Abstract: Described herein are chimeric proteins including membrane-cleavable chimeric proteins and degron-fusion chimeric proteins. Also described herein are nucleic acids, pharmaceutical compositions, methods, and methods of treatment directed to the same.

Abstract: Disclosed are compositions neoantigens and T cell receptors (TCRs) specific for one or more neoantigens as well as methods of their use for treating cancer.

Abstract: Novel anti-effector moiety antibodies or antigen binding domains thereof and CARs that contain such effector moiety antigen binding domains, either with or without one or more booster elements, and host cells expressing the receptors, and nucleic acid molecules encoding the receptors are provided herein, as well as methods of use of same in a patient-specific immunotherapy that can be used to treat solid tumor cancers and other diseases and conditions.

Abstract: The presently disclosed subject matter provides novel T cell receptors (TCRs) that target a mutated RAS protooncogene. The presently disclosed subject matter further provides cells comprising such TCRs, and methods of using such cells for treating cancers associated with RAS.

Abstract: There is provided a method for producing a composition containing a pharmaceutically acceptable salt of citric acid, a hydrate thereof, or a mixture thereof and having a moisture content of 4.0% by mass or less, the method including irradiating a composition containing a pharmaceutically acceptable salt of citric acid, a hydrate thereof, or a mixture thereof with microwaves.

Abstract: The present invention relates to a sensitizer-peptide conjugate for use in the treatment of cancer. In particular, the present invention relates to a sensitizer-peptide conjugate for use in the treatment of melanoma. The use of such sensitizer-peptide conjugate in photodynamic therapy or sonodynamic therapy is also disclosed. According to the present invention, there is provided a sensitizer-peptide conjugate for use in the treatment of cancer; wherein the sensitizer-peptide conjugate comprises at least one sensitizer and at least one peptide.

Abstract: Provided herein are, inter ilia, methods and compositions for the treatment of cancer. The methods include administering a combination of an anti-STAT3-Toll-like receptor 9 (TLR9)-binding conjugate and a checkpoint inhibitor. The anti-STAT3-Toll-like receptor 9 (TLR9)-binding conjugate provide herein may be a CpG moiety bound to an anti-STAT3 siRNA through a covalent linker and the checkpoint inhibitor may be an anti-CTLA4 antibody. Administration of a combined effective amount of the anti-STAT3-Toll-like receptor 9 (TLR9)-binding conjugate and the checkpoint inhibitor results in surprisingly increased anti-tumor efficacy and CDS T cell activity.

Abstract: Provided herein are compounds, conjugate products thereof, methods, and pharmaceutical compositions for use in treatment and diagnosis.

Abstract: The present invention relates to the field of pharmaceutical and chemical engineering, and specifically relates to a weakly acidic microenvironment-sensitive aptamer for tumors, a triptolide conjugate. The conjugate is formed by conjugation between the 14-position hydroxyl group of triptolide and the aptamer via an acetal ester linking bond, which is an acid-sensitive linking bond with a cleavage condition of (pH=3.5-6.5), which is much less pH-sensitive and is more likely to cleave under the tumor microenvironment. Based on the characteristics of the aptamer targeting the highly expressed proteins on the membrane surface of tumor cells, the conjugate delivered triptolide targeted to tumor cells and mediated endocytosis to reach the lysosome; based on the characteristics of the acidic environment of lysosomes, the acetal ester linking bond released intact triptolide in the lysosomal acidic environment, targeting and killing of tumor cells.

Abstract: The present disclosure provides palatable orally disintegrating tablet formulations of drotaverine or a salt thereof, methods of their preparation, and their use in treatment.

Abstract: The present invention relates to multimers of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also describes the multimerization of polypeptides through various chemical linkers and hinges of various lengths and rigidity using different sites of attachments within polypeptides. In particular, the invention describes multimers of peptides which are high affinity binders of ACE2. The invention also includes pharmaceutical compositions comprising said polypeptides and to the use of said polypeptides in suppressing or treating a disease or disorder mediated by ACE2, such as infection of COVID-19 or for providing prophylaxis to a subject at risk of infection of COVID-19.

