Abstract: Disclosed is a general, reversible bicyclization strategy to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell-penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell-permeability. Once inside the cell, the disulfide bonds are reduced to produce a linear, biologically active peptide. This strategy was applied to generate a cell-permeable bicyclic peptidyl inhibitor against the NEMO-IKK interaction.

Abstract: The invention provides methods for treating a patient with constipation-predominant irritable bowel syndrome by administering a therapeutically effective dose of linaclotide.

Abstract: This disclosure provides a novel compositions and methods to deliver cyclosporine A using genetically engineered protein polymers.

Abstract: A method of treating staphylococcal infections includes administering to a subject an effective amount of an antibacterial composition having a broad bactericidal activity. The antibacterial composition includes a first antibacterial protein consisting of the amino acid sequence as set forth in SEQ. ID. NO: 1 and/or a second antibacterial protein consisting of the amino acid sequence as set forth in SEQ. ID. NO: 2.

Abstract: A method of treating an eye disease comprising administering an adeno-associated virus (AAV) vector to a mammalian subject by subretinal injection, wherein the AAV vector comprises a nucleotide sequence encoding melanopsin operably linked to an expression control sequence to promote expression of melanopsin in cells of the eye of the subject.

Abstract: The present disclosure relates to methods for increasing telomere length in one or more human cells and/or increasing genome stability of one or more human cells, for example by contacting one or more human cells with an agent that increases expression of Zscan4 in the one or more human cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a genomic and/or chromosome abnormality, of rejuvenating one or more human cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human cells in the subject with an agent that increases expression of Zscan4, or by administering to a subject in need thereof, an agent that increases expression of Zscan4 are also provided.

Abstract: The present disclosure relates to methods for increasing telomere length in one or more human cells and/or increasing genome stability of one or more human cells, for example by contacting one or more human cells with an agent that increases expression of Zscan4 in the one or more human cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a genomic and/or chromosome abnormality, of rejuvenating one or more human cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human cells in the subject with an agent that increases expression of Zscan4, or by administering to a subject in need thereof, an agent that increases expression of Zscan4 are also provided.

Abstract: Compositions and formulations comprising chlorotoxin conjugate compounds are provided, including native and modified variants of chlorotoxin peptide conjugated to detectable agents or active agents. Methods of detecting and treating ductal carcinoma in situ breast cancer, invasive ductal carcinoma breast cancer, lobular carcinoma in situ, invasive lobular carcinoma, and triple-negative breast cancer with chlorotoxin conjugate compounds are also provided, including methods of imaging tumor tissues and cells.

Abstract: This invention is directed to methods and compositions for increasing the expression or activity of neprilysin in, for example, the frontal cortex or the entorhinal cortex using a progranulin polypeptide or effector. The present invention is further directed to methods of reducing microglia in the brain of a patient with neurodegenerative disease using a progranulin polypeptide or effector.

Abstract: The invention features polypeptides that include an extracellular ActRlla variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRlla variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving bone damage, e.g., primary osteoporosis, secondary osteoporosis, osteopenia, osteopetrosis, facture, bone cancer or cancer metastasis-related bone loss, Paget's disease, renal osteodystrophy, treatment-related bone loss, diet-related bone loss, bone loss associated with the treatment of obesity, low gravity-related bone loss, or immobility-related bone loss.

Abstract: Embodiments of the disclosure concern methods and compositions that relate to increasing or decreasing the weight (including, for example, by increasing or decreasing the adipose mass) in individuals in need thereof. Such methods and compositions, in particular embodiments, concern providing an effective amount of the hormone asprosin to increase adipose mass in an individual with insufficient adipose mass and providing an antibody or inhibitor of asprosin in an individual with obesity or diabetes, for example, to reduce adipose mass.

Abstract: The present invention provides methods for treating a stiffened joint in a subject that comprise administering relaxin, e.g., a PEGylated relaxin-2, to the subject. The relaxin may be administered intra-articularly as a sustained release formulation. The present invention also provides sustained release formulations in the form of a hydrogel for administering polypeptides that are covalently attached to a polymer, e.g., PEG.

