Abstract: The invention relates to the field of immuno-oncology. More in particular, it relates to applying the mixed-lineage kinase domain-like protein (MLKL) or variants thereof in immunotherapeutic treatment of cancer. The MLKL or variant thereof is inducing an adaptive immune response to cancer cells leading to treatment of primary tumors and preventing development of secondary tumor or tumor metastasis.

Abstract: The present provides methods for treating spinal muscular atrophy using a self-complementary recombinant adeno-associated virus (rAAV) viral particle comprising a transgene expressing SMN. In one aspect, the viral particles are administered in the spinal column or cisterna magna in a human subject; for example, a pediatric human subject. Viral particles comprising AAV9 capsids are contemplated.

Abstract: The present invention provides methods for treating angiogenic eye disorders by sequentially administering multiple doses of a VEGF antagonist to a patient. The methods of the present invention include the administration of multiple doses of a VEGF antagonist to a patient at a frequency of once every 8 or more weeks. The methods of the present invention are useful for the treatment of angiogenic eye disorders such as age related macular degeneration, diabetic retinopathy, diabetic macular edema, central retinal vein occlusion, branch retinal vein occlusion, and corneal neovascularization.

Abstract: Provided are compositions comprising silk fibroin, perfluorocarbon (PFC), and surfactant, and methods of use thereof. The compositions can further comprise a drug, an antibody, or a vaccine. Compositions of the invention are useful in the treatment of certain lung diseases and conditions, including in particular those characterized by surfactant deficiency. Compositions of the invention are particularly useful in the treatment of respiratory distress syndrome (RDS). Also provided are methods for making the compositions, and kits comprising components of the compositions.

Abstract: The present invention relates to novel peptides derived from Kita-kyushu lung cancer antigen 1 (CT83), complexes comprising such peptides bound to recombinant MHC molecules, and cells presenting said peptide in complex with MHC molecules. Also provided by the present invention are binding moieties that bind to the peptides and/or complexes of the invention. Such moieties are useful for the development of immunotherapeutic reagents for the treatment of diseases such as cancer.

Abstract: Disclosed herein are methods of treating minimal residual cancer in a subject. The methods involve contacting disseminated cancer cells (DCCs) in a subject with a bone morphogenic protein 7 (BMP7) derivative protein, where the contacting induces or maintains dormancy in the contacted DCCs of the subject to treat minimal residual cancer in the subject. Also disclosed are methods that involve contacting DCCs in a subject with a protein kinase RNA-like endoplasmic reticulum kinase (PERK) inhibitor selected from LY2, LY3, and LY4, where said contacting eradicates DCCs in the subject to treat minimal residual cancer in the subject.

Abstract: The present invention provides compositions comprising as an essential feature granulocyte-macrophage colony-stimulating factor (GM-CSF) together with fosfomycin for the treatment of bacterial lung infections by administration via the air-ways.

Abstract: A stable form of hybrid Fc fused Granulocyte Colony Stimulating Factor (G-CSF) formulation is disclosed. The formulation includes (i) a therapeutically effective amount of hybrid Fc fusion G-CSF, (ii) a buffer system, (iii) at least one stabilizer and (iv) at least one surfactant, and (v) optionally propylene glycol as organic solvent, suitable for administration via a subcutaneous (SC) route.

Abstract: Computational and functional analysis identified the neuropeptide receptor Nmur1 as selectively expressed on Type 2 innate lymphoid cells (ILC2s). While both IL-33 and IL-25 promote ILC activation in vivo, IL-33 induces robust ILC proliferation, whereas ILCs activated with IL-25 do not proliferate as robustly and up-regulate Nmur1 expression. Treatment with neuromedin U (NMU), the neuropeptide ligand of Nmur1, had little effect on its own. Co-administration of IL-25 with NMU, however, dramatically amplified allergic lung inflammation and induced the proliferation and expansion of specific ILC2 subsets, characterized by a molecular signature unique to pro-inflammatory ILC2s. The results demonstrate that Nmur1 signaling strongly modulates IL-25-mediated ILC2 responses, resulting in highly proliferative pro-inflammatory ILCs, and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.

Abstract: The present invention provides for a dosing schedule for the intratumoral delivery of an immunostimulatory cytokine in combination with systemic delivery of a checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine, e.g., IL-12, using intratumoral electroporation, and the systemic delivery of a PD-1 antagonist.

Abstract: The invention relates to the use of interleukin-2 in treating Sjögren's syndrome in a subject, wherein IL-2 is to be administered at a low dose of less than about 3.5 MIU/day.

Abstract: This disclosure features methods and compositions for treating diseases of the gastrointestinal tract with IL-10 or an IL-10 agonist.

