JP5450402B2 - インフルエンザを阻害する組成物および方法 - Google Patents
インフルエンザを阻害する組成物および方法 Download PDFInfo
- Publication number
- JP5450402B2 JP5450402B2 JP2010514799A JP2010514799A JP5450402B2 JP 5450402 B2 JP5450402 B2 JP 5450402B2 JP 2010514799 A JP2010514799 A JP 2010514799A JP 2010514799 A JP2010514799 A JP 2010514799A JP 5450402 B2 JP5450402 B2 JP 5450402B2
- Authority
- JP
- Japan
- Prior art keywords
- influenza
- peptide
- amino acid
- seq
- residues
- 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
- 230000002401 inhibitory effect Effects 0.000 title claims description 14
- 206010022000 influenza Diseases 0.000 title description 56
- 238000000034 method Methods 0.000 title description 16
- 239000000203 mixture Substances 0.000 title description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 177
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 47
- 125000000539 amino acid group Chemical group 0.000 claims description 43
- 238000006467 substitution reaction Methods 0.000 claims description 40
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 38
- 230000004927 fusion Effects 0.000 claims description 34
- 241000712461 unidentified influenza virus Species 0.000 claims description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 229920001184 polypeptide Polymers 0.000 claims description 9
- 210000000170 cell membrane Anatomy 0.000 claims description 8
- 108010003533 Viral Envelope Proteins Proteins 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 5
- 230000009385 viral infection Effects 0.000 claims description 4
- 239000007975 buffered saline Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000003473 lipid group Chemical group 0.000 claims description 3
- 101710146275 Hemagglutinin 2 Proteins 0.000 description 103
- 238000002169 hydrotherapy Methods 0.000 description 40
- 208000037797 influenza A Diseases 0.000 description 37
- 235000001014 amino acid Nutrition 0.000 description 36
- 241000700605 Viruses Species 0.000 description 33
- 241000282339 Mustela Species 0.000 description 29
- 108090000623 proteins and genes Proteins 0.000 description 27
- 102000004169 proteins and genes Human genes 0.000 description 27
- 229940024606 amino acid Drugs 0.000 description 26
- 235000018102 proteins Nutrition 0.000 description 26
- 150000001413 amino acids Chemical class 0.000 description 23
- 241000712431 Influenza A virus Species 0.000 description 21
- 210000004899 c-terminal region Anatomy 0.000 description 21
- 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 19
- 208000037798 influenza B Diseases 0.000 description 19
- 230000003612 virological effect Effects 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- 102000037865 fusion proteins Human genes 0.000 description 13
- 108020001507 fusion proteins Proteins 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 238000003556 assay Methods 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 8
- 210000004379 membrane Anatomy 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- 210000002345 respiratory system Anatomy 0.000 description 8
- 241000282412 Homo Species 0.000 description 7
- 241000282341 Mustela putorius furo Species 0.000 description 7
- 230000035931 haemagglutination Effects 0.000 description 7
- 230000000977 initiatory effect Effects 0.000 description 7
- 210000002845 virion Anatomy 0.000 description 7
- 208000000059 Dyspnea Diseases 0.000 description 6
- 206010013975 Dyspnoeas Diseases 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 101710154606 Hemagglutinin Proteins 0.000 description 6
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 6
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 6
- 101710176177 Protein A56 Proteins 0.000 description 6
- 239000000185 hemagglutinin Substances 0.000 description 6
- 230000002209 hydrophobic effect Effects 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 206010064097 avian influenza Diseases 0.000 description 5
