Abstract: Proteolysis-targeting chimeras (PROTACs) and chimeric compounds that inhibit B-Cell Lymphoma-2 (Bcl-2) protein, and methods of using the same, are provided for treating disease.

Abstract: Described herein, in part, are compounds that mediate the degradation of cyclin-dependent kinase 2 (CDK2), and are therefore useful in the treatment of various disorders, such as cancer.

Abstract: The present invention relates to: a deoxycholic acid-peptide conjugate having anti-obesity activity by inhibiting lipid production and promoting lipolysis; and a use for preventing, ameliorating or treating obesity comprising the conjugate as an active ingredient.

Abstract: The instant disclosure provides (among other things) novel water-soluble polymer reagents capable of selective conjugation to histidine residues. e.g., in peptides and proteins, as well the resulting conjugates and related compositions. In addition, provided are methods of preparing the polymer reagents, as well as methods for conjugating the polymer reagents to active agents and other substances, pharmaceutical compositions, and methods for administering the conjugates.

Abstract: The present invention relates to the field of compounds intended for the treatment of cancer. Selectivity of these compounds is gained through the presence of a specific tetrapeptidic moiety allowing selective release of the drug. The drug in particular is a cytostatic, cytotoxic, or anti-cancer drug. A protective capping group can be introduced to ensure stability of the compound in blood. The tetrapeptidic moieties are ALLP or APKP.

Abstract: Disclosed are conjugates of an oligonucleotide and a peptide covalently bonded or linked via a linker to the oligonucleotide, the peptide including at least one cationic domain comprising at least 4 amino acid residues and at least one hydrophobic domain comprising at least 3 amino acid residues, provided that the peptide includes a total of 7 to 40 amino acid residues and does not include any artificial amino acid residues; and the oligonucleotide including a total of 12 to 40 contiguous nucleobases, where at least 12 contiguous nucleobases are complementary to a target sequence in a human dystrophin gene.

Abstract: The disclosure provides a peptide comprising no more than 50 amino acids and comprising the amino acid sequence wherein the peptide comprises the amino acid sequence of Formula (1): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-F-L-N/V-P-K-G, including peptides comprising the amino acid sequence of any one of SEQ ID NO: 1-72. The disclosure further provides methods of delivering a payload peptide to an eye of a subject, as well as a method of treating an ocular disorder in a subject in need thereof.

Abstract: The present disclosure relates to isolated non-naturally occurring delivery constructs comprising a bacterial toxin-derived delivery construct coupled to a biologically active therapeutic cargo; wherein the delivery construct is capable of delivering the biologically active cargo via transcytosis transport across an epithelial cell; and wherein the delivery construct does not comprise a bacterial toxin-derived translocation domain or a bacterial toxin-derived catalytic (cytotoxic) domain.

Abstract: Provided herein are compounds and compositions that are reversible agonists of the PDZ3 domain of PSD-95. Methods of their use in treating conditions of neural stress, inflammation, and viability are also provided.

Abstract: Disclosed herein is a recombinant polypeptide comprising 1 to 20 copies of an IL-17RB inactivation site (IRIS) sequence. Also disclosed herein is the use of the recombinant polypeptide in the preparation of a conjugate for the treatment of cancers.

Abstract: The present disclosure provides methods for treating bone diseases, such as bone cancers, bone metastasis of cancers, or osteoporosis, by administering a bone-targeting polypeptide conjugate. The bone-targeting polypeptide conjugate may be a bone-targeting antibody conjugate.

Abstract: The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more 2-amino-4-carboxamide-benzazepine derivatives. The invention also provides 2-amino-4-carboxamide-benzazepine 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 present disclosure relates to methods of using antibody conjugates with binding specificity for BCMA (BCMA) and its isoforms and homologs in combination with a gamma secretase inhibitor (GSI), such as in therapeutic methods. Also provided are pharmaceutical compositions and kits comprising the antibody conjugates and GSI.

