Abstract: Methods for treating liquid cancer, determined to lack a p53 deactivation mutation, in a subject are provided. Also provided are peptidomimetic macrocycles for use in treatment of a liquid cancer, determined to lack a p53 deactivation mutation, in a subject.

Abstract: The purpose of the present invention is to provide a cross-linked peptide containing a novel non-peptide cross-linked structure, and a method for synthesizing the same. A cross-linked peptide having a novel non-peptide cross-linked structure, a useful intermediate for synthesizing the cross-linked peptide, and a method for synthesizing the novel cross-linked peptide and the intermediate are provided. The cross-linked peptide is characterized by having an —NR— bond in the cross-linked structure. By using the method for synthesizing the cross-linked peptide, a cross-link can be freely designed and an change can be freely made to a cross-link.

Abstract: Template-fixed ?-hairpin peptidomimetics of the general formulae wherein Z is a chain of 11 ?-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, or Pro(4NHCOPhe), or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to inhibit proteases, in particular serine proteases, especially Cathepsin G or Elastase or Tryptase. These ?-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

Abstract: The purpose of the present invention is to provide a cross-linked peptide containing a novel non-peptide cross-linked structure, and a method for synthesizing the same. A cross-linked peptide having a novel non-peptide cross-linked structure, a useful intermediate for synthesizing the cross-linked peptide, and a method for synthesizing the novel cross-linked peptide and the intermediate are provided. The cross-linked peptide is characterized by having an —NR— bond in the cross-linked structure. By using the method for synthesizing the cross-linked peptide, a cross-link can be freely designed and an change can be freely made to a cross-link.

Abstract: ?-Hairpin peptidomimetics of the general formula cyclo(-Xaa1-Xaa2-Thr3-Xaa4-Ser5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-) and pharmaceutically acceptable salts thereof, with Xaa1, Xaa2, Xaa4, Xaa6, Xaa7, Xaa8, Xaa9, Xaa10, Xaa11, Xaa12 and Xaa13 being amino acid residues of certain types which are defined in the description and the claims, have elastase inhibitory properties, especially against human neutrophil elastase, and can be used for preventing infections or diseases related to such infections in healthy individuals or for slowing infections in infected patients. The compounds of the invention can further be used where cancer, or immunological diseases, or pulmonary diseases, or cardiovascular diseases, or neurodegenerative diseases, or inflammation, or diseases related to inflammation, are mediated or resulting from elastase activity. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Abstract: A method of inhibiting a binding event between a target protein and a binding protein, comprising administering to a cell in vitro an effective amount of a non-naturally occurring bifunctional inhibitor molecule including (a) protein binding moiety, and (b) an effector region, wherein the protein binding moiety binds to a blocking protein, and wherein the effector region binds to the target protein in order to bind the target protein and the blocking protein and prevent access of the binding protein to the target protein. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The invention provides methods, compositions and kits for treating and or preventing an HIV infection. For example, HIV envelope-like polypeptides (wild-type HIV polypeptides and mimotopes) may be administered to an individual so as to induce a protective immune response to HIV. Alternatively, antibodies directed to the HIV envelope-like polypeptides may be administered to an individual to treat or prevent an HIV infection and/or one or more symptoms associated with the infection (e.g., AIDS).

Abstract: The present invention relates to compositions and methods for the prevention and treatment of Borrelia infection. Particularly, the present invention relates to a polypeptide comprising a hybrid C-terminal fragment of an outer surface protein A (OspA), a nucleic acid coding the same, an antibody specifically binding the same, a pharmaceutical composition (particularly for use as a medicament or in a method of treating or preventing a Borrelia infection) comprising the polypeptide and/or the nucleic acid and/or the antibody, a method of treating or preventing a Borrelia infection and a method of immunizing a subject.

Abstract: The present invention is directed to the cells, compositions and methods for the production of recombinant protein. In particular, the invention is directed to a production process for obtaining high levels of soluble recombinant CRM197 protein from E. coli. Cells preferably contain one or more mutations of disulfide reductase genes, so that disulfide reductase activity is reduced. The invention also relates to purification method for CRM197 as well as characterization of properly folded CRM197 protein.

Abstract: The present invention relates to the use of novel promoters for heterologous gene expression, preferably for expression of genes in organisms of the genus Yarrowia, to the genetically modified organisms of the genus Yarrowia, and to a process for producing biosynthetic products by cultivating the genetically modified organisms.