- 238000007499 fusion processing Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 208000036071 Rhinorrhea Diseases 0.000 description 4
- 206010039101 Rhinorrhoea Diseases 0.000 description 4
- 229940124277 aminobutyric acid Drugs 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- 230000002458 infectious effect Effects 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 210000004779 membrane envelope Anatomy 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 235000019833 protease Nutrition 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 206010041232 sneezing Diseases 0.000 description 4
- 102000001189 Cyclic Peptides Human genes 0.000 description 3
- 108010069514 Cyclic Peptides Proteins 0.000 description 3
- 150000008574 D-amino acids Chemical group 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 101710146287 Hemagglutinin 1 Proteins 0.000 description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
- 208000002979 Influenza in Birds Diseases 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 102000005348 Neuraminidase Human genes 0.000 description 3
- 108010006232 Neuraminidase Proteins 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000004590 computer program Methods 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 241001493065 dsRNA viruses Species 0.000 description 3
- 229960002591 hydroxyproline Drugs 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000002962 plaque-reduction assay Methods 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 102220325345 rs186707302 Human genes 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000001932 seasonal effect Effects 0.000 description 3
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 3
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
- 102220617592 B1 bradykinin receptor_S42C_mutation Human genes 0.000 description 2
- 102220479102 CD59 glycoprotein_N33Q_mutation Human genes 0.000 description 2
- 102220484369 E3 ubiquitin-protein ligase RNF168_I18A_mutation Human genes 0.000 description 2
- 108010032976 Enfuvirtide Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241001500351 Influenzavirus A Species 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 102220638933 Lactoylglutathione lyase_Q34E_mutation Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108010061100 Nucleoproteins Proteins 0.000 description 2
- 102100033008 Poly(U)-binding-splicing factor PUF60 Human genes 0.000 description 2
- 102220556885 Protein ALEX_K11M_mutation Human genes 0.000 description 2
- 102220556891 Protein ALEX_K17V_mutation Human genes 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 108010059722 Viral Fusion Proteins Proteins 0.000 description 2
- 108020000999 Viral RNA Proteins 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- -1 amino acids aspartate Chemical class 0.000 description 2
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 2
- 230000004596 appetite loss Effects 0.000 description 2
- 108010029566 avian influenza A virus hemagglutinin Proteins 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 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 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001413 far-infrared spectroscopy Methods 0.000 description 2
- 229940099052 fuzeon Drugs 0.000 description 2
- 208000021760 high fever Diseases 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 208000019017 loss of appetite Diseases 0.000 description 2
- 235000021266 loss of appetite Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 102200029469 rs63750123 Human genes 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical group CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- VZQHRKZCAZCACO-PYJNHQTQSA-N (2s)-2-[[(2s)-2-[2-[[(2s)-2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]prop-2-enoylamino]-3-methylbutanoyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)C(=C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCNC(N)=N VZQHRKZCAZCACO-PYJNHQTQSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 102220625006 2-(3-amino-3-carboxypropyl)histidine synthase subunit 1_E10A_mutation Human genes 0.000 description 1
