There has been no shortage of revelations concerning covert digital surveillance this summer, but H.M. Pharma Consultancy plows onward with its own surveillance program for drug repurposing — which is entirely based on very public documents such as those five patent applications reviewed below. If you want to make use of our know-how in this promising space of life science developments, please contact us — with any degree of confidentiality you think is appropriate. – Please note that, in response to suggestions from our readers, we are now linking compound names or codes to their PubChem records.
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New Uses for Beta-3 Adrenergic Receptor Agonists
In WO/2013/113141(Individuals [CN]; Aug. 8, 2013) the inventors claim effects of beta-3 adrenoceptor activation on “pathways such as SIRT1, mTOR, and p53, (…) treating (…) malignancy, hypertrophic cardiomyopathy, pulmonary hypertension, cirrhosis, rheumatoid arthritis, renal failure, and Alzheimer’s disease.” Experiments used the selective beta-3 blockers SR-59230Aand BRL-37344(SB 206606), but apparently not selective agonists such as amibegron(Sanofi’s SR 58611A, discontinued in 2008 after entering Phase III for depression) or Cyanamid’s CL 316,243. Claims pertain only to β3 agonists in a general.
Vigabatrin for Tourette Syndrome
Eighteen years ago a paper titled “Gamma-vinyl-GABA treatment of tardive dyskinesia and other movement disorders” was published (Biol Psychiatry 1985; 20(8):888-93; PMID: 3861199), reporting a 7-patient micro-trial with vigabatrinwhich included one case of Tourette syndrome. Now, WO/2013/112363(Catalyst Pharma et al. [US]; Aug. 1, 2013)tries to obtain intellectual property for this application of the old third-line antiepileptic drug which is fraught with visual system side effects. Alternatively the inventors suggest CPP-115, a vigabatrine derivative from Northwestern University that is a much more potent irreversible inhibitor of GABA aminotransferase than its parent compound. Catalyst had acquired worldwide rights to commercialize CPP-115 and related compounds under a 2009 license agreement, and is developing it for cocaine addiction (see NCT01493596and J Med Chem. 2012; 55(1):357-66; PMID: 22128851). The approach is interesting with regard to GABAergic neurons’ impact on dopaminergic pathways, which are believed to be of central importance in Tourette motor tic manifestations. The 1985 paper is not cited in the application, nor did the patent examiner pick up on it.
Panobinostat for HIV Infection
Novartis’ pan-histone deacetylase (HDAC) inhibitor, panobinostat(LBH589; a cinnamic hydroxamic acid analog very similar to vorinostat[Merck & Co.’s Zolinza]) already has an impressive history of completed and still-recruiting clinical trials (see here). Most of these are for cancer; Novartis’ primary development goals are multiple myeloma and acute myeloid leukemia (Expert Opin Investig Drugs 2013; 22(9):1211-23; PMID: 23826641). The CLEAR trial (NCT01680094), for which positive results were reported at the 7th IAS Conference on HIV Pathogenesis Treatment and Prevention in July 2013, had tested whether panobinostat in cyclic dosing (20 mg p.o. 3 times per week every other week, repeated 4 times for a total of 8 weeks) could lead to viral reactivation in virologically suppressed HIV-1 infected patients, and potentially achieve eradication. The corresponding international patent application, WO/2013/110280(Aarhus Univ. [DK]; Aug. 1, 2013) shows no involvement of Novartis, but the company was a co-sponsor of the CLEAR trial.
Yet Another Use for Melatonin
WO/2013/109016(Chonbuk Natl. Univ. [KR]; July 25, 2013) provides no machine-translatable body text and our Korean is not so good these days, so it is not easy to elucidate directly on what basis the claims for the efficacy of melatonin against prion diseases are being made. The figures and the few English-written text fragments indicate that the inventors used an Annexin-Vassay and PrP(106-126) prion protein in SH-SY5Yneuroblastoma cells. The inventors’ companion peer-review paper (J Pineal Res. 2012; 53(2):138-46; PMID: 22335252), which claims to be the first report demonstrating melatonin protection against prion neurotoxicity, likely provides more information although the experimental data do not seem to overlap entirely.
A Histamine Receptor Inverse Agonist for Multiple Sclerosis
Under the less than enlightening title “Therapeutic uses,” WO/2013/107336(GlaxoSmithKline [CN]; July 25, 2013) claims 1-{6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-2-pyrrolidinone, an inverse agonist at H3 histamine receptors, for the treatment of multiple sclerosis. A quick scan of our databases reveals this to be GSK-189,254(JPET 2007;321(3):1032-45, PMID:1732748) which had been first disclosed in WO/2004/056369,had entered the clinical stage in 2005, and had been investigated in early-stage trials for Alzheimer’s disease (NCT00474513) and narcolepsy (NCT00366080). The calculated oral doses to modulate progression of MS disability by enhancing remyelination – 10-150 µg/day – are extremely low. Remyelination data from the cuprizone MS model (J Mol Neurosci.2013 May 12; PMID: 23666824) are provided.