Abstract: Formulated and/or co-formulated nanocarriers (e.g., LNPs and/or SLNPs) comprising PD-1 Prodrugs and methods of making the nanocarriers are disclosed herein. The PD-1 Prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit PD-1-L1/L2. The PD-1 Prodrugs can be formulated and/or co-formulated into a nanocarrier to provide a method of treating cancer, immunological disorders, and other disease by utilizing a targeted drug delivery vehicle.

Abstract: An object is to provide a technique of forming CpG oligonucleotides and hydrophobized polysaccharides into complexes. This object is achieved by a complex comprising a modified CpG oligonucleotide containing a hydrophobic group A having a sterol skeleton, and a modified polysaccharide containing a hydrophobic group B.

Abstract: The invention relates to novel prodrugs or conjugates of the general formula (Ia) in which La, n, R and D have the definitions given in the description and which have a structural motif reduced to an asparagine derivative as cleavage site for tumour-associated proteases such as legumain, in which cytotoxic drugs, for example kinesin spindle protein inhibitors, are released by legumain cleavage, and to the use of these prodrugs or conjugates for treatment and/or prevention of diseases, and to the use of these prodrugs or conjugates for production of medicaments for treatment and/or prevention of diseases, especially of hyperproliferative and/or angiogenic disorders, for example cancers. Reduction of the legumain-cleavable substrate peptide sequence to an asparagine derivative as structural motif, as a result of slowed legumain cleavage, achieves an increase in stability in the lysosomes of healthy organs while simultaneously maintaining the high anti-tumour effect.

Abstract: The invention relates to prostate specific membrane antigen humanized antibodies (anti-PSMA) and anti-PSMA antibody drug conjugates. The invention also relates to methods and compositions for using anti-PSMA antibody drug conjugates in inhibiting, preventing or treating PSMA related diseases or cancers.

Abstract: Methods for producing and screening for antibodies that specifically bind to glycosylated immune checkpoint proteins (ICPs) relative to non-glycosylated ICPs are provided. Such antibodies recognize specific epitopes of glycosylated ICPs and can prevent or block the binding of a glycosylated ICP with its ligand, such as another ICP, and can inhibit the interactions between the two proteins that can lead to immunosuppression, as exemplified by the human PD-L1/PD-1 interaction. By way of specific example, human PD-L1 and PD-1 polypeptides comprising glycosylated amino acid residues within their extracellular domains are provided for generating anti-glycosylated PD-L1 or anti-glycosylated PD-1 antibodies that specifically bind PD-L1 or PD-1, respectively, and inhibit the PD-L1/PD-1 interaction. The antibodies produced and selected by the methods are especially useful as cancer therapeutics for disrupting, blocking, or neutralizing the ICP system and specific ICP interactions therein.

Abstract: A targeted nanocarriers also termed nanomedicines and methods of preferentially, or actively, targeting and delivering a tool for gene transfer or genome editing (i.e., a plasmid or a restriction enzyme such as a zinc finger nuclease, a CRISPR/Cas system, or a TALEN) or a tool for gene silencing or post-transcriptional regulation of gene expression (i.e., a microRNA, a siRNA, a mRNA, an antisense oligonucleotide, or a sense oligonucleotide) to a range of mammalian cell species. Cell specific targeting is achieved by using nanocarriers featuring suitable targeting anchors having a targeting moiety that can be a carbohydrate, an antibody or an antibody fragment, a non-antibody protein derivative, an aptamer, a lipoprotein or a fragment thereof, a peptidoglycan, a lipopolysaccharide or a fragment thereof, or a CpG DNA. Such targeting anchors may or may not include a polymeric spacer like polyethylene glycol.