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- 102220505255 5-hydroxytryptamine receptor 1B_L31I_mutation Human genes 0.000 description 1
- 101710187898 60S ribosomal protein L28 Proteins 0.000 description 1
- 102220491145 ADP-ribosylation factor-like protein 14_L20C_mutation Human genes 0.000 description 1
- 102220489853 ATP synthase subunit O, mitochondrial_L28I_mutation Human genes 0.000 description 1
- 102220587867 Acidic mammalian chitinase_S22T_mutation Human genes 0.000 description 1
- 239000004229 Alkannin Substances 0.000 description 1
- 102220547890 Apoptosis-associated speck-like protein containing a CARD_E14R_mutation Human genes 0.000 description 1
- 102220547848 Apoptosis-associated speck-like protein containing a CARD_L20A_mutation Human genes 0.000 description 1
- 102220547853 Apoptosis-associated speck-like protein containing a CARD_L27A_mutation Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102220624725 Atrial natriuretic peptide receptor 2_N24Q_mutation Human genes 0.000 description 1
- 102220534209 B-cell lymphoma/leukemia 10_L28A_mutation Human genes 0.000 description 1
- 102220484866 C-type lectin domain family 4 member A_W21A_mutation Human genes 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 102220473060 Dolichol-phosphate mannosyltransferase subunit 3_Y23S_mutation Human genes 0.000 description 1
- 102220512227 Endosomal/lysosomal potassium channel TMEM175_D41N_mutation Human genes 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 102220606755 Gap junction beta-1 protein_V13M_mutation Human genes 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102220537630 Glutathione S-transferase LANCL1_E14D_mutation Human genes 0.000 description 1
- 102220537648 Glutathione S-transferase LANCL1_E14K_mutation Human genes 0.000 description 1
- 102220529896 Glutathione S-transferase LANCL1_L20M_mutation Human genes 0.000 description 1
- 102220529903 Glutathione S-transferase LANCL1_T36S_mutation Human genes 0.000 description 1
- 206010069767 H1N1 influenza Diseases 0.000 description 1
- 102220603451 Homeobox protein SIX3_I37A_mutation Human genes 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010021079 Hypopnoea Diseases 0.000 description 1
- 241000713196 Influenza B virus Species 0.000 description 1
- 102100034349 Integrase Human genes 0.000 description 1
- 102220479320 Interferon alpha-10_S42L_mutation Human genes 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 102220574221 Lipopolysaccharide-induced tumor necrosis factor-alpha factor_Y23A_mutation Human genes 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102220470425 Melanoregulin_H35N_mutation Human genes 0.000 description 1
- 108010027796 Membrane Fusion Proteins Proteins 0.000 description 1
- 102000018897 Membrane Fusion Proteins Human genes 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102220582219 Mitochondrial antiviral-signaling protein_E26R_mutation Human genes 0.000 description 1
- 102220482931 Mitochondrial tRNA-specific 2-thiouridylase 1_H35K_mutation Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102220467825 MyoD family inhibitor domain-containing protein 2_E26D_mutation Human genes 0.000 description 1
- 102220467826 MyoD family inhibitor domain-containing protein 2_E26H_mutation Human genes 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 1
- 102220580237 Non-receptor tyrosine-protein kinase TYK2_S22A_mutation Human genes 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 102220484776 Olfactory receptor 5A1_L27I_mutation Human genes 0.000 description 1
- 208000009620 Orthomyxoviridae Infections Diseases 0.000 description 1
- 102220478178 Peptidyl-prolyl cis-trans isomerase E_L39A_mutation Human genes 0.000 description 1
- 102220633858 Phytanoyl-CoA hydroxylase-interacting protein-like_Q34T_mutation Human genes 0.000 description 1