Abstract: This disclosure relates to a drug delivery system comprising an intraocular pressure lowering agent, a neurotrophic agent, such as a CNTF compound, a C-type Natriuretic Peptide (CNP) compound, a Tie-2 agonist, a Natriuretic Peptide Receptor-B (NPR-B) compound, or an apoptosis signaling fragment inhibitor (FAS) or FAS-ligand (FASL) inhibitor, including any combination of these compounds and a sustained delivery component. Methods of treating a glaucoma or related conditions, medicaments, kits, uses and methods of manufacturing are also described.

Abstract: The present invention provides modified von Willebrand Factor molecules, methods for their preparation and uses thereof. The invention further provides pharmaceutical compositions for treating coagulation disorders.

Abstract: Some embodiments provided herein relate to methods and pharmaceutical compositions comprising recombinant human surfactant protein D or active fragments thereof. Some such embodiments include solutions or suspensions, and lyophilized solid forms of recombinant human surfactant protein D or active fragments thereof.

Abstract: The present invention provides compositions and methods of treating hyperphenylalaninemia (e.g., phenylketonuria) in a subject in need thereof comprising administering to the subject an effective amount of a phenylalanine dehydrogenase (PheDH) polypeptide. The present invention also provides pharmaceutical formulations comprising PheDH for lowering the phenylalanine concentration in the subject (e.g., in the intestines and/or blood).

Abstract: A micro-environment bioreaction aggregate (“MEBA”) is formed by combining a non-digestible carrier system with redox potential (“Eh”) regulating compounds. The bioreaction aggregate is introduced into a microbial environment, such as soil, hydroponic systems, or gastrointestinal tracts of animals or humans. Said MEBA regulates the Eh of the microbial microhabitat and its surroundings, thereby providing numerous benefits towards the prevention and treatment of diseases and dysbiosis.

Abstract: The present invention relates to methods of modulating the expression and/or activity of Myeloperoxidase (MPO) in a mammalian subject, by modulating ex vivo and/or in vivo MPO levels and/or activity in undifferentiated bone marrow (BM) cells of the subject. The invention further provide therapeutic methods and compositions for treating MPO-related disorders.

Abstract: The present invention provides novel artificial tears containing a recombinant human lysozyme. The novel artificial tears comprise main components and an auxiliary material. The main components are a recombinant human lysozyme and a sodium hyaluronate, wherein the recombinant human lysozyme and the sodium hyaluronate are contained in an amount from 0.075%-0.300% and from 0.10%-0.30%, respectively in the total mass of the novel artificial tears. A drug for external use is prepared by combining the recombinant human lysozyme, the sodium hyaluronate and an excipient for treating light and moderate dry eye syndrome.

Abstract: Methods for treating neurological or neuropsychiatric disorder and related symptoms by administering a CGRP antagonist and a Clostridial derivative are described.

Abstract: The present invention relates to a composition for the delivery of drug molecules, especially therapeutic proteins via oral route, sublingual, and buccal routes. The embodiments herein provide delivery of therapeutic proteins with the help of neurotoxin associated proteins (NAPs) from Clostridium botulinum type A or type E. The NAPs combine with proteins and/or drug molecules to form a composition for oral or sublingual delivery.

Abstract: The present invention utilizes patient-specific landmarks in order to treat headache pain. In one aspect, the present invention relates to the administration of Clostridial toxins, such as a botulinum neurotoxin, to a patient suffering from a headache pain, where the location of administration of the botulinum toxin is based upon at least one suture line of the patient's skull.

Abstract: The present invention refers to polypeptides with asparaginase activity that have an increased rate of self-processing compared to human wild L-asparaginase (ASRGL1), with mutation in the ASRGL1 glycine rich loop called HGG loop (Histidine 8-Glycine 9-Glycine 10). Polynucleotides that encode the polypeptides of invention are also described here, expression cassettes comprising so-called polynucleotides, expression vectors, host cells, pharmaceutical compositions, uses of the invention polypeptide in the manufacture of a preventive medicine or cancer treatment and methods to produce the polypeptide of invention and to prevent or treat cancer.

Abstract: Methods of preparing mammalian enteroids, and methods producing T. gondii oocysts in vitro and in vivo in heterologous systems, are provided.

Abstract: The present invention relates to immunogens directed against lung cancer associated proliferative peptides and growth factors and its uses thereof in conjunction with chemotherapeutics in the early and advanced treatment of various malignant diseases, especially including lung cancers, both small cell lung carcinomas (SCLC), non-small cell lung (NSCLC) cancers and neuroendocrine-type cancers.

Abstract: Peptides derived from Progesterone-associated endometrial protein (PAEP), complexes comprising such peptides bound to recombinant MHC molecules, and cells presenting said peptide in complex with MHC molecules as described. Also provided by the present invention are binding moieties that bind to the peptides and/or complexes of the invention. Such moieties are useful for the development of immunotherapeutic reagents for the treatment of diseases such as cancer.

