JP4217004B2 - 血液成分への結合体化を介するペプチダーゼ活性からの内因性治療用ペプチドの保護 - Google Patents
血液成分への結合体化を介するペプチダーゼ活性からの内因性治療用ペプチドの保護 Download PDFInfo
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- JP4217004B2 JP4217004B2 JP2000618316A JP2000618316A JP4217004B2 JP 4217004 B2 JP4217004 B2 JP 4217004B2 JP 2000618316 A JP2000618316 A JP 2000618316A JP 2000618316 A JP2000618316 A JP 2000618316A JP 4217004 B2 JP4217004 B2 JP 4217004B2
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Classifications
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
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- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
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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
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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
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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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
- C07K14/465—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from birds
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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
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- C07K14/575—Hormones
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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
- C07K14/575—Hormones
- C07K14/57545—Neuropeptide Y
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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
- C07K14/575—Hormones
- C07K14/605—Glucagons
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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
- C07K14/575—Hormones
- C07K14/62—Insulins
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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
- C07K14/76—Albumins
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Endocrinology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13440699P | 1999-05-17 | 1999-05-17 | |
| US60/134,406 | 1999-05-17 | ||
| US15340699P | 1999-09-10 | 1999-09-10 | |
| US60/153,406 | 1999-09-10 | ||
| US15978399P | 1999-10-15 | 1999-10-15 | |
| US60/159,783 | 1999-10-15 | ||
| PCT/US2000/013576 WO2000069900A2 (en) | 1999-05-17 | 2000-05-17 | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
Related Child Applications (4)
| Application Number | Title | Priority Date | Filing Date |
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| JP2005115175A Division JP4219339B2 (ja) | 1999-05-17 | 2005-04-12 | 改変されたペプチドｙｙおよびそれらの結合体 |
| JP2005140407A Division JP4221392B2 (ja) | 1999-05-17 | 2005-05-12 | 改変されたインスリンペプチドおよびその合成方法 |
| JP2008008555A Division JP2008150384A (ja) | 1999-05-17 | 2008-01-17 | 改変されたペプチドｙｙおよびそれらの結合体 |
| JP2008246982A Division JP2009079048A (ja) | 1999-05-17 | 2008-09-25 | 改変されたペプチドｙｙおよびそれらの結合体 |
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| JP2003508350A JP2003508350A (ja) | 2003-03-04 |
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| JP2005115175A Expired - Fee Related JP4219339B2 (ja) | 1999-05-17 | 2005-04-12 | 改変されたペプチドｙｙおよびそれらの結合体 |
| JP2005140407A Expired - Fee Related JP4221392B2 (ja) | 1999-05-17 | 2005-05-12 | 改変されたインスリンペプチドおよびその合成方法 |
