Abstract: In permeability lung edema, cardiogenic lung edema or neonatal respiratory distress, there is heterogeneous liquid distribution throughout the lungs. The excess alveolar liquid reduces gas exchange. Mechanical ventilation is used to improve gas exchange. In the presence of heterogeneous liquid distribution, there are surface tension-dependent stress concentrations in septa separating aerated from flooded alveoli. Mechanical ventilation, by inflating the lung above normal volumes, thus increasing surface tension above normal, exacerbates the stress concentrations and consequently injures, or exacerbates pre-existing injury of, the alveolar-capillary barrier. Any means of lowering surface tension should lessen ventilation injury of the lung. In the present invention, dilute exogenous surfactant solution or surfactant protein C solution interacts with albumin to lower surface tension, likely through effective promotion of surfactant lipid adsorption.

Abstract: Provided herein are methods and compositions for the diagnosis, prognosis and treatment of a cancer associated disorders using the Fhit gene.

Abstract: The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.

Abstract: The disclosure provides compositions and methods for treating or preventing intracerebral hemorrhage (ICH) in a subject by administering a variant of FXa.

Abstract: The invention relates to modified Factor IX coding sequence, expression cassette, vectors such as viral (e.g., lenti- or adeno-associated viral) vectors, and gene transfer methods and uses. In particular, to target Factor IX nucleic acid to cells, tissues or organs for expression (transcription) of Factor IX.

Abstract: The present invention relates to formulations of ADAMTS13 with enhanced or desirable properties. As such, the invention provides liquid and lyophilized formulations of ADAMTS13 that are suitable for pharmaceutical administration. Among other aspects, the present invention also provides methods of treating various diseases and conditions related to VWF and/or ADAMTS13 dysfunction in a subject. Also provided herein are kits comprising ADAMTS13 formulations useful for the treatment of various diseases and conditions.

Abstract: The present invention relates to methods and compositions for treating various side effects associated with the administration of one or more therapeutic compounds. In particular embodiments, the present invention relates to methods of reducing one or more adverse side effects associated with one or more therapeutic compounds by administering a neurotoxin, such as botulinum toxin, in combination with the one or more therapeutic compounds.

Abstract: The invention provides a method for reducing or preventing body weight gain in a subject comprising administering to the subject enolase 1 (Eno1). The invention also provides methods of treating obesity, and of reducing body weight in a subject afflicted with an overweight condition, comprising administering to the subject enolase 1 (Eno1). In certain embodiments, the body weight gain, obesity or overweight condition is caused by a therapeutic treatment, such as a diabetic drug. In certain methods of the invention, the Eno1 is delivered to muscle.

Abstract: The invention relates to newly identified peptides of that are capable of inducing tolerance to cow's milk, especially to ?-lactoglobulin. The peptides may be administered to mammals, especially to young infants who are at risk of allergy to cow's milk proteins, to induce oral tolerance to cow's milk; they may also be administered to children or adults who are allergic to cow's milk to allow “desensitization” towards the allergenic milk proteins, especially ?-lactoglobulin, to occur. The peptides may also be used to induce tolerance to goat's and buffalo's milk proteins, especially ?-lactoglobulin. The peptides are capable of modulating the mammalian immune response to allergens.

Abstract: The present disclosure provides (a) isolated immunogenic PAA polypeptides; (b) isolated nucleic acid molecules encoding immunogenic PAA polypeptides; (c) vaccine compositions comprising an immunogenic PAA polypeptide or an isolated nucleic acid molecule encoding an immunogenic PAA polypeptide; (d) methods relating to uses of the polypeptides, nucleic acid molecules, and compositions; and (e) vaccine-based immunotherapy regimens which involve co-administration of a vaccine in combination with an immune-suppressive-cell inhibitor and an immune-effector-cell enhancer.

Abstract: The present invention relates to a method of treating Stage IV melanoma in a subject. The method includes the step of administering to the subject a therapeutically effective amount of a melanoma cell lysate and/or an immunotherapeutic extract, component or antigen thereof.

Abstract: The invention relates to the compositions of synthetic oligo-?-(1?6)-2-amino-2-deoxy-D-glu-copyranosides conjugated to carriers, and methods for making and use same.

Abstract: Provided is an immunogenic composition comprising 13 different polysaccharide-protein conjugates. Each of the conjugates comprises a capsular polysaccharide prepared from a different serotype Streptococcus pneumoniae conjugated to a carrier protein, that is, 12 serotypes selected from the group consisting of 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and serotype 2 or 9N. The immunogenic composition formulated into a vaccine comprising an aluminum-based adjuvant increases coverage with respect to pneumococcal diseases in infants and children.

