NZ518860A - Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors - Google Patents
Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectorsInfo
- Publication number
- NZ518860A NZ518860A NZ518860A NZ51886000A NZ518860A NZ 518860 A NZ518860 A NZ 518860A NZ 518860 A NZ518860 A NZ 518860A NZ 51886000 A NZ51886000 A NZ 51886000A NZ 518860 A NZ518860 A NZ 518860A
- Authority
- NZ
- New Zealand
- Prior art keywords
- mmol
- phosphono
- composition
- salt
- group
- Prior art date
Links
- -1 Aminoalkyl glucosaminide phosphate compounds Chemical class 0.000 title claims abstract description 98
- 239000002671 adjuvant Substances 0.000 title abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 270
- 150000003839 salts Chemical class 0.000 claims abstract description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 52
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims abstract description 42
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 29
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 26
- 239000001257 hydrogen Substances 0.000 claims abstract description 18
- 150000008271 glucosaminides Chemical class 0.000 claims abstract description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 15
- 150000002148 esters Chemical class 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 13
- 150000001408 amides Chemical class 0.000 claims abstract description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 239000007787 solid Substances 0.000 claims description 112
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 87
- 239000000203 mixture Substances 0.000 claims description 72
- 241000699670 Mus sp. Species 0.000 claims description 64
- 238000002360 preparation method Methods 0.000 claims description 51
- 229910001868 water Inorganic materials 0.000 claims description 44
- 150000002190 fatty acyls Chemical group 0.000 claims description 37
- 229960005486 vaccine Drugs 0.000 claims description 35
- 102000036639 antigens Human genes 0.000 claims description 34
- 108091007433 antigens Proteins 0.000 claims description 34
- 239000000427 antigen Substances 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 230000028993 immune response Effects 0.000 claims description 12
- 239000000839 emulsion Substances 0.000 claims description 11
- 239000004094 surface-active agent Substances 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 230000004071 biological effect Effects 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000003786 synthesis reaction Methods 0.000 claims description 4
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 3
- 239000006185 dispersion Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 239000011859 microparticle Substances 0.000 claims description 3
- 239000004005 microsphere Substances 0.000 claims description 3
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 3
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 claims 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 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 239000002156 adsorbate Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 2
- 239000000920 calcium hydroxide Substances 0.000 claims description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 229940009976 deoxycholate Drugs 0.000 claims description 2
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 claims description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 2
- 244000309464 bull Species 0.000 claims 3
- 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 claims 3
- 230000000259 anti-tumor effect Effects 0.000 claims 2
- 239000007788 liquid Substances 0.000 claims 2
- 125000003607 serino group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 2
- NEZDNQCXEZDCBI-WJOKGBTCSA-N (2-aminoethoxy)[(2r)-2,3-bis(tetradecanoyloxy)propoxy]phosphinic acid Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCC NEZDNQCXEZDCBI-WJOKGBTCSA-N 0.000 claims 1
- 239000003963 antioxidant agent Substances 0.000 claims 1
- 230000003078 antioxidant effect Effects 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 16
- 241001465754 Metazoa Species 0.000 abstract description 9
- 125000004103 aminoalkyl group Chemical group 0.000 abstract description 5
- 230000016784 immunoglobulin production Effects 0.000 abstract description 5
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- 229910019142 PO4 Inorganic materials 0.000 abstract description 3