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| JP2010020780A Pending JP2010168384A (ja) | 1999-05-17 | 2010-02-01 | 改変されたペプチドｙｙおよびそれらの結合体 |
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| JP2005115175A Expired - Fee Related JP4219339B2 (ja) | 1999-05-17 | 2005-04-12 | 改変されたペプチドｙｙおよびそれらの結合体 |
| JP2005140407A Expired - Fee Related JP4221392B2 (ja) | 1999-05-17 | 2005-05-12 | 改変されたインスリンペプチドおよびその合成方法 |
| JP2008008555A Withdrawn JP2008150384A (ja) | 1999-05-17 | 2008-01-17 | 改変されたペプチドｙｙおよびそれらの結合体 |
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| US6887470B1 (en) | 1999-09-10 | 2005-05-03 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| DK1180121T3 (da) | 1999-05-17 | 2004-03-01 | Conjuchem Inc | Langtidsvirkende insulinotrope peptider |
| US7601691B2 (en) | 1999-05-17 | 2009-10-13 | Conjuchem Biotechnologies Inc. | Anti-obesity agents |
| WO2004011498A2 (en) * | 2002-07-31 | 2004-02-05 | Conjuchem Inc. | Long lasting natriuretic peptide derivatives |
| AU2002239414A1 (en) * | 2000-11-02 | 2002-05-27 | Bristol-Myers Squibb Company | Modified plasminogen related peptide fragments and their use as angiogenesis inhibitors |
| BR0206919A (pt) | 2001-02-02 | 2004-07-06 | Conjuchem Inc | Derivados de fator de liberação de hormÈnio de crescimento de longa duração |
| US7112567B2 (en) | 2001-02-16 | 2006-09-26 | Conjuchem Inc. | Long lasting glucagon-like peptide 2 (glp-2) for the treatment of gastrointestinal diseases and disorders |
| EP1573024A4 (en) | 2001-04-10 | 2007-08-29 | Agensys Inc | NUCLEIC ACIDS AND SUITABLE PROTEINS SUITABLE FOR THE TREATMENT AND EVIDENCE OF VARIOUS CANCER DISEASES |
| EP1381627B8 (en) * | 2001-04-18 | 2011-01-12 | The Open University | Polypeptides derived from amyloid precursor peptide (app) and their uses |
| US7491702B2 (en) | 2001-04-18 | 2009-02-17 | The Open University | Polypeptides related to amyloid precursor protein, pharmaceutical compositions thereof, and methods of treatment using the same |
| WO2002092781A2 (en) * | 2001-05-17 | 2002-11-21 | Ceremedix, Inc. | Peptide compounds for counteracting reactive oxygen species and free radicals |
| US7691639B2 (en) | 2001-05-31 | 2010-04-06 | Adlyfe, Inc. | Misfolded protein sensor method |
| US20050026165A1 (en) * | 2001-05-31 | 2005-02-03 | Cindy Orser | Detection of conformationally altered proteins and prions |
| ES2242860T3 (es) | 2001-05-31 | 2005-11-16 | Conjuchem, Inc. | Inhibidores peptidicos de fusion de larga vida contra infecciones por vih. |
| EP1435999B1 (en) * | 2001-10-18 | 2012-07-18 | Zlatko Ademovic | Combination of two bioactive regions of pro-opiomelanocortin hormone |
| US6822073B2 (en) * | 2001-12-20 | 2004-11-23 | Kimberly-Clark Worldwide, Inc. | Modular peptide-based reagent |
| CN1753909A (zh) * | 2002-03-19 | 2006-03-29 | 株式会社康福来 | 肽,含有该肽的药物组合物和用于治疗癌症的药物组合物 |
| JP2004008027A (ja) * | 2002-06-04 | 2004-01-15 | Japan Science & Technology Corp | ｃＡＭＰの産生活性を有する新規ペプチド |
| WO2004011595A2 (fr) * | 2002-07-26 | 2004-02-05 | Institut Pasteur | Vecteurs destines au transfert de molecules d'interet dans des cellules cibles |
