Goch, A., Banach, M., Mikhailidis, D. P., Rysz, J. & Goch, J. H. Endothelial dysfunction in patients with noncomplicated and complicated hypertension. Clinical and experimental hypertension 31, 20–30, doi: 10.1080/10641960802409846 (2009).

Regulation (EC) 1901/2006 (as amended by Regulation (EC) 1902/2006) was adopted on December 12, 2006. This Regulation governs the development of medicinal products for human use in order to meet the specific therapeutic needs of the pediatric population. It requires any application for marketing authorization made after July 26, 2008 in respect of a product not authorized in the European Community on January 26, 2007 (the time the Regulation entered into force), to include the results of all studies performed and details of all information collected in compliance with a pediatric investigation plan agreed by the Pediatric Committee of the EMA, unless the product is subject to an agreed waiver or deferral or unless the product is excluded from the scope of Regulation 1901/2006 (generics, hybrid medicinal products, biosimilars, homeopathic and traditional (herbal) medicinal products and medicinal products containing one or more active substances of well-established medicinal use) according to its Art. 9. Waivers can be granted in certain circumstances where pediatric studies are not required or desirable. Deferrals can be granted in certain circumstances where the initiation or completion of pediatric studies should be deferred until appropriate studies in adults have been performed. The EMA does not evaluate an application for market authorization that is not exempt from Regulation (EC) 1901/2006 if there is no agreed PIP, deferral or waiver. Moreover, this regulation imposes the same obligation from January 26, 2009 on an applicant seeking approval of a new indication, pharmaceutical form or route of administration for a product already authorized and still protected by a supplementary protection certificate granted under Regulation EC 469/2009 and its precursor Regulation (EEC) 1768/92 or by a patent that qualifies for the granting of such a supplementary protection certificate. The pediatric Regulation (EC) 1901/2006 also provides, subject to certain conditions, a reward for performing such pediatric studies, regardless of whether the pediatric results provided resulted in the grant of a pediatric indication. This reward comes in the form of an extension of six months to the supplementary protection certificate granted in respect of the product, unless the product is subject to orphan drug designation, in which case the 10-year market exclusivity period for such an orphan product is extended to 12 years. If any of the non-centralized procedures for marketing authorization have been used, the six month extension of the supplementary protection certificate is only granted if the medicinal product is authorized in all member states.

Time spent on securing marketing approval for regulated products, such as pharmaceuticals, medical devices and agrochemicals effectively shortens the term of patent protection during which an innovator can recover its investment without fear of generic competition. Even a few months of additional patent term can mean the difference between millions of dollars or several billion dollars. This short article will highlight the provisions put in place for patent owners to be compensated for up to 5 years of patent term lost while developing a product and obtaining FDA approval.

Nevertheless, under the Companies Law, a company may not indemnify, exculpate or insure an Office Holder against any of the following:

We found that the sustained Ca2+ signaling, mediated by ADPR and TRPM2, was correlated with polarized degranulation and cytolytic activity of NK cells against the melanoma tumor cell line B16F10. Furthermore, we have shown the importance of acidic environments for CD38 activity in NK cells, because the presence vacuolar H+ pump inhibitors resulted in the failure of ADPR production, Ca2+ mobilization, and cytolytic activity induced by CD38. All the CD38 activities in NK cells we described depend exclusively on the tumors contacted or the PME prepared from tumor cells. Finally, our results unveiled the critical role of TRPM2 in NK cell cytotoxicity against tumor cells when NK cells were introduced to mice bearing B16F10 cells as passive immunotherapy.

