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1. WO2016023001 - MULTISPECIFIC HIGH AFFINITY PD-1 AGENTS AND METHODS OF USE

Publication Number WO/2016/023001
Publication Date 11.02.2016
International Application No. PCT/US2015/044363
International Filing Date 07.08.2015
IPC
C07K 19/00 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
19Hybrid peptides
A61K 38/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
C12N 15/00 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
CPC
A61K 38/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
C07K 14/70503
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435from animals; from humans
705Receptors; Cell surface antigens; Cell surface determinants
70503Immunoglobulin superfamily
C07K 14/70596
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435from animals; from humans
705Receptors; Cell surface antigens; Cell surface determinants
70596Molecules with a "CD"-designation not provided for elsewhere
C07K 2319/00
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2319Fusion polypeptide
Applicants
  • THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY [US]/[US]
Inventors
  • RING, Aaron Michael
  • KRUSE, Andrew
  • MANGLIK, Aashish
  • WEISSMAN, Irving L.
Agents
  • GURLEY, Kyle A.
Priority Data
62/035,31608.08.2014US
62/150,79921.04.2015US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) MULTISPECIFIC HIGH AFFINITY PD-1 AGENTS AND METHODS OF USE
(FR) AGENTS PD-1 À HAUTE AFFINITÉ MULTISPÉCIFIQUES ET PROCÉDÉS D'UTILISATION
Abstract
(EN)
Multispecific high affinity PD-1 mimic polypeptides are provided, which comprise: (a) a first region comprising an amino acid sequence of a high affinity PD-1 mimic polypeptide that is a variant of a wild-type PD1 sequence; and (b) a second region comprising an amino acid sequence of a high affinity SIRP-alpha variant that specifically binds to CD47, where the high affinity SIRP-alpha variant is CV1. Compositions and methods are provided for modulating the activity of immune cells in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a subject multispecific high affinity PD-1 mimic polypeptide, which blocks the physiological binding interaction between PD-1 and its ligand PD-L1 and/or PD-L2.
(FR)
L'invention concerne des polypeptides imitant PD-1 à haute affinité multispécifiques, qui comprennent : (a) une première région comprenant une séquence d'acides aminés d'un polypeptide imitant PD-1 à haute affinité qui est un variant d'une séquence de PD-1 sauvage ; et (b) une seconde région comprenant une séquence d'acides aminés d'un variant de SIRP-alpha à haute affinité qui se lie spécifiquement à CD47, le variant de SIRP-alpha de haute affinité étant CV1. L'invention concerne des compositions et des procédés permettant de moduler l'activité de cellules immunitaires chez un mammifère par administration d'une dose thérapeutique d'une composition pharmaceutique comprenant un polypeptide imitant PD-1 à haute affinité multispécifique de l'invention, qui bloque l'interaction de liaison physiologique entre PD-1 et son ligand PD-L1 et/ou PD-L2.
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