ES2600491T3 - Una variante estabilizada de receptor IIB de activina - Google Patents

Una variante estabilizada de receptor IIB de activina Download PDF

Info

Publication number
ES2600491T3
ES2600491T3 ES09761055.4T ES09761055T ES2600491T3 ES 2600491 T3 ES2600491 T3 ES 2600491T3 ES 09761055 T ES09761055 T ES 09761055T ES 2600491 T3 ES2600491 T3 ES 2600491T3
Authority
ES
Spain
Prior art keywords
polypeptide
sequence
svactriib
seq
signal sequence
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
ES09761055.4T
Other languages
English (en)
Inventor
Jeonghoon Sun
Lei-Ting Tony Tam
Mark Leo Michaels
Thomas C. Boone
Rohini Deshpande
Yue-Sheng Li
Hq Han
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Amgen Inc
Original Assignee
Amgen Inc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=41693455&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ES2600491(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Amgen Inc filed Critical Amgen Inc
Application granted granted Critical
Publication of ES2600491T3 publication Critical patent/ES2600491T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • 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
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • 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
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/26—Androgens
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • 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
    • C07K14/495—Transforming growth factor [TGF]
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • 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)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Diabetes (AREA)
  • Toxicology (AREA)
  • Cell Biology (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Endocrinology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)