Abstract: The present invention relates to a botulinum toxin freeze-dried dosage form composition storable for a long time, comprising botulinum toxin, protamine sulfate, an isotonic agent and a buffer agent, and a botulinum toxin freeze-dried dosage form according to the present invention lowers the inactivation rate of botulinum toxin during freeze-drying, can maintain the stability of botulinum toxin for longer than a conventional botulinum toxin freeze-dried dosage form, forms a uniform particle size so that the effect exhibited at the site of administration is the same and can prevent the side effect in which an excessive toxin administration effect is exhibited only at some sites.

Abstract: The invention provides immunoconjugates of Formula I comprising an anti-HER2 antibody linked by conjugation to one or more 8-Het-2-aminobenzazepine derivatives. The invention also provides 8-Het-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

Abstract: Described are anti-doppel antibody-drug conjugates, compositions comprising them, and related methods of treating doppel-associated diseases and conditions, including cancer.

Abstract: Disclosed herein are surfactant free lyophilized formulations of antibody-drug conjugates (ADCs), such as anti-tissue factor ADCs, and reconstituted formulations, processes and uses thereof. The formulations are particularly suitable for an anti-TF ADC based on an auristatin derivative or other similarly hydrophobic drug. Typically, the excipients of the formulations comprise or consist of histidine, sucrose, trehalose, mannitol and glycine.

Abstract: The present disclosure provides SEZ6 antibody drug conjugates (ADCs), including compositions and methods of using such ADCs.

Abstract: The present invention relates to a novel antibody fragment based antimicrobial conjugate selectively targeting Pseudomonas spp., preferably Pseudomonas aeruginosa, comprising of at least one antimicrobial peptide at one end of the conjugate preferably human Histatin-5; at least one antibody fragment at the other end of the conjugate, preferably a VHH targeting C4 decarboxylase transporter antigen of Pseudomonas aeruginosa; at least one protease cleavage sequence, preferably susceptible to cleavage by Pseudomonas aeruginosa specific virulent protease, Elastase B, and at least one flexible polypeptide linker in tandem with the protease cleavage sequence, and the protease cleavage sequence and the flexible polypeptide linker placed in between the antimicrobial peptide and antibody fragment. The antibody fragment-based antimicrobial conjugate has an in vitro MIC-99 against Pseudomonas aeruginosa of 0.5 ?M, and MIC-50 less than 0.125 ?M.

Abstract: A nanoparticle composed of buckminsterfullerene bonded to glutamine, gamma amino butyric acid (GABA) and adenosine triphosphate is provided. This nanoparticle helps to regulate the energy metabolism, neural excitability, and signal transduction within the synapse and between the astrocytes and the neuronal networks of the human brain when these become dysfunctional. It is intended as a treatment for Alzheimer's disease, Lewy Body disease and other neuropathological diseases of the glutamine-glutamate-GABA cycle. Utility for remediating comorbid sexual dysfunction is promoted, as well as the antioxidant and protein oligomer disassembly properties. The adenosine triphosphate adduct provides a reversible inorganic phosphate energy storage and supply, the glutamine adduct provides a stable reservoir of this amino acid that is resistant to breakdown by reactive oxygen species, reactive nitrogen species, and astrocytes.

Abstract: The present disclosure relates to ophthalmic compositions containing solid complexes of active pharmaceutical ingredient and cyclodextrin, to their method of preparation and their uses. The compositions can include an active agent drug/cyclodextrin complex substantially dissolved in an aqueous eye drop vehicle. The ophthalmic composition is generally in the form of a microsuspension including an active agent complex having a diameter of less than about 100 ?m.

Abstract: The present disclosure provides recombinant adeno-associated virus (AAV) virions with altered capsid protein, where the recombinant AAV (rAAV) virions exhibit greater ability to cross barriers between intravitreal fluid and retinal cells, and thus greater infectivity of a retinal cell compared to wild-type AAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a retinal cell in an individual.

Abstract: The present invention includes methods for treating a disease or disorder that is associated with aberrant or absent dystrophin, by upregulating a brain isoform of dystrophin (e.g. purkinje and/or cortical) in a subject in need thereof. The method comprises administering to the subject a composition that upregulates a brain isoform of dystrophin.

