Abstract: Specific binder-drug conjugates (ADCs) of kinesin spindle protein inhibitors, effective metabolites of these ADCs, processes for preparing these ADCs, the use of these ADCs for the treatment and/or prevention of diseases and to the use of these ADCs for preparing medicaments for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases, are described.

Abstract: The present invention provides improved methods for formulating therapeutic compositions comprising an antibody drug conjugate (“ADC”) that reduce potency variability between batches of ADC and provide for administration of such therapeutic compositions within a narrow intended range.

Abstract: Antisense oligomers complementary to a selected target site in the human dystrophin gene to induce exon 52 skipping are described.

Abstract: Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 52 skipping are described.

Abstract: The response of subjects suffering from cancer to MAPK inhibitors is dramatically impaired by secondary resistances and rapid relapse. So far, the molecular mechanisms driving these resistances are not completely understood. The inventors show that expression of 10 SLITRK6 (SLIT and NTRK-like family, member 6) is induced by a MAPK inhibitor (e.g. Vemurafenib) and the inhibition of its induction in presence of the MAPK inhibitor induces synthetic lethality. Thus, the only inhibition of SLITRK6 by an inhibitor of activity or expression should potentiate the antitumor effect of the MAPK inhibitors and avoid the emergence of a resistance to those compounds. Furthermore the specific expression of 15 SLITRK6 also paves the way of strategies based on depletion of the residual cancer cells by targeting them with anti-SLITRK6 antibodies capable of mediating ADCC or antibody-drug conjugates binding to SLITRK6.

Abstract: A system and method configured to achieve hydrogel particle treatment for the reduction of metastatic burden in an immunocompetent syngeneic mouse model is described. The system seeks to achieve methodic optimization for the extraction and purification of extracellular vesicles (EVs) from cultured cells as well as from fresh breast cancer interstitium. Similarly, the system provides for lymph node remodeling by human breast cancer EVs in a humanized mouse model. Hydrogel particles are employed to convey cytokine releasing and EV-displaying treatment to afflicted bodies.

Abstract: Elastin-like polymers (ELP) are shown to demonstrate dynamic behavior atop silica, similar to visco-elastic polymer dewetting. A combination of multiple factors are shown to contribute to this behavior including the hydrophilicity of the silica preventing the adsorption of ELP, the formation of a salt layer between ELP and silica, and the ability of the silica and salt layer to hold on to minute amounts of water for prolonged periods. Further, the addition of a polyethyleneimine (PEI) block to the terminal end of ELP allows the particle radius as well as LCST to be controlled by changing any combination of polymer concentration, NaCl concentration, and pH. The addition of the PEI block also provides the ability to crosslink the copolymers and achieve a stable particle radius after formation in harsh environments.

Abstract: The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices.

Abstract: Described herein are lipid nanoparticles comprising cationic lipids and other lipids and also comprising engineered nucleases facilitate transfer of nucleic acids to cells.

Abstract: The invention relates to chimeric AAV capsids targeted to the central nervous system, virus vectors comprising the same, and methods of using the vectors to target the central nervous system. The invention further relates to chimeric AAV capsids targeted to oligodendrocytes, virus vectors comprising the same, and methods of using the vectors to target oligodendrocytes.

Abstract: Polynucleotides and vectors can be used for the expression of a transgene in cells, such as liver cells. The expression of the transgene from the polynucleotides and vectors can be useful in gene therapy. Various methods can be used for expressing the transgene from the polynucleotides and vectors in liver cells.

Abstract: The present invention relates to a composition for photodynamic therapy of cancer diseases using a gene expressing a fluorescent protein and a photosensitizer, and a photodynamic therapy method using the same. More specifically, the present invention provides a composition for photodynamic therapy capable of selectively killing cancer cells only without affecting normal cells by treating the cancer cells, into which various fluorescent proteins have been introduced, with a photosensitizer and then irradiating a light source to the cancer cells, and a photodynamic therapy method using the same.

Abstract: The presently disclosed subject matter provides compositions and methods for the expression of CRISPR guide RNAs using the H1 promoter. In particular, compositions and methods are provided for the use of the H1 promoter to express CRISPR guide RNA (gRNA) with altered specificity of the 5? nucleotide, as well as use of the H1 promoter sequence as a bidirectional promoter to express Cas9 nuclease and the gRNA simultaneously. Compositions and methods are also provided for the expression and regulation of gRNA expression in vivo through the use of RNA ribozymes and regulatable aptazymes.

