HRP20191109T1 - Gdf klopke za uporabu u liječenju anemije - Google Patents
Gdf klopke za uporabu u liječenju anemije Download PDFInfo
- Publication number
- HRP20191109T1 HRP20191109T1 HRP20191109TT HRP20191109T HRP20191109T1 HR P20191109 T1 HRP20191109 T1 HR P20191109T1 HR P20191109T T HRP20191109T T HR P20191109TT HR P20191109 T HRP20191109 T HR P20191109T HR P20191109 T1 HRP20191109 T1 HR P20191109T1
- Authority
- HR
- Croatia
- Prior art keywords
- seq
- polypeptide
- amino acids
- use according
- sequence
- Prior art date
Links
Classifications
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- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/179—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1796—Receptors; Cell surface antigens; Cell surface determinants for hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- 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
-
- 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
- C07K14/475—Growth factors; Growth regulators
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6897—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/11—Protein-serine/threonine kinases (2.7.11)
- C12Y207/1103—Receptor protein serine/threonine kinase (2.7.11.30)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Wood Science & Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18909408P | 2008-08-14 | 2008-08-14 | |
| EP09806981.8A EP2340031B1 (en) | 2008-08-14 | 2009-08-13 | Gdf traps for use to treat anemia |
| PCT/US2009/004659 WO2010019261A1 (en) | 2008-08-14 | 2009-08-13 | Use of gdf traps to increase red blood cell levels |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20191109T1 true HRP20191109T1 (hr) | 2019-09-20 |
Family
ID=41669153
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20230761TT HRP20230761T1 (hr) | 2008-08-14 | 2009-08-13 | Gdf zamke |
| HRP20191109TT HRP20191109T1 (hr) | 2008-08-14 | 2009-08-13 | Gdf klopke za uporabu u liječenju anemije |
| HRP20201185TT HRP20201185T1 (hr) | 2008-08-14 | 2020-07-29 | Gdf zamke |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20230761TT HRP20230761T1 (hr) | 2008-08-14 | 2009-08-13 | Gdf zamke |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20201185TT HRP20201185T1 (hr) | 2008-08-14 | 2020-07-29 | Gdf zamke |
Country Status (22)
| Country | Link |
|---|---|
| US (10) | US8058229B2 (https=) |
| EP (3) | EP3494986B1 (https=) |
| JP (6) | JP5922928B2 (https=) |
| AU (1) | AU2009282441B2 (https=) |
| CA (1) | CA2733911C (https=) |
| CY (3) | CY1121971T1 (https=) |
| DK (3) | DK3494986T3 (https=) |
| ES (3) | ES2949049T3 (https=) |
| FI (1) | FI3750552T3 (https=) |
| FR (1) | FR20C1066I2 (https=) |
| HR (3) | HRP20230761T1 (https=) |
| HU (4) | HUE063136T2 (https=) |
| LT (4) | LT3750552T (https=) |
| NL (1) | NL301082I2 (https=) |
| NO (1) | NO2020045I1 (https=) |
| PL (3) | PL3750552T3 (https=) |
| PT (3) | PT2340031T (https=) |
| SI (3) | SI3750552T1 (https=) |
| SM (3) | SMT202000436T1 (https=) |
| TR (1) | TR201910890T4 (https=) |
| TW (7) | TW201803586A (https=) |
| WO (1) | WO2010019261A1 (https=) |
Families Citing this family (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008507288A (ja) * | 2004-07-23 | 2008-03-13 | アクセルロン ファーマ インコーポレーテッド | ActRII受容体ポリペプチド、方法、および組成物 |
| EP1855694B1 (en) | 2005-02-09 | 2020-12-02 | Sarepta Therapeutics, Inc. | Antisense composition for treating muscle atrophy |
| US8067562B2 (en) | 2005-11-01 | 2011-11-29 | Amgen Inc. | Isolated nucleic acid molecule comprising the amino acid sequence of SEQ ID NO:1 |
| ES2649983T3 (es) | 2005-11-23 | 2018-01-16 | Acceleron Pharma, Inc. | Antagonistas de activina-ActRIIa en su uso para promover el crecimiento óseo |
| US8128933B2 (en) | 2005-11-23 | 2012-03-06 | Acceleron Pharma, Inc. | Method of promoting bone growth by an anti-activin B antibody |
