Abstract: The present invention relates to: a fusion polypeptide in which an anti-inflammatory polypeptide and a ferritin monomer fragment are bound; and a pharmaceutical composition for treating inflammatory diseases, containing the same as an active ingredient and, more specifically, to: a fusion polypeptide in which an anti-inflammatory polypeptide is fused to an N-terminus and/or a C-terminus of a ferritin monomer fragment from which a portion of a fourth loop and a fifth helix, of a human derived ferritin monomer, are removed; and a use thereof for treating inflammatory diseases.

Abstract: Disclosed are a mutated HPV11 L1 protein (or a variant thereof), a sequence encoding the same, a method for preparing the same, and a virus-like particle comprising the same, wherein the protein (or a variant thereof) and the virus-like particle can induce the generation of neutralizing antibodies against at least two HPV types (e.g. HPV11 and HPV6), and therefore can be used to prevent infection by said at least two HPV types, and a disease caused by said infection, such as cervical cancer and condyloma acuminatum. Also disclosed is use of the protein and the virus-like particle in the manufacture of a pharmaceutical composition or a vaccine for preventing infection by said at least two HPV types, and a disease caused by said infection, such as cervical cancer and condyloma acuminatum.

Abstract: Disclosed is a method for refolding a protein or peptide that does not contain essential disulfides and that contains at least one free cysteine residue. Also disclosed are polymer IFN-? conjugates that have been created by the chemical coupling of polymers such as polyethylene glycol moieties to IFN-?, particularly via a free cysteine in the protein. Also disclosed are analogs of bioactive peptides that may be used to create longer acting versions of the peptides, including analogs of glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, Gastric inhibitory peptide (GIP), PYY, exendin, ghrelin, gastrin, amylin, and oxyntomodulin.

Abstract: One aspect as reported herein is a method for detecting a rat antibody in a serum or plasma sample (obtained) from a mouse comprising the steps of a) providing the sample to be analyzed, b) incubating said serum or plasma sample with an antibody that specifically binds to rat IgG and that does not specifically bind to mouse IgG, wherein the antibody is i) a mixture of an antibody binding to rat kappa light chain and an antibody binding to rat lambda light chain, or ii) a mixture of an antibody binding to rat IgG1 with an avidity of 4.1×1010 M?1 or more, an antibody binding to rat IgG2a with an avidity of 8.6×109 M?1 or more, an antibody binding to rat IgG2b with an avidity of 6.4×1010 M?1 or more and an antibody binding to rat IgG2c with an avidity of 9.

Abstract: Described herein are nanoparticle drug conjugates (NDCs), which, in certain embodiments, comprise a non-toxic, multi-modality, clinically proven silica-based nanoparticle platform with covalently attached drug molecules/moieties. The nanoparticle drug conjugates (NDCs) demonstrate imaging capability and targeting ligands which efficiently clear through the kidneys. Furthermore, the conjugates incorporate therapeutic agents for cancer detection, prevention, and/or treatment.

Abstract: The present invention develops a vaccine composition against and treatment or prevention on inflammation and lung injury (particularly hyperoxia-induced lung injury) and progression of periodontitis. Tn immunization increases serum anti-Tn antibody titers, while it decreases lavaged protein and cytokines, and also decreases mean linear intercept and lung injury score. Furthermore, the improvement in lung injury is accompanied by a decrease in NF-?B activity.

Abstract: This disclosure describes compositions and methods for selectively recruiting antigen-specific T cells and re-direct them to kill targeted cells, particularly tumor cells. This approach permits selective engagement of specific effector cell populations and, by using nanoparticles, overcomes the geometric limitations associated with previous approaches.

Abstract: In certain embodiments, this present invention provides antibodies and Fc fusion proteins with enhanced pharmacokinetics, such as biotinylated antibodies or biotinylated Fc fusion polypeptides.

Abstract: The disclosure provides GITRL fusion polypeptide subunits comprising an IgG Fc domain, a trimerization domain, and the receptor binding domain of GITR ligand, where the fusion polypeptide subunits can self-assemble into hexameric proteins. Also provided are methods of making fusion polypeptide subunits and hexameric proteins, and methods of use, e.g., treatment of cancer.