Abstract: The invention discloses microorganism cell culture conditions that result in increased cellular and media concentrations of a biological pigment. The invention has applications in use as a natural food colouring, as antioxidants in the food supplement industries, in the nutraceutical, pharmaceutical, and cosmeceutical industries, and a non-toxic ink. The method results in pigment that is relatively easy to separate from the microorganism culture.

Abstract: An isolated and purified nucleic acid molecule that encodes a polypeptide comprising at least eight contiguous amino acids of SEQ ID NO: 1, 2, or 3, wherein the at least eight contiguous amino acids have anti-viral activity, as well as an isolated and purified nucleic acid molecule that encodes a polypeptide comprising at least eight contiguous amino acids of SEQ ID NO: 1, 2, or 3, wherein the at least eight contiguous amino acids have anti-viral activity, a vector comprising such an isolated and purified nucleic acid molecule, a host cell comprising the nucleic acid molecule, optionally in the form of a vector, a method of producing an antiviral polypeptide or conjugate thereof, the anti-viral polypeptide itself, a conjugate or fusion protein comprising the anti-viral polypeptide, and compositions comprising an effective amount of the anti-viral polypeptide or conjugate or fusion protein thereof. Further provided are methods of inhibiting prophylactically or therapeutically a viral infection of a host.

Abstract: Fluorescent and non-fluorescent fusion tags derived from green fluorescent protein (GFP). The fusion tags harbor substitutions with respect to GFP that increase expression of target proteins to which the fusion tags are fused; increase solubility; prevent dimerization and oligomerization, particularly in oxidizing environments such as the endoplasmic reticulum (ER); and, in some cases, enhance fluorescence of the fusion tag itself. The substitutions include various combinations of substitutions at select cysteine residues in GFP, substitutions in or near the GFP chromophore, and/or other substitutions. The fusion tags can be used for increasing expression of target proteins for mass production thereof or as a fluorescent tag.

Abstract: Antimicrobial agents, including antimicrobial peptides (AMPs) and uses thereof. Compositions and methods of using dermaseptin-type and piscidin-type antimicrobial peptides that demonstrate activity and improved therapeutic indices against microbial pathogens. The peptide compositions demonstrate the ability to not only maintain or improve antimicrobial activity against bacterial pathogens including Gram-negative microorganisms Acinetobacter baumannii and Pseudomonas aeruginosa, but also significantly decrease hemolytic activity against human red blood cells. Specificity determinants within the AMPS change selectivity from broad spectrum antimicrobial activity to AMPS with gram-negative selectivity.

Abstract: The disclosure provides novel forms of tau species and applications thereof, as well as methods of diagnosing and/or treating tau-associated neurodegeneration. the inventors have shown that tau-null neurons lacked activation of AP-induced mitochondrial intrinsic caspase cascades in the neurons and were subsequently protected from A3-induced dendritic spine loss and neurodegeneration. Accordingly, embodiments of various aspects described herein relate to compositions comprising soluble HMW tau species that is responsible for inter-neuron propagation and applications thereof. Methods of treating and diagnosing tau-associated neurodegeneration in a subject are also provided herein.

Abstract: Described herein are novel compositions comprising multimodal TRAIL agents and cells engineered to express such multimodal TRAIL agents, including cells encapsulated in a scaffold or matrix, for use in the treatment of disorders such as cancer.

Abstract: The invention relates to a peptide having a length of no more than 100 amino acids and comprising at least 19 contiguous amino acids from the amino acid sequence of the human PRAME protein, wherein the peptide comprises at least one HLA class II epitope and at least one HLA class I epitope from the amino acid sequence of the human PRAME protein and to its use as such or in a composition as a medicament for the treatment and/or prevention of cancer.

Abstract: In the present invention a method for purifying erythropoietin comprising at least one chromatography step using a stationary phase containing hydroxyapatite is reported. The method comprises the following steps i) the erythropoietin in a solution containing Calcium-ions is brought into contact with a stationary phase containing hydroxyapatite equilibrated with a solution containing Calcium-ions and namely under conditions under which the erythropoietin binds to the stationary phase containing hydroxyapatite, ii) a solution is passed over the stationary phase containing hydroxyapatite from i) which contains less Calcium-ions than the previous solution and the erythropoietin is not detached from stationary phase containing hydroxyapatite, and iii) a further solution which contains less than 0.5 mM Calcium-ions is passed over the stationary phase containing hydroxyapatite from ii) whereby the erythropoietin is detached from the stationary phase containing hydroxyapatite.