Abstract: The present invention provides biodegradable, biomimetic particles for interacting with cells, including immune cells. In various embodiments, the particles comprise a polymer blend comprising a polyester, such as poly(lactic-co-glycolic acid) (PLGA) and a polyamine, such as poly(beta-amino ester) (PBAE). The particles further comprise, on their surface, one or more ligands for one or more cell surface receptor(s) or cell surface molecule(s). In some embodiments, the cell surface receptor or cell surface molecule is on an immune cell, such as a lymphocyte (T cell or B cell), natural killer cell, dendritic cell, or other cell of the immune system or tumor microenvironment.

Abstract: The present disclosure describes compositions, preparations, nanoparticles (such as lipid nanoparticles), and/or nanomaterials and methods of their use.

Abstract: An inhibitor of p53 activation for use in haematopoietic stem and/or progenitor cell gene therapy, preferably wherein the inhibitor is an inhibitor of p53 phosphorylation, more preferably an inhibitor of p53 Serine 15 phosphorylation.

Abstract: The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

Abstract: The present invention relates to methods and compositions for inhibiting metastatic spread of cancer and/or inhibiting progression of pre-existing metastatic disease in a subject using L1CAM inhibition.

Abstract: Compounds, systems, and methods are provided for the design and assembly of a non-invasive, analyte sensing dressing. The dressing can be therapeutic. The dressing includes a sensor and a matrix. The sensor is capable of detecting analytes such as molecular oxygen, carbon dioxide, nitric oxides, dissolved analytes in plasma, and hydrogen ions. The matrix is at least partially permeable to the analyte. The device emits a detectable signal when the sensor is excited in the presence of the analyte. In one version of the dressing, the sensor includes a meso-unsubstituted metallated porphyrin that is sensitive towards oxygen. The metallated porphyrin can be excited when illuminated at a first wavelength, followed by emission of phosphorescence at a second wavelength whose intensity can be used as an indicator for oxygen concentration.

Abstract: Activity-based probe compounds for use in labeling a cysteine protease are provided. The compounds are targeted to the protease through a specific targeting element. The compounds additionally include a detectable element, such as a fluorescent label, a radiolabel, or a chelator. In some cases, the compounds additionally include a quenching element that is released upon reaction with the protease. Also provided are compositions comprising the compounds and methods for using the compounds, for example in labeling a protease in an animal and in visualizing a tumor in an animal.

Abstract: The invention relates to a process of producing a dental zirconia restoration, the dental zirconia restoration having an outer and an inner surface, the process comprising the step of firing a porous dental zirconia restoration and a glass until the porous dental zirconia restoration is sintered, the glass being located during the firing step on at least a portion of the outer surface of the porous dental zirconia restoration, wherein the zirconia material of the porous dental zirconia restoration and the glass are selected such that during the firing step the glass infiltrates the pores of the porous dental zirconia restoration to an extent of not more than 5 ?m in depth. The invention also relates to a sintered dental zirconia restoration obtainable by such a process and a kit of parts comprising a porous dental zirconia mill blank and a surface treating agent containing a glass for use in such a process.

Abstract: A method for producing a powder lead is disclosed, wherein at least one colourant, at least one filler and at least one binder are mixed with a carrier liquid, leads are shaped from the wet compound, the leads shaped in step b) are guided through a chamber in which they are exposed to a pulverulent covering agent, and the powdered leads are guided into a drying apparatus and dried therein.

Abstract: A personal cleansing comprising, in an aqueous continuous phase: a total amount of anionic surfactant, amphoteric surfactant and zwitterionic surfactant consisting of: (i) from 3 wt % to less than 7 wt %, by weight of the total composition at 100% activity, of an alkyl ether sulfate anionic surfactant of general formula (I): R—O—(CH2CH2—O)n—SO3?M+ in which R is selected from linear or branched alkyl groups having from 10 to 14 carbon atoms and mixtures thereof; n is a number that represents the average degree of ethoxylation and ranges from 1.5 to 2.

