | 2004-06-23 | Celltech R&D Ltd | Biological products |
| GB0412181D0 (en) | 2004-06-01 | 2004-06-30 | Celltech R&D Ltd | Biological products |
| CA2592015A1 (en) | 2004-12-27 | 2006-07-06 | Progenics Pharmaceuticals (Nevada), Inc. | Orally deliverable and anti-toxin antibodies and methods for making and using them |
| US9433206B2 (en) | 2004-12-27 | 2016-09-06 | Huntsman Corporation Australia Pty Limited | Reduced foam dispersions and formulations therefor |
| CN101500581B (zh) * | 2006-06-08 | 2013-10-30 | 科内尔研究基金会 | 编码艰难梭菌毒素a和毒素b受体结合域的密码子优化dna分子及其使用方法 |
| GB0619291D0 (en) | 2006-09-29 | 2006-11-08 | Ucb Sa | Altered antibodies |
| EP2195341B1 (en) | 2007-09-26 | 2017-03-22 | UCB Biopharma SPRL | Dual specificity antibody fusions |
| AU2009219358A1 (en) * | 2008-02-28 | 2009-09-03 | 3M Innovative Properties Company | Antibodies to Clostridium difficile spores and uses thereof |
| LT3216803T (lt) * | 2008-06-25 | 2020-06-10 | Novartis Ag | Stabilūs ir tirpūs antikūnai, slopinantys vegf |
| CA2737241C (en) | 2008-09-26 | 2017-08-29 | Ucb Pharma S.A. | Multivalent antibody fusion proteins |
| AU2010215275B2 (en) * | 2009-02-20 | 2016-03-31 | Micropharm Limited | Antibodies to Clostridium difficile toxins |
| BR112012026021B1 (pt) * | 2010-04-15 | 2022-05-03 | Progenics Pharmaceuticals, Inc | Anticorpos, seus fragmentos de ligação ao antígeno e seus usos, composições e uso das mesmas, linhagem de células de hibridoma, kit, ácido nucleico, e vetor de expressão |
| CA2815888C (en) * | 2010-10-25 | 2020-06-30 | National Research Council Of Canada | Clostridium difficile-specific antibodies and uses thereof |
| US9815889B2 (en) * | 2011-08-02 | 2017-11-14 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V. | Antibodies for prevention and treatment of diseases caused by clostridium difficile |
| CN108424449A (zh) * | 2011-09-16 | 2018-08-21 | Ucb医药有限公司 | 针对艰难梭菌的主要外毒素TcdA和TcdB的中和抗体 |
| UA112203C2 (uk) * | 2011-11-11 | 2016-08-10 | Юсб Фарма С.А. | Злитий білок біоспецифічного антитіла, який зв'язується з ox40 людини та сироватковим альбуміном людини |
| US20150259402A1 (en) * | 2012-10-19 | 2015-09-17 | Evec Inc. | Human antibody specific to toxin produced from clostridium difficile, or antigen-binding fragment thereof |
| GB201411320D0 (en) * | 2014-06-25 | 2014-08-06 | Ucb Biopharma Sprl | Antibody construct |
| GB201411420D0 (en) * | 2014-06-26 | 2014-08-13 | Ucb Biopharma Sprl | Antibody constructs |
| US9107906B1 (en) * | 2014-10-28 | 2015-08-18 | Adma Biologics, Inc. | Compositions and methods for the treatment of immunodeficiency |
-
2012
- 2012-09-10 CN CN201810242539.6A patent/CN108424449A/zh active Pending
- 2012-09-10 DK DK12761789.2T patent/DK2758432T3/da active
- 2012-09-10 HK HK14113105.9A patent/HK1199463A1/xx unknown
- 2012-09-10 CN CN201280049537.6A patent/CN103958544B/zh not_active Expired - Fee Related
- 2012-09-10 JP JP2014530307A patent/JP6152107B2/ja not_active Expired - Fee Related
- 2012-09-10 SG SG10201701055WA patent/SG10201701055WA/en unknown
- 2012-09-10 EP EP19160911.4A patent/EP3617227A3/en not_active Withdrawn
- 2012-09-10 HR HRP20190917TT patent/HRP20190917T1/hr unknown
- 2012-09-10 SG SG11201400193SA patent/SG11201400193SA/en unknown