Abstract: A combination of components to promote an innate and adaptive immune response comprising of a TAA/ecdCD40L vaccine and a complex between the CD1d receptor and an alpha galactosyl ceramide like glycolipid (AGCLGL), to activate NKT cells and activate the CD40 receptor on the DCs and increase the level of the adaptive immune response induced by the TAA/ecdCD40L vaccine to the TAA. The result and advantage of using both the TAA/ecdCD40L vaccine and the ?-galactosylceramide-CD1d complex (or a related bacterial or other antigen related to ?-galactosylceramide) to stimulate the immune response through the CD40L/CD40 axis on dendritic cells, is that the magnitude of the stimulation is robust and increased significantly more than additive—i.e. synergistically due to the interaction, cross-talk and/or cross-stimulation of the glycolipid-CD1d pathway and TAA/ecdCD40L pathway. As a result, a potent immune response is induced against lipid target antigens as well as protein target antigens.

Abstract: Compounds which selectively bind to and inhibit the activity of the potassium channel Kv1.3 are described. Pharmaceutical compositions comprising such compounds and the use of said compounds and said pharmaceutical compositions for the treatment or prevention of autoimmune diseases, obesity, parodontitis and/or tissue transplant rejection are also described.

Abstract: The present application in one aspect provide Fc-containing polypeptide conjugates comprising an Fc-containing polypeptide conjugated to a conjugate moiety, wherein the Fc-containing polypeptide comprises an N-glycosylated Fc region comprising an acceptor glutamine residue flanked by an N-glycosylation site and wherein the conjugate moiety is conjugated to the Fc-containing polypeptide via the acceptor glutamine residue. Also provided are methods of making such Fc-containing polypeptide conjugates by using a wildtype or engineered transglutaminases. Further provided are engineered transglutaminases specifically designed for carrying out such reactions.

Abstract: Enediyne compounds having a structure according to formula (I), where R1, R2, R3, R4, R5, R6, R7 and X are defined herein.

Abstract: Fusion proteins containing a half-life extension protein, a linker, and a GDF15 protein are described. Also described are nucleic acids encoding the fusion proteins, recombinant cells thereof, compositions comprising the fusion proteins, and methods of using the fusion proteins for treating or preventing metabolic diseases, disorders or conditions.

Abstract: Compositions and methods that include stabilized protein drugs are described. In addition, protein drug formulations that are more stable under ambient conditions are described. The formulations include one or more poly amino acid ligands of the protein drug.

Abstract: Death-domain receptor 3 (DR3) variants having increased binding affinity to TL1A, and composition comprising same, are provided. Further, methods of use of said peptides or composition, including, but not limited to treatment of autoimmune and/or inflammatory disease are provided.

Abstract: The invention provides an agent for preventing or treating a condition characterised by the presence of unwanted cells, the agent comprising: (i) a targeting moiety that is capable of targeting to the unwanted cells; and (ii) a T cell antigen, wherein the T cell antigen can be released from the targeting moiety by selective cleavage of a cleavage site in the agent in the vicinity of the unwanted cells.

Abstract: The present disclosure provides protease-activatable procoagulant compounds comprising a procoagulant polypeptide, e.g., a procoagulant peptide and/or clotting factor, and a linker comprising a protease-cleavable substrate (e.g., a synthetic thrombin substrate) and a self-immolative spacer (e.g., p-amino benzyl carbamate). Upon cleavage of the protease-cleavable substrate by a protease (e.g., thrombin), the self-immolative spacer cleaves itself from the procoagulant polypeptide such that the polypeptide is in an underivatized and active form. Also provided are pharmaceutical compositions, methods for treating bleeding disorders using the disclosed compounds, methods of enhancing in vivo efficacy of procoagulant polypeptides, methods of increasing the efficacy of proteolytic cleavage of compounds comprising procoagulant polypeptides, methods of activating procoagulant polypeptides, and methods of releasing a procoagulant polypeptide from a heterologous moiety such as PEG.