Abstract: The compositions of various embodiments include a tocopherol phosphate mixture (TPM) comprising a liposome having a lipid bilayer and an internal aqueous compartment, a lipophilic ingredient, a polar solvent system, an alcohol, a base, and a water soluble phase, wherein the liposome is made of a tocopherol phosphate derivative, wherein the lipophilic ingredients are entrapped in the lipophilic bilayer of the liposome, and wherein a water soluble ingredient is dissolved in the water soluble phase and is in the internal compartment of the liposome. The methods include improving the look of skin particularly of the neck and décolletage, increasing expression of an extracellular matrix proteins in skin, improving a keloid scar in a subject, and improving aging skin. Additionally, methods for preparing the compositions are described herein.

Abstract: Matrix compositions comprising structurally diverse matrix particles (1) formed from at least five different types of primary particles distinguishable from one another due to different characteristics, shape characteristics, or both, (2) that constitute 15-50% of the matrix composition by weight, (3) that comprise or more types of particle agglomerates, (4) where at least 33% of the weight concentration of the matrix particle mixture being composed of UV-protectant metal oxide particles having a minimum particle size of over 100 nm, (5) where scanning electron microscope analysis of the composition fails to identify any significant number of discrete matrix particles of having a size of 100 nm or less, and (6) the composition exhibits one or more of sun protection factor (SPF) of at least 30, a critical wavelength of at least 370 nm, UVA/UVB ratio of at least 0.333, and a UVA1 to UV ratio of at least 0.7.

Abstract: The present invention relates to sulfate-free aqueous personal care composition comprising from about 0.2 pbw to about 15 pbw of a derivatized cationic guar comprising cationic substituent groups and non ionic substituent groups, at least 0.05 pbw of an oil and from about 2 pbw to about 20 pbw of a surfactant system comprising at least one lauramphoacetate, and one sulfosuccinate. It is also directed toward the use of such a composition for washing keratin substrates, in particular the hair or the scalp.

Abstract: An oil-in-water emulsion composition for skin includes 0.2 to 2.5% by mass of polyisobutene having a relative mass in a range of 30,000 to 100,000. The composition is applied to skin except for a lip.

Abstract: The present invention relates to avobenzone-dendrimer conjugates comprising: a polyamide dendrimer conjugated with 1 to 18 units of avobenzone. Also disclosed are sunscreen formulations comprising an avobenzone-dendrimer conjugate and a dermatologically acceptable vehicle.

Abstract: A method for topically treating skin is disclosed. The method can include applying to skin a composition that includes tetrahexyldecyl ascorbate, Morus alba fruit extract, Acmella oleracea extract, and retinol, wherein topical application of the composition treats the skin.

Abstract: A transdermal formulation for the delivery of one or more active agents to a subject is provided. The formulation can be applied to the treatment of various diseases or conditions associated with an elevated CD38 level.

Abstract: The present disclosure provides methods of treating inflammation of the upper gastrointestinal tract, especially the esophagus, by administering an oral corticosteroid. In some cases, the methods include treating eosinophilic esophagitis (EoE) by administering an oral corticosteroid in an induction phase and a maintenance phase to improve peak eosinophilic counts and symptoms. In embodiments, the methods include treating EoE by administering the oral corticosteroid at nighttime and/or while the patient is lying down.

Abstract: The present invention provides a use of platelet dry powder (PDP) for relieving inflammation or injury in an airway portion, wherein per gram of platelet dry powder (PDP) comprises at least 100,000 platelets.

Abstract: The present invention relates to a composition comprising a mixture of empty liposomes, wherein said mixture of empty liposomes comprises (a) a first empty liposome comprising cholesterol, wherein the amount of cholesterol is at least 30% (weight per weight); and (b) a second empty liposome comprising sphingomyelin, for use in adjunctive treatment of 5 pneumonia in a human patient.

Abstract: Irinotecan phospholipid liposomes with improved storage stability are provided, with related methods of treatment and manufacture. The irinotecan liposomes can have reduced formation of lyso-phosphatidylcholine (lyso-PC) during storage, and prior to administration to a patient.

