Abstract: The present disclosure relates to compositions and methods for targeting antigenically variable pathogens and diseases. Embodiments of the present disclosure involve of the construction of variable epitope libraries (VELs) containing mutated versions of epitopes derived from antigens associated with various diseases for treating subjects in both therapeutic and prophylactic settings. The present disclosure also provides compositions and methods for the production of VELs based on CTL-derived epitopes of survivin, an oncogenic inhibitor-of-apoptosis. Given the large number of potential epitopes expressed in tumors, and the dynamic nature of the tumor epitope landscape, there is a need to develop compositions and methods for targeting various antigenic epitopes to counteract immune escape.

Abstract: An HLA-A*1101-restricted WT1 peptide, specifically, a peptide comprising an amino acid sequence consisting of 9 contiguous amino acids from a WT1 protein, wherein the peptide has an ability to bind to an HLA-A*1101 molecule, and has an ability to induce a CTL is described. A peptide dimer having an ability to bind to an HLA-A*1101 molecule and having an ability to induce a CTL, in which two peptide monomers each comprising an amino acid sequence consisting of 9 contiguous amino acids from a WT1 protein and comprising at least one cysteine residue are bound to each other through a disulfide bond is also described. Furthermore, a polynucleotide encoding the peptide, a pharmaceutical composition for the treatment and/or prevention of a cancer comprising the same and the like are provided.

Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

Abstract: The present invention features incapacitated whole-cell bacterial immunogenic compositions and methods of their production, which compositions are useful to deliver antigens in a manner resembling the live infectious organism in terms of elicitation of a robust immune response, but with reduced risk or no risk of disease. The compositions of the invention are produced by rendering a bacterium bacteriostatic through expression of a recombinant promoter in the bacterial cell, which promoter can be operably linked to a polynucleotide encoding a recombinant gene product. In one embodiment, where the bacterium is a gram negative host, the recombinant gene product provides for reduced toxicity of LPS. In one embodiment, the gene product is a bacteriophage protein, such as endolysin, holin, or ndd.

Abstract: Provided herein is a genetically modified Y. pestis that includes three alterations compared to a control Y. pestis. Two alterations include decreased mRNA, decreased protein, or a combination thereof, encoded by a lpp coding region and encoded by a msbB coding region. The third alteration is selected from an alteration of an intergenic region between the coding regions ypo1119 and ypo1120, and decreased mRNA, decreased protein, or a combination thereof, encoded by a coding region selected from pla, ypol717, ypmt1.80c, rbsA (ypo2500), ypo0498, vasK (ypo3603), ypo3164, hxuB (ypo3248), ypo1616, ypo1119, ypo1120, and ail. Also provided are compositions that include the genetically modified Y. pestis, and methods of using the genetically modified Y. pestis.

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: The present invention provides attenuated M. haemolitica strains that elicit an immune response in animal against M. haemolitica, compositions comprising said strains, methods of vaccination against M. haemolitica, and kits for use with such methods and compositions. The invention further provides multi-valent vaccines, which provide protective immunity when administered in an effective amount to animals susceptible to “shipping fever” or bovine respiratory disease.

Abstract: The present invention provides methods of production of a purified enveloped virus antigen. In particular, it provides purified Ross River Virus (RRV) antigens, and vaccines comprising purified, inactivated Ross River Virus (RRV) antigen.

Abstract: The present invention relates to T cell receptors (TCRs) which bind the HLA-A2 restricted CLGGLLTMV peptide (SEQ ID NO: 1) derived from the LMP2A protein from Epstein Barr Virus (EBY). TCRs of the invention comprise a TCR alpha chain variable domain and/or a TCR beta variable domain. Certain preferred TCRs also bind the natural peptide variants SLGGLLTMV (SEQ ID NO: 17) and CLGGLITMV (SEQ ID NO: 18) presented as a peptide-HLA-A2 complex. The TCRs of the invention demonstrate excellent specificity profiles for those LMP2A epitopes and have binding affinities for the complex which result in an enhanced ability to recognize the complex compared to a soluble reference TCR having the extracellular sequence of the native EBY LMP2A TCR alpha chain given in FIG. 3 (SEQ ID No: 4) and the extracellular sequence of the native EBY LMP2A TCR beta chain given in FIG. 4 (SEQ ID No: 5).

Abstract: Described are methods for preparing virosomes comprising the steps of: (a) providing an enveloped virus, and optionally inactivating the virus; (b) solubilizing the viral envelopes in a first solubilizing agent; (c) pre-solubilizing exogenous components in a second solubilizing agent; (d) adding the pre-solubilized exogenous components to the solubilized viral envelopes; and (e) reconstituting virosomal membranes by removing the solubilizing agent. According to the disclosure, the viral envelopes and the exogenous components are (pre-)solubilized at a temperature below 33° C.