Abstract

Una proteína aislada que comprende un polipéptido receptor IIB de activina estabilizado, en la que dicho polipéptido se selecciona del grupo consistente en: (a) un polipéptido consistente en la secuencia expuesta en el grupo consistente en las SEQ ID NO: 4, 6, 12 y 14; (b) un polipéptido que tiene al menos un 90 % de identidad de secuencia con (a), en la que el polipéptido tiene W o Y en la posición correspondiente a la posición 28 de la SEQ ID NO:2 y T en la posición correspondiente a la posición 44 de la SEQ ID NO:2, en la que el polipéptido es capaz de unirse a miostatina, activina A o GDF-11, y (c) polipéptidos que tienen al menos un 95 % de identidad de secuencia con (a), en la que el polipéptido tiene W o Y en la posición correspondiente a la posición 28 de la SEQ ID NO:2 y T en la posición correspondiente a la posición 44 de la SEQ ID NO:2, en la que el polipéptido es capaz de unirse a miostatina, activina A o GDF-11.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
imagen8
imagen9
imagen10
imagen11
imagen12
imagen13
imagen14
imagen15
imagen16
imagen17
imagen18
ActRIIB-Fc
Secuencia de ActRIIB Ligador de bisagra Fc de IgG2
svActRIIB-IgG2Fc (E28W, S44T)
imagen19 imagen20 imagen21
(SEQ ID NO: 10)
imagen20 imagen22
ActRIIB-IgG2Fc (E28W) (SEQ ID NO: 21)
imagen23 imagen20 imagen24
Ejemplo 2
Caracterización de polipéptidos
5 Se diluyeron muestras de polipéptidos svActRIIB-Fc (E28W, S44T) (SEQ ID NO: 10) purificado mediante la etapa de MabSelect™ y ActRIIB-Fc (E28W) (SEQ ID NO: 21) purificado mediante la etapa de columna SP-HP, como se describe anteriormente, con PBS, pH 7,4 a 0,2 mg/ml. Se determinó entonces el perfil de glicosilación de los polipéptidos usando SEC como se describe a continuación.
Cromatografía de exclusión por tamaño (SEC). Se efectuaron los experimentos en un sistema de HPLC Agilent 1100
10 con dos columnas (TOSOHAAS G3000swxl, 7,8 x 300 mm) en serie. Se usó 2x PBS como fase móvil a 0,5 ml/minuto.
La Figura 1 muestra una comparación entre ActRIIB-Fc (E28W) y svActRIIB-Fc (E28W, S44T) en una columna de SEC usando los protocolos descritos anteriormente. svActRIIB-Fc (E28W, S44T) muestra un solo pico en comparación con ActRIIB-Fc (E28W), que muestra tres picos. Estos corresponden al grado de glicosilación N-ligada 15 en la posición N42 de los dímeros de Fc de ambas proteínas. El pico único del polipéptido svActRIIB-Fc (E28W, S44T) corresponde a asparaginas N-ligadas totalmente glicosiladas en la posición N42 del dímero. Los tres picos de ActRIIB-Fc (E28W) corresponden a (de izquierda a derecha) asparaginas totalmente glicosiladas en N42, asparaginas parcialmente glicosiladas en N42 y asparaginas no glicosiladas en N42. Por lo tanto, esto demuestra que la molécula de svActRIIB-Fc (E28W, S44T) está totalmente glicosilada en comparación con ActRIIB-Fc (E28W),
20 que es heterogénea con respecto a este sitio de glicosilación, y por tanto más difícil de purificar. Además, estudios preliminares indican que la molécula de svActRIIB-Fc (E28W, S44T) tiene además propiedades de fabricabilidad mejoradas como se expone a continuación. Estudios adicionales demostraron también que el pico menos glicosilado de ActRIIB-Fc (E28W) tiene menor estabilidad física y térmica que las moléculas parcial y totalmente glicosiladas.
La determinación de los valores de KD y CI50 de los polipéptidos receptores para activina A, miostatina y GDF-11 se 25 obtuvo como se describe a continuación.
Ensayos de equilibrio KINEX A™
