Abstract: The present disclosure relates to salts and compositions of isophosphoramide mustard and isophosphoramide mustard analogs. In one embodiment the salts can be represented by the formula I: (I) wherein A+ represents an ammonium species selected from the protonated (conjugate acid) or quaternary forms of aliphatic amines and aromatic amines, including basic amino acids, heterocyclic amines, substituted and unsubstituted pyridines, guanidines and amidines; and X and Y independently represent leaving groups. Also disclosed herein are methods for making such compounds and formulating pharmaceutical compositions thereof. Methods for administering the disclosed compounds to subjects, particularly to treat hyperproliferative disorders, also are disclosed.

Abstract: The invention relates to kisspeptide-pentasaccharide conjugates having the general formula (I) wherein Z1 is Tyr or D-Tyr; Z3 is Trp, Hyp, Phe or Lys(R2); Z5 is Thr, Aib or Ala; Z7 is Gly or azaGly; Z8 is Leu; or Z7 and Z8 together represent; Z10 is Phe or Trp; n is 0 or 1; or R2, when present, represents a pentasaccharide derivative having the formula (II) wherein R is methyl or SO3X; X is a positively charged counterion; with the proviso that when R2 is present, R1 is H or (C1-6) alkylcarbonyl; R3 is H or (C1-3)alkyl; and L represents a pharmacologically inactive linker moiety having 10-50 atoms; or a pharmaceutically acceptable salt thereof; to pharmaceutical compositions comprising the same as well as to the use of said kisspeptide-pentasaccharide conjugates in the treatment of female infertility.

Abstract: The present invention provides for silk-derived compositions for treating a wide variety of ocular conditions. The composition is produced by processing the silk cocoon into a water-based solution (i.e., a dissolved silk), which is then cast into a film. The film may be transparent to visible light, and curved in shape for easy application to the ocular surface. The silk film may either self-adhere or be sutured to cover the wound. The degradation time of the film may range from 1 minute to 24 hours, or from 2 hours to 20 hours. The present compositions can help regenerate damaged corneal tissue, thus promoting healing.

Abstract: There is disclosed herein a composition for treating gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, travelers diarrhea, chronic idiopathic nausea, IBD-associated constipation and diarrhea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinsons disease, MS, Alzheimers Disease, Motor Neurone Disease or autism, the composition comprising: (i) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or (ii) at least one anti-clostridial agent selected from the above combined with an opioid blocking agent.

Abstract: Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.

Abstract: The invention relates to substituted anionic compounds consisting of a backbone made up of a discrete number u of between 1 and 8 (1?u?8) of identical or different saccharide units, linked via identical or different glycosidic bonds, said saccharide units being chosen from the group consisting of pentoses, hexoses, uronic acids, N-acetylhexosamines in cyclic form or in open reduced form, which are randomly substituted. It also relates to the process for the preparation thereof and to the pharmaceutical compositions comprising same.

Abstract: A therapeutic formulation containing mucin glycans derived from one or a number of nutritionally appropriate sources is described.

Abstract: The embodiment of the invention is a virus-like particle vector, a process for the manufacture thereof, use of the virus-like particle vector and a pharmaceutical composition, which contains the virus-like particle vector. The vector is intended for the delivery of therapeutic agents into specific mammalian tissues, especially low molecular weight agents, in particular low molecular weight anti-cancer drugs into cancer tissues. More specifically, the invention relates to the virus-like particle vector, which constitutes an adenoviral dodecahedron with the therapeutic substance encapsulated or covalently linked.

Abstract: Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.

Abstract: The present invention provides a hydrophobic group-introduced hyaluronic acid derivative comprising at least one repeating unit represented by the formula (I): wherein R1, R2, R3, R4, Z, n, Ra, Y, and X1 are as defined in the specification.

Abstract: The subject-matter of the present invention are nanocomplexes of polyanions and cationic peptides which are, e.g., suitable for the transport of drugs into cells and their controlled release in the organism, as well as a complex material in which the nanocomplexes are bonded to a biologically active unit for the selective recognition of tissues, cells or organelles.

Abstract: The present invention relates to a macromolecule comprising a dendrimer having surface amino groups to which at least two different terminal groups are attached including a pharmaceutically active agent and a pharmacokinetic modifying agent, the pharmaceutically active agent comprising a hydroxyl group and being attached to the surface amino group of the dendrimer through a diacid linker. Pharmaceutical compositions comprising the macromolecules and methods of treatment using the macromolecules are also described.

Abstract: The present disclosure provides peptides and peptide compositions, which facilitate the delivery of an active agent or an active agent carrier wherein the compositions are capable of penetrating the stratum corneum (SC) and/or the cellular membranes of viable cells.

