UA80098C2 - Cross-linked glycopeptide-cephalosporin antibiotics - Google Patents
Cross-linked glycopeptide-cephalosporin antibiotics Download PDFInfo
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- UA80098C2 UA80098C2 UA20040503518A UA20040503518A UA80098C2 UA 80098 C2 UA80098 C2 UA 80098C2 UA 20040503518 A UA20040503518 A UA 20040503518A UA 20040503518 A UA20040503518 A UA 20040503518A UA 80098 C2 UA80098 C2 UA 80098C2
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- 229920002258 tannic acid Polymers 0.000 description 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- KOEUYOLNKBSCJM-UHFFFAOYSA-N tert-butyl 4-methylpyridine-3-carboxylate Chemical compound C(C)(C)(C)OC(C1=CN=CC=C1C)=O KOEUYOLNKBSCJM-UHFFFAOYSA-N 0.000 description 1
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- 238000009210 therapy by ultrasound Methods 0.000 description 1
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- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
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- 210000001519 tissue Anatomy 0.000 description 1
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- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
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- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
- C07D501/46—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof with the 7-amino radical acylated by carboxylic acids containing hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
- C07K9/006—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure
- C07K9/008—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure directly attached to a hetero atom of the saccharide radical, e.g. actaplanin, avoparcin, ristomycin, vancomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US32888901P | 2001-10-12 | 2001-10-12 | |
PCT/US2002/032534 WO2003031449A2 (en) | 2001-10-12 | 2002-10-11 | Cross-linked glycopeptide-cephalosporin antibiotics |
Publications (1)
Publication Number | Publication Date |
---|---|
UA80098C2 true UA80098C2 (en) | 2007-08-27 |
Family
ID=23282891
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UA20040503518A UA80098C2 (en) | 2001-10-12 | 2002-11-10 | Cross-linked glycopeptide-cephalosporin antibiotics |
Country Status (30)
Country | Link |
---|---|
US (11) | US6974797B2 (xx) |
EP (1) | EP1434779B1 (xx) |
JP (3) | JP4249023B2 (xx) |
KR (1) | KR100888660B1 (xx) |
CN (2) | CN100358901C (xx) |
AT (1) | ATE314376T1 (xx) |
AU (1) | AU2002332111B2 (xx) |
BR (2) | BR0213154A (xx) |
CA (1) | CA2463544C (xx) |
CO (1) | CO5580782A2 (xx) |
DE (1) | DE60208404T2 (xx) |
DK (1) | DK1434779T3 (xx) |
EA (1) | EA007001B1 (xx) |
ES (1) | ES2254738T3 (xx) |
HK (1) | HK1066007A1 (xx) |
HR (1) | HRP20040243B1 (xx) |
HU (1) | HU230158B1 (xx) |
IL (2) | IL160846A0 (xx) |
IS (1) | IS2422B (xx) |
MX (1) | MXPA04003273A (xx) |
NO (1) | NO334092B1 (xx) |
NZ (1) | NZ531576A (xx) |
PL (1) | PL209757B1 (xx) |
RS (1) | RS50888B (xx) |
SI (1) | SI1434779T1 (xx) |
SK (1) | SK2052004A3 (xx) |
TW (1) | TWI335332B (xx) |
UA (1) | UA80098C2 (xx) |
WO (1) | WO2003031449A2 (xx) |
ZA (1) | ZA200402732B (xx) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI335332B (en) * | 2001-10-12 | 2011-01-01 | Theravance Inc | Cross-linked vancomycin-cephalosporin antibiotics |
ES2384707T3 (es) | 2002-05-24 | 2012-07-11 | Theravance, Inc. | Antibióticos entrecruzados de glucopéptidos y cefalosporinas |
ES2335013T3 (es) * | 2003-05-23 | 2010-03-18 | Theravance, Inc. | Antibioticos de glucopeptido-cefalosporina reticulados. |
DE602004012269T2 (de) | 2003-07-11 | 2009-04-30 | Theravance, Inc., South San Francisco | Quervernetzte glycopeptid-cephalosporin-antibiotika |