- 230000016396 cytokine production Effects 0.000 abstract description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract description 2
- 239000010452 phosphate Substances 0.000 abstract description 2
- 125000001924 fatty-acyl group Chemical group 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 147
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 89
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 85
- 239000000243 solution Substances 0.000 description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 44
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 43
- OKKJLVBELUTLKV-MZCSYVLQSA-N CD3OD Substances [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 42
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 38
- 239000000463 material Substances 0.000 description 37
- 239000003981 vehicle Substances 0.000 description 37
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- 229910052725 zinc Inorganic materials 0.000 description 34
- 239000011701 zinc Substances 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 28
- 229910003446 platinum oxide Inorganic materials 0.000 description 28
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 description 27
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 26
- 230000003053 immunization Effects 0.000 description 25
- 238000002649 immunization Methods 0.000 description 25
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 17
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 17
- 210000002966 serum Anatomy 0.000 description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
- 125000005640 glucopyranosyl group Chemical group 0.000 description 16
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 16
- 238000002255 vaccination Methods 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 15
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- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 15
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
- BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 13
- IIDNACBMUWTYIV-VIFPVBQESA-N benzyl (2s)-2-amino-3-hydroxypropanoate Chemical compound OC[C@H](N)C(=O)OCC1=CC=CC=C1 IIDNACBMUWTYIV-VIFPVBQESA-N 0.000 description 13
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
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- DKVBOUDTNWVDEP-NJCHZNEYSA-N teicoplanin aglycone Chemical group N([C@H](C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)OC=1C=C3C=C(C=1O)OC1=CC=C(C=C1Cl)C[C@H](C(=O)N1)NC([C@H](N)C=4C=C(O5)C(O)=CC=4)=O)C(=O)[C@@H]2NC(=O)[C@@H]3NC(=O)[C@@H]1C1=CC5=CC(O)=C1 DKVBOUDTNWVDEP-NJCHZNEYSA-N 0.000 description 10
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
- C07H13/06—Fatty acids
-
- 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
-
- 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
-
- 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
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/439,839 US6303347B1 (en) | 1997-05-08 | 1999-11-12 | Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors |
| PCT/US2000/031340 WO2001034617A2 (en) | 1999-11-12 | 2000-11-13 | Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ518860A true NZ518860A (en) | 2004-11-26 |
Family
ID=23746342
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ518860A NZ518860A (en) | 1999-11-12 | 2000-11-13 | Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6303347B1 (https=) |
| EP (1) | EP1230250A2 (https=) |
| JP (1) | JP2003514783A (https=) |
| CN (1) | CN1409720A (https=) |
| AR (1) | AR026443A1 (https=) |
| BR (1) | BR0015501A (https=) |
| CA (1) | CA2391299A1 (https=) |
| CO (1) | CO5261562A1 (https=) |
| MX (1) | MXPA02004774A (https=) |
| NO (1) | NO20022207L (https=) |
| NZ (1) | NZ518860A (https=) |
| WO (1) | WO2001034617A2 (https=) |
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| US7063967B2 (en) * | 1997-05-08 | 2006-06-20 | Corixa Corporation | Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors |
| US7541020B2 (en) * | 1997-05-08 | 2009-06-02 | Corixa Corporation | Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors |
| US6764840B2 (en) * | 1997-05-08 | 2004-07-20 | Corixa Corporation | Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors |
| US20030235557A1 (en) | 1998-09-30 | 2003-12-25 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