| AU2003275116A1 (en) * | 2002-09-24 | 2004-04-19 | Frontier Biotechnologies Co., Ltd | Peptide derivative fusion inhibitors of hiv infection |
| US7378495B2 (en) * | 2002-10-21 | 2008-05-27 | Pevion Biotech, Ltd. | PTH-rP related peptide cancer therapeutics |
| AU2003290563A1 (en) * | 2002-10-31 | 2004-05-25 | Clf Medical Technology Acceleration Program, Inc. | Leptin-related peptides |
| EP1575511A4 (en) * | 2002-11-07 | 2006-06-28 | Us Gov Health & Human Serv | NEW TARGET FOR ANGIOGENESIS AND ANTI-ANGIOGENESIS THERAPY |
| DE60331584D1 (de) * | 2002-11-26 | 2010-04-15 | Biocon Ltd | Modifizierte natriuretic verbindungen, konjugate und ihre verwendungen |
| US7648962B2 (en) | 2002-11-26 | 2010-01-19 | Biocon Limited | Natriuretic compounds, conjugates, and uses thereof |
| AU2003292685A1 (en) * | 2003-01-10 | 2004-08-10 | Niigata Tlo Corporation | Vector for gene therapy and method of quantifying target protein in mammal or cultured cells with the administration of the vector for gene theraphy |
| AU2003210714A1 (en) * | 2003-01-29 | 2004-08-30 | Advanced Research And Technology Institute, Inc. | Immunoregulating compounds and an associated method |
| DE10316583A1 (de) * | 2003-04-10 | 2004-10-28 | B.R.A.H.M.S Aktiengesellschaft | Bestimmung eines midregionalen Proadrenomedullin-Teilpeptids in biologischen Flüssigkeiten zu diagnostischen Zwecken, sowie Immunoassays für die Durchführung einer solchen Bestimmung |
| JP2007523844A (ja) * | 2003-04-25 | 2007-08-23 | ジェノバ・リミテッド | 心臓血管障害において減少する分泌ポリペプチド種 |
| AU2004261319B2 (en) * | 2003-07-25 | 2010-12-23 | Conjuchem Biotechnologies Inc. | Long lasting insulin derivatives and methods thereof |
| WO2005077094A2 (en) * | 2004-02-11 | 2005-08-25 | Amylin Pharmaceuticals, Inc. | Pancreatic polypeptide family motifs and polypeptides comprising the same |
| WO2005090399A1 (ja) * | 2004-03-24 | 2005-09-29 | Gifu International Institute Of Biotechnology | 各種細胞の増殖・分化を認識する抗体、その抗体を用いた増殖・分化の評価方法 |
| JP5095391B2 (ja) * | 2004-04-20 | 2012-12-12 | スフィンゴテック・ゲーエムベーハー | 医療診断におけるタキキニンの前駆体および／またはその断片の使用 |
| DE602005027461D1 (de) | 2004-04-21 | 2011-05-26 | Enobia Pharma Inc | Konjugate zur zuführung an knochen und verfahren zu deren verwendung beim hinführen von proteinen zum knochen |
| AU2005235634B2 (en) | 2004-04-23 | 2011-10-20 | Conjuchem Biotechnologies Inc. | Method for the purification of albumin conjugates |
| ATE502305T1 (de) * | 2004-05-13 | 2011-04-15 | Brahms Gmbh | Verwendung von vorstufen von enkephalinen und/oder deren fragmenten in der medizinischen diagnostik |
| AU2012202855B2 (en) * | 2004-09-03 | 2015-02-26 | Philipps-Universitat Marburg | GLP-1 and exendin related invention |
| DE102004043153B4 (de) * | 2004-09-03 | 2013-11-21 | Philipps-Universität Marburg | Erfindung betreffend GLP-1 und Exendin |
| EP1814575A4 (en) | 2004-11-24 | 2010-07-07 | Neopro Labs Llc | METHOD AND COMPOSITIONS FOR TREATING SUFFERING |
| JP4720175B2 (ja) * | 2004-12-15 | 2011-07-13 | 富士ゼロックス株式会社 | マレイミジル基含有材料およびその製造方法 |
| DE102005003687A1 (de) | 2005-01-26 | 2006-07-27 | Sphingo Tec Gmbh | Immunoassay zur Bestimmung der Freisetzung von Neurotensin in die Zirkulation |
| US8372593B2 (en) | 2005-02-15 | 2013-02-12 | Adlyfe, Inc. | Method for detecting misfolded proteins and prions |