Abstract: The present disclosure relates to methods for preparing RNA lipoplex particles for delivery of RNA to target tissues after parenteral administration, in particular after intravenous administration, and compositions comprising such RNA lipoplex particles. The present disclosure also relates to methods which allow preparing RNA lipoplex particles in an industrial GMP-compliant manner. Furthermore, the present disclosure relates to methods and compositions for storing RNA lipoplex particles without substantial loss of the product quality and, in particular, without substantial loss of RNA activity.

Abstract: Provided herein is technology relating to incorporation of drugs into liposomes and particularly, but not exclusively, to methods for incorporating drugs into liposomes using a weak base and related compositions.

Abstract: Disclosed herein are therapeutic constructs including a delivery particle, at least one mitotic kinase inhibitor, and at least one immune checkpoint inhibitor. Also disclosed are therapeutic constructs including a mitotic kinase inhibitor, an immune checkpoint inhibitor, and a chemical linker. These therapeutic constructs cause cancer death by both therapeutic and immune effects and promote targeted delivery of more therapeutics to the surviving cancer cells in a positive feed-back loop. They enhance therapeutic index of free drugs and can be used intratumorally or systemically. This strategy can treat broad cancer types and is particular useful for cancer without obvious receptors for cancer-targeted delivery of otherwise toxic therapeutics.

Abstract: The present application provides an orally-disintegrating tablet having excellent tablet hardness and disintegrability. The present application further provides a method of producing a disintegrative particulate composition including three components consisting of a first disintegrator component of an acid-type carboxymethylcellulose, a second disintegrator component and an excipient. The method includes a first wet granulation step using any two of the three components, and a second wet granulation step using granules obtained in the first wet granulation step and the remaining one component of the three components not used in the first wet granulation step. The production method may further includes a crystalline cellulose as a fourth component or a third step of mixing a crystalline cellulose into granules obtained in the second wet granulation step. Disintegrative particulate compositions obtained by these methods are also disclosed.

Abstract: The present invention relates to a pharmaceutical composition comprising an HDAC inhibitor, a pharmaceutically acceptable acid or salt thereof or a mixture of the acid and salt, provided both in a immediate release form and in an extended release form wherein 70-90 weight % of the HDAC inhibitor is provided in the immediate release form and the remainder of the HDAC inhibitor is provided in the extended release form. In further aspects the present invention relates to a kit comprising a number of doses of an HDAC inhibitor, a pharmaceutically acceptable acid or salt thereof or a mixture of the acid and salt thereof provided both in an immediate release form and in an extended release form.

Abstract: In this specification, a method for the manufacture of solid dosage forms is disclosed. The method includes extruding a plasticized matrix through an exit port of an extrusion channel to form one or more plasticized fibers, structuring said fibers to a three dimensional structural network by patterning on a translating or rotating stage, and solidifying the patterned structure.

Abstract: A process for producing superabsorbent particles by polymerizing a monomer solution or suspension, comprising drying of the resultant aqueous polymer gel in an air circulation belt drier, grinding, classifying, and optionally thermal surface postcrosslinking, wherein the aqueous polymer gel is introduced into the air circulation belt drier by means of an oscillating conveyor belt, the underside of the revolving conveyor belt is freed of adhering polymer gel by means of at least one stripper device, and the underside of the revolving conveyor belt is sprayed with water.

Abstract: Provided is an air conditioner including an irradiation unit that irradiates an irradiation area of an indoor unit with ultraviolet rays, a temperature detection unit that detects an ambient temperature of the irradiation unit, and a control unit that controls an irradiation time of the irradiation unit. The control unit controls the irradiation time in accordance with the ambient temperature detected by the temperature detection unit.