Se usaron ensayos de unión en equilibrio basados en disolución usando la tecnología KinExA™ (Sapidyne Instruments, Inc.) para determinar el equilibrio de disociación (KD) de la unión de ligando a polipéptidos ActRIIB-Fc. Se prerrecubrieron perlas UltraLink Biosupport (Pierce) con aproximadamente 100 µg/ml de cada uno de miostatina, 30 GDF-11 y activina A durante una noche y se bloquearon entonces con BSA. Se incubaron muestras de ActRIIB-Fc (E28W) (SEQ ID NO: 21) y svActRIIB-Fc (E28W, S44T) (SEQ ID NO: 10) 1 pM y 3 pM con diversas concentraciones
20
imagen25
imagen26
imagen27
imagen28
SEQ ID NO:
DESCRIPCIÓN
4
polipéptido de svActRIIB (E28W, S44T) con secuencia señal
polinucleótido de svActRIIB (E28W, S44T) sin secuencia señal
6
polipéptido de svActRIIB (E28W, S44T) sin secuencia señal
7
polinucleótido de svActRIIB-Fc (E28W, S44T) con secuencia señal
8
polipéptido de svActRIIB-Fc (E28W, S44T) con secuencia señal
9
polinucleótido de svActRIIB-Fc (E28W, S44T) sin secuencia señal
polipéptido de svActRIIB-Fc (E28W, S44T) sin secuencia señal
11
polinucleótido de svActRIIB (E28Y, S44T) con secuencia señal
12
polipéptido de svActRIIB (E28Y, S44T) con secuencia señal
13
polinucleótido de svActRIIB (E28Y, S44T) sin secuencia señal
14
polipéptido de svActRIIB (E28Y, S44T) sin secuencia señal
polinucleótido de svActRIIB-Fc (E28Y, S44T) con secuencia señal
16
polipéptido de svActRIIB-Fc (E28Y, S44T) con secuencia señal
17
polinucleótido de svActRIIB-Fc (E28Y, S44T) sin secuencia señal
18
polipéptido de svActRIIB-Fc (E28Y, S44T) sin secuencia señal
19
polipéptido de ActRIIB (E28W) sin secuencia señal
polinucleótido de ActRIIB-Fc (E28W) sin secuencia señal
21
polipéptido de ActRIIBFc (E28W) sin secuencia señal
22
secuencia polipeptídica de IgG2Fc
23
secuencia polipeptídica de IgG1Fc
24
secuencia polipeptídica de IgG4Fc
secuencia aminoacídica de ligador
26
secuencia polinucleotídica de ligador de bisagra nº 1
27
secuencia peptídica de ligador de bisagra nº 1
28
región de bisagra de IgG2
29
región de bisagra de IgG1
región de bisagra de IgG4
25
SEQ ID NO:
DESCRIPCIÓN
31
secuencia señal alternativa, polipéptido
32
secuencia señal, polipéptido
33
ActRIIB de tipo silvestre de acceso NP 001097
34
secuencia polipeptídica de activina
35
secuencia polipeptídica de miostatina
36
secuencia polipeptídica de GDF-11
37
secuencia de ligador de bisagra nº 2, polinucleótido
38
secuencia de ligador de bisagra nº 2, péptido
39
secuencia de ligador de bisagra nº 3, polinucleótido
40
secuencia de ligador de bisagra nº 3, péptido
41
secuencia de ligador de bisagra nº 4, polinucleótido
42
secuencia de ligador de bisagra nº 4, péptido
43
secuencia de ligador de bisagra nº 5, polinucleótido
44
secuencia de ligador de bisagra nº 5, péptido
45
secuencia de ligador de bisagra nº 6, péptido
46
secuencia de ligador de bisagra nº 7, péptido
47
secuencia polipeptídica de Fc de IgG1 modificada
48
secuencia de ligador de bisagra nº 8, péptido
49
secuencia de ligador de bisagra nº 9, péptido
50
secuencia de ligador de bisagra nº 10, péptido
La presente invención no está limitada en el alcance por las realizaciones específicas descritas en la presente memoria, que se pretenden como simples ilustraciones de aspectos individuales de la invención, y métodos y componentes funcionalmente equivalentes están dentro del alcance de la invención. Es más, resultarán evidentes para el especialista en la materia diversas modificaciones de la invención, además de las mostradas y descritas en la presente memoria, a partir de la descripción anterior y los dibujos acompañantes. Dichas modificaciones pretenden entrar dentro del alcance de las reivindicaciones adjuntas.
26

