Research

Biotech patents

IRCCS Ospedale San Raffaele gathers a wide range of talented scientists and clinicians devoted to basic, clinical and translational research, whose know-how can greatly benefit pharma and biotech companies. The Office of Biotechnology Transfer aims at promoting partnerships with pharma and biotech companies through intellectual property management, negotiation of sponsored research projects and licensing of intellectual property rights. 

In particular, the Office of Biotechnology Transfer has filed 163 patent families (patented technologies), on behalf of IRCCS Ospedale San Raffaele, of which 55 are still alive at 2017. The latter correspond to a portfolio of 399 patents and patent applications, with 331 being licensed or optioned at 2017. 

Cancer

Human Tie2-expressing proangiogenic monocytes (TEMs). Human Tie2+ monocytes (TEMs) represent potential targets of novel antiangiogenic therapies as well as biological readouts in the circulation to monitor pathological angiogenesis. Furthermore, TEMs can be used as gene delivery vehicles in the setting of an autologous bone marrow transplant or adoptive transfer.

Tumor targeted conjugable peptides. The present invention is a new head-to-tail-cyclized hexapeptide containing the isoAsp-Gly-Arg (isoDGR) motif that, after chemical conjugation to human serum albumin (HSA), recognizes αvβ3 with very good selectivity, binds to tumor vessels, inhibits tumor growth and works as an efficient ligand for the delivery of nanomedicines to tumor vasculature.

Targeting leukemia by CD1c-restricted T cells specific for a novel lipid antigen. The present invention is an immunotherapy-based platform based on TCR having antigenic specificity for CD1c molecules associated with a self-lipid, named as methyl-lysophosphatidic acids (mLPAs), for treating leukemia.

Novel targets in multiple myeloma and other disorders. The inventors propose a new synthetic-lethal strategy to treat multiple myeloma and other hematological cancers, including lymphoma and leukemia, by selectively targeting cancer cells presenting with endogenous DNA damage and low YAP1 levels.

Side-chain modified ergosterol and stigmasterol derivatives as liver X receptor modulators. The present invention relates to a novel steroidal stigmasterol and ergosterol derivatives, characterized by the precense of oxygenated functions at C-22 and C-23 positions, able to work as potential Liver X Receptor (LXR) agonist for the treatment of of diseases associated with LXR, such as cancer, inflammation, metabolic and autoimmune diseases.

Immune diseases

Clinical use of Rapamycin-expanded regulatory-T cells for the treatment of T-cell mediated diseases. The invention related to the use of rapamycin to expand in vitro CD4+CD25+FOXP3+ Tr cells for cellular therapy in T-cell–mediated diseases, in association with organ transplantation or bone marrow transplantation, and in the treatment or prevention of GvHD.

Tr1-dendritic cells and uses thereof. IL-10 promotes the differentiation of a new subset of tolerogenic dendritic cells (Tr1-DC) which can be used to generate anergic Tr1 cells with limited in vitro manipulation and suitable for potential clinical use to restore peripheral tolerance.

Regenerative medicine

Stem cells and regenerative medicine

Periangioblasts, adult skeletal muscle stem cells for the treatment of muscular dystrophies. The present invention relates to skeletal muscle disorders such as Duchenne and other forms of muscular dystrophy, including but not limited to limb girdle, facio-scapulo-homeral, myotonic, Emery-Dreyfuss etc, as well as inflammatory myopathies, which may all be treated with skeletal muscle periangioblasts.

Use of neural stem cells to induce neuroprotection in inflammatory CNS disorders. Undifferentiated adult neural stem/progenitor cells (aNPCs) have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection in inflamed CNS perivascular area on the one hand, and brain repair on the other.

A non-oxidable HMGB1 mutant for wound healing. Inventors’ work demonstrates how different redox states of HMGB1 impact on its chemotactic properties, revealing its therapeutic potential for the treatment of pathologies requiring tissue regeneration, such as wounds, fractures and physical trauma recovery, ischemia and recovery thereof of various tissues and organs.

