Abstract: This invention relates to inhibitors of CXC receptor 4 (CXCR4)-G protein-coupled receptor (GPCR) heteromers (CXCR4-GPCR heteromers) associated with cancers, where CXCR4 forms a functional heteromer with other G protein-coupled receptors (GPCRx). More specifically, this invention relates to GPCRx that form heteromers with CXCR4, which upon co-stimulation with CXCR4 agonists and GPCRx agonists leads to enhanced signaling downstream of CXCR4. This invention also provides for the use of inhibitors of the interacting GPCR partner of the CXCR4-GPCRx heteromer or CXCR4-GPCRx heteromer-specific inhibitors including inhibitors of the formation of the CXCR4-GPCRx heteromer and CXCR4-GPCRx heteromer-specific antibodies, and in the diagnosis and/or therapy for cancer.

Abstract: Cancer is a complex group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Described herein are compositions and methods for the treatment of cancer.

Abstract: Long-acting agonistic analogs for CLR/RAMP receptors are provided that have an extended half-live in vivo.

Abstract: The present invention is in the field of pharmaceutical compositions for the treatment of medical conditions relating to diabetes. More specifically the invention provides pharmaceutical compositions comprising a long-acting acylated derivative of a human insulin analogue, and to the medical use of such compositions for basal insulin administration therapy.

Abstract: There is provided inter alia an aqueous solution composition comprising insulin glargine as an active ingredient and an amino acid selected from aspartic acid and glutamic acid as a stabilising agent, wherein the amino acid is present at a concentration of 1-50 mM.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: Disclosed herein are synthetic particles that are shaped like red blood cells. The particles include pectin and oligochitosan and optionally a bioactive agent. In addition, methods of making the synthetic particles via electrospray techniques are provided.

Abstract: Compositions comprising a combination of myeloperoxidase and a peroxide-producing oxidase and methods of using the compositions to inactivate gram negative bacterial lipopolysaccharides and lipid A endotoxin are provided.

Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.

Abstract: Methods and compositions for the treatment or prevention of amyloidosis are provided. In some embodiments, the methods comprise administering to the subject a therapeutically effective amount of at least one catabolic enzyme or a biologically active fragment thereof. Such methods and compositions may be employed to reduce, prevent, degrade and/or eliminate amyloid formation in the lysosome and/or extracellularly.

Abstract: Compositions and methods of modulating cellular function and treatment of disease in mammals comprising locally administering a regulated SNARE inhibitor and a translocating agent to the mammal. Regulated SNARE inhibitors include clostridial neurotoxins, tetanus neurotoxin and their free light chain portions and IgA protease. Translocating agents include acids, encapsulating vectors, and transduction domains.

Abstract: Methods to minimize scarring during the wound healing process are described. Methods to improve appearance of a scar that forms over a wound are also described. The methods comprise administering a therapeutically effective amount of botulinum toxin subtype E (BoNT/E) in the proximity of a wound.

Abstract: The invention relates to stable liquid neurotoxin formulations which are free of animal proteins, comprising a surfactant, an amino acid selected from tryptophan and tyrosine, a buffer comprising sodium, chloride and phosphate ions, which have a pH between 5.5 and 8, and which are stable for 2 months. These compositions are suitable for use in therapy and in particular for administration to a patient to achieve a desired therapeutic or aesthetic effect. The invention also relates to the use of an amino acid selected from tryptophan and tyrosine to protect a proteinaceous neurotoxin from degradation in a liquid composition which is free of animal derived proteins.

Abstract: This invention relates to therapeutic compounds which are inhibitors of serine proteases, to pharmaceutical compositions thereof and to their use in the treatment of the human or animal body. More specifically, the present invention relates to a method for the treatment, diagnosis or prognosis of skin diseases comprising the administration to a subject in need thereof of a therapeutically effective amount of a Serine protease inhibitor.

Abstract: Described herein are compositions which include digestive enzymes and which are formulated to reduce one or more symptoms of a neuropsychiatric disorder. Also described herein is a method for treating an individual with a neuropsychiatric disorder using digestive enzymes and their derivatives to alleviate the symptoms of neuropsychiatric disorders. The method comprises administering to the individual an effective amount of digestive enzymes that are either naturally or recombinantly derived, or their derivatives, in an amount effective to reduce one or more symptoms of the neuropsychiatric disorder.

Abstract: The invention relates to a method for determining a dosing scheme for the treatment of hereditary angioedema and/or the prevention of hereditary angioedema attacks with C1 esterase inhibitor to optimize treatment response in an individual patient. Accordingly, the present invention provides means for determining individual C1 esterase inhibitor dosing schemes that result in an optimal treatment/prevention outcome.

Abstract: Biomaterial systems, e.g., gel scaffolds, are used in vivo to recruit immune cells and promote their activation towards a non-inflammatory phenotype, thereby leading suppression of inflammation. The compositions and methods are useful to reduce the severity of autoimmunity, chronic inflammation, allergy, and periodontal disease.

Abstract: The invention is directed to T cell epitopes wherein said epitopes comprises a peptide or polypeptide chain comprising at least a portion of an immunoglobulin constant or variable region. The invention also relates to methods of using and methods of making the epitopes of the invention.

Abstract: The invention is directed to T cell epitopes wherein said epitopes comprises a peptide or polypeptide chain comprising at least a portion of an immunoglobulin constant or variable region. The invention also relates to methods of using and methods of making the epitopes of the invention.

Abstract: Provided are a method of ex-vivo culture of natural killer (NK) cells by treating the cells with a reactive oxygen species (ROS) inhibitor and/or a p53 protein inhibitor; and a composition comprising the cultured NK cells. By reducing the activity of ROS and p53 proteins during ex-vivo culture, NK cells may have achieved greater expansion efficiency without altering their anti-tumor cytotoxicity.

Abstract: The present invention relates to a method for producing a DNA vaccine for cancer immunotherapy comprising at least the steps of (a) transforming an attenuated strain of Salmonella with at least one DNA molecule comprising at least one expression cassette encoding at least one antigen or at least one fragment thereof; (b) characterizing at least one transformed cell clone obtained in step (a); and (c) selecting at least one of the transformed cell clone(s) characterized in step (b) and further characterizing said at least one selected transformed cell clone. The present invention further relates to a DNA vaccine obtainable by the method according to the present invention.

Abstract: Provided herein are methods of sorting antigen-specific IgM memory B cells (MBCs), compositions and methods comprising such antigen-specific IgM MBCs, and recombinant antibody or antigen-binding fragments isolated from such antigen-specific IgM MBCs. As demonstrated herein, IgM and IgD MBCs are unique populations of cells with distinct phenotypic, functional and survival properties. Accordingly, the antigen-specific IgM MBCs and antibodies and antigen-binding fragments derived from these cells described herein are useful in therapeutic applications in vaccine strategies and treatment of infectious diseases.

Abstract: Immunogenic compositions comprising an M72 related antigen, wherein the conductivity of the composition is 13 mS/cm or lower, or the concentration of salts of the composition is 130 mM or lower, and their use in medicine, are provided.

Abstract: A first aspect of the invention provides meningococcal outer membrane vesicles in which NHBA is over-expressed. A second aspect of the invention provides meningococcal outer membrane vesicles in which NadA is over-expressed. A third aspect of the invention provides a panel of bacterial strains, each member of which is isogenic except for a single gene which in each strain encodes a different variant antigen of interest.

Abstract: Reported herein are novel recombinant respiratory syncytial viruses (RSV) having an attenuated phenotype in which the native positions of the NS1 and/or NS2 genes in the RSV genome are shifted to a higher position, that is at positions that are more distal to the promoter. The changes in the gene positions may be present in combination with mutations at other loci to achieve desired levels of attenuation and immunogenicity. The recombinant RSV strains described here are suitable for use as live-attenuated RSV vaccines. Also provided are polynucleotide sequences capable of encoding the described viruses, as well as methods for producing and using the viruses.

Abstract: Embodiments of the present invention provide for novel compositions and methods for making and using a thermally stable human papilloma virus (HPV) formulation or other stabilized multimeric virus formulation. Certain embodiments concern lyophilizing HPV formulations in the presence or absence of adjuvants. Other embodiments concern lypophilizing HPV capsomere vaccines in order to increase stability of an immunogenic composition against HPV infection for storage, delivery and use. In yet other embodiments, a single immunogenic composition can include a thermally stable formulation of multiple virus serotypes.

Abstract: The present invention relates to novel CD4+ and CD8+ T cell epitopes that are specific for HPV-specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions comprising these peptides for use in methods for the prevention and/or treatment of HPV related diseases. Preferred epitopes are recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node, and are presented by an HLA-DQ or HLA-DP molecule, or an HLA-B.

Abstract: The invention is in the field of prevention or treatment of diseases, in particular infectious diseases, and more particularly in the field of multivalent vaccines. The inventors characterized 5? copy-back DI-RNAs produced by recombinant MV strains, including rMV-based vaccines and wild-type MV (wt-MV). The efficiency of these DI-RNAs productions in different cell types was compared. For the first time 5? copy-back DI-RNAs specific binding to RIG-I, MDA5 and LGP2 was assessed and linked to functional outcome in type-I IFN signalling. The inventors provide a composition of products comprising at least (i) a mixture of particles of a rescued recombinant MV-derived virus encoding at least one antigen (ii) a recombinant and/or purified protein, comprising at least one antigen. Regardless of the presentation of the products, and in particular regardless of whether the products are separated or readily separable or presented as a mixture.

Abstract: Embodiments herein relate to compositions and methods for stabilizing Flaviviruses. In certain embodiments, compositions and methods disclosed herein concern stabilizing live, attenuated or unattenuated (e.g. live whole) flaviviruses. Other embodiments relate to compositions and methods for reducing degradation of live, attenuated or unattenuated flaviviruses. Other embodiments relate to improved formulations for prolonging stabilization of live attenuated or unattenuated Flaviviruses during manufacturing, storage, accelerated storage and transport. Yet other embodiments relate to uses of compositions disclosed herein in kits for transportable applications and methods.

Abstract: The present invention provides a composition and method for treating diseases associated with demyelination of the nerves, such as ALS, RA, Tremors/Parkinson's Disease, and MS, Alzheimer's disease, ALS, Guillain-Barre syndrome, atherosclerosis, schizophrenia, Tremors/Parkinson's disease, senile dementia, Muscular Dystrophy, Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder, Complex Regional Pain Syndrome, Diabetes, Neuropathic Pain, Spider Arthritis West Nile Virus, Fibromyalgia, Shingles, Gout, Migraine Headaches, Post Polio Syndrome, Central Virus Deafness, Asthma, Chronic Pain Of Unknown Origin and Hepatitis C and for treating non-viral based cancers. By administering measured doses of an immunity-provoking agent and a bacterial antigen activator, patients suffering from ALS, RA, MS, Tremors/Parkinson's Disease, and prostate cancer and others realized immediate beneficial results with no side effects.

Abstract: Described herein are in vitro-transcribed (IVT) RNA molecules comprising, a 5? cap structure, a coding region encoding an antigen polypeptide, an immunostimulatory RNA sequence, and a poly(A) tail.

Abstract: The invention provides influenza vaccines and methods which improve the safety of influenza vaccines further, in particular in relation to the risk of causing narcolepsy in adjuvanted vaccines.

Abstract: Methods and compositions are provided that can be used to vaccinate against and treat HIV. Specifically contemplated are vaccine compositions and methods of using these compositions treat HIV in patients. Aspects of the disclosure relate to an anti-CD40 antibody-HIV antigen fusion protein comprising (i) an anti-CD40 heavy chain (HCD40)-HIV antigen (Ag) fusion protein comprising the formula: HCD40-Ag, wherein Ag is a polypeptide with at least 80% sequence identity to SEQ ID NO:1; and (ii) an anti-CD40 light chain (LCD40).

Abstract: The compositions and methods are described for generating an immune response to a hepatitis B virus. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to a hepatitis B virus, in the subject to which the vector is administered. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat an infection caused by hepatitis B virus.

Abstract: Methods and apparatus for the reproducible, consistent and efficacious delivery of an HBV vaccine to a subject. The disclosure comprises apparatus for the controlled administration of the HBV vaccine through an orifice to the subject, a plurality of penetrating electrodes arranged with a predetermined spatial relationship relative to the orifice, and an electrical signal generator operatively connected to the electrodes.

Abstract: Provided herein are Modified Vaccinia Ankara (MVA) vectors and adenovirus vectors encoding HBV antigens. Also provided are methods of enhancing an immune response in a human subject by utilizing the MVA and adenovirus vectors encoding HBV antigens in a prime/boost regimen to the enhance the immune response in the human subject.

Abstract: The invention discloses a transdermal drug delivery scheme for preparing a specific nanobody biopharmaceutical through penetrating skin tissue, and its preparation method and application. Due to biological characteristics such as unstable activity of traditional antibodies or protein macromolecules, the administration of biopharmaceuticals is basically limited to injections. Nanobodies are the smallest units currently known to bind target antigens. The three-dimensional structure of nanobodies determines the relative stability of their structure and biological activity and their biological properties. Nanobodies have the characteristics of high temperature resistance, activity in a certain acid-base environment, good water solubility, and strong tissue penetration. Therefore, by optimizing the formulation of the carrier, the stability of the nanobody and the penetration of the skin tissue can be maintained and increased, so as to achieve a transdermal delivery formulation of the nanobody biopharmaceutical.

Abstract: Conjugates of synthetic nanocarriers, complexed with syngeneic (self) proteins adducted with haptens or other poorly immunogenic antigens (antigens of low immunogenicity), elicit selective humoral responses or antibodies against the hapten or antigen and not to self-protein. Compositions include these conjugates, which can be used as vaccines. Methods of making and using them are described herein. In a typical embodiment, a conjugate including a hapten or antigen of low immunogenicity associated with a particular disease (e.g., infection, cancer) can be used as a vaccine by eliciting antibodies that specifically neutralize the hapten or antigen. These hapten (and other poorly immunogenic antigen)-carrying nanocarriers selectively target antigen presenting cells resulting in a strong anti-hapten humoral response, and thus find use in vaccines for cancer (e.g., cancers of lung, cervix, breast, brain, liver pancreas, ovaries, skin, etc.

Abstract: Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: or a salt thereof. R1 includes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R2 is —N+H3, —N+H2Z, —N+HZ2, or —N+Z3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.

Abstract: The present invention relates to an approach for the treatment of adverse neurological sensations in a certain body surface area such as the skin, in particular treatment of pain or itching. The invention is based on the finding that administration of a targeting molecule which specifically binds a cell or receptor responsible for the adverse sensation in the respective body surface area of a patient, and which is coupled/conjugated to a photosensitive inhibitor or cytotoxic agent can enable the irradiation dependent ablation of cells responsible for the sensation. This approach allows a targeted and specific treatment of body surface areas by irradiation. Provided are conjugate compounds for use in the photoablation treatment of the invention and pharmaceutical compositions which comprise these compounds.

Abstract: The present invention relates to ophthalmic compositions for treatment of conditions in the eye. More specifically, the present invention relates to ophthalmic compositions comprising a polyquaternium compound and an anionic polymer. Methods for reducing and/or preventing the incompatibility of polyquaternium compounds with anionic polymers are also disclosed.

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

Abstract: The present invention provides a phosphorothioate-modified oligonucleotide comprising a structure shown below: The present invention also provides a phosphorothioate-modified oligonucleotide comprising a structure having formula (CIII):

Abstract: The invention provides a hydrogel comprising an aqueous chitosan solution and a water-soluble linker agent. The linker agent is a block copolymer composing non-degradable block such as poly(ethylene glycol) and hydrolytic degradable block such as poly(amino acid) and polyester. Both ends of the block copolymer are terminated with active group such as glyoxylic acid, uronic acid and aldehyde benzoic acid. When the two main components are mixed together, the resulting solution will undergo spontaneous gelation at mild condition. The resulting hydrogel is able to retain the stability of biopharmaceuticals fully, therefore, which is qualified to serve as drug vehicles used in vivo and topical applications.

Abstract: A process for making esterified cellulose ethers which have i) a combination of aliphatic monovalent acyl groups and groups of the formula —C(O)—R—COOA wherein R is a divalent aliphatic or aromatic hydrocarbon group and A is hydrogen or a cation, ii) a weight average molecular weight Mw of from 80,000 Dalton to 350,000 Dalton, iii) a Polydispersity Mw/Mn of from 1.3 to 4.1, and iv) a viscosity of up to 4.0 mPa·s, measured as a 2.0 wt % solution of the esterified cellulose ether in 0.43 wt % aqueous NaOH at 20° C., are useful as enteric polymers for pharmaceutical dosage forms.

Abstract: A porphyrin compound and composition made therefrom comprising a therapeutically effective dose of a porphyrin bound via a linker to an anti-cancer agent useful in treating cancer in a patient in need thereof or to treat cancer cells in-vitro. The compounds and compositions may be delivered by a drug delivery device as disclosed here and be part of a kit.

Abstract: A compound, or a pharmaceutically acceptable salt thereof, having a structure of: wherein L is a cleavable linker group; X is a cargo moiety-containing group; and R1 and R2 are each independently hydrogen, alkyl, or substituted alkyl; or R1 and R2 together form a boronic ester ring or a substituted boronic ester group.

Abstract: The present invention provides a glycosaminoglycan derivative in which a group derived from glycosaminoglycan and a group derived from a physiologically active substance having at least one of a carboxy group and a hydroxy group are coupled by covalent bond with a spacer therebetween, in which the spacer is selected in accordance with the decomposition rate of the covalent bond to the group derived from the physiologically active substance.

Abstract: Disclosed herein are functionalized hyaluronic acid (HA), a responsive elastic polymer system comprising functionalized HA, and methods of fabrication and utilization of the same. This polymer system may be used for controlled local or systemic drug delivery release of analgesics, anesthetics, antibiotics and other drugs as well as tissue engineering articles.

Abstract: The present invention relates to polypeptides which are covalently bound to non-aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of the Eph receptor tyrosine kinase A2 (EphA2). The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder characterised by overexpression of EphA2 in diseased tissue (such as a tumour).