Abstract: Provided herein are HIV-1-specific transforming antibodies (tAbs) and antigens that are recognized by HIV-1-specific tAbs. Also provided herein are methods for screening and/or generating HIV-1-specific tAbs and uses of tAbs for prevention and treatment of HIV-1 infection.

Abstract: The disclosed embodiments include downhole gamma-ray generators and methods to utilize downhole gamma-ray generators in a downhole environment. In one embodiment, a downhole gamma-ray generator includes a target foil formed from a first material. The downhole gamma-ray generator also includes a second layer deposited along a back surface of the target foil. The downhole gamma-ray generator further includes a laser system operable to direct optical pulses onto a front surface of the target foil to ionize atoms of the first material, where electrons produced by ionization of the first material propagate through the target foil and decelerates when the electrons interact with the high density material, and where the deceleration of the electrons produces gamma-rays that are utilized to obtain one or more formation properties of a downhole formation.

Abstract: A peptide-polymer conjugate prepared by a method for preparing a peptide-polymer conjugate according to the present disclosure stably maintains the two-dimensional structure of multiple ?-helix ligands so that its biological interaction is improved while maintaining the specific structure of the peptide ligands.

Abstract: The present invention relates to novel CD4+ and CD8+ T cell epitopes that are specific for HPV-specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions comprising these peptides for use in methods for the prevention and/or treatment of HPV related diseases. Preferred epitopes are recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node, and are presented by an HLA-DQ or HLA-DP molecule, or an HLA-B.

Abstract: The invention provides antibodies against Fibroblast Activation Protein (FAP) and methods of using the same.

Abstract: Herein is reported a non-covalent complex of a haptenylated antibody that specifically binds to human tau(pS422) and an anti-blood brain barrier receptor/hapten bispecific antibody.

Abstract: The present invention relates to monomeric polypeptides comprising an engineered monomeric antibody fragment (e.g., monomeric Fc-containing polypeptides) wherein the monomeric Fc comprises one or more engineered N-linked glycosylation sites in the CH3-CH3 dimerization interface. Methods for producing such engineered monomeric antibody fragments and their use in diagnostics and therapeutics are also provided.

Abstract: The present invention relates to exosomes, loaded with genetic material and methods of producing them and to the use of such exosomes for delivering genetic material in vivo, in particular the use of such exosomes in methods of gene therapy or gene silencing.

Abstract: Disclosed is a peptide consisting of an amino acid sequence of HisThrSerThrGluAlaLys (SEQ ID NO: 1). This peptide is effective in the enhancement of fibroblast cell migration, which promotes wound healing. Also provided are a pharmaceutical composition for promoting wound healing comprising the peptide, and a method for promoting wound healing using the peptide.

Abstract: The present disclosure provides methods of administering chimeric and hybrid Factor VIII (FVIII) polypeptides comprising FVIII and Fc to subjects at risk of developing inhibitory FVIII immune responses, including anti-FVIII antibodies and/or cell-mediated immunity. The administration is sufficient to promote coagulation and to induce immune tolerance to FVIII. The chimeric polypeptide can comprise full-length FVIII or a FVIII polypeptide containing a deletion, e.g., a full or partial deletion of the B domain.

Abstract: There is provided herein methods of treating leukemia or lymphoma in a subject in need thereof, with double negative T cells (DNTs) in combination with Interferon-?.

Abstract: The invention provides chimeric clotting factors comprising an activatable clotting factor and an enhancer moiety. The activatable clotting factor allows the chimeric clotting factor to be activated at the site of coagulation. The enhancer moiety can additionally improve procoagulation activities of the chimeric clotting factors. The chimeric clotting factors can further be improved by fusion to a half-life extender, which improves a pharmacokinetics property of the chimeric clotting factor. The invention also includes methods of making and methods of using these chimeric clotting factors.

Abstract: Methods and compositions for treating tumors, especially skin tumors, by locally administering single doses of tumor necrosis factor alpha (TNF?) and interleukin-2 (IL2) at the tumor site, where the TNF? and IL2 are delivered as immunoconjugates comprising an antibody targeted to a splice isoform of an extracellular matrix component such as fibronectin.

