ANTI-CD3 SINGLE-CHAIN ANTIBODIES HAVING HUMAN C mu 3 AND C mu 4 DOMAINS

• Main Authors: LITTLE, MELVYN, SANDLIE, INGER, CHOI, INGRID
• Format: Patent
• Language: English; French; German
• Published: 19.07.2001
• Edition: 7
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

Disclosed is a single-chain antibody which is characterised in that said antibody (a) contains a variable domain (scFv) that specifically binds to human CD3 and (b) that the constant domains thereof stem from a human IgM-molecule and comprise the C mu 3 domain and C mu 4 domain, however, do not comprise the C mu 1 domain and C mu 2 domain. In a preferred embodiment, the inventive antibody contains a human IgG3-hinge region between the variable and the constant domain. The invention also relates to DNA sequences coding for said antibody, expression vectors containing said DNA sequences and medicaments containing the aforementioned compounds. Said medicaments are preferably used for the prevention of acute rejection reactions after organ transplantations. Disclosed is a single-chain antibody which is characterised in that said antibody (a) contains a variable domain (scFv) that specifically binds to human CD3 and (b) that the constant domains thereof stem from a human IgM-molecule and comprise the C mu 3 domain and C mu 4 domain, however, do not comprise the C mu 1 domain and C mu 2 domain. In a preferred embodiment, the inventive antibody contains a human IgG3-hinge region between the variable and the constant domain. The invention also relates to DNA sequences coding for said antibody, expression vectors containing said DNA sequences and medicaments containing the aforementioned compounds. Said medicaments are preferably used for the prevention of acute rejection reactions after organ transplantations. Beschrieben wird ein Einzelketten-Antikörper, der dadurch gekennzeichnet ist, dass er (a) eine an humanes CD3 spezifisch bindende variable Domäne (scFv) enthält, und (b) seine konstanten Domänen von einem humanen IgM-Molekül stammen und die C mu 3-Domäne und C mu 4-Domäne, jedoch nicht die C mu 1-Domäne und C mu 2-Domäne umfassen. In einer bevorzugten Ausführungsform enthält der erfindungsgemässe Antikörper eine humane IgG3-Gelenkregion zwischen der variablen und konstanten Domäne. Beschrieben werden ausserdem diesen Antikörper codierende DNA-Sequenzen und diese DNA-Sequenzen enthaltende Expressionsvektoren und schliesslich die vorstehenden Verbindungen enthaltende Arzeimittel, vorzugsweise zur Prävention akuter Abstossungsreaktionen nach Organtransplantation. L'invention concerne un anticorps monocaténaire qui se caractérise en ce que (a) il présente un domaine (scFv) variable se liant spécifiquement au CD3 humain, et (b) ses domaines constants proviennent d'une molécule IgM humaine et les domaines C mu 3 et C mu 4 ne comprennent toutefois pas les domaines C mu 1 et C mu 2. Dans un mode de réalisation préféré, l'anticorps selon l'invention contient une région d'articulation IgG3 humaine entre le domaine variable et les domaines constants. L'invention concerne en outre des séquences d'ADN codant pour cet anticorps et des vecteurs d'expression contenant ces séquences d'ADN. Elle concerne enfin des médicaments contenant les composés susmentionnés, utilisés de préférence pour la prévention de réactions de rejet aiguës après des transplantations d'organes.