Abstract: Compositions and methods are provided including a transporter peptide derived from the loop2 domain of the neuronally-derived lynx1 protein which can be conjugated to an effector agent to form a transporter-effector complex for transport of the therapeutic effector agent to a target that is found across the blood brain barrier.

Abstract: The present invention provides novel amino-lipids, compositions comprising such amino-lipids and methods of producing them. In addition, lipid nanoparticles comprising the novel amino-lipids and a biologically active compound are provided, as well as methods of production and their use for intracellular drug delivery.

Abstract: Disclosed are biologically active protein conjugates that comprise a biologically active polypeptide coupled via a peptide bond to a polypeptide comprising from 2 to about 500 units of a repeating peptide motif, wherein the biologically active protein conjugate exhibits a modified plasma half-life compared to the intrinsic half-life of the unconjugated biologically active polypeptide or protein. Also disclosed are methods of making and using the conjugated proteins, as well as methods for determining whether a given conjugate exhibits a modified half life relative to the intrinsic half life of the unconjugated polypeptide.

Abstract: Conjugates of a saccharide and a biomolecule, covalently linked therebetween via a non-hydrophobic linker and methods of preparing same are disclosed. Also disclosed are medical uses utilizing such conjugates. Glycosylation reagents for use in preparing these conjugates are also disclosed. Glycosylated proteins, characterized by improved performance, are also disclosed.

Abstract: The present invention concerns compositions and methods of extracting infectious pathogens from a volume of blood. In one embodiment, the method includes the steps of creating a fibrin aggregate confining the pathogens and introducing a fibrin lysis reagent to expose the pathogens for analysis. The present invention also concerns materials and methods for removing aurintricarboxylic acid (ATA) from a sample.

Abstract: At least some embodiments of the invention relates to an implant having a coating that contains or is composed of a functionalized RGD peptidomimetic RGD-P1 having the formula (1) and/or a functionalized RGD peptidomimetic RGD-P2 having the formula (2), and an associated manufacturing method.

Abstract: The present disclosure provides methods for analyzing structure and/or composition of glycoproteins and glycans of glycoproteins. Such methods can include subjecting a glycoprotein preparation to a condition that removes at least one O-linked glycan from the glycoprotein. Such methods can include subjecting a glycoprotein preparation to a condition that releases an N-glycan from the glycoprotein, e.g., prior to subjecting the glycoprotein to a condition that releases an O-glycan from the glycoprotein.

Abstract: The present invention describes oxidized avidin, suitable for inhalation, for conditioning the lung affected by inoperable/diffuse diseases, enabling the targeted delivery of biotinylated therapeutic agents to it.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: The present invention provides methods of identifying candidate compounds for the treatment of type I diabetes and also provides methods for treating patients with type I diabetes and for limiting pancreatic beta cell apoptosis. The present invention also provides methods for diagnosing type I diabetes or a propensity to develop type I diabetes and methods for identifying diabetic patients to be treated with anti-apoCIII therapy.

Abstract: The present invention relates to a method for treating or preventing either one or both of an inflammatory disease and an autoimmune disease in a patient, wherein the method comprises providing a pharmaceutical composition containing a therapeutically effective amount of soluble Fc?R; administering said composition to a patient, followed by a safety period of several weeks, followed by a subsequent treatment cycle of at least two weekly administrations, wherein said therapeutically effective amount is effective to treat or prevent said disease in said patient. The present invention also provides a pharmaceutical composition in the form of a multiple-dosage-kit which contains sufficient amounts of administration doses of soluble Fc?R for effectively treating or preventing inflammatory diseases and/or autoimmune diseases in a patient.

Abstract: The present invention relates to triazolopyridine compounds of general formula (I): in which R1, R2, R3, R4, and R5 are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

Abstract: The present invention relates to novel complex peptidomimetic products comprising multiple homogeneous or heterogeneous pendant groups that are site-specifically positioned along a linear oligomer or polymer scaffold and methods of making thereof. More specifically, the invention relates to N-substituted glycine peptoid oligomers or peptoids and their use as substrates for azide-alkyne [3+2]-cycloaddition conjugation reactions and subsequent additional rounds of oligomerization and cycloaddition. The methods of the invention may also be used to generate peptoid-peptide hybrid or peptide products comprising multiple homogeneous or heterogeneous pendant groups, which are positioned precisely along the linear oligomer or polymer scaffold.

Abstract: The invention provides methods and compositions for improving fetal and child health and development through nutritional supplementation with, for example, sialic acid. Sialic acid can be provided to a female before, during and/or after pregnancy to improve the health and development of a fetus and/or child. The sialic acid can be in a variety of forms in the supplements.