Abstract: Provided herein are methods and compositions for treatment of CLN2 Disease. Such compositions include a recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising (a) an AAV 5? inverted terminal repeat (ITR) sequence; (b) a promoter; (c) a CLN2 coding sequence encoding a human TPP1; (d) an AAV 3? ITR. Also provided herein are methods of treating CLN2 Disease comprising administering to a subject in need thereof the rAAV described herein via more than one route. Also provide herein are pharmaceutical compositions comprising the rAAV described herein and related methods of treating CLN2 Disease.

Abstract: Provided herein are nucleic acid trans-splicing molecules (e.g., pre-mRNA trans-splicing molecules (RTMs); RNA exon editing molecules) capable of correcting mutations in the ABCA4 gene. Such molecules are useful in the treatment of disorders such as ABCA4-associated retinal dystrophies (e.g., Stargardt Disease or cone-rod dystrophy). Also described herein are methods of using the nucleic acid trans-splicing molecules described herein to correct mutations in ABCA4, thereby treating disorders associated with mutations in ABCA4 and use of the nucleic acid trans-splicing molecules described herein for treating disorders associated with mutations in ABCA4 and in the preparation of medicaments for the treatment of disorders associated with mutations in ABCA4.

Abstract: The present disclosure is in the field of gene therapy, in particular for the treatment of cholestatic disease. More specifically, the present invention relates to a minimal bile acid inducible promoter and its use for gene therapy in cholestatic disease.

Abstract: The present application relates to the fields of biotechnology, virology, genetics, and molecular biology. More specifically, the present invention relates to an isolated nucleic acid for producing a gene therapy viral product, said isolated nucleic acid comprising a nucleic acid that encodes the SMN1 protein having the amino acid sequence of SEQ ID NO: 1, and a nucleic acid that encodes the microRNA miR-23a, an expression cassette and a vector based thereon, as well as an AAV9-based recombinant virus for expressing the SMN1 gene in target cells, a pharmaceutical composition that includes said recombinant virus, and various uses of the above recombinant virus and the above composition.

Abstract: A method for the systemic delivery of a polypeptide within a subject is provided by creating genetically modified skin cells via topical introduction of a genetically engineered virus which delivers a nucleic acid encoding a therapeutic polypeptide for expression by the skin cells, wherein the expressed therapeutic polypeptide is secreted by the skin cells and is introduced into the circulatory system of the subject.

Abstract: Combined administration of a selective glucocorticoid receptor modulator (SGRM; e.g., relacorilant or exicorilant) and a cancer therapeutic (e.g., a taxane or antiandrogen) is useful for identifying elevated cortisol activity in patients with cancer or with Cushing's syndrome, and for treating patients with cancer (e.g., ovarian, pancreatic, or prostate cancer). An at least 40% change in RNA levels encoding CDKN1C, TNFRSF17, BRIP1, PDK1, CLEC10A, FPR3, CCR2, LTLRB4, or CD86 indicates that the patient with cancer is likely to benefit from the combined treatment (e.g., likely to have longer survival than similar patients not receiving combined treatment). An active SGRM dose is identified where RNA levels encoding CDKN1C, TNFRSF17, BRIP1, or PDK1 decrease, or where RNA levels encoding CLEC10A, FPR3, CCR2, LTLRB4, and CD86 increase, by at least 40%. Changes in RNA levels encoding CLEC10A, FPR3, CCR2, LTLRB4, and CD86 identify patients with cancer or with Cushing's having elevated cortisol activity.

Abstract: Embodiments of the instantly claimed inventions include, but are not limited to, chimeric viral constructs, non-human primate models, in vivo screening systems for antiviral agents, gene therapy delivery systems, and methods of making and using the same. In some embodiments, chimeric viral constructs include a non-human primate infecting virus nucleic acid sequence and a exclusively human pathogenic virus nucleic acid sequence for use in creating a non-human primate model and uses thereof. In other embodiments, systems for testing antiviral agents are disclosed. In other embodiments, gene therapy delivery systems disclosed herein can be used to deliver a vector containing or associated with an agent to a human subject for treating conditions of the skin and neuronal ganglia in the subject.

Abstract: The present invention provides methods for guiding preservation of human neurons or human nerves during surgery, as well as labeling and mapping nerves in targeted organs for map-guided surgery, by administering a fluorescently-labeled peptide that specifically binds to the human neurons or human nerves. The invention further provides human neuron or nerve targeting molecules comprising fluorescently-labeled peptides that specifically bind to human neurons or human nerves and compositions thereof.