Claims (1)

  1. imagen1
    imagen2
    imagen3
ES09761055.4T 2008-11-26 2009-11-24 Una variante estabilizada de receptor IIB de activina Active ES2600491T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US20025008P 2008-11-26 2008-11-26
US200250P 2008-11-26
US25906009P 2009-11-06 2009-11-06
US259060P 2009-11-06
PCT/US2009/006252 WO2010062383A2 (en) 2008-11-26 2009-11-24 Stabilized receptor polypeptides and uses thereof

Publications (1)

Publication Number Publication Date
ES2600491T3 true ES2600491T3 (es) 2017-02-09

Family

ID=41693455

Family Applications (1)

Application Number Title Priority Date Filing Date
ES09761055.4T Active ES2600491T3 (es) 2008-11-26 2009-11-24 Una variante estabilizada de receptor IIB de activina

Country Status (38)

Country Link
US (5) US8410043B2 (es)
EP (2) EP2370463B1 (es)
JP (3) JP5611222B2 (es)
KR (3) KR101778134B1 (es)
CN (2) CN102245634B (es)
AR (1) AR074397A1 (es)
AU (1) AU2009320364B2 (es)
BR (1) BRPI0920962A2 (es)
CA (2) CA2997971A1 (es)
CL (1) CL2011001239A1 (es)
CO (1) CO6382163A2 (es)
CR (2) CR20160443A (es)
CY (1) CY1118754T1 (es)
DK (1) DK2370463T3 (es)
EA (2) EA201791940A3 (es)
ES (1) ES2600491T3 (es)
HK (1) HK1162545A1 (es)
HR (1) HRP20161450T1 (es)
HU (1) HUE032090T2 (es)
IL (2) IL212773A (es)
LT (1) LT2370463T (es)
MA (1) MA32936B1 (es)
ME (1) ME02652B (es)
MX (1) MX2011005505A (es)
MY (1) MY159483A (es)
NZ (2) NZ604818A (es)
PE (2) PE20150680A1 (es)
PL (1) PL2370463T3 (es)
PT (1) PT2370463T (es)
RS (1) RS55369B1 (es)
SG (2) SG10201703067QA (es)
SI (1) SI2370463T1 (es)
SM (1) SMT201600417B (es)
TN (1) TN2011000238A1 (es)
TW (1) TWI486166B (es)
UA (1) UA107921C2 (es)
WO (1) WO2010062383A2 (es)
ZA (1) ZA201104648B (es)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8067562B2 (en) 2005-11-01 2011-11-29 Amgen Inc. Isolated nucleic acid molecule comprising the amino acid sequence of SEQ ID NO:1
US8128933B2 (en) 2005-11-23 2012-03-06 Acceleron Pharma, Inc. Method of promoting bone growth by an anti-activin B antibody
CN104844713B (zh) 2005-11-23 2021-05-14 阿塞勒隆制药公司 Activin-ActRIIa拮抗剂及其促进骨骼生长的应用
CL2007002567A1 (es) 2006-09-08 2008-02-01 Amgen Inc Proteinas aisladas de enlace a activina a humana.
US8895016B2 (en) 2006-12-18 2014-11-25 Acceleron Pharma, Inc. Antagonists of activin-actriia and uses for increasing red blood cell levels
BRPI0806861A2 (pt) 2007-02-01 2014-08-05 Acceleron Pharma Inc Antagonistas de ativina-actriia e usos para tratar ou prevenir câncer de mama
TW201940502A (zh) 2007-02-02 2019-10-16 美商艾瑟勒朗法瑪公司 衍生自ＡｃｔＲＩＩＢ的變體與其用途
TWI525102B (zh) 2007-02-09 2016-03-11 艾瑟勒朗法瑪公司 包含ＡｃｔＲＩＩａ-Ｆｃ融合蛋白的醫藥組合物；ＡｃｔＲＩＩａ-Ｆｃ融合蛋白於治療或預防與癌症相關的骨質流失之用途；ＡｃｔＲＩＩａ-Ｆｃ融合蛋白於治療或預防多發性骨髓瘤之用途
US8501678B2 (en) 2007-03-06 2013-08-06 Atara Biotherapeutics, Inc. Variant activin receptor polypeptides and uses thereof
TW201718635A (zh) 2007-03-06 2017-06-01 安美基公司 變異之活動素受體多肽及其用途
CN103877564A (zh) 2007-09-18 2014-06-25 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
TWI784538B (zh) 2008-08-14 2022-11-21 美商艾瑟勒朗法瑪公司 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
EA201791940A3 (ru) 2008-11-26 2018-04-30 Амген Инк. Варианты полипептидов рецептора iib активина и их использование
KR20180026795A (ko) 2009-06-12 2018-03-13 악셀레론 파마 인코포레이티드 절두된 ＡｃｔＲＩＩＢ-ＦＣ 융합 단백질
ES2658292T3 (es) 2009-11-17 2018-03-09 Acceleron Pharma, Inc. Proteínas ActRIIB y variantes y usos de las mismas con respecto a la inducción de la utrofina para el tratamiento de la distrofia muscular