Abstract: Implant devices are coated with biologically active compounds, in particular with plant extracts from vinification residues. The implant devices are bone implants, and in particular dental implants. A method for functionalizing a surface of an implant device is includes the steps of a) optionally, treating the surface of the implant device with air, oxygen, argon, nitrogen plasma, and plasma capable of removing the surface layer of hydrocarbon contamination, b) treating the surface of the implant with an amine substrate, c) treating the surface of the implant resulting from step b), alternatively with a marcs extract, and drying the functionalized surface, or by co-adsorbing a marcs extract and hyaluronic acid, and drying the functionalized surface, or by adsorbing hyaluronic acid and post-adsorbing a marcs extract, and drying of the functionalized surface.

Abstract: The composition comprises a polyol crosslinked with a) a multifunctional epoxide; or b) an epihalohydrin; or c) a molecule or crosslinker mixture comprising multiple epihalohydrin and/or epoxide groups or molecules. The composition has a number N1 of effective ether crosslinks per crosslinker molecule as calculated by subtracting 1 from the average number of distinct polyol repeat units bound per crosslinker molecule. The remaining reactive groups on the crosslinker are ineffective in crosslinking and provide a number N2 of pendant groups per crosslinker molecule. Among the N2 groups per crosslinker there are N3 groups per crosslinker that are unreacted or otherwise retain reactivity against nucleophiles. The relationship between N1 and N2 is: N1>0.35 (N1+N2).

Abstract: Systems and methods for the automated demineralization of bone and decellularization of soft tissue include a mixing assembly communicatively coupled with a control and reporting system. The mixing assembly includes a housing that supports a cannister sub-assembly forming a mixing chamber having a reagent inlet, a reagent outlet, and an internal fluid agitator. A motor is operably coupled with the agitator and configured to spin the agitator in first and second directions relative to the cannister, thereby agitating fluid contained within the mixing chamber. At least one pump is configured to progressively inject measured quantities of a plurality of reagents into the mixing chamber. The associated control and reporting system includes a user terminal that displays a graphical user interface enabling a user to initiate an automated demineralization or decellularization procedure in which the mixing assembly demineralizes tissue placed within the mixing chamber. Other embodiments are also disclosed.

Abstract: Disclosed is a method of regenerating a skin wound using a perforated dermal regeneration matrix combined with autograft in a single-stage procedure. The size of the perforations and the spacing between perforations in the dermal matrix are selected to facilitate drainage, encourage vessel growth and minimize scar tissue formation.

Abstract: A biodegradable matrix for preventing post-surgical adhesions, in particular after soft tissue repair in abdominal surgery within the body of a mammal is disclosed. The matrix includes a top layer made of a first biocompatible polymer material and a bottom layer made of a second biocompatible polymer material. The first polymer material comprises poly(lactic acid) as a main component and the second polymer material comprises as a main component at least one polymer selected from the group consisting of poly(glycolic acid), poly(lactic acid), poly(glycolic acid-lactic acid) and mixtures thereof, wherein the poly(lactic acid)content of the first polymer material is higher than in the second polymer material, and wherein both layers are formed as porous scaffolds with the top layer being hydrophilic, having a water contact angle of less than 75°, and the bottom layer being hydrophobic, having a water contact angle of more than 90°.

Abstract: A dissolvable composition is disclosed. The composition includes a first material (e.g., an anode), a second material (e.g., a cathode), and a third material (electrolytic material). The third material is reactive with water to form an electrolyte. The first material and the second material are electrochemically different such that the first material and the second material are capable of galvanic reaction in the presence of water and electrolytes. Also disclosed are tools or other apparatus made from the composition, as well as processes, systems, and apparatus for making and using such compositions, tools, and other apparatus.

Abstract: An isolation section assembly includes a section housing defining an interior space. The section housing includes a door with access to the interior space. The isolation section assembly includes an enclosure abutting the door. The airlock enclosure defines an interior airlock space. The interior airlock space is configured and adapted to be at a negative pressure relative to a cabin area. An air recirculation system in fluid communication with at least one of the interior space of the section housing or the interior airlock space.