Abstract: Therapeutic combinations of immunoconjugates that bind to FOLR1 (e.g., IMGN853) with anti-PD-1 antibodies or antigen-binding fragments thereof (e.g., pembrolizumab) are provided. Methods of administering the combinations to treat cancers, e.g., ovarian, peritoneal, or fallopian tube cancers, with greater clinical efficacy and/or decreased toxicity are also provided.

Abstract: The present application relates to a nitrogen-containing compound, a conjugate containing said compound, and an application thereof. Specifically, the present application provides a compound represented by formula (I), a solvate thereof, a pharmaceutically acceptable salt thereof, or a solvate of a pharmaceutically acceptable salt thereof. The nitrogen-containing compound has a good regulating effect on TLR8 and can effectively treat, alleviate, and/or prevent various diseases caused by immunosuppression, such as a cancer or a viral infection.

Abstract: The present invention provides a novel antibody-pyrrolodiazepine derivative and a novel antibody-pyrrolodiazepine derivative conjugate using the same, and a novel CLDN6 and/or CLDN9 antibody.

Abstract: This application discloses anti-PMEL17 antibodies, antigen binding fragments thereof, and antibody drug conjugates of said antibodies or antigen binding fragments conjugated to a GNAQ/GNA11 inhibitor. The invention also relates to methods of treating or preventing cancer using the antibodies, antigen binding fragments, and antibody drug conjugates. Also disclosed herein are methods of making the antibodies, antigen binding fragments, and antibody drug conjugates, and methods of using the antibodies and antigen binding fragments as diagnostic reagents.

Abstract: Provided herein are conjugates comprising proteins that bind to a transferrin receptor and oligonucleotides that are capable of modulating the expression of a target gene or sequence, as well as methods of use thereof.

Abstract: Provided are targeting conjugates comprising a targeting moiety and an effector molecule, wherein the effector molecule is conjugated to the targeting moiety via a conjugation site, wherein the effector molecule can be released from the targeting conjugate via cleavage. Also provided are compositions and methods of treatment or diagnosis using the targeting conjugates.

Abstract: The present invention relates to cell-derived vesicles with increased cellular uptake capacity and a method for producing same. The cell-derived vesicles of the present invention are produced by migrating cells to micropores, and exhibit the characteristic of expressing a protein marker that is different from that of exosomes naturally secreted by cells. The cell-derived vesicles with increased cellular uptake capacity, according to the present invention, have remarkably superior cellular uptake capacity as compared to natural exosomes secreted by cells, and thus can be effectively used to deliver various active substances, such as drugs and marker substances, into target cells.

Abstract: An oral delivery salt nano-precipitate for oral delivery of protein therapeutics such as insulin. The salt nano-precipitate comprises a cation-providing inorganic metal salt and an anion-providing salt. The protein molecule is bound to the salt nano-precipitate by way of electrostatic interactions. Both the cation-providing and anion-providing salts are present in the nano-precipitate at a sufficiently high concentration to enable adequate saturation of cationic and anionic salts, per volume of the nano-precipitate, such that the target protein molecule is strongly bound therewith and buffered against premature release at an acidic pH.

Abstract: The present disclosure provides compositions and methods for treating joint disorders that are characterized by an inflammatory component. In some aspects, the compositions and methods are to prevent the progression of osteoarthritis and other arthritides and to treat osteoarthritis and other arthritides in a mammalian joint.

Abstract: Provided herein are pharmaceutical compositions comprising a lipid nanoparticle (LNP) and a therapeutic nucleic acid (TNA), wherein the LNP comprises an ApoE polypeptide, or a fragment thereof and/or an ApoB polypeptide, or a fragment thereof, linked to the LNP, and at least one pharmaceutically acceptable excipient. The ApoE polypeptide, or the fragment thereof, and/or the ApoB polypeptide, or the fragment thereof, are capable of binding a low-density lipoprotein (LDL) receptor, or LDL receptor family member, advantageously providing LNP compositions that can be directed to any cell or tissue expressing the LDL receptor.