CA2804501C (en) * 2010-07-06 2021-01-26 Novartis Ag Noro virus derived immunogenic compositions and methods
SG187867A1 (en) 2010-08-16 2013-03-28 Amgen Inc Antibodies that bind myostatin, compositions and methods
CN103298832A (zh) 2010-11-08 2013-09-11 阿塞勒隆制药公司 Actriia结合剂及其用途
EP2793925B1 (en) 2011-12-19 2019-03-20 Amgen Inc. Variant activin receptor polypeptides, alone or in combination with chemotherapy, and uses thereof
BR112014031028A2 (pt) 2012-06-11 2017-08-15 Amgen Inc Proteína de ligação ao antígeno isolado, ácido nucléico isolado, vetor de expressão, célula hospedeira, método para produzir uma proteína de ligação ao antígeno, composição, método para reduzir ou bloquear a atividade de miostatina, activin a ou gdf-11, método para aumentar a firmeza da massa muscular ou aumentar a proporção da firmeza da massa muscular para massa adiposo em um indivíduo necessitado do referido tratamento, método para tratar ou prevenir uma doença prejudicial do músculo em um indivíduo sofrendo do referido distúrbio e anticorpo receptor duplo antagonista
EP3964224A1 (en) 2012-11-02 2022-03-09 Celgene Corporation Activin-actrii antagonists and uses for use in treating renal disease
JP2016508504A (ja) 2013-02-01 2016-03-22 サンタ マリア バイオセラピューティクス インコーポレイテッド 対象に対する抗アクチビン−ａ化合物の投与
US20140220033A1 (en) * 2013-02-01 2014-08-07 Santa Maria Biotherapeutics, Inc. Administration of an Anti-Activin-A Compound to a Subject
TWI655207B (zh) * 2013-07-30 2019-04-01 再生元醫藥公司 抗活化素ａ之抗體及其用途
CN104693270B (zh) * 2013-12-10 2018-10-16 清华大学 一种用于融合蛋白的连接肽
EP3094751A4 (en) * 2014-01-14 2017-06-07 Santa Maria Biotherapeutics, Inc. Activin inhibitor response prediction and uses for treatment
JP2017519009A (ja) * 2014-06-13 2017-07-13 サンタ マリア バイオセラピューティクス インコーポレイテッド 製剤化された受容体ポリペプチドおよび関連する方法
BR122023023170A2 (pt) 2014-06-13 2024-02-20 Acceleron Pharma Inc. Uso de um antagonista de actrii no tratamento ou prevenção de úlcera cutânea associada com beta-talassemia
MA41052A (fr) * 2014-10-09 2017-08-15 Celgene Corp Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii
SI3280727T1 (sl) * 2015-04-06 2021-07-30 Acceleron Pharma Inc. Enoskupinske fuzijske beljakovine receptorjev tipa I in tipa II ter njihova uporaba
EP3889171A1 (en) 2015-04-06 2021-10-06 Acceleron Pharma Inc. Tgf-beta superfamily type i and type ii receptor heteromultimers and uses thereof
MA41919A (fr) 2015-04-06 2018-02-13 Acceleron Pharma Inc Hétéromultimères alk4:actriib et leurs utilisations
ES2856001T3 (es) 2015-04-22 2021-09-27 Biogen Ma Inc Nuevas proteínas híbridas de bloqueo del ligando actriib para tratar enfermedades de atrofia muscular
EP3426680A4 (en) 2016-03-10 2020-03-11 Acceleron Pharma Inc. TYPE 2 ACTIVIN RECEPTOR BINDING PROTEINS AND USES THEREOF
US10934532B2 (en) 2016-10-05 2021-03-02 Acceleron Pharma Inc. ALK4.ActRIIB heteromultimers
AU2017357944A1 (en) 2016-11-10 2019-06-20 Keros Therapeutics, Inc. Activin receptor type IIa variants and methods of use thereof
KR20200085832A (ko) 2017-11-09 2020-07-15 케로스 테라퓨틱스, 인크. 액티빈 수용체 유형 iia 변이체 및 그의 사용 방법
EP3737406A4 (en) 2018-01-12 2021-11-03 Keros Therapeutics, Inc. ACTIVIN RECEPTOR TYPE IIB VARIANTS AND THEIR METHODS OF USE
CN109320597B (zh) * 2018-10-26 2021-10-26 中国农业科学院特产研究所 狐亚科激活素a蛋白及其制备与应用
WO2023108137A1 (en) 2021-12-10 2023-06-15 Biogen Ma Inc. Modified actriib proteins and methods of use thereof