Abstract: The present invention relates to a therapeutic polypeptide and methods for its creation and use for modulating an immune response in a host organism in need thereof. In particular, the invention relates to the administration to an organism in need thereof, of an effective amount of a pre-coupled polypeptide complex comprising a lymphokine polypeptide portion, for example IL-15 (SEQ ID NO: 5, 6), IL-2 (SEQ ID NO: 10, 12)or combinations of both, and an interleukin receptor polypeptide portion, for example IL-15Ra (SEQ ID NO: 7, 8), IL-2Ra (SEQ ID NO: 9, 11) or combinations of both, for augmenting the immune system in, for example, cancer, SCID, AIDS, or vaccination; or inhibiting the immune system in, for example, rheumatoid arthritis, or Lupus. The therapeutic complex of the invention surprisingly demonstrates increased half-life, and efficacy in vivo.

Abstract: Somatostatin derivative compounds of general formula (I) that may be readily labelled with the isotope fluorine-18 and that have affinity and selectivity for cellular somatostatin receptors are provided. The labelled compounds are useful clinically as radioactive tracers in various in vivo imaging applications (for example, using positron emission tomography (PET) and related techniques) to detect somatostatin-expressing cells and tissues, including tumours, or as therapeutic agents.

Abstract: A light-sensitive G-protein coupled receptor includes a light sensitive extracellular cone opsin or melanopsin domain and a hetorologous intracellular domain capable of modulating an intracellular signaling pathway.

Abstract: Short bioactive sequences derived from the 2nd loop of the 7-transmembranal receptor of endothelial differentiation gene 3 (EDG3) useful in stimulation of angiogenesis, and peptide conjugates comprising a permeability enhancing moiety, are provided. Also provided are pharmaceutical compositions comprising the peptides and methods of use in conditions were insufficient blood-supply occurs, or which are associated with endothelia dysfunction such as peripheral vascular diseases, coronary artery diseases, cerebrovascular diseases, diabetes and delayed wound healing, pulmonary disease, eye diseases and pathological condition related to severe infection.

Abstract: It is demonstrated that hyperpolarization-activated cyclic nucleotide-gated (HCN)-based biological pacing, especially that achieved by transduction of the HCN2 gene into cardiac cells in vivo, was significantly improved by co-transduction of the skeletal muscle sodium channel 1 (SkMI) gene. Expression of both genes hyperpolarized the action potential (AP) threshold. When viral biological pacemaker constructs carrying genes for HCN2 and SkMI were injected into the heart of dogs in vivo, the pacemaker function was facilitated by the slow depolarizing HCN2 current and the hyperpolarized AP threshold generated by SkMI. This dual gene therapy provided both highly efficient pacing and a brisk autonomic response that is superior to those of previously developed gene- or cell-based approaches.

Abstract: Provided is directed to the field of immunotherapy. Specifically, provided are compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the subject matter are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.

Abstract: The present invention concerns peptides comprising at least one motif having the amino acid sequence B1-X3-10-B2, wherein B1 and B2 are identical or different and each is a basic amino acid and X3-10 is a sequence of 3 to 10 identical or different non-acidic amino acids, and wherein the N-terminus of the peptide comprises a D-amino acid and/or includes a protecting group, collagen or hyaluronic acid conjugates comprising the same peptides and a therapeutic or diagnostic agent, and compositions and uses thereof. It also concerns peptides comprising at least one motif having the amino acid sequence B1-X3-10-B2, wherein B1 and B2 are identical or different and each is a basic amino acid and X3-10 is a sequence of 3 to 10 identical or different non-acidic amino acids, for use in the treatment or prevention of ocular diseases or conditions.

Abstract: The present invention relates to a novel polypeptide having specific modifications compared to the natural polypeptide. The said novel polypeptide has improved binding characteristics. The present invention also relates to a method of obtaining the said novel polypeptide and to the use of the said novel polypeptides for the treatment of respiratory disorders.

Abstract: This invention provides antibodies or fragments thereof that are capable of specifically binding to at least one conformational epitope of enterovirus 71 (EV71), wherein the antibody individually comprises at least one variable light chain and at least one variable heavy chain. There is also provided a method of producing an antibody capable of specifically binding to at least one conformational epitope of enterovirus 71 (EV71).