| WO2006108686A2 (en) * | 2005-04-14 | 2006-10-19 | Aic | Bnp agonists |
| US7833979B2 (en) | 2005-04-22 | 2010-11-16 | Amgen Inc. | Toxin peptide therapeutic agents |
| WO2006121869A2 (en) * | 2005-05-05 | 2006-11-16 | The Board Of Trustees Of The University Of Illinois | Compositions and methods for treating mood and anxiety disorders |
| WO2007049940A1 (en) * | 2005-10-27 | 2007-05-03 | Peptron Co., Ltd | Bioactive substance-blood protein conjugate and stabilization of a bioactive substance using the same |
| CA2647835A1 (en) | 2006-03-28 | 2007-10-04 | Neopro Labs, Llc | Methods and compositions for treating conditions |
| US7982018B2 (en) | 2006-10-16 | 2011-07-19 | Conjuchem, Llc | Modified corticotropin releasing factor peptides and uses thereof |
| WO2008052043A2 (en) * | 2006-10-24 | 2008-05-02 | Cogenesys, Inc. | Opioid receptor agonist fusion proteins |
| US7910102B2 (en) | 2006-10-25 | 2011-03-22 | Amgen Inc. | Methods of using conjugated toxin peptide therapeutic agents |
| JP5631201B2 (ja) | 2007-03-28 | 2014-11-26 | プレジデント アンド フェローズ オブ ハーバード カレッジ | ステッチングされたポリペプチド |
| EP2152725A1 (en) | 2007-05-17 | 2010-02-17 | Neopro Labs, LLC | Crystalline and amorphous forms of peptide |
| JP5591691B2 (ja) | 2007-05-22 | 2014-09-17 | アムジエン・インコーポレーテツド | 生物活性を有する融合タンパク質を作製するための組成物及び方法 |
| WO2009023125A1 (en) * | 2007-08-14 | 2009-02-19 | The Board Of Trustees Of The Leland Stanford Junior University | Neuronostatin and its uses |
| CA2699169A1 (en) * | 2007-09-11 | 2009-04-16 | Mondobiotech Laboratories Ag | Therapeutic uses of intermedin 47 and 53 peptides |
| RU2010114059A (ru) * | 2007-09-11 | 2011-10-20 | Мондобайотек Лабораториз Аг (Li) | Применение фибронектинового фрагмента (196-203) в качестве терапевтического средства |
| EP2197469A2 (en) * | 2007-09-11 | 2010-06-23 | Mondobiotech Laboratories AG | Use of nf-kappab inhibitor sn50 and optionally angiotensin iii as therapeutic agents in the treatment of eg hbv infection |
| KR20100057063A (ko) * | 2007-09-11 | 2010-05-28 | 몬도바이오테크 래보래토리즈 아게 | 치료제로서의 펩티드의 용도 |
| MX2010008024A (es) | 2008-02-01 | 2010-12-21 | Ascendis Pharma As | Profarmaco que comprende un enlazador que se puede separar por si mismo. |
| ES2563553T3 (es) | 2008-04-01 | 2016-03-15 | Novo Nordisk A/S | Conjugados de insulina-albúmina |
| WO2009142727A2 (en) * | 2008-05-19 | 2009-11-26 | Vasogenix Pharmaceuticals, Inc. | Sequence modified calcitonin gene related peptides (cgrp) |
| CA2751730A1 (en) | 2009-02-25 | 2010-09-02 | Merck Sharp & Dohme Corp. | Metabolic engineering of a galactose assimilation pathway in the glycoengineered yeast pichia pastoris |
| MY161842A (en) * | 2009-07-29 | 2017-05-15 | Daiichi Sankyo Co Ltd | Motilin-like peptide compound having transmucosal absorbability imparted thereto |
| NZ598021A (en) | 2009-07-31 | 2014-05-30 | Sanofi Aventis Deutschland | Prodrugs comprising an insulin linker conjugate |
| KR101759499B1 (ko) | 2009-07-31 | 2017-07-19 | 사노피-아벤티스 도이칠란트 게엠베하 | 지속형 인슐린 조성물 |
| CA2779161A1 (en) | 2009-10-28 | 2011-05-05 | University Of Manitoba | Yellow pea seed protein-derived peptides |