Abstract: A breast pump device (1) comprises an expression kit (2), a vacuum unit (3), and a conduit (5) for establishing an air path between an air outlet (27) of the expression kit (2) and an air inlet (35) of the vacuum unit (3). The expression kit (2) is equipped with a barrier portion (26) for preventing milk leakage from the expression kit (2) towards the hose (5) and the vacuum unit (3). In case some droplets of milk enter the barrier portion (26) and/or drawn through the barrier portion (26) by an ongoing pumping action, aspects of the behavior of the motor (32) for driving the pump (31) are influenced, and the insight that this happens is used for terminating operation of the motor (32) as soon as a too large deviation of one or more operational characteristics of the motor (32) with respect to a reference is found.

Abstract: The present invention relates to a breast shield used in a breast pump configured to pump human breast milk. The breast shield includes a hard base portion including both ends and a sidewall connecting the both ends to include a hollow in the base portion in which the both ends are open and a human mamma is accommodated in the hollow through any one of the both ends, through holes passing through the sidewall, and a soft portion configured to surround an outer surface and an inner surface of the base portion, prevent an airflow through the through holes, and have flexibility.

Abstract: The present disclosure provides a milk distribution system, components thereof, and methods of use thereof.

Abstract: A blood circuit assembly for a dialysis unit may include an organizing tray, a pair of pneumatic pumps mounted to the organizing tray for circulating blood received from a patient through a circuit including a dialyzer unit and returned to the patient, an air trap mounted to the organizing tray arranged to remove air from blood circulating in the circuit, a pair of dialyzer connections arranged to connect to the inlet and outlet of a dialyzer unit, and a pair of blood line connectors, one inlet blood line connector for receiving blood from the patient and providing blood to the pneumatic pumps and the other outlet blood line connector for returning blood to the patient.

Abstract: Dialysis systems and methods for operating dialysis machines (e.g., peritoneal dialysis machines) for conducting dialysis treatments are disclosed. The dialysis system may include a dialysis machine for transferring dialysate to a patient from a dialysate bag. The dialysate may flow from the dialysate bag through a disposable cartridge or cassette positionable within the dialysis machine. A filter may be included in, coupled to, etc., the dialysis machine. In use, the filter may be configured to filter out air content from the dialysate. In some embodiments, the filter may be incorporated into and/or operatively coupled to the disposable cartridge or cassette inserted into the dialysis machine.

Abstract: A device for the continuous monitoring of blood characteristic quantities in an external cardiovascular supporting circuit, said circuit including a venous line which conveys blood from the patient to an oxygenator, and along which at least one pump is arranged, and an arterial line which returns blood from the oxygenator to the patient, where said oxygenator comprises at least one blood inlet port connected to said venous line and at least one blood outlet port connected to said arterial line, at least one inlet channel and at least one outlet channel of a work gas intended to supply oxygen to the blood and/or to remove carbon dioxide from the same.

Abstract: A circuit for measuring the conductivity of a medical fluid, the circuit comprising: a data collecting cell through which a medical fluid is configured to flow; an input voltage source that provides an input voltage to the data collecting cell; a voltage measurement unit configured to measure the input voltage and an output voltage of the data collecting cell; and a switch in communication with the voltage measurement unit, the switch configured to switch between a first state in which the voltage measurement unit is configured to measure the input voltage and a second state in which the voltage measurement unit is configured to measure the output voltage of the data collecting cell.

Abstract: A priming sensor for a medical fluid delivery device is disclosed. In an example, the priming sensor includes light emitters and a detector. The detector is configured to detect light emitted by the emitters that interacts with a patient tube connected to the priming sensor. A processor of a medical fluid delivery device causes the emitters to operate in a sweep pattern during a sweep period. The processor receives output data from the detector that is indicative of light detected during the sweep period. The processor creates an output waveform corresponding to the sweep period based on the output data and compares the output waveform to at least one reference waveform to determine one of (a) a no-tube state, (b) a dry tube state, or (c) a wet tube state. The processor provides an output indicative of the comparison for operation of the medical fluid delivery device.