Creabilis Therapeutics S.p.a.

Creabilis Therapeutics S.r.l.

Creabilis S.a.

Chiara Lorenzetto

Silvano Fumero

Valentina Mainero

Silvio Traversa

Luca Beccaria

Luisa Bertarione Rava Rossa

Domenico Barone

Lila Drittanti

Thierry Guyon

Gilles Borrelly

Carlo Pincelli

Alessandra Marconi

Sebastiano Morena

Raffaella Bagnod

Barbara Canepa

Domenico Criscuolo

Cecilia Oderda

Domenico G Barone

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

The present invention relates to polypeptide variants of the HMGB-1 high affinity binding domain Box-A (HMGB1 Box-A) or to a biologically active fragment of HMGB1 Box-A, which are obtained through systematic mutations of single amino acids of the wild-type HMGB1 Box-A protein and which show an increased resistance to proteases and which are therefore characterized by more favorable pharmacokinetic and pharmacodynamic profiles. Moreover, the present invention concerns the use of said polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and associated with RAGE.

HMGB1 high affinity binding domain Box-A mutants

Protease resistant mutant of human HMGB1 high affinity binding domain Box-A (HMGB1 Box-A)

Growing community of inventors

Villafranca Piemonte, Italy

Chiara Lorenzetto