Abstract: The present invention relates to the field of gene therapy for the treatment of sensorineural hearing loss. In particular, the invention discloses a composition comprising a 3rd generation lentiviral vector pseudotyped with a viral envelope glycoprotein capable of binding to a receptor expressed in a cell of the inner ear for use in the treatment or prevention of sensorineural hearing loss, wherein said composition has a viral titer of at least 107 TU/mL and is administered to the inner ear of a subject suffering from or in danger to undergo sensorineural hearing loss. The viral envelope glycoprotein is capable of binding to a receptor selected from the group consisting of the LDL-receptor and LDL-R family members, the SLC1 A5-receptor, the Pit1/2-receptor and the PIRYV-G-receptor. Preferably, the viral glycoprotein is MARAV-G, COCV-G, VSV-G, VSV-G ts or PIRYV-G, most preferably, MARAV-G. The lentiviral vector further comprises a cargo sequence comprising, e.g.

Abstract: The present invention relates to adenovirus-associated virus comprising an influenza-derived neuraminidase transgene, used alone or together with an immune checkpoint inhibitor to treat a patient diagnosed with a solid cancer.

Abstract: This disclosure relates to modified guide RNAs having improved in vitro and in vivo activity in gene editing methods. This disclosure also relates to N. meningitidis Cas9 (NmeCas9) gene editing systems with modified guide RNAs.

Abstract: The present invention relates to a pharmaceutical composition comprising a compound promoting the expression and/or the activity of the non-coding RNA (ncRNA) of SEQ ID NO: 1 or a sequence being at least 85% identical thereto.

Abstract: Disclosed are engineered meganucleases that bind and cleave a recognition sequence within a hydroxyacid oxidase 1 (HAO1) gene. The present invention also encompasses methods of using such engineered meganucleases to make genetically-modified cells. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or nucleic acids encoding engineered meganucleases of the invention, and the use of such compositions for treatment of primary hyperoxaluria type I (PH1).

Abstract: In various embodiments, AAV serotypes capable of transducing skeletal muscle fibers and skeletal muscle stem cells (MuSC) with reduced off target tissue tropism are provided.

Abstract: The present invention relates to a method for identifying a candidate therapeutic for a disease caused by infection with a human cytomegalovirus (HCMV) having a glycoprotein B (gB) polypeptide, comprising contacting the HCMV gB polypeptide comprising a druggable region with a compound, wherein binding of said compound indicates a candidate therapeutic. The present invention also relates to candidate therapeutics comprising modulators and inhibitors of HCMV activity and pharmaceutical compositions comprising said modulators and inhibitors and methods of use thereof.

Abstract: The invention relates to a method of visualising a peripheral nerve, the method comprising contacting the nerve with a 5-aminolevulinate or a derivative thereof.

Abstract: The invention relates to compositions and methods for diagnosing as well as treating cancer diseases associated with choline kinase (ChoK). Specifically, the invention relates to a composition comprising an intrinsically fluorescent choline kinase (ChoK) inhibitor or a ChoK inhibitor operably linked to a fluorescent dye. The composition is capable of diagnosing and/or treating cancer diseases associated with ChoK.

Abstract: The present disclosure relates to Fibroblast Activating Protein(FAP) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing Fibroblast Activating Protein(FAP). The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.

Abstract: The present invention relates to compounds of formula (I) and formula (II). The compounds of the invention may be used in a method of treatment of a fungal infection, a bacterial infection, or an ameobic infection.

Abstract: The invention relates generally to the use of an ophthalmic solution comprising two or more dyes to enhance visualization of tissues and boundaries of openings in tissues during cataract surgery. The combined dye concentration is for example greater than or equal to 0.3% and less than or equal to 0.45% by weight. The ophthalmic solution is packaged in a delivery device configured for example to introduce the solution into the anterior chamber of an eye and apply it to the anterior lens capsule in the eye.

