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1. NZ739249 - INSERTABLE VARIABLE FRAGMENTS OF ANTIBODIES AND MODIFIED A1-A2 DOMAINS OF NKG2D LIGANDS, AND NON-NATURAL NKG2D LIGANDS THAT BIND NON-NATURAL NKG2D RECEPTORS

Office
New Zealand
Application Number 739249
Application Date 18.01.2018
Publication Number 739249
Publication Date 26.01.2018
Publication Kind A1
IPC
C07K 16/28
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
C07K 14/74
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
74Major histocompatibility complex (MHC)
C07K 14/47
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435from animals; from humans
46from vertebrates
47from mammals
C12N 5/0783
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
5Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
07Animal cells or tissues
071Vertebrate cells or tissues, e.g. human cells or tissues
078Cells from blood or from the immune system
0783T cells; NK cells; Progenitors of T or NK cells
C07K 16/32
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
32against translation products from oncogenes
Applicants XYPHOS BIOSCIENCES INC.
Inventors LANDGRAF, Kyle
STEIGER, Daniel, P.
BARON, Tarah
GEBHART, Dana
Agents Spruson & Ferguson Pty Ltd
Priority Data 62/200,949 04.08.2015 US
Title
(EN) INSERTABLE VARIABLE FRAGMENTS OF ANTIBODIES AND MODIFIED A1-A2 DOMAINS OF NKG2D LIGANDS, AND NON-NATURAL NKG2D LIGANDS THAT BIND NON-NATURAL NKG2D RECEPTORS
Abstract
(EN) This present invention relates to a non-natural, modified α1-α2 domain of a natural NKG2D ligand molecule comprising an amino acid sequence having at least 90% identity to a natural α1-α2 domain from human MICA, MICB, ULBP2 or ULBP3, said modified α1-α2 domain containing amino acid substitutions: at three or more of positions 71, 72, 74, 155, 156, 157, 158 and 159 of the natural α1-α2 domain of MICA or MICB; at two or more of positions 154, 155, 156, 157, 158 and 159 of the natural α1-α2 domain of ULBP2; or at two or more of positions 155, 156, 157, 158 and 159 of the natural α1-α2 domain of ULBP3, wherein said substitutions increase the binding affinity of the non-natural, modified α1-α2 domain to a non-natural NKG2D receptor ectodomain, and wherein the non-natural NKG2D receptor ectodomain has a tyrosine to alanine substitution at position 152. The invention also relates to the use of such non-natural modified ligands for the manufacture of a medicament for activation of cells in a mammal in need thereof, wherein said cells have a non-natural NKG2D receptor ectodomain attached thereto.