| US20100028332A1 (en) * | 2006-12-18 | 2010-02-04 | Acceleron Pharma Inc. | Antagonists of actriib and uses for increasing red blood cell levels |
| US8895016B2 (en) * | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| MX2009008222A (es) * | 2007-02-01 | 2009-10-12 | Acceleron Pharma Inc | Antagonistas de activina-actriia y usos para tratar o prevenir cancer de mama. |
| TW201803890A (zh) | 2007-02-02 | 2018-02-01 | 艾瑟勒朗法瑪公司 | 衍生自ActRIIB的變體與其用途 |
| EA018221B1 (ru) | 2007-02-09 | 2013-06-28 | Акселерон Фарма Инк. | АНТАГОНИСТЫ АКТИВИНА-ActRIIa И ПРИМЕНЕНИЕ ДЛЯ СТИМУЛЯЦИИ РОСТА КОСТИ У БОЛЬНЫХ РАКОМ |
| US8501678B2 (en) | 2007-03-06 | 2013-08-06 | Atara Biotherapeutics, Inc. | Variant activin receptor polypeptides and uses thereof |
| US7947646B2 (en) | 2007-03-06 | 2011-05-24 | Amgen Inc. | Variant activin receptor polypeptides |
| CN101861161B (zh) | 2007-09-18 | 2017-04-19 | 阿塞勒隆制药公司 | 活化素‑actriia拮抗剂和减少或抑制fsh分泌的用途 |
| CN102131822A (zh) * | 2008-06-26 | 2011-07-20 | 阿塞勒隆制药公司 | 进行激活素-ActRIIa拮抗剂给药和监测受治疗患者的方法 |
| TW201803586A (zh) | 2008-08-14 | 2018-02-01 | 艾瑟勒朗法瑪公司 | 使用gdf阱以增加紅血球水平 |
| US8216997B2 (en) | 2008-08-14 | 2012-07-10 | Acceleron Pharma, Inc. | Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators |
| JP5611222B2 (ja) | 2008-11-26 | 2014-10-22 | アムジエン・インコーポレーテツド | アクチビンiib受容体ポリペプチドの変異体及びその使用 |
| AU2010204985A1 (en) | 2009-01-13 | 2011-08-04 | Acceleron Pharma Inc. | Methods for increasing adiponectin |
| KR20120049214A (ko) | 2009-06-08 | 2012-05-16 | 악셀레론 파마 인코포레이티드 | 발열성 지방세포를 증가시키는 방법 |
| KR20180026795A (ko) | 2009-06-12 | 2018-03-13 | 악셀레론 파마 인코포레이티드 | 절두된 ActRIIB-FC 융합 단백질 |
| AU2010282361B2 (en) * | 2009-08-13 | 2015-03-19 | Acceleron Pharma Inc. | Combined use of GDF traps and erythropoietin receptor activators to increase red blood cell levels |
| AU2015203400A1 (en) * | 2009-08-13 | 2015-07-16 | Acceleron Pharma Inc. | Combined use of GDF traps and erythropoietin receptor activators to increase red blood cell levels |
| EP3202459B1 (en) * | 2009-09-09 | 2021-04-14 | Acceleron Pharma Inc. | Actriib antagonists and dosing and uses thereof for treating obesity or type 2 diabetes by regulating body fat content |
| AU2010315245B2 (en) * | 2009-11-03 | 2016-11-03 | Acceleron Pharma Inc. | Methods for treating fatty liver disease |
| EP3332796A1 (en) | 2009-11-17 | 2018-06-13 | Acceleron Pharma Inc. | Actriib proteins and variants and uses therefore relating to utrophin induction for muscular dystrophy therapy |
| JP2013512674A (ja) * | 2009-12-02 | 2013-04-18 | アクセルロン ファーマ, インコーポレイテッド | Fc融合タンパク質の血清半減期を増加させるための組成物および方法 |
| JO3340B1 (ar) | 2010-05-26 | 2019-03-13 | Regeneron Pharma | مضادات حيوية لـعامل تمايز النمو 8 البشري |
| EP2583973B1 (en) * | 2010-06-21 | 2018-03-21 | Kyowa Hakko Kirin Co., Ltd. | Method for purifying protein using amino acid |
| AU2011326586A1 (en) | 2010-11-08 | 2013-05-30 | Acceleron Pharma, Inc. | ActRIIA binding agents and uses thereof |
| EP2718328A4 (en) * | 2011-06-08 | 2014-12-24 | Acceleron Pharma Inc | COMPOSITIONS AND METHODS FOR INCREASING THE HALF TIME OF SERUM |
| US20130085139A1 (en) | 2011-10-04 | 2013-04-04 | Royal Holloway And Bedford New College | Oligomers |
| KR20140084211A (ko) * | 2011-10-17 | 2014-07-04 | 악셀레론 파마 인코포레이티드 | 효과가 없는 적혈구생성 치료를 위한 방법 및 조성물 |
| DK2780368T3 (en) | 2011-11-14 | 2018-02-05 | Regeneron Pharma | COMPOSITIONS AND PROCEDURES FOR INCREASING MUSCLE MASS AND MUSCLE STRENGTH BY SPECIFIC ANTAGONIZATION OF GDF8 AND / OR ACTIVIN A |
| HK1203384A1 (en) * | 2011-12-19 | 2015-12-11 | Amgen Inc. | Variant activin receptor polypeptides, alone or in combination with chemotherapy, and uses thereof |
| US9809636B2 (en) | 2012-04-06 | 2017-11-07 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels comprising administering BMP9 |