- 241000139306 Platt Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 102220543869 Protocadherin-10_S42G_mutation Human genes 0.000 description 1
- 102220612914 Putative uncharacterized protein PIK3CD-AS1_Y12W_mutation Human genes 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 101000663557 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L17-A Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010032838 Sialoglycoproteins Proteins 0.000 description 1
- 102000007365 Sialoglycoproteins Human genes 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102220560204 Stromal cell-derived factor 1_V13T_mutation Human genes 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102220608302 Transcription factor SOX-2_Y23W_mutation Human genes 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 229940118555 Viral entry inhibitor Drugs 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 108700039655 Viroporin Proteins Proteins 0.000 description 1
- 102220506789 Vitelline membrane outer layer protein 1 homolog_L31A_mutation Human genes 0.000 description 1
- 102220477449 YY1-associated factor 2_D15E_mutation Human genes 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 239000003012 bilayer membrane Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 102220430030 c.109A>G Human genes 0.000 description 1
- 102220363170 c.112G>A Human genes 0.000 description 1
- 102220364302 c.86T>C Human genes 0.000 description 1
- 102220366446 c.94G>C Human genes 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002498 deadly effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000035618 desquamation Effects 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000011832 ferret model Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 229960003971 influenza vaccine Drugs 0.000 description 1
- 108700010900 influenza virus proteins Proteins 0.000 description 1
- 108091006086 inhibitor proteins Proteins 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000008606 intracellular interaction Effects 0.000 description 1
- 230000009545 invasion Effects 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
- 210000003734 kidney Anatomy 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 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
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 102220283291 rs1000113630 Human genes 0.000 description 1
- 102200108092 rs104894539 Human genes 0.000 description 1
- 102200153403 rs104894820 Human genes 0.000 description 1
- 102220198039 rs1057519836 Human genes 0.000 description 1
- 102220198040 rs1057519836 Human genes 0.000 description 1
- 102220229765 rs1064794750 Human genes 0.000 description 1
- 102200143559 rs11550103 Human genes 0.000 description 1
- 102200061297 rs121909233 Human genes 0.000 description 1
- 102200131586 rs121912432 Human genes 0.000 description 1
- 102220142406 rs141137691 Human genes 0.000 description 1
- 102220328414 rs1453134737 Human genes 0.000 description 1
- 102220271762 rs146066553 Human genes 0.000 description 1
- 102220316629 rs1553619289 Human genes 0.000 description 1
- 102220317882 rs1553902342 Human genes 0.000 description 1
- 102220287616 rs1555570422 Human genes 0.000 description 1
- 102220242553 rs201901274 Human genes 0.000 description 1
- 102220321320 rs202148988 Human genes 0.000 description 1
- 102200044417 rs28931612 Human genes 0.000 description 1
- 102200138511 rs339445 Human genes 0.000 description 1
- 102220109856 rs34316889 Human genes 0.000 description 1
- 102220005414 rs35210126 Human genes 0.000 description 1
- 102200087970 rs35462442 Human genes 0.000 description 1
- 102220032811 rs367543159 Human genes 0.000 description 1
- 102220297938 rs375722926 Human genes 0.000 description 1
- 102200144074 rs56079734 Human genes 0.000 description 1
- 102220041060 rs587778596 Human genes 0.000 description 1
- 102220027326 rs587779074 Human genes 0.000 description 1