| US6699846B2 (en) * | 2000-03-17 | 2004-03-02 | Corixa Corporation | Mono- and disaccharides for the treatment of nitric oxide related disorders |
| EP2000144A1 (en) * | 2000-05-19 | 2008-12-10 | Corixa Corporation | Prophylactic and therapeutic treatment of infectious, autoimmune and allergic diseases with mono-and disaccharide-based compounds |
| US20030105032A1 (en) * | 2000-05-19 | 2003-06-05 | Persing David H. | Phophylactic and therapeutic treatment of infectious and other diseases with mono-and disaccharide-based compounds |
| US20030139356A1 (en) * | 2001-05-18 | 2003-07-24 | Persing David H. | Prophylactic and therapeutic treatment of infectious and other diseases with mono- and disaccharide-based compounds |
| US20060142202A1 (en) * | 2000-12-08 | 2006-06-29 | 3M Innovative Properties Company | Compositions and methods for targeted delivery of immune response modifiers |
| US7361352B2 (en) | 2001-08-15 | 2008-04-22 | Acambis, Inc. | Influenza immunogen and vaccine |
| AU2002350181A1 (en) * | 2001-10-31 | 2003-05-12 | Corixa Corporation | Compositions and methods for viral delivery |
| US6911434B2 (en) * | 2002-02-04 | 2005-06-28 | Corixa Corporation | Prophylactic and therapeutic treatment of infectious and other diseases with immunoeffector compounds |
| US20030190333A1 (en) * | 2002-02-04 | 2003-10-09 | Corixa Corporation | Immunostimulant compositions comprising aminoalkyl glucosaminide phosphates and saponins |
| US7030094B2 (en) * | 2002-02-04 | 2006-04-18 | Corixa Corporation | Immunostimulant compositions comprising an aminoalkyl glucosaminide phosphate and QS-21 |
| US7351413B2 (en) * | 2002-02-21 | 2008-04-01 | Lorantis, Limited | Stabilized HBc chimer particles as immunogens for chronic hepatitis |
| NZ534566A (en) * | 2002-02-22 | 2007-02-23 | 3M Innovative Properties Co | Method of reducing and treating UVB-induced immunosuppression |
| WO2003073827A2 (en) * | 2002-02-28 | 2003-09-12 | Corixa Corporation | Methods of modulating dendritic cells using adjuvants |
| US7288640B2 (en) * | 2002-07-08 | 2007-10-30 | Corixa Corporation | Processes for the production of aminoalkyl glucosaminide phosphate and disaccharide immunoeffectors, and intermediates therefor |
| RU2340621C2 (ru) * | 2002-07-08 | 2008-12-10 | Корикса Корпорейшн | Способы получения аминоалкилглюкозаминидфосфатов и дисахаридных иммуноэффекторов и их промежуточных соединений |
| AU2003299994A1 (en) * | 2002-12-27 | 2004-07-29 | Chiron Corporation | Immunogenic compositions containing phospholpid |
| AU2003300184B8 (en) | 2002-12-30 | 2009-12-03 | 3M Innovative Properties Company | Immunostimulatory combinations |
| CA2512108C (en) * | 2003-01-06 | 2013-04-02 | Corixa Corporation | Certain aminoalkyl glucosaminide phosphate compounds and their use |
| US7960522B2 (en) * | 2003-01-06 | 2011-06-14 | Corixa Corporation | Certain aminoalkyl glucosaminide phosphate compounds and their use |
| JP2006517974A (ja) * | 2003-02-13 | 2006-08-03 | スリーエム イノベイティブ プロパティズ カンパニー | Ｉｒｍ化合物およびトル様受容体８に関する方法および組成物 |
| US7485432B2 (en) * | 2003-02-27 | 2009-02-03 | 3M Innovative Properties Company | Selective modulation of TLR-mediated biological activity |
| US8110582B2 (en) | 2003-03-04 | 2012-02-07 | 3M Innovative Properties Company | Prophylactic treatment of UV-induced epidermal neoplasia |
| AU2004220465A1 (en) | 2003-03-13 | 2004-09-23 | 3M Innovative Properties Company | Method of tattoo removal |
| MXPA05009694A (es) * | 2003-03-13 | 2005-10-20 | 3M Innovative Properties Co | Metodos para mejorar la calidad de la piel. |
| US20040192585A1 (en) * | 2003-03-25 | 2004-09-30 | 3M Innovative Properties Company | Treatment for basal cell carcinoma |
| AU2004244962A1 (en) * | 2003-04-10 | 2004-12-16 | 3M Innovative Properties Company | Delivery of immune response modifier compounds using metal-containing particulate support materials |
| US20040265351A1 (en) * | 2003-04-10 | 2004-12-30 | Miller Richard L. | Methods and compositions for enhancing immune response |
| CA2534625A1 (en) * | 2003-08-05 | 2005-02-24 | 3M Innovative Properties Company | Infection prophylaxis using immune response modifier compounds |
| BRPI0413558A (pt) | 2003-08-12 | 2006-10-17 | 3M Innovative Properties Co | compostos contendo imidazo substituìdo por hidroxilamina |
| AU2004266162A1 (en) * | 2003-08-25 | 2005-03-03 | 3M Innovative Properties Company | Immunostimulatory combinations and treatments |
