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1. WO1993004700 - V$g(a)12.1 T-CELL RECEPTOR-SPECIFIC REAGENTS FOR DIAGNOSING AND TREATING RHEUMATOID ARTHRITIS

Publication Number WO/1993/004700
Publication Date 18.03.1993
International Application No. PCT/US1992/007357
International Filing Date 27.08.1992
Chapter 2 Demand Filed 22.03.1993
IPC
A61K 38/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
C07K 14/725 2006.01
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
725T-cell receptors
C07K 16/02 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
02from eggs
C07K 16/28 2006.01
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
G01N 33/50 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
G01N 33/564 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
564for pre-existing immune complex or autoimmune disease
CPC
A61K 38/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
C07K 14/7051
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
7051T-cell receptor (TcR)-CD3 complex
C07K 16/02
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
02from eggs
C07K 16/2809
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
2809against the T-cell receptor (TcR)-CD3 complex
G01N 2800/102
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
2800Detection or diagnosis of diseases
10Musculoskeletal or connective tissue disorders
101Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
102Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
G01N 2800/24
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
2800Detection or diagnosis of diseases
24Immunology or allergic disorders
Applicants
  • THE DANA-FARBER CANCER INSTITUTE [US]/[US]
  • BRIGHAM AND WOMEN'S HOSPITAL [US]/[US]
Inventors
  • BRENNER, Michael, B.
  • DER SIMONIAN, Harout
Agents
  • HART, Julia, D.
Priority Data
07/750,98628.08.1991US
07/936,26726.08.1992US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) V$g(a)12.1 T-CELL RECEPTOR-SPECIFIC REAGENTS FOR DIAGNOSING AND TREATING RHEUMATOID ARTHRITIS
(FR) REACTIFS SPECIFIQUES AU RECEPTEUR DE LYMPHOCYTES-T, V$g(a)12.1, UTILISES POUR LE DIAGNOSTIC ET LE TRAITEMENT DE LA POLYARTHRITE RHUMATOIDE
Abstract
(EN)
Provided are monoclonal antibodies, fragments, and derivatives thereof reactive with an epitope of the T cell receptor alpha chain variable region, V$g(a)12.1, on human T lymphocytes. The monoclonal antibodies are reactive with approximately 2 % of CD4+ T lymphocytes and with approximately 5 % of CD8+ T lymphocytes in peripheral blood cells in normal individuals and define a subset of individuals afflicted with an autoimmune disease, especially rheumatoid arthritis, that exhibit increased expression of the V$g(a)12.1 gene on CD8+ peripheral blood T lymphocytes when compared to normal individuals. Also provided are methods for diagnosing, treating, and monitoring the progression of rheumatoid arthritis in a subject using V$g(a)12.1-specific reagents, especially the monoclonal antibodies, fragments, and derivatives of the invention, that bind to a cellular component of T cells and detect V$g(a)12.1 gene usage. Higher levels of assurance in the diagnosis of RA can be made by establishing that the expansion of V$g(a)12.1 gene usage is clonal or oligoclonal and that the V$g(a)12.1 expansion correlates with the occurrence ofthe MHC allele, HLA-DQw2.
(FR)
On décrit des anti-corps monoclonaux, ainsi que des fragments et des dérivés de ces anticorps, qui réagissent avec une épitope de la région variable de chaîne alpha du récepteur de lymphocyte-T, V$g(a)12.1, sur des lymphocytes T humains. Ces anticorps monoclonaux réagissent avec 2 % environ des lymphocytes-T CD4+, et avec 5 % environ des lymphocytes-T CD8+ dans des cellules de sang périphériques chez des individus normaux, et définissent un sous-ensemble d'individus souffrant d'une maladie autoimmune, en particulier la polyarthrite rhumatoïde, et qui présentent une expression accrue du gêne V$g(a)12.1 sur des lymphocytes-T CD8+ de sang périphérique par rapport aux individus normaux. On décrit également des procédés servant à diagnostiquer, traiter et surveiller la progression de la polyarthrite rhumatoÏde chez un patient, au moyen de réactifs spécifiques au V$g(a)12.1, en particulier les anticorps monoclonaux, les fragments et les dérivés de cette invention, qui se lient à un constituant cellulaire des lymphocytes-T et détectent l'utilisation du gène V$g(A)12.1. L'on parvient à diagnostiquer la polyarthrite rhumatoïde avec un niveau de certitude supérieur en établissant le fait que l'expansion de l'utilisation du gène v$g(a)12.1 est clonale ou oligoclonale et que cette expansion est corrélée à l'apparition de l'allèle du complexe d'histocompatibilité majeure (MHC), HLA-DQw2.
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