MX357674B - Polipeptidos biosinteticos de espira aleatoria de prolina/alanina y sus usos. - Google Patents

Polipeptidos biosinteticos de espira aleatoria de prolina/alanina y sus usos.

Info

Publication number
MX357674B
MX357674B MX2016005860A MX2016005860A MX357674B MX 357674 B MX357674 B MX 357674B MX 2016005860 A MX2016005860 A MX 2016005860A MX 2016005860 A MX2016005860 A MX 2016005860A MX 357674 B MX357674 B MX 357674B
Authority
MX
Mexico
Prior art keywords
polypeptide
amino acid
random coil
biosynthetic
proline
Prior art date
Application number
MX2016005860A
Other languages
English (en)
Spanish (es)
Inventor
Arne Skerra
Uli Binder
Martin Schlapschy
Original Assignee
Xl Protein Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Xl Protein Gmbh filed Critical Xl Protein Gmbh
Publication of MX357674B publication Critical patent/MX357674B/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • 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
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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
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C07K14/56—IFN-alpha
    • 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
    • C07K14/61—Growth hormone [GH], i.e. somatotropin
    • C07K14/615—Extraction from natural sources
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Diabetes (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Obesity (AREA)
  • Toxicology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Communicable Diseases (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Heart & Thoracic Surgery (AREA)
MX2016005860A 2010-05-21 2011-05-20 Polipeptidos biosinteticos de espira aleatoria de prolina/alanina y sus usos. MX357674B (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP10163564 2010-05-21
US201061428016P 2010-12-29 2010-12-29
PCT/EP2011/058307 WO2011144756A1 (en) 2010-05-21 2011-05-20 Biosynthetic proline/alanine random coil polypeptides and their uses

Publications (1)

Publication Number Publication Date
MX357674B true MX357674B (es) 2018-07-18

Family

ID=42629445

Family Applications (2)

Application Number Title Priority Date Filing Date
MX2016005860A MX357674B (es) 2010-05-21 2011-05-20 Polipeptidos biosinteticos de espira aleatoria de prolina/alanina y sus usos.
MX2012013286A MX338914B (es) 2010-05-21 2011-05-20 Polipeptidos biosinteticos de espira aleatoria de prolina/alanina y sus usos.

Family Applications After (1)

Application Number Title Priority Date Filing Date
MX2012013286A MX338914B (es) 2010-05-21 2011-05-20 Polipeptidos biosinteticos de espira aleatoria de prolina/alanina y sus usos.

Country Status (18)

Country Link
US (3) US9221882B2 (https=)
EP (2) EP2571510B1 (https=)
JP (2) JP5828889B2 (https=)
KR (1) KR101872541B1 (https=)
CN (2) CN102883734B (https=)
AU (1) AU2011254564B2 (https=)
BR (1) BR112012029577B1 (https=)
CA (1) CA2794614C (https=)
DK (1) DK2571510T3 (https=)
EA (1) EA024755B1 (https=)
ES (1) ES2691642T3 (https=)
LT (1) LT2571510T (https=)
MX (2) MX357674B (https=)
NZ (1) NZ602522A (https=)
PL (1) PL2571510T3 (https=)
SG (1) SG185440A1 (https=)
SI (1) SI2571510T1 (https=)
WO (1) WO2011144756A1 (https=)

