RU2012107812A - Препараты мутеинов липокалинов с контролируемым высвобождением - Google Patents
Препараты мутеинов липокалинов с контролируемым высвобождением Download PDFInfo
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- RU2012107812A RU2012107812A RU2012107812/15A RU2012107812A RU2012107812A RU 2012107812 A RU2012107812 A RU 2012107812A RU 2012107812/15 A RU2012107812/15 A RU 2012107812/15A RU 2012107812 A RU2012107812 A RU 2012107812A RU 2012107812 A RU2012107812 A RU 2012107812A
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- Prior art keywords
- pharmaceutical composition
- composition according
- lipocalin
- lipocalin mutein
- group
- Prior art date
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- 102000019298 Lipocalin Human genes 0.000 title claims abstract 38
- 108050006654 Lipocalin Proteins 0.000 title claims abstract 38
- 238000013270 controlled release Methods 0.000 title claims abstract 8
- 238000002360 preparation method Methods 0.000 title claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 46
- 229920001577 copolymer Polymers 0.000 claims abstract 18
- 229920000747 poly(lactic acid) Polymers 0.000 claims abstract 16
- 229920000954 Polyglycolide Polymers 0.000 claims abstract 14
- 229920002988 biodegradable polymer Polymers 0.000 claims abstract 12
- 239000004621 biodegradable polymer Substances 0.000 claims abstract 12
- 239000000203 mixture Substances 0.000 claims abstract 10
- 229920000642 polymer Polymers 0.000 claims abstract 9
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract 8
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract 8
- 102000004169 proteins and genes Human genes 0.000 claims abstract 8
- 108090000623 proteins and genes Proteins 0.000 claims abstract 8
- -1 polyacetyls Polymers 0.000 claims abstract 7
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims abstract 6
- 239000002502 liposome Substances 0.000 claims abstract 6
- 229920002732 Polyanhydride Polymers 0.000 claims abstract 5
- 229920001273 Polyhydroxy acid Polymers 0.000 claims abstract 5
- 229920001710 Polyorthoester Polymers 0.000 claims abstract 5
- 150000004676 glycans Chemical class 0.000 claims abstract 4
- 229920001282 polysaccharide Polymers 0.000 claims abstract 4
- 239000005017 polysaccharide Substances 0.000 claims abstract 4
- 239000004952 Polyamide Substances 0.000 claims abstract 3
- 150000002632 lipids Chemical class 0.000 claims abstract 3
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 claims abstract 3
- 229920002647 polyamide Polymers 0.000 claims abstract 3
- 229920001610 polycaprolactone Polymers 0.000 claims abstract 3
- 229920000515 polycarbonate Polymers 0.000 claims abstract 3
- 239000004417 polycarbonate Substances 0.000 claims abstract 3
- 229920002721 polycyanoacrylate Polymers 0.000 claims abstract 3
- 239000000622 polydioxanone Substances 0.000 claims abstract 3
- 229920002635 polyurethane Polymers 0.000 claims abstract 3
- 239000004814 polyurethane Substances 0.000 claims abstract 3
- 229920001308 poly(aminoacid) Polymers 0.000 claims abstract 2
- 229920000570 polyether Polymers 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims 26
- 102000009027 Albumins Human genes 0.000 claims 12
- 108010088751 Albumins Proteins 0.000 claims 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims 8
- 101000946124 Homo sapiens Lipocalin-1 Proteins 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 239000012634 fragment Substances 0.000 claims 6
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- 239000008346 aqueous phase Substances 0.000 claims 5
- 238000002347 injection Methods 0.000 claims 5
- 239000007924 injection Substances 0.000 claims 5
- 102100034724 Lipocalin-1 Human genes 0.000 claims 4
- 239000012074 organic phase Substances 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 3
- 102000014914 Carrier Proteins Human genes 0.000 claims 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- 102000013382 Gelatinases Human genes 0.000 claims 3
- 108010026132 Gelatinases Proteins 0.000 claims 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- 102100035405 Neutrophil gelatinase-associated lipocalin Human genes 0.000 claims 3
- 125000000539 amino acid group Chemical group 0.000 claims 3
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- 239000003995 emulsifying agent Substances 0.000 claims 3
- 150000002500 ions Chemical class 0.000 claims 3
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical group CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims 3
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 101000757556 Homo sapiens Apolipoprotein D Proteins 0.000 claims 2
- 108060003951 Immunoglobulin Proteins 0.000 claims 2
- 108010057281 Lipocalin 1 Proteins 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims 2
- 241000255969 Pieris brassicae Species 0.000 claims 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims 2
- 108090000848 Ubiquitin Proteins 0.000 claims 2
- 102000044159 Ubiquitin Human genes 0.000 claims 2
- 239000013566 allergen Substances 0.000 claims 2
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- 239000006184 cosolvent Substances 0.000 claims 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims 2
- 238000004945 emulsification Methods 0.000 claims 2
- 235000019441 ethanol Nutrition 0.000 claims 2