| MXPA06002199A (es) | 2003-08-27 | 2006-05-22 | 3M Innovative Properties Co | Imidazoquinolinas sustituidas con grupos ariloxi o arilalquilenoxi. |
| CA2537763A1 (en) * | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for cd5+ b cell lymphoma |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| CA2540541C (en) | 2003-10-03 | 2012-03-27 | 3M Innovative Properties Company | Alkoxy substituted imidazoquinolines |
| EP1680080A4 (en) * | 2003-10-31 | 2007-10-31 | 3M Innovative Properties Co | NEUTROPHILIC ACTIVATION THROUGH COMPOUNDS TO MODIFY THE IMMUNE RESPONSE |
| US7897767B2 (en) | 2003-11-14 | 2011-03-01 | 3M Innovative Properties Company | Oxime substituted imidazoquinolines |
| WO2005048945A2 (en) | 2003-11-14 | 2005-06-02 | 3M Innovative Properties Company | Hydroxylamine substituted imidazo ring compounds |
| WO2005051317A2 (en) | 2003-11-25 | 2005-06-09 | 3M Innovative Properties Company | Substituted imidazo ring systems and methods |
| US20050226878A1 (en) * | 2003-12-02 | 2005-10-13 | 3M Innovative Properties Company | Therapeutic combinations and methods including IRM compounds |
| US8940755B2 (en) * | 2003-12-02 | 2015-01-27 | 3M Innovative Properties Company | Therapeutic combinations and methods including IRM compounds |
| JP2007517035A (ja) | 2003-12-29 | 2007-06-28 | スリーエム イノベイティブ プロパティズ カンパニー | アリールアルケニルおよびアリールアルキニル置換されたイミダゾキノリン |
| JP2007517055A (ja) * | 2003-12-30 | 2007-06-28 | スリーエム イノベイティブ プロパティズ カンパニー | 免疫応答の増強 |
| EP1699788A2 (en) | 2003-12-30 | 2006-09-13 | 3M Innovative Properties Company | Imidazoquinolinyl, imidazopyridinyl and imidazonaphthyridinyl sulfonamides |
| WO2005094531A2 (en) | 2004-03-24 | 2005-10-13 | 3M Innovative Properties Company | Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines |
| CA2564180A1 (en) * | 2004-04-22 | 2005-11-03 | Dainippon Sumitomo Pharma Co., Ltd. | Pharmaceutical preparation containing bacterial cell wall skeleton component |
| CA2564855A1 (en) * | 2004-04-28 | 2005-10-28 | 3M Innovative Properties Company | Compositions and methods for mucosal vaccination |
| US20050267145A1 (en) * | 2004-05-28 | 2005-12-01 | Merrill Bryon A | Treatment for lung cancer |
| US8017779B2 (en) | 2004-06-15 | 2011-09-13 | 3M Innovative Properties Company | Nitrogen containing heterocyclyl substituted imidazoquinolines and imidazonaphthyridines |
| US7897609B2 (en) | 2004-06-18 | 2011-03-01 | 3M Innovative Properties Company | Aryl substituted imidazonaphthyridines |
| US7915281B2 (en) | 2004-06-18 | 2011-03-29 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and method |
| US8026366B2 (en) | 2004-06-18 | 2011-09-27 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted thiazoloquinolines and thiazolonaphthyridines |
| WO2006026470A2 (en) * | 2004-08-27 | 2006-03-09 | 3M Innovative Properties Company | Hiv immunostimulatory compositions |
| EP1804583A4 (en) * | 2004-10-08 | 2009-05-20 | 3M Innovative Properties Co | ADJUVANT FOR DNA VACCINE |
| CA2594253C (en) | 2004-12-30 | 2015-08-11 | 3M Innovative Properties Company | Treatment for cutaneous metastases |
| JP5543068B2 (ja) | 2004-12-30 | 2014-07-09 | スリーエム イノベイティブ プロパティズ カンパニー | キラル縮合［１，２］イミダゾ［４，５−ｃ］環状化合物 |
| AU2005326708C1 (en) | 2004-12-30 | 2012-08-30 | 3M Innovative Properties Company | Substituted chiral fused [1,2]imidazo[4,5-c] ring compounds |
| WO2006084251A2 (en) | 2005-02-04 | 2006-08-10 | Coley Pharmaceutical Group, Inc. | Aqueous gel formulations containing immune reponse modifiers |
| CA2597587A1 (en) | 2005-02-11 | 2006-08-17 | Coley Pharmaceutical Group, Inc. | Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods |
| JP2008535832A (ja) | 2005-04-01 | 2008-09-04 | コーリー ファーマシューティカル グループ，インコーポレイテッド | ピラゾロピリジン−１，４−ジアミン、およびそのアナログ |
| JP2008538550A (ja) | 2005-04-01 | 2008-10-30 | コーリー ファーマシューティカル グループ，インコーポレイテッド | ウイルス感染および腫瘍性疾患を処置するためのサイトカイン生合成の調節因子としての１−置換ピラゾロ（３，４−ｃ）環状化合物 |
| EP1881844A2 (en) * | 2005-05-19 | 2008-01-30 | GlaxoSmithKline Biologicals S.A. | Vaccine composition comprising b-subunit of e.coli heat labile toxin and an antigen and an adjuvant |
| GB0512751D0 (en) * | 2005-06-22 | 2005-07-27 | Glaxo Group Ltd | New adjuvant |
| EP1924279A2 (en) * | 2005-09-07 | 2008-05-28 | The Secretary of State for Defence | Adjuvanted vaccine |
| GB0524409D0 (en) * | 2005-11-30 | 2006-01-11 | Glaxosmithkline Biolog Sa | Vaccines |
| GB0524408D0 (en) * | 2005-11-30 | 2006-01-11 | Glaxosmithkline Biolog Sa | Vaccines |