KR100808414B1 (ko) * | 2004-06-08 | 2008-02-29 | 엘지전자 주식회사 | 이동단말의 클라이언트 세션 복구방법 |
US20060105941A1 (en) * | 2004-11-12 | 2006-05-18 | Allergan, Inc. | Mixed antibiotic codrugs |
EP2862569A1 (en) | 2011-09-09 | 2015-04-22 | Cubist Pharmaceuticals, Inc. | Methods for treating intrapulmonary infections |
US8809314B1 (en) | 2012-09-07 | 2014-08-19 | Cubist Pharmacueticals, Inc. | Cephalosporin compound |
US8476425B1 (en) | 2012-09-27 | 2013-07-02 | Cubist Pharmaceuticals, Inc. | Tazobactam arginine compositions |
EP2970164B1 (en) * | 2013-03-13 | 2017-05-03 | Theravance Biopharma Antibiotics IP, LLC | Crystalline form of a substituted thiazolylacetic acid triethylamine salt |
MD4599C1 (ro) * | 2013-03-13 | 2019-06-30 | Theravance Biopharma Antibiotics Ip, Llc | Săruri de hidroclorură a unui compus antibiotic |
US9872906B2 (en) | 2013-03-15 | 2018-01-23 | Merck Sharp & Dohme Corp. | Ceftolozane antibiotic compositions |
KR102226197B1 (ko) | 2013-03-15 | 2021-03-11 | 머크 샤프 앤드 돔 코포레이션 | 세프톨로잔 항균성 조성물 |
US9320740B2 (en) | 2013-03-15 | 2016-04-26 | Merck Sharp & Dohme Corp. | Ceftolozane-tazobactam pharmaceutical compositions |
WO2015035376A2 (en) | 2013-09-09 | 2015-03-12 | Calixa Therapeutics, Inc. | Treating infections with ceftolozane/tazobactam in subjects having impaired renal function |
US20150094293A1 (en) | 2013-09-27 | 2015-04-02 | Calixa Therapeutics, Inc. | Solid forms of ceftolozane |
US10943049B2 (en) * | 2018-09-28 | 2021-03-09 | Taiwan Semiconductor Manufacturing Co., Ltd. | Rule check violation prediction systems and methods |
NL2023883B1 (en) * | 2019-09-24 | 2021-04-26 | Univ Leiden | Antibiotic compounds |
TW202404581A (zh) | 2022-05-25 | 2024-02-01 | 美商醫肯納腫瘤學公司 | Mek抑制劑及其用途 |
Family Cites Families (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US457926A (en) * | 1891-08-18 | Steam-engine | ||
US4668783A (en) * | 1974-12-19 | 1987-05-26 | Takeda Chemical Industries, Ltd. | Thiazolylacetamido cephalosporin compounds |
FR2347706A1 (fr) * | 1976-04-08 | 1977-11-04 | Issec Labo Physicochimie Appli | Nouveau procede photographique d'impression en couleurs sur divers substrats |
JPS5994B2 (ja) * | 1976-09-14 | 1984-01-05 | 富士写真フイルム株式会社 | 感光性組成物 |
US4155909A (en) * | 1977-06-13 | 1979-05-22 | Philip Morris Incorporated | 2-Alkyl nicotinoids and processes for their production |
DE2758001A1 (de) | 1977-12-24 | 1979-07-12 | Hoechst Ag | Cephalosporinderivate und verfahren zu ihrer herstellung |
US4284631A (en) | 1978-07-31 | 1981-08-18 | Fujisawa Pharmaceutical Co., Ltd. | 7-Substituted cephem compounds and pharmaceutical antibacterial compositions containing them |
GB2033377B (en) | 1978-09-11 | 1983-05-05 | Fujisawa Pharmaceuticalco Ltd | Cephem compounds and processes for preparation thereof |
US4341775A (en) | 1978-09-11 | 1982-07-27 | Fujisawa Pharmaceutical Co., Ltd. | Cephem compounds |
US4220761A (en) | 1978-09-12 | 1980-09-02 | Fujisawa Pharmaceutical Co., Ltd. | 7-[Substituted oximinoacetamido]-3-[hydroxy alkyltetrazolo]cephalosporin derivatives |
DE3006888A1 (de) * | 1980-02-23 | 1981-09-10 | Hoechst Ag, 6000 Frankfurt | Cephalosporinderivate und verfahren zu ihrer herstellung |
US4427677A (en) * | 1980-12-31 | 1984-01-24 | Fujisawa Pharmaceutical Co., Ltd. | Cephem compounds |
DE3118732A1 (de) * | 1981-05-12 | 1982-12-02 | Hoechst Ag, 6000 Frankfurt | Cephalosporinderivate und verfahren zu ihrer herstellung |
JPS5859991A (ja) * | 1981-09-14 | 1983-04-09 | Fujisawa Pharmaceut Co Ltd | 新規セフェム化合物 |
US4427877A (en) * | 1981-09-28 | 1984-01-24 | Raychem Corporation | Printing on low surface energy polymers |
DE3207840A1 (de) * | 1982-03-04 | 1983-09-15 | Hoechst Ag, 6230 Frankfurt | "cephalosporinderivate und verfahren zu ihrer herstellung" |
DE3316798A1 (de) * | 1983-05-07 | 1984-11-08 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von cephemverbindungen |
JPS6041682A (ja) | 1983-08-16 | 1985-03-05 | Meiji Seika Kaisha Ltd | 新規セフアロスポリン化合物及びその製造法 |
DE3418482A1 (de) * | 1984-05-18 | 1985-11-21 | Basf Ag, 6700 Ludwigshafen | Magnetische aufzeichnungstraeger |
US4840945A (en) * | 1985-04-01 | 1989-06-20 | Mochida Pharmaceutical Co., Ltd. | Cephalosporin derivatives |
US4921851A (en) | 1986-06-09 | 1990-05-01 | Takeda Chemical Industries, Ltd. | Cephem compounds, their production and use |
AU1630988A (en) | 1987-05-30 | 1988-12-01 | Kyoto Pharmaceutical Industries, Ltd. | Cephalosporin compound and pharmaceutical composition thereof |
US4974797A (en) * | 1988-03-17 | 1990-12-04 | Consolidated Rail Corporation | Hot bearing simulator |
US4943587A (en) * | 1988-05-19 | 1990-07-24 | Warner-Lambert Company | Hydroxamate derivatives of selected nonsteroidal antiinflammatory acyl residues and their use for cyclooxygenase and 5-lipoxygenase inhibition |
US5693791A (en) * | 1995-04-11 | 1997-12-02 | Truett; William L. | Antibiotics and process for preparation |
AUPN955596A0 (en) * | 1996-04-30 | 1996-05-23 | Fujisawa Pharmaceutical Co., Ltd. | New compound |
JP3906938B2 (ja) * | 1997-02-18 | 2007-04-18 | 富士フイルム株式会社 | 画像再生方法及び画像データ管理方法 |
EP1060189A1 (en) * | 1998-02-20 | 2000-12-20 | Advanced Medicine, Inc. | Derivatives of glycopeptide antibacterial agents |
US6437119B1 (en) | 1998-05-07 | 2002-08-20 | William Lawrence Truett | Compounds formed from two or three antibiotics and their processes of preparation |
CA2319495A1 (en) * | 1998-06-08 | 1999-12-16 | Advanced Medicine, Inc. | Multibinding inhibitors of microsomal triglyceride transferase protein |
IL140093A0 (en) * | 1998-12-23 | 2002-02-10 | Advanced Medicine Inc | Glycopeptide derivatives and pharmaceutical compositions containing the same |
WO2000064049A1 (en) | 1999-04-19 | 2000-10-26 | Attila Lenkehegyi | Dually adjustable electromechanical means for handling and system of these, and dually adjustable digital potentiometer |
US20070196859A1 (en) | 1999-05-24 | 2007-08-23 | Christensen Burton G | Novel antibacterial agents |
ATE269737T1 (de) | 2000-04-06 | 2004-07-15 | Unomedical As | Verbindungsvorrichtung |
JP4107792B2 (ja) * | 2000-08-28 | 2008-06-25 | 独立行政法人科学技術振興機構 | 可視光応答性を有する金属オキシナイトライドからなる光触媒 |
US6885138B1 (en) * | 2000-09-20 | 2005-04-26 | Samsung Electronics Co., Ltd. | Ferroelectric emitter |
US7087482B2 (en) * | 2001-01-19 | 2006-08-08 | Samsung Electronics Co., Ltd. | Method of forming material using atomic layer deposition and method of forming capacitor of semiconductor device using the same |
US20030009681A1 (en) * | 2001-07-09 | 2003-01-09 | Shunji Harada | Digital work protection system, recording medium apparatus, transmission apparatus, and playback apparatus |
TWI335332B (en) * | 2001-10-12 | 2011-01-01 | Theravance Inc | Cross-linked vancomycin-cephalosporin antibiotics |
ES2384707T3 (es) | 2002-05-24 | 2012-07-11 | Theravance, Inc. | Antibióticos entrecruzados de glucopéptidos y cefalosporinas |
ES2335013T3 (es) | 2003-05-23 | 2010-03-18 | Theravance, Inc. | Antibioticos de glucopeptido-cefalosporina reticulados. |
DE602004012269T2 (de) | 2003-07-11 | 2009-04-30 | Theravance, Inc., South San Francisco | Quervernetzte glycopeptid-cephalosporin-antibiotika |
CN100352223C (zh) * | 2004-12-31 | 2007-11-28 | 华为技术有限公司 | 一种在城域传输网络中保护数据业务的方法 |
ES2402748T3 (es) | 2007-12-11 | 2013-05-08 | Theravance, Inc. | Compuestos de aminotetralina como antagonistas del receptor de opioide mu |