Abstract: The present invention describes oligosaccharide sequences, which are specifically expressed by human tumors. The present invention is related to a method of determining an oligosaccharide sequence, which comprises a tumor specific terminal N-acetylglucosamine residue, in a biological sample, the presence of said sequence in said sample being an indication of the presence of cancer. The present invention provides antigenic substances comprising said oligosaccharide sequences in a polyvalent form and it further provides diagnostic agents, pharmaceutical compositions and cancer vaccines comprising said oligosaccharide sequences or substances binding to said oligosaccharide sequences. The present invention is also related to methods for the treatment of cancer.

Abstract: Methods and compositions for modulating an immune response in a subject are provided. Methods include administering to the subject a composition comprising an effective amount of a lymphocyte differentiation factor, e.g., protein A (PA), sufficient to modulate the immune response. Compositions include a lymphocyte differentiation factor, e.g., protein A (PA), in an amount less than 1 ?g.

Abstract: The present invention relates to a pyridonaphthyridine compound as represented by general formula (I), which has a dual PI3K and mTOR inhibition effect, and its pharmaceutically acceptable salt, stereoisomer and deuteride thereof, wherein R1, R2, R3, R4, R5, R6, R7 and X are as defined in the specification; the present invention also relates to a method for preparing said compound, a pharmaceutical composition and a pharmaceutical formulation containing said compound, and uses of said compound in treating and/or preventing a proliferative disease and in the manufacture of a medicament for treating and/or preventing a proliferative disease.

Abstract: The present invention provides for novel sustained release silk-based delivery systems. The invention further provides methods for producing such formulations. In general, a silk fibroin solution is combined with a therapeutic agent to form a silk fibroin article. The article is then treated in such a way as to alter its conformation. The change in conformation increases its crystallinity or liquid crystallinity, thus controlling the release of a therapeutic agent from the formulation. This can be accomplished as single material carriers or in a layer-by-layer fashion to load different therapeutic agents or different concentrations of these agents in each layer.

Abstract: An injector system for delivery of a pharmacological agent to biological tissue having a plurality of needles arranged in an array, a plurality of reservoirs configured to receive a pharmacological composition therein, the reservoirs being in fluid communication with a respective one of the plurality of needles, a pneumatic pressure source, a pneumatic drive system that is configured to induce a first discharge of the pharmacological composition out of the reservoirs and needles in a plurality of delivery modes, agent delivery volume control means for controlling volume of the pharmacological composition discharged from the needles, and a control system having actuation control means for controlling said pneumatic drive system. The control system is programmed to control the delivery modes.

Abstract: The invention provides for a mucin3 polypeptide, a polypeptide including a mucin3 EGF like domain, and nucleic acids encoding such polypeptides. The invention also provides for methods of treating an individual that has or is at risk of developing a disease or condition of the alimentary canal using such polypeptides or nucleic acids.

Abstract: A novel antiproliferative factor comprising a glycopeptide is disclosed. In specific embodiments, the novel antiproliferative factor is associated with the bladder. Compositions, diagnostic kits and reagents, and methods of using the compounds for identifying and/or treating interstitial cystitis and cancer are disclosed.

Abstract: The invention features a tribonectin and a method of tribosupplementation carried out by administering tribonectins directly to an injured or arthritic joint.

Abstract: The invention provides methods and compositions for improving fetal and child health and development through nutritional supplementation with, for example, sialic acid. Sialic acid can be provided to a female before, during and/or after pregnancy to improve the health and development of a fetus and/or child. The sialic acid can be in a variety of forms in the supplements.

Abstract: The present invention features compositions and methods for delivering a therapeutic agent to the cytoplasm of a cell. We have developed, inter alia, a system in which two or more distinct moieties—at least one therapeutic moiety and at least one potentiating moiety—selectively target and specifically bind cell surface molecules that are then internalized to an intracellular, membrane-bound compartment, such as an endosome. In some embodiments, as discussed further below, a third moiety that induces clustering of the targeted cell surface molecule can also be employed. Regardless of whether the compositions and methods include two or three moieties, the therapeutic agent can be any agent one wishes to deliver to the cytoplasm of a cell, and the potentiating agent can be any agent that destabilizes the intracellular, sub-cellular compartment in which the therapeutic agent is sequestered. The potentiating moiety can include, for example, a lytic agent (i.e.

Abstract: Disclosed herein are ?7?1 integrin modulatory agents and methods of using such to treat conditions associated with decreased ?7?1 integrin expression or activity, including muscular dystrophy. In one example, methods for treating a subject with muscular dystrophy are disclosed. The methods include administering an effective amount of an ?7?1 integrin modulatory agent to the subject with muscular dystrophy, wherein the ?7?1 integrin modulatory agent increases ?7?1 integrin expression or activity as compared to ?7?1 integrin expression or activity prior to treatment, thereby treating the subject with muscular dystrophy. Also disclosed are methods of enhancing muscle regeneration, repair, or maintenance in a subject and methods of enhancing ?7?1 integrin expression by use of the disclosed ?7?1 integrin modulatory agents. Methods of prospectively preventing or reducing muscle injury or damage in a subject are also disclosed.

