ES2638278T3 - Antagonistas de wnt y métodos de tratamiento - Google Patents

Antagonistas de wnt y métodos de tratamiento Download PDF

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Publication number
ES2638278T3
ES2638278T3 ES11733316.1T ES11733316T ES2638278T3 ES 2638278 T3 ES2638278 T3 ES 2638278T3 ES 11733316 T ES11733316 T ES 11733316T ES 2638278 T3 ES2638278 T3 ES 2638278T3
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seq
amino acids
polypeptide
sequence
amino
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Sanjeev H. Satyal
Satyajit Sujit Kumar Mitra
Austin L. Gurney
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Mereo Biopharma 5 Inc
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Oncomed Pharmaceuticals Inc
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    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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    • 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
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    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K39/00—Medicinal preparations containing antigens or antibodies
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    • 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
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    • C07—ORGANIC CHEMISTRY
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    • 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
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    • G01—MEASURING; TESTING
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    • C07K2319/00—Fusion polypeptide
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Abstract

1. Un polipéptido que comprende: (i) un agente de unión a Wnt que comprende la secuencia de aminoácidos de SEQ ID NO: 53; y (ii) una secuencia señal seleccionada del grupo que consiste en: SEQ ID NO:72, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:73 y SEQ ID NO:74.

Description

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primer polipéptido consta de aminoácidos 31-158 de la SEQ ID NO:30. En algunas realizaciones, el segundo polipéptido consta de aminoácidos 1-232 de la SEQ ID NO:43. En algunas realizaciones, el segundo polipéptido consta de aminoácidos 3-232 de la SEQ ID NP:43. En algunas realizaciones, el segundo polipéptido consta de aminoácidos 6-232 de la SEQ ID NO:43. En algunas realizaciones, el primer polipéptido es la SEQ ID NO:39 y el
5 segundo polipéptido es la SEQ ID NO:43. En algunas realizaciones, el primer polipéptido es la SEQ ID NO:39 y el segundo polipéptido es la SEQ ID NO:42. En algunas realizaciones, el primer polipéptido es la SEQ ID NO:39 y el segundo polipéptido es la SEQ ID NO:18.
En algunas realizaciones, el agente de unión a Wnt es un polipéptido que comprende un primer polipéptido y un 10 segundo polipéptido, en donde los polipéptidos se seleccionan de la Tabla 2.
Tabla 2
Primer Polipéptido
Segundo Polipéptido
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 25-158 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 26-158 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 27-158 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 28-158 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
15
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 25-161 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 26-161 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 27-161 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 28-161 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 25-164 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
16
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 26-164 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 27-164 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 1-232 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 1-231 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 2-232 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 2-231 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 3-232 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 3-231 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 4-232 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 4-231 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 5-232 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 5-231 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 6-232 de SEQ ID NO:43
Aminoácidos 28-164 de SEQ ID NO:30
Aminoácidos 6-231 de SEQ ID NO:43
En algunas realizaciones, el agente de unión a Wnt comprende una secuencia de aminoácidos seleccionada del grupo que consta de: SEQ ID NO:1, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:65 y SEQ ID NO:66.
5 En determinadas realizaciones, el agente de unión a Wnt comprende la secuencia SEQ ID NO:1. En determinadas realizaciones alternativas, el agente comprende la secuencia de la SEQ ID NO:1., que comprende una o más (por ejemplo, una, dos, tres, cuatro, cinco, seis, siete, ocho, nueve, diez, etc.) sustituciones conservadoras. En determinadas realizaciones, el agente comprende una secuencia que tiene al menos alrededor de 90 %, alrededor
10 de 95 % o alrededor de 98 % de identidad de secuencia con la SEQ ID NO:1. En determinadas realizaciones, las variantes de la SEQ ID NO:1 mantienen la capacidad de unirse a una o más Wnt humanas.
En determinadas realizaciones, el agente de unión a Wnt comprende la secuencia de la SEQ ID NO:46. En algunas realizaciones, el agente de unión a Wnt es la SEQ ID NO:46. En determinadas realizaciones alternativas, el agente
15 comprende la secuencia de la SEQ ID NO:46, que comprende una o más (por ejemplo, una, dos, tres, cuatro, cinco, seis, siete, ocho, nueve, diez, etc.) sustituciones conservadoras. En determinadas realizaciones, el agente comprende una secuencia que tiene al menos alrededor de 90 %, alrededor de 95 % o alrededor de 98 % de identidad de secuencia con la SEQ ID NO:46. En determinadas realizaciones, las variantes de la SEQ ID NO:46 mantienen la capacidad de unirse a una o más Wnt humanas.
20 En determinadas realizaciones, el agente de unión a Wnt comprende la secuencia de la SEQ ID NO:48. En algunas realizaciones, el agente de unión a Wnt es la SEQ ID NO:48. En determinadas realizaciones alternativas, el agente comprende la secuencia de la SEQ ID NO:48, que comprende una o más (por ejemplo, una, dos, tres, cuatro, cinco, seis, siete, ocho, nueve, diez, etc.) sustituciones conservadoras. En determinadas realizaciones, el agente
25 comprende una secuencia que tiene al menos alrededor de 90 %, alrededor de 95 % o alrededor de 98 % de identidad de secuencia con la SEQ ID NO:48. En determinadas realizaciones, las variantes de la SEQ ID NO:48 mantienen la capacidad de unirse a una o más Wnt humanas.
En determinadas realizaciones, el agente de unión a Wnt comprende la secuencia de la SEQ ID NO:50. En algunas
30 realizaciones, el agente de unión a Wnt es la SEQ ID NO:50. En determinadas realizaciones alternativas, el agente comprende la secuencia de la SEQ ID NO:50, que comprende una o más (por ejemplo, una, dos, tres, cuatro, cinco, seis, siete, ocho, nueve, diez, etc.) sustituciones conservadoras. En determinadas realizaciones, el agente comprende una secuencia que tiene al menos alrededor de 90 %, alrededor de 95 % o alrededor de 98 % de
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AU2011205405B2 (en) 2015-07-09
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AU2015238849A1 (en) 2015-10-29
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RS56242B1 (sr) 2017-11-30
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US20160082079A1 (en) 2016-03-24
TWI535445B (zh) 2016-06-01
WO2011088123A3 (en) 2011-10-13
US20170218041A1 (en) 2017-08-03
RU2593947C2 (ru) 2016-08-10
KR20120125493A (ko) 2012-11-15
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HUE034466T2 (en) 2018-02-28
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