Bracco Imaging S.p.a.

Creabilis Therapeutics S.p.a.

Creabilis Therapeutics S.r.l.

Creabilis S.a.

Valentina Mainero

Silvio Aime

Chiara Lorenzetto

Silvio Traversa

Luca Beccaria

Silvano Fumero

Claudia Cabella

Luisa Bertarione Rava Rossa

Alessandro Barge

Carlo Pincelli

Alessandra Marconi

Sebastiano Morena

Simonetta Chirich Geninatti

Raffaella Bagnod

Fulvio Uggeri

Enzo Terreno

Domenico Barone

Dario Livio Longo

Domenico Criscuolo

Cecilia Oderda

Walter Dastrù

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 invention provides MRI detectable species of formula (I)D-S-N&#x2003;&#x2003;(I)wherein These compounds are useful for internalizing into tumor cells an amount of the MRI detectable moiety that is distinguishably higher than the amount internalized in normal healthy cells thus allowing the diagnosis of tumors. The internalization of the MRI detectable moiety involves the nutrients or pseudo-nutrients transporting system. Preferred compounds of formula (I) are those wherein D is the chelated complex of a paramagnetic metal ion.

Agents for magnetic imaging method

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 invention concerns a method for obtaining diagnostic images of a human or animal body organ, region, fluid or tissue by using combined X-ray and/or Magnetization Transfer (MT) based MRI techniques and iodinated radiographic compounds as contrast agents, as well as improved Chemical Exchange dependent Saturation Transfer (CESDT or CEST) based MRI procedures in which a iodinated contrast agents is used for in vivo determining a physiological parameter of diagnostic interest.

Ionic and non-ionic radiographic contrast agents for use in combined X-ray and nuclear magnetic resonance diagnostics

The invention discloses the use of ionic and non-ionic radiographic contrast agents for combined X-ray and nuclear magnetic resonance (MRI) diagnostics.

Ionic and non-ionic radiograhic contrast agents for use in combined X-ray and nuclear magnetic resonance diagnostics

The invention provides MRI detectable species of formula (I): D-S-N, wherein D is a MRI detectable moiety; S is a spacer; N is a molecule of a nutrient or pseudo-nutrient; n is 0 or an integer, m is an integer and p is an integer. These compounds are useful for internalizing into tumor cells an amount of the MRI detectable moiety that is distinguishably higher than the amount internalized in normal healthy cells thus allowing the diagnosis of tumors. The internalization of the MRI detectable moiety involves the nutrients or pseudo-nutrients transporting system. Preferred compounds of formula (I) are those wherein D is the chelated complex of a paramagnetic metal ion.

Growing community of inventors

Ivrea, Italy

Valentina Mainero