On February 14, 2018, we announced topline results from the investigator initiated ARRIVE Study for HIV associated lipodystrophy and NAFLD patients. HIV patients have advanced liver disease which is a major cause for morbidity and mortality. ARRIVE, a Phase 2a, investigator initiated clinical trial conducted at the University of California San Diego by Professor Rohit Loomba was a randomized, double-blinded, placebo-controlled, 12 weeks, proof-of-concept study that evaluated the safety and efficacy of Aramchol at 600mg/day versus placebo in 50 patients with HIV-associated lipodystrophy and NAFLD. The primary end point of successful therapy was improvement in hepatic steatosis at 12 weeks, as measured by MRI-PDFF. Secondary endpoints were improvement in total body fat, metabolic profile, and liver biochemistry. Liver biopsies were not included as part of the evaluation in this pilot trial. The trial showed no difference between HIV patients receiving Aramchol for 12 weeks when compared with HIV patients in the placebo arm. Aramchol showed a favorable safety and tolerability profile. Although the pathology (fatty liver) is similar to “garden variety” NASH, the pathogenesis involved in the HIV lipodystrophy and NAFLD is different and multi factorial including the effect of the virus itself and the anti-HIV medications.

Total RNA was extracted with RNAiso Plus (Takara biotechnology Co., Dalian, China) and quantified using the NanoDrop 2000c Spectrophotometer (Thermo Fisher Scientific, Wilmington, DE). Isolated RNA was polyadenylated with poly(A) Polymerase Tailing Kit (Epicentre) in accordance with the manufacturer’s instructions. Then, reverse transcription and quantitative real-time PCR were performed using the S-Poly (T) method, as previously reported by us40. Primers used for reverse transcription and quantitative PCR are as follows: miR-322, RT primer (5- GTG CAG GGT CCG AGG TCA GAG CCA CCT GGG CAA TTT TTT TTT TTT CCA AA -3) and forward primer (5- GCC CGC CAG CAG CAA TTC ATG T -3); sno202 RT primer (5- GTG CAG GGT CCG AGG TCA GAG CCA CCT GGG CAA TTT TTT TTT TTC ATC AG -3) and forward primer (5- GTA CTT TTG AAC CCT TTT CCA T -3).

(A) Histologic changes in the cortex and medulla of kidneys from P311+/+ and P311−/− mice. Representative hematoxylin and eosin staining of renal cortex and medulla sections from the Sham and UUO groups of both P311+/+ (left) (n = 6) and P311−/− (right) (n = 6) mice on day 7. Black arrowhead indicates the remarkable tubular atrophy. (B) Representative photomicrographs of Masson’s trichrome staining of kidney sections from P311+/+ (n = 6) and P311−/− (n = 6) mice at day 7 after UUO. Black arrowhead indicates the interstitial collagen fibril deposition. (C) Fibrotic areas were quantified in stained sections from P311+/+ (n = 6) and P311−/− (n = 6) mice at day 7 after UUO. (D) RNA was isolated from kidneys of P311+/+ (n = 6) and P311−/− (n = 6) mice after UUO or sham operation. Collagen I mRNA expression was determined by real-time PCR. (E) Western blot analysis of vimentin protein levels. (F) Quantification of vimentin protein levels in each treatment group (n = 3 per group). A-F are representative of at least three similar experiments. Scale bar: 100 μm. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01.

        We must successfully complete pre-clinical testing for zilucoplan and our other programs, which may include demonstrating activity and comprehensive studies to show the lack of toxicity and other adverse effects in established animal models, before commencing clinical trials for any product candidate. Many pharmaceutical and biological products do not successfully complete pre-clinical testing and, even if pre-clinical testing is successfully completed, may fail in clinical trials. In addition, there can be no assurance that positive results from pre-clinical studies will be predictive of results obtained from subsequent pre-clinical studies or clinical trials. We also cannot be certain that any product candidates that do advance into clinical trials will successfully demonstrate safety and efficacy in clinical trials. Even if we achieve positive results in early clinical trials, they may not be predictive of the results in later trials.

If the conditions set forth above are not met, the purchaser may not acquire additional shares of the company from shareholders who accepted the tender offer to the extent that following such acquisition, the purchaser would own more than 90% of the company’s issued and outstanding share capital.

I agree that the purpose of biotech companies is to make money, whether they have a useful drug or not. From time to time, a few turn out to have a useful drug. For example, I am thinking of CAR-T (Kite, Juno). But no doubt there are lots of scam out there.

Ok, we could act against one of the fundamental laws of nature: all natural processes are irreversible.