On July 15th H.M Pharma Consultancy’s CEO Hermann Mucke presented patent analysis data at Arrowhead’s 3rd Annual Drug Repositioning, Repurposing and Rescue Conference in Boston. One of the most interesting results was that the most frequent applicants filing drug repurposing patents published between January 2012 and April 2014 were European, while the general interesting pharma patents had the U.S. as the leader of the pack, as expected. Stay tuned for more interesting findings!
https://www.hmpharmacon.com| office@hmpharmacon.com| Confidential communitations through Bitmessage: BM-2DB4Z3ee6C9mbtKx92q56Xt1uT1YNBeiq9
——————–
A Gout Drug for Tumor Lysis Syndrome
When a substantial neoplasm is treated with dramatic success, the body has to deal with an unusual amount of cellular decay and catabolism products within a short time. The result is the tumor lysis syndrome, with hyperuricemia as one important component. WO/2014/065275(University of Fukui [JP]; May 1, 2014) claims a 2-phenylthiazole compound that is identifiable as febuxostat, a xanthine oxidase inhibitor and uric acid lowering drug (Adenuric®in Europe and New Zealand, Febutaz® in India and Takeda’s Uloric® in the United States). – In 2013 the Menarini Group completed the Phase III clinical study “Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies” (FLORENCE; NCT01724528). Febuxostat is also among the drugs discussed in an older review of the tumor lysis syndrome (Semin Thromb Hemost. 2007; 33(4): 397-407, here)
Antidiabetics for Pulmonary Hypertension
Inhibitors of dipeptidyl peptidase IV block the enzymatic degradation of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic peptide; agents such as alogliptin(Takeda’s Nesina®, approved in Japan 2010 and in the U.S. in 2013; co-promoted in China with Sanofi) are the newest antidiabetics. However, incretins and their tissue receptors are widely distributed and have pleiotropic effects (Indian J Endocrinol Metab. 2012; 16 Suppl 1: S47-56, here) and according to WO/2014/064811and WO/2014/065370(Takeda [JP]; May 1, 2014) alogliptin is also good as a preventive or therapeutic for pulmonary hypertension; this is quite conceivable given the effect of incretins on chemokine expression.
A Transplant Rejection Agent for Osteoporosis
Belatacept, a recombinant fusion protein consisting of an extracellular domain of human cytotoxic T lymphocyte antigen-4 (CTLA-4) and a fragment of a modified Fc portion of human IgG1, has been developed from abatacept by introducing a two amino acid substitution (L104E and A29Y). It binds to CD 80/86 ligands of antigen-stimulating cells and thereby inhibits the CD-28-mediated T-cell co-stimulation. Belatacept received FDA approval for the prophylaxis of organ rejection in adult EBV-positive patients receiving a kidney transplant (effectively, as an alternative to cyclosporine), and is marketed as Nulojix®by Bristol-Myers Squibb. WO/2014/070840(Emory University [US]; May 8, 2014) is a classic case of third-party on-target repurposing, but still unusual because the compound is not a small molecule: it claims “methods of growing bone or increasing bone mineral density and/or volume.” The companion peer review paper, published in April, is Arthritis Rheumatol. 2014; 66(4): 990-9, seen here.
Adrenergic Receptor Agonists For Liver Damage
The inventors of WO/2014/076453(UCL Business [GB]; May 22, 2014) state that the β-adrenergic receptor antagonist propranolol significantly increased biochemical and histological markers of liver injury and cell death under in vivo conditions simulating non-alcoholic steatohepatitis. Hepatocyte death was effected through both the extrinsic and intrinsic apoptotic pathways as judged by upregulation of FAS receptor, caspase-8 proteins, and cytochrome C. And indeed, adrenergic beta (isoproterenol) or alpha agonists (phenylephrine) protected mice against the hepatotoxic effects of high-dose paracetamol (acetaminophen) at least as good as N-acetylcysteine (the current gold-standard treatment for fulminant liver failure), but were superior in a delayed-administration setting. The companion peer review paper was advance-published in Hepatology at the same time as the patent application (see here).