Abstract: The present disclosure provides materials and methods for treating a patient with one or more conditions or disorders associated with COL7A1 whether ex vivo or in vivo. For example, the present disclosure provides materials and methods for treating a patient with Dystrophic Epidermolysis Bullosa (DEB). Also provided are materials and methods for editing a COL7A1 gene in a cell by genome editing. The present disclosure also provides materials and methods for altering the contiguous genomic sequence of a COL7A1 gene in a cell. In addition, the present disclosure provides one or more gRNAs for editing a COL7A1 gene. Also provided are therapeutics comprising at least one or more gRNAs for editing a COL7A1 gene. In addition, the present disclosure provides therapeutics for treating patients with a COL7A1 related condition or disorder.

Abstract: The present invention relates to the formulation of adenoviral vectors in sorbitol containing compositions in combination with a further amorphous sugar, its formulation as well as a method for obtaining a dried composition.

Abstract: The present invention relates to a compound or a pharmaceutically acceptable salt thereof having a chemical structure comprising: (A) at least one motif specifically binding to cell membranes of neoplastic cells; (B) at least one chelator moiety of radiometals; and (C) at least one dye moiety; wherein said compound has a molecular weight of not more than 5 kDa. Further, the invention refers to a method for producing such compound and to the in vivo and in vitro uses thereof.

Abstract: Disclosed are methods, compositions of matter, and protocols useful for the detection of altered cells in a patient. Immune cells capable of clonal expansion are engineered to produce a soluble signal upon activation and/or clonal expansion. The cells may possess a suicide gene, inducible upon administration pharmacological or light/radiation activatable, so as to eliminate the cells from body when desired. In another embodiment, immune cells produce a localized marker, the marker being visible with imaging technology. In other embodiments cells capable of non-clonal expansion are utilized. The disclosure provides means of utilizing the immunosurveillance properties of immune cells to diagnose and localize diseases associated with alteration of host cells.

Abstract: Disclosed herein are complexes of gadolinium metal, ligand and meglumine that are substantially free of non-aqueous solvents. In particular, solvent-free complexes of 1) gadopentetate dimeglumine and 2) gadoterate meglumine are disclosed and methods of their preparation are disclosed. In addition, methods are disclosed for purifying reactants, monitoring and controlling pH, quantifying the free gadolinium content, quantifying the concentration of gadolinium-ligand complex in aqueous solution, and procedures for producing a drug product in one step. The one step process eliminates the need to dry the gadolinium-ligand complex, which is typically highly hygroscopic. The one step process includes purification steps that do not require the use of non-aqueous solvents.

Abstract: Provided are methods of evaluating an ability of a therapeutic composition to modulate a dopaminergic activity in an organ of a mammalian subject having a dopaminergic disorder. Also provided are methods of assessing and monitoring the progression of a dopaminergic disorder in tan organ of a mammalian subject, and of optimizing the treatment of such a disorder.

Abstract: The present invention is generally directed towards compositions comprising ascorbic acid or ascorbate salt and an imaging agent, and related methods. In some embodiments, the imaging agent comprises pyridaben or a pyridaben analog attached to an imaging moiety.

Abstract: A method for disinfecting a water system of an aircraft includes letting-in of hot water at an inlet of the water system by a first ground service unit; flushing the hot water from the inlet, through water pipes of the water system, to an outlet of the water system; and letting-out of the hot water at the outlet, by the first ground service unit or a second ground service unit; the hot water being flushed into the inlet and out of the outlet over a predefined disinfection period; and the hot water being provided at the inlet via a continuous-flow heater of the first ground service unit.

Abstract: Methods and systems are provided for calibrating a UV lamp having a plurality of arrays or channels of light emitting diodes. The calibration involves adjusting a drive current applied to the UV lamp based on an actual irradiance output by its light-emitting diodes relative to a target irradiance. The calibration is selectively performed when a stabilized temperature condition of the lamp is met.

Abstract: A Sterilization Unit includes: a UV-C radiation source configured to emit UV-C radiation; and a room partition selectably configurable between two or more different partition geometries and configured, in each of the two or more different partition geometries, to (a) physically separate floor space of a room into sterilization target area and a non-target area, and (b) direct the UV-C radiation to the target area from at least two different directions while shielding the non-target area from the UV-C radiation.