Abstract: The invention relates to a novel use of a Bordetella adenylcyclase toxin in the manufacturing of vectors for targeting in vivo a molecule of interest, specifically to CD11b expressing cells. The invention also relates to an immunogenic composition that primes immune responses, to pharmaceutical compositions and to a new vector for molecule delivery to CD11b expressing cells.

Abstract: The present invention provides synthetic Moraxella catarrhalis lipooligosaccharide (LOS)-based oligosaccharides and conjugates containing various M. catarrhalis serotype-specific oligosaccharide antigens or various core M. catarrhalis oligosaccharide structures or motifs corresponding to one or more of the three major serotypes and/or members within a given serotype. The oligosaccharides may be synthesized by a chemical assembly methodology relying on a limited number of monosaccharide and disaccharide building blocks. The invention further provides M. catarrhalis LOS-based immunogenic and immunoprotective compositions and antibodies derived therefrom for diagnosing, treating, and preventing infections caused by M. catarrhalis.

Abstract: Disclosed herein are single nucleic acid constructs comprising a vector, wherein the vector comprises: a first nucleic acid sequence, wherein the first nucleic acid sequence comprises one or more antigenic sequences of interest, one or more spacer sequences and one or more hydrophobic anchor sequences, operably linked to a first transcriptional control element; a second nucleic acid sequence, wherein the second nucleic acid sequence comprises one or more pathogen-associated molecular pattern (PAMP) sequences operably linked to a second transcriptional control element; a third nucleic acid sequence, wherein the third nucleic acid sequence comprises one or more cell surface receptor binding sequences operably linked to a third transcriptional control element; and a selectable marker. Also described herein, are methods of making the single nucleic acid constructs and methods of administering the single nucleic acid constructs for the treatment or prevention of infections and cancer.

Abstract: The present invention encompasses recombinant porcine reproductive and respiratory syndrome virus (PRRSV) vaccines or compositions. In particular, the invention encompasses recombinant adenovirus vectors encoding and expressing PRRSV gp2, gp3, gp4, gp5a, gp5 and/or E antigens, proteins, epitopes or immunogens. Such vaccines or compositions can be used to protect animals from PRRSV.

Abstract: Described herein are dengue virus E-glycoprotein polypeptides containing mutations that eliminate immunodominant cross-reactive epitopes associated with immune enhancement. The disclosed dengue virus E-glycoproteins optionally further include mutations that introduce a strong CD4 T cell epitope. The disclosed E-glycoprotein polypeptides, or nucleic acid molecules encoding the polypeptides, can be used, for example, in monovalent or tetravalent vaccines against dengue virus.

Abstract: The immune response to an antigen of interest, especially one in purified form, can be significantly enhanced by the simultaneous administration of an alphavirus replicon particle which expresses the same antigen. This allows for the use of significantly smaller quantities of the protein antigen than in conventional immunization strategies, and this new immunization strategy can also eliminate the need for boosting administration of the antigen or it can reduce the number of boosts required for an effective immune response to the antigen.

Abstract: The present invention provides therapies, vaccines, and predictive methods for infectious salmon anemia virus and provides compounds for diagnosing, preventing, and treating outbreaks of infectious salmon anemia virus including compounds for diagnosing, preventing, and treating infectious salmon anemia across different strains of virus.

Abstract: The present invention includes compositions and methods for making and using anti DC-ASGPR antibodies that can, e.g., activate DCs and other cells.

Abstract: A novel method for producing an immunogenic composition or vaccine comprising inactivated lentivirus, in particular inactivated HIV, wherein producer cells producing, preferably constituvely producing lentivirus particles are provided, the lentivirus particles are produced by these producer cells in the presence of an antiretroviral (ARV) agent which is an inhibitor of the IN-LEDGF/p75 interaction, the inactivated lentivirus is recovered and formulated in a pharmaceutically acceptable vehicle or carrier. The invention also relates to immunogenic compositions or vaccines and to methods for the therapeutic or prophylactic treatment of a mammal, especially a human, and various therapy combinations involving the administration of said immunogenic compositions or vaccines.

Abstract: A live, attenuated HIV vaccine is provided, and methods of making a attenuated HIV vaccine are provided.

Abstract: The present invention relates to novel peptides and methods for inducing an immune response in a subject against an antigen and for treatment, diagnosis and prognosis of infections or autoimmune diseases including infections with HCV, HIV, CMV and Flu. The invention further relates to methods for identifying and providing peptides useful for the treatment and diagnosis.