| WO2014030683A1 (ja) * | 2012-08-21 | 2014-02-27 | 国立大学法人九州大学 | 貧血患者の貧血の要因を検出するためのバイオマーカー |
| CN104968801B (zh) * | 2012-10-24 | 2021-06-15 | 细胞基因公司 | 用于治疗贫血症的生物标志物 |
| HK1214504A1 (zh) * | 2012-10-24 | 2016-07-29 | 细胞基因公司 | 用於治療貧血的方法 |
| US10195249B2 (en) | 2012-11-02 | 2019-02-05 | Celgene Corporation | Activin-ActRII antagonists and uses for treating bone and other disorders |
| AU2014212014A1 (en) | 2013-02-01 | 2015-08-27 | Amgen Inc. | Administration of an anti-activin-A compound to a subject |
| TW201920262A (zh) | 2013-07-30 | 2019-06-01 | 美商再生元醫藥公司 | 抗活化素a之抗體及其用途 |
| JP2017509647A (ja) * | 2014-03-21 | 2017-04-06 | アクセルロン ファーマ, インコーポレイテッド | アクチビンbおよび/またはgdf11の阻害によって赤血球レベルを増大させ、無効赤血球生成を処置する方法 |
| EP3808778A1 (en) * | 2014-04-18 | 2021-04-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating sickle-cell disease |
| CN114699529A (zh) | 2014-06-13 | 2022-07-05 | 阿塞勒隆制药公司 | 用于治疗溃疡的方法和组合物 |
| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| US10603359B2 (en) | 2014-10-30 | 2020-03-31 | Acceleron Pharma Inc. | Methods and compositions using GDF15 polypeptides for increasing red blood cells |
| JP2018501307A (ja) | 2014-12-03 | 2018-01-18 | セルジーン コーポレイション | アクチビン−ActRIIアンタゴニスト及び貧血を治療するための使用 |
| MA41119A (fr) * | 2014-12-03 | 2017-10-10 | Acceleron Pharma Inc | Méthodes de traitement de syndromes myélodysplasiques et d'anémie sidéroblastique |
| WO2016128523A1 (en) | 2015-02-12 | 2016-08-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the responsiveness of a patient affected with malignant hematological disease to chemotherapy treatment and methods of treatment of such disease |
| MA41795A (fr) | 2015-03-18 | 2018-01-23 | Sarepta Therapeutics Inc | Exclusion d'un exon induite par des composés antisens dans la myostatine |
| MA41920B1 (fr) | 2015-04-06 | 2021-05-31 | Acceleron Pharma Inc | Protéines de fusion de récepteur type i et type ii à bras unique et leurs utilisations |
| MA41919A (fr) | 2015-04-06 | 2018-02-13 | Acceleron Pharma Inc | Hétéromultimères alk4:actriib et leurs utilisations |
| US10358476B2 (en) | 2015-04-06 | 2019-07-23 | Acceleron Pharma Inc. | Single arm type I and type II receptor fusion proteins and uses thereof |
| KR20170135967A (ko) | 2015-04-15 | 2017-12-08 | 리제너론 파마슈티칼스 인코포레이티드 | Gdf8 억제제를 사용하여 강도 및 기능을 증가시키는 방법 |
| CA2983440C (en) | 2015-04-22 | 2024-03-12 | Alivegen Usa Inc. | Novel hybrid actriib ligand trap proteins for treating muscle wasting diseases |
| US20180125928A1 (en) * | 2015-05-13 | 2018-05-10 | Celgene Corporation | Treatment of beta-thalassemia using actrii ligand traps |
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| CA3031028C (en) | 2016-07-25 | 2024-02-13 | Lu Wang | Affinity chromatography wash buffer |
| MA45811A (fr) | 2016-07-27 | 2019-06-05 | Acceleron Pharma Inc | Méthodes et compositions de traitement de maladie. |
| CA3039573A1 (en) | 2016-10-05 | 2018-04-12 | Acceleron Pharma Inc. | Alk4:actriib heteromultimers and uses thereof |
| CN110036025B (zh) | 2016-10-05 | 2024-03-22 | 阿塞勒隆制药公司 | 变体ActRIIB蛋白及其用途 |
| JOP20190085A1 (ar) | 2016-10-20 | 2019-04-17 | Biogen Ma Inc | طرق علاج الضمور العضلي ومرض العظام باستخدام بروتينات احتجاز مركب ترابطي actriib هجين حديثة |
| NZ754161A (en) | 2016-11-10 | 2025-11-28 | Keros Therapeutics Inc | Activin receptor type iia variants and methods of use thereof |
| JOP20180036A1 (ar) | 2017-04-18 | 2019-01-30 | Vifor Int Ag | أملاح لمثبطات فروبورتين جديدة |
| PL3638243T3 (pl) | 2017-06-14 | 2025-02-10 | Celgene Corporation | Sposoby leczenia mielofibrozy związanej z nowotworem mieloproliferacyjnym i niedokrwistości |
| CA3082146A1 (en) | 2017-11-09 | 2019-05-16 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
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