Abstract: The present invention relates to a process for preparing a hydrated phospholipids solvent mixture, by: —dissolving a first phospholipid at a temperature above the phase transition temperature of the phospholipids in an organic solvent to form a dissolved phospholipid solvent mixture; —dissolving a second phospholipid at a temperature above the phase transition temperature of the phospholipids in the dissolved phospholipid solvent mixture to form a dissolved phospholipids solvent mixture; —adding an aqueous phosphate buffer to the dissolved phospholipids solvent mixture to form a buffered phospholipids solvent mixture; and —stirring the buffered phospholipids solvent mixture to form a hydrated phospholipids solvent mixture.

Abstract: The present disclosure provides a compound targeting prostate specific membrane antigen (PSMA), wherein the compound has the following structure shown in Formula (I); R1 is a compound structure targeting prostate specific membrane antigen; L1 is —(X)n—(CH2)m—(Y)q—, X and Y are independently selected from lysine, glutamic acid or a derivative structure containing lysine and glutamic acid, n is an integer from 0 to 12, m is an integer from 0 to 60, q is an integer from 0 to 12, and each CH2 may be individually substituted with —O—, —NH(CO)—, or —(CO)—NH—; L2 is —(CH2)p—, p is an integer from 0 to 30, and each CH2 may be individually substituted with —O—, —NH(CO)—, or —(CO)—NH—; and R2 is a nuclide chelating group. The present disclosure also provides a radiolabeled complex based on the structure of the compound.

Abstract: The present invention provides valuable peptidomimetics for therapeutic and diagnostic purposes as well as compositions, methods, uses and kits based on these peptidomimetics. In particular, the peptidomimetics of the present invention are incorporated by CCK2R expressing cells, for instance, cancer cells. This allows, for instance, to selectively destroy cancer cells or to selectively image cancer cells that express CCK2R.

Abstract: The present invention relates to MOFs for use in radiotherapy. More particularly, the invention provides a particle comprising a MOF, optionally at least one targeting moiety and at least one radionuclide; a composition comprising said particle; said particle or composition for use as a medicament; said particle or composition for use in a method for the treatment of a proliferative disease; said particle or composition for use in a method for the treatment of a chronic inflammatory disease; and a kit comprising a particle comprising a MOF, an optional targeting moiety, and a radionuclide cation.

Abstract: An endoscopic irradiation device for inactivating pathogens is disclosed. The device includes a control element and a probe that is directed by the control element. A source of UVC light providing a peak irradiation of about 222 nm is integrated with at least one of the probes and the control element. An attenuating element attenuates irradiation above about 235 nm is located in a path of UVC light generated by the source of UVC light. The attenuating element is integrated with at least one of said medical probe and said control element. In one embodiment, attenuating element takes the form of a band pass filter placed between the source of UVC light and biological tissue being irradiated by the UVC light. Alternatively, the attenuating element is a dopant disposed within a crystalline structure of a light emitting diode that restricts or attenuates transmission above about 235 nm.

Abstract: A method of disinfecting using a light diffusing fiber includes optically coupling a light source to a light diffusing optical fiber having a core, a cladding surrounding the core, an outer surface, and a plurality of scattering structures positioned within the core, the cladding, or both the core and the cladding. The method further includes positioning the light diffusing optical fiber in optical engagement with a pathogen sample and directing light output by the light source into the light diffusing optical fiber for a first time interval. The scattering structures scatter light propagating along the light diffusing optical fiber toward the outer surface and a portion of the light diffuses through the outer surface thereby irradiating the pathogen sample with light having an average power density of about 5 mW/cm2 to about 30 mW/cm2 at a wavelength from about 380 nm to about 495 nm for an exposure time from about 2 hours to about 24 hours.

Abstract: A floor covering for an aircraft interior including a substrate and a plurality of UV lights distributed across the surface of the substrate. The floor covering further includes at least one sensor configured to detect the presence of an object on the substrate. At least one of the plurality of UV lights emits UV radiation when the at least one sensor detects the presence of an object on the substrate. The UV lights may be configured to act as a germicide, and the object may be a foot or footwear. Therefore, the floor covering may be provided as a safety measure for an aircraft.

