Commissariat a L'energie Atomique

Andre Menez

Jean-Claude Boulain

Frederic Ducancel

Serge Chwetzoff

Daniel Gillet

Paul Boquet

Laurence Cattolico

Modified alkaline phosphatases of bacterial origin (BAP or bacterial alkaline phosphatase) which consist of a bacterial alkaline phosphatase sequence in which at least one of the amino acid residues in position 329 or in position 330 is replaced by another amino acid residue, which modified bacterial alkaline phosphatases exhibit both significantly improved enzymic properties and an increased thermal stability, and their applications, in particular in immunoenzymic assays (reagents and diagnostic kits). Method for selecting mutants of alkaline phosphatases which possess significantly improved enzymic properties.

Modified bacterial alkaline phosphatases and their applications

A kit for carrying out an immunoenzymological assay for protein, containing a diagnostic reagent consisting of a hybrid protein comprising, in order, a polypeptide P1 which is an N-terminal portion of mature alkaline phosphatase comprising from 6 to 28 of the N-terminal amino acids of said mature alkaline phosphatase, joined to a polypeptide P2, capable of interacting with an antibody or antigen joined to a polypeptide P3 which is selected from the group consisting of a) the C-terminal remaining amino acids of said mature alkaline phosphatase, b) the mature sequence of alkaline phosphatase, and c) enzymatically active fragments of b).

Hybrid proteins between an extracytoplasmic enzyme and at least another

The disclosed invention involves a DNA encoding a hybrid tripartite protein comprising an amino portion consisting of from 6 to 28 amino acid residues from the N-terminal of a mature E. coli alkaline phosphatase, a central portion corresponding to a heterologous polypeptide and a carboxyl portion which consists of the remainder of the mature E. coli alkaline phosphatase, a different alkaline phosphatase or an enzymatically active fragment of either. The tripartite proteins produced with this DNA can be used as a diagnostic reagent and in the screening of nucleic acid libraries or in the selection of recombinant clones.

The present invention relates to a basic protein called phospholipase A2 (PLA2), isolated from the venom of a snake of the family Elapidae, especially of a Naja snake and more particularly Naja nigricollis and/or Naja mossambica pallida, to the fragments and derivatives of the said protein, to their methods of preparation, to pharmaceutical compositions which can be used to human and/or veterinary medicine, and to diagnostic agents in which the said protein and/or its derivatives and/or its fragments are present. The said protein comprises 118 amino acids, its molecular weight is of the order of 13,300 Daltons and its isoelectric point is of the order of 8.6. The derivatives of the said protein are modified at one of the histidines by fixation of an alkyl group of the formula R--CH.sub.2 --X. Application to the detection of tumoral cells.

Basic protein phospholiphase A2

The present invention relates to a basic protein called phospholipase A2 (PLA2), isolated from the venom of a snake of the family Elapidae, especially of a Naja snake and more particularly Naja nigricollis and/or Naja mossambica pallida, to the fragments and derivatives of the said protein, to their methods of preparation, to pharmaceutical compositions which can be used in human and/or veterinary medicine, and to diagnostic agents in which the said protein and/or its derivatives and/or its fragments are present. The said protein comprises 118 amino acids, its molecular weight is of the order of 13,300 Daltons and its isoelectric point is of the order of 8.6. The derivatives of the said protein are modified at one of the histidines by fixation of an alkyl group of the formula R--CH.sub.2 --X. Application to the detection of tumoral cells are discussed.

Phospholipase A2 conjugated to a tarqeting moiety and their therapeutic

The present invention relates to a basic protein called phospholipase A2 (PLA2), isolated from the venom of a snake of the family Elapidae, especially of a Naja snake and more particularly Naja nigricollis and/or Naja mossambica pallida, to the fragments and derivatives of the said protein, to their methods of preparation, to pharmaceutical compositions which can be used in human and/or veterinary medicine, and to diagnostic agents in which the said protein and/or its derivatives and/or its fragments are present. The said protein comprises 118 amino acids, its molecular weight is of the order of 13,300 Daltons and its isoelectric point is of the order of 8.6. The derivatives of the said protein are modified at one of the histidines by fixation of an alkyl group of the formula R--CH.sub.2 --X. Application to the detection of tumoral cells.

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St. Remy les Chevreuse, France

Andre Menez