Abstract: A system and a kit for microbial control within an enclosure comprising an electronic component are provided. The enclosure includes an access cover configured to move to enable access to an interior of the enclosure with the electronic component at least partially positioned within the interior of the enclosure. An oxidant generator is configured to generate an oxidizing agent in a gaseous state and distribute the oxidizing agent in the gaseous state within the interior of the enclosure. The oxidant generator may be positioned within the interior of the enclosure, or the oxidant generator may be in fluid communication with the interior of the enclosure. The oxidant generator may be an ozone generator, such as an ultraviolet (UV) light source or an electrical discharge source, and the oxidizing agent may be ozone. Alternatively, the oxidant generator may be a chlorine dioxide generator, and the oxidizing agent may be chlorine dioxide.

Abstract: An appliance having one or more scented packaging materials is provided. The scented packaging materials removably attach to or support the appliance, e.g., during shipping. A preselected scent emanates from the scented packaging materials. Thus, when the appliance is delivered to a consumer, the preselected scent emanating from the scented packaging materials provides the appliance with an attractive smell.

Abstract: Embodiments of the invention relate to devices, systems, and methods for selectively emitting scent control material responsive to local conditions of a scent control device. The local conditions may dictate the effectiveness of a given set of output parameters of a scent control device. The scent control device accepts as input, one or more conditional inputs carrying information about the local conditions around the scent control device, such as weather conditions, elevation, barometric pressure, or functional status of the scent control device. Operational programs corresponding to the conditional inputs may be automatically selected based on the combination of conditional inputs to cause the output parameters of the scent control device to match or take into account the local conditions. The scent control device then outputs scent control material such as ozone at a rate effective to control one or more scents to a level that is not perceivable by animals or humans.

Abstract: Provided are an aroma diffusing apparatus and an oil supply method. The aroma diffusing apparatus includes a main body and an oil storage tube. The main body is provided with a liquid storage chamber which is configured to store a liquid. The oil storage tube is configured to store an essential oil. When the aroma diffusing apparatus works, a bottom portion of the oil storage tube may be in fluidic communication with the liquid storage chamber thus allowing the essential oil in the oil storage tube to flow from the bottom of the oil storage tube into the liquid storage chamber as the liquid in the liquid storage chamber is being consumed.

Abstract: A microfluidic cartridge is provided. The microfluidic cartridge includes a reservoir for containing a fluid composition, a first face, and a second face joined with the first face. The electrical circuit has a first end portion and a second end portion. The first end portion of the electrical circuit is disposed on the first face and the second end portion of the electrical circuit is disposed on the second face. The first end portion includes electrical contacts and one or more circuit minor openings that are configured to mate with minor guideposts on the housing of a microfluidic delivery device. The microfluidic cartridge may include one or more major openings that are configured to mate with major guideposts on the housing. The microfluidic cartridge includes a microfluidic die disposed on the second face.

Abstract: Provided is a use for a peptide in surface-treating a medical device or medical material to be used in contact with blood, with which it is possible to obtain a medical device or medical material that can achieve highly efficient vascular endothelialization through the use of a peptide uniquely binding to vascular endothelial cells. Also provided are: a peptide suitable for use in said surface treatment; a method for producing a medical device or medical material surfaced-treated with said peptide and to be used in contact with blood; and a surface treatment agent including said peptide, said agent to be used in surface-treating a medical device or medical material to be used in contact with blood. In the present invention, a medical device or medical material is surface-treated using a peptide that includes any one of ten specific amino acid sequences and uniquely binds to the surface of endothelial progenitor cells.

Abstract: A method for promoting spine fusion inside intersomatic cages, comprising placing a fusion cage between two vertebral bodies, and injecting a bone cement paste inside said fusion cage, said bone cement paste containing a powder component comprising ?-tricalcium phosphate (?-TCP) particles having an average size greater than or equal to 9 ?m, and a liquid component comprising blood.

Abstract: The present invention provides compositions and methods for promoting fusion of bones in spine fusion procedures. In some embodiments, a method of performing a spine fusion procedure comprises providing a composition comprising PDGF disposed in a biocompatible matrix and applying the composition to a site of desired spine fusion.

Abstract: To provide a cell or tissue embedding device highly capable of supplying a physiologically active substance, by curbing the reduction of living cells or living tissue in the process of preparing a PVA gel containing the living cells or living tissue. An aqueous gel to form an immunoisolation layer of a cell or tissue embedding device has a denatured polyvinyl alcohol resin having an activated carbonyl group (A) and a crosslinking agent (B) as its components.

Abstract: The present invention provides a lyophilized placental composite sheet as a tissue graft for wound care and a method for preparing the lyophilized placental composite sheet. The lyophilized placental composite sheet includes an amniotic membrane and a processed chorion layer for treating various types of wounds and tissue regenerative processes.

