Bracco Suisse Sa

Other

Bracco International Bv

Samir Cherkaoui

Philippe Bussat

Bernard Lamy

Rolf E Swenson

Palaniappa Nanjappan

Radhakrishna K Pillai

Bo Song

Sibylle Pochon

Hong (Helen) Fan

Thierry Bettinger

Federico Maisano

Anne Lassus

Federico Crivellin

Irene Guilbert-Brigger

David Lazarus

Christian Koller

Adrian Lobito

Michel Schneider

Peter Frinking

Christian Guillot

Emmanuel Gaud

Tim Segers

Eric Allémann

Hong (helen) Fan

Hong Helen Fan

Hong Fan

Formulations of gas-filled microvesicles comprising a ligand, which may advantageously be used in methods for separating cells or biological materials. The formulations comprise a phospholipid and a suitable mixture of a pegylated phospholipid and of a pegylated phospholipid comprising a ligand.

Gas-filled microvesicles with ligand

Technical field The invention relates to new calibrated-size gas-filled microvesicles bearing an overall positive charge, to their use and to their method of manufacturing. The gas-filled microvesicles have a geometric standard deviation (GSD) value of at least 1.25 or lower and a stabilizing envelope comprising an amphiphilic material, said amphiphilic material comprising a cationic lipid and a neutral or cationic amphiphilic polymeric compound.

Cationic calibrated-size gas-filled microvesicles

The invention discloses a recombinant protein (P-selectin glycoprotein ligand-1 and Neural Retina-specific Leucine Zipper) PSGL-1-NRL chimeric protein comprising a Selectin Binding domain and a non-covalent dimerization domain, which is a leucine zipper and is more preferably the leucine zipper domain of the human or mouse Neural Retina-specific Leucine Zipper. The chimeric protein further comprises a covalent dimerization domain with at least one cysteine suitable to form a disulfide bridge with another chimeric protein to form a homodimer. In the chimeric protein, the PSGL-1 domain corresponds to the extracellular region of Human PSGL-1 and is more preferably the selectin binding region of the mature protein. The chimeric protein is correctly post-translationally modified and is efficiently expressed in a mammalian system. It is sulfated, O-linked glycosylated and sialylated and binds P, E and L selectin, allowing in vivo and in vitro targeting for diagnostic or therapeutic purposes.

Recombinant chimeric protein for selectins targeting

Lipid formulation particularly for preparing stable gas-filled microvesicles, comprising distearoyl-phosphatidylcholine (DSPC), dipalmitoylphosphatidylethanolamine-PEG5000 (DPPE-PEG5000) and palmitic acid in an advantageous relative molar ratio. The formulation is useful in particular for therapeutic application with ultrasounds.

Gas-filled microvesicles

A method for preparing a suspension of size-controlled microparticles stabilized by a layer of amphiphilic material. The method, which may be applied to preparations using microfluidic techniques, comprises controlling the temperature of the microparticles during the preparation process and preferably while collecting the formed microparticles.

Preparation of size-controlled microparticles

Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Targeting vector-phospholipid conjugates

Gas-filled microvesicles associated with a polypeptide comprising a sequence of amino acids, said sequence exhibiting binding affinity for selectins, particularly p-selectin. The gas-filled microvesicles can be used in ultrasound imaging.

Targeting constructs

Targeted gas-filled microvesicles

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Feigeres, France

Samir Cherkaoui