Developability studies before initiation of process development

Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other therapeutic proteins, examples of projects that are suspended due to the instability of the molecule are not uncommon. Developability assessment studies have therefore been devised to identify early during process development problems associated with stability, solubility that is insufficient to meet expected dosing or sensitivity to stress. This set of experiments includes short-term stability studies at 2−8 þC, 25 þC and 40 þC, freeze-thaw studies, limited forced degradation studies and determination of the viscosity of high concentration samples. We present here three case studies reflecting three typical outcomes: (1) no major or unexpected degradation is found and the study results are used to inform early identification of degradation pathways and potential critical quality attributes within the Quality by Design framework defined by US Food and Drug Administration guidance documents; (2) identification of specific degradation pathway(s) that do not affect potency of the molecule, with subsequent definition of proper process control and formulation strategies; and (3) identification of degradation that affects potency, resulting in program termination and reallocation of resources.     

Antagonistic Action of Lactobacilli and Bifidobacteria in Relation to Staphylococcus aureus and Their Influence on the Immune Response in Cases of Intravaginal Staphylococcosis in Mice

The antibacterial activity of Lactobacillus casei IMV B-7280, Lact. acidophilus IMV B-7279, Bifidobacterium longum VK1, and B. bifidum VK2 strains or their various compositions in relation to Staphylococcus aureus in vitro and on models of experimental intravaginal staphylococcosis of mice was determined. It was found that under the influence of these strains and their various compositions, the in vitro growth of Staph. aureus was inhibited, and the number of colonies of Staph. aureus plated from the vagina of infected mice was significantly reduced. The antibacterial activity of these strains separately and in compositions correlated with their ability to improve the performance of the immune response. These strains were the most effective in the following compositions: Lact. casei IMV B-7280-B. longum VK1-B. bifidum VK2. Strains of Lact. casei IMV B-7280, Lact. acidophilus IMV B-7279, B. bifidum VK2, and B. longum VK1 are prospective components of future probiotic drugs efficient in treating staphylococcosis and for immunity correction.     

Molecular insights into the recruitment of TFIIH to sites of DNA damage

XPB and XPD subunits of TFIIH are central genome caretakers involved in nucleotide excision repair (NER), although their respective role within this DNA repair pathway remains difficult to delineate. To obtain insight into the function of XPB and XPD, we studied cell lines expressing XPB or XPD ATPase‐deficient complexes. We show the involvement of XPB, but not XPD, in the accumulation of TFIIH to sites of DNA damage. Recruitment of TFIIH occurs independently of the helicase activity of XPB, but requires two recently identified motifs, a R‐E‐D residue loop and a Thumb‐like domain. Furthermore, we show that these motifs are specifically involved in the DNA‐induced stimulation of the ATPase activity of XPB. Together, our data demonstrate that the recruitment of TFIIH to sites of damage is an active process, under the control of the ATPase motifs of XPB and suggest that this subunit functions as an ATP‐driven hook to stabilize the binding of the TFIIH to damaged DNA.     

Do we live in a quantum world? Advances in multidimensional coherent spectroscopies refine our understanding of quantum coherences and structural dynamics of biological systems

The issue of quantum effects in biological functions reduces to determining the relevant length and/or time scales over which phase relationships (coherence) in the wave properties of matter are conserved and lead to observable interference effects. Recent advances in femtosecond laser-based two-dimensional spectroscopy and coherent control have made it possible to directly determine the relevant timescales of quantum coherence in biological systems and even manipulate such effects, respectively, and also provide direct information on the interactions between the different degrees of freedom (electronic and nuclear) with sufficient time resolution to catch the very chemical processes driving biological functions in action. The picture that is emerging is that there are primary events in biological processes that occur on timescales commensurate with quantum coherence effects.     

Gas-Aggregated Copper Nanoparticles with Long-term Plasmon Resonance Stability

Metal nanoparticles (NPs) possessing localized surface plasmon resonance (LSPR) are of high interest for applications in optics, electronics, catalysis, and sensing. The practically important issue is the stability of the LSPR, which often limits the use of some metals due to their chemical reactivity leading to degradation of the NP functionality. In this work, copper NPs of two distinct sizes are produced by magnetron sputtering gas aggregation. This method ensures formation of the particles with high purity and monocrystallinity, enhancing the chemical inertness and providing a superior time stability of the plasmonic properties. Additionally, a simple UV-ozone treatment, which leads to the formation of an oxide shell around the copper NPs, is found to be an efficient method to prevent following gradual oxidation and assure the LSPR stability in ambient atmospheric conditions for periods over 100 days even for small (10–12 nm in diameter) NPs. The obtained results allow for significant improvement of the competitiveness of copper NPs with gold or silver nanostructures, which are traditionally used in plasmonics.

     

Characteristics of Plasmon Resonance of Gold Nanoparticles in Three-Layer Systems AuNP-Al2O3-PdO(Pd)

Plasmonics - This work deals with plasmonic properties of gold nanoparticles (NP) in the three-layers system comprising this NP, isolating (Al2O3), and conducting (PdO, Pd) layers. A sequence of...