- 102200028554 rs61754421 Human genes 0.000 description 1
- 102220075316 rs747896321 Human genes 0.000 description 1
- 102220227358 rs748198457 Human genes 0.000 description 1
- 102220058920 rs761960690 Human genes 0.000 description 1
- 102220240346 rs764757062 Human genes 0.000 description 1
- 102220131073 rs766853710 Human genes 0.000 description 1
- 102220326505 rs767809270 Human genes 0.000 description 1
- 102220166659 rs76788243 Human genes 0.000 description 1
- 102220062570 rs786204065 Human genes 0.000 description 1
- 102200000909 rs7905009 Human genes 0.000 description 1
- 102200016161 rs864309488 Human genes 0.000 description 1
- 102220094195 rs876660417 Human genes 0.000 description 1
- 102220089470 rs879255591 Human genes 0.000 description 1
- 102220145560 rs886058951 Human genes 0.000 description 1
- 102220150308 rs886062031 Human genes 0.000 description 1
- 102220258020 rs919338576 Human genes 0.000 description 1
- 102220214799 rs963501454 Human genes 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 108010061514 sialic acid receptor Proteins 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 201000010740 swine influenza Diseases 0.000 description 1
- 210000004876 tela submucosa Anatomy 0.000 description 1
- 238000011191 terminal modification Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 210000003956 transport vesicle Anatomy 0.000 description 1
- 210000001944 turbinate Anatomy 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
- 239000004474 valine Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000007502 viral entry Effects 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
- C07K14/08—RNA viruses
- C07K14/11—Orthomyxoviridae, e.g. influenza virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/162—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/145—Orthomyxoviridae, e.g. influenza virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/42—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum viral
-
- 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
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2/00—Peptides of undefined number of amino acids; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/00033—Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Virology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
本出願は、2007年6月25日に出願された米国仮特許出願第60/937120号の利益を主張するものであり、2003年11月4日に出願された米国仮特許出願第60/517181号の利益を主張する2004年11月3日に出願された米国特許出願第10/578013号の一部継続出願であり、これらはそれぞれ、参照によりその全体が本明細書に組み込まれる。
インフルエンザAウイルスには複数の亜型が存在する。それぞれのウイルス亜型は、ウイルスの脂質膜エンベロープ内に埋め込まれた2つの糖タンパク質の変形物の、1つの特定の組み合わせを含む。亜型を規定する2つの糖タンパク質は、血球凝集素2(HA2)およびノイラミニダーゼである。HA2にはそれぞれH1からH16と呼ばれる16個の既知の変異体が存在し、ノイラミニダーゼにはそれぞれN1からN9と呼ばれる9個の既知の変異体が存在する。それぞれのウイルス亜型は、その血球凝集素2変異体およびノイラミニダーゼ変異体の数によって特定され、特徴付けられる。例えば、インフルエンザA亜型H3N2はブタインフルエンザであり、亜型H5N1はトリインフルエンザである。
F3は、それぞれのHA2タンパク質の全ての配列および構造の両方において顕著な多様性を示す広範なH1、H3、H5、およびインフルエンザBウイルスに対する強力な感染阻害活性を有する。F3の広範な活性は、少なくとも部分的に、FIR、特に全ての既知のインフルエンザA亜型およびインフルエンザBの残基84〜99で表されるFIRの部分が、HA2タンパク質における最も高度に保存された領域の1つであるという事実に関連している可能性がある。理論に拘泥されるものではないが、F3と野生型HA2亜型の対応領域(残基84〜99)との間の配列類似性により、ペプチドがHA亜型の全てでFIRの対応部分に効果的に結合するかまたはそれと相互作用することが可能になると考えられる。この相互作用は、融合プロセスの際のHAタンパク質の正常な働きに干渉する(例えば、融合プロセスが進行するために必要なタンパク質凝集または立体構造の変化に干渉することによる)。
フェレットは通常、ヒトのインフルエンザウイルス感染についての最良のモデルであると考えられる(Govorkovaら、2005年;Hampson、2006年;MaherおよびDeStefano、2004年;van Rielら、2007年)。実際、インフルエンザワクチンの有効性についての欧州連合のガイダンスでは、フェレットモデルでの試験が必要とされている。マウスおよび他の小さな哺乳動物をインフルエンザAウイルスのヒト株に感染させることはできるが、これは典型的には、季節性株の場合、新たな宿主へのウイルスの適合を必要とする。逆に、フェレットは、適合させることなく、ヒトインフルエンザAウイルスのほとんどの株に感染させることができる。マウスにおける適合させたインフルエンザAウイルスの組織分布および発症機序は、ヒトの疾患において生じるものと異なる(Luら、1999年)。フェレットにおけるインフルエンザAウイルスの感染の発症機序は、ヒトにおいて観察されるものと非常に類似している。フェレットに、実験的に鼻腔内に接種すると、上気道におけるウイルスの局所的な複製が生じる。フェレットの気道におけるシアル酸受容体の分布はヒトに類似している(van Rielら、2006年;Yenら、2007年)。