Abstract: This invention provides a base material comprising a plastic-containing support and, on its surface, a hydrophilic layer comprising an ethylene glycol chain (an EG chain) composed of one or more ethylene glycol units, as well as a method for producing such base material. A polysiloxane-containing primer layer is provided on the support comprising a plastic material on its surface, and the EG chain is covalently bound to a polysiloxane side chain of the primer layer. Thus, a hydrophilic layer comprising the EG chain can be provided on the surface of the plastic-containing support.

Abstract: The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance).

Abstract: Disclosed herein is a bi-specific antibody that specifically directs a therapeutic agent to a cancer cell by targeting a tumor antigen of the cancer cell, and thereby suppresses the growth of the cancer or blocking the invasion or metastasis of the cancer. The bi-specific antibody of the present disclosure includes a first antigen binding site that binds to polyethylene glycol (PEG); and a second antigen binding site that binds to a target ligand, such as a tumor antigen.

Abstract: The present invention relates to extended recombinant polypeptide (XTEN) compositions, conjugate compositions comprising XTEN and XTEN linked to cross-linkers useful for conjugation to pharmacologically active payloads, methods of making highly purified XTEN, methods of making XTEN-linker and XTEN-payload conjugates, and methods of using the XTEN-cross-linker and XTEN-payload compositions.

Abstract: The invention generally relates to synthetic mimics of cell penetrating peptides. More particularly, the invention relates to certain novel monomers, oligomers and polymers (e.g., co-polymers) that are useful for the preparation of synthetic mimics of cell penetrating peptides, their compositions, preparations and use.

Abstract: The present invention relates to conjugates, in particular antibody-drug conjugates and immunotoxins, having the formula I: A-(L-D)p (I) or a pharmaceutically acceptable salts or solvates thereof, wherein: A is an antibody that selectively binds FAP; L is a linker; D is a drug comprising a cytolysin or a Nigrin-b A-chain; and p is 1 to 10, and to use of such conjugates in the therapeutic treatment of tumors. Methods of producing such conjugates and components for use in such methods are disclosed.

Abstract: The present invention relates to methods for determining the risk of severe complications in hemolytic diseases. The present invention relates to a method for determining whether a patient suffering from sickle cell disease is at risk for a vaso-occlusive crisis comprising the steps consisting of i) determining the level of cell microparticles in a blood sample obtained from said patient and ii) determining the level of heme and/or hemoglobin contained in said cell microparticles. The present invention also relates to a method for a method the severe complication in hemolytic diseases comprising the steps consisting of i) determining the level of cell microparticles in a blood sample obtained from said patient and ii) determining the level of heme and/or hemoglobin contained in said cell microparticles.

Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. In preferred embodiments, the antibody may be an hRS7 antibody. The methods and compostions are of use to treat Trop-2 expressing cancers in human patients, preferably in patients who are resistant to or relapsed from at least one prior anti-cancer therapy, more preferably in patients who are resistant to or relapsed from treatment with irinotecan. The immunoconjugate may be administered at a dosage of 3 mg/kg to 18 mg/kg, preferably 8 to 12 mg/kg, more preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size and reduce or eliminate metastases.

Abstract: The present invention provides a chimeric protein comprising a VWF protein comprising the D? domain and D3 domain of VWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain comprising a VWF fragment of the invention binds to or is associated with a polypeptide chain comprising a FVIII protein linked to an XTEN sequence and the polypeptide chain comprising the VWF fragment can prevent or inhibit binding of endogenous VWF to the FVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to the FVIII protein, which is a half-life limiting factor for FVIII, the VWF fragment can induce extension of half-life of the chimeric protein comprising a FVIII protein.

Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 24 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

Abstract: The present invention provides a protein or antibody in which, of a pair of hydrophobic amino acids selected from within a hydrophobic interaction site of the protein, one hydrophobic amino acid is transformed into a substance having a positive electrical charge and the other hydrophobic amino acid is transformed into a substance having a negative electrical charge, and electrostatic interaction is introduced within the hydrophobic interaction site of the protein by means of the positive charge and the negative charge. The present invention also provides a method for preparing the protein or antibody, and a method for measuring the degree of coupling between a heavy chain and a light chain, using the antibody. The protein or antibody in accordance with to the present invention has a low contamination by a homodimer or a monomer, and thus a heterodimer can be obtained in high purity.

