Additionally, for certain of our in-licensed patent rights, we do not have the right to bring suit for infringement and must rely on third parties to enforce these rights for us. If we cannot or choose not to take action against those we believe infringe our intellectual property rights, we may have difficulty competing in certain markets where such potential infringers conduct their business, and our commercialization efforts may suffer as a result.

It is estimated that the global prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD), the precondition to NASH, is approximately 25% in the general population and much higher in certain high risk groups. This disease is also now recognized as one of the most common liver disorders, and a significant growing public health problem. In the US alone, 80-100 million people are said to be affected by NAFLD, and its prevalence is rapidly growing in parallel with metabolic syndromes, particularly obesity and diabetes.

        As of December 31, 2018, we had an accumulated deficit of $188.2 million. Our net losses were $64.9 million and $54.4 million for the years ended December 31, 2018 and 2017, respectively. We have incurred significant net operating losses in every year since our inception and expect to continue to incur increasing net operating losses and significant expenses for the foreseeable future. Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase significantly as we:

        Under the new revenue standard, the Company recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration that the Company expects to receive in exchange for those goods or services. The Company recognizes revenue following the five-step model prescribed under ASC 606:

Under the terms of the Samil Agreement, the Company received an up-front payment of approximately $2.1 million. Samil has also agreed to pay additional clinical and regulatory-based milestone payments, which may aggregate up to $6.0 million, as well as tiered, double-digit royalties payable on sales (under certain limitations). In September, 2018 the Company received a milestone payment of $1.5 million from Samil in connection with the completion of its ARREST study.

In the 1970s, there was a lot of interest in controlled-release research for pharmaceutical applications. Much of this activity focused on the development of long-acting contraceptives. The goal was to develop formulations that released contraceptive steroids at a programmed rate for one month or longer following a single parenteral administration. Initially, researchers in the contraception field used non-biodegradable silicone materials as controlled-release excipients (2). PLG polymers were later found to have good biocompatibility and desirable bioabsorption properties; as a result, many investigators began to formulate contraceptive steroids with PLG as functional polymers. Various dosage forms, including injectable microparticles, implants, and fibers, were investigated for both systemic and local delivery (3).

U.S. Holders should consult their own tax advisors regarding the U.S. federal income tax consequences of receiving currency other than U.S. dollars upon the disposition of their ordinary shares.

During early times, laboratories had to make their own PLG polymers and monomers. These polymers, especially polymers with high glycolide content (e.g., 50:50 lactide:glycolide polymers) had solubility challenges due to their long glycolide blocks. Also, polymer solubility varied from batch to batch, making it difficult to perform robust formulation processing and achieve reproducible drug-delivery performance from microparticles and implants. Resomer polymers offer more consistent properties with better and reproducible solubility. 

There are a lot impressive creative scientists. I quoted Einstein because of the “imagination” component.

However, regulators must now grapple with the question of how members of a class of potent probable carcinogens wound up in the pharmaceutical supply chain in the first place.  NDMA, widely used in cancer research, was the poison of choice in two sensational murders in the U.S. and Germany (7) in 1978, while growing evidence of its impact and that of other nitrosamines helped drive public area smoking bans and intensive process changes in the food industry.  

For miRNA overexpression experiments in rat PASMCs, lentiviral vectors based on pLVX-Puro backbone (Clontech, Mountain View, CA) were used to express miR-322 as described before22. To study the effect of the miRNAs on HIF-1α accumulation, adenovirus expressing oxygen dependent degradation domains (ODDD: HIF-1αamino acid 531–575) or mutated ODDD (ODDD-mut: P564A) were used to generate cells with or without stable endogenous total α-type HIF proteins as previously reported22. Plasmid vectors containing short hairpin RNA targeted to HIF-1α (shHIF-1α), HIF-2α (shHIF-2α) and nonspecific control (shControl) were constructed based on pLVX-hU6. The shRNA sequences containing the BamHI and MluI restriction sites were synthesized as follows: shHIF-1α, 5- GAT CCG AGA GGT GGA TAT GTC TGG GTC AAG AGC CCA GAC ATA TCC ACC TCT TTT TT -3; shHIF-2α, 5- GAT CCG TTG ATG AAT CCT CGA CTT ATC AAG AGT AAG TCG AGG ATT CAT CAA TTT TT -3; shControl, 5- GAT CCG GGT CTG TAT AGG TGG AGA TCA AGA GTC TCC ACC TAT ACA GAC CCT TTT T -3. Synthetic siRNAs for BMPR1a and Smad5 knockdown were purchased from GenePharma Co.,Ltd (GenePharma, Shanghai, China). Knockdown of miR-322 was achieved by using dTuD constructs against mature rno-miR-322, which was modified from TuD vector39 with one more TuD expression cassette. The sequence against cel-miR-39, an elegans miRNA, was used as a negative control. All constructs were subsequently confirmed by DNA sequencing.

Secondly, one of their assumptions is that somatic degradation does happen inevitably. Note that this is not a proof but an assumption. You could argue that in the 23th. century, we’ll have the technology (think nanotechnology, nanobots, ..) to prevent that. At that time, we will be in total control of our genome stability. Just a speculation.