Gene therapy

MicroRNA-regulated viral vectors. The present invention describes a gene transfer vector system that utilizes the microRNA post-transcriptional gene silencing machinery for regulating transgene expression. Lentiviral vectors for transgene expression for gene therapy can be engineered with microRNAs target sequence in order to be recognized by endogenous microRNAs which are cell-type specific. The invention could be employed to prevent immune-mediated rejection of the transferred gene.

New promoters and new lentiviral vectors: efficient and coordinated expression of multiple genes. The present invention describes new promoters designed and constructed for multiple gene expression that have been incorporated into state-of-the-art, self-inactivating lentiviral vectors to reach stable integration and efficient, coordinated expression in all transduced cells. 

A method for the ex vivo production of fully functional gene-modified human T lymphocytes. Inventors have identified two essential requisites for the ex vivo production of fully alloreactive gene-modified human T lymphocytes: (i) the activation with anti-CD3 and anti-CD28 monoclonal antibodies coupled to cell-sized paramagnetic beads (CD3/CD28-beads) prior to genetic modification with viral vectors, and (ii) the culture of gene-modified T cells with a combination  of IL-7 and IL-15.

New gene therapy approach to induce antigen-specific immunological tolerance. Inventors report in vivo induction of antigen-specific Treg and active immune tolerance against foreign antigens by hepatocyte-targeted Integrase-Deficient Lentiviral Vectors (IDLV). In particular, the present invention describes a new strategy exploiting endogenous miR-142 regulation in combination with IDLV.

Inheritable silencing of endogenous genes by hit and run targeted epigenetic editing. The invention relates to engineered transcriptional repressors (ETRs) encompassing a custom-made DNA binding domain (DBD) fused to the effector domain of key players involved in the ERVs’ silencing cascade, including KRAB, the catalytic domain of DNMT3A and DNMT3L. The ETR platform represents an attractive option for both clinical and research applications that require permanent repression of specific genes.

Genetic disorders

Compounds for use in polycystic kidney disease. Using a metabolomic approach the inventors identified a new pathogenic ADPKD pathway involving defective glucose metabolism, and showed that inhibition of glycolysis using glucose analogs ameliorates PKD in preclinical models, thus representing a novel therapeutic strategy in ADPKD.

FKBP12 as druggable target for the treatment of iron-overload diseases. Inventors show that disruption of the FKBP12-ALK2 interaction could be relevant in conditions of iron overload characterized by increased BMP6. In particular, Tacrolimus (FK506) and rapamycin, by interacting with the same FKBP12-binding pocket, are able to activate hepcidin through the BMP/SMAD pathway.

Neuroscience

Myeloid microvescicles are a marker and therapeutic target for neuroinflammation. Our findings identify myeloid Microvesicles (MVs)  as a valuable marker and therapeutic target of brain inflammation. The inventors also propose that MVs produced by microglia/macrophages and leaking into the CSF may represent a rich source of information on microglia/macrophage activation in the brain, which may lead to the identification of specific disease cell signatures through the analysis of their content.

Technologies and medical devices

Medical devices

Composite scaffold for tissue repair. Orthopaedic surgeons in collaboration with engineers have developed a biphasic scaffold for the regeneration of the osteochondral tissue, composed of collagen 1 and hydroxyapatite. This scaffold can be used as a cell-free implant or in combination with a source of cells, it has good press-fit properties facilitating the filling of the defect and it is stable throughout long-term regenerative applications.

Technologies

Optical platform for ion channel drug screening. Inventors propose an optical platform based on a proprietary method, that is aimed to screen candidate compounds acting on ion channels. The method allows to derive experimentally a dose-response curve concerning specific agonist-receptor interactions by a fully automated procedure that fits the requirements of high throughput screening and offers a competitive alternative to traditional electrophysiological techniques.

Multiparametric whole blood dissection: a one-shot comprehensive picture of the human hematopoietic system. The present invention relates to a novel flow cytometry protocol (kit), called Whole Blood Dissection (WBD. Starting from a limited amount of whole blood, WBD allows analyzing and quantifying at once and in a single test tube up to 23 different blood cell types composing either bone marrow (BM) or peripheral blood (PB) samples, including human stem progenitor cell (HSPC) subpopulations and all the major cell lineages at different stages of maturations.