Monoclonal antibodies play an increasingly important role for the development of new drugs across multiple therapy areas. The term 'developability' encompasses the feasibility of molecules to successfully progress from discovery to development via evaluation of their physicochemical properties. These properties include the tendency for self-interaction and aggregation, thermal stability, colloidal stability, and optimization of their properties through sequence engineering. Selection of the best antibody molecule based on biological function, efficacy, safety, and developability allows for a streamlined and successful CMC phase. An efficient and practical high-throughput developability workflow (100 s-1,000 s of molecules) implemented during early antibody generation and screening is crucial to select the best lead candidates. This involves careful assessment of critical developability parameters, combined with binding affinity and biological properties evaluation using small amounts of purified material (<1 mg), as well as an efficient data management and database system. Herein, a panel of 152 various human or humanized monoclonal antibodies was analyzed in biophysical property assays. Correlations between assays for different sets of properties were established. We demonstrated in two case studies that physicochemical properties and key assay endpoints correlate with key downstream process parameters. The workflow allows the elimination of antibodies with suboptimal properties and a rank ordering of molecules for further evaluation early in the candidate selection process. This enables any further engineering for problematic sequence attributes without affecting program timelines.

Pan-microbial inactivation technologies that do not require high temperatures, reactive chemical compounds, or UV radiation could address gaps in current infection control strategies and provide efficient sterilization of biologics in the biotechnological industry. Here, we demonstrate that femtosecond (fs) laser irradiation of resonant gold nanoparticles (NPs) under conditions that allow for E-field mediated cavitation and shockwave generation achieve an efficient plasmon-enhanced photonic microbial pathogen inactivation. We demonstrate that this NP-enhanced, physical inactivation approach is effective against a diverse group of pathogens, including both enveloped and nonenveloped viruses, and a variety of bacteria and mycoplasma. Photonic inactivation is wavelengthdependent and in the absence of plasmonic enhancement from NPs, negligible levels of microbial inactivation are observed in the near-infrared (NIR) at 800 nm. This changes upon addition of resonant plasmonic NPs, which provide a strong enhancement of inactivation of viral and bacterial contaminants. Importantly, the plasmon-enhanced 800 nm femtosecond (fs)pulse induced inactivation was selective to pathogens and was obtained without specific targeting of the NPs to the pathogens. No measurable damage was observed for antibodies included as representative biologics under identical conditions.

The competition between toroidal and rod-like conformations as possible ground states for DNA condensation is studied as a function of the stiffness, the length of the DNA, and the form of the long-range interactions between neighboring molecules, using analytical theory supported by Monte Carlo simulations. Both conformations considered are characterized by a local nematic order with hexagonal packing symmetry of neighboring DNA molecules, but differ in global configuration of the chain and the distribution of its curvature as it wraps around to form a condensate. The long-range interactions driving the DNA condensation are assumed to be of the form pertaining to the attractive depletion potential as well as the attractive counterion induced soft potential. In the stiffness-length plane we find a transition between rod-like to toroid condensate for increasing stiffness at a fixed chain length L. Strikingly, the transition line is found to have a L(1/3) dependence irrespective of the details of the long-range interactions between neighboring molecules. When realistic DNA parameters are used, our description reproduces rather well some of the experimental features observed in DNA condensates.

Cationic polyacrylamide (CPAM) emulsifier is widely applied in the wastewater treatment industry, mining industry, paper industry, cosmetic chemistry, etc. However, optimization of input parameters in the synthesis of CPAM by using the traditional approach (i.e., changing one factor while leaving the others fixed at a particular set of conditions) would require a long time and a high cost of input materials. Onsite mass production of CPAM requires fast optimization of input parameters (i.e., stirring speed, reaction temperature and time, the amount of initiator, etc.) to minimize the production cost of specific–molecular–weight CPAM. Therefore, in this study, we synthesized CPAM using reverse emulsion copolymerization, and proposed response surface models for predicting the average molecular weight and reaction yield based on those input parameters. This study offers a time–saving tool for onsite mass production of specific–molecular–weight CPAM. Based on our response surface models, we obtained the optimal conditions for the synthesis of CPAM emulsions, which yielded medium–molecular–weight polymers and high conversion, with a reaction temperature of 60–62 °C, stirring speed of 2500–2600 rpm, and reaction time of 7 h. Quadratic models showed a good fit for predicting molecular weight (Adj.R2 = 0.9888, coefficient of variation = 2.08%) and reaction yield (Adj.R2 = 0.9982, coefficient of variation = 0.50%). The models suggested by our study would benefit the cost–minimization of CPAM mass production, where one could find optimal conditions for synthesizing different molecular weights of CPAM more quickly than via the traditional approach.

Human Arginase 1 (hArg1) is a metalloenzyme that catalyzes the hydrolysis of l-arginine to l-ornithine and urea, and modulates T-cell-mediated immune response. Arginase-targeted therapies have been pursued across several disease areas including immunology, oncology, nervous system dysfunction, and cardiovascular dysfunction and diseases. Currently, all published hArg1 inhibitors are small molecules usually less than 350 Da in size. Here we report the cryo-electron microscopy structures of potent and inhibitory anti-hArg antibodies bound to hArg1 which form distinct macromolecular complexes that are greater than 650 kDa. With local resolutions of 3.5 Å or better we unambiguously mapped epitopes and paratopes for all five antibodies and determined that the antibodies act through orthosteric and allosteric mechanisms. These hArg1:antibody complexes present an alternative mechanism to inhibit hArg1 activity and highlight the ability to utilize antibodies as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.