Family Cites Families (71)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US4263428A (en) 1978-03-24 1981-04-21 The Regents Of The University Of California Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same
IE52535B1 (en) 1981-02-16 1987-12-09 Ici Plc Continuous release pharmaceutical compositions
US4411993A (en) 1981-04-29 1983-10-25 Steven Gillis Hybridoma antibody which inhibits interleukin 2 activity
USRE32011E (en) 1981-12-14 1985-10-22 Scripps Clinic And Research Foundation Ultrapurification of factor VIII using monoclonal antibodies
EP0088046B1 (de) 1982-02-17 1987-12-09 Ciba-Geigy Ag Lipide in wässriger Phase
US4543439A (en) 1982-12-13 1985-09-24 Massachusetts Institute Of Technology Production and use of monoclonal antibodies to phosphotyrosine-containing proteins
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
HUT35524A (en) 1983-08-02 1985-07-29 Hoechst Ag Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance
EP0143949B1 (en) 1983-11-01 1988-10-12 TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION Pharmaceutical composition containing urokinase
US4902614A (en) 1984-12-03 1990-02-20 Teijin Limited Monoclonal antibody to human protein C
US5618920A (en) 1985-11-01 1997-04-08 Xoma Corporation Modular assembly of antibody genes, antibodies prepared thereby and use
US5750375A (en) 1988-01-22 1998-05-12 Zymogenetics, Inc. Methods of producing secreted receptor analogs and biologically active dimerized polypeptide fusions
US5567584A (en) 1988-01-22 1996-10-22 Zymogenetics, Inc. Methods of using biologically active dimerized polypeptide fusions to detect PDGF
JP2877509B2 (ja) 1989-05-19 1999-03-31 アムジエン・インコーポレーテツド メタロプロテイナーゼ阻害剤
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US6565841B1 (en) 1991-03-15 2003-05-20 Amgen, Inc. Pulmonary administration of granulocyte colony stimulating factor
US6162896A (en) 1991-05-10 2000-12-19 The Salk Institute For Biological Studies Recombinant vertebrate activin receptors
US5885794A (en) 1991-05-10 1999-03-23 The Salk Institute For Biological Studies Recombinant production of vertebrate activin receptor polypeptides and identification of receptor DNAs in the activin/TGF-β superfamily
US20050186593A1 (en) 1991-05-10 2005-08-25 The Salk Institute For Biological Studies Cloning and recombinant production of CRF receptor(s)
WO1993015722A1 (en) 1992-02-07 1993-08-19 Syntex (Usa) Inc. Controlled delivery of pharmaceuticals from preformed porous microparticles
US6153407A (en) 1992-07-28 2000-11-28 Beth Israel Deaconess Medical Center Erythropoietin DNA having modified 5' and 3' sequences and its use to prepare EPO therapeutics
GB9223377D0 (en) 1992-11-04 1992-12-23 Medarex Inc Humanized antibodies to fc receptors for immunoglobulin on human mononuclear phagocytes
US5837821A (en) 1992-11-04 1998-11-17 City Of Hope Antibody construct
CA2157577C (en) 1993-03-19 2009-11-17 Se-Jin Lee Growth differentiation factor-8
US5994618A (en) 1997-02-05 1999-11-30 Johns Hopkins University School Of Medicine Growth differentiation factor-8 transgenic mice
US6465239B1 (en) 1993-03-19 2002-10-15 The John Hopkins University School Of Medicine Growth differentiation factor-8 nucleic acid and polypeptides from aquatic species and non-human transgenic aquatic species
US6607884B1 (en) 1993-03-19 2003-08-19 The Johns Hopkins University School Of Medicine Methods of detecting growth differentiation factor-8
AU702163B2 (en) 1994-04-29 1999-02-18 Creative Biomolecules, Inc. Morphogenic protein-specific cell surface receptors and uses therefor
US6891082B2 (en) 1997-08-01 2005-05-10 The Johns Hopkins University School Of Medicine Transgenic non-human animals expressing a truncated activintype II receptor
US6656475B1 (en) 1997-08-01 2003-12-02 The Johns Hopkins University School Of Medicine Growth differentiation factor receptors, agonists and antagonists thereof, and methods of using same
US6472179B2 (en) 1998-09-25 2002-10-29 Regeneron Pharmaceuticals, Inc. Receptor based antagonists and methods of making and using
