Erytech Pharma

Geneohm Sciences, Inc.

Becton Dickinson Infusion Therapy Systems Inc.

Yann Godfrin

Pierre-Olivier Goineau

Seng H Cheng

Nelson S Yew

Fabien Gay

Vanessa Bourgeaux

Thomas Cortese

Alice Banz

Sébastien Ribault

Jean-Pierre Hermet

Isabelle Besson-Faure

Anne Monnot Des Angles

Sebastien Ribault

Jerome Bailly

Willy Berlier

Emmanuelle Dufour

Jérôme Bailly

Karine Aguera

Emmanuelle-Cécile Dufour

Alice Marchand

Emmanuelle-Cecile Dufour

The invention relates to a pharmaceutical composition containing a PLP-dependent enzyme and optionally its cofactor, pyridoxal phosphate (PLP), and/or a phosphate or non-phosphate precursor of PLP, its use as a drug, its production method and a therapeutic treatment method related to it. The pharmaceutical composition comprises erythrocytes and a pharmaceutically acceptable vehicle, the erythrocytes encapsulating the PLP-dependent enzyme. The PLP-dependent enzyme may be methioninase, tyrosine phenol-lyase, tyrosine aminotransferase or cystathionine beta-synthase.

Pharmaceutical composition comprising erythrocytes encapsulating a PLP-dependent enzyme and, a non-phosphate PLP precursor

The invention is related to a new method for treating liquid and solid cancers, in a mammal, including human, wherein methioninase is administered before asparaginase. The invention also encompasses the use of a dietary methionine deprivation, possibly combined with methioninase administration, in advance of asparaginase treatment. Methioninase and asparaginase may be used in particular under free form, pegylated form or encapsulated into erythrocytes.

Method of treating a mammal, including human, against cancer using methionine and asparagine depletion

The invention relates to a composition which induces, in a host, a cytotoxic cell response directed against cells expressing an antigen, in particular tumour cells, and which comprises red blood cells containing said antigen. These red blood cells may be in the form of an immune complex with an immunoglobulin, in particular IgG, which recognizes an epitope at the surface of the red blood cells, and/or be heat-treated or chemically treated so as to promote phagocytosis of said red blood cells by dendritic cells. As a variant, the red blood cells may be xenogenic red blood cells. The invention also relates to a therapeutic especially anti-tumour vaccine containing such a composition.

Composition and therapeutic anti-tumour vaccine

The invention relates to a pharmaceutical kit containing a) an injectable suspension of erythrocytes encapsulating a pyridoxal phosphate (PLP)-dependent enzyme and b) a non-phosphate PLP precursor. The invention further relates to methods of producing component(s) of the kit and to therapeutic treatment methods related to the kit. The PLP-dependent enzyme may be a methioninase, a tyrosine phenol-lyase, a tyrosine aminotransferase or a cystathionine beta-synthase.

Pharmaceutical kit comprising erythrocytes encapsulating a PLP-dependent enzyme and, a non-phosphate PLP precursor

A method for obtaining a stabilized suspension of red blood cells encapsulating an active ingredient, from resealed RBCs incorporating the active ingredient, the method comprising the incubation of the resealed RBCs in an incubation solution at an osmolality of no less than 280 m Osmol/kg, for a time of 30 minutes or more, the incubation solution being a solution that does not contain an agent which is denaturating for the RBC membrane, the liquid medium is then removed from the incubated suspension and the RBCs obtained are placed in suspension in a solution allowing the injection of the suspension in a patient. The suspensions obtained are particularly characterized by an extracellular haemoglobin level maintained at 0.5 or lower, in particular 0.2 g/dl or lower and/or a hemolysis rate maintained at 2 or less, in particular 1% or less, at 72 h after placing in suspension in a preservation solution and at a temperature of between 2 and 8&#xb0; C.

Method for stabilising suspensions of red blood cells encapsulating an active ingredient

A lysis/resealing process for preparing erythrocytes containing active ingredient is provided comprising placing a globular concentrate in suspension in an isotonic solution having a haematocrit level which is equal to or greater than 65%, with refrigeration at 1 to 8&#xb0; C.; measuring the osmotic fragility based on a sample of erythrocytes from that same globular concentrate, preferably on a sample of the suspension; lysis and internalization procedure of the active ingredient, inside the same chamber, at a temperature maintained at 1 to 8&#xb0; C., comprising allowing the erythrocyte suspension having a haematocrit level equal to or greater than 65% and a hypotonic lysis solution which is refrigerated at 1 to 8&#xb0; C., to circulate in a dialysis cartridge; the lysis parameters being adjusted in accordance with the osmotic fragility previously measured; and resealing in a second chamber at a temperature of from 30 to 40&#xb0; C. by means of a hypertonic solution.

Lysis/resealing process and device for incorporating an active ingredient, in particular asparaginase or inositol hexaphosphate, in erythrocytes

Method of treatment using a pharmaceutical composition comprising erythrocytes encapsulating a PLP-dependent enzyme and its cofactor

Use of erythrocytes containing arginine deirainase for the preparation of a medicinal product for lowering the plasma concentration of arginine in vivo. The use relates in particular to the treatment of arginine-dependent tumors, such as hepatocarcinoma and malignant melanoma, or inhibition of the synthesis of nitric oxide, and the prevention and/or treatment of septic shock.

Erythrocytes containing arginine deiminase

The invention relates to a composition which induces, in a host, a cytotoxic cell response directed against cells expressing an antigen, in particular tumor cells, and which comprises red blood cells containing said antigen. These red blood cells may be in the form of an immune complex with an immunoglobulin, in particular IgG, which recognizes an epitope at the surface of the red blood cells, and/or be heat-treated or chemically treated so as to promote phagocytosis of said red blood cells by dendritic cells. As a variant, the red blood cells may be xenogenic red blood cells. The invention also relates to a therapeutic especially anti-tumor vaccine containing such a composition.

Method of in vitro measurement of the presence of factors that are able to neutralize asparaginase activity in a sample of blood, plasma, serum or derived medium that may contain asparaginase neutralizing factors, obtained from a patient, comprising mixing of said sample with asparaginase, incubation of said mixture, then measurement of the residual asparaginase activity in the mixture and determination or quantification of the presence of said neutralizing factors. Method for predicting the efficacy of a treatment with asparaginase.

Test for predicting neutralization of asparaginase activity

Compostition and therapeutic anti-tumour vaccine

The invention relates to a suspension of red corpuscles encapsulating asparaginase as a medicament for treating pancreatic cancer. It in particular concerns a therapeutic composition or medicament intended for the treatment of pancreatic cancer, containing an effective quantity of such a suspension of red corpuscles.

Medicament for the treatment of cancer of the pancreas

The invention concerns a device and a method for concentrating pathogenic germs potentially present in blood products or derivatives and for detecting said germs comprising the following steps: (a) subjecting a sample of said blood product to a blood cell aggregating treatment, (b) eliminating the aggregates formed at step (a) by passing the treated sample over a first filter allowing through the contaminating germs but not the cell aggregates, (c) selectively lyzing the residual cells of the filtrate obtained at step (b), (d) recuperating the contaminating germs by passing the lysate of step (c) over a second filter to detect the contaminating germs possibly trapped.

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Lyons, France

Yann Godfrin