Abstract: Monoclonal neutralizing antibodies are disclosed that specifically bind to the HIV-1 gp41 membrane-proximal external region (MPER). Also disclosed are compositions including the disclosed antibodies that specifically bind gp41, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of HIV-1 in a biological sample, or detecting an HIV-1 infection or diagnosing AIDS in a subject. In additional, the broad neutralization breadth of the disclosed antibodies makes them ideal for treating a subject with an HIV infection. Thus, disclosed are methods of treating and/or preventing HIV infection.

Abstract: This disclosure provides a comprehensive approach to specifically target various immune functions to the site of infection by a variety of fusion proteins that consist of a bacteriocin cell wall targeting domain (CWT) and an immune function mediating component (IFMC). The CWT targets the fusion protein to the bacterial surface leading to accumulation at the site of infection. The IFMC mediates various immune functions such as toxin neutralization or recruitment of immune cells that can clear the bacteria.

Abstract: Antibodies, and particularly human antibodies, are disclosed that demonstrate activity in the treatment of demyelinating diseases as well as other diseases of the central nervous system that are of viral, bacterial or idiopathic origin, including neural dysfunction caused by spinal cord injury. Neuromodulatory agents are set forth that include and comprise a material selected from the group consisting of an antibody capable of binding structures or cells in the central nervous system, a peptide analog, a hapten, active fragments thereof, agonists thereof, mimics thereof, monomers thereof and combinations thereof. The neuromodulatory agent has one or more of the following characteristics: it is capable of inducing remyelination; binding to neural tissue; promoting Ca?? signaling with oligodendrocytes; and promoting cellular proliferation of glial cells. Amino acid and DNA sequences of exemplary antibodies are disclosed.

Abstract: An aglycosylated humanized anti-C3b (AAC3b) antibody or antigen binding fragment thereof includes a modification at a conserved N-linked site in the CH2 domains of an Fc portion of the antibody or antigen binding fragment thereof.

Abstract: An aglycosylated humanized anti-Bb (AAfBb) antibody or antigen binding fragment thereof includes a modification at a conserved N-linked site in the CH2 domains of an Fc portion of the antibody or antigen binding fragment thereof.

Abstract: The technology described herein is directed to the treatment of sepsis and/or septic shock by, e.g. administering an agent that can reduce the level of circulating citrullated histones.

Abstract: An anti-C3d antibody or antibody fragment; method for use thereof to kill cancer cells; and related methods and compositions.

Abstract: Provided herein are therapeutic agents having specificity for human CLPTM1 L polypeptide, including therapeutic agents comprising one or more CLPTM1 L-targeting agents, compositions comprising such therapeutic agents, and methods of using such compositions for treating or preventing a cancer, pre-cancerous lesion, or other disease condition associated with CLPTM1 L protein dysfunction (e.g., pathogenic production, modification, or function).

Abstract: The present invention relates to antibodies against specific domains of Olfml3 and the use of such in angiogenesis. In particular aspects, angiogenesis-related conditions, such as cancer, can be treated by the composition comprising the Olfml3 antagonists.

Abstract: The present invention is related to the anti-p40 antibodies, kits, cocktails, and use of anti-p40 antibodies for detection of cancer.

Abstract: The present invention relates to antigen binding proteins, such as antibodies, which bind to serum amyloid P component (SAP), polynucleotides encoding such antigen binding proteins, pharmaceutical compositions comprising said antigen binding proteins and methods of manufacture. The present invention also concerns the use of such antigen binding proteins in the treatment or prophylaxis of diseases associated with amyloid deposition including systemic amyloidosis, local amyloidosis, Alzheimer's disease, and type 2 diabetes.

Abstract: A method of treating patients suffering from cancers driven by deregulated Human Epidermal Growth Factor Receptor (HER1/Human EGFR) comprising administering to a patient in need of such treatment a flexible and active regimen for combining a tyrosine kinase inhibitor (TKI) and anti-EGF antibodies for inhibition of the pathway activated by EGF-EGFR binding (mAb). The anti-EGF antibodies can be produced by active immunization or provided passively by the administration of antibodies that are anti-EGF. The method comprises TKI administered according to a continuous regimen based on an average daily dose in the range of 10 to 150 mg and the mAb is co-administered either actively or passively according to a dosing regimen achieving a therapeutic effective amount repeated thrice, twice or once a week, once in two weeks, once in three weeks or at least once monthly.

Abstract: The present invention provides method, uses and agents for preventing or reducing cognitive decline in a patient following a planned inflammatory trigger. Such planned inflammatory trigger can be a surgical procedure or chemotherapy. The invention further provides methods, uses and agents for reducing cognitive decline in a patient with a cognitive disorder, wherein said patient has been exposed to an inflammatory trigger. Pharmaceutical compositions and kits are also provided.