US6660843B1 (en) 1998-10-23 2003-12-09 Amgen Inc. Modified peptides as therapeutic agents
IL143034A0 (en) 1998-11-13 2002-04-21 Immunex Corp Human tslp dna and polypeptides
MXPA01007366A (es) 1999-01-21 2002-06-04 Metamorphix Inc Inhibidores de factores de crecimiento y diferenciacion y usos de los mismos.
JP4487376B2 (ja) 2000-03-31 2010-06-23 味の素株式会社 腎疾患治療剤
US6812339B1 (en) * 2000-09-08 2004-11-02 Applera Corporation Polymorphisms in known genes associated with human disease, methods of detection and uses thereof
GB0209896D0 (en) 2002-04-30 2002-06-05 Molmed Spa Conjugate
US20040223966A1 (en) 2002-10-25 2004-11-11 Wolfman Neil M. ActRIIB fusion polypeptides and uses therefor
US7511012B2 (en) 2002-12-20 2009-03-31 Amgen Inc. Myostatin binding agents
UA85055C2 (ru) 2003-06-02 2008-12-25 Уайт Применение ингибиторов миостатика (gdf8) в сочетании с кортикостероидами для лечения нервно-мышечных заболеваний
CN103212084B (zh) 2003-11-13 2018-07-13 韩美科学株式会社 含有免疫球蛋白fc区作为载体的药物组合物
US8110665B2 (en) 2003-11-13 2012-02-07 Hanmi Holdings Co., Ltd. Pharmaceutical composition comprising an immunoglobulin FC region as a carrier
EP2314617B1 (en) 2004-07-23 2015-06-24 Acceleron Pharma Inc. ActRII receptor polypeptides
US20060034831A1 (en) 2004-08-12 2006-02-16 Wyeth Combination therapy for diabetes, obesity and cardiovascular diseases using GDF-8 inhibitors
CA2580796C (en) 2004-09-24 2013-03-26 Amgen Inc. Modified fc molecules having peptides inserted in internal loop regions
KR100754667B1 (ko) 2005-04-08 2007-09-03 한미약품 주식회사 비펩타이드성 중합체로 개질된 면역글로불린 Ｆｃ 단편 및이를 포함하는 약제학적 조성물
UA94060C2 (ru) 2005-09-07 2011-04-11 Эмджен Фримонт Инк. Моноклональное антитело, которое специфически связывает alk-1
US8067562B2 (en) * 2005-11-01 2011-11-29 Amgen Inc. Isolated nucleic acid molecule comprising the amino acid sequence of SEQ ID NO:1
WO2007105377A2 (en) * 2006-03-02 2007-09-20 Ishihara Sangyo Kaisha, Ltd. Solid herbicidal composition
CL2007002567A1 (es) 2006-09-08 2008-02-01 Amgen Inc Proteinas aisladas de enlace a activina a humana.
BRPI0720476B1 (pt) 2006-12-18 2022-05-31 Acceleron Pharma Inc Uso de um polipeptídeo de actrii para tratar anemia em um paciente humano
TW201940502A (zh) 2007-02-02 2019-10-16 美商艾瑟勒朗法瑪公司 衍生自ＡｃｔＲＩＩＢ的變體與其用途
TW201718635A (zh) 2007-03-06 2017-06-01 安美基公司 變異之活動素受體多肽及其用途
US8501678B2 (en) 2007-03-06 2013-08-06 Atara Biotherapeutics, Inc. Variant activin receptor polypeptides and uses thereof
EP2578684B1 (en) * 2007-03-19 2016-02-24 National Research Council Of Canada Antagonists of ligands and uses thereof
CN103877564A (zh) 2007-09-18 2014-06-25 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
ES2554812T3 (es) 2007-11-09 2015-12-23 Genentech, Inc. Composiciones de antagonistas de quinasa 1 de tipo receptor de activina y métodos de uso
US20100015144A1 (en) 2008-06-26 2010-01-21 Acceleron Pharma Inc. Methods for dosing an activin-actriia antagonist and monitoring of treated patients
TWI784538B (zh) 2008-08-14 2022-11-21 美商艾瑟勒朗法瑪公司 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
EA201791940A3 (ru) 2008-11-26 2018-04-30 Амген Инк. Варианты полипептидов рецептора iib активина и их использование
WO2010083034A1 (en) 2009-01-13 2010-07-22 Acceleron Pharma Inc. Methods for increasing adiponectin
NO2424895T3 (es) 2009-04-27 2018-02-03
CN102482339B (zh) 2009-06-08 2015-06-17 阿塞勒隆制药公司 用于增加产热脂肪细胞的方法
US20120295814A1 (en) 2010-01-08 2012-11-22 The Brigham And Women's Hospital, Inc. CA-125 Immune Complexes as Biomarkers of Ovarian Cancer
CA2794513A1 (en) 2010-03-31 2011-10-06 Aeterna Zentaris Gmbh Perifosine and capecitabine as a combined treatment for cancer
CN103298832A (zh) 2010-11-08 2013-09-11 阿塞勒隆制药公司 Actriia结合剂及其用途
WO2013106715A1 (en) 2012-01-13 2013-07-18 Allergan, Inc. Crosslinked hyaluronic acid-collagen gels for improving tissue graft viability and soft tissue augmentation
WO2013180295A1 (ja) 2012-06-01 2013-12-05 日本電信電話株式会社 パケット転送処理方法およびパケット転送処理装置
US9300829B2 (en) 2014-04-04 2016-03-29 Canon Kabushiki Kaisha Image reading apparatus and correction method thereof