Abstract: The invention relates to compositions and methods for increasing sialic acid uptake and/or incorporation into tissue following gastrointestinal ingestion of compositions that contain sialic acid.

Abstract: The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treatment using the novel heterocyclic compounds of the invention.

Abstract: The present invention relates to novel compositions of therapeutic cyclodextrin containing polymeric compounds designed as a carrier for small molecule therapeutics delivery and pharmaceutical compositions thereof. These cyclodextrin-containing polymers improve drug stability and solubility, and reduce toxicity of the small molecule therapeutic when used in vivo. Furthermore, by selecting from a variety of linker groups and targeting ligands the polymers present methods for controlled delivery of the therapeutic agents. The invention also relates to methods of treating subjects with the therapeutic compositions described herein. The invention further relates to methods for conducting pharmaceutical business comprising manufacturing, licensing, or distributing kits containing or relating to the polymeric compounds described herein.

Abstract: The present disclosure provides methods for predicting a patient's response to biglycan therapy for diseases or conditions associated with an abnormal level or activity of biglycan; disorders associated with an unstable cytoplasmic membrane, for example, due to an unstable dystrophin associated protein complex (DAPC); disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. Examples of such diseases include muscular dystrophies, such as Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, neuromuscular disorders and neurological disorders. This application also provides combination therapeutics, such as a biglycan therapeutic and a utrophin therapeutic.

Abstract: The following class of molecule is disclosed: a dimer containing a first neublastin polypeptide and a second neublastin polypeptide, wherein: (a) at least one of the polypeptides is glycosylated; (b) at least one of the polypeptides is conjugated at its N-terminus to a water-soluble synthetic polymer; and (c) neither of the polypeptides is conjugated to a water-soluble synthetic polymer at a position other than the N-terminus. Such dimers possess the biological activity of wild-type neublastin while displaying enhanced serum half-life and enhanced potency relative to wild-type neublastin.

Abstract: Synthetic cholesterylamine-linkers can include derivatives of cholesterol, cholesteryl, or sitosteryl coupled through the linker to an agent for delivery into cells. The cholesterylamines are thought to mimic cholesterol in the capacity and mechanism for enhanced entry into cells. The configuration of the cholesterylamine-linker that is thought to provide for enhanced entry into cells includes a cholesterylamine that is coupled to a linker from the amine, and which linker includes a negative charge at a spatial distance from the amine of the cholesterylamine.

Abstract: Methods and reagents for the formation of disulfide bonds, particularly in proteins, peptides and amino acids. The methods and reagents are particularly useful for the controlled glycosylation of proteins, peptides and amino acids. The methods utilize thiosulfonate or selenenylsulfide compounds as reagents or intermediates. Some proteins and peptides comprising selenenyl-sulfide groups also form part of the invention.

Abstract: Disclosed are glycopeptides that are substituted with one or more substituents each comprising one or more phosphono groups; and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.

Abstract: The present invention provides thermo-sensitive, mucoadhesive biopolymer formulations that enhance the penetration of therapeutics across the skin or mucosal surfaces. In a preferred embodiment, the biopolymer formulation comprises co-polymer of poloxamer 188 and propylene glycol, laurocapram and, optionally, one or more therapeutic agents. Also provided are uses of the biopolymer formulations for topical therapy of cancer including cervical cancer.

Abstract: Functionalized Single Wall Carbon Nanotube (SWCNT) complexed with nanochitosan for use in the delivery of bioaffecting substances and diagnostic applications. fSWCNT complexed with the chitosan NG042 were used for delivery of DNA-encoding EGFP reporter protein and peptide. The results demonstrate that shown CNT-chitosan hybrid nanoparticles exhibit significantly higher transfection efficiency in vivo than chitosan alone. Furthermore, the functionalized nanotubes were tested for peptide transfer into HEK293 cells. The results showed that the hybrid nanoparticles efficiently transferred peptides. Together, these results show that hybrid SWCNT-chitosan particles increase DNA and peptide transfer into cells.

Abstract: Multimeric compounds that bind to P-Selectin Glycoprotein 1 (PSGL-1) on the surface of T cells or natural killer (NK) cells can be used to induce T cell or NK cell depletion and/or to induce T cell or NK cell apoptosis. The multimeric compounds and methods of the invention can be used to control unwanted T cell- or NK cell-mediated immune responses in conditions such as inflammatory diseases, autoimmune diseases, transplant rejection, and allergic diseases.