Abstract: A manually guided device has an electrically insulating housing in which power electronics operated by high voltage are accommodated. The device is used in particular for treating an object, in particular by way of plasma. Increased comfort and simplified manufacturing of the device result from an electrically conductive equipotential bonding device which is electrically isolated from the power electronics and which forms, at least in part, an outer surface of the device with which a user's hand is in contact during use.

Abstract: A disinfection device may include a disinfection chamber, an ozone generator configured to generate ozone, and a humidifier configured to generate humidity and configured to be fluidly coupled to the disinfection chamber and the ozone generator, the humidifier being configured to encourage a mixing of generated ozone with generated humidity.

Abstract: An oil-leakage prevention atomizer and an essential oil diffuser are provided. The oil-leakage prevention atomizer includes a carrier, a reaction chamber, an atomizing core, a separator, and an oil supply chamber, wherein the carrier is provided with a carrier cavity; an air inlet and an air outlet are arranged on a cavity wall of the carrier cavity; the reaction chamber is mounted in the carrier cavity and is internally provided with a reaction cavity; an oil inlet hole, an atomizing port, and an air hole are arranged on a cavity wall of the reaction cavity; the atomizing core is mounted at the atomizing port; the separator is mounted on the reaction chamber and is provided with an oil guide pipe communicated to the oil inlet hole and an air guide pipe communicated to the air hole.

Abstract: Apparatus and methods for variable-control fragrance dispensing. The disclosed device brings customization to the fragrance industry. Interchanging sub-containers and selecting the amounts of each sub-container allows a user to customize their scents. A mixing chamber contained to receive and mix a variable amount of each liquid from a plurality of sub-containers is described. The mixed liquid is sprayable out a spray head of the device. Selector knobs may be used to control valves which control the variable amount of each liquid dispensed.

Abstract: The present disclosure provides a medical grade nanofibrillar cellulose hydrogel comprising plant-based chemically and enzymatically unmodified nanofibrillar cellulose hydrogel having a concentration of the nanofibrillar cellulose in the range of 1.4-3.4% by weight, the nanofibrillar cellulose having a number-average diameter of fibrils and/or fibril bundles of 100 nm or less, and a storage modulus in the range of 1-35 Pa. The present disclosure also provides a method for treating a subject in need of treatment of body with implantable material, and a method for manufacturing medical grade nanofibrillar cellulose hydrogel.

Abstract: The present invention relates to an antimicrobial dressing for wounds comprising Vitamin D or Vitamin E as carrier loaded with an antimicrobial agent. More specifically, the present invention relates to antimicrobial wound dressings comprising vitamin D or vitamin E as carrier loaded with an antimicrobial agent for controlling infections and managing potentially infected wounds or infected wounds or treating infected implants used in orthopaedic surgery and various other conditions leading to healing of the wounds and avoidance of development of antibacterial resistance and avoiding complications related to the use of prolonged antibiotics by systemic route.

Abstract: The present disclosure pertains to crosslinkable compositions and systems as well as methods for forming crosslinked compositions in situ, including the use of the same for embolizing vasculature including the neurovasculature within a patient, among many other uses.

Abstract: The present disclosure pertains to crosslinkable compositions and systems as well as methods for forming crosslinked compositions in situ, including the use of the same for embolizing vasculature including the neurovasculature within a patient, among many other uses.

Abstract: Embolic particles are described. The particles are reaction products of a prepolymer solution including at least one polyether macromer and an appropriate monomer.

Abstract: Provided is a novel device (implantation device) containing a gelatin. The implantation device is made of a bioabsorbable non-woven fabric containing a gelatin.

Abstract: Methods for preparing and using collagen extracts and collagen scaffolds are provided. Additionally, methods and related kits for the repair of articular tissue using the collagen material are provided.

Abstract: The present disclosure relates to multicomponent hydrogels that may be use, for example, as dermal fillers for treating fine lines and wrinkles of the skin. Also disclosed herein are methods for making and using the disclosed hydrogels and related compositions.

Abstract: A cartilage tissue engineering complex, e.g., a graft, has a cartilage gel or perichondral particles containing chondrocytes as well as a porous frame structure. The cartilage gel or perichondral particles is/are loaded on the porous frame structure to form a cartilage gel/perichondral particle-frame structure complex. The method for preparing the cartilage tissue engineering graft and a use of said graft in repair and reconstruction of articular cartilage are also provided.