Abstract: Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.

Abstract: The invention relates to an isolated immunoglobulin heavy chain polypeptide and an isolated immunoglobulin light chain polypeptide that bind to interleukin-33 (IL-33). The invention provides an IL-33-binding agent that comprises the aforementioned immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide. The invention also provides related vectors, compositions, and methods of using the IL-33-binding agent to treat a disorder in a mammal that is responsive to IL-33 inhibition.

Abstract: The present invention relates to anti-IL-23p19 binding compounds, in particular new humanized anti-IL-23p19 antibodies and therapeutic and diagnostic methods and compositions for using the same.

Abstract: The present invention aims to provide a pharmaceutical composition for cancer treatment, which comprises a novel monoclonal antibody binding to SLC6A6 or its extracellular region and a chemotherapeutic agent conjugated therewith, as well as a therapeutic method in which the monoclonal antibody or a therapeutic agent composed of the monoclonal antibody conjugated with a chemotherapeutic agent is used in combination with a chemotherapeutic agent. The present invention provides a pharmaceutical composition comprising an antibody conjugate configured such that a monoclonal antibody having higher affinity than conventional antibodies and recognizing native SLC6A6 or a native polypeptide of an extracellular region of SLC6A6 is conjugated with an anticancer agent or the like having activity against cancer and other hyperproliferative diseases.

Abstract: Methods are provided for treatment of lung cancers, particularly small cell lung cancer with targeted therapy, which optionally includes an agent that selectively blocks CD47 binding to SIRP?.

Abstract: The present invention relates to a new generation of chimeric antigen receptors (CAR), under single-chain or multi-chain forms, the specificity of which, to a desired antigen, is conferred by a VNAR polypeptide derived from monomeric antibodies from cartilaginous fish. Such CARs, which aim to redirect immune cell specificity toward selected undesired malignant cells, are compact and thus particularly adapted to target hollow antigens such as ions channels of efflux pumps present at the surface of drug-resistant cells. The invention encompasses the polynucleotides, vectors encoding said multi-chain CAR and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy.

Abstract: The present invention relates to humanized or chimeric antibodies binding CD3. It furthermore relates to bispecific antibodies, compositions, pharmaceutical compositions, use of said antibodies in the treatment of a disease, and method of treatment.

Abstract: The present invention discloses antibodies to canine PD-1 that have specific sequences and a high binding affinity for canine PD-1. The invention also discloses the use of the antibodies of the present invention in the treatment of cancer in dogs.

Abstract: Methods are provided for the treatment of a HIV infection. The methods can include administering to a subject with an HIV infection a therapeutically effective amount of an agent that interferes with the interaction of gp120 and ?4 integrin, such as a ?4?1 or ?4?7 integrin antagonist, thereby treating the HIV infection. In several examples, the ?4 integrin antagonist is a monoclonal antibody that specifically binds to a ?4, ?1 or ?7 integrin subunit or a cyclic hexapeptide with the amino acid sequence of CWLDVC. Methods are also provided to reduce HIV replication or infection. The methods include contacting a cell with an effective amount of an agent that interferes with the interaction of gp120 and ?4 integrin, such as a ?4?1 or ?4?7 integrin antagonist. Moreover, methods are provided for determining if an agent is useful to treat HIV.

Abstract: The present invention provides compositions and methods of use of anti-IGF-1R antibodies or antibody fragments. Preferably the antibodies bind to IGF-1R but not IR; are not agonists for IGF-1R; do not block binding of IGF-1 or IGF-2 to isolated IGF-1R, but effectively neutralize activation of IGF-1R by IGF-1 in intact cells; and block binding of an R1 antibody to IGF-1R. The antibodies may be murine, chimeric, humanized or human R1 antibodies comprising the heavy chain CDR sequences DYYMY (SEQ ID NO:1), YITNYGGSTYYPDTVKG (SEQ ID NO:2) and QSNYDYDGWFAY (SEQ ID NO:3) and the light chain CDR sequences KASQEVGTAVA (SEQ ID NO:4), WASTRHT (SEQ ID NO:5) and QQYSNYPLT (SEQ ID NO:6). Preferably the antibodies bind to an epitope of IGF-1R comprising the first half of the cysteine-rich domain of IGF-1R (residues 151-222). The anti-IGF-1R antibodies may be used for diagnosis or therapy of various diseases such as cancer.