Abstract: The present invention provides a powder formulation containing glucagon or a glucagon analog for nasal administration, useful in the treatment of hypoglycemia, and in particular the treatment of severe hypoglycemia. The present invention also provides a method of making this powder formulation, and to devices and methods for using the powder formulation.

Abstract: There is provided inter alia an aqueous liquid pharmaceutical formulation comprising (i) an insulin compound at a concentration of 500-1000 U/ml, (ii) ionic zinc, (iii) a zinc binding species at a concentration of 1 mM or more selected from species having a logK with respect to zinc ion binding in the range 4.5-12.3 at 25° C., and (iv) a non-ionic surfactant; and wherein the formulation is substantially free of EDTA and any other zinc binding species having a logK with respect to zinc ion binding of more than 12.3 at 25° C.

Abstract: The present invention relates to a pharmaceutical composition comprising a PTH compound, wherein after subcutaneous administration the pharmacokinetic profile of the PTH compound exhibits a peak to trough ratio of less than 4 within one injection interval.

Abstract: A biologically active complex comprising a polypeptide having the sequence of a naturally occurring protein or a variant thereof, wherein said polypeptide is at least partially unfolded as compared to the said naturally occurring protein for example as a result of a modification of at least one cysteine residue; or a peptide of up to 50 amino acids; and a fatty acid or lipid or a salt thereof, for use in prophylactic treatment of cancers, in particular of the gastrointestinal tract. Compositions that may comprise the complex and have use as nutraceuticals are obtainable from milk or milk fractions and form a further aspect of the invention. Methods of treatment in particular for the prevention of cancer form a further aspect of the invention.

Abstract: A synthetic or recombinant human lecithin cholesterol acyltransferase (LCAT) variant is provided which comprises an LCAT enzyme having a substitution at position 114 based on the residue numbering of wild-type (WT) human LCAT [SEQ ID NO:1], wherein said variant is characterized by one or more of: (i) an esterification rate higher than the esterification rate of WT human LCAT; and/or (ii) an association with higher density lipoprotein levels as compared to subjects having WT LCAT. Also provided are vectors encoding the variant, compositions containing same, and methods of using the variant proteins and vectors for treatment of a variety of disorders associated with defective wt LCAT.

Abstract: The present invention provides methods of treating LAL deficiency comprising administering to a mammal a therapeutically effective amount of lysosomal acid lipase with an effective dosage frequency. Methods of improving growth and river function, increasing LAL tissue concentration, and increasing LAL activity in a human patient suffering from LAL deficiency are also provided.

Abstract: This invention relates to compositions and methods for activating and promoting mineralization in tissue that does not normally mineralize, specifically intervertebral discs. The composition comprises agents that increase the expression of the gene that encodes TNAP and/or the activation, amount or activity of TNAP protein, and agents that decrease the expression of ANK and/or ENPP and/or the activation, amount or activity of these proteins. The composition can be in the form of a cell or cells. The invention also relates to methods of using the composition.

Abstract: Methods and compositions for the treatment of biofilms, particularly comprising Staphylococcal strains, of particular use in treating MRSA infections, including dormant or difficult to treat biofilm forms.

Abstract: Provided are methods and kits for reducing the severity of muscle stiffness. The method comprises delivering to one or more specific locations in the deep fascia of an affected muscle a composition comprising a therapeutically effective amount of hyaluronidase.

Abstract: Provided is a dental pretreatment material for dental tissue regeneration by use of dental pulp stem cells, particularly a dental pretreatment material effectively enabling dental tissue regeneration even by use of dental pulp stem cells of middle-aged or older individuals. The dental pretreatment material is characterized by comprising a serine protease, specifically trypsin. The dental pretreatment material comprising trypsin is used as an injection into a root canal before a root canal filling material comprising dental pulp stem cells and an extracellular matrix is inserted into the root canal as an attempt to regenerate a dental pulp and a dentin. The root canal filling material includes an ALK5 inhibitor, a CCR3 antagonist, or a CCL11 neutralizing antibody.