Also Published As

Publication number Publication date
US20200283504A9 (en) 2020-09-10
SMT201600417B (it) 2017-01-10
JP5969557B2 (ja) 2016-08-17
AU2009320364A1 (en) 2010-06-03
CA2997971A1 (en) 2010-06-03
KR20170036114A (ko) 2017-03-31
ME02652B (me) 2017-06-20
EA201791940A2 (ru) 2018-01-31
JP2016199577A (ja) 2016-12-01
JP2015037403A (ja) 2015-02-26
US20130225484A1 (en) 2013-08-29
EP3101029A1 (en) 2016-12-07
MY159483A (en) 2017-01-13
US10308704B2 (en) 2019-06-04
MA32936B1 (fr) 2012-01-02
TWI486166B (zh) 2015-06-01
CN102245634A (zh) 2011-11-16
IL212773A0 (en) 2011-07-31
IL212773A (en) 2016-10-31
NZ627111A (en) 2015-10-30
HRP20161450T1 (hr) 2017-01-13
RS55369B1 (sr) 2017-03-31
WO2010062383A2 (en) 2010-06-03
US8410043B2 (en) 2013-04-02
PL2370463T3 (pl) 2017-03-31
CR20110364A (es) 2011-09-07
KR20110106322A (ko) 2011-09-28
EA201791940A3 (ru) 2018-04-30
CN104371024A (zh) 2015-02-25
DK2370463T3 (en) 2016-11-28
SG171813A1 (en) 2011-07-28
CA2743850A1 (en) 2010-06-03
US20190389932A1 (en) 2019-12-26
NZ604818A (en) 2014-07-25
CA2743850C (en) 2018-04-17
US20230295267A1 (en) 2023-09-21
SG10201703067QA (en) 2017-05-30
JP2012509687A (ja) 2012-04-26
HK1162545A1 (zh) 2012-08-31
BRPI0920962A2 (pt) 2016-07-12
EA201100832A1 (ru) 2011-12-30
KR20170105124A (ko) 2017-09-18
AU2009320364B2 (en) 2013-05-16
CN102245634B (zh) 2014-10-08
JP5611222B2 (ja) 2014-10-22
US11685770B2 (en) 2023-06-27
UA107921C2 (en) 2015-03-10
CR20160443A (es) 2016-11-08
IL248128A0 (en) 2016-11-30
KR101778134B1 (ko) 2017-09-13
KR101720143B1 (ko) 2017-03-27
EP2370463A2 (en) 2011-10-05
AR074397A1 (es) 2011-01-12
US20100168020A1 (en) 2010-07-01
CY1118754T1 (el) 2017-07-12
HUE032090T2 (en) 2017-09-28
CO6382163A2 (es) 2012-02-15
TW201021826A (en) 2010-06-16
PE20120206A1 (es) 2012-03-09
EP2370463B1 (en) 2016-08-31
PE20150680A1 (es) 2015-05-16
US9273114B2 (en) 2016-03-01
WO2010062383A3 (en) 2010-08-19
TN2011000238A1 (en) 2012-12-17
EP3101029B1 (en) 2019-04-03
SI2370463T1 (sl) 2017-01-31
PT2370463T (pt) 2016-11-04
LT2370463T (lt) 2016-12-12
US20160137718A1 (en) 2016-05-19
MX2011005505A (es) 2011-09-01
CL2011001239A1 (es) 2011-09-16
US20170183391A9 (en) 2017-06-29
ZA201104648B (en) 2012-03-28

Similar Documents

Publication Publication Date Title
ES2600491T3 (es) Una variante estabilizada de receptor IIB de activina
HRP20200036T1 (hr) Postupci liječenja tauopatije
ES2962260T3 (es) Proteínas de fusión SIRPa alfa-anticuerpo
ES2902901T3 (es) Anticuerpos de unión a APRIL modificados
RU2020124172A (ru) Слитые серпиновые полипептиды и способы их применения
PE20221909A1 (es) Moleculas de union a antigeno que comprenden un trimero de ligando de la familia de tnf
CA2972990A1 (en) Tumor necrosis factor (tnf) superfamily receptor binding molecules and uses thereof
HRP20191920T1 (hr) Kimerni polipeptidi faktora viii i njihova uporaba
JP2017527272A5 (es)
HRP20150664T1 (hr) Antikancerogeni fuzijski protein
HRP20200085T1 (hr) Topljivi cd33 za liječenje mijelodisplastičnih sindroma (mds)
RU2017144098A (ru) Гетеродимеризованный полипептид
RU2012151205A (ru) Модифицированные связывающие белки, ингибирующие взаимодействие vegf-a рецептора
ES2676023T3 (es) Polipéptidos de IL-22 y proteínas de fusión de IL-22 Fc y métodos de uso
JP2014530253A5 (es)
BRPI0812795C1 (pt) domínio variável único de imunoglobulina, antagonista tipo 1 do receptor tnfalfa, uso de um domínio ou antagonista de tnfr1, ácido nucleico recombinante, vetor, célula hospedeira, e, composição farmacêutica
NO20055852L (no) Nye peptider som binder til erytropoietinreseptoren
JP2014040483A5 (es)
NO20043891L (no) Anti-A-beta-antistoffer og deres anvendelse
HRP20110334T1 (hr) PROTUTIJELA SPECIFIČNA ZA TGF-ß1
HRP20201651T1 (hr) Uporaba cd24 za snižavanje razina lipoproteina niske gustoće kolesterola
RU2020115037A (ru) МУТАНТНЫЕ ВАРИАНТЫ Fc IgG1, ЛИШЕННЫЕ ЭФФЕКТОРНЫХ ФУНКЦИЙ
JP2016531546A5 (es)
WO2017060322A3 (en) Ptefb-inhibitor-adc
CA3173919A1 (en) Use of a multimeric anti-dr5 binding molecule in combination with a cancer therapy for treating cancer