| GB0607088D0 (en) | 2006-04-07 | 2006-05-17 | Glaxosmithkline Biolog Sa | Vaccine |
| PL1973564T3 (pl) | 2005-12-22 | 2017-04-28 | Glaxosmithkline Biologicals S.A. | Szczepionki zawierające koniugaty polisacharydu otoczkowego streptococcus pneumoniae |
| EP1988896A4 (en) | 2006-02-22 | 2011-07-27 | 3M Innovative Properties Co | CONJUGATES TO MODIFY IMMUNE REACTIONS |
| MY148405A (en) | 2006-03-30 | 2013-04-30 | Glaxosmithkline Biolog Sa | Immunogenic composition |
| EP2032719A2 (en) | 2006-06-02 | 2009-03-11 | GlaxoSmithKline Biologicals S.A. | Method for identifying whether a patient will be responder or not to immunotherapy |
| US7906506B2 (en) | 2006-07-12 | 2011-03-15 | 3M Innovative Properties Company | Substituted chiral fused [1,2] imidazo [4,5-c] ring compounds and methods |
| ES2437082T3 (es) | 2006-07-18 | 2014-01-08 | Glaxosmithkline Biologicals S.A. | Vacunas contra la malaria |
| WO2008012538A2 (en) * | 2006-07-25 | 2008-01-31 | The Secretary Of State For Defence | Live vaccine strains of francisella |
| PL2086582T3 (pl) | 2006-10-12 | 2013-04-30 | Glaxosmithkline Biologicals Sa | Kompozycja zawierająca adiuwant w postaci emulsji typu olej w wodzie |
| US20080149123A1 (en) | 2006-12-22 | 2008-06-26 | Mckay William D | Particulate material dispensing hairbrush with combination bristles |
| HRP20161606T1 (hr) | 2007-03-02 | 2017-01-13 | Glaxosmithkline Biologicals Sa | Novi postupak i pripravci |
| US9452209B2 (en) | 2007-04-20 | 2016-09-27 | Glaxosmithkline Biologicals Sa | Influenza vaccine |
| SI2167121T1 (sl) | 2007-06-26 | 2015-12-31 | Glaxosmithkline Biologicals S.A. | Cepivo, ki obsega kapsularne polisaharidne konjugate Streptococcusa pneumoniae |
| EP2173376B1 (en) * | 2007-08-02 | 2015-03-25 | Biondvax Pharmaceuticals Ltd. | Multimeric multiepitope influenza vaccines |
| CA2699853A1 (en) | 2007-09-17 | 2009-03-26 | Oncomethylome Sciences Sa | Improved detection of mage-a expression |
| US20090215710A1 (en) * | 2007-09-24 | 2009-08-27 | Reliance Life Sciences Pvt. Ltd. | Carbohydrate based toll-like receptor (tlr) antagonists |
| ES2626634T3 (es) | 2007-12-19 | 2017-07-25 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Formas solubles de la glucoproteína F del virus de Hendra y Nipah y usos de la misma |
| PL2222710T3 (pl) | 2007-12-24 | 2017-01-31 | Id Biomedical Corporation Of Quebec | Rekombinowane antygeny rsv |
| SI2271360T1 (sl) | 2008-04-16 | 2015-12-31 | Glaxosmithkline Biologicals S.A. | Cepivo |
| GB0815872D0 (en) * | 2008-09-01 | 2008-10-08 | Pasteur Institut | Novel method and compositions |
| US20110236470A1 (en) | 2008-12-03 | 2011-09-29 | Yaffa Mizrachi Nebenzahl | GLUTAMYL tRNA SYNTHETASE (GtS) FRAGMENTS |
| WO2010079081A1 (en) | 2009-01-07 | 2010-07-15 | Glaxosmithkline Biologicals S.A. | Methods for recovering a virus or a viral antigen produced by cell culture |
| GB0901423D0 (en) | 2009-01-29 | 2009-03-11 | Secr Defence | Treatment |
| GB0901411D0 (en) | 2009-01-29 | 2009-03-11 | Secr Defence | Treatment |
| CA2750055A1 (en) | 2009-02-06 | 2010-08-12 | Glaxosmithkline Biologicals S.A. | Method for purifying viruses using a density gradient |
| AR075437A1 (es) | 2009-02-17 | 2011-03-30 | Glaxosmithkline Biolog Sa | Composicion inmunogenica que comprende al menos un antigeno del virus del dengue inactivado y un adyuvante sin aluminio, metodo para producir dicha vacuna y su uso para preparar un medicamento |
| CA2755734A1 (en) | 2009-03-17 | 2010-09-23 | Gaetan Otto | Improved detection of gene expression |
| GB0906234D0 (en) | 2009-04-14 | 2009-05-20 | Secr Defence | Vaccine |
| MX2012000035A (es) | 2009-06-24 | 2012-02-28 | Id Biomedical Corp Quebec | Antigenos de virus de sincicio respiratorio recombinantes. |
| AU2010264686A1 (en) | 2009-06-24 | 2012-01-19 | Glaxosmithkline Biologicals S.A. | Vaccine |
| US9907746B2 (en) | 2009-07-06 | 2018-03-06 | Variation Biotechnologies, Inc. | Methods for preparing vesicles and formulations produced therefrom |
| AU2010270722B2 (en) | 2009-07-06 | 2015-06-04 | Variation Biotechnologies, Inc. | Methods for preparing vesicles and formulations produced therefrom |
| EP4218799A1 (en) | 2009-07-15 | 2023-08-02 | GlaxoSmithKline Biologicals S.A. | Rsv f protein compositions and methods for making same |
| GB0913680D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