Abstract: The invention relates to a hemostatic composition in powder form comprising collagen of the fibrillar type comprising a content of fibrous collagen and/or fibrillar collagen of at least 70% by weight relative to the total weight of the collagen, and at least one monosaccharide, and optionally, at least one compound selected from coagulation factors and glyclosaminoglycans. The invention further relates to a method for preparing such composition, and to a unit comprising such composition and a spraying device.

Abstract: A method of disrupting or reducing a biofilm, the methods comprising contacting the biofilm with a matrix metalloproteinase (MMP). The biofilm may be present on inanimate or biological surfaces. Also, the MMP may be used to prevent the growth of a biofilm on an item, such as a medical device, by applying the MMP to the item. Also, therapeutic compositions comprising the MMP, which may be used to treat an individual having a biofilm-associated disease or disorder.

Abstract: There is provided a method for treating or reducing the effects of fructose intolerance and health problems associated with excessive fructose intake by administration of glucose isomerase. Other embodiments are also disclosed.

Abstract: Disclosed herein are polynucleotides encoding multi-epitope polypeptides and assemblies thereof, and their use for treating or limiting Toxoplasma gondii infection.

Abstract: A method of generating an antibody and cellular immune response against a Plasmodium in a primate, comprising administering at least 103 genetically modified live Plasmodium to the primate, wherein the genetically modified live Plasmodium is a species selected from Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Plasmodium knowlesi, Plasmodium coatneyi, Plasmodium cynomolgi, and Plasmodium simium, and wherein the genetically modified live Plasmodium does not produce functional histamine releasing factor (HRF) protein, to thereby induce an antibody and cellular immune response against the Plasmodium in the primate. In some embodiments at least 104 genetically modified live Plasmodium is administered to the primate.

Abstract: The present invention relates to an immunogenic complex comprising an amino acid sequence having at least 80% sequence identity with the amino acid sequence of the N-terminal region of a group B Streptococcus surface protein, and a capsular polysaccharide. The immunogenic complex is capable of eliciting protective immunity against group B Streptococcus. The invention further pertains to an immunogenic product comprising the immunogenic complex and an immunogenic fusion protein, the vaccine, the immunogenic complex, or the immunogenic product for use in a method of preventing or treating a group B Streptococcus infection, as well as a method of preventing or treating a group B Streptococcus infection.

Abstract: Provided herein are host cells capable of producing hybrid oligosaccharides and polysaccharides, wherein said hybrid oligosaccharides and polysaccharides do not comprise a hexose at the reducing end of their first repeat unit. Also provided herein are hybrid oligosaccharides or polysaccharides and bioconjugates which can be produced by the host cells described herein, wherein said bioconjugates comprise a carrier protein linked to a hybrid oligosaccharide or polysaccharide that does not comprise a hexose at the reducing end of its first repeat unit.

Abstract: The invention relates to methods and compositions for use in stimulating an immune response against a target antigen. More specifically, it relates to use of domains III and IV of the Staphylococcal Sbi protein as an immunological adjuvant, for enhancing an immune response against a target antigen.

Abstract: A method for immunizing a subject in need thereof against Neisseria gonorrhoeae by administering an immunogenic composition comprising meningococcal outer membrane vesicles (OMVs).

Abstract: The invention provides Chlamydia antigens for use in the treatment, prevention and/or diagnosis of Chlamydia infection. In particular, the invention provides antigens CT733, CTI 53, CT601, CT279, CT443, CT372, CT456, CT381, CT255, CT341, CT716, CT745, CT387, CT812, CT869, CT166, CT175, CT163, CT214, CT721, CT127, CT043, CT823 and/or CT600 from C. trachomatis for the treatment, prevention or diagnosis of Chlamydia infection.

Abstract: Methods for purifying human Calciviruses are disclosed, including Noroviruses and Sapoviruses.

Abstract: The present disclosure provides a DNA vaccine or immunogenic composition expressing consensus hemagglutinin-esterase-fusion (HEF) protein (FluD-Vax) and a protein-based vaccine utilizing the HEF consensus protein. Methods of making and using the compositions are also provided herein.

Abstract: Disclosed is a hemagglutinin-binding peptide producing an anti-influenza virus effect higher than that of existing peptides. Also disclosed are hemagglutinin-binding peptides comprising a polypeptide having any of the following amino acid sequences (i) to (iv): (i) Thr-MeGly-Asp-MePhe-MePhe-Ser-MeSer-His-Tyr-Thr-Val-Pro-Arg (SEQ ID NO: 1); (ii) Arg-Val-Ser-MePhe-Thr-Tyr-MePhe-MeSer-Tyr-Thr-Pro-Ser (SEQ ID NO: 2); (iii) an amino acid sequence with deletions, additions, or substitutions of one or several amino acids in SEQ ID NO: 1 or 2; and (iv) an amino acid sequence having 90% or more sequence identity to that of SEQ ID NO: 1 or 2.

Abstract: Provided is a method for producing an artificial recombinant virus of the family Reoviridae, the method comprising the steps of: (1) introducing a FAST protein expression vector and/or a capping enzyme expression vector into host cells; (2) introducing a vector containing expression cassettes for individual RNA genome segments of a virus or introducing a set of single-stranded RNA transcripts from the expression cassettes into host cells; and (3) culturing the host cells. The method of the present invention allows more efficient production of an artificial recombinant virus of the family Reoviridae as compared with conventional methods and allows artificial recombinant rotavirus production without using a helper virus.

Abstract: Provided herein are recombinant respiratory syncytial viruses that contain mutations that make the disclosed viruses attractive vaccine candidates. The viruses disclosed contain attenuating mutations designed to have increased genetic and phenotypic stability. Desired combinations of these mutations can be made to achieve desired levels of attenuation. Exemplary vaccine candidates are described. Also provided are polynucleotides capable of encoding the described viruses, as wells as methods for producing the viruses and methods of use.

Abstract: The present invention relates to a composition comprising Epstein-Barr Virus (EBV) particles for use in vaccination of a subject, wherein said EBV particles comprise a significantly reduced chromosome instability-inducing EBV polypeptide activity. The present invention also relates to a composition comprising EBV particles for use in vaccination of a subject, wherein said vaccination comprises avoiding contacting the cytosol and/or nucleus of cells of said subject with a chromosome instability-inducing EBV polypeptide activity. Moreover, the present invention relates to polynucleotides, host cells, methods, and uses related to the aforesaid compositions.

Abstract: The invention relates to a pharmaceutical composition for the modulation of T cell and B cell responses made of one or more preparations and comprising a therapeutically effective dose of at least one inhibitor of TNFR1-mediated functions and of at least one antigen or allergen.

Abstract: The present invention provides methods and compositions for the stimulation of immune responses. In particular, the invention provides methods and compositions for enhancing an immune response to one or more antigens. Compositions and methods of the invention are useful for the treatment and/or prevention of microbial infections, such as infections caused by bacteria, viruses, fungi and parasites, as well as the treatment and/or prevention of cancer and malignant diseases. Compositions and methods of the invention include one or more antigens/immunogens together with an adjuvant formulation comprising an emulsion delivery system in combination with one or more immunostimulatory compounds (e.g., a compound that stimulates the innate immune system (e.g., a toll-like receptor antagonist (e.g., synthetic oligodeoxynucleotides (ODN)))) that enhance immune responses to the one or more antigens/immunogens when administered to a subject.

Abstract: Immunoprotective primary mesenchymal stems cells (IP-MSC) which episomally express immunoreactive polypeptides that specifically target a pathogen (e.g., an infectious species of virus, bacterium, or parasite) or toxin are described herein. The immunoreactive polypeptides can be, e.g., full antibodies, single-chain antibodies (ScFV), Fab or F(ab)2 antibody fragments, diabodies, tribodies, and the like). Optionally IP-MSC are transfected to express one or more other immunomodulating polypeptides, e.g., a cytokine such as an interleukin (e.g., IL-2, IL-4, IL-6, IL-7, IL-9, and IL-12), an interferon (e.g., IFN?, IFN?, or IFN?), and the like, which can enhance the effectiveness of the immunoreactive polypeptides.

Abstract: This invention related to manufactured microbubbles, as well as methods of using manufactured microbubbles, for example, in medicinal applications. The invention pertains to the physical structure and materials of the microbubbles, as well as to methods for manufacturing microbubbles, methods for targeting microbubbles for specific medicinal applications, and methods for delivering microbubbles in medical treatment.

Abstract: Provided herein are conjugates, compositions and methods for use in photoimmunotherapy, such as photoimmunotherapy induced by activation of a phthalocyanine dye conjugated to a targeting molecule that binds a protein on cell, for example, an IR700-antibody conjugate. In some embodiments, the phthalocyanine-dye conjugate can be activated by irradiation with near-infrared light. Features of the conjugates, compositions and methods, including the dose of the conjugate, provide various advantages, such as lower toxicity and/or improved efficacy. In some embodiments, also provided is a dual label phthalocyanine-dye conjugate in which the targeting molecule is conjugated to an additional fluorescent dye, which can be used for photoimmunotherapy while, for example, also exhibiting improved performance for imaging or detection. Also provided are therapeutic methods using the conjugates and compositions for treatment of diseases and conditions, including tumors or cancers.

Abstract: A method to increase the penetration of active agents through mucosal membranes, the method comprising the step of: a) administering to a subject in need a composition comprising: i) one or more hydrotropes in a total amount of less than 15% by weight of the composition; and ii) an active agent with a partition co-efficient (log P) or distribution coefficient (log D) of between 0 and 5.

Abstract: This disclosure provides a novel pharmaceutical composition capable of forming micelles upon exposure to the gastric environment. The pharmaceutical composition is suitable for delivering steroid hormones, and progesterone in particular, to a subject in need thereof.

Abstract: The invention provides methods, compositions and kits relating to hyaluronan based matrices using oxidized glutathione as a crosslinking agent.

Abstract: The present invention relates to cyclic peptide compounds which inhibit or antagonize the binding of methylglyoxal (MG) and/or other reactive carbonyl species (RCS) to an arginine-or lysine-containing protein. Preferred scavenger compounds are said cyclic peptides comprising a specific amino acid motif and a hydrophobic modification, and pharmaceutical compositions thereof. The present invention furthermore relates to the use of the cyclic peptides as scavenger or antagonists of methylglyoxal and/or related reactive carbonyl species (RCS). The present invention furthermore relates to the use of the cyclic peptides for the prevention and/or treatment of a disease caused by or associated with methylglyoxal (MG) and/or reactive carbonyl species (RCS), in particular caused by or associated with elevated MG levels, such as diabetes and its associated complications, cardiovascular diseases and obesity.

Abstract: The present invention relates to a polymer-drug conjugate wherein the polymer is hyaluronic acid and the drug is an anticancer compound. The anticancer compound is covalently linked to the hyaluronic acid by a pH-labile boronic acid-containing linkage. These conjugates can be used for the treatment of cancer.

Abstract: There is provided a molecule comprising a chain of seven or more contiguous units of 4,6-dideoxy-4-acylamido-?-pyranose, each pair of units joined by a C1-C2 or a C1-C3 link, the chain having a terminal end and a reducing end, wherein the pyranose ring in the unit of the chain most distal from the reducing end is linked to a cap structure. The cap structure is not a 4,6-dideoxy-4-acylamido-?-pyranose. There are also provided vaccine compositions comprising the molecule and methods of vaccinating an animal NI against infection by a Brucella organism, including methods of distinguishing between a vaccinated and an infected animal. There are further provided novel methods of detecting the presence in a sample of an anti-Brucella antibody.

Abstract: Disclosed herein are ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) complexes and synthetic molecules that interact with an ENPP protein. In some embodiments, also disclosed herein are modified ENPP polypeptides in complex with a synthetic molecule described herein.