- 2012-09-10 PT PT12761789T patent/PT2758432T/pt unknown
- 2012-09-10 EA EA201400345A patent/EA032475B1/ru not_active IP Right Cessation
- 2012-09-10 LT LTEP12761789.2T patent/LT2758432T/lt unknown
- 2012-09-10 PL PL12761789T patent/PL2758432T3/pl unknown
- 2012-09-10 US US14/344,637 patent/US10752676B2/en not_active Expired - Fee Related
- 2012-09-10 WO PCT/GB2012/052222 patent/WO2013038156A1/en not_active Ceased
- 2012-09-10 AU AU2012307157A patent/AU2012307157B2/en not_active Expired - Fee Related
- 2012-09-10 SI SI201231613T patent/SI2758432T1/sl unknown
- 2012-09-10 HU HUE12761789A patent/HUE043661T2/hu unknown
- 2012-09-10 PH PH1/2014/500456A patent/PH12014500456A1/en unknown
- 2012-09-10 BR BR112014006175-0A patent/BR112014006175B1/pt not_active IP Right Cessation
- 2012-09-10 EP EP12761789.2A patent/EP2758432B1/en active Active
- 2012-09-10 KR KR1020147010064A patent/KR20140063825A/ko not_active Withdrawn
- 2012-09-10 PE PE2014000353A patent/PE20141547A1/es not_active Application Discontinuation
- 2012-09-10 ES ES12761789T patent/ES2729278T3/es active Active
- 2012-09-10 MX MX2014002769A patent/MX2014002769A/es unknown
- 2012-09-10 CA CA2848611A patent/CA2848611A1/en not_active Abandoned
-
2014
- 2014-02-26 IL IL231167A patent/IL231167A0/en unknown
- 2014-02-27 CL CL2014000491A patent/CL2014000491A1/es unknown
- 2014-03-07 TN TNP2014000101A patent/TN2014000101A1/en unknown
- 2014-04-15 ZA ZA2014/02760A patent/ZA201402760B/en unknown
- 2014-04-15 CO CO14082286A patent/CO6930310A2/es unknown
- 2014-04-16 EC ECSP14013316 patent/ECSP14013316A/es unknown
-
2017
- 2017-05-26 JP JP2017104698A patent/JP6603685B2/ja not_active Expired - Fee Related
-
2019
- 2019-06-05 CY CY20191100596T patent/CY1121673T1/el unknown
- 2019-10-11 JP JP2019187271A patent/JP2020037555A/ja not_active Ceased
-
2020
- 2020-07-02 US US16/919,576 patent/US20200377578A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006121422A2 (en) * | 2004-02-06 | 2006-11-16 | University Of Massachusetts | Antibodies against clostridium difficile toxins and uses thereof |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2012307157B2 (en) | Neutralising antibodies to the major exotoxins TcdA and TcdB of Clostridium difficile | |
| US10766956B2 (en) | Antagonist antibodies that bind to human TGFB1, TGFB2 and to TGFB3 and their use for the treatment of lung fibrosis | |
| KR102742965B1 (ko) | 타우 결합 항체 | |
| ES2689470T3 (es) | Anticuerpos de Fab-Fv de conector único y métodos para producirlos | |
| CN103562227B (zh) | Pcsk9拮抗剂 | |
| MX2011008697A (es) | Moleculas de anticuerpos que tiene especificidad para ox40 humano. | |
| HRP20191293T1 (hr) | Anti-transglutaminaza 2 antitijela | |
| CN105121466A (zh) | 靶向m-csf的抗体 | |
| US20170137509A1 (en) | Vaccines and monoclonal antibodies targeting truncated variants of osteopontin and uses thereof | |
| US20240301073A1 (en) | LTBP COMPLEX-SPECIFIC INHIBITORS OF TGFb1 AND USES THEREOF | |
| NZ623293B2 (en) | Neutralising antibodies to the major exotoxins tcda and tcdb of clostridium difficile | |
| HK1244828B (zh) | Pcsk9抗体、其抗原结合片段及其医药用途 | |
| HK1245810B (zh) | Tau 结合抗体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |