Abstract: A drug product comprising a combination of highly purified collagenase I and collagenase II from Clostridium histolyticum is disclosed. The drug product includes collagenase I and collagenase II in a ratio of about 1 to 1, with a purity of greater than at least 95%. The invention further disclosed improved fermentation and purification processes for preparing the said drug product.

Abstract: Pharmaceutical compositions that stabilize a Clostridial toxin active ingredient are described. The compositions can be liquid or solid compositions, and comprise a surfactant and an antioxidant. In some embodiments, the compositions comprise a surfactant selected from a poloxamer and a polysorbate; an antioxidant selected from methionine, N-acetyl cysteine, ethylenediaminetetraacetic acid and combinations thereof; and, optionally, a tonicity agent and/or a lyoprotector selected from, for example, trehalose and sucrose.

Abstract: The present disclosure describes the grafting of epitope residues from human PCSK9 to non-human PCSK9 or PCSK9 structural homologs and elimination of 9-mers oligopeptides that are found in human protein to reduce self-targeting response. Anti-genicity of the epitope-scaffold constructs was demonstrated toward anti-human PCSK9 antibodies. similar to wild type human PCSK9. It was shown that disclosed PCSK9 immunogens could significantly reduce LDL and cholesterol levels in immunized mice.

Abstract: This invention relates to an immunogen comprising a gonadotropin releasing hormone (GnRH) peptide sequence, a kisspeptin peptide sequence and a stimulant of raising an immune response, such an immunogen for use in a method to regulate the release of hormones in a vertebrate including modulation of reproductive hormones, to reduce fertility in a vertebrate and to treat hormone-dependent diseases including hormone-dependent tumours including prostate tumours, breast, ovary and endometrial tumours, benign hyperplasia including benign prostatic hyperplasia and uterine fibroids, endometriosis, polycystic ovarian disease, infertility, sexual dysfunction and any disorder that would benefit from an increased or decreased GnRH-dependent activity and a vaccine formulation comprising the immunogen. The invention also relates to the use of the immunogen in the preparation of a medicament for use in a method to regulate the release of hormones in a vertebrate.

Abstract: This disclosure describes, in one aspect, immunogens effective for treating and/or diagnosing tauopathy, and immunotherapeutic compositions and methods involving those immunogens. Generally, the immunogen includes an antigen presentation component and a microtubule-associated tau protein (MAPT) component linked to at least a portion of the antigen presentation component. This disclosure describes, in another aspect, a transgenic mouse. Generally, the transgenic mouse possesses brain cells that have a polynucleotide that encodes human microtubule-associated protein tau (MAPT). The polynucleotide further exhibits a deletion of at least a portion of endogenous mouse MAPT. The transgenic mouse also includes a forebrain neuron-specific deletion of a polynucleotide that encodes Myeloid Differentiation Primary Response Gene 88 (MyD88). In a further aspect, this disclosure describes a method of producing the transgenic mouse.

Abstract: This disclosure describes a nucleic acid construct that contains sequences for an Endotope construct, a STAT1c, and miR142 target sites. In one example, disclosed is composition comprising an Endotope construct and a STAT1 construct including a nucleic acid sequence encoding a constitutively active STAT1 (e.g. STAT1c), wherein the Endotope and the STAT1 constructs each include miR142 target sites. In alternative examples, disclosed is a single construct that includes the Endotope construct and STAT1 construct along with miR142 target sites. The nucleic acid constructs can be packaged into polycationic molecules or liposome to create nanoparticles for efficient cell transfection.

Abstract: The present invention relates to a method for prevention and/or treatment of an autoimmune disease, comprising administering a composition, said composition comprising at least one beta cell autoantigen, to a subject The subject may have a serum vitamin-D level above 50 nanomole/liter or the composition may be administered by intralymphatic injection or injection directly into a lymph node, or over a period of weeks, months, or years.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.

Abstract: The disclosure provides a method of treating cancer in a human subject. The method comprises, e.g., administering a dose of nanoparticles every two weeks for an initial treatment period, then administering a dose of nanoparticles once a month for a subsequent treatment period. The nanoparticles comprise a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, each nucleic acid layer being positioned between a cationic lipid bilayer, wherein the nucleic acids are derived from a cancer cell. The dose comprises about 0.00050 mg/kg to about 1.5 mg/kg of nucleic acid.

Abstract: The present invention provides a universal, yet adaptable, anti-tag chimeric antigen receptor (AT-CAR) system which provides T cells with the ability and specificity to recognize and kill target cells, such as tumor cells, that have been marked by tagged antibodies. As an example, ?FITC-CAR-expressing T cells have been developed that specifically recognize various human cancer cells when those cells are bound by cancer-reactive FITC-labeled antibodies. The activation of ?FITC-CAR-expressing T cells is shown to induce efficient target lysis, T cell proliferation, and cytokine/chemokine production. The system can be used to treating subjects having cancer.

Abstract: The present invention relates to the branch of Biotechnology and Medicine, particularly to a method for the selection and treatment of patients with carcinomas of epithelial origin that co-express the HER1 and HER2 receptors without increased expression of these receptors or with the presence of RAS activating mutations. In particular, this method is based on the application of bivalent vaccine compositions which have as active principle the extracellular domains of the HER1 and HER2 receptors or portions thereof and as an adjuvant the very small proteoliposomes derived from the outer membrane proteins of Neisseria meningitidis and the GM3 ganglioside. This method is useful for the treatment of patients whose expression levels of HER1 and HER2 do not allow the monoclonal antibodies against HER1 and/or HER2 to have a therapeutic effect.

Abstract: Disclosed are compositions and methods for targeted treatment of CD99-expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill CD99-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a CD99-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs. Also disclosed are multivalent antibodies are disclosed that are able to engage T-cells to destroy CD99-expressing malignant cells.

Abstract: Synthetic mini circular RNA vaccine constructs are provided. The synthetic mini circular RNA constructs encode one or more antigens and are used, for example, as vaccines against cancer or infectious agents. In some aspects, the one or more antigens are translated as concatemer peptides by rolling cycle translation (RCT) of the mini circular RNA.

Abstract: Two-component vaccine formulations and methods are contemplated where the vaccine has an adjuvant component and a therapeutic component. The therapeutic component comprises preferably a recombinant therapeutic virus encoding a therapeutic antigen while the adjuvant component comprises a non-host cell or immune stimulating portion thereof. Notably, use of the adjuvant component will result in significant uptake of the therapeutic component into immune competent cells, even in the absence of receptors for entry of the therapeutic component. In addition, such adjuvant also stimulates expression of the therapeutic antigen.

Abstract: Disclosed are compositions comprising a Gram negative needle tip protein and a translocator protein and methods of their use.

Abstract: The invention relates to immunogenic compositions comprising a capsular polysaccharide (CP) from Streptococcus agalactiae, commonly referred to as group B Streptococcus (GBS), conjugated to a carrier protein, and optionally including an aluminum-based adjuvant. The invention further relates to methods for inducing an immune response in subjects against GBS and/or for reducing or preventing invasive GBS disease in subjects using the compositions disclosed herein. The resulting antibodies can be used to treat or prevent GBS infection via passive immunotherapy.

Abstract: This invention relates to compositions (e.g., vaccine compositions) which can be used to immunise against Chlamydia infections. The compositions comprise Chlamydia sp. antigens and antigen combinations which can be used to immunise against Chlamydia sp., used in the form of nucleic acids (e.g., mRNAs) encoding antigenic proteins or in the form of recombinant protein antigens.

Abstract: The disclosure relates to respiratory syncytial virus (RSV) ribonucleic acid (RNA) vaccines as well as methods of using the vaccines and compositions comprising the vaccines. The vaccine can be formulated in a lipid nanoparticle.

Abstract: The presently described and disclosed technology includes, in one example, a method, comprising: extracting a sequence of a spike protein of a first virus from a first non-human mammal that is previously exposed to an infection by the first virus; identifying a target antigen specific to the spike protein; and injecting an mRNA therapeutic comprising an mRNA encoding the target antigen into a human patient that has antibodies to a second virus.

Abstract: The invention relates to an immunization regimen whereby an infant is protected against respiratory syncytial virus (RSV) through administration of a first anti-RSV immune response inducing composition to his or her mother during pregnancy, followed by administration of a second anti-RSV immune response inducing composition to the infant after birth.

Abstract: The present invention relates to DNA vaccine against SARS-Coronavirus-2 (SARS-CoV-2) infection. In particular, the present invention relates to a DNA vaccine encoding the SARS-Coronavirus-2 spike protein for use in prevention or treatment of viral infection in humans and/or animals. The DNA vaccine including the DNA construct has several features in its design that together provide a more safe and broad protection against SARS-Cov-2 strains in humans and animals, e.g. mink, ferrets, pigs and cats. The DNA construct encodes the SPIKE protein derived from the pandemic strain; Wuhan-Hu-1 (MN908947). The sequence is codon optimized for high expression in human and mammalian cells and the DNA construct is inserted in a selected DNA plasmid for eukaryotic in vivo and in vitro expression.

Abstract: Described herein are compositions of extracellular vesicles, and methods and systems of producing the extracellular vesicles. Also described herein are methods of using the extracellular vesicles.

Abstract: A method of producing blood plasma useful in the treatment of a virus causing a viral infection characterized by an uncontrolled release of proinflammatory cytokines in a human affected by the viral infection comprises the following steps: adding a quantity of sodium citrate to a tube; delivering a blood collected from a human donor having antibodies to the virus to the tube; incubating the blood at a temperature of about 37° C. for about 6 hours to about 24 hours; centrifuging the blood to separate the blood into a plasma component and a cellular fraction; and collecting the plasma component. The plasma component can be administered to patient infected with a virus causing a viral infection characterized by an uncontrolled release of proinflammatory cytokines.

Abstract: The disclosure describes coronavirus ribonucleic acid (RNA) vaccines as well as methods of using the vaccines and compositions comprising the vaccines. The RNA vaccines encode domains and subunits of coronavirus.

Abstract: Provided herein are vaccine delivery systems including a polymer hydrogel non-covalently crossed-linked with a plurality of nanoparticles, a dinucleotide adjuvant encapsulated in the hydrogel, and an antigen encapsulated in the hydrogel. The provided vaccine delivery systems are particularly useful for slowly releasing the antigen and adjuvant within a subject, thereby triggering a more therapeutically effective immune response. Also provided are kits including the disclosed vaccine delivery systems, and methods of using the disclosed materials.

Abstract: Described herein are modified SARS-CoV-2 variants. These viruses have been recoded, for example, codon deoptimized or codon pair bias deoptimized and are useful for reducing the likelihood or severity of a SARS-CoV-2 variant infection, preventing a SARS-CoV-2 variant infection, eliciting and immune response, or treating a SARS-CoV-2 variant infection.

Abstract: The disclosure provides messenger ribonucleic acids (mRNAs) encoding an antigenic protein capable of eliciting an immune response to a coronavirus. The disclosure also provides antigen proteins encoded by the mRNAs. The disclosure further provides methods for eliciting an immune response in a subject, and methods for preventing and/or treating a coronavirus infection in a subject.

Abstract: Compositions containing compositions of heparosan polymers linked to a particle, such as a metallic or polymeric or lipid-containing nanoparticle are described, for use in cell delivery applications.

Abstract: This disclosure provides compositions and methods for promoting the formation, expansion and recruitment of TR1 cells and/or B cells in an antigen-specific manner and treating diseases and disorders in a subject in need thereof.

Abstract: An immunogenic composition comprising: (i) a non-virion influenza virus antigen, prepared from a virus grown in cell culture; and (ii) an adjuvant. Preferred adjuvants comprise oil-in-water emulsions.

Abstract: The present invention relates to agents for use in the treatment of glioma, in particular astrocytoma WHO II° and III°, as well as IV° (glioblastoma), in a subject.

