Discovery, Development, Inventions, and Patent Trends on Mobocertinib Succinate: The First-in-Class Oral Treatment for NSCLC with EGFR Exon 20 Insertions

The majority of lung cancers are non-small-cell lung cancer (NSCLC) having a low survival rate. Recent studies have indicated the involvement of epidermal growth factor receptor (EGFR) oncogene mutations like EGFR exon 20 insertions (EGFRex20ins) mutation among NSCLC patients. The response of patients of NSCLC with the EGFRex20ins mutation to the currently available EGFR inhibitor is negligible. Mobocertinib is the first oral treatment that has been approved by the USFDA, on 15 September 2021, to treat NSCLC with the EGFRex20ins mutation. This patent review discusses the inventions and patent literature of mobocertinib that will help the scientific community to develop additional and improved inventions related to mobocertinib. The structure of mobocertinib was first reported in 2015. Therefore, this article covered the patents/patent applications related to mobocertinib from 2015 to 25 October 2021. The patent search revealed 27 patents/patent applications related to compound, method of treatment, salt, polymorph, process, composition, and drug combinations of mobocertinib. The authors foresee an exciting prospect for developing a treatment for NSCLC with EGFRex20ins mutation, and other cancers employing a combination of mobocertinib with other approved anticancer agents. The inventions related to novel dosage forms, processes, and intermediates used in the synthesis of mobocertinib are also anticipated.

Sand-sodium-silicate mixtures grains composition optimization for structuring by steam-microwave solidification method

Mixture sizes of sand-sodium-silicate conglomerates and sodium silicate solute content in them influences on the basic physical and technological indicators of molding and core mixtures structured in steam-microwave environment have been investigated. Sand-sodium-silicate mixture structured by steam-microwave environment (steam-microwave solidification method – SMS-process) composition has been optimized. Standard and generally accepted methods and techniques of molding mixtures investigation have beenused in this study. For mixtures manufacturing have been used: quartz sand brand 1K2O202; sodium silicate solute with silicate modulus of 2.8…3.0 and specific gravity of 1.42…1.44 g/cm3. Quartz sand cladding has been implemented with 0.5 and 2.5% sodium silicate solute (by weight, over 100% sand). Sand-sodium-silicate conglomerates have been scattered in sieves and conglomerates with sizes less than 0.315mm and with sizes from 0.315 to 0.63mm have been used for research. Mixture composition has been optimized according to results of simplex planning and experimental data by simplex triangles constructing and superimposing their formatted images on each other with darkened fields between isolines that do not meet of each parameters required level. To plot simplex lattices, model with simplex lattice plan of incomplete cube in Scheffe’s triple system has been used. For the first time, influence of mixture sand-sodium-silicate conglomerates sizes and sodium-silicate-solute content in them on basic indicators of mold and rod mixtures structured in steam-microwave environment has been established, and their composition has been optimized. Data obtained will be useful in molds and rods structured by SMS-process manufacturing. They will have predictable indicators of properties that correspond to their allowable level. Optimal composition of sand-sodium-silicate mixture, structured by SMS-process, is mixture of quartz sand, part of which passed through sieve with cell of 0.315 mm and have sodium silicate solute content (МSiO2=2.8…3.0, 2=1.42…1.44 g/сm3) in amount of 1.5% (by weight, over 100% quartz sand). Keywords.Sand, silicon silicate solute, steam-microwave solidification, optimization, conglomerates, strength, gas permeability, crushability, density, beam deflection, knockout energy.

Laser Additive Manufacturing of Intermetallic Alloys for High-Temperature Applications

Intermetallic alloys like e.g. Iron-Aluminides, Titanium-Aluminides or Molybdenum- Silizides are prospective materials for high-temperature applications. For additive manufacturing (AM) intermetallic structural materials are particularly challenging due to their high melting points, oxygen susceptibility and low temperature brittleness. The feasibility of manufacturing intermetallic Mo-Si-B alloys with the laser additive manufacturing process of direct energy deposition (DED) is demonstrated and recent results in characterizing rapidly solidified material with respect to correlations between process, composition and microstructures are presented. The possibility to dope the material with Yttrium oxide (Y2O3) for dispersion is successfully demonstrated. Current challenges, e.g. homogenous distribution of alloying elements and applicability are addressed.

Dynamic Programming Algorithms Applied to Musical Counterpoint in Process Composition: An Example Using Henri Pousseur’s Scambi

The Needleman-Wunsch process is a classic tool in bioinformatics, being a dynamic programming algorithm that performs a pairwise alignment of two input biological sequences, either protein or nucleic acid. A distance matrix between the tokens used in the sequences is also required as input. The distance matrix is used to generate a positional pairwise similarity matrix between the input sequences, which is in turn used to generate a dynamic programming matrix. The best path through the dynamic programming matrix is navigated using a traceback procedure that maximises similarity, inserting gaps as necessary. Needleman-Wunsch can align both nucleic acids or proteins, which use alphabets of size 4 and 20 tokens respectively. It can also be applied to any other kind of sequence where distance matrices can be specified. Here, we apply it to chains of Pousseur’s Scambi electronic music fragments, of which there are 32, and which Pousseur categorised by their sonic properties, thus permitting the consecutive construction of distance, similarity and dynamic programming matrices. Traceback through the dynamic programming matrix thus produces contrapuntal duet compositions in which two Scambi chains are played in the maximally euphonious manner, providing also an illustration of the principles of biological sequence alignment in sound.

Scambi fushi tarazu: A Musical Representation of a Drosophila Gene Expression Pattern

The term Bio-Art has entered common usage to describe the interaction between the arts and the biological sciences. Although Bio-Art implies that Bio-Music would be one of its obvious sub-disciplines, the latter term has been much less frequently used. Nevertheless, there has been no shortage of projects that have brought together music and the biological sciences. Most of these projects have allowed the biological data to dictate to a large extent the sound produced, for instance the translation of genome or protein sequences into musical phrases, and therefore may be regarded as process compositions. Here I describe a Bio-Music process composition that derives its biological input from a visual representation of the expression pattern of the gene fushi tarazu in the Drosophila embryo. An equivalent pattern is constructed from the Scambi portfolio of short electronic music fragments created by Henri Pousseur in the 1950s. This general form of the resulting electronic composition follows that of the fushi tarazu pattern, while satisfying the rules of the Scambi compositional framework devised by Pousseur. The range and flexibility of Scambi make it ideally suited to other Bio-Music projects wherever there is a requirement, or desire, to build larger sonic structures from small units.

ADSORPTION OF Pb(II) BY POLYANILINE/SILICA GEL COMPOSITE: KINETICS AND ISOTHERM STUDIES

Research on the study of kinetics and isotherm adsorption of Pb(II) by polyaniline/silica gel (PANI/SiO2) composite from glass waste has successfully been done. The polymerization of silica gel was prepared by sol-gel process. Meanwhile, PANI/SiO2 composite was prepared using sulfuric acid (H2SO4) as its dopants and hydrogen peroxide (H2O2) for oxidation process. Composition of oxide compound in PANI/SiO2 composite was analyzed by X-Ray Fluorosence (XRF) and Gas Sorption Analyzer (GSA). Adsorption of Pb(II) was carried out by contacting PANI/SiO2 with Pb(NO3)2 solution for 20, 40, 60 and 80 minutes, with concentrations of 150, 200, 250, 300, 350 and 400 mg/L. The optimum contact time was reached at 40 minutes. This adsorption followed pseudo-second order model with R2= 0.996. The first optimum adsorption capacity was reached in the concentration of 250 mg/L. Isotherm adsorption followed Langmuir models with R2= 0.954 (monolayer capacity= 51.02 mg/g).