Creabilis Therapeutics S.p.a.

Ares Trading S.a.

Creabilis Therapeutics S.r.l.

Creabilis S.a.

Silvio Traversa

Valentina Mainero

Chiara Lorenzetto

Luca Beccaria

Silvano Fumero

Luisa Bertarione Rava Rossa

Carlo Pincelli

Alessandra Marconi

Sebastiano Morena

Raffaella Bagnod

Domenico Barone

Domenico Criscuolo

Cecilia Oderda

Gilles Piquet

Luca Barbero

Monica Gatti

The present invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A) or of a biologically active fragment of HMGB1 Box-A. Further, the invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A). Moreover, the present invention concerns the use of said polymer conjugates of polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and/or associated with an increased expression of RAGE.

Polymer conjugates of Box-A of HMGB1 and Box-A variants of HMGB1

The present invention relates to a process for the preparation of polymer conjugates of indolocarbaxole compounds, in particular of polymer conjugates of K-252a and derivatives thereof, by a synthetic route which results in a highly pure product, with a high product yield. In a further aspect the present invention relates to novel polymer conjugates of K-252a and derivatives thereof, wherein the chemical group linking the polymer unity to the K-252a or to the K-252a derivative compound is characterized by a 5-member oxazolidindionic cyclic structure. These novel polymer conjugates are obtained through the novel synthetic route with high purity and high yields.

Synthesis of polymer conjugates of indolocarbazole compounds

The present invention relates to novel polymer conjugates of K-252a and derivatives thereof and to their use for the preparation of a pharmaceutical composition useful for the prevention, alleviation and treatment of kinase-associated pathologies. In particular, the present invention relates to the prevention, alleviation and treatment of HMGB1-associated pathologies. The invention relates to the use of the novel polymer conjugates of K-252a and derivatives thereof in the preparation of a pharmaceutical composition useful for the prevention, alleviation and treatment of a) neurological disorders, neuropathies and neurodegenerative disorders of the central and peripheral nervous system; b) dermal pathologies, in particular dermal pathologies associated with an excessive keratinocyte proliferation, in particular psoriasis; and c) NGF-related pain. More specifically, the present invention relates to a polymer conjugate of K-252a and derivatives thereof, wherein the polymer is polyethylene glycol or methoxy-polyethylene glycol formula (I).

Polymer conjugates of K-252A and derivatives thereof

A method is described for a method for the regioselective liquid-phase pegylation of GRF, which increases the yield of the GRF-PEG conjugate having 1 PEG molecule covalently bound to the e-amino group of Lys. This method is characterized in that the reaction is carried out in a structuring solvent, such as trifluorethanol.

Regioselective liquid phase pegylation

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Palazzo Canavese, Italy

Silvio Traversa