Bachem and Axon Neuroscience SE today announced that the two companies have entered into a collaboration under which Bachem manufactures Axon’s investigational API and supplies it as a finished dosage form under Bachem’s Clinalfa brand.

/s/ DAVID C. LUBNER David C. Lubner Executive Vice President and Chief Financial Officer (Principal Financial and Accounting Officer)

In summary, present study elucidates the cellular and molecular mechanisms of β-BA in blood vessels and human endothelial cells. Specifically, it is firstly demonstrated that β-BA can attenuate endothelial cells injury in blood stasis model, and protect HUVECs against OGD-induced cell death by activating the eNOS/NO/cGMP pathway. Collectively, it is proved that the unexplored potential of β-BA for the treatment of blood stasis damage and pharmacological activation of NO/cGMP pathway can ensure endothelial protection.

Kielstein, A., Tsikas, D., Galloway, G. P. & Mendelson, J. E. Asymmetric dimethylarginine (ADMA)—A modulator of nociception in opiate tolerance and addiction?Nitric oxide: biology and chemistry/official journal of the Nitric Oxide Society 17, 55–59 (2007).

        Proceedings to enforce our patent rights in foreign jurisdictions, whether or not successful, could result in substantial costs and divert our efforts and resources from other aspects of our business. Moreover, such proceedings could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Furthermore, while we intend to protect our intellectual property rights in major markets for our products, we cannot ensure that we will be able to initiate or maintain similar efforts in all jurisdictions in which we may wish to market our products. Accordingly, our efforts to protect our intellectual property rights in such countries may be inadequate.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

Whole-cell currents were recorded from CHO-K1 cells transfected with HCN1, HCN2, or HCN4 channels 24–48 hours post-transfection. Glass pipettes were pulled to a final resistance of 2–4 MΩ. The external and internal solution were symmetrical and contained (in mM): 150 KCl, 10 HEPES pH 7.3, 2 MgCl2 and 1 EGTA. All recordings were performed after 2 mins of dialyzing the internal solution following membrane rupture in order to avoid issues of current rundown. Data were collected at 22–25 °C at 10 kHz with a 1 kHz low-pass Bessel filter using a conventional Axopatch 200B Amplifier and Digidata 1440A digitizer. Capacitance and series resistance were electronically compensated. Activation was assessed by stepping to voltages between −160 mV and −40 mV (Δ + 10 mV) from a holding potential (VH) of 0 mV, followed by a step to +30 mV. Steady-state activation curves were assessed from the peak of the tail currents. Non-equilibrium experiments involved a pre-pulse to −70 mV prior to the activation steps for a duration of 100 ms, 500 ms, or 1000 ms for HCN1, HCN2, and HCN4 respectively. Deactivation was assessed by a pre-pulse to −130 mV followed by test pulses from +50 mV to −60 mV (Δ-10 mV). Hysteresis was also assessed by ramps from 0 mV to −150 mV and back at varying speeds. For every protocol, each test pulse was followed by a 17–24 s interpulse interval at VH to ensure complete channel deactivation. Data were analyzed using pClamp 10 and Origin8.0 software packages.

Gasser, A. et al. Activation of T cell calcium influx by the second messenger ADP-ribose. J. Biol. Chem. 281, 2489–2496 (2006).

Cholesterol has been shown to regulate numerous ion channels. HCN channels represent the molecular correlate of If or Ih in sinoatrial node (SAN) and neuronal cells. Previous studies have implicated a role for cholesterol in the regulation of rabbit HCN4 channels with effects on pacing in the rabbit SAN. Using electrophysiological and biochemical approaches, we examined the effect of cholesterol modulation on human HCN1, HCN2 and HCN4 isoforms. Patch-clamp experiments uncovered isoform specific differences in the effect of cholesterol on gating kinetics upon depletion by MβCD or mevastatin or enrichment using MβCD/cholesterol. Most dramatically cholesterol had isoform specific effects on mode-shifting, which has been suggested to play a key role in stabilizing firing rate and preventing arrhythmic firing in SAN cells and neurons. Mode-shifting in HCN1 channels was insensitive to cholesterol manipulation, while HCN2 and HCN4 were strongly affected. Trafficking of each isoform to the plasma membrane was also affected by cholesterol modulation differentially between isoforms, however, each isoform remained localized in lipid raft domains after cholesterol depletion. These effects may contribute to the side effects of cholesterol reducing therapies including disrupted heart rhythm and neuropathic pain, as well as the susceptibility of sinus dysfunction in patients with elevated cholesterol.

Emergent BioSolutions, Inc. (NYSE:EBS ) Emergent BioSolutions Inc. is a biopharmaceutical company focused on the development, manufacture and commercialization of immune-related biologic products, consisting of vaccines and therapeutics that assist the body’s immune system to prevent or treat disease. Emergent’s marketed product, BioThrax® (Anthrax Vaccine Adsorbed), is the only vaccine approved by the U.S. Food and Drug Administration for the prevention of anthrax infection. Emergent’s clinical pipeline includes programs focused on anthrax, botulism, typhoid, tuberculosis, hepatitis B and chlamydia.

Ulens, C. & Tytgat, J. Functional heteromerization of HCN1 and HCN2 pacemaker channels. J Biol Chem 276, 6069–72 (2001).

        In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA requirements, including ensuring that quality control and manufacturing procedures conform to current good manufacturing practices, or cGMPs, which include requirements relating to quality control and quality assurance as well as the corresponding maintenance of records and documentation and reporting requirements. We, our contract manufacturers, any future collaborators and their contract manufacturers could be subject to periodic unannounced inspections by the FDA to monitor and ensure compliance with cGMPs.