Abstract: The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy for the treatment of cancer with TILs in combination with CT-LA-4 and PD-1 inhibitors and/or PD-L1 inhibitors as described herein.

Abstract: The present invention provides methods for expanding TILs and producing therapeutic populations of TILs. According to exemplary embodiments, at least a portion of the therapeutic population of TILs are gene-edited to enhance their therapeutic effect. According to further embodiments, methods for gene-editing TILs include intratumoral delivery of expression vectors for immune checkpoint inhibitors using an electroporation system prior to harvesting the tumor for TIL production. According to yet further embodiments, an adjuvant therapy for cancer includes delivery of expression vectors for immune checkpoint inhibitors before, after or before and after infusion of TILs for treating cancer.

Abstract: The present disclosure provides orthogonal chimeric cytokine receptor/orthogonal cytokine pairs and compositions and methods for modified immune cells or precursors thereof (e.g., modified T cells) comprising an orthogonal chimeric cytokine receptor (e.g., an oIL2R-IL9R chimeric receptor) and a chimeric antigen receptor (CAR) or a T cell receptor (TCR). The present disclosure further provides an oncolytic adenoviral vector comprising a nucleic acid sequence encoding an orthogonal cytokine (e.g., oIL2), as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof.

Abstract: Described herein are compositions comprising human natural killer (NK) cells engineered to reduce or eliminate Cbl-b and with or without a chimeric antigen receptor (CAR), methods of making such compositions, and methods of using such compositions (e.g., killing cancer cells, treating a subject having cancer or viral infection).

Abstract: The present disclosure pertains to modified immune cells comprising fusion proteins and methods of using and making immune cells comprising fusion proteins. The present disclosure also pertains to modified immune cells comprising exogenous cytokines and chimeric antigen receptors and methods of using and making said immune cells.

Abstract: Provided are compositions and methods for prophylaxis or therapy of cancer. The compositions comprise ?-type-1 dendritic cells that have been treated with intact proteins that comprise cancer antigens, or peptides that comprise cancer antigens, or combinations thereof. The approaches can also include adding a chemokine-modulating regimen.

Abstract: The present disclosure relates generally to the field of immunology, and particularly relates to hybrid chimeric antigen receptors designed to combine fast time-scale intracellular signal transduction and long time-scale transcription regulation. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions or diseases, such as cancers.

Abstract: Engineered T cell receptor (TCR) sequences, cells expressing such sequences and methods of use thereof are provided. The engineered receptors are mutagenized in vitro, and selected for target activation potency in combination with selection for a pMHC affinity that is sufficiently low to reduce off-target cross-reactivity.

Abstract: The invention describes ultrasound-responsive particles comprising a polypeptide shell. The surface of the particle has one or more indentations which are generally able to entrap a gas bubble. The particles are capable of generating inertial cavitation on exposure to ultrasound. The particles are therefore useful in methods of treatment which involve inertial cavitation and in the delivery of drugs to target sites via inertial cavitation.

Abstract: The present invention relates to nutritional formulations for increasing sports and other physical performance and that have beneficial effects on health and wellness for various populations. The invention includes molecular compounds as disclosed. A preferred embodiment is a molecule type based on a glycerol backbone, with three glycerol functional groups B1, B2, B3, wherein one or more of the B groups may correspond to one of the functional energy groups A1, A2 or A3, as disclosed. The invention includes nutritional formulations, some based on the inventive molecular compounds. The invention also includes method of using, administering, and implementing the above, including computer implemented and computer assisted methods.

Abstract: An aqueous composition, containing indocyanine green (a), and a compound (b) chosen from ascorbic acid, its salts, and mixtures thereof. A weight ratio of compound (b) to indocyanine green (a) ranges from 0.15 to 15 and a concentration of the indocyanine green (a) in the aqueous composition is between 0.1 and 30 mg/ml.