Abstract: The present invention relates generally to an immunotherapeutic composition. More particularly, the present invention relates to an immunotherapeutic composition which interacts immunologically with T lymphocytes in subjects having peanut allergy or allergy to other tree nuts. This composition is preferably immunointeractive with T cells in subjects having an allergy to the Ara h 1 and/or Ara h 2 allergens. The composition of the present invention is useful in the therapeutic or prophylactic treatment of conditions characterised by an aberrant, inappropriate or otherwise unwanted immune response to peanut, Ara h 1 and/or Ara h 2 or derivative or homologue thereof.

Abstract: Provided herein are methods for rational design of nicotine haptens. More particularly, provided herein are methods for designing, selecting, and synthesizing nicotine haptens and nicotine hapten conjugates. Also provided herein are novel nicotine haptens and methods for using nicotine haptens to treat nicotine addiction.

Abstract: The present invention generally relates to homogeneous suspensions of small molecule immune potentiators (SMIPs) that are capable of stimulating or modulating an immune response in a subject in need thereof. The homogeneous suspensions may be used in combinations with various antigens or adjuvants for vaccine therapies.

Abstract: The present invention relates to methods of producing lyophilized pharmaceutical compositions comprising a high concentration of therapeutic protein or antibody prior to lyophilization, wherein the lyophilized formulation can be reconstituted with a diluent in about 15 minutes or less. The invention also relates to the high concentration lyophilized formulations produced by the methods described herein. The lyophilized formulations produced by the methods of the invention are stable and are suitable for veterinary and human medical use and are suitable for modes of administration including oral, pulmonary and parenteral, such as intravenous, intramuscular, intraperitoneal, or subcutaneous injection. Also provided by the invention are high concentration pharmaceutical compositions that have long term stability and can be reconstituted, following lyophilization, in a short period of time, preferably 15 minutes or less.

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 phenylalkylcarboxylic acid compounds and compositions containing such compounds which facilitate the delivery of biologically active agents.

Abstract: The present invention relates to a carrier composition comprising a phosphate compound of an electron transfer agent and a polar aprotic solvent. Biologically active compounds formulated with the carrier composition have been shown to have improved properties.

Abstract: The present invention provides targeting lipids of structure L100-linker-L101??(CI), where L100 is a lipid, lipophile, alkyl, alkenyl or alkynyl, L101 is a ligand or —CH2CH2(OCH2CH2)pO(CH2)qCH2-ligand, p is 1-1000, and q is 1-20. In addition, the invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo.

Abstract: The present invention relates to a consumer goods product comprising a consumer goods product ingredient and a functionalised lignin oligomer, wherein the functionalised lignin oligomer: (a) comprises less than 1 wt % sulphur content; (b) has a number average molecular weight (Mn) of from 800 Da to 1,800 Da; and (c) comprises at least one functional group selected from carboxyl, ketone, aldehyde, amino and quaternary ammonium, wherein only one type of functional group selected from the group consisting of list is present at a level of at least 0.8 mmol/g, and wherein if any other functional group selected from the group consisting of list is present, it is present at a level of below 0.8 mmol/g, wherein the lignin oligomer is derived from corn, sugar cane, wheat and any combination thereof, and wherein the consumer goods product is selected from an oral care composition, an antiseptic cream, or a detergent composition.

Abstract: Amino acid based polymers and polymer blends. Compositions comprising at least one amino acid based polymer or polymer blend, at least one bioactive agent, and optionally at least one filler. Additionally, compositions comprising at least one bacteriophage and at least one salt or buffer, which, for example, are in the form of a dry powder, and methods of preparing thereof are disclosed.

Abstract: Compositions comprised of a delivery vehicle or delivery system and an active agent dispersed within the delivery vehicle or system, wherein the delivery vehicle or system contains a polyorthoester polymer and a polar aprotic solvent. Also disclosed are low viscosity delivery systems for administration of active agents. The low viscosity delivery systems have a polyorthoester polymer, a polar aprotic solvent and a solvent containing a triglyceride viscosity reducing agent. Compositions described include an amide- or anilide-type local anesthetic of the “caine” classification, and a non-steroidal anti-inflammatory drug (NSAID), along with related methods, e.g., for treatment of post-operative pain or for prophylactic treatment of pain. The compositions are suitable for delivery via, e.g., direct application and instillation, intradermal injection, subcutaneous injection, and nerve block (perineural).