Abstract: The invention provides binding agents and assays tor insulin signal peptide. The agents and assays are useful in methods tor predicting, diagnosing, assessing or monitoring acute cardiac disorders, glucose handling disorders and diabetes in a subject. Also provided are nucleotides, polypeptides, and kits useful in the methods of the invention.

Abstract: The present invention provides compounds represented by formula (I) and pharmaceutical acceptable salts thereof, preparation method therefor and pharmaceutical composition containing the compounds represented by formula (I) and pharmaceutical acceptable salts thereof. In the compounds of the present invention, each terminal group of polyethylene glycol molecule can bond with a plurality of rapamycin molecules by cactus oligopeptide, with the loading rate of the pharmaceutical being increased. The compounds can be used to induce immunosuppression and treat graft rejection, autoimmune disease, solid tumors, fungal infection, and cardiovascular and cerebrovascular disease.

Abstract: Cysteine engineered antibodies comprising a free cysteine amino acid in the heavy chain or light chain are prepared by mutagenizing a nucleic acid sequence of a parent antibody and replacing one or more amino acid residues by cysteine to encode the cysteine engineered antibody; expressing the cysteine engineered antibody; and isolating the cysteine engineered antibody.

Abstract: One embodiment relates to methods for the enzymatic functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

Abstract: The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolyzed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolyzing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

Abstract: The present invention relates to a method of identifying cancer subjects, in particular human patients, who are suitable for anti-lymphangiogenesis therapy to prevent tumor growth and tumor metastasis. The present invention also relates to a new approach, which uses nucleolin as a bait to search and screen for lymphangiogenesis inhibitors or cancer suppressors, which function in a manner that is analogous to endostatin. The invention is based upon the discovery that nucleolin is specifically expressed on lymphangiogenic vessels and functions as a specific receptor for endostatin, and thus is involved in the signal transduction pathway of endostatin as an anti-lymphangiogenesis inhibitor. The present invention also discloses that cell surface nucleolin on lymphatic endothelial cells is a biomarker for lymphangiogenic vessels, which could be used for the prediction of tumor metastasis.

Abstract: The present invention is directed to novel non-invasive diagnostic tools/compounds to image cancers, especially, melanoma, including metastatic melanoma in vivo. The present compounds exhibit enhanced uptake in cancerous cells and tissue and decreased renal uptake in kidney, evidencing favorable pharmacokinetics of compounds of the present invention. The compounds according to the present invention represent an advance in the diagnosis and treatment of melanoma, including metastatic melanoma using non-invasive molecular imaging techniques. The novel probes of the present invention are also useful for initiating therapy for melanoma as well as monitor patients' response to chemotherapy treatments and other interventions or therapies used in the treatment of melanoma/metastatic melanoma. Compounds according to the present invention may be used as diagnostic tools for a number of conditions and diseases states as well as therapeutic agents for treating such conditions and disease states.

Abstract: A targeted T-cell engaging agent for treating a condition characterized by the presence of unwanted cells includes (a) a targeting moiety that is capable of targeting the unwanted cells; (b) a first T-cell engaging domain capable of T-cell engaging activity when binding a second T-cell engaging domain, wherein the second T-cell engaging domain is not part of the agent; (c) at least one inert binding partner capable of binding to the first T-cell engaging domain such that the first T-cell engaging domain does not bind to the second T-cell engaging domain unless the inert binding partner is removed; and (d) at least one cleavage site separating the first T-cell engaging domain and the inert binding partner, wherein the cleavage site is: (i) cleaved by an enzyme expressed by the unwanted cells; (ii) cleaved through a pH-sensitive cleavage reaction inside the unwanted cell; (iii) cleaved by a complement-dependent cleavage reaction; or (iv) cleaved by a protease that is colocalized to the unwanted cell by a target