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2002
- 2002-10-07 TW TW091123091A patent/TWI335332B/zh not_active IP Right Cessation
- 2002-10-11 EP EP02769054A patent/EP1434779B1/en not_active Expired - Lifetime
- 2002-10-11 CN CNB2005101296193A patent/CN100358901C/zh not_active Expired - Lifetime
- 2002-10-11 ES ES02769054T patent/ES2254738T3/es not_active Expired - Lifetime
- 2002-10-11 PL PL368451A patent/PL209757B1/pl unknown
- 2002-10-11 NZ NZ531576A patent/NZ531576A/en not_active IP Right Cessation
- 2002-10-11 DK DK02769054T patent/DK1434779T3/da active
- 2002-10-11 SK SK2052004A patent/SK2052004A3/sk unknown
- 2002-10-11 US US10/269,471 patent/US6974797B2/en not_active Expired - Lifetime
- 2002-10-11 MX MXPA04003273A patent/MXPA04003273A/es active IP Right Grant
- 2002-10-11 RS YUP-295/04A patent/RS50888B/sr unknown
- 2002-10-11 HU HU0401596A patent/HU230158B1/hu not_active IP Right Cessation
- 2002-10-11 AU AU2002332111A patent/AU2002332111B2/en not_active Ceased
- 2002-10-11 DE DE60208404T patent/DE60208404T2/de not_active Expired - Lifetime
- 2002-10-11 CA CA2463544A patent/CA2463544C/en not_active Expired - Fee Related
- 2002-10-11 BR BR0213154-4A patent/BR0213154A/pt not_active IP Right Cessation
- 2002-10-11 SI SI200230282T patent/SI1434779T1/sl unknown
- 2002-10-11 IL IL16084602A patent/IL160846A0/xx unknown
- 2002-10-11 BR BRPI0213154-4A patent/BRPI0213154B1/pt unknown
- 2002-10-11 CN CNB028202376A patent/CN1329397C/zh not_active Expired - Lifetime
- 2002-10-11 EA EA200400530A patent/EA007001B1/ru unknown
- 2002-10-11 AT AT02769054T patent/ATE314376T1/de active
- 2002-10-11 JP JP2003534432A patent/JP4249023B2/ja not_active Expired - Lifetime
- 2002-10-11 WO PCT/US2002/032534 patent/WO2003031449A2/en active IP Right Grant
- 2002-10-11 KR KR1020047004708A patent/KR100888660B1/ko not_active IP Right Cessation
- 2002-11-10 UA UA20040503518A patent/UA80098C2/uk unknown
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2004
- 2004-03-04 IS IS7172A patent/IS2422B/is unknown
- 2004-03-11 IL IL160846A patent/IL160846A/en not_active IP Right Cessation
- 2004-03-12 HR HR20040243A patent/HRP20040243B1/xx not_active IP Right Cessation
- 2004-04-05 CO CO04032190A patent/CO5580782A2/es active IP Right Grant
- 2004-04-07 ZA ZA2004/02732A patent/ZA200402732B/en unknown
- 2004-05-10 NO NO20041912A patent/NO334092B1/no not_active IP Right Cessation
- 2004-11-12 HK HK04108964A patent/HK1066007A1/xx not_active IP Right Cessation
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2005
- 2005-06-30 US US11/172,303 patent/US7341993B2/en not_active Expired - Lifetime
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- 2007-08-24 US US11/895,534 patent/US7728127B2/en not_active Expired - Lifetime
- 2007-08-24 US US11/895,531 patent/US7601690B2/en not_active Expired - Lifetime
- 2007-08-24 US US11/895,533 patent/US7713931B2/en not_active Expired - Lifetime
- 2007-08-24 US US11/895,555 patent/US7655621B2/en not_active Expired - Lifetime
- 2007-08-24 US US11/895,553 patent/US7649080B2/en not_active Expired - Lifetime
- 2007-08-24 US US11/895,369 patent/US7553962B2/en not_active Expired - Lifetime
- 2007-10-25 US US11/977,604 patent/US7612037B2/en not_active Expired - Lifetime
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2008
- 2008-10-16 JP JP2008267993A patent/JP4445028B2/ja not_active Expired - Lifetime
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2009
- 2009-03-23 JP JP2009071011A patent/JP2009143962A/ja active Pending
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2010
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2011
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