| AU2011220878A1 (en) | 2010-02-24 | 2012-08-23 | Merck Sharp & Dohme Corp. | Method for increasing N-glycosylation site occupancy on therapeutic glycoproteins produced in Pichia pastoris |
| AU2011231503C1 (en) * | 2010-03-26 | 2016-03-03 | Novo Nordisk A/S | Novel glucagon analogues |
| MX355543B (es) | 2010-08-13 | 2018-04-20 | Aileron Therapeutics Inc Star | Macrociclos peptidomiméticos. |
| EP2438930A1 (en) | 2010-09-17 | 2012-04-11 | Sanofi-Aventis Deutschland GmbH | Prodrugs comprising an exendin linker conjugate |
| CA2823066A1 (en) | 2010-12-27 | 2012-07-05 | Alexion Pharma International Sarl | Compositions comprising natriuretic peptides and methods of use thereof |
| CA2849673A1 (en) | 2011-09-23 | 2013-03-28 | Novo Nordisk A/S | Novel glucagon analogues |
| TWI643868B (zh) | 2011-10-18 | 2018-12-11 | 艾利倫治療公司 | 擬肽巨環化合物 |
| SG11201404648PA (en) | 2012-02-15 | 2014-09-26 | Aileron Therapeutics Inc | Peptidomimetic macrocycles |
| EP2819688A4 (en) | 2012-02-15 | 2015-10-28 | Aileron Therapeutics Inc | PEPTIDOMIMETIC MACROCYCLES CROSS-LINKED WITH TRIAZOLE AND THIOETHER |
| JP2013179884A (ja) * | 2012-03-01 | 2013-09-12 | Mitsubishi Rayon Co Ltd | メラニンカスケードに関与する成分を評価するための核酸マイクロアレイ及びメラニンカスケードに関与する成分の評価方法 |
| AU2013263349B2 (en) | 2012-05-17 | 2016-09-08 | Extend Biosciences, Inc | Carriers for improved drug delivery |
| US10052366B2 (en) | 2012-05-21 | 2018-08-21 | Alexion Pharmaceuticsl, Inc. | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof |
| KR20150082307A (ko) | 2012-11-01 | 2015-07-15 | 에일러론 테라퓨틱스 인코포레이티드 | 이치환 아미노산 및 이의 제조 및 사용 방법 |
| PL2986313T3 (pl) | 2013-04-18 | 2019-12-31 | Novo Nordisk A/S | Stabilni, dłużej działający współagoniści receptora glp-1/glukagonu do zastosowań medycznych |
| PT3016671T (pt) * | 2013-07-04 | 2021-12-02 | Univ Barcelona | Péptidos ativamente transportados e resistentes à protease como transportes bbb e construtos de transporte de carga |
| AU2015207776B2 (en) * | 2014-01-15 | 2017-06-15 | Fyziologicky Ustav Akademie Ved Cr, V.V.I. | Lipidated peptides for lowering blood glucose |
| JP2017525656A (ja) | 2014-06-04 | 2017-09-07 | ノヴォ ノルディスク アー／エス | 医療用のｇｌｐ−１／グルカゴン受容体コアゴニスト |
| WO2016007873A1 (en) | 2014-07-11 | 2016-01-14 | The Regents Of The University Of Michigan | Compositions and methods for treating craniosynostosis |
| SG11201702223UA (en) | 2014-09-24 | 2017-04-27 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| US9789197B2 (en) | 2014-10-22 | 2017-10-17 | Extend Biosciences, Inc. | RNAi vitamin D conjugates |
| US9616109B2 (en) | 2014-10-22 | 2017-04-11 | Extend Biosciences, Inc. | Insulin vitamin D conjugates |
| WO2016065042A1 (en) | 2014-10-22 | 2016-04-28 | Extend Biosciences, Inc. | Therapeutic vitamin d conjugates |
| RU2708068C2 (ru) | 2014-12-05 | 2019-12-04 | Алексион Фармасьютикалз, Инк. | Лечение судорог с использованием рекомбинантной щелочной фосфатазы |
| AU2016211447B2 (en) | 2015-01-28 | 2021-09-23 | Alexion Pharmaceuticals, Inc. | Methods of treating a subject with an alkaline phosphatase deficiency |
| ES2740273T3 (es) * | 2015-02-22 | 2020-02-05 | Omnix Medical Ltd | Péptidos antimicrobianos |
| KR20170129879A (ko) | 2015-03-20 | 2017-11-27 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티드모방 거대고리 및 이의 용도 |