Families Citing this family (100)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX344559B (es) 2008-04-29 2016-12-20 Ascendis Pharma As Compuestos de hormona de crecimiento humana recombinante unidos al peg.
MX337432B (es) 2009-12-15 2016-03-04 Ascendis Pharma As Composicion de la hormona del crecimiento seca enlazada transitoriamente a un portador del polimero.
US9221882B2 (en) 2010-05-21 2015-12-29 Technische Universitat Munchen Biosynthetic proline/alanine random coil polypeptides and their uses
AU2012296951B2 (en) * 2011-08-12 2016-09-15 Ascendis Pharma A/S Protein carrier-linked prodrugs
JP6355563B2 (ja) * 2012-02-27 2018-07-11 アムニクス オペレーティング インコーポレイテッド Ｘｔｅｎ共役組成物およびそれを製造する方法
CN108686203A (zh) 2012-04-04 2018-10-23 哈洛齐梅公司 使用抗透明质酸剂和肿瘤靶向紫杉烷的组合疗法
WO2014114660A1 (en) * 2013-01-22 2014-07-31 Deutsches Zentrum Für Neurodegenerative Erkrankungen E.V. (Dzne) Dipeptide-repeat proteins as therapeutic target in neurodegenerative diseases with hexanucleotide repeat expansion
JP6259208B2 (ja) * 2013-06-17 2018-01-10 雪印メグミルク株式会社 ヒアルロン酸産生促進剤
JP6259207B2 (ja) * 2013-06-17 2018-01-10 雪印メグミルク株式会社 エラスチン産生促進剤
JP6259209B2 (ja) * 2013-06-17 2018-01-10 雪印メグミルク株式会社 コラーゲン産生促進剤
EP3068438A1 (en) 2013-11-11 2016-09-21 Ascendis Pharma Relaxin Division A/S Relaxin prodrugs
US9618507B2 (en) 2014-02-24 2017-04-11 Betanien Hospital Methods of treating rheumatoid arthritis
WO2015132004A1 (en) 2014-03-05 2015-09-11 Merz Pharma Gmbh & Co. Kgaa Novel recombinant clostridial neurotoxins with increased duration of effect
PL228341B1 (pl) * 2014-04-21 2018-03-30 Bio Ventures Inst Spolka Z Ograniczona Odpowiedzialnoscia Sposób uzyskiwania białka poliepitopowego oraz wektor DNA do realizacji tego sposobu
US10821152B2 (en) 2014-08-26 2020-11-03 Betanien Hospital Methods, agents and compositions for treatment of inflammatory conditions
SG11201703870UA (en) 2014-11-18 2017-06-29 Ascendis Pharma Endocrinology Div As Novel polymeric hgh prodrugs
PT3220892T (pt) 2014-11-21 2021-11-05 Ascendis Pharma Endocrinology Div A/S Formas de dosagem de hormona do crescimento de longa ação
ES2784603T3 (es) 2015-06-02 2020-09-29 Novo Nordisk As Insulinas con extensiones recombinantes polares
TW201718627A (zh) 2015-06-11 2017-06-01 梅茲製藥有限兩合公司 重組梭菌神經毒素及其使用與形成方法、包括其之醫藥組合物及對應其之前驅物、編碼前驅物之核酸序列及其獲得方法與前驅物之形成方法、載體與包括核酸序列之重組宿主細胞
EP3347874B1 (en) * 2015-09-09 2021-05-12 Technische Universiteit Eindhoven Imaging of dispersion and velocity of contrast agents
EP3355931B1 (en) 2015-10-01 2024-06-26 Novo Nordisk A/S Protein conjugates
EP4491735A3 (en) * 2015-10-08 2025-04-16 The Governors of the University of Alberta Hepatitis c virus e1/e2 heterodimers and methods of producing same
WO2017109087A1 (en) * 2015-12-22 2017-06-29 Xl-Protein Gmbh Nucleic acids encoding repetitive amino acid sequences rich in proline and alanine residues that have low repetitive nucleotide sequences
CN108697768B (zh) 2015-12-23 2022-07-22 约翰霍普金斯大学 长效glp-1r激动剂作为神经系统病状和神经退行性病状的治疗方法
IL259827B2 (en) 2016-01-08 2025-07-01 Ascendis Pharma Growth Disorders As Controlled-release CNP agonists with low initial NPR-B activity
CA3007976C (en) 2016-01-08 2023-09-26 Ascendis Pharma Growth Disorders A/S Cnp prodrugs with large carrier moieties
EP3400021A1 (en) 2016-01-08 2018-11-14 Ascendis Pharma Growth Disorders A/S Controlled-release cnp agonists with low npr-c binding
DK3400019T3 (da) 2016-01-08 2022-10-24 Ascendis Pharma Growth Disorders As CNP-prodrugs med bærerbinding ved ringenheden
ES3064816T3 (en) 2016-01-08 2026-04-29 Ascendis Pharma Growth Disorders As Controlled-release cnp agonists with reduced side-effects
WO2017118700A1 (en) 2016-01-08 2017-07-13 Ascendis Pharma Growth Disorders A/S Controlled-release cnp agonists with increased nep stability
US11078472B2 (en) 2016-01-20 2021-08-03 Merz Pharma Gmbh & Co., Kgaa Recombinant clostridial neurotoxins with increased duration of effect