Abstract: A hydrophilic biocompatible sustained-release material is disclosed. The material comprises amounts of an ethylene oxide/propylene oxide block copolymer, HPMC, and water, effective to produce a composition of sufficiently low viscosity at room temperature to be injectable into an internal body cavity via a tube inserted within a urinary catheter. At body temperature, the material exhibits a much higher viscosity and will stably adhere to the internal surface of a body cavity. As the material dissolves, a therapeutic agent incorporated therein is slowly released to the body cavity, while the material itself is excreted from the body.

Abstract: The invention provides a composition for use as a delivery vehicle comprising at least one thermo-responsive polymer (polymer A) and at least one ion-sensitive polymer (polymer B) in a liquid formulation. Polymer A is preferably a polyoxyethylene-poly-oxypropylene block copolymer or a cellulose derivative. Polymer B is preferably a polysaccharide. The composition can include an active substance for delivery or can be used as a delivery vehicle for a substance added at the time of administration such as mesenchymal stem cells.

Abstract: The present invention relates to pharmaceutical compositions comprising particular preservatives.

Abstract: The present disclosure relates in one aspect to constructs comprising a lipophilic membrane dye covalently linked through a linker to a cargo. In another aspect, the present disclosure relates to a method of delivering a cargo to a tumor in a subject in need thereof, the method comprising administering a construct of the disclosure to the subject. In certain embodiments, the tumor is a brain tumor.

Abstract: The invention is in the field of medical sciences. It provides new pharmaceutical methods and preparations. The invention relates to methods for improving the pharmacokinetic, physicochemical or pharmaceutical properties of drugs by converting the drug into a promoiety-containing 1-substituted disulfanylalkyl carbonate, thiocarbamate or carbamate prodrug. In particular, the invention relates to methods for improving the solubility, permeability, stability and/or oral bioavailability of a drug by converting the drug into a promoiety-containing 1-(disulfanylalkyl) carbonate, thiocarbonate or carbamate prodrug. The invention also provides new compositions comprising a drug covalently attached to a promoiety-containing 1-(disulfanylalkyl) carbonate, thiocarbonate or carbamate.

Abstract: Provided herein are agents and methods for selectively killing senescent cells that are associated with numerous pathologies and diseases, including age-related pathologies and diseases. As disclosed herein, senescent cell-associated diseases and disorders may be treated or prevented by administering at least one senolytic agent or pharmaceutical compositions thereof. The senescent cell-associated diseases or disorders treated or prevented by the agents and methods described herein include, but are not limited to, cardiovascular diseases or disorders, cardiovascular diseases and disorders associated with arteriosclerosis, such as atherosclerosis, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), osteoarthritis, inflammatory or autoimmune diseases or disorders, pulmonary diseases or disorders, neurological diseases or disorders, dermatological diseases or disorders, chemotherapeutic side effects, radiotherapy side effects, metastasis and metabolic diseases.

Abstract: Disclosed in the present invention are a magnolol and sulforaphane conjugate, and a preparation method and use thereof. The magnolol and sulforaphane conjugate comprises C25H29NO2S2 (CT-1), C25H29NO4S2(CT-2), and C25H29NO3S2(CT-3). By using the drug combination principle, the present invention achieved the first synthesis of the magnolol and sulforaphane conjugate (CT-1, CT-2, CT-3). According to biological evaluation, the conjugate has an antitumor effect remarkably superior to that of magnolol and sulforaphane, has a broad spectrum of antitumor activity and strong druggability. It is an antitumor compound with development potential, and also provides new ideas and approaches for development of a novel antitumor drug.

Abstract: The present invention relates to the field of biomedicine, and specifically relates to a proteolysis-targeting chimera (PROTAC) compound. The structure of the PROTAC compound can be represented by general formula LGP-LK-LGE, wherein LGP is a ligand for binding a deoxyribonucleic acid (DNA) polymerase; LGE is a ligand for binding an E3 ubiquitin ligase; and LK is a linker linking the two above ligands. The compound prevents virus replication and kills viruses by means of degrading a deoxyribonucleic acid (DNA) polymerase that inhibits the viruses, and thus performs the function of treating and intervening in viral infectious diseases such as hepatitis B and secondary diseases, and the acquired immunodeficiency syndrome.