Abstract: The present invention relates to a tissue-engineered intervertebral disc (IVD) suitable for total disc replacement in a mammal and methods of fabrication. The IVD comprises a nucleus pulposus structure comprising a first population of living cells that secrete a hydrophilic protein and an annulus fibrosis structure surrounding and in contact with the nucleus pulposus structure, the annulus fibrosis structure comprising a second population of living cells and type I collagen. The collagen fibrils in the annulus fibrosis structure are circumferentially aligned around the nucleus pulposus region due to cell-mediated contraction in the annulus fibrosis structure. Also disclosed are methods of fabricating tissue-engineered intervertebral discs.

Abstract: Tissue scaffolds are described herein. Also described are devices for treating wounds and methods of treating wounds using tissue scaffolds.

Abstract: The present disclosure relates to a human cardiac tissue construct, to the method for producing thereof and its uses in disease modelling, compound screening and properties evaluation, and/or therapeutic uses in heart regeneration. It further relates to a perfusion bioreactor with electrical stimulation capabilities and its use in the production of said human cardiac tissue construct. In still a further aspect, the disclosure provides a method for the non-destructive evaluation of electrophysiological activity in a cellular construct, such as a cardiac tissue construct of the disclosure.

Abstract: The present invention provides a tissue scaffold mold apparatus and methods for use of the mold apparatus to simply, rapidly and easily form molded tissue scaffolds from fibrous proteins such as collagen, and with other matrix components having complex 3-dimensional designs that can be seeded with stem cells for creating biologically and mechanically functional tissues/grafts. The inventive methods and apparatus allows for tissue engineering of hollow or concave and tubular organs and tissues, and will have immediate impact in a wide range of biomedical areas from tissue engineering, regeneration and reconstructive surgery.

Abstract: Disclosed herein are novel wavy, multi-component vascular grafts (WMVGs) with a wavy inner layer of rigid biopolymer fibers and an outer layer of elastic biopolymer fibers and a method for preparing WMVGs via electrospinning using a special assembled collector. The fabricated WMVGs closely mimic the non-linear tensile stress-strain relationship of native blood vessels and showed sufficient mechanical strength needed for implantation.

Abstract: Disclosed herein are methods for modifying a substrate having a hydrophobic surface. Also disclosed are modified hydrophobic substrates. The modified hydrophobic substrates and methods disclosed herein advantageously improve cell affinity and antithrombogenicity of hydrophobic surfaces.

Abstract: The invention provides, inter alia, ultra-thin conformal coated biological surfaces, such as living cells, cell clusters, tissues, organs, and hybrid synthetic organs, and methods of making the same, e.g., using click reactive water soluble polymers, under conditions that do not damage or significantly modify the biological surfaces. In some embodiments, the coated biological surfaces are suitable for delivery to a subject in need thereof.

Abstract: A method of preparing an implantable spacer device utilizing an elastomeric material containing antibiotic(s), radiation-emitting seeds, and/or other bio-active substance to treat diseased, infected and/or injured bony structures, soft tissue, or neural structures. The elastomeric material may include silicone elastomers.

Abstract: Modularizable implants and stents made with bio-absorbable metal wire alloys (‘bio-metals’, e.g. magnesium and alloys), and methods for making such implants and stents. The stents or implants may include one or more wire-formed rings or comprise inter-connected cells that form nets that may serve as modules that are assembled mechanically into stents, without the need for certain manufacturing processes that may affect the durability and physical properties thereof. The wires may be formed into rings mechanically and held in place using joining cuffs, and/or adjacent wires may be secured to one other mechanically using joining cuffs to form nets which can be used as implants or formed into stents. The stents can include radiopaque portions, e.g. associated with one or more joining cuffs, to aid in the positioning and evaluation of stents in the body by serving as visual indicators of alignment and expansion that can be detected using X-rays.

Abstract: A three-dimensional electrospun nanofiber scaffold for use in repairing a defect in a tissue substrate is provided. The three-dimensional electrospun nanofiber scaffold includes a first layer formed by a first plurality of electrospun polymeric fibers and a second layer formed by a second plurality of electrospun polymeric fibers. The second layer is coupled to the first layer using a coupling process and includes a plurality of varying densities formed by the second plurality of electrospun polymeric fibers. The first and second layers are configured to degrade via hydrolysis after at least one of a predetermined time or an environmental condition. The three-dimensional electrospun nanofiber scaffold is configured to be applied to the tissue substrate containing the defect.