| GB0917457D0 (en) | 2009-10-06 | 2009-11-18 | Glaxosmithkline Biolog Sa | Method |
| US9341623B2 (en) | 2009-09-25 | 2016-05-17 | Glaxosmithkline Biologicals Sa | Immunodiffusion assay for influenza virus |
| GB0919117D0 (en) | 2009-10-30 | 2009-12-16 | Glaxosmithkline Biolog Sa | Process |
| WO2011067758A2 (en) | 2009-12-02 | 2011-06-09 | Protea Vaccine Technologies Ltd. | Immunogenic fragments and multimers from streptococcus pneumoniae proteins |
| US20130039943A1 (en) | 2010-05-03 | 2013-02-14 | Bruno Rene Andre | Novel method |
| GB201009273D0 (en) | 2010-06-03 | 2010-07-21 | Glaxosmithkline Biolog Sa | Novel vaccine |
| EP2575877B1 (en) * | 2010-06-04 | 2016-10-19 | INSERM - Institut National de la Santé et de la Recherche Médicale | Novel immunoadjuvant compounds and uses thereof |
| MX342138B (es) | 2010-07-06 | 2016-09-14 | Variation Biotechnologies Inc | Composiciones y metodos para el tratamiento de influenza. |
| US8764642B2 (en) | 2010-10-14 | 2014-07-01 | Medivators Inc. | Combined irrigation and rinsing tube set |
| EP2627235B1 (en) | 2010-10-14 | 2019-02-20 | Medivators Inc. | A universal cap |
| GB201101331D0 (en) | 2011-01-26 | 2011-03-09 | Glaxosmithkline Biolog Sa | Compositions and uses |
| PL2651436T3 (pl) | 2010-12-14 | 2016-10-31 | Kompozycja antygenów mykobakteryjnych | |
| CA2862864C (en) | 2011-01-13 | 2018-12-11 | Variation Biotechnologies Inc. | Compositions and methods for treating viral infections |
| CA2828068C (en) | 2011-02-22 | 2019-03-19 | Biondvax Pharmaceuticals Ltd. | Multimeric multiepitope polypeptides in improved seasonal and pandemic influenza vaccines |
| DK2707385T3 (da) | 2011-05-13 | 2017-11-20 | Glaxosmithkline Biologicals Sa | RSV-F-præfusionsantigener |
| WO2012156391A1 (en) | 2011-05-17 | 2012-11-22 | Glaxosmithkline Biologicals S.A. | Vaccine against streptococcus pneumoniae |
| EP3153180A1 (en) | 2011-06-03 | 2017-04-12 | 3M Innovative Properties Company | Heterobifunctional linkers with polyethylene glycol segments and immune response modifier conjugates made therefrom |
| WO2012167088A1 (en) | 2011-06-03 | 2012-12-06 | 3M Innovative Properties Company | Heterobifunctional linkers with polyethylene glycol segments and immune response modifier conjugates made therefrom |
| GB201113570D0 (en) | 2011-08-05 | 2011-09-21 | Glaxosmithkline Biolog Sa | Vaccine |
| GB201116248D0 (en) | 2011-09-20 | 2011-11-02 | Glaxosmithkline Biolog Sa | Liposome production using isopropanol |
| GB201120000D0 (en) | 2011-11-20 | 2012-01-04 | Glaxosmithkline Biolog Sa | Vaccine |
| GB201119999D0 (en) | 2011-11-20 | 2012-01-04 | Glaxosmithkline Biolog Sa | Vaccine |
| US20140356399A1 (en) | 2012-01-12 | 2014-12-04 | Variation Biotechnologies, Inc. | Compositions and methods for treating viral infections |
| US20150079077A1 (en) | 2012-01-27 | 2015-03-19 | Variation Biotechnologies, Inc. | Methods and compositions for therapeutic agents |
| WO2013139744A1 (en) | 2012-03-18 | 2013-09-26 | Glaxosmithkline Biologicals S.A. | Method of vaccination against human papillomavirus |
| EP2833900B1 (en) | 2012-04-01 | 2018-09-19 | Technion Research & Development Foundation Limited | Extracellular matrix metalloproteinase inducer (emmprin) peptides and binding antibodies |
| US20140037680A1 (en) | 2012-08-06 | 2014-02-06 | Glaxosmithkline Biologicals, S.A. | Novel method |
| WO2014024026A1 (en) | 2012-08-06 | 2014-02-13 | Glaxosmithkline Biologicals S.A. | Method for eliciting in infants an immune response against rsv and b. pertussis |
| IN2014CH00395A (https=) | 2013-02-05 | 2015-04-03 | Nitto Denko Corp | |
| EP2762154A3 (en) | 2013-02-05 | 2015-01-21 | Nitto Denko Corporation | Vaccine composition for transdermal administration |
| RU2014102941A (ru) | 2013-02-05 | 2015-08-10 | Нитто Денко Корпорейшн | Вакцинная композиция для введения через слизистую оболочку |
| KR102050931B1 (ko) | 2013-02-05 | 2019-12-02 | 닛토덴코 가부시키가이샤 | 경피 투여용 ｗｔ1 펩티드 암 백신 테이프제 |
| EP2762158A1 (en) | 2013-02-05 | 2014-08-06 | Nitto Denko Corporation | E75-vaccine composition for transdermal administration |
| EP3662927A3 (en) | 2013-02-05 | 2020-10-21 | Nitto Denko Corporation | Vaccine composition |
| EP2762152A1 (en) | 2013-02-05 | 2014-08-06 | Nitto Denko Corporation | WT1 peptide cancer vaccine composition for transdermal administration |
| KR20140100419A (ko) | 2013-02-05 | 2014-08-14 | 닛토덴코 가부시키가이샤 | 경피 투여용 ｗｔ1 펩티드 암 백신 조성물 |