| RU2745528C2 (ru) | 2015-08-17 | 2021-03-26 | Алексион Фармасьютикалз, Инк. | Производство щелочных фосфатаз |
| EP3355904A4 (en) | 2015-09-28 | 2019-06-12 | Alexion Pharmaceuticals, Inc. | IDENTIFICATION OF EFFECTIVE DOSE SHEETS FOR TISSUE-SPECIFIC ALKALINE PHOSPHATASE ENZYMERSAT THERAPY OF HYPOPHOSPHATASIA |
| US11400140B2 (en) | 2015-10-30 | 2022-08-02 | Alexion Pharmaceuticals, Inc. | Methods for treating craniosynostosis in a patient |
| US11530243B2 (en) * | 2016-02-18 | 2022-12-20 | Veiove Animal Health Inc. | Non-cleavable substance P conjugates and methods of use thereof |
| WO2017155569A1 (en) | 2016-03-08 | 2017-09-14 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in children |
| EP3436052A4 (en) | 2016-04-01 | 2019-10-09 | Alexion Pharmaceuticals, Inc. | TREATMENT OF MUSCLE WEAKNESS WITH ALKALINE PHOSPHATASES |
| US10898549B2 (en) | 2016-04-01 | 2021-01-26 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in adolescents and adults |
| US10988744B2 (en) | 2016-06-06 | 2021-04-27 | Alexion Pharmaceuticals, Inc. | Method of producing alkaline phosphatase |
| EP3500289B1 (en) | 2016-08-18 | 2024-10-09 | Alexion Pharmaceuticals, Inc. | Asfotase alfa for use in treating tracheobronchomalacia |
| JP6965362B2 (ja) | 2017-03-01 | 2021-11-10 | チェンドゥ フイタイ バイオメディスン カンパニー リミテッドChengdu Huitai Biomedicine Co., Ltd. | ポリペプチド、ポリペプチド断片及びその誘導体、並びに応用 |
| BR112019020506A2 (pt) | 2017-03-31 | 2020-08-04 | Alexion Pharmaceuticals, Inc. | métodos para o tratamento de hipofosfatasia (hpp) em adultos e adolescentes |
| US12297227B2 (en) | 2017-06-02 | 2025-05-13 | Mediford Corporation | Method for extracting target protein from biological sample and method for analyzing target protein |
| CN109503700A (zh) * | 2017-09-14 | 2019-03-22 | 南京安吉生物科技有限公司 | 马来酰亚胺基团修饰的血管生成抑制剂hm-1及其应用 |
| EP3717508A1 (en) | 2017-12-01 | 2020-10-07 | The University of Copenhagen | Peptide hormone with one or more o-glycans |
| EP3773684A1 (en) | 2018-03-30 | 2021-02-17 | Alexion Pharmaceuticals, Inc. | Manufacturing of glycoproteins |
| WO2019197313A1 (en) | 2018-04-09 | 2019-10-17 | Svar Life Science Ab | Glucagon Assay |
| WO2020033867A2 (en) | 2018-08-10 | 2020-02-13 | Alexion Pharmaceuticals, Inc. | Methods of treating neurofibromatosis type 1 and related conditions with alkaline phosphatase |
| EP3906316A4 (en) * | 2018-12-31 | 2022-11-30 | United Neuroscience Limited | PEPTIDE IMMUNOGENS FOR TARGETING CALCITONINGEN-RELATED PEPTIDE (CGRP) AND FORMULATIONS THEREOF FOR THE PREVENTION AND TREATMENT OF MIGRAINE |
| KR20220111693A (ko) | 2019-12-09 | 2022-08-09 | 알렉시온 파마슈티칼스, 인코포레이티드 | 알칼리성 포스파타제 폴리펩티드 및 이의 이용 방법 |
| IT202000007720A1 (it) * | 2020-04-10 | 2021-10-10 | Alessandra Marconi | Peptidi e loro usi |
| JP2023550784A (ja) * | 2020-11-25 | 2023-12-05 | プロリンクス エルエルシー | Ｃ－ナトリウム利尿ペプチドの徐放性ヒドロゲルコンジュゲート |
| KR20230145120A (ko) | 2021-02-12 | 2023-10-17 | 알렉시온 파마슈티칼스, 인코포레이티드 | 알칼리성 포스파타제 폴리펩타이드 및 이의 사용 방법 |
| EP4593867A2 (en) | 2022-09-30 | 2025-08-06 | Extend Biosciences, Inc. | Long-acting parathyroid hormone |
| GB202215797D0 (en) | 2022-10-25 | 2022-12-07 | Solasta Bio Ltd | Insect neuropeptide analogues |