Abstract: The present disclosure relates to compositions and methods for using a modified virus that infects a cell only if the virus presents a candidate antigen that binds with high affinity to a target antibody, thereby allowing for generation and identification of immunogens useful, for example, as vaccines.

Abstract: This invention relates to Hendra virus and Nipah virus immunogenic compositions and methods of use. The invention further relates to immunogenic compositions comprising Hendra virus G glycoprotein, and methods of protecting against Nipah virus infection and disease. The invention also relates to methods of distinguishing subjects vaccinated with the immunogenic compositions of the invention from those infected with Hendra and/or Nipah virus.

Abstract: The present invention provides vectors that contain and express in vivo or in vitro CDV polypeptides or antigens that elicit an immune response in animal against CDV, compositions comprising said vectors and/or CDV polypeptides, and methods of vaccination against CDV. The invention further provides methods for inducing an immunogenic or protective response against CDV and other canine virus, as well as methods for preventing or treating CDV and other canine virus or disease state(s) caused by CDV and other canine virus.

Abstract: Disclosed is a vaccine comprising a fiber protein, selected from fiber-2 protein of Fowl Adenovirus C (FAdV-C), fiber-2 protein of Fowl Adenovirus A (FAdV-A), fiber protein of Fowl Adenovirus B, D and E (FAdV-B, FAdV-D and FAdV-E), or an immunogenic fragment thereof for use in preventing hepatitis-hydropericardium Syndrome (HHS) or inclusion body hepatitis (IBH) or Gizzard Erosion (GE) in birds, preferably in poultry, especially in broilers.

Abstract: The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure wherein: R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ?-aminoalkyls, ?-(substituted)aminoalkyls, ?-phosphoalkyls, ?-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40 K), optionally substituted mPEG (mw 120-40 K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

Abstract: An improved method for the manufacture of an oil-in-water emulsion comprises using a microfluidisation device whose interaction chamber comprises a plurality of Z-type channels upstream of a back pressure chamber.

Abstract: Methods of treating proliferative disorders are described. In particular, combination treatment with a GITR agonist and a PD-1 antagonist are provided.

Abstract: The present invention relates to an insulin-like growth factor (IGF) receptor antagonist for use in the treatment of prostate neoplasia, including benign prostatic hyperplasia (BPH), prostate cancer, and particularly CRPC, wherein the antagonist is used in combination with an androgen receptor antagonist. An embodiment of the invention is where the androgen receptor antagonist is enzalutamide.

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 invention relates to trans carotenoid compounds and salts thereof as well as compositions thereof, methods for making them, and uses thereof. These compounds are useful in improving diffusivity of oxygen between red blood cells and body tissues in mammals including humans.

Abstract: The present invention generally relates to compounds that include one or more thermally labile protecting groups, compositions including the compounds, methods of making the compounds and compositions and methods of using the compounds and compositions. In one aspect, the present invention is directed to a compound of the structure XO—CH2—SM-B-A. The substituent X is H, an acid labile protecting group, a solid support, —P(O—R1)NR2R3, —P(O)(OH)H, —P(O)(OR1)H, —P(O)(OH)2, —P(O)(OH)O—P(O)(OH)OP(O)(OH)2 or salts thereof. The substituent R1 is CNE (i.e., cyanoethyl), alkyl, or heteroalkyl and R2 and R3 are independently alkyl. The substituent SM is a sugar moiety or analogue thereof that is not a natural furanosyl, B is a base moiety or analogue thereof, and A is a moiety attached to a nitrogen on or in the base moiety of the structure —C(O)OR4, wherein R4 is tertiary alkyl.

Abstract: The present invention relates to the use of microfine pigments in medical and cosmetic phototherapy.

Abstract: Topical compositions comprising a corticosteroid and at least one penetration enhancing agent, wherein the composition is substantially free of propylene glycol.

Abstract: The present invention relates to use of certain alkylglycoside compositions for the prevention of aggregation and oxidation of antibodies and other proteins in therapeutically useful formulations thereof.

Abstract: The present invention relates to compositions useful for biomedical procedures. More specifically the compositions are useful in procedures involving vascular embolization. The compositions are consist of solutions of aqueous-insoluble C2-C3 linked polyethers of 1,6:2,3-dianhydrohexopyranose derivatives in biocompatible solvents.

Abstract: The present invention is based on the surprising discovery that the inclusion of an anionic polymer in the adenovirus formulation enhances long-term stability of the vector composition. An aqueous formulation comprising an adenovirus vector and at least one anionic polymer is provided, together with methods of the preparation of a storage stable adenovirus aqueous formulation.

Abstract: The present invention provides a formulation for reducing the hydrophobicity of ACAT-1 inhibitors. Methods for using the formulation of the present invention are also provided.

Abstract: Skin penetration enhancers comprising peptides are disclosed. Compositions comprising the skin penetration enhancers are also provided. The compositions further comprise an active agent, such as a pharmaceutically active agent, a vaccine, a cosmetic agent, and a. nutritional supplement. Methods of transdermal ly delivering a pharmaceutically active agent, a vaccine, a cosmetic agent, or a nutritional supplement are also provided.

Abstract: The invention provides uses for phospholipid conjugates of TLR agonists as enhancers of an innate immune response. Specifically, purine derivatives which are conjugated to a phospholipid or an analog thereof are disclosed as having activity as TLR7 agonists, capable of inducing an innate immune response upon administration in an effective amount to a subject. The phospholipid moiety of the TLR7 agonist contains one or more alkyl ether or ester moieties.

Abstract: A system for detecting cancer cells that targets the cubilin receptor for the vitamin B12 binding protein, intrinsic factor. A B12 conjugate and intrinsic factor is injected into the blood of a patient. The binding of intrinsic factor to cubilin will allow for receptor-mediated endocytosis and cellular internalization by cancerous cells, thereby allowing for detection via imaging or treatment.

Abstract: The present invention provides multi-armed high MW polymers containing hydrophilic groups conjugated to Factor VIII, and methods of preparing such polymers.

Abstract: Graft copolymer polyelectrolyte complexes are disclosed for the efficient delivery of anionic, cationic or polyelectrolyte therapeutic agents into biological cells, and for maintaining the biological activity of these molecules while in serum and other aqueous environments are provided. Such complexes comprise (1) an anionic graft copolymer containing an anionic polymer backbone, with pendent carboxylic acid groups and pendant chains containing amphipathic or hydrophilic polymers covalently bonded to a portion of the pendant carboxylic acid groups, (2) one or more anionic, cationic or polyelectrolyte therapeutic agents, and (3) optionally a liposome optionally containing an additional therapeutic agent. Also disclosed are functional nanoparticles containing the complexes.

Abstract: The present invention relates, in general, to materials and methods for the preparation of modified blood factors which have low levels of water soluble polymer molecules conjugated to the blood factor but exhibit biological activity similar to or better than molecules having a higher number of water soluble polymer moieties.

Abstract: The present invention relates to an improved macromolecule transduction domain (MTD), which facilitates permeating the cell membrane of a biologically active molecule, having enhanced cell permeability. Specifically, an improved MTD according to the present invention, compared to an existing MTD, can transmit various types of biologically active molecule from inside the body and inside a test tube more effectively, and thus can be effectively used in a method to genetically alter a biologically active molecule so as to have cell permeability or in a method to transport a biologically active molecule into a cell, or the like. Additionally, the improved MTD can be very useful in development of new drugs and incrementally modified drugs as uses of the improved MTD are possible in drug delivery systems, recombinant protein vaccines or DNA/RNA therapeutic agents, gene or protein therapies, and pharmacologically or medically useful protein production or medical, pharmacological and pharmaceutical compositions.

Abstract: The present invention relates to a peptide which consists of more than 50% of sequence sections of the formula -(An-Bm-Co)-, and to a conjugate containing the peptide and at least one covalently bonded active compound, and to a process for the preparation of the conjugate. The present invention furthermore relates to the use of the peptide and the conjugate for targeting of the kidney, and to a medicament comprising the peptide or conjugate.

Abstract: The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein (e.g., a eukaryotic target protein such as a mammalian target protein or a fungal target protein or a prokaryotic target protein such as a bacterial target protein). These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of intracellular target proteins. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of the targeted protein's activity.

Abstract: The present invention relates to methods for preventing or treating head and neck spuamous cell cancer and bladder cancer using an immunotoxin comprising (a) a ligand that binds to a protein on the cancer cell attached to; (b) a toxin that is cytotoxic to the cancer cell. In a specific embodiment, the invention is directed to the prevention or treatment of head and neck squamous cell cancer or bladder cancer using Vb4-845, which is a recombinant immunotixin comprising a humanized, MOC31-derived, single-chain antibody fragment that is fused to a truncated form of Pseudomonas exotoxin A. Also encompassed by the invention are combination therapy methods, including the use of reduced dosages of chemotherapeutic agents, for the prevention or treatment of cancer. Also encompassed by the invention are formulations and methods for direct administration of the recombinant immunotoxin to the carcinoma, for the prevention or treatment of cancer.

Abstract: The invention provides anti-Ly6E antibodies, immunoconjugates and methods of using the same.

