Pharmacia & Upjohn Ab

Active Biotech Ab

Pharmacia Ab

Active Biotech Ag

Mikael Dohlsten

Terje Kalland

Lars B Abrahmsen

Gunnar Hedlund

Per Antonsson

Per Bjork

Johan Hansson

Peter A Lando

Göran Forsberg

Lars Abrahms&eacute;n

Per Axel Bj&ouml;rk

Eva Akerblom

Morten Soegaard

Peter Lando

G&ouml;ran Forsberg

Eva &angst;kerblom

A method for the treatment of a disease in a mammal by administering a therapeutically effective amount of a conjugate comprising a biospecific affinity counterpart and a peptide, wherein the peptide contains an amino acid sequence that is derived from staphylococcal enterotoxin A, binds to a V&#x3b2; of a T cell receptor, and has a D227A mutation so that the peptide has a modified ability to bind to MHC class II antigens.

Conjugate between a modified superantigen and a target-seeking compound and the use of the conjugate

A conjugate between a target-seeking moiety and a modified superantigen, characterized in that the superantigen is a wild-type superantigen (SA I) in which an amino acid residue in a superantigen region (region I) determining binding to TCR, preferably TCRV&#x3b2;, and T cell activation have been replaced by another amino acid residue while retaining the ability to activate a subset of T cells. In preferred embodiment the modified superantigen is a chimer between at least two wild-type superantigens (SA I, SA II etc) characterized in that one or more amino acid residues in a region determining binding to TCR and T cell activation have been interchanged between various wild-type superantigens. A therapeutic method making use of modified/chimeric superantigens as defined in the preceding paragraphs. An antibody preparation in which the cysteine residues that provide for interchain disulfide bonds have been mutated so as to forbid interchain disulfide bridges, preferably to serine residues, for use as pharmaceutical.

Modified Chimeric superantigens and their use

A method for inactivating target cells in the presence of T cells by bringing the two types of cells in contact with a superantigen (SAG) in the presence of an immune modulator, characterized in that at least one of the superantigen and the immune modulator is in the form of a conjugate between a 'free' superantigen (Sag) and a moiety targeting the conjugate to the target cells. A superantigen conjugate complying with the formula (1) (T)(Sag)(IM); a) T is a targeting moiety, Sag corresponds to a free superantigen, IM is an immune modulator that is not a superantigen and T, Sag and IM are linked together via organic linkers B; b) x, y and z are integers that typically are selected among 0-10 and represent the number of moieties T, Sag and IM, respectively, in a given conjugate molecule, with the provision that y&#x3e;0 and also one or both of x and z&#x3e;0. The superantigen conjugate is preferably a triple fusion protein. A targeted immune modulator, characterized in that it is a conjugate between a targeting moiety (T&#x2033;') and a modified immune modulator (IM&#x2033;&#x2032;). The conjugate complies with a formula analogous to formula (1) except for the imperative presence of the modified immune modulator. A superantigen moiety may be present. A DNA molecule encoding a superantigen and an immune modulator.

Cytolysis of target cells by superantigen conjugates inducing T-cell activation

Modified/chimeric superantigens and their use

A soluble antibody conjugate comprising an antibody linked to a structure which is recognized by T-cells and has the ability to direct T-cells to lyse the target cell, which is recognized by the antibody. The conjugate is characterized by the structure being a superantigen. One important mode is a method for the lysis of target cells, wherein the target cells are contacted with a target cell lysis effective amount of the conjugate. The method of lysis is part of a potent treatment regime for cancer, autoimmunity, parasitic infestations and fungal, viral and bacterial infections. The specification also describes modes such as the synthesis of the conjugate and pharmaceutical compositions and their manufacture.

Antibody conjugates

A soluble antibody conjugate comprising an antibody linked to a structure which is recognizable by T-cells and has the ability to direct T-cells to lyse the target cell, which is recognized by the antibody. The conjugate is characterized by the structure being a superantigen. One important mode is a method for the lysis of target cells, wherein the target cells are contacted with a target cell lysis effective amount of the conjugate. The method of lysis is part of a potent treatment regime for cancer, autoimmunity, parasitic infestations and fungal, viral and bacterial infections The specification also describes modes such as the synthesis of the conjugate and pharmaceutical compositions and their manufacture.

Target specific antibody-superantigen conjugates and their preparation

Growing community of inventors

Lund, Sweden

Mikael Dohlsten