| US12356995B2 (en) | 2023-10-23 | 2025-07-15 | Solasta Bio Limited | Insect neuropeptides 9 |
| US12281143B1 (en) | 2023-10-23 | 2025-04-22 | Solasta Bio Limited | Insect neuropeptides 1 |
| US12302908B2 (en) | 2023-10-23 | 2025-05-20 | Solasta Bio Limited | Insect neuropeptides 4 |
| US12245588B1 (en) | 2023-10-23 | 2025-03-11 | Solasta Bio Limited | Insect neuropeptides 2 |
| US12279621B1 (en) | 2023-10-23 | 2025-04-22 | Solasta Bio Limited | Insect neuropeptides 3 |
| US12245596B1 (en) | 2023-10-23 | 2025-03-11 | Solasta Bio Limited | Insect neuropeptides 8 |
| WO2025196125A1 (en) * | 2024-03-19 | 2025-09-25 | Epoqe Pharma Aps | N-terminally modified calcitonin gene-related peptide analogues |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3719667A (en) | 1970-08-24 | 1973-03-06 | Lilly Co Eli | Epimerization of 6-acylamido and 6-imido penicillin sulfoxide esters |
| US3840556A (en) | 1971-05-28 | 1974-10-08 | Lilly Co Eli | Penicillin conversion by halogen electrophiles and anti-bacterials derived thereby |
| BE795238A (fr) * | 1972-02-09 | 1973-08-09 | Schering Ag | Derives d'insuline reticules de maniere intramoleculaire, leur procede de preparation et leur utilisation |
| US4462941A (en) | 1982-06-10 | 1984-07-31 | The Regents Of The University Of California | Dynorphin amide analogs |
| DE3604868A1 (de) * | 1986-02-15 | 1987-08-20 | Behringwerke Ag | Insulinderivate, verfahren zu ihrer herstellung und ihre verwendung |
| DD252539A1 (de) * | 1986-09-17 | 1987-12-23 | Berlin Chemie Veb | Verfahren zur oralen anwendung biologisch aktiver peptide mit verzoegerter wirkung |
| US5612034A (en) * | 1990-10-03 | 1997-03-18 | Redcell, Inc. | Super-globuling for in vivo extended lifetimes |
| US5422339A (en) * | 1991-03-19 | 1995-06-06 | Joslin Diabetes Center, Inc. | Peptides having insulin autoantibody but not insulin receptor binding capacity |
| AU666853B2 (en) | 1991-04-05 | 1996-02-29 | Genentech Inc. | Platelet aggregation inhibitors having high specificity for GP IIbIIIa |
| CZ281630B6 (cs) | 1992-06-12 | 1996-11-13 | Des-Tyr Dynorphin Partnership | Analogy des-tyr dynorfinu |
| EP0602290B1 (en) * | 1992-12-04 | 1999-08-25 | ConjuChem, Inc. | Antibody-conjugated Hepatitis B surface antigen and use thereof |
| US5446128A (en) * | 1993-06-18 | 1995-08-29 | The Board Of Trustees Of The University Of Illinois | Alpha-helix mimetics and methods relating thereto |
| US5580853A (en) * | 1994-03-22 | 1996-12-03 | New England Deaconess Hospital | Modified polypeptides with increased biological activity |
| WO1996006626A1 (en) | 1994-08-26 | 1996-03-07 | Lee Nancy M | Analgesic method with dynorphin analogues truncated at the n-terminus |
| US5654276A (en) * | 1995-06-07 | 1997-08-05 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-5 receptor |
| EP0981611A1 (en) * | 1997-02-05 | 2000-03-01 | 1149336 Ontario Inc. | Polynucleotides encoding proexendin, and methods and uses thereof |
| ATE218892T1 (de) * | 1997-11-07 | 2002-06-15 | Conjuchem Inc | Affinitätsmarkierer für menschliches serum albumin |
| IL135835A0 (en) * | 1997-11-07 | 2001-05-20 | Conjuchem Inc | Novel conjugates of opioids and endogenous carriers |