MY208384A (en) 2016-03-01 2025-05-05 Ascendis Pharma Bone Diseases As Pth prodrugs
CN108463242A (zh) 2016-03-02 2018-08-28 梅尔兹制药公司 包含肉毒杆菌毒素的组合物
US11306130B2 (en) 2016-04-01 2022-04-19 Arizona Board Of Regents On Behalf Of The University Of Arizona PAR3 mimetic peptides and uses thereof
US11813336B2 (en) * 2016-05-04 2023-11-14 Navigo Proteins Gmbh Targeted compounds for the site-specific coupling of chemical moieties comprising a peptide linker
US11896671B2 (en) 2016-07-13 2024-02-13 Ascendis Pharma A/S Conjugation method for carrier-linked prodrugs
US11564974B2 (en) 2016-09-29 2023-01-31 Ascendis Pharma Growth Disorders A/S Combination therapy with controlled-release CNP agonists
KR102627405B1 (ko) 2016-09-29 2024-01-18 아센디스 파마 본 디지즈 에이/에스 조절 방출 pth 화합물을 위한 투여 용법
US12453778B2 (en) 2016-09-29 2025-10-28 Ascendis Pharma Bone Diseases A/S Incremental dose finding in controlled-release PTH compounds
HRP20230383T1 (hr) 2016-09-29 2023-07-07 Ascendis Pharma Bone Diseases A/S Pth spojevi s malim omjerima maksimalne prema minimalnoj koncentraciji
US10738338B2 (en) 2016-10-18 2020-08-11 The Research Foundation for the State University Method and composition for biocatalytic protein-oligonucleotide conjugation and protein-oligonucleotide conjugate
US11807671B2 (en) * 2016-11-16 2023-11-07 Auckland Uniservices Limited Methods for protein ligation and uses thereof
JP2020513019A (ja) 2017-04-05 2020-04-30 ノヴォ ノルディスク アー／エス オリゴマー伸長インスリン−Ｆｃコンジュゲート
WO2018233813A1 (en) 2017-06-20 2018-12-27 Merz Pharma Gmbh & Co. Kgaa NOVEL RECOMBINANT BOTULINUM TOXINS WITH INCREASED DURATION
US10174302B1 (en) 2017-06-21 2019-01-08 Xl-Protein Gmbh Modified L-asparaginase
CN110891612A (zh) * 2017-06-21 2020-03-17 Xl-蛋白有限责任公司 蛋白质药物与p/a肽的缀合物
SG11201912625QA (en) 2017-06-21 2020-01-30 Jazz Pharmaceuticals Ireland Ltd Modified l-asparaginase
EP3418383A1 (en) 2017-06-21 2018-12-26 XL-protein GmbH Modified l-asparaginase
EP3649143B1 (en) 2017-07-06 2022-08-31 Merz Pharma GmbH & Co. KGaA Novel recombinant botulinum neurotoxins with increased duration of effect
EP3483619A1 (en) * 2017-11-13 2019-05-15 Technische Universität München Automated noninvasive determining the sex of an embryo of and the fertility of a bird's egg
US20200354706A1 (en) * 2017-11-22 2020-11-12 Merz Pharma Gmbh & Co. Kgaa Novel recombinant botulinum toxin with increased duration of effect
US20190184028A1 (en) * 2017-12-14 2019-06-20 Janssen Biotech, Inc. Targeting with firbronectin type iii like domain molecules
GB201804092D0 (en) * 2018-03-14 2018-04-25 Imperial Innovations Ltd Methods and compositions
CN111918665B (zh) 2018-03-28 2024-11-26 阿森迪斯药物肿瘤股份有限公司 Il-2缀合物
AU2019246390B2 (en) 2018-03-28 2025-03-27 Ascendis Pharma A/S Conjugates
TWI724392B (zh) * 2018-04-06 2021-04-11 美商美國禮來大藥廠 生長分化因子15促效劑化合物及其使用方法
CN112334152A (zh) 2018-05-18 2021-02-05 阿森迪斯药物骨疾病股份有限公司 Pth缀合物的起始剂量
CN119264211A (zh) 2018-08-27 2025-01-07 瑞泽恩制药公司 拉曼光谱在下游纯化中的应用
US20220002370A1 (en) 2018-09-27 2022-01-06 Xilio Development, Inc. Masked cytokine polypeptides
CN111153965A (zh) * 2018-11-07 2020-05-15 浙江道尔生物科技有限公司 用于改善活性蛋白或多肽性能的人工重组蛋白及其应用
EP3887393A1 (en) 2018-11-26 2021-10-06 Novartis AG Lpl-gpihbp1 fusion polypeptides
US20240018190A1 (en) * 2019-01-10 2024-01-18 Roswell Biotechnologies, Inc. Conductive synthetic peptides for molecular electronics
MY209748A (en) 2019-02-11 2025-07-31 Ascendis Pharma Bone Diseases As Liquid pharmaceutical formulations of pth conjugates
MX2021008708A (es) 2019-02-11 2021-09-21 Ascendis Pharma Growth Disorders As Formulaciones farmaceuticas secas de conjugados de peptido natriuretico tipo c (cnp).
AU2020233198B2 (en) 2019-03-04 2025-05-15 Ascendis Pharma Endocrinology Division A/S Long-acting growth hormone dosage forms with superior efficacy to daily somatropin
EP3714909A1 (en) * 2019-03-28 2020-09-30 Industrie Biomediche Insubri S.A. Improved bone implant matrix comprising proline-rich peptide and method of preparing the same
