Sorry Ladies and Gentlemen for our two months of silence. We had business to conduct like you won’t believe… actually couldn’t spare the few hours per month that it takes writing these commentaries. OK, we are still extremely busy… but this little blog is back again. In order to catch up we will shorten the commentaries a bit, and present them in much more rapid succession.
On July 15th H.M Pharma Consultancy’s CEO Hermann Mucke will tele-present patent analysis data at Arrowhead’s 3rd Annual Drug Repositioning, Repurposing and Rescue Conference in Boston (see the agenda).
https://www.hmpharmacon.com| office@hmpharmacon.com| Confidential communitations through Bitmessage: BM-2DB4Z3ee6C9mbtKx92q56Xt1uT1YNBeiq9
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Theophylline et al. for Smell and Taste Disorders
WO/2014/055801(Individual [US]; April 10, 2014) claims intranasal or lingual administration of phosphodiesterase inhibitors to improve compromised taste or smell acuity. Disclosed are steroid-free dosage units for intranasal administration comprising theophyllinefor treating anosmia, hyposmia, dysosmia, ageusia, hypogeusia, or dysgeusia comprising less than 1 mg of theophylline in a liquid carrier with a slightly alkaline pH. Most known PDE inhibitors are claimed. For companion peer review papers see Am J Med Sci. 2011; 341(1): 17-22 (here) and J Clin Pathol. 2012; 65(5): 447-51 (here). Also see Arch Otolaryngol Head Neck Surg. 2009; 135(3): 291-5, here) for pentoxifylline (also a PDE inhibitor) in the treatment of olfactory loss.
A Microjump From COPD to Cough
Boehringer Ingelheim is developing the highly selective inhaled long-acting beta2-agonist, olodaterol(Striverdi®) as a combination partner for tiotropium (Spiriva®) to provide once-daily bronchodilation in the maintenance of patients with chronic obstructive pulmonary disease. In WO/2014/056840(Boehringer Ingelheim [DE]; April 17, 2014) the company says that olodaterol has anti-tussive activity already at its minimum effective dose for bronchoprotection (0.01 μg/kg i.t). – True, that sounds more like originator-based use extension than repurposing: most COPD patients have cough, and tiotropium is also used for cough. But chronic cough is an astoundingly complex condition that also occurs in the absence of COPD; and other beta agonists have no anti-tussive action at all (e.g., indacterol), or only at much higher doses (formoterol).
MEK Inhibitors for Influenza
Ten years ago in FEBS Lett. 2004; 561(1-3): 37-43 (here), the inventors who have now filed WO/2014/056894(Univ. Münster [DE]; April 17, 2014) had shown that the MEK inhibitor U0126impairs influenza B virus propagation without inducing resistance, suggesting that influenza viruses cannot easily adapt to the inhibited cellular function that is required for the viral nuclear export process. In Antiviral Res. 2011; 92(2):195-203 (here) they demonstrated that this same mechanism also works against current influenza A virus strains in vivo. The pertinent document provides additional data for MEK inhibitors refametinib, CI-1040, PD-0325901, AS-703026, AZD-6244, AZD-8330, PLX-4032, and others. All these compounds had initially been characterized as anticancer agents, and the Université Paris Descartes had claimed several of these in WO/2012/160130for spinal muscular atrophy (see our discussion in Issue #16 of this blog).
Conivaptan for Ischemic Stroke
Conivaptan(Astellas Pharma’s / Cumberland Pharmaceuticals’ Vaprisol®) is an antagonist of arginine vasopressin receptors V2 and V1A that induces diuresis, with electrolyte-sparing effects on the kidney. It is approved for the treatment of hyponatremia in hospitalized patients. WO/2014/062888(Univ. South Florida [US]; April 27, 2014) claims that conivaptan can be administered to a subject believed to have suffered a stroke up to approximately 12 hours after the event, apparently to ameliorate the resulting cerebral edema – as reported in Neurotherapeutics 2012; 9(1): 65-72 (here).
Adenosine Agonists Keep Orthopedic Implants in Place
The most common cause for joint replacement failure requiring revision is peri-implant osteolysis leading to loosening of the prosthesis. It results from the inflammatory response to wear particles which stimulates osteoclast differentiation and bone resorption. Now, WO/2014/063134(New York Univ. [US]; April 24, 2014): through a complex mechanism, adenosine A2A agonists such as sonedenoson(MRE-0094; was under development for diabetic foot ulcers; first disclosed in WO/1991/13082) or the cardiac stress agent for myocardial perfusion imaging, binodenoson(MRE-0470; see Circulation 2004; 109(4): 457-64, here) can counteract this by inhibiting chemorepulsant axonal guidance proteins such as netrin-1, or its receptor unc5b (see Brain Res. 2000; 878(1-2): 204-9, here).