Abstract: A process for making hemoglobin based oxygen carrier (HBOC) containing pharmaceutical composition suitable for oral delivery and the composition formed thereby are described. There are three exemplary composition configurations which include (1) hemoglobin-loaded nanoparticles solution, (2) enteric-coated hemoglobin capsules and (3) enteric-coated hemoglobin tablets. To facilitate the bioavailability and bio-compatibility of hemoglobin, intestinal absorption enhancers are added in each of the HBOC formulations. Protective layers ensure delivery of an intact hemoglobin structure in intestinal tract without degradation in the stomach. The HBOC formulations may be used for preventive or immediate treatment of high altitude syndrome (HAS) or for treatment of hypoxic conditions including blood loss, anemia, hypoxic cancerous tissue, and other oxygen-deprivation disorders.

Abstract: The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

Abstract: The invention relates to branched polymer comprising a support moiety and at least three homopolymer chains each covalently coupled to and extending from the support moiety, wherein the at least three homopolymer chains include a cationic homopolymer chain, a hydrophilic homopolymer chain, and a hydrophobic homopolymer chain.

Abstract: Described herein are MetAP-2 inhibitors and compositions and formulations thereof, and more particularly compositions and formulations of MetAP-2 inhibitors wherein the MetAP-2 inhibitor is associated with a block copolymer comprising a hydrophilic polymer moiety and a hydrophobic polymer moiety. The present invention also relates to compositions and formulations comprising MetAP-2 inhibitors for oral administration or administration via routes such as topical or ocular administration. The present invention also provides methods to treat conditions associated with or related to the over-expression or over-activity of MetAP-2 by administering the compositions and formulations comprising MetAP-2 inhibitors as disclosed herein.

Abstract: The invention relates to improvements in the field of drug delivery. More particularly, the invention relates to polypeptides having a hydrolyzable covalent bond to a therapeutic agent that includes, etoposide, etoposide 4?-dimethylglycine or doxorubicin. These polypeptide conjugates can be used as vectors to transport the podophyllotoxin derivative across the blood brain barrier (BBB) or into particular cell types such as ovary, liver, lung, or kidney. The invention also relates to pharmaceutical compositions that include the compounds of the invention and to uses thereof in methods of treatment.

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

Abstract: Provided herein are maytansinoid derivatives, conjugates thereof, and methods of treating or preventing proliferative diseases with the same.

Abstract: Provided are compounds for targeted immunotherapy. The compounds are useful in the treatment of EGFR expressing tumors/cancers. Also provided are compositions comprising the compounds.

Abstract: The invention provides compositions and methods for, inter alia, augmenting cell-based therapies in vivo by repeatedly stimulating target cells of interest over a period of time.

Abstract: The invention comprises compounds, methods of making, and methods of using. A group of polymer-cyclodextrin-lipid conjugates having a center backbone and three or four appended functional groups are disclosed, wherein one of the hydrophilic components is cyclodextrin. The compounds may have a backbone with three or four appended functional groups: one or two lipophilic compounds including sterols or “fat soluble” vitamins or fatty acids, one or two hydrophilic polymer and one cyclodextrin. Specific functional groups may be selected for specific applications in formulating pharmaceuticals, cosmetics, nutriceuticals, and the like. Typical coupling reaction of the conjugates may involve one or more or combinations or in series of alkylation including N-alkylation or O-alkylation, etherification, esterification and amidation chemical processes.

Abstract: The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells, when administered via intravitreal injection, compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

Abstract: The present invention provides HIV-derived lentivectors which are safe, highly efficient, and very potent for expressing transgenes for human gene therapy, especially, in human hematopoietic progenitor cells as well as in all other blood cell derivatives. The lentiviral vectors comprise a self-inactivating configuration for biosafety and promoters such as the EF1? promoter as one example. Additional promoters are also described. The vectors can also comprise additional transcription enhancing elements such as the wood chuck hepatitis virus post-transcriptional regulatory element. These vectors therefore provide useful tools for genetic treatments such as inherited and acquired lympho-hematological disorders, gene-therapies for cancers especially the hematological cancers, as well as for the study of hematopoiesis via lentivector-mediated modification of human HSCs.

Abstract: The present disclosure relates to compounds that are useful as near-infrared fluorescence probes, wherein the compounds include i) a pteroyl ligand that binds to a target receptor protein, ii) a dye molecule, and iii) a linker molecule that comprises an amino acid or derivative thereof. The disclosure further describes methods and compositions for incorporating the compounds as used for the targeted imaging of tumors. Conjugation of the amino acid linking groups increase specificity and detection of the compound. Methods and compositions for use thereof in diagnostic imaging are contemplated.

Abstract: Provided herein are compositions Gd(III)-dithiolane gold nanoparticle conjugates and methods of use thereof. In particular, compositions and method find use in in vivo imaging (e.g., magnetic resonance imaging (MRI)), for example, of pancreatic tissue.

Abstract: Compounds and methods for imaging and/or assessing collagen are described. The compounds can include collagen binding peptides.