Abstract: Disclosed are pharmaceutical compositions for inducing an immune response against tumor cells comprising tumor cells which are made apoptotic by treatment with high hydrostatic pressure and dendritic cells, and methods for producing such compositions.

Abstract: Described herein are methods and compositions relating to methods of inhibiting neutrophils, e.g., inhibiting NET release or NETosis, by means of a DEspR inhibitor, e.g., an anti-DEspR antibody reagent. In some embodiments, the methods can relate to the treatment of a disease, e.g., cancer or a disease wherein neutrophils; NETs; or NETosing or NETting neutrophils contribute to pathogenesis, chronicity, or worsening of disease. In some embodiments, the DEspR inhibitor can be a bi-specific reagent or an antibody-drug conjugate.

Abstract: Provided herein are methods and compositions for the treatment of melanoma using anti-tumor immune cells treated with a PTD-MYC fusion protein (e.g., an HIV TAT-MYC fusion protein).

Abstract: Peptides derived from melanoma-associated antigen C2 (MAGEC2), complexes comprising such peptides bound to recombinant MHC molecules, and cells presenting said peptide in complex with MHC molecules are described. Also provided by the present invention are binding moieties that bind to the peptides and/or complexes of the invention. Such moieties are useful for the development of immunotherapeutic reagents for the treatment of diseases such as cancer.

Abstract: The present invention relates to the composition and method of preparing an immunogen designated as I-spga consisting of a complex antigen prepared from 18 to 26 species of pathogenic microorganisms isolated from patients, inactivated with binary ethyleneamine (BEI) and formalin, diluted in a SPGA immunopotentiator mixed with QS-21 adjuvant. By inoculating the hens with the I-spga immunogen, hyperimmune eggs (Immunospga) are obtained which contain immunologically active proteins specific to the 18-26 antigens used for immunization. The immune response of the hens is specific to the used antigens by amplification of the antigenic signal by the SPGA immunopotentiator and due to a special immunization program that allows the immune system to act complex and intense: The I-spga complex antigen contains 18-26 microorganisms isolated from patients, bacterial bodies, components from bodies obtained by ultrasonography, cilia, exotoxins, endotoxins, spores, viruses, fungi or yeasts.

Abstract: The invention relates to a multivalent Shigella/Enterotoxigenic Escherichia coli vaccine for use in prophylaxis and treatment of diarrheal disease. The Shigella-ETEC vaccine provides increased coverage of a broader range of ETEC and Shigella isolates than prior vaccines, and includes CS14 antigens and serotypes (S. flexneri 7a, or S. flexneri 1b).

Abstract: This present invention provides C-TAB.G5 and C-TAB.G5.1 isolated polypeptides comprising the receptor binding domains of C. difficile toxin A and toxin B as set forth in the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 4. The C-TAB.G5 and C-TAB.G5.1 isolated polypeptides may be used to neutralize toxic effects of C. difficile toxin A and/or toxin B.

Abstract: The invention relates to isolated Streptococcus pneumoniae serotype 15B capsular polysaccharide and processes for their preparation. The invention also relates to immunogenic conjugates comprising Streptococcus pneumoniae serotype 15B capsular polysaccharide covalently linked to a carrier protein, processes for their preparation and immunogenic compositions comprising them.

Abstract: The present invention relates to improved epicutaneous administration methods for vaccination of a subject. In particular, the present invention discloses the use of an antigen for epicutaneous immunization, wherein the antigen is administered by epicutaneous application with a skin patch device in combination with an epidermal skin treatment.

Abstract: The present invention relates to a novel genotype of severe fever with thrombocytopenia syndrome viruses and use thereof as an immunogenic composition. The severe fever with thrombocytopenia syndrome viruses of the present invention are genetically different from conventional severe fever with thrombocytopenia syndrome viruses and are novel viruses taxonomically belonging to three sub-groups of genotype B. In view of the vaccine property that specific genotype viruses alone show only limited protective potential, the novel viruses of the present invention may be advantageously used as a vaccine having excellent cross-immunogenicity for SFTSV.

Abstract: Embodiments herein relate to compositions and methods for stabilizing Flaviviruses. In certain embodiments, compositions and methods disclosed herein concern stabilizing live, attenuated or unattenuated (e.g. live whole) flaviviruses. Other embodiments relate to compositions and methods for reducing degradation of live, attenuated or unattenuated flaviviruses. Other embodiments relate to improved formulations for prolonging stabilization of live attenuated or unattenuated Flaviviruses during manufacturing, storage, accelerated storage and transport. Yet other embodiments relate to uses of compositions disclosed herein in kits for transportable applications and methods.