Abstract: Drug eluting stents, methods of making, using, and verifying long-term stability of the drug eluting stents, and methods for predicting long term stent efficacy and patient safety after implantation of a drug eluting stent are disclosured. In one embodiment, a drug eluting stent may include a stent framework; a drug-containing layer; a drug embedded in the drug-containing layer; and a biocompatible base layer disposed over the stent framework and supporting the drug-containing layer. The drug-containing layer may have an uneven coating thickness. In addition or in alternative, the drug-containing layer may be configured to significantly dissolve/dissipate/disappear between 45 days and 60 days after stent implantation. Stents may reduce, minimize, or eliminate patient risks associated with the implantation of a stent, including, for example, restenosis, thrombosis, and/or MACE.

Abstract: A fluid medical waste canister has interior surfaces that are exposed only to compressive stresses when a vacuum is applied, thereby eliminating the potential for environmental stress cracking. The canister is compatible with medical procedures that generate fluids having high fat/lipid content, such as liposuction procedures. The canister avoids certain stress concentration distributions that cause cracks to close onto themselves, which can cause one or more pieces of the canister wall to rupture into its interior volume. Because the canister is designed to avoid conditions that initiate canister implosion during liposuction procedures, low-cost polystyrene may be used as a waste canister material for such procedures.

Abstract: An appliance is provided for negative-pressure therapy of wounds on the human or animal body in which, on the one hand, a substance is delivered to a wound bed (W) and, on the other hand, fluids, in particular an exudate and the delivered substance, are aspirated from the wound bed by negative pressure. The appliance has a suction pump housing, with a suction pump arranged therein for aspirating the fluids from the wound bed (W), and a fluid collection container for collecting the aspirated fluids. Moreover, the appliance has a first measuring device and a second measuring device. The first measuring device serves to determine the quantity of the aspirated fluids, and the second measuring device serves to determine the quantity of the substance delivered to the body.

Abstract: A mechanical vacuum dressing comprising: a first valve layer comprising a first one-way valve; a second valve layer comprising a second one-way valve; the first valve layer being joined to the second valve layer so as to define a chamber therebetween; the first one-way valve being configured to admit fluid into the chamber through the first one-way valve but prevent fluid from exiting the chamber through the first one-way valve; the second one-way valve being configured to exhaust fluid from the chamber through the second one-way valve but prevent fluid from entering the chamber through the second one-way valve; and the second valve layer comprising an elastomeric material such that (i) when the second valve layer is moved away from the first valve layer, the volume of the chamber is increased, and (ii) when the second valve layer is thereafter released, the second valve layer moves back towards the first valve layer and the volume of the chamber is decreased.

Abstract: A manually-actuated, constant reduced-pressure apparatus for use with a reduced-pressure system for treating tissue at a tissue site includes a flexible, collapsible member that is operable to move between a compressed position and an extended position. The collapsible member may be disposed between a carrier member and a slider member that move between a compressed position and an extended position. The carrier member and slider member are urged away from each other by a constant-force biasing member, e.g., a constant force coil spring. As the apparatus moves from the compressed position to the extended position, a constant reduced-pressure is generated and delivered to a reduced-pressure port. Methods of manufacturing a manually-actuated, constant reduced-pressure apparatus and methods of treating a tissue site are also provided.

Abstract: Provided is a method of cleaning a body cavity using a device by coupling a distal end portion of a first cannula to the housing such that a lumen is in fluid communication with the first portion of the inner volume, the first cannula coupled to a vacuum source, then coupling a distal end portion of a second cannula to the housing such that a lumen is in fluid communication with the second portion of the inner volume, the second cannula being coupled to a fluid source, inserting a portion of the housing into a body cavity, conveying a fluid from the fluid source to the body cavity via the lumen of the second cannula, and withdrawing the fluid from the body cavity into the vacuum source concurrently with the conveying the fluid, via the lumen of at least the first cannula.

Abstract: A nasal irrigation device communicates an irrigant to a device user and comprises a mechanics module and a reservoir assembly wherein a source of saline comprising a cartridge is disposed within the mechanics module adjacent a lid assembly for piercing the cartridge upon closing of a lid for releasing the cartridge contents into the reservoir assembly. A faux collapsible cartridge for testing operability of a nasal irrigation device comprises a housing including a shaft, a spring biased rod extending from the housing shaft, and a flange depending from a housing wall whereby the rod and flange are disposed to actuate a trigger assembly of the nasal irrigation device.