US10784093B1 (en) * 2019-04-04 2020-09-22 Thermo Finnigan Llc Chunking algorithm for processing long scan data from a sequence of mass spectrometry ion images
WO2020254603A1 (en) 2019-06-21 2020-12-24 Ascendis Pharma A/S CONJUGATES OF π-ELECTRON-PAIR-DONATING HETEROAROMATIC NITROGEN-COMPRISING COMPOUNDS
AU2020296297B2 (en) 2019-06-21 2025-06-12 Ascendis Pharma A/S Conjugates of heteroaromatic nitrogen-comprising compounds
US20220304993A1 (en) 2019-06-21 2022-09-29 Ascendis Pharma A/S Conjugates of an electron-donating nitrogen or tertiary amine comprising compounds
AU2020338947A1 (en) 2019-08-27 2022-03-31 Tonix Pharma Limited Modified TFF2 polypeptides
CA3156066A1 (en) 2019-10-25 2021-04-29 Mi Rim Choi Recombinant l-asparaginase
WO2021113434A1 (en) * 2019-12-03 2021-06-10 Rodan & Fields, Llc Peptides and compositions for inhibiting hair growth
US20230242655A1 (en) 2019-12-03 2023-08-03 Evotec International Gmbh Interferon-associated antigen binding proteins and uses thereof
EP4071178A4 (en) * 2019-12-06 2024-10-09 Ajinomoto Co., Inc. METHOD FOR PREPARING A PEPTIDE WITH PHYSIOLOGICAL ACTIVITY AND A PEPTIDE WITH A SHORT LINKER
JP7851853B2 (ja) 2020-01-03 2026-04-27 アセンディス ファーマ エー／エス 分子内転位を受けるコンジュゲート
MX2022007371A (es) 2020-01-13 2022-07-12 Ascendis Pharma Bone Diseases As Tratamiento del hipoparatiroidismo.
CN113527485B (zh) * 2020-04-17 2024-11-15 湖南麦济生物技术股份有限公司 抗人白细胞介素-4受体α抗体及其制备方法和应用
GB202007106D0 (en) * 2020-05-14 2020-07-01 Ucl Business Plc Cyclosporine analogues
KR20230019889A (ko) 2020-06-03 2023-02-09 아센디스 파마 온콜로지 디비전 에이/에스 Il-2 서열 및 이의 용도
WO2022029178A1 (en) 2020-08-05 2022-02-10 Ascendis Pharma A/S Conjugates comprising reversible linkers and uses thereof
CA3192744A1 (en) 2020-09-23 2022-03-31 Oskar SMRZKA Compound for the sequestration of undesirable anti-peg antibodies in a patient
WO2022064035A1 (en) 2020-09-28 2022-03-31 Ascendis Pharma Bone Diseases A/S Improvement of physical and mental well-being of patients with hypoparathyroidism
KR20230124637A (ko) 2020-12-22 2023-08-25 엑스엘-프로테인 게엠베하 구조적으로 무질서한 서열에 대해 특이적인 항체
CN112843222B (zh) * 2021-01-21 2023-01-31 暨南大学 Ankrd22蛋白在制备治疗或延缓自身免疫性疾病的产品中的应用
JP2024514095A (ja) 2021-04-01 2024-03-28 アセンディス ファーマ エー／エス 炎症によって誘発される疾患を治療するための長時間作用型成長ホルモンの使用
IL311539A (en) 2021-09-22 2024-05-01 Ascendis Pharma Bone Diseases As Long-acting pth compound treatments
WO2023110758A1 (en) 2021-12-13 2023-06-22 Ascendis Pharma Growth Disorders A/S Effective doses of cnp conjugates
EP4529454A1 (en) 2022-05-23 2025-04-02 Ascendis Pharma Growth Disorders A/S Liquid pharmaceutical formulations of cnp compounds
WO2023234416A1 (ja) 2022-06-02 2023-12-07 味の素株式会社 親和性物質、化合物、抗体およびそれらの塩
CN115927347B (zh) * 2022-10-14 2026-01-16 杭州佰辰医学检验所有限公司 特异性结合利培酮的核酸适配体及衍生物、应用、试剂盒
JP2025537527A (ja) 2022-11-02 2025-11-18 アセンディス ファーマ ボーン ディジージズ エー／エス ２つのｐｔｈ化合物を含むｐｔｈ治療レジメン
WO2024104922A1 (en) 2022-11-14 2024-05-23 Ascendis Pharma Growth Disorders A/S Method of improving skeletal muscle function
GB202218084D0 (en) 2022-12-01 2023-01-18 Volution Immuno Pharmaceuticals Sa Fusion proteins
AU2024240722A1 (en) 2023-03-20 2025-09-18 Ascendis Pharma Growth Disorders A/S Method of treatment of a thoracolumbar deformity in a human subject with achondroplasia
IL326658A (en) 2023-09-04 2026-04-01 Ascendis Pharma Bone Diseases As PTH treatment in chronic kidney disease
WO2025088193A1 (en) 2023-10-27 2025-05-01 Xl-Protein Gmbh Methods for efficient recombinant production of polypeptides
WO2025088192A1 (en) 2023-10-27 2025-05-01 Xl-Protein Gmbh Methods for the coupling of di(alkyl)amines to polypeptides
WO2025233381A1 (en) 2024-05-07 2025-11-13 Technische Universität München, in Vertretung des Freistaates Bayern Enzymes that eliminate pyrimidine and/or purine nucleosides for treating cancer
GB202408081D0 (en) 2024-06-06 2024-07-24 Volution Immuno Pharmaceuticals Sa Methods of removing impurities