| US20140220079A1 (en) | 2013-02-05 | 2014-08-07 | Nitto Denko Corporation | Vaccine composition for mucosal administration |
| JP6497691B2 (ja) | 2013-02-05 | 2019-04-10 | 日東電工株式会社 | 粘膜投与用ｗｔ１ペプチド癌ワクチン組成物 |
| FI2970398T3 (fi) | 2013-03-13 | 2024-08-06 | Us Health | Rsv f -prefuusioproteiineja ja niiden käyttö |
| UY35418A (es) | 2013-03-15 | 2014-10-31 | Glaxosmithkline Biolog Sa | Vacuna que proporciona protección frente a diferentes Picornavirus humanos. |
| AU2014304545A1 (en) | 2013-08-05 | 2016-02-25 | Glaxosmithkline Biologicals S.A. | Combination immunogenic compositions |
| US10392603B2 (en) | 2013-08-30 | 2019-08-27 | The Chemo-Sero-Therapeutic Research Institute | Method of viral purification |
| CN104436157A (zh) | 2013-09-23 | 2015-03-25 | 恩金生物有限公司 | 流感疫苗和治疗 |
| WO2015092710A1 (en) | 2013-12-19 | 2015-06-25 | Glaxosmithkline Biologicals, S.A. | Contralateral co-administration of vaccines |
| US10821175B2 (en) | 2014-02-25 | 2020-11-03 | Merck Sharp & Dohme Corp. | Lipid nanoparticle vaccine adjuvants and antigen delivery systems |
| KR20160132088A (ko) * | 2014-03-12 | 2016-11-16 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 점막 전달용 리포솜 조성물 |
| KR20160127828A (ko) * | 2014-03-12 | 2016-11-04 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 면역원성 리포솜 제형 |
| US10426828B2 (en) | 2014-04-03 | 2019-10-01 | Biondvax Pharmaceuticals Ltd. | Compositions of multimeric-multiepitope influenza polypeptides and their production |
| CN106659777A (zh) | 2014-06-13 | 2017-05-10 | 葛兰素史密丝克莱恩生物有限公司 | 免疫原性组合产品 |
| AU2015384786B2 (en) | 2015-03-03 | 2020-08-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Display platform from bacterial spore coat proteins |
| WO2017059280A1 (en) | 2015-10-02 | 2017-04-06 | The University Of North Carolina At Chapel Hill | Novel pan-tam inhibitors and mer/axl dual inhibitors |
| US10772946B2 (en) | 2015-10-13 | 2020-09-15 | Sanofi Pasteur | Immunogenic compositions against S. aureus |
| TN2018000112A1 (en) | 2015-10-29 | 2019-10-04 | Novartis Ag | Antibody conjugates comprising toll-like receptor agonist |
| US20180318415A1 (en) | 2015-12-08 | 2018-11-08 | Glaxosmithkline Biologicals, Sa | Novel adjuvant formulations |
| WO2017137085A1 (en) | 2016-02-11 | 2017-08-17 | Sanofi Pasteur | Meningitidis vaccines comprising subtilinases |
| MX2019002178A (es) | 2016-08-23 | 2019-09-18 | Glaxosmithkline Biologicals Sa | Peptidos de fusion con antigenos enlazados a fragmentos cortos de cadena invariante (cd74). |
| EP3518966A1 (en) | 2016-09-29 | 2019-08-07 | GlaxoSmithKline Biologicals S.A. | Compositions and methods of treatment of persistent hpv infection |
| GB201616904D0 (en) | 2016-10-05 | 2016-11-16 | Glaxosmithkline Biologicals Sa | Vaccine |
| BR112019011286A2 (pt) | 2016-12-07 | 2019-10-15 | Glaxosmithkline Biologicals S.A. | métodos para produzir uma composição de lipossoma, para preparar uma composição de vacina e para preparar um kit de vacina. |
| GB201620968D0 (en) | 2016-12-09 | 2017-01-25 | Glaxosmithkline Biologicals Sa | Adenovirus polynucleotides and polypeptides |
| US11084850B2 (en) | 2016-12-16 | 2021-08-10 | The Pirbright Institute | Recombinant prefusion RSV F proteins and uses thereof |
| GB201621686D0 (en) | 2016-12-20 | 2017-02-01 | Glaxosmithkline Biologicals Sa | Novel methods for inducing an immune response |
| UA129243C2 (uk) | 2017-04-19 | 2025-02-26 | Інстітьют Фо Рісьорч Ін Біомедцін | Антитіло, що зв'язується зі спорозоїтами p. falciparum |
| EP3615061A1 (en) | 2017-04-28 | 2020-03-04 | GlaxoSmithKline Biologicals S.A. | Vaccination |
| US11389465B2 (en) | 2017-05-01 | 2022-07-19 | Vanderbilt University | Phosphorylated hexaacyl disaccharides (PHADs) for treating or preventing infections |
| GB201707700D0 (en) | 2017-05-12 | 2017-06-28 | Glaxosmithkline Biologicals Sa | Dried composition |
| CA3063954A1 (en) | 2017-05-30 | 2018-12-06 | Glaxosmithline Biologicals S.A. | Methods for manufacturing an adjuvant |
| US11123415B2 (en) | 2017-08-16 | 2021-09-21 | Ohio State Innovation Foundation | Nanoparticle compositions for Salmonella vaccines |
| KR20250006307A (ko) | 2017-09-13 | 2025-01-10 | 사노피 파스퇴르 | 인간 시토메갈로바이러스 면역원성 조성물 |
| ES2985591T3 (es) | 2018-02-12 | 2024-11-06 | Inimmune Corp | Ligandos de receptores tipo Toll |
| JP2021516045A (ja) | 2018-02-28 | 2021-07-01 | ファイザー・インク | Ｉｌ−１５バリアントおよびその使用 |