- 229930195729 fatty acid Natural products 0.000 claims 2
- 239000000194 fatty acid Substances 0.000 claims 2
- 150000004665 fatty acids Chemical class 0.000 claims 2
- 210000004907 gland Anatomy 0.000 claims 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims 2
- 102000056778 human APOD Human genes 0.000 claims 2
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- 102000018358 immunoglobulin Human genes 0.000 claims 2
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- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical group CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- 210000000056 organ Anatomy 0.000 claims 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims 2
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- 102000029752 retinol binding Human genes 0.000 claims 2
- 108091000053 retinol binding Proteins 0.000 claims 2
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 claims 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical group O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims 2
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 claims 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 claims 1
- UOBYKYZJUGYBDK-UHFFFAOYSA-M 2-naphthoate Chemical compound C1=CC=CC2=CC(C(=O)[O-])=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-M 0.000 claims 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 claims 1
- JJTUDXZGHPGLLC-IMJSIDKUSA-N 4511-42-6 Chemical compound C[C@@H]1OC(=O)[C@H](C)OC1=O JJTUDXZGHPGLLC-IMJSIDKUSA-N 0.000 claims 1
- 102000009333 Apolipoprotein D Human genes 0.000 claims 1
- 108010025614 Apolipoproteins D Proteins 0.000 claims 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 claims 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims 1
- 229940045513 CTLA4 antagonist Drugs 0.000 claims 1
- 241000282472 Canis lupus familiaris Species 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims 1
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
- 102100022103 Histone-lysine N-methyltransferase 2A Human genes 0.000 claims 1
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- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims 1
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- 208000001344 Macular Edema Diseases 0.000 claims 1
- 206010025415 Macular oedema Diseases 0.000 claims 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical group O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims 1
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- 206010028980 Neoplasm Diseases 0.000 claims 1
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 235000021314 Palmitic acid Nutrition 0.000 claims 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 claims 1
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- 206010038933 Retinopathy of prematurity Diseases 0.000 claims 1
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- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 claims 1
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- 208000000208 Wet Macular Degeneration Diseases 0.000 claims 1
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- 150000001298 alcohols Chemical class 0.000 claims 1
- 150000001299 aldehydes Chemical group 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
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- 150000007942 carboxylates Chemical class 0.000 claims 1
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- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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| US23136509P | 2009-08-05 | 2009-08-05 | |
| US61/231,365 | 2009-08-05 | ||
| PCT/EP2010/061436 WO2011015634A2 (en) | 2009-08-05 | 2010-08-05 | Controlled release formulations of lipocalin muteins |
Publications (1)
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| RU2012107812A true RU2012107812A (ru) | 2013-09-10 |
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| EP (2) | EP2461800A2 (show.php) |
| JP (2) | JP2013501033A (show.php) |
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| IN (1) | IN2012DN00407A (show.php) |
| RU (1) | RU2012107812A (show.php) |
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| WO2011106702A2 (en) | 2010-02-25 | 2011-09-01 | The Johns Hopkins University | Sustained delivery of therapeutic agents to an eye compartment |
| US9327037B2 (en) | 2011-02-08 | 2016-05-03 | The Johns Hopkins University | Mucus penetrating gene carriers |
| US9701732B2 (en) | 2011-02-28 | 2017-07-11 | Korea University Research And Business Foundation | Fusion protein comprising albumin and retinol-binding protein |
| US10064915B2 (en) | 2011-02-28 | 2018-09-04 | Korea University Research And Business Foundation | Fusion protein comprising albumin and retinol-binding protein |
| US9273116B2 (en) * | 2011-02-28 | 2016-03-01 | Korea University Research And Business Foundation | Fusion protein comprising albumin and retinol-binding protein |
| KR102038677B1 (ko) * | 2011-06-14 | 2019-10-30 | 입센 파마 에스.에이.에스 | 활성 성분으로 멜라노코르틴 수용체 리간드를 함유하는 지속-방출형 조성물 |
| WO2013068590A1 (en) * | 2011-11-11 | 2013-05-16 | Pieris Ag | Lipocalin muteins as vegf antagonists for use in treating diseases caused or promoted by increased vascularization |
| AP2014007792A0 (en) | 2012-01-09 | 2014-07-31 | Pieris Ag | Methods for preventing, treating or diagnosing disorders |