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI92601C (fi) 1992-03-11 1994-12-12 Marja Makarow Menetelmä hyötyproteiinien erittämiseksi hiivoista
US6639050B1 (en) * 1997-07-21 2003-10-28 Ohio University Synthetic genes for plant gums and other hydroxyproline-rich glycoproteins
US20030190740A1 (en) 1998-10-13 2003-10-09 The University Of Georgia Research Foundation, Inc Stabilized bioactive peptides and methods of identification, synthesis, and use
CA2412882A1 (en) 2000-06-30 2002-01-10 Maxygen Aps Peptide extended glycosylated polypeptides
US20020169125A1 (en) 2001-03-21 2002-11-14 Cell Therapeutics, Inc. Recombinant production of polyanionic polymers and uses thereof
US20060252120A1 (en) * 2003-05-09 2006-11-09 Kieliszewski Marcia J Synthetic genes for plant gums and other hydroxyproline-rich glycoproteins
CA2556032A1 (en) 2004-03-15 2005-09-29 Trimeris, Inc. Site-specific chemical modification of hiv gp41-derived peptides
JP4650798B2 (ja) * 2004-04-19 2011-03-16 デンカ生研株式会社 ウイルスの生産方法
BRPI0606934A2 (pt) 2005-01-25 2017-07-11 Cell Therapeutics Inc Conjugado de proteína biologicamente ativa, composição, molécula de dna quimérica, vetor, célula, e, métodos para preparar conjugado de proteína biologicamente ativa, e para determinar se um dado conjugado de proteína exibe uma meia-vida de plasma modificada comparada com a meia-vida intrínseca do polipeptídeo biologicamente ativo não conjungado
AU2007223855B2 (en) 2006-03-06 2013-05-16 Amunix Operating Inc. Unstructured recombinant polymers and uses thereof
ES2602610T3 (es) 2007-05-31 2017-02-21 Medigene Ag Proteína estructural mutada de un parvovirus
SI2173890T1 (sl) * 2007-06-21 2011-06-30 Univ Muenchen Tech Biološko aktivni proteini, ki imajo povečano in vivo in/ali in vitro stabilnost
TW200936156A (en) * 2008-01-28 2009-09-01 Novartis Ag Methods and compositions using Klotho-FGF fusion polypeptides
ES2610356T3 (es) 2009-02-03 2017-04-27 Amunix Operating Inc. Polipéptidos recombinantes extendidos y composiciones que comprenden los mismos
KR101813727B1 (ko) 2009-06-08 2018-01-02 아뮤닉스 오퍼레이팅 인코포레이티드 성장 호르몬 폴리펩타이드 및 이를 제조하고 사용하는 방법
US9221882B2 (en) 2010-05-21 2015-12-29 Technische Universitat Munchen Biosynthetic proline/alanine random coil polypeptides and their uses

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