| SI3797121T1 (sl) | 2018-05-23 | 2024-09-30 | Pfizer Inc. | Protitelesa, specifična za CD3, in njihova uporaba |
| MX2020012607A (es) | 2018-05-23 | 2021-01-29 | Pfizer | Anticuerpos especificos para gucy2c y sus usos. |
| JP2021526831A (ja) | 2018-06-12 | 2021-10-11 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | アデノウイルスポリヌクレオチド及びポリペプチド |
| EP3581201A1 (en) | 2018-06-15 | 2019-12-18 | GlaxoSmithKline Biologicals S.A. | Escherichia coli o157:h7 proteins and uses thereof |
| WO2020007760A1 (en) | 2018-07-03 | 2020-01-09 | Glaxosmithkline Intellectual Property Development Limited | Tlr4 compounds or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions or formulations, methods of preparation, treatment or uses |
| ES3038006T3 (en) | 2018-07-31 | 2025-10-08 | Glaxosmithkline Biologicals Sa | Antigen purification method |
| WO2020128893A1 (en) | 2018-12-21 | 2020-06-25 | Pfizer Inc. | Combination treatments of cancer comprising a tlr agonist |
| EP3897846A1 (en) | 2018-12-21 | 2021-10-27 | GlaxoSmithKline Biologicals SA | Methods of inducing an immune response |
| KR20220035457A (ko) | 2019-07-21 | 2022-03-22 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 치료 바이러스 백신 |
| WO2021048081A1 (en) | 2019-09-09 | 2021-03-18 | Glaxosmithkline Biologicals Sa | Immunotherapeutic compositions |
| US12533418B2 (en) | 2019-11-22 | 2026-01-27 | Glaxosmithkline Biologicals Sa | Dosage and administration of a bacterial saccharide glycoconjugate vaccine |
| JP7369297B2 (ja) | 2019-12-17 | 2023-10-25 | ファイザー・インク | Ｃｄ４７、ｐｄ－ｌ１に特異的な抗体、およびその使用 |
| US20230277657A1 (en) | 2020-05-05 | 2023-09-07 | Glaxosmithkline Biologicals Sa | Microfluidic mixing device and methods of use |
| US20230234992A1 (en) | 2020-06-05 | 2023-07-27 | Glaxosmithkline Biologicals Sa | Modified betacoronavirus spike proteins |
| MX2022016181A (es) | 2020-06-22 | 2023-02-13 | Sumitomo Pharma Co Ltd | Adyuvante con actividad agonista del receptor tipo toll 4 (tlr4). |
| TW202216779A (zh) | 2020-07-17 | 2022-05-01 | 美商輝瑞股份有限公司 | 治療性抗體類和彼等之用途 |
| EP4032547A1 (en) | 2021-01-20 | 2022-07-27 | GlaxoSmithKline Biologicals S.A. | Hsv1 fce derived fragements for the treatment of hsv |
| JP2024506364A (ja) | 2021-02-11 | 2024-02-13 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | Ｈｐｖワクチンの製造 |
| WO2023020992A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
| WO2023020993A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
| WO2023020994A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
| WO2023114727A1 (en) | 2021-12-13 | 2023-06-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bacteriophage lambda-vaccine system |
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|---|---|---|---|---|
| US4912094B1 (en) | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
| US6113918A (en) | 1997-05-08 | 2000-09-05 | Ribi Immunochem Research, Inc. | Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors |
-
1999
- 1999-11-12 US US09/439,839 patent/US6303347B1/en not_active Expired - Lifetime
-
2000
- 2000-11-10 AR ARP000105962A patent/AR026443A1/es not_active Application Discontinuation
- 2000-11-10 CO CO00085801A patent/CO5261562A1/es not_active Application Discontinuation
- 2000-11-13 EP EP00982119A patent/EP1230250A2/en not_active Withdrawn
- 2000-11-13 CA CA002391299A patent/CA2391299A1/en not_active Abandoned
- 2000-11-13 WO PCT/US2000/031340 patent/WO2001034617A2/en not_active Ceased
- 2000-11-13 NZ NZ518860A patent/NZ518860A/en not_active IP Right Cessation
- 2000-11-13 CN CN00816859A patent/CN1409720A/zh active Pending
- 2000-11-13 BR BR0015501-2A patent/BR0015501A/pt not_active IP Right Cessation
- 2000-11-13 MX MXPA02004774A patent/MXPA02004774A/es active IP Right Grant
- 2000-11-13 JP JP2001537329A patent/JP2003514783A/ja active Pending
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2002
- 2002-05-08 NO NO20022207A patent/NO20022207L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1230250A2 (en) | 2002-08-14 |
| MXPA02004774A (es) | 2003-01-28 |
| NO20022207L (no) | 2002-07-10 |
| CN1409720A (zh) | 2003-04-09 |
| BR0015501A (pt) | 2003-02-25 |
| WO2001034617A3 (en) | 2001-11-08 |
| AR026443A1 (es) | 2003-02-12 |
| JP2003514783A (ja) | 2003-04-22 |
| NO20022207D0 (no) | 2002-05-08 |
| WO2001034617A2 (en) | 2001-05-17 |
| US6303347B1 (en) | 2001-10-16 |
| CA2391299A1 (en) | 2001-05-17 |
| CO5261562A1 (es) | 2003-03-31 |
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