| WO2013113820A1 (en) * | 2012-02-02 | 2013-08-08 | Esbatech - A Novartis Company Llc | Antibody-containing sustained-release formulation for ocular administration |
| EP2825207B1 (en) | 2012-03-16 | 2020-08-19 | The Johns Hopkins University | Non-linear multiblock copolymer-drug conjugates for the delivery of active agents |
| CN104363924B (zh) | 2012-03-16 | 2018-04-17 | 约翰霍普金斯大学 | 用于递送hif‑1抑制剂的控制释放调配物 |
| US9533068B2 (en) | 2012-05-04 | 2017-01-03 | The Johns Hopkins University | Drug loaded microfiber sutures for ophthalmic application |
| US10568975B2 (en) | 2013-02-05 | 2020-02-25 | The Johns Hopkins University | Nanoparticles for magnetic resonance imaging tracking and methods of making and using thereof |
| CN103360609B (zh) * | 2013-07-16 | 2015-08-19 | 天津大学 | 一种双亲性的蛋白质-高分子键合体及其制备方法 |
| CN103394094B (zh) * | 2013-07-16 | 2015-05-13 | 天津大学 | 基于牛血清白蛋白-聚己内酯的高分子脂质体及其制备方法 |
| WO2015104406A2 (en) * | 2014-01-13 | 2015-07-16 | Pieris Ag | Multi-specific polypeptide useful for localized tumor immunomodulation |
| US20160151511A1 (en) * | 2014-12-02 | 2016-06-02 | Antriabio, Inc. | Proteins and protein conjugates with increased hydrophobicity |
| CA2974715C (en) | 2015-01-27 | 2020-05-05 | The Johns Hopkins University | Hypotonic hydrogel formulations for enhanced transport of active agents at mucosal surfaces |
| BR112017020434A2 (pt) | 2015-05-04 | 2018-06-26 | Pieris Pharmaceuticals Gmbh | polipeptídeos de fusão, molécula de ácido nucleico, célula hospedeira, método para produzir um polipeptídeo de fusão, usos do polipeptídeo de fusão, métodos para ativar as vias de sinalização, para coestimular células, para induzir a proliferação de linfócitos t, para direcionar o agrupamento de cd137, para induzir uma resposta local de células t, para induzir uma resposta local de células nk e para induzir a produção de il-2 |
| RU2736590C2 (ru) * | 2016-02-16 | 2020-11-18 | Стронгбридж Даблин Лимитед | Велдореотид, обладающий плохой растворимостью в физиологических условиях, для применения при лечении акромегалии, акромегалии со злокачественным новообразованием, экспрессирующих sst-r5 опухолей, диабета 2 типа, гипергликемии и опухолей, связанных с гормонами |
| US12496279B2 (en) | 2019-04-11 | 2025-12-16 | The Johns Hopkins University | Nanoparticles for drug delivery to brain |
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| US6403564B1 (en) | 1998-10-16 | 2002-06-11 | Schering Corporation | Ribavirin-interferon alfa combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection |
| DE19926068C1 (de) | 1999-06-08 | 2001-01-11 | Arne Skerra | Muteine des Bilin-Bindungsproteins |
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| AU2000202A (en) | 2000-10-31 | 2002-05-15 | Pr Pharmaceuticals Inc | Methods and compositions for enhanced delivery of bioactive molecules |
| AU2002335930B2 (en) | 2001-03-09 | 2005-07-28 | Morphosys Ag | Serum albumin binding moieties |
| WO2003029462A1 (en) | 2001-09-27 | 2003-04-10 | Pieris Proteolab Ag | Muteins of human neutrophil gelatinase-associated lipocalin and related proteins |
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| US7691970B2 (en) | 2003-08-25 | 2010-04-06 | Pieris Ag | Muteins of a bilin-binding protein with affinity for a given target |
| US7892827B2 (en) | 2004-11-26 | 2011-02-22 | Pieris Ag | Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4) |
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| US8178483B2 (en) * | 2007-03-30 | 2012-05-15 | Colgate-Palmolive Company | Polymeric encapsulates having a quaternary ammonium salt and methods for producing the same |
| BRPI0810016A2 (pt) * | 2007-04-26 | 2014-10-14 | Basf Se | Processo para produzir microcápsulas, microcápsulas, dispersões, usos de microcápsulas e de dispersões, formulação agroquímica, processos para combater o crescimento de plantas indesejadas, e para combater a infestação de insetos ou ácaros indesejados em plantas e/ou para combater fungos fitopatogênicos, e, material de semente |
| SI2170287T1 (sl) * | 2007-07-26 | 2014-04-30 | Aqtis Ip Bv | Mikrodelci, ki vsebujejo pcl in njihova uporaba |
| RU2537139C2 (ru) * | 2008-01-15 | 2014-12-27 | Эбботт Гмбх Унд Ко.Кг | Порошковые белковые композиции и способы их получения |
| BRPI0905752B1 (pt) * | 2008-01-30 | 2021-11-23 | Pieris Ag | Muteína de lipocalina da lágrima humana (htlc), composição farmacêutica, método para a produção de uma muteína de lipocalina da lágrima humana e uso in vitro de uma muteína de lipocalina da lágrima humana |
| US20090274623A1 (en) * | 2008-01-30 | 2009-11-05 | General Electric Company | In vivo imaging agents for met receptor tyrosine kinase |
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| CA2770149A1 (en) | 2011-02-10 |
| AU2010280688A1 (en) | 2012-02-23 |
| US20120201873A1 (en) | 2012-08-09 |
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| WO2011015634A2 (en) | 2011-02-10 |
| JP2013501033A (ja) | 2013-01-10 |
| CN102612362A (zh) | 2012-07-25 |
| JP5774557B2 (ja) | 2015-09-09 |
| CN106139123A (zh) | 2016-11-23 |
| BR112012002709A2 (pt) | 2019-04-30 |
| EP2461800A2 (en) | 2012-06-13 |
| EP2550958B1 (en) | 2018-10-10 |
| KR20120099371A (ko) | 2012-09-10 |
| JP2012255007A (ja) | 2012-12-27 |
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| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
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