Abstract: Methods of treating individuals with a glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

Abstract: The present invention provides methods of treating a retinal disorder comprising administering an effective amount of a neurotrophic factor to a subject having the retinal disorder. The neurotrophic factors useful in the invention include mesencephalic astrocyte-derived neurotrophic factor (MANF) and conserved dopamine neurotrophic factor (CDNF). The present invention further comprises pharmaceutical compositions and kits containing MANF and CDNF.

Abstract: The present invention provides microparticles that deliver in vivo predictable release profiles of at least one chemokine to create a biomimetic chemokine concentration gradient that induces the migration of multipotent stem cells to the anatomical site of the microparticles. Various release profiles are demonstrated that depend upon the relative concentration of alginate in the chemokine-loaded microparticle. Local administration and/or intraarticular injection of the microparticles are useful in conditions such as osteoarthritis. Targeted systemic delivery of the alginate chemokine microparticles to distant anatomical sites subjected to autoimmune disease symptomology can be performed by encapsulation within liposomes having targeting ligands. Consequently, upon the creation of the appropriate chemokine gradient, multipotent stem cells will migrate to the distant anatomical site where the liposomes are attached.

Abstract: Methods and compositions for treating tumors, especially skin tumors, by locally administering single doses of tumor necrosis factor alpha (TNF?) and interleukin-2 (IL2) at the tumor site, where the TNF? and IL2 are delivered as immunoconjugates comprising an antibody targeted to a splice isoform of an extracellular matrix component such as fibronectin.

Abstract: A pharmaceutical compound for the treatment of obesity related disorder that is a conjugate of myristic acid and a leptin-related peptide. Preferably, the leptin-related peptide is OB3 that has been D-substituted at Leu-4. The resulting conjugate significantly improved the pharmacokinetic profile of the leptin-related peptide by extending its half-life from less than one hour to as long as twenty-eight hours, depending on the route of delivery, increasing uptake, reducing the rate of plasma clearance, and enabling the minimal effective dose to be reduced several fold.

Abstract: The invention relates to a derivative of a GLP-1 analogue, optionally C-terminally extended, which derivative comprises a first and a second protracting moiety in the form of a C20 or C22 diacid radical, a bis-amino branched linker, and a first and a second further linker each comprising an OEG-like linker element; wherein these elements are interconnected via amide bonds and attached to a Lys residue of the GLP-1 analogue. The invention also relates to intermediate products in the form of novel GLP-1 analogues incorporated in the derivatives of the invention, as well pharmaceutical compositions and medical uses of the derivatives. The derivatives have very long half-lives while maintaining a satisfactory potency, which makes them potentially suitable for once-monthly administration.

Abstract: Disclosed is a formulation of the following enzymes: Beta Glucanase, Chymotrypsin, Phytase, Lactase, and Invertase, which has been found to be effective in treating salicylate intolerant people, and causing a significant improvement in a wide variety of pathologies and symptoms, including, but not limited to: acid reflux disease, stuttering, migraines, ADHD, behavioral deficits, Tourettes disease, seizures, autism (ASD), atrial fibrillation, anxiety, depression, joint pain, cognitive and perceptual disorders, respiratory difficulties and non-diabetic neuropathy. The formulation is also for treating or reducing intolerance of gluten, corn or soy.

Abstract: The present invention relates to compositions and methods for the prevention and treatment of neurodegenerative diseases, such Alzheimer's disease, that are caused by misfolding, aggregating proteins. The compositions and methods of the present invention comprise a vaccine formulation comprising an antigen selected from the group consisting of i) amyloid-? or a peptide that has in its amino acid sequence part of the amyloid-? amino acid sequence, ii) hyperphosphorylated tau protein or one of its hyperphoshorylated peptides, or iii) a combination of antigens derived from groups i) and ii) and that are formulated with a non-acylated or deacylated, natural or synthetic, bidesmosidic triterpene glycoside carrying an aldehyde or ketone group, which acts as an adjuvant or immune agonist. These vaccine formulations are capable of stimulating a Th2 immunity or antibody response against antigens such as amyloid-? and tau derived antigens, but not a Th1 immune response.

Abstract: The present invention provides a cancer vaccine tape preparation for inducing cellular immunity, comprising: a support, an adhesive layer comprising an adhesive disposed on one side of the support, wherein the adhesive layer carries a combination of: (i) a WT1 peptide and/or a modified WT1 peptide; and (ii) a first cellular immunity induction promoter. The tape preparation can provides high efficacy.

Abstract: Provided herein are compositions comprising substantially non-viable Gram-negative bacterial organisms that have a substantial reduction in endotoxin activity and/or pyrogenicity and methods for treating a cancer using the same. Also provided are methods for treating cancer provided herein, comprising administering to a mammal diagnosed with cancer, substantially non-viable Gram-negative bacteria having a substantial reduction in endotoxin activity and/or pyrogenicity, in an amount sufficient to inhibit growth or metastasis of the cancer. An additional method is provided comprising administering viable or non-viable Gram-negative bacterial organisms that have a genetic defect that results in a substantial loss of lipopolysaccharide within the outer membrane of the bacteria. Further provided are methods for reducing endotoxin activity and/or pyrogenicity in Gram-negative bacteria comprising treatment with polymyxin and glutaraldehyde.

Abstract: The present invention provides polypeptides useful as antigens expressed at the pre-erythrocytic stage of the malaria parasite. The antigens can be utilized to induce an immune response and sterile protection against malaria in a mammal by administering the antigens in vaccine formulations or expressing the antigens in DNA or other recombinant protein expression systems delivered as a vaccine formulation.

Abstract: The present disclosure provides for an adjuvant composition that is suited for injectable as well as transdermal administration. The adjuvant composition generally comprises a lipophile, a polymer of acrylic or methacrylic acid, saline, cholesterol, a saponin, and sodium hydroxide. A vaccine composition is also provided for that generally includes the vaccine composition of the present disclosure and an antigen. A method for vaccinating animals and humans utilizing the adjuvant composition of the present disclosure is also provided.

Abstract: Provided herein are immunogenic compositions and vaccines for the treatment and prevention of Staphylococcus aureus infections. These immunogenic compositions and vaccines comprise combinations of bioconjugates capsular polysaccharides that are N-linked to one or more carrier proteins.

Abstract: An effective Staphylococcus aureus vaccine may require several antigenic components, and so various combinations of S. aureus antigens are identified for use in immunisation. These polypeptides may optionally be used in combination with S. aureus saccharides.

Abstract: The invention uses polypeptide antigens and/or OMVs to immunize against serogroups A, C, W135 and Y (and against serogroup Y in particular). Serogroup B polypeptides can achieve this protection, thus permitting a single polypeptide-based vaccine to be used for protecting against all of serogroups A, B, C, W135 and Y.

Abstract: Disclosed are transmission blocking vaccines for prevention or spread of one or more flaviviruses, and in particular, for prevention or spread of dengue virus. Vaccines can incorporate a polypeptide or a recombinant virus encoding a polypeptide that is non-homologous to human proteins and that is involved in flavivirus infection in a mosquito. Vaccines can include multiple components for multi-level attack against mosquito-borne diseases including flaviviruses and malaria.

Abstract: The present invention relates to a versatile influenza virus vaccine composition using the HA2 helical domain of a hemagglutinin protein, which is an influenza surface protein, and to a pharmaceutical composition for preventing or treating influenza virus infectious diseases. The polypeptide expressed by SEQ ID NO: 3 and the polypeptide expressed by residues 379 to 474 of SEQ ID NO: 1 of the present invention can be mass-produced in E. coli, and effectively produce neutralizing antibodies to various influenza virus subtypes, and thus the polypeptides can be widely utilized as versatile vaccines for influenza virus subtypes and new influenza virus variants.

Abstract: In a first aspect, the present invention relates to the use of a TLR 9 agonist and/or a TLR 4 agonist in a prophylactic or therapeutic vaccine. According to the present vaccination strategy, the TLR 9 agonist and/or TLR 4 agonist is adapted or designed for use as a multiplying jump agent to enhance numbers and functionality of CD8 T cells in a prime-jump vaccination strategy for jump T cell expansion. In particular, the TLR 9 agonist and/or TLR 4 agonist is used as a component to be administered after priming of the individual to be vaccinated. The vaccination strategy is particularly useful against acute and chronic infections with intracellular pathogens or for anti-tumor vaccination. In another aspect, the present invention relates to a kit of part containing a prime agent and a multiplying jump agent according to the present invention.

Abstract: Provided herein are nucleic acid sequences that encode novel consensus amino acid sequences of HBV core protein, as well as genetic constructs/vectors and vaccines that express said protein sequences. Also provided herein are methods for generating an immune response against HBV using the nucleic acid sequences that are provided.

Abstract: The present invention relates to the induction of tolerance to antigens, by mucosal, preferably oral delivery of the antigen in combination with an immunomodulating compound producing micro-organism. More specifically, the invention relates to the induction of Foxp3+ and/or IL-10 and/or TGF-? producing regulatory T-cells, capable of suppressing undesired immune responses toward an antigen, by oral delivery of said antigen in combination with an immunosuppressing cytokine secreting micro-organism.

Abstract: This peptide/?-1,3-glucan complex includes ?-1,3-glucan and a peptide/polynucleotide conjugate in which an antigenic peptide is bonded covalently to a polynucleotide or a derivative thereof. The polynucleotide or derivative thereof of the peptide/polynucleotide conjugate bonds via a hydrogen bond with ?-1,3-glucan, forming a complex having a triple helix structure including a single molecular chain of the polynucleotide or derivative thereof and two molecular chains of the ?-1,3-glucan. Alternatively, the side chain of the ?-1,3-glucan and the antigenic peptide are bonded covalently formed by either a cycloaddition reaction between an alkyne and an azide derivative, or a reaction between a maleimide group or a vinyl sulfone group and a thiol group.

Abstract: The present invention addresses the problem of providing an antibody titer-increasing agent, such as an adjuvant, capable of sustaining an effect achieved by, for example, vaccination, which is an antibody titer-increasing agent such as an adjuvant that is safe, convenient and economical and can be easily taken irrespective of age, and a method for manufacturing the same. A method for increasing an antibody titer and a method for enhancing the effect of a vaccine, each method comprising using Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 or a culture thereof; and an antibody titer-increasing agent such as an adjuvant that comprises Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 or a culture thereof.

Abstract: A chimeric antigen receptor (CAR) contains a human Fc?RI? extracellular domain or a mutant Fc?RI? extracellular domain that has a reduced binding affinity for human IgE compared to wild type human Fc?RI? extracellular domain. The CAR further contains an intracellular signaling domain comprising at least one immunoreceptor-based activation motif (ITAM). The CAR may further comprise a costimulatory signaling domain, such as an intracellular domain of at least one of the costimulatory molecules 4-1BB, CD27, CD28, CD134 or ICOS. T cells transduced with vectors encoding the CAR are used in CAR-based adoptive T-cell therapy for targeting IgE-expressing B cells and treating IgE-mediated allergic diseases.

Abstract: The invention relates to methods of modulating immune cells in a patient by altering microbiota of the patient. The invention also relates to methods of modulating treatments or therapies in a subject organism by altering microbiota of the subject. The invention also relates to cell populations, systems, arrays, cells, RNA, kits and other means for effecting this. In an example, advantageously selective targeting of a particular species in a human gut microbiota using guided nucleic acid modification is carried out to effect the alteration.

Abstract: Methods of modulating immune responses in subjects having oncology- and immune-related diseases, disorders and conditions by the administration of an IL-10 agent, including pegylated IL-10.

Abstract: The invention provides aqueous pharmaceutical adalimumab compositions suitable for long-term storage of adalimumab, methods of manufacture of these compositions, methods of administration, and kits containing same.

Abstract: A method for the production of hydrolyzed allergens from allergens comprising the steps of: a) extracting a source of allergens comprising allergenic proteins to form an extract, b) purifying the extract to remove non-protein components to form a purified extract, c) denaturing the purified extract with a first denaturing agent to form a purified denatured extract, d) refining the purified denatured extract to remove impurities to form a refined denatured extract, e) denaturing the refined denatured extract with a second denaturing agent to form denatured allergen mixture, and f) hydrolyzing the denatured allergen mixture to form the hydrolyzed allergens.

Abstract: This invention provides compositions and methods to treat a condition or disease without the use of exogenous targeting sequences or chemical compositions. The present invention relates to single-domain antibodies (sdAbs), proteins and polypeptides comprising the sdAbs that are directed against targets that cause a condition or disease. The invention also includes nucleic acids encoding the sdAbs, proteins and polypeptides, and compositions comprising the sdAbs. The invention includes the use of the compositions, sdAbs, and nucleic acids encoding the sdAbs for prophylactic, therapeutic or diagnostic purposes.

Abstract: Disclosed herein are compositions comprising an NSAID such as meloxicam in combination with a cyclodextrin and/or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of conditions such as pain.

Abstract: Disclosed herein are compositions comprising an NSAID such as meloxicam in combination with a cyclodextrin and/or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of conditions such as arthritis.

Abstract: The present invention provides lipid aggregate compositions having at least two cationic lipids in combination with one or optionally more than one non-cationic lipids for the in vitro and/or in vivo delivery of biologically active molecules including nucleic acids, specifically DNA and RNA, and proteins into cells and tissues. Methods are also provided that use the compounds of the present invention to deliver biologically active molecules, into cells and tissues to facilitate the expression of target proteins therein. In some non-limiting embodiments, the subject lipid aggregate compositions can be used to deliver nucleic acid molecules to facilitate the expression of proteins involved in cellular reprogramming and genome editing applications.

Abstract: The present application relates to formulations of anti-CD105 antibodies, antigen-binding fragments thereof, and uses thereof. Another aspect relates to pre-filled syringes of the formulations of anti-CD105 antibodies or antigen-binding fragments thereof. Another aspect relates to the use of the formulations to reduce one or more signs or symptoms of an angiogenesis-related disorder such as cancers and ophthalmologic diseases.

Abstract: Described herein are compositions of alginate formulations that include water, divalent ions, and alginate cross-linked by the divalent ions, and their use for treating incisional wounds, such as intra-incisional application.

Abstract: The present disclosure provides conjugate structures and hydrazinyl-substituted heteroaryl compounds used to produce these conjugates. The disclosure also encompasses methods of production of such conjugates and compounds, as well as methods of using the same.

Abstract: The present invention provides compositions and methods for providing controllable local delivery of a therapeutic agent to promote bone formation. In certain embodiments, the invention is used as a treatment for a subject with osteoporosis, bone cancer or bone fracture. The invention provides a therapeutic agent that is tethered to a polymer to form a therapeutic-tethered macromer, where the therapeutic agent is controllably released from the conjugate by degradation of the tether. In certain embodiments, the therapeutic agent is an inhibitor of GSK3?. In certain embodiments, the composition of the invention is specifically targeted to a site in need of bone formation or treatment.

Abstract: This invention relates to a complex for cancer cell chemotherapy and, more particularly, to an AGTR1 aptamer-anticancer drug complex for chemotherapy of cancer cells, which includes a nucleic acid aptamer specifically binding to AGTR1 and an anticancer drug linked with the nucleic acid aptamer, so that AGTR1-positive (overexpressed) breast cancer cells are selectively targeted and killed.

Abstract: A conjugate for delivery of drugs, such as genetic drugs, [e.g., siRNA, dsiRNA, or antisense oligonucleotides (ASO)] across biological membranes is provided. The conjugates of the Invention are capable of delivering drugs in both presence and absence of plasma proteins.

Abstract: A first aspect of the invention relates to a single chain insulin analog comprising: (A) the A-chain of human or animal insulin, or an analog or derivative thereof; (B) the B-chain of human or animal insulin, or an analog or derivative thereof; (C) one or more disulfide bonds between said A-chain and said B-chain; and (D) a further covalent link, L, between a functional group of an amino acid in the A-chain and a functional group of an amino acid in the B-chain, at least one of said functional groups being an amino acid side chain functional group. Further aspects of the invention relate to pharmaceutical compositions comprising said single chain insulin derivatives, and therapeutic uses thereof.

Abstract: As an antitumor drug which is excellent in terms of antitumor effect and safety, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an antibody via a linker having a structure represented by the following formula: -L1-L2-LP-NH—(CH2)n1-La-Lb-Lc- wherein the antibody is connected to the terminal of L1, and the antitumor compound is connected to the terminal of Lc with the nitrogen atom of the amino group at position 1 as a connecting position.

Abstract: The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates) comprising specific acyl donor glutamine-containing tags and amine donor agents. The invention also provides methods of making such engineered polypeptide conjugates using transglutaminase and methods of using thereof.

Abstract: The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

Abstract: The invention relates to methods, processes and apparatuses for the manufacture of lipid nanoparticles having a therapeutic payload.

Abstract: The present invention concerns a method for the treatment of recessive Catecholaminergic Polymorphic Ventricular Tachycardia comprising delivering a gene into a cardiac cell.

Abstract: A method and device for the diagnosis of gastrointestinal allergy. The method and the device expose a surface to at least one antigen at a fixed depth. The device includes an application point each having an antigen allowing for the application of the antigen to the surface at a fixed depth. The device may include multiple applications points each with an antigen for simultaneously applying the antigens to the surface.

Abstract: This disclosure relates to a tattoo decal containing bacteria that can be applied to skin and function as both a monitoring sensor and a visual indicator. In particular, a temporary tattoo containing a bacteria composite that may be selected or “programmed” to sense, detect, or otherwise react to a variety of stimuli for use in a variety of applications and industries is disclosed.

Abstract: A process for purifying a compound of formula 1, includes the following steps: a) adding an acid to an aqueous solution of the compound of formula 1, including salts and hydrates thereof so as to obtain a slurry having a pH?3; and b) filtering the slurry and at least one time washing the obtained precipitate with a liquid comprising water; and c) dissolving the precipitate obtained in step b) in water to obtain an aqueous solution; and d) filtering of the solution obtained in step c) over a nanofiltration membrane having a Molecular Weight Cut Off in the range from 150 to 500 and wherein optionally, between step c) and step d) the pH of the aqueous solution is adjusted to a pH value in the pH range as specified by the manufacturer of the nanofiltration membrane. A process for preparing a gadolinium complex of the purified compound of formula 1 is also disclosed. This gadolinium complex can be used for making a pharmaceutical composition as a contrast agent for magnetic resonance imaging.

Abstract: The present invention provides contrast agents for photoacoustic imaging which exhibit high degrees of accumulation in tumor and low degrees of retention in the blood and can be administered into the blood. The contrast agents for photoacoustic imaging include a conjugate of a dye and a polyethyleneglycol represented by Formula (1), (5), (6), or (7) and an additive represented by Formula (301).

Abstract: Iron garnet nanoparticles and or iron garnet particles containing various activatable nuclides, such as holmium-165 (165Ho) and dysprosium-164 (164Dy), are disclosed in this application. The iron garnet (e.g., HoIG and DyIG) nanoparticles and iron garnet particles can prepared using hydroxide co-precipitation methods. In some embodiments, radiosensitizers can be loaded on radioactive magnetic nanoparticles or radioactive iron garnet particles and, optionally, coated with suitable lipid bilayers. Methods of using the disclosed nanoparticles and particles for mediating therapeutic benefit in diseases responsive to radiation therapy are also provided. Another aspect of the invention provides films, electrospun fabrics or bandage coverings for the delivery of radiation to the site of a skin lesion amenable to treatment with radiation (e.g., skin cancers or psoriasis).

Abstract: Sanitizing surfaces in a location related to aircraft. There are multiple rows of seats. A sanitization device includes a mobile body configured to travel along the aisle of the aircraft. An arm extends from the sanitization device laterally from the mobile body across the seats, and a source of UV radiation mounted on the sanitization device is directed across the seats exposing surfaces in the passenger area to UV radiation. There is a data collector to collect information in the aircraft. A passive RFID tag mounted on elements can be read by an RFID reader. The device can include one or more sniffer cells for scanning the aircraft for unwanted or dangerous devices or chemicals.

Abstract: Methods and systems are provided for sterilization. In one example, a device may include a body with a flexible tether and a receiving aperture having a central axis, the body forming an internal cavity, the cavity housing at least one circular battery with a central axis perpendicular to the central axis of the aperture; and a UV source positioned at an end of the receiving aperture. Various other additional features and alternative configurations are included.