Abstract: The present disclosure relates to CXCR3 ligands having CXCR3-expressing-cell migration-inducing activity, and specifically to amino acid modifications and amino acid sequences that are important for CXCR3-expressing-cell migration-inducing activity.

Abstract: The present invention generally relates to immunoconjugates, particularly immunoconjugates comprising a mutant interleukin-2 polypeptide and an antibody that binds to PD-1. In addition, the invention relates to polynucleotide molecules encoding the immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

Abstract: The present disclosure relates to methods, formulations and dosage regimen for treating pediatric central precocious puberty. The solid oral dosage form of the present disclosure provides an improved alternative to other methods of treatment of central precocious puberty, which are all injectable products. An oral tablet formulation of leuprolide offers a convenient and painless treatment option that allows for flexible dose adjustment or stopping treatment, in contrast to the injectable depot formulations.

Abstract: The present disclosure provides for, and includes, pharmaceutical formulations comprising an MANP peptide, methods of preparing such formulations, and uses of such formulations in the treatment of diseases and conditions for which use of the peptide contained in such formulations is indicated. The present disclosure further provides for, and includes, methods for increasing the stability by a peptide formulation and for reducing aggregation during production of a peptide formulation.

Abstract: The invention relates to a dosage regime for compounds having agonist activity at the GLP-1 (glucagon-like-peptide 1) and GLP-2 (glucagon-like peptide 2) receptors for use in the treatment of obesity and related conditions.

Abstract: The disclosure provides for compounds, compositions, and methods of use thereof for treating diabetes (e.g., type 1 diabetes, type 2 diabetes). In some aspects, methods comprise administering first, second, third, fourth, and fifth daily doses of insulin-like growth factor 2 (“IGF-2”) or a variant thereof to the subject at respective first, second, third, fourth, and fifth different times, wherein each of the daily doses comprises at least 65 ?g of IGF-2. In other aspects, compounds, compositions, and methods containing IGF-2 or variants thereof are used for treating a disorder in a patient in need thereof, such as type 1 or type 2 diabetes.

Abstract: Disclosed are compositions comprised of fibrinogen, Factor VIII, and a positively charged amino acid, wherein the ratio of the positively charged amino acid to Factor VIII ranges from above 1.4 to below about 8.3 mg/IU, respectively, the compositions being for use e.g., for intravenous administration. Further disclosed are methods for the preparation of the compositions.

Abstract: The present invention relates to nucleic acid molecules encoding Lamin A, vectors, AAV and pharmaceutical compositions comprising said nucleic acid molecules for use in treatment of laminopathies.

Abstract: The present invention relates to functional foods comprising DAO and their use for the prevention or treatment of diseases or pathological conditions associated with high levels of histamine in blood, in particular for the prevention or treatment of migraine, chronic fatigue, fibromyalgia, spondylitis and pain caused by muscle contractures.

Abstract: The present invention relates to functional foods comprising DAO and their use for the prevention or treatment of diseases or pathological conditions associated with high levels of histamine in blood, in particular for the prevention or treatment of migraine, chronic fatigue, fibromyalgia, spondylitis and pain caused by muscle contractures.

Abstract: This invention provides for methods of treating one or more of endotoxemia, sepsis, colitis, elevated cytokine levels and an inflammatory condition in a subject in need thereof, which comprises administering an effective amount of a composition comprising purified choline acetyl transferase (ChAT) or purified ChAT conjugated to polyethylene glycol (PEGylated ChAT) and a pharmaceutically acceptable carrier to said subject.

Abstract: Described herein are methods of treating pyruvate kinase deficiency (PKD), sickle cell disease or thalassemia with mitapivat or a pharmaceutically acceptable salt thereof, or use of the drug for the treatment of these conditions, in combination with or in the absence of with a secondary drug, such as an inducer or an inhibitor of cytochrome P450. Various doses and dosing regimens of mitapivat in monotherapy and in concomitant medications are described.

Abstract: In certain aspects, the present invention provides novel lyophilized formulations of ENPP1 polypeptides, as well as methods for using such lyophilized formulations and reconstituted formulations of ENPP1 to treat an indication associated an ENPP1 deficiency. The formulations and methods provided herein are useful in treating diseases associated with an ENPP1 deficiency such as pathological calcification or pathological ossification.

Abstract: The present invention provides, among other things, methods of treatment of Metachromatic Leukodystrophy Disease (MLD) and compositions comprising recombinant arylsulfatase A (ASA) protein using enzyme replacement therapy.

Abstract: The present invention relates methods for treating cancer by comprising administering to the subject an agent for reducing at least one NEAA, inhibiting the PPP pathway, inhibiting the sorbitol pathway, inhibiting heme biosynthesis, or any combination thereof. The invention also includes methods of treating cancer comprising detecting a tumor as having increased ROS administering to the subject an agent for reducing at least one NEAA, inhibiting the PPP pathway, inhibiting the sorbitol pathway or inhibiting heme biosynthesis, or any combination thereof.

Abstract: A composition comprising, for example, chemically modified RNA (cmRNA) encoding CST6 or a polypeptide with at least 80% amino acid sequence identity thereto, and methods of making and using the cmRNA, are provided.

Abstract: The invention of the current disclosure includes methods and compositions useful for producing personalized cancer immunotherapies which target tumor-associated neoepitopes. Also included are methods for treating cancer in subjects in need thereof.

Abstract: The invention relates to genetically modified arenaviruses suitable for the treatment of neoplastic diseases, such as cancer. The arenaviruses described herein may be suitable for treatment of neoplastic diseases and/or for the use in immunotherapies. In particular, provided herein are methods and compositions for treating a neoplastic disease by administering a genetically modified arenavirus, wherein the arenavirus has been engineered to include a nucleotide sequence encoding one or more antigenic fragment(s) of mutant KRAS alone or to further include a nucleotide sequence encoding one or more antigenic fragment(s) of a mutated cancer driver gene (e.g., a mutant TP53) or a tumor-associated antigen.

Abstract: Embodiments of the present disclosure pertain generally to head and neck squamous cell carcinomas (HNSCCs) related to human papillomavirus subtype 16 (HPV16) infections. More particularly, the present disclosure provides novel immunogenic epitopes from HPV16 E2, E6 and E7 antigens restricted by common human leukocyte antigen (HLA) alleles for the diagnosis and treatment of HNSCC. The HPV16 epitopes identified in the present disclosure can be used in combination with blockade of HPV16+ HNSCC-specific checkpoints for targeted immunotherapy.

Abstract: The present invention relates to a process for producing an immunogenic live attenuated Chikungunya virus, as well as pharmaceutical compositions comprising the same.

Abstract: Provided herein are methods and compositions for inducing in a subject a broad neutralizing antibody response to human immunodeficiency virus (HIV) infection.

Abstract: Disclosed are trimeric complexes comprising an uncleaved prefusion optimized gp140 env trimer. Disclosed are compositions comprising a trimeric complex, wherein the trimeric complex comprises an uncleaved prefusion optimized gp140 env trimer. Disclosed are methods of inducing an immune response against HIV in a subject comprising administering one or more of the disclosed compositions to a subject in need thereof. Disclosed are methods of generating neutralizing antibodies (nAbs) to HIV in a subject comprising administering one or more of the disclosed compositions to a subject in need thereof. Disclosed are method of treating a subject infected with HIV comprising administering one or more of the disclosed compositions to a subject in need thereof.

Abstract: The invention generally relates to a novel ‘One Process’ for production of polypeptides comprising an anti-idiotypic, mirror image of the antigenic determinants of an agent of interest such as a disease-causing agent. In particular, the polypeptides are used to pre-treat samples prior to indirect ELISA assays and in its incorporation in vaccines. When used in indirect ELISA assays, the result is a significant reduction in false positives, while its inclusion in vaccines provides an additive induction of immunity in humans and different animal species by the proteinaceous mirror image of weak immunogens including, lipid, carbohydrate, and low molecular weight molecules of the agent of interest. The incorporation of anti-idiotypes produced by the ‘One Process’ in vaccines induces antibodies that is used in cocktail of therapeutics for treatment of injurious antigens and autoimmune reactions in humans and animals.

Abstract: The present invention is directed to novel nucleotide and amino acid sequences of Porcine Epidemic Diarrhea Virus (“PEDV”), including novel genotypes thereof, all of which are useful in the preparation of vaccines for treating and preventing diseases in swine and other animals. Vaccines provided according to the practice of the invention are effective against multiple swine PEDV genotypes and isolates. Diagnostic and therapeutic polyclonal and monoclonal antibodies are also a feature of the present invention, as are infectious clones useful in the propagation of the virus and in the preparation of vaccines. Particularly important aspects of the invention include polynucleotide constructs that replicate in tissue culture and in host swine. The invention also provides for novel full length PEDV genomes that can replicate efficiently in host animals and tissue culture.

Abstract: An improved method of deoptimization of nucleic acids, particularly nucleic acids associated with genes and/or open reading frames (ORFs) of a variety of pathogens including viruses, retroviruses, bacteria, fungi, and the like. Nucleic acids may be related to genes and/or ORFs from infectious viruses or other diseases and be associated with the elicitation of a protective response when inserted, using recombinant techniques, into a vector and used in a vaccine composition. The nucleic acid sequence of one or more ORFs may be optimized or deoptimized for use in an improved recombinant vaccine to elicit an immune response against an infectious agent when administered to a subject using a variety of dosing and timing regimens.

Abstract: The invention discloses a lentiviral vector and lentiviral vector particles for treating hepatitis B infection. The lentiviral vector and particles of the invention contain a nucleotide sequence coding an hepatitis B virus antigen. The large S antigen of hepatitis B virus was in particular selected as candidate and can be applied in pharmaceutical compositions or vaccines for treating and/or preventing hepatitis B virus infection or treating and/or preventing diseases caused by hepatitis B virus infection, which has excellent therapeutic and preventive effects in subjects in need thereof.

Abstract: This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize epitope(s) from tumor antigens FANCI, RAD51, and PBK. Accordingly, aspects of the disclosure relate to an engineered T-cell Receptors (TCRs), nucleic acids encoding the TCRs, and cells comprising the nucleic acids and TCRs. Also provided are compositions comprising the cells, nucleic acids, or engineered TCRs of the disclosure, methods of making the cells and methods of using the embodiments of the disclosure for therapeutic treatments.

Abstract: The disclosure provides for a vaccine depot formulation that comprises a biodegradable thermosensitive hydrogel that has been loaded or embedded with nanoparticles that comprise an antigen and adjuvant, and uses thereof for protecting a subject from an infection or disease.

Abstract: The present disclosure relates to a pharmaceutical composition comprising chiral nanozyme and method of preventing or treating proliferative diseases using the same. A first nanozyme and/or a second nanozyme according to embodiments of the present disclosure has a chiral structure, and their enzymatic activity is maximized when circularly polarized light with the same directionality as the first nanozyme and/or the second nanozyme is irradiated.

Abstract: Described herein are compositions comprising, and methods for using, biocompatible cold slurries and methods of administering the same to provide reversible inhibition of peripheral nerves in a subject in need thereof.

Abstract: A skin-permeable peptide, a derivative thereof, or a fragment thereof of the present disclosure effectively delivers skin bioactive molecules deep into the skin tissues through assembly or fusion methods, thereby providing outstanding skin permeability as well as excellent skin residual effect of bioactive materials to maximize bioactive efficacy. Accordingly, the skin-permeable peptide, derivative thereof, or fragment thereof may be widely used as an active ingredient of a pharmaceutical composition for external use and a functional cosmetic composition that target skin tissues including mucous membranes.

Abstract: Provided herein are novel compounds of Formula I, pharmaceutical compositions, and methods of using related to membrane bound protein, such as GPR40. The compounds herein are typically GPR40 agonists, which can be used for treating a variety of disorders, conditions or diseases such as Type 2 diabetes.

Abstract: The specification relates to conjugates comprising a linker of Formula (IMA): and pharmaceutically acceptable salts thereof. The specification also relates the use of the conjugates for the treatment of diseases such as cancer, and intermediates useful for the synthesis of the conjugates.

Abstract: The disclosure includes compounds of Formula (I), wherein each of Z, R0, R1, R2, R3, R4, R5, R6, R, L1, L2, L3, L4, L5, L6, Q1, Q2, W, m, n, r, and s, are defined herein. Also disclosed is a method for treating a neoplastic disease, autoimmune disease, and inflammatory disorder with these compounds.

Abstract: The present invention relates to a novel heterocyclic compound and a composition, for preventing or treating a cancer, an autoimmune disease, and an inflammatory disease, comprising same. The novel heterocyclic compound of the present invention is a bifunctional compound having a Bruton's tyrosine kinase (BTK) degradation function via a ubiquitin proteasome pathway, and may be utilized as a composition for preventing or treating a cancer, an autoimmune disease, and Parkinson's disease.

Abstract: Provided herein are hyperbranched poly(?-amino esters) polymers that serve as effective transfection carriers of small interfering RNA (siRNA) for RNA interference (RNAi) mediated gene silencing therapy. These disclosed polymers exhibit outstanding gene silencing efficiency in both easy-to-transfect and hard-to-transfect cells. Furthermore, they are biodegradable and non-toxic.

Abstract: The present disclosure provides compositions comprising protein encapsulated nanoparticles, and methods of making said compositions. In an aspect, a composition may comprise a drug delivery vector and a therapeutic substance, wherein the composition elutes at least 1.0 pg of the therapeutic substance per 100,000 particles of the drug delivery vector over a period of time under conditions of a drug delivery vector release buffer, wherein the therapeutic substance, drug delivery vector and drug delivery vector release buffer comprise a solution, wherein the solution is centrifuged and a portion stored at about 1 to 10° C., and wherein the elution of the therapeutic substance is determined by ELISA assay. This disclosure further describes a method of controlling an immunophenotype in a patient suffering from a disease which impacts the immune system.

Abstract: Disclosed is a method of treating a subject having a malignant glioma comprising: administering by convection-enhanced delivery (CED) for a period of up to 96 hours a therapeutically effective amount of a mutagenized IL13 linked to a cytotoxin (cmIL13); wherein the malignant glioma expresses an interleukin 13 receptor ? 2 (IL13R?2). Also disclosed is a mutagenized IL13 for use in methods of treating a subject having a malignant glioma expressing IL13R?2, wherein the method comprises administering by convection-enhanced delivery (CED) for a period of up to 96 hours a therapeutically effective amount of a mutagenized IL13 linked to a cytotoxin (cmIL13).

Abstract: The subject matter described herein is directed to molecules referred to herein as chemical inducers of degradation (CIDEs) and antibody-conjugated CIDEs (Ab-CIDEs), wherein the Ab-CIDEs comprise an antibody covalently bound to the CIDE through a linker, wherein the CIDE can be further covalently bound to a phosphate moiety, and to the uses of the molecules in treating diseases and conditions where targeted protein degradation is beneficial.

Abstract: The present disclosure relates generally to the fields of immunology and molecular biology. More specifically, provided herein are pharmaceutical combinations comprising antibodies, or antigen-binding portions thereof, directed against LY75, and a platin; methods for preparing pharmaceutical combinations; and methods for the treatment of diseases, such as cancers mediated by LY75 expression or activity.

Abstract: The present invention relates to an antibody-drug conjugate (ADC) targeting Claudin18.2 and a composition containing the molecule. The present invention further relates to therapeutic and diagnostic uses of the antibodies and antibody fragments.

Abstract: Antibody conjugates with camptothecin compounds are described, with methods of use and preparations.

Abstract: The present invention relates to a technique for delivering an antibody to the brain or a tumor tissue. The present invention provides a modified antibody that is targeted. The present invention provides an inactivated antibody that is targeted, wherein the antibody is a modified antibody that is reactivated in the brain or a tumor tissue.

Abstract: Provided herein are compositions, systems, and methods for delivering cargo to a target cell. The compositions, systems, and methods comprise one or more polynucleotides encoding one or more LTR retroelement polypeptides for forming a delivery vesicle and one or more capture moieties for packaging a cargo within the delivery vesicle. The one or more LTR retroelement polypeptides for forming a delivery vesicle may comprise two or more of an LTR retroelement gag protein, a retroelement envelope protein, an LTR retroelement reverse transcriptase, or a combination thereof. The LTR retroelement polypeptide alone, the LTR retroelement envelope protein alone, or both the LTR retroelement-derived polypeptide and LTR retroelement envelope protein may be endogenous.

Abstract: The present invention provides, among other things, improved mRNA-encapsulating lipid nanoparticles that are particularly effective for pulmonary delivery by nebulization. The lipid nanoparticles comprise a lipid component consisting of a cationic lipid, a non-cationic lipid, a PEG-modified lipid, and a cholesterol or cholesterol analogue with a lower molar ratio of the non-cationic lipid than is typically present in lipid nanoparticles delivered via this route of administration.

Abstract: Provided herein are prime editing methods and compositions for treatment of genetic disorders such as Fragile X Syndrome.

Abstract: Methods of using vectors comprising nucleic acid and nucleic acid variants encoding FVIII protein are disclosed. In particular embodiments, a method of treating a human having hemophilia A includes administering a recombinant adeno-associated virus (rAAV) vector comprising a nucleic acid encoding Factor VIII (FVIII) or nucleic acid variant encoding Factor VIII (FVIII) having a B domain deletion (hFVIII-BDD). In some aspects, a nucleic acid variant has 95% or greater identity to SEQ ID NO:7 and/or a nucleic acid variant has no more than 2 cytosine-guanine dinucleotides (CpGs). In other aspects, a rAAV vector is administered to the human at a dose of less than about 6×1012 vector genomes per kilogram (vg/kg).

Abstract: This disclosure relates compositions and methods to delivery of various agents to the inner ear of a subject.

Abstract: The present disclosure relates to CD44-binding peptide reagents, methods for detecting cells such as hepatocellular carcinoma cells using the peptide reagents, and methods for targeting such cells using the peptide reagents.

Abstract: In some aspects, the present disclosure pertains to a polymer that comprises a plurality of polymer arms, wherein a first portion of the polymer arms comprise a reactive end group and wherein a second portion of the polymer arms comprise a branched end group that comprise a plurality of covalently attached diagnostic and/or therapeutic groups, which may be, for example, radiocontrast groups or radioactive groups. Other aspects pertain to a system that comprises (a) a first composition comprising such a polymer and (b) a second composition comprising a multifunctional compound that comprises reactive functional groups that are reactive with the reactive end group of the multi-arm polymer. Still other aspects pertain to a crosslinked reaction product of (a) such a polymer and (b) a multifunctional compound that comprises functional groups that are reactive with the reactive end group of the multi-arm polymer.