フェレットは、1日に1回または2回、鼻腔内経路によって、約0.3mg/Kgの用量で、ウイルス暴露の前に2日間にわたり(−2日目および−1日目)、F3、またはペプチドのスクランブルされた対照変形物(配列番号14)で前処理した。最後の処理の12時間後、動物を、感染用量を見出す研究において決定された最少感染用量の少なくとも100倍である、約105pfuのH3N2インフルエンザA/Cal/07/04株を鼻腔内に接種することにより感染させた。ペプチドを、0日目の約12時間後、ならびにウイルス暴露後の1日目および2日目に、0.3mg/Kg用量でフェレットに再投与した。2日目に、スクランブルされた対照ペプチドで処理した全てのフェレットは、顕著な呼吸困難(速くて浅い呼吸)、高熱、およびくしゃみを発症していた。逆に、F3で処理した動物はいずれも重篤な呼吸困難は有していなかったが、一部(前投与を1日に2回行った群の2/5、前投与を1日に1回行った群の1/6)が、いくつかの非常に軽度の呼吸徴候およびわずかな熱を示した。3日目に、F3で処理した全てのフェレットはインフルエンザの臨床徴候を示していなかったが、スクランブルされた対照ペプチドで処理したフェレットの50%は依然として倦怠状態であり、スクランブルされた対照ペプチドで処理したフェレットの100%が顕著な鼻水を示していた。明らかに、F3はこの最初の曝露実験において、顕著でかつ驚くほど効果的な処理の利益を提供するものである。
第2の曝露研究において、12頭のフェレットがF3処理群に含まれ、12頭のフェレットが対照ペプチド群に含まれた。動物は約105pfuのインフルエンザA/Cal/07/04に感染させた。しかし、この研究において、フェレットは、事前のウイルス暴露処理を行うことなく、0日目のウイルス暴露の4時間後に、0.3mg/KgのF3または対照ペプチドで処理した。2日目に、スクランブルされた対照ペプチドで処理した全ての12頭のフェレットは、顕著な呼吸困難、高熱、およびくしゃみを発症していた。逆に、F3で処理した動物はいずれも、この時点では、呼吸困難の何らかの徴候またはインフルエンザの他の徴候は有していなかった。図6は、生存中の研究期間にわたる両方の処理群についての呼吸困難(パネルA)、鼻水(パネルB)、および活性(パネルC)の観察によって得られた、研究の間にフェレットにおいて観察された病理的応答を示す。
インフルエンザウイルスのFIRのカルボキシ末端は、N−ヘリックスのカルボキシ末端(残基104)を越えて見られるWimley−White界面ヒドロパシープロットにおいて正に増大する界面疎水性を示す、最初のペプチド配列の直前の残基として定義することができる。以下の表3は、1996年にWimleyおよびWhiteにより記載された、膜界面でのタンパク質についてのWimley−White界面疎水性スケールを示す。この疎水性またはヒドロパシーのスケールは、疎水性膜の2重層の界面から水性相へのペプチド残基の移動に必要な自由エネルギー変化に基づくものである。このスケールにおいて、モル当たりのキロカロリーで示されている正の自由エネルギー(ΔG)は、より疎水性の残基を示す(すなわち、疎水性膜から水へ疎水性残基が移動するためにはエネルギーが加えられなくてはならない。同様に、負の自由エネルギーは、より親水性の残基を示す。
高度に保存された配列であるYNAELL(配列番号1)が、13個の配列決定されたHA2亜型の11個のFIR内に存在すること、および配列番号1において単一のアミノ酸置換を示す対応配列であるYNAKLL(配列番号16)が他の2つの亜型において見られることが観察されている。13個の配列決定されたHA2変異体のうち1つの他の配列のみが、YNAELL(配列番号1)よりも高度に保存されている。その配列であるAIAGFIE(配列番号31、完全長タンパク質の残基5〜11)はHA2タンパク質の融合ペプチド内またはFP内にある。FPドメインは、クラスIウイルス融合タンパク質の5個のこれまでに知られているドメインの1つであり、FPドメインは、ウイルスの細胞への融合プロセスにおいて重要な役割を果たすことがこれまでに知られていた。
Claims (7)
- インフルエンザウイルスと宿主細胞膜との融合を阻害することによりインフルエンザウイルス感染症を治療するための薬学的組成物であって、
薬学的に許容可能な担体と、
配列番号3のアミノ酸配列および配列番号4のアミノ酸配列からなる群より選択されるアミノ酸配列からなる単離されたポリペプチド
とを含む、
薬学的組成物。 - 前記薬学的組成物がインフルエンザウイルスと接触することにより、インフルエンザウイルスエンベロープと宿主細胞膜との融合を阻害する、請求項1に記載の薬学的組成物。
- 前記薬学的に許容可能な担体が緩衝生理食塩水を含む、請求項1または2に記載の薬学的組成物。
- 吸入可能な粉末の形態である、請求項1または2に記載の薬学的組成物。
- 前記ポリペプチドが、ポリペプチドのアミノ酸残基に結合している脂質置換部位を含む、請求項1〜4のいずれか1項に記載の薬学的組成物。
- インフルエンザウイルスと宿主細胞膜との融合を阻害することによりインフルエンザウイルス感染症を治療するための薬学的組成物であって、
緩衝生理食塩水と、
配列番号3のアミノ酸配列からなる単離されたポリペプチド
とを含む、
薬学的組成物。 - 前記ポリペプチドが、ポリペプチドのアミノ酸残基に結合している脂質置換部位を含む、請求項6に記載の薬学的組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US93712007P | 2007-06-25 | 2007-06-25 | |
US60/937,120 | 2007-06-25 | ||
PCT/US2008/007918 WO2009002516A1 (en) | 2007-06-25 | 2008-06-25 | Influenza inhibiting compositions and methods |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013148405A Division JP5764621B2 (ja) | 2007-06-25 | 2013-07-17 | インフルエンザを阻害する組成物および方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2010531362A JP2010531362A (ja) | 2010-09-24 |
JP5450402B2 true JP5450402B2 (ja) | 2014-03-26 |
Family
ID=40185954
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010514799A Expired - Fee Related JP5450402B2 (ja) | 2007-06-25 | 2008-06-25 | インフルエンザを阻害する組成物および方法 |
JP2013148405A Expired - Fee Related JP5764621B2 (ja) | 2007-06-25 | 2013-07-17 | インフルエンザを阻害する組成物および方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013148405A Expired - Fee Related JP5764621B2 (ja) | 2007-06-25 | 2013-07-17 | インフルエンザを阻害する組成物および方法 |
Country Status (18)
Country | Link |
---|---|
US (2) | US8604165B2 (ja) |
EP (1) | EP2170365B1 (ja) |
JP (2) | JP5450402B2 (ja) |
KR (4) | KR20160113331A (ja) |
CN (2) | CN101848719B (ja) |
BR (1) | BRPI0813922A2 (ja) |
CA (1) | CA2691358C (ja) |
DK (1) | DK2170365T3 (ja) |
EA (1) | EA017957B1 (ja) |
ES (1) | ES2581381T3 (ja) |
HK (2) | HK1142804A1 (ja) |
HU (1) | HUE029921T2 (ja) |
IL (2) | IL202450A (ja) |
MX (2) | MX363240B (ja) |
PL (1) | PL2170365T3 (ja) |
PT (1) | PT2170365T (ja) |
WO (1) | WO2009002516A1 (ja) |
ZA (1) | ZA200909130B (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110126501A1 (en) | 2009-10-16 | 2011-06-02 | Woongjin Coway Co., Ltd. | Composition for prevention of influenza viral infection comprising tannic acid, air filter comprising the same and air cleaning device comprising the filter |