Abstract: Disclosed are methods of preparing an isolated population of human papillomavirus (HPV)-specific T cells comprise dividing an HPV-positive tumor sample into multiple fragments; separately culturing the multiple fragments; obtaining T cells from the cultured multiple fragments; testing the T cells for specific autologous HPV-positive tumor recognition; selecting the T cells that exhibit specific autologous HPV-positive tumor recognition; and expanding the number of selected T cells to produce a population of HPV-specific T cells for adoptive cell therapy. Related methods of treating or preventing cancer using the T cells are also disclosed.

Abstract: Improved anti-HPV immunogens and nucleic acid molecules that encode them are disclosed. Immunogens disclosed include those having consensus HPV39 E6E7 and HPV45 E6E7. Pharmaceutical composition, recombinant vaccines comprising DNA plasmid and live attenuated vaccines are disclosed as well methods of inducing an immune response in an individual against HPV are disclosed.

Abstract: The present invention relates generally to immunotherapy for preventing HIV infection in HIV-negative individuals. In particular, the methods include in vivo and/or ex vivo enrichment of HIV-specific CD4+ T cells.

Abstract: A medicament for treatment and/or prevention of cancer, comprising an antibody or a fragment thereof having an immunological reactivity with a CAPRIN-1 protein, and imiquimod together or separately in combination can treat and/or prevent cancer specifically expressing CAPRIN-1 protein on a cell surface.

Abstract: The present invention relates to a pharmaceutical combination which comprises (a) at least one antibody molecule (e.g., humanized antibody molecules) that bind to Programmed Death 1 (PD-1), and (b) at least one c-Met receptor tyrosine kinase inhibitor or pharmaceutically acceptable salt thereof, for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly a c-Met dependent proliferative disease; a pharmaceutical composition comprising such combination; a method of treating a subject having a proliferative disease comprising administration of said combination to a subject in need thereof; use of such combination for the treatment of proliferative disease; and a commercial package comprising such combination.

Abstract: The invention relates to the combination therapy comprising oncolytic adenovirus vector and a checkpoint inhibitor or checkpoint inhibitors. More specifically, the invention relates to oncolytic adenovirus vector and checkpoint inhibitor or checkpoint inhibitors for use in a cancer therapy.

Abstract: The present invention provides a method of treating a tau-mediated cognitive or neurodegenerative disease, comprising administering to a patient in need of such treatment an effective amount of an anti-Tau antibody and an effective amount of an OGA inhibitor.

Abstract: The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, an acetate buffering agent/system such as sodium acetate/acetic acid, and a sugar stabiliser such as trehalose. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.

Abstract: The invention provides an aqueous formulation comprising water and a protein, and methods of making the same. The aqueous formulation of the invention may be a high protein formulation and/or may have low levels of conductivity resulting from the low levels of ionic excipients. Also included in the invention are formulations comprising water and proteins having low osmolality.

Abstract: Disclosed is a method of preventing or treating a condition of the gastrointestinal tract. The method includes the steps of providing a DNA repair composition, the DNA repair composition comprising at least one DNA repair enzyme, the DNA repair composition configured for administration within the gastrointestinal tract of a patient; and administering the DNA repair composition to the patient, such that the DNA repair composition is absorbed within the gastrointestinal tract of the patient to treat the condition of the gastrointestinal tract.

Abstract: Described herein are systems and methods for particle-based photodynamic therapy (PDT) for the treatment of diseases such as cancer of the oral cavity and/or ovarian cancer metastases along the lining of the pelvis. The technology includes an imaging system (e.g., a multichannel imaging camera) configured to perform diagnostic and/or therapeutic treatment on diseased tissue. In certain embodiments, the imaging system comprises one or more excitation sources (e.g., one or more lasers) to assess and/or treat diseased tissue.

Abstract: The invention provides mitochondria-targeted chemiluminescent agents and their use in methods of photodynamic therapy (PDT). In particular, the invention provides compounds of general formula (I), and their pharmaceutically acceptable salts: (I) in which A represents a chemiluminescent moiety; each L, which may be the same or different, is either a direct bond or a linker; each B, which may be the same or different, represents a mitotropic moiety; n is an integer from 1 to 3, preferably 1; and x is an integer from 1 to 3, preferably 1. Such compounds find particular use in the treatment of deeply-sited tumours, e.g. glioblastoma multiforme (GBM), when used in combination with a photosensitizer or photosensitizer precursor.

Abstract: Methods of reducing aggregation of an aggregating IL-1ra comprising incubating IL-1ra with at least one accessory molecule are provided. Kits comprising IL-1ra and at least one accessory molecule are also provided. Pharmaceutical compositions comprising IL-1ra and at least one accessory molecule are also provided.