Abstract: Disclosed is the surprising discovery that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are specific, accessible and stable markers of the luminal surface of tumor blood vessels. The present invention thus provides aminophospholipid-targeted diagnostic and therapeutic constructs for use in tumor intervention. Antibody-therapeutic agent conjugates and constructs that bind to aminophospholipids are particularly provided, as are methods of specifically delivering therapeutic agents, including toxins and coagulants, to the stably-expressed aminophospholipids of tumor blood vessels, thereby inducing thrombosis, necrosis and tumor regression.

Abstract: Benzodiazepine dimers having a structure represented by wherein X comprises a heteroaromatic moiety and is as further defined in the application; R1 is and the other variables in formulae (I), (Ia), and (Ib) are as defined in the application. Such dimers are useful as anti-cancer agents, especially when used in an antibody-drug conjugate (ADC).

Abstract: The present invention provides methods and compositions for protein delivery. The invention features virus like particles, methods of making virus like particles and methods of using virus like particles to deliver proteins to a cell, to provide protein therapy and to treat diseases or disorders. The invention also features methods of targeting a protein to a cell, methods of protein therapy and methods of treating diseases or disorders using a TUS protein, a NLS or NES identified from full length TUS.

Abstract: A medicinal composition for diseases caused by dyslipidemia and/or autophagy dysfunction, etc., said medicinal composition comprising polyrotaxane that carries bulky substituents introduced, via intracellularly degradable bonds, into both ends of a linear molecule penetrating through plural cyclic molecules.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: The present invention provides a laparoscopic surgery method comprising inspection of peritoneal surfaces under an isotonic solution comprising a contrast enhancing agent using near contact scanning by a laparoscope. Accordingly, the method according to the current invention comprises introducing the solution and the contrast enhancing agent into the retroperitoneal space through a catheter or a channel of a laparoscope using an irrigation pump. The present invention provides also an isotonic laparoscopy solution comprising a contrast enhancing agent enhancing the contrast of the laparoscopic view.

Abstract: Disclosed herein is a composition for imaging nerve cells. The composition includes a fluorescent dye; and a viral component including a neurotropic herpes varicellae unable to replicate in nerve cells, a viral protein of a neurotropic herpes varicellae unable to replicate in nerve cells, a capsid of a neurotropic herpes varicellae unable to replicate in nerve cells, or a combination thereof. The fluorescent dye is bound to the viral component to form a dye/viral component complex that is capable of penetrating nerve cells.

Abstract: The present disclosure relates to a novel type of recognitive biodegradable nanoparticles and their preparations. In particular, the present disclosure relates to combinations of MIPs and biodegradable nanoparticles.

Abstract: The methods of the invention exploit the capabilities of manganese-enhanced MRI (MEMRI), which provides viability-specific biological contrast agent through the intracellular accumulation of Mn2+. A typical contrast agent utilizes non-chelated Mn2+ in combination with Ca2+, e.g. as calcium gluconate. Active intracellular accumulation of Mn2+ generates high signal from the viable cells in normal tissue, or normal regions of heterogeneous tissue; no signal from the non-viable cells; and intermediate signal from viable but injured cells. The intermediate signal defines a “gray zone” of potentially salvageable cells.

Abstract: The present invention is directed generally to eukaryotic cells comprising single-celled organisms that are introduced into the eukaryotic cell through human intervention and which transfer to daughter cells of the eukaryotic cell, and methods of introducing such single-celled organisms into eukaryotic cells. The invention provides single-celled organisms that introduce a phenotype to eukaryotic cells that is maintained in daughter cells. The invention additionally provides eukaryotic cells containing magnetic bacteria. The invention further provides eukaryotic cells engineered with single-celled organisms to allow for multimodal observation of the eukaryotic cells. Each imaging method (or modality) allows the visualization of different aspects of anatomy and physiology, and combining these allows the imager to learn more about the subject being imaged.

Abstract: Fibrin-specific imaging agents that contain at least two imaging reporters are described, as well as methods of making and using the contrast agents.

Abstract: The present invention provides a compound represented by the formula (1) or a salt thereof, or a complex of the compound or the salt with a metal, in the formula (1), A1 represents a chelate group; R1 represents a hydrogen atom or the like; R2 represents a hydrogen atom or the like; and Z1, Z2, Z3, Z4, and Z5 are the same or different and each represent a nitrogen atom or CR3 or the like wherein R3 represents a hydrogen atom or an optionally substituted C1-6 alkyl group or the like; L1 represents a group represented by the formula (3) wherein R13, R14, R15, and R16 are the same or different and each represent a hydrogen atom or the like; L2 represents an optionally substituted C1-6 alkylene group; and L3 represents an optionally substituted C1-6 alkylene group.