| IL138214A0 (en) * | 1998-03-09 | 2001-10-31 | Zealand Pharmaceuticals As | Pharmacolgically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| JP2002512640A (ja) * | 1998-03-23 | 2002-04-23 | コンジュケム，インコーポレーテッド | 持続性治療薬の局所送達 |
-
2000
- 2000-05-17 EP EP00936023A patent/EP1105409B1/en not_active Expired - Lifetime
- 2000-05-17 EP EP05108328A patent/EP1623994A3/en not_active Withdrawn
- 2000-05-17 WO PCT/US2000/013576 patent/WO2000069900A2/en not_active Ceased
- 2000-05-17 CA CA002623458A patent/CA2623458A1/en not_active Abandoned
- 2000-05-17 EP EP05105384A patent/EP1591453A1/en not_active Withdrawn
- 2000-05-17 PT PT00936023T patent/PT1105409E/pt unknown
- 2000-05-17 CA CA002505617A patent/CA2505617A1/en not_active Abandoned
- 2000-05-17 AU AU51393/00A patent/AU765753B2/en not_active Ceased
- 2000-05-17 EP EP08158878A patent/EP2100901A1/en not_active Withdrawn
- 2000-05-17 ES ES00936023T patent/ES2257298T3/es not_active Expired - Lifetime
- 2000-05-17 CA CA002373680A patent/CA2373680C/en not_active Expired - Fee Related
- 2000-05-17 DE DE60026300T patent/DE60026300T2/de not_active Expired - Lifetime
- 2000-05-17 CA CA002499211A patent/CA2499211A1/en not_active Abandoned
- 2000-05-17 AT AT00936023T patent/ATE318835T1/de active
- 2000-05-17 EP EP05105387A patent/EP1598365A1/en not_active Withdrawn
- 2000-05-17 DK DK00936023T patent/DK1105409T3/da active
- 2000-05-17 JP JP2000618316A patent/JP4217004B2/ja not_active Expired - Fee Related
- 2000-05-17 SI SI200030836T patent/SI1105409T1/sl unknown
-
2005
- 2005-04-12 JP JP2005115175A patent/JP4219339B2/ja not_active Expired - Fee Related
- 2005-05-12 JP JP2005140407A patent/JP4221392B2/ja not_active Expired - Fee Related
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2008
- 2008-01-17 JP JP2008008555A patent/JP2008150384A/ja not_active Withdrawn
- 2008-09-25 JP JP2008246982A patent/JP2009079048A/ja not_active Withdrawn
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2010
- 2010-02-01 JP JP2010020780A patent/JP2010168384A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| SI1105409T1 (sl) | 2006-06-30 |
| WO2000069900A9 (en) | 2002-07-04 |
| EP2100901A1 (en) | 2009-09-16 |
| EP1623994A3 (en) | 2008-07-16 |
| CA2499211A1 (en) | 2000-11-23 |
| DE60026300T2 (de) | 2006-11-16 |
| WO2000069900A2 (en) | 2000-11-23 |
| PT1105409E (pt) | 2006-07-31 |
| ATE318835T1 (de) | 2006-03-15 |
| EP1105409A2 (en) | 2001-06-13 |
| EP1623994A2 (en) | 2006-02-08 |
| CA2373680A1 (en) | 2000-11-23 |
| JP4221392B2 (ja) | 2009-02-12 |
| JP2005263807A (ja) | 2005-09-29 |
| DK1105409T3 (da) | 2006-07-03 |
| JP2005239736A (ja) | 2005-09-08 |
| AU5139300A (en) | 2000-12-05 |
| WO2000069900A3 (en) | 2001-02-15 |
| CA2623458A1 (en) | 2000-11-23 |
| JP2003508350A (ja) | 2003-03-04 |
| JP2010168384A (ja) | 2010-08-05 |
| AU765753B2 (en) | 2003-09-25 |
| JP2009079048A (ja) | 2009-04-16 |
| DE60026300D1 (de) | 2006-04-27 |
| EP1105409B1 (en) | 2006-03-01 |
| CA2373680C (en) | 2008-07-29 |
| CA2505617A1 (en) | 2000-11-23 |
| EP1591453A1 (en) | 2005-11-02 |
| JP4219339B2 (ja) | 2009-02-04 |
| ES2257298T3 (es) | 2006-08-01 |
| EP1598365A1 (en) | 2005-11-23 |
| JP2008150384A (ja) | 2008-07-03 |
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