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1. WO2007030451 - ANTIBODIES AS T CELL RECEPTOR MIMICS, METHODS OF PRODUCTION AND USES THEREOF

Publication Number WO/2007/030451
Publication Date 15.03.2007
International Application No. PCT/US2006/034547
International Filing Date 07.09.2006
IPC
A61K 39/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
C07K 5/10 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
5Peptides having up to four amino acids in a fully defined sequence; Derivatives thereof
04containing only normal peptide links
10Tetrapeptides
C07K 16/00 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
G01N 33/574 2006.01
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48Biological material, e.g. blood, urine; Haemocytometers
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
53Immunoassay; Biospecific binding assay; Materials therefor
574for cancer
A61B 5/055 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
BDIAGNOSIS; SURGERY; IDENTIFICATION
5Measuring for diagnostic purposes; Identification of persons
05Measuring for diagnosis by means of electric currents or magnetic fields
055involving electronic or nuclear magnetic resonance, e.g. magnetic resonance imaging
C07H 21/02 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
21Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
02with ribosyl as saccharide radical
CPC
C07K 14/70539
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
70539MHC-molecules, e.g. HLA-molecules
C07K 16/00
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
C07K 16/26
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
26against hormones ; ; against hormone releasing or inhibiting factors
C07K 16/2833
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
2803against the immunoglobulin superfamily
2833against MHC-molecules, e.g. HLA-molecules
C07K 16/30
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
30from tumour cells
C07K 16/32
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
32against translation products of oncogenes
Applicants
  • RECEPTOR LOGIC, LTD. [US]/[US] (AllExceptUS)
  • WEIDANZ, Jon, A. [US]/[US] (UsOnly)
  • WITTMAN, Vaughan [US]/[US] (UsOnly)
Inventors
  • WEIDANZ, Jon, A.
  • WITTMAN, Vaughan
Agents
  • HESTER, Kathryn, L.
Priority Data
60/714,62107.09.2005US
60/751,54219.12.2005US
60/752,73720.12.2005US
60/838,27617.08.2006US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) ANTIBODIES AS T CELL RECEPTOR MIMICS, METHODS OF PRODUCTION AND USES THEREOF
(FR) ANTICORPS UTILISES COMME MIMETIQUES DE RECEPTEURS DE LYMPHOCYTES T, LEURS METHODES DE PRODUCTION ET LEURS APPLICATIONS
Abstract
(EN)
The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies will mimic the specificity of a T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherein the peptide of interest is capable of being presented by an MHC molecule. Then, an immunogen comprising at least one peptide/MHC complex is formed, wherein the peptide of the peptide/MHC complex is the peptide of interest. An effective amount of the immunogen is then administered to a host for eliciting an immune response, and serum collected from the host is assayed to determine if desired antibodies that recognize a three-dimensional presentation of the peptide in the binding groove of the MHC molecule are being produced. The desired antibodies can differentiate the peptide/MHC complex from the MHC molecule alone, the peptide alone, and a complex of MHC and irrelevant peptide. Finally, the desired antibodies are isolated.
(FR)
La présente invention concerne une méthode permettant de produire des anticorps qui reconnaissent des peptides associés à un état oncogène ou pathologique, les peptides se présentant dans le contexte de molécules HLA. Ces anticorps produisent un effet semblable à la spécificité d'un récepteur des lymphocytes T (TCR), mais possèdent une affinité de liaison supérieure, ce qui signifie que les molécules peuvent être utilisées comme réactifs dans des applications thérapeutiques et diagnostiques et dans la recherche. La méthode de la présente invention destinée à la production d'un mimétique de récepteur de lymphocytes T consiste à identifier un peptide d'intérêt capable d'être présenté par une molécule CMH, à former un immunogène comprenant au moins un complexe peptide/CMH dont le peptide est le peptide d'intérêt, puis à administrer une dose utile de l'immunogène à un hôte pour déclencher une réaction immunitaire et à analyser le sérum prélevé chez l'hôte pour déterminer si les anticorps désirés qui reconnaissent une présentation tridimensionnelle du peptide dans le sillon de fixation de la molécule CMH sont produits. Ces anticorps désirés peuvent différencier le complexe peptide/CMH par rapport à une molécule CMH seule, le peptide seul, et un complexe formé par un CMH et un peptide sans intérêt. La méthode de l'invention consiste enfin à isoler les anticorps désirés.
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