Abstract: The present disclosure describes hyperpolarized materials for use in nuclear magnetic resonance, magnetic resonance imaging, or similar applications. The present disclosure describes methods for producing hyperpolarized materials for use in nuclear magnetic resonance, magnetic resonance imaging, or similar applications. The present disclosure describes precursor compounds for use in producing hyperpolarized materials for use in nuclear magnetic resonance, magnetic resonance imaging, or similar applications.

Abstract: The invention relates to a process for the manufacturing of a solution of a dimeric C gadolinium complex, such as [?-[1-[bis[2-(hydroxy-xO)-3-[4,7,10-tris[(carboxy-xO)methyl]-1,4,7,10-tetraazacyclododec-1-yl-?N1,?N4, ?N7,?N10]propyl]amino]-1-deoxy-D-glucitolate(6-)]]digadoliniumcomplex, which is useful in the field of diagnostic imaging and of contrast agents in Magnetic Resonance Imaging (MRI), comprising the steps of precipitating a portion of free gadolinium metal ions by means of a precipitating agent. The invention further relates to a process for isolating the dimeric gadolinium complex from said solution, and to the solution and the isolated dimeric gadolinium complex obtainable by such processes.

Abstract: Described herein is a composition including a compound according to Formula I: wherein M is a Group 7 transition metal. R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, and phenethyl; R2 is selected from the group consisting of —H and methyl; R3 is selected from the group consisting of —H, methyl, ethyl, propyl, butyl, and phenethyl; and R4 is selected from the group consisting of —H, methyl, and -L-Z, wherein L is a linker and Z is a targeting unit. Also disclosed are methods including administering, to a patient suffering from a cancer or suspected of suffering from a cancer, the composition. Further disclosed are kits comprising the composition and instructions to perform the method.

Abstract: Conjugates that include two or more chelators (e.g., a chelator of a radiotherapy isotope and a chelator of an imaging isotope) covalently attached to one or more binding moieties are provided herein. The conjugates can be used for treating cancer or non-cancer conditions, and can serve as both an imaging and a radiotherapy molecule when the imaging isotope is complexed to the chelator of the imaging isotope and the radiotherapy isotope is complexed to the chelator of the radiotherapy isotope.

Abstract: This disclosure relates to using 3-iodopropyl-1,2,3-triazol-1-yl or 3-bromopropyl-1,2,3-triazol-1-yl as linking groups for generating labeled conjugates. In certain embodiments, disclosure relates to using 3-iodopropyl-1,2,3-triazol-1-yl or 3-bromo-propyl-1,2,3-triazol-1-yl as linking groups for generating labeled polysaccharide conjugates or derivatives. In certain embodiments, this disclosure relates to methods of generating radionuclides.

Abstract: Among the various aspects of the present disclosure is the provision of compositions of imaging agents and methods for use in detecting, monitoring, and evaluating CCR2 associated diseases, disorders, and conditions.

Abstract: The present invention provides a multivalent compound for targeted molecular imaging and/or targeted drug delivery, wherein two components or targeting molecules each interacts with one or more biomarkers on a cell. The present invention further provides a multifunctional chelator to combine the targeting molecules. The present invention also provides an in vitro high-throughput screening assay to determine the length of the spacer molecules. The present invention also relates to compounds/probes, kits and methods for use in targeted molecular imaging and/or targeted drug delivery.

Abstract: Provided are methods for treating acute myeloid leukemia that include administering a regimen of venetoclax and lintuzumab-Ac225, in which (a) the regimen includes a plurality of cycles, each cycle lasting from 28 to 60 days, (b) the regimen includes (i) orally administering venetoclax on days 1 and 2 of the first cycle at a ramp-up dosage, and thereafter orally administering 400 mg of venetoclax daily on days 3-21 of the first cycle and days 1-21 of each subsequent cycle, and (ii) intravenously administering lintuzumab-Ac225 on day 4, 5, 6 or 7 of each cycle at a dose of from 0.1 ?Ci/kg to 2.0 ?Ci/kg, and (c) the subject has a peripheral blast burden at or below 1,000 blast cells/?l. Also provided are related methods in which the regimen includes intravenously administering lintuzumab-Ac225 twice during each cycle.

Abstract: The use of anti-LAG3 antibodies or antigen-binding fragments thereof in immuno-PET imaging of tumors and treating patients are provided, along with compositions, formulations, and kits comprising the anti-LAG3 antibodies or antigen-binding fragments thereof.

Abstract: A fast harmless treatment device for a hazardous flexible material is provided. The fast harmless treatment device includes a container body and a container lid, where a bottom plate is fixed at a near-bottom position of the container body; a movable plate is provided in the container body; there is a gap between an outer edge of the movable plate and an inner wall of the container body; a movement mechanism is configured to compress a hazardous flexible material on the movable plate towards the container lid; the container lid and the movable plate each are provided therein with a heating tube; and a heating tube and a blowing device are provided on the bottom plate to cause high-temperature convection and disinfect an aerosol-mixed gas.

Abstract: The present disclosure relates to ultraviolet (UV) disinfection devices, systems and methods for automatically preheating a plurality of UV emitters of the UV disinfection device in response to the UV disinfection device being coupled to a power source, independent of the activation of the plurality of EV emitters, or a ballast or power supply thereof, in order to minimize a total disinfection cycle time. In certain optional embodiments, the present disclosure relates to UV disinfection devices, systems and methods for dynamically adjusting a power-level of each of the plurality of UV emitters based on corresponding UV sensor measurements in order to further minimize the total disinfection cycle time. In other optional embodiments, the present disclosure relates to UV disinfection devices, systems and methods for optimizing alignment of each of a plurality of UV emitters within a room in order to further minimize the total disinfection cycle time.

Abstract: A self-sanitizing handrail system includes an elongate handle extending along a central axis and including an exterior surface graspable by users of the handrail system, an annular sanitizing module positioned around the handle and including an outer housing and a sanitizer positioned in the housing and configured to sanitize by a sanitizing light emitted by the sanitizer pathogens located on the exterior surface of the handle, a linear drive extending along the central axis of the handle and coupled to the sanitizing module, and a motor coupled to the linear drive and configured to transport the sanitizing module rectilinearly along the central axis of the handle in response to activation of the motor.

Abstract: A disinfection system is disclosed. The disinfection system includes a base, a first arm mechanically coupled to the base at a first joint, a second arm mechanically coupled to the first arm at a second joint, and an emission module mechanically coupled to the second arm at a third joint. The emission module may include a third arm that includes one or more scanners configured to emit electromagnetic energy further configured to disinfect a first surface. The emission module may also include the one or more scanners, focusing lens, a lens frame, and a rotary actuator, wherein the rotary actuator is configured to align one of the one or more scanners with the focusing lens to produce a narrow electromagnetic beam, or position the focusing lens out of alignment with the one of the one or more scanners to produce a broad electromagnetic beam.

Abstract: An autonomous or semi-autonomous cleaning device having a disinfection module mounted therein for disinfecting walls and objects in the areas it operates. The disinfection module consists of a fan, atomizer nozzle, an electrostatic module and a disinfection tank to store disinfection solution. The nozzle of the disinfection module will spray a stream of disinfection solution towards walls and objects to disinfect these surfaces. The system activates an electrostatically charged disinfection misting system which is designed to disinfect vertical surfaces and select horizontal surfaces.

Abstract: The present disclosure relates to UV disinfection devices, systems, and methods for dynamically adjusting a power-level of each of a plurality of UV emitters of the UV disinfection device based on corresponding UV sensor measurements to minimize the total disinfection cycle time. In certain optional embodiments, the present disclosure relates to UV disinfection devices, systems, and methods for optimizing alignment of each of a plurality of UV emitters within a room to minimize the total disinfection cycle time. In other optional embodiments, the present disclosure relates to UV disinfection devices, systems, and methods for automatically preheating the plurality of UV emitters in response to the UV disinfection device being coupled to a power source, independent of a ballast (or power supply) of the plurality of UV emitters in order to minimize the total disinfection cycle time.