KR101153630B1 (ko) * | 2009-10-16 | 2012-06-18 | 웅진코웨이주식회사 | 타닌산을 포함하는 인플루엔자 바이러스 감염의 예방용 조성물, 상기 조성물을 포함하는 기상필터 및 상기 필터를 포함하는 공기청정기 |
US9683030B2 (en) * | 2012-05-10 | 2017-06-20 | Massachusetts Institute Of Technology | Agents for influenza neutralization |
US9649375B2 (en) | 2013-03-14 | 2017-05-16 | The Administrators Of The Tulane Educational Fund | Immunogenic peptide conjugate and method for inducing an anti-influenza therapeutic antibody response therewith |
US20180128545A1 (en) * | 2016-11-08 | 2018-05-10 | Berry Metal Company | Modular furnace cooling wall |
WO2018102753A1 (en) * | 2016-12-02 | 2018-06-07 | Emory University | Peptides and uses for managing viral infections |
US11918641B2 (en) | 2020-05-08 | 2024-03-05 | Academia Sinica | Chimeric influenza vaccines |
WO2021253172A1 (zh) * | 2020-06-15 | 2021-12-23 | 上海市公共卫生临床中心 | 利用受体识别域诱导抗新冠病毒中和抗体的方法 |
CN113801206A (zh) * | 2020-06-15 | 2021-12-17 | 上海市公共卫生临床中心 | 利用受体识别域诱导抗新冠病毒中和抗体的方法 |
TW202334429A (zh) | 2021-10-01 | 2023-09-01 | 中央研究院 | Sars-cov-2棘蛋白特異性抗體及其用途 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1711888A (en) | 1987-04-24 | 1988-12-02 | Biogen, Inc. | Immunotherapeutic methods and compositions |
US5747239A (en) | 1990-02-16 | 1998-05-05 | United Biomedical, Inc. | Synthetic peptides specific for the detection of antibodies to HCV, diagnosis of HCV infection and preventions thereof as vaccines |
US5567805A (en) | 1990-03-09 | 1996-10-22 | Administrators Of The Tulane Educational Fund | The cellular receptor for the CS3 peptide of human immunodeficiency virus |
WO1994017826A1 (en) | 1993-02-01 | 1994-08-18 | Smithkline Beecham Corporation | Vaccinal polypeptides |
US5464933A (en) | 1993-06-07 | 1995-11-07 | Duke University | Synthetic peptide inhibitors of HIV transmission |
US6310180B1 (en) * | 1993-06-21 | 2001-10-30 | Vanderbilt University | Method for synthesis of proteins |
US6037348A (en) | 1996-02-09 | 2000-03-14 | Eli Lilly And Company | Inhibition of viral replication |
CA2271249C (en) * | 1996-11-14 | 2010-07-20 | Biota Scientific Management Pty. Ltd. | Macromolecular neuraminidase-binding compounds |
GB9712892D0 (en) * | 1997-06-20 | 1997-08-20 | Eclagen Ltd | Identification of mhc binding peptides |
US6750008B1 (en) | 1999-07-09 | 2004-06-15 | Trimeris, Inc. | Methods and compositions for inhibition of membrane fusion-associated events, including HIV transmission |
AU3334001A (en) | 2000-02-10 | 2001-08-20 | Panacos Pharmaceuticals Inc | Assay for detection of viral fusion inhibitors |
GB0022969D0 (en) * | 2000-09-19 | 2000-11-01 | Chiron Spa | Influenza a virus subtype H16 |
US7189800B2 (en) * | 2001-03-27 | 2007-03-13 | Samuel Bogoch | Replikin peptides in rapid replication of glioma cells and in influenza epidemics |
US7894999B2 (en) | 2001-03-27 | 2011-02-22 | Samuel Bogoch | Systems and methods for identifying Replikin Scaffolds and uses of said Replikin Scaffolds |
JP2006519775A (ja) * | 2003-03-07 | 2006-08-31 | メルク エンド カムパニー インコーポレーテッド | インフルエンザウイルスワクチン |
WO2005016238A2 (en) | 2003-05-08 | 2005-02-24 | Duke University | Severe acute respiratory syndrome |
CA2533113A1 (en) | 2003-07-21 | 2005-02-03 | Government Of The United States Of America As Represented By The Secreta Ry Of The Department Of Health And Human Services National Institutes Of | Soluble fragments of the sars-cov spike glycoprotein |
ES2392891T3 (es) | 2003-11-04 | 2012-12-14 | The Administrators Of The Tulane Educational Fund | Procedimiento de prevención de la fusión virus célula inhibiendo la función de la región de iniciación de fusión de virus de ARN que tienen proteínas de envoltura fusogénicas de membrana de clase I |
US7871626B2 (en) * | 2005-08-04 | 2011-01-18 | St. Jude Children's Research Hospital | Modified influenza virus for monitoring and improving vaccine efficiency |
