Abstract: The present invention relates to polypeptides and analogues thereof for use in the treatment of diabetes and bone disorders. Also disclosed are pharmaceutical compositions comprising the polypeptides and analogues thereof, and methods for the treatment of diabetes and bone disorders.

Abstract: A medicament for preventing or treating heart failure containing an antagonist of the corticotropin releasing hormone receptor 2 as an active ingredient.

Abstract: The present invention relates to pharmaceutical compositions of the GLP-1 peptide semaglutide comprising a stabilizer such as histidine, their preparation, kits comprising such compositions as well as medical uses thereof.

Abstract: The invention provides methods of treating a subject having diabetes mellitus and/or a metabolic derangement.

Abstract: The present disclosure is concerned with compositions comprising insulin and a pharmaceutically acceptable topical carrier. The present disclosure is also concerned with methods of using these compositions for the treatment of a skin ailment such as a diabetic ulcer. The present disclosure is also concerned with methods of using these compositions for the treatment of an ocular ailment. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Provided herein are methods for treating osteoporosis and increasing bone mass density, that includes administering once a day, for about 5 minutes, a transdermal patch loaded with about 300 ?g of abaloparatide, and ZnCl2 at a molar ratio of 2.2:1 of ZnCl2:abaloparatide. Also provided are the single-use transdermal patches loaded with about 300 ?g of abaloparatide, and ZnCl2 at a molar ratio of 2.2:1 of ZnCl2:abaloparatide.

Abstract: The present disclosure relates to compositions and methods for the treatment of bleeding disorders, such as hemophilia A, hemophilia B, von Willebrand (vWF) disease, and factor XII deficiency, by reducing the circulating concentration of tissue factor pathway inhibitor (TFPI), with a factor Xa derivative.

Abstract: Compositions and methods for treating an animal who has been exposed to pyrethroid are provided. An effective amount of a pyrethroid detoxifying enzyme to prevent or treat pyrethroid toxicity. The pyrethroid detoxifying enzyme is one or more pyrethroid-hydrolyzing carboxylesterases.

Abstract: Disclosed herein is a liquid pharmaceutical composition of botulinum toxin which is improved in stability. It comprises botulinum toxin, polysorbate 20, and methionine and optionally isoleucine. Employing, instead of the animal-derived protein albumin or gelatin, a combination of polysorbate 20 and methionine and optionally isoleucine as botulinum toxin stabilizers, the liquid pharmaceutical composition eliminates the risk of contaminating the body with serum-derived pathogens or microorganisms and can be administered safely to the body. Also, the composition is convenient for use as a direct injection for patients. Superior to conventional compositions employing either detergents or amino acids in terms of the storage stability of botulinum toxin at 25˜37° C. as well as at refrigerated temperatures, the liquid pharmaceutical composition of the present invention is very useful for storing botulinum toxin under an emergency condition such as an environment without maintaining low temperature.

Abstract: The present specification discloses methods and uses for treating a migraine disorder. The disclosed method comprising extramuscularly administering a Botulinum toxin to an individual in one of more areas of a fronto-fascial layer located in a frontal head region of the individual, one of more areas of a temporoparietal-fascial layer located in a temporal head region of the individual, and one or more areas of an occipito-fascial layer located in an occipital head region of the individual. The disclosed methods and uses further comprise extramuscularly administering a Botulinum toxin to one or more nerve exit points and/or one or more subcutaneous locations in the head and neck as well as one or more sites of an epicranial aponeurosis. The disclosed methods and uses further comprise intramuscularly administering a Botulinum toxin to one or more locations within the left and right Splenius Capitus muscle, the left and right Masseter muscles, the left and right Trapezius muscles, or any combination thereof.

Abstract: Methods and compositions therefor of treating GAMT deficiency or guanidino acetate (GAA) toxicity in a subject comprising administration of an arginine depleting enzyme. An therapeutic formulation can include an arginase, an arginine deiminase or a combination thereof and optionally other compounds, and can be adapted for intravenous or subcutaneous administration to a subject.

Abstract: The present disclosure relates to methods for profiling subject specific and personalized T cell receptor (TCR) repertoires using a single-cell sequencing method. More particularly, disclosed are methods for determining binding of T cell receptors to subject specific neoantigens. In addition, the techniques herein may identify the antigenic targets of T cell receptors in the context of tumor neoantigens. Moreover, the present disclosure enables the discovery of T cell targets in numerous diseases, with implications for understanding the basic mechanisms of the mammalian immune response and for developing antigen-specific diagnostic markers and therapies. Finally, cloned TCRs can be used to formulate personalized immunotherapies for those inflicted with a disease, such as cancer.

Abstract: The present invention relates to polypeptides comprising a fragment of a teleost invariant chain optionally fused to one or more antigens or a teleost invariant chain fused to one or more antigens or antigenic fragments thereof, a polynucleotide encoding such polypeptides, vectors comprising such polynucleotides, collection of vectors comprising such polynucleotides and use of such polypeptides, polynucleotides, vectors for treating or preventing diseases, in particular tumor diseases. The teleost invariant chain polypeptides or fragments thereof act as “T cell enhancer” converting non-immunogenic antigenic sequences into immunogenic T cell antigens.

Abstract: The present invention relates to a method for selecting cancer neoantigens for use in a personalized vaccine. This invention relates as well to a method for constructing a vector or collection of vectors carrying the neoantigens for a personalized vaccine. This invention further relates to vector and collection of vectors comprising the personalized genetic vaccine and the use of said vectors in cancer treatment.

Abstract: Provided herein are methods, kits and compositions for the treatment and/or prevention of ovarian cancer through the induction of an immune response against Anti-Mullerian Hormone Receptor, Type II (AMHR2).

Abstract: A composition comprising particles formed of poly(diamidosulfide) and one or more leptospiral antigens, and methods of making and using the composition, are provided.

Abstract: A multivalent immunogenic composition is provided, including one or more recombinant proteins selected from the group consisting of a recombinant attenuated Staphylococcus pseudintermedius Protein A (SEQ ID NO:2), a recombinant attenuated Staphylococcus pseudintermedius Leukotoxin S (SEQ ID NO:4), a recombinant attenuated Staphylococcus pseudintermedius Nucleotidase adenosine synthase protein (AdsA) (SEQ ID NO:6), a recombinant attenuated Staphylococcus pseudintermedius coagulase (SEQ ID NO:8), a recombinant attenuated Staphylococcus pseudintermedius Leukotoxin F (SEQ ID NO:10), and a recombinant attenuated Staphylococcus pseudintermedius exotoxin 15 (SEQ ID NO:12). Synthetic genes expressing the attenuated recombinant proteins and optimized for expression in E. coli are provided. Vaccines and therapeutic compositions comprising the one or more recombinant proteins are provided.

Abstract: The invention is related to multivalent immunogenic compositions comprising more than one S. pneumoniae polysaccharide protein conjugates, wherein each of the conjugates comprises a polysaccharide from an S. pneumoniae serotype conjugated to a carrier protein, wherein the serotypes of S. pneumoniae are as defined herein. In some embodiments, at least one of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. In further embodiments, each of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. Also provided are methods for inducing a protective immune response in a human patient comprising administering the multivalent immunogenic compositions of the invention to the patient. The multivalent immunogenic compositions are useful for providing protection against S. pneumoniae infection and diseases caused by S. pneumoniae.

Abstract: Provided is a pharmaceutical composition including attenuated Streptococcus pneumoniae strains, and a method thereof for prevention or treatment of inflammatory diseases, respiratory viral infections, bacterial infectious diseases, or allergic diseases.

Abstract: Novel methods for exporting target proteins from the cytosol to the extracellular surface of bacterial cells are provided. The methods are useful in that they permit the preparation of vaccines for the prevention of bacterial infectious diseases.

Abstract: The technology is directed to HIV envelopes which comprise sequence modifications wherein these modifications prevent CD4-induced transitions of the HIV envelope. Specifically, the disclosure provides recombinant HIV-1 Env proteins comprising mutations, wherein the envelope is a protomer, and wherein three protomers form a trimer stabilized by the presence of the mutations. Provided also are compositions comprising envelopes of the technology, and methods of use.

Abstract: The invention is directed to modified HIV-1 envelopes, compositions comprising these modified envelopes, nucleic acids encoding these modified envelopes, compositions comprising these nucleic acids, and methods of using these modified HIV-1 envelopes and/or these nucleic acids to induce immune responses.

Abstract: Provided herein are universal prophylactic compositions for preventing infection with influenza viruses by directing the immune response to highly conserved regions of the virus. Also provided are universal therapeutic compositions for treating influenza infection by targeting the highly conserved regions. Methods for using the prophylactic and therapeutic compositions are also provided.

Abstract: Provided herein are non-naturally occurring, broadly reactive, pan-epitopic antigens derived from H3 influenza virus that are immunogenic and are capable of eliciting a broadly reactive immune response, such as a broadly reactive neutralizing antibody response, against H3 vims following introduction into a subject. Also provided are non-naturally, broadly reactive occurring immunogens, vaccines, virus-like particles (VLPs) and compositions comprising the immunogens and vaccines. Methods of generating an immune response in a subject by administering the immunogens, vaccines, VLPs, or compositions thereof are provided. In particular, the immunogens comprise the hemagglutinin (HA) protein of H3 influenza vims strains.

Abstract: The present invention is directed to a nucleic acid suitable for use in treatment or prophylaxis of an infection with a coronavirus, preferably with a Coronavirus SARS-CoV-2, or a disorder related to such an infection, preferably COVID-19. The present invention is also directed to compositions, polypeptides, and vaccines. The compositions and vaccines preferably comprise at least one of said nucleic acid sequences, preferably nucleic acid sequences in association a lipid nanoparticle (LNP). The invention is also directed to first and second medical uses of the nucleic acid, the composition, the polypeptide, the combination, the vaccine, and the kit, and to methods of treating or preventing a coronavirus infection, preferably a Coronavirus infection.

Abstract: The present invention relates to the construction of, and immunization with viral vaccines. In particular, bivalent vaccines that are capable of providing simultaneous virus infection protection for two or more different viruses. Furthermore, the bivalent vaccines contemplated herein are contemplated as being effective in a neonatal mammal. One such bivalent viral vaccine comprises two antigenic epitopes against the dengue viruses and at least one antigenic epitope against hepatitis B virus. Immunization cross-reactivity may also provide infection protection against other viruses as well.

Abstract: Formulation and use of antibodies which bind human APRIL for the treatment of conditions related to IgA overproduction or deposition, including IgA Nephropathy.

Abstract: The present invention relates to Eutectic Mixtures (EM), and preferably Deep Eutectic Solvents (DES), that are used in or as oral pharmaceutical formulation platforms. These platforms improve the solubility and bioavailability of active pharmaceutical ingredients (API), and especially of poorly water-soluble APIs. The deep eutectic solvent (DES) compositions of the invention make use of a combination of a glycol with a polymer solubilizer component in specific molar ratios.

Abstract: Disclosed herein are methods for improving a parameter of a protein-related process comprising providing a viscosity-reducing excipient compound selected from the group consisting of hindered amines, aromatics and anionic aromatics, functionalized amino acids, oligopeptides, short-chain organic acids, low molecular weight aliphatic polyacids, diones and sulfones, zwitterionic excipients, and crowding agents with hydrogen bonding elements, and adding a viscosity-reducing amount of the viscosity-reducing excipient compound to a carrier solution for the protein-related process, wherein the carrier solution contains a protein of interest, and carrier solutions comprising a liquid medium in which is dissolved a protein of interest, and a viscosity-reducing excipient, wherein the viscosity of the carrier solution has a lower viscosity that that of a control solution that is substantially similar to the carrier solution except for the presence of the viscosity-reducing excipient.

Abstract: The present invention relates to excipients for special protein formulations, which are suitable to improve the thermal stability against denaturation and deactivation. In particular, the present invention relates to additives for thermostabilizing of vaccine formulations.

Abstract: The present document describes a process for the preparation of a low functionalization polysaccharide having carboxyl groups, comprising a) swelling of a polysaccharide granule in boiling water or a water/polyol mixture, to obtain a swollen polysaccharide; b) partial gelatinization of said swollen polysaccharide in an alkaline solvent mixture of water and alcohol and/or polyol, to obtain a partially gelatinized polysaccharide; and c) partial functionalization of said partially gelatinized polysaccharide with a functionalizing agent, to obtain the low functionalization polysaccharide.

Abstract: A method for the precise cellular destruction of an oncogenic non-coding RNA with a RNA-binding small molecule conjugated with bleomycin A5 is described. The method affords reversal of phenotype. Bleomycin A5 was coupled to an RNA-binding molecule that selectively binds the microRNA-96 hairpin precursor (pri-miR-96). By coupling of bleomycin A5's free amine to the RNA-binding molecule, its affinity for binding to pri-miR-96 is >100-fold stronger than to DNA. The conjugate compound selectively cleaves pri-miR-96 in triple negative breast cancer (TNBC) cells. Selective cleavage of pri-miR-96 enhances expression of FOXO1 protein, a pro-apoptotic transcription factor that miR-96 silences, and triggers apoptosis in TNBC cells. No effects were observed in healthy breast epithelial cells. This method provides programmable control for targeting RNA through the selection of an RNA-binding molecule/bleomycin A5 conjugate and provides a facile method of mapping the cellular binding sites of an RNA-binding molecule.

Abstract: This disclosure provides peptide conjugates that are useful for inhibiting the progression of a hyperproliferative disorder, inhibiting the progression of sepsis, inhibiting the progression of an infectious disease, enhancing a response to a vaccine, or inhibiting the progression of a synucleinopathy.

Abstract: Disclosed are proteasome inhibitors, fibroblast activation protein (FAP)-activated prodrugs of proteasome inhibitors, and pharmaceutically acceptable salts of the inhibitors and prodrugs. Also disclosed are related pharmaceutical compositions, and methods of using the inhibitors and prodrugs and compositions thereof, for example, in treating cancer or other cell proliferative diseases. In vitro and in vivo methods of quantifying the expression of FAP in a biopsy sample and a mammal, respectively, are also disclosed.

Abstract: A mitochondrial-targeted PARP inhibitor is provided herein, as well as methods of making and using the mitochondrial-targeted PARP inhibitor.

Abstract: Disclosed herein are extracellular vesicles such as exosomes that selectively target cells such as skeletal muscle cells. Such vesicles include skeletal muscle targeting moieties and can be used to selectively deliver a payload to skeletal muscle cells or tissue.

Abstract: The present disclosure relates to an applicable bio-conjugation process for preparing antibody-drug conjugates (ADCs) with improved homogeneity. As compared with conventional conjugation process, the homogeneity of antibody-drug conjugate (ADC) products generated from the bio-conjugation process can be dramatically improved. Specifically, in the ADCs prepared by the process of the present disclosure, the content of D0+D8 is less than 10 wt % and the content of D6 is less than 10 wt %. Moreover, the content of D4 is generally more than 65 wt %, for example, more than 70 wt %, and more than 77 wt %, while the content of D4 is normally less than 40 wt % in the ADCs prepared by conventional conjugation processes.

Abstract: The present invention relates to binding protein-toxin conjugates comprising one or more anthracycline toxin moieties, and the use thereof in immunooncological applications.

Abstract: Described herein are compositions and methods useful for the depletion of CD117+ or CD45+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. The compositions and methods described herein can be used to treat a disorder, for instance, by depleting a population of CD117+ or CD45+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for allogeneic hematopoietic stem cell transplant therapy and to improve the engraftment of allogeneic hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.

Abstract: The present invention relates to a method for producing a conjugate of two substrates, the method comprising the steps of (a) providing two substrates, each substrate being independently selected from the one or more of the groups consisting of small molecules, and proteins, and (b) enzymatically conjugating the two substrates using a sortase F enzyme, or a catalytic domain thereof. One substrate comprises a sortase F recognition motif, while the other substrate comprises at least one motif selected from a Glyn motif, an Alan motif, or a motif consisting of a mixture of Ala and Gly residues the motif totaling n residues, where n is an integer from ?1 to ?21. The reaction takes place in an aqueous reaction medium comprising a salt concentration of from about ?0.01 to ?3 M, thereby producing a conjugated product of the two substrates.

Abstract: The present invention relates to dual-targeting lipid-polymer hybrid nanoparticles (T-hNPs) comprising a polymer core comprising a heme oxygenase 1 inhibitor and a lipid membrane (shell) comprising a targeting moiety, a kit for preparing the dual-targeting lipid-polymer hybrid nanoparticles, a pharmaceutical composition comprising the dual-targeting lipid-polymer hybrid nanoparticles as an active ingredient, and a method of preventing or treating cancer comprising administering the pharmaceutical composition to a subject in need thereof.

Abstract: Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation.

Abstract: Treatment of neurodegenerative diseases with copper nanoclusters (CuNCs), where the neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), and glaucoma.

Abstract: Disclosed herein are compositions comprising complexes of cyclodextrins and lipid-modified stem cell proteins. Also disclosed are topical compositions the complexes. Methods of using the compositions for the therapeutic purposes are also disclosed as well as methods of producing the compositions.

Abstract: This disclosure provides gene therapy vectors comprising a polynucleotide encoding one or more isoforms of lysosome-associated membrane protein 2 (LAMP-2), and methods of using such gene therapy vectors for the treatment of Danon disease and other autophagy disorders.

Abstract: A composition comprising at least one AAV vector formulated for intrathecal delivery to the central nervous system is described. The composition comprises at least one expression cassette which contains sequences encoding an immunoglobulin construct linked to expression control sequences therefor and a pharmaceutically acceptable carrier. The immunoglobulin construct may be an immunoglobulin modified to have decreased or no measurable affinity for neonatal Fc receptor (FcRn).

Abstract: The present invention relates to a nucleic acid molecule encoding human albumin for increasing the levels and/or activity of a protein or polypeptide encoded by a transgene, comprising a sequence defined by SEQ ID NO: 14 or a sequence having at least 80% sequence identity to said sequence, its use in nucleic acid expression cassettes and vectors containing liver-specific regulatory elements and codon-optimized factor IX, factor VIII, factor VII or factor VIIa transgenes, methods employing these expression cassettes and vectors and uses thereof. The present invention is particularly useful for applications using liver-directed gene therapy, in particular for the treatment of hemophilia A, hemophilia B or factor VII deficiency.

Abstract: The present disclosure relates to a method for calculating a tolerated dose of a human body to sugar alcohol and functional sugar.

Abstract: The present invention is related to the in vitro use of lyso-Gb1 as a draggable target in the development of a drug, and to antagonist of lyso-Gb1 for use in the treatment and/or prevention of a disease, wherein the disease is Gaucher disease or Parkinson's disease

Abstract: A method for measuring, adjusting and maintaining the level of blood volume in a patient is described. A blood volume expander composition includes, in combination, a standard unmodified protein, colloid or crystalloid and a fluorescently-labeled protein, colloid or crystalloid of approximately the same molecular weight. The use of blood volume expanders to measure, adjust and maintain the level of blood volume in a patient also is described.