DE102005060920A1 (de) * | 2005-12-18 | 2007-06-21 | Charité - Universitätsmedizin Berlin | Peptide für die Wechselwirkung mit alpha-helikalen Coiled-Coil-Strukturen und/oder Coiled-Coil-Sequenzen, davon abgeleitete Mittel und ihre Verwendung |
WO2008039267A2 (en) * | 2006-07-21 | 2008-04-03 | Pharmexa Inc. | Inducing cellular immune responses to influenza virus using peptide and nucleic acid compositions |
-
2008
- 2008-06-25 PT PT87797635T patent/PT2170365T/pt unknown
- 2008-06-25 BR BRPI0813922A patent/BRPI0813922A2/pt not_active Application Discontinuation
- 2008-06-25 CN CN200880021890.7A patent/CN101848719B/zh not_active Expired - Fee Related
- 2008-06-25 KR KR1020167025897A patent/KR20160113331A/ko active Application Filing
- 2008-06-25 PL PL08779763T patent/PL2170365T3/pl unknown
- 2008-06-25 KR KR1020187005216A patent/KR20180021930A/ko not_active Application Discontinuation
- 2008-06-25 MX MX2014004158A patent/MX363240B/es unknown
- 2008-06-25 KR KR1020107001579A patent/KR101660363B1/ko active IP Right Grant
- 2008-06-25 HU HUE08779763A patent/HUE029921T2/en unknown
- 2008-06-25 CN CN201510511651.1A patent/CN105237629B/zh not_active Expired - Fee Related
- 2008-06-25 CA CA2691358A patent/CA2691358C/en not_active Expired - Fee Related
- 2008-06-25 ES ES08779763.5T patent/ES2581381T3/es active Active
- 2008-06-25 MX MX2009013635A patent/MX2009013635A/es active IP Right Grant
- 2008-06-25 EP EP08779763.5A patent/EP2170365B1/en not_active Not-in-force
- 2008-06-25 JP JP2010514799A patent/JP5450402B2/ja not_active Expired - Fee Related
- 2008-06-25 US US12/452,240 patent/US8604165B2/en active Active
- 2008-06-25 KR KR1020157026965A patent/KR101719135B1/ko active IP Right Grant
- 2008-06-25 EA EA201070053A patent/EA017957B1/ru not_active IP Right Cessation
- 2008-06-25 WO PCT/US2008/007918 patent/WO2009002516A1/en active Application Filing
- 2008-06-25 DK DK08779763.5T patent/DK2170365T3/en active
-
2009
- 2009-12-01 IL IL202450A patent/IL202450A/en active IP Right Grant
- 2009-12-21 ZA ZA200909130A patent/ZA200909130B/xx unknown
-
2010
- 2010-09-27 HK HK10109216.7A patent/HK1142804A1/zh not_active IP Right Cessation
-
2013
- 2013-07-17 JP JP2013148405A patent/JP5764621B2/ja not_active Expired - Fee Related
- 2013-12-10 US US14/101,452 patent/US9353157B2/en not_active Expired - Fee Related
-
2015
- 2015-04-21 IL IL238404A patent/IL238404A/en active IP Right Grant
-
2016
- 2016-03-16 HK HK16103026.4A patent/HK1215037A1/zh unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5764621B2 (ja) | インフルエンザを阻害する組成物および方法 | |
CN107106642B (zh) | 拟肽大环化合物及其制剂 | |
US20140370042A1 (en) | Stabilized Antiviral Fusion Helices | |
JP7439367B2 (ja) | 最適化化合物 | |
US8222204B2 (en) | Influenza inhibiting compositions and methods | |
US11299518B2 (en) | Fusion respiratory syncytial virus inhibitors and use thereof | |
WO2018084247A1 (ja) | 免疫誘導剤 | |
WO2018038168A1 (ja) | ヘマグルチニン結合ペプチド、および、これを含むインフルエンザウイルス感染症の予防・治療薬 | |
JP2011524373A (ja) | インフルエンザウイルスに対する新規抗ウイルスペプチド | |
AU2008269081B2 (en) | Influenza inhibiting compositions and methods | |
US20210177795A1 (en) | Administering compounds | |
KR20190122229A (ko) | 인플루엔자에 대한 면역원성 조성물 | |
US20240108713A1 (en) | Novel replication deficient influenza a virus inducing high levels of type i interferon |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100623 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100623 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121016 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130115 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130402 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130717 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20130822 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131015 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131030 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20131126 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131225 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5450402 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |