Abstract: The present invention provides redesigned soluble coronavirus S protein derived immunogens that are stabilized via specific modifications in the wildtype soluble S sequences. Also provided in the invention are nanoparticle vaccines that contain the redesigned soluble S immunogens displayed on self-assembling nanoparticles. Polynucleotide sequences encoding the redesigned immunogens and the nanoparticle vaccines are also provided in the invention. The invention further provides methods of using the vaccine compositions in various therapeutic applications, e.g., for preventing or treating coronaviral infections.

Abstract: Provided herein are engineered hMPV F proteins. In some aspects, the engineered F proteins exhibit enhanced conformational stability and/or antigenicity. Methods are also provided for use of the engineered F proteins as diagnostics, in screening platforms, and/or in vaccine compositions.

Abstract: The present invention relates to a method of determining an analyte in a sample, said method comprising (a) contacting said sample with (i) a binding compound binding to said analyte, said binding compound comprising a binding agent and a first partner of an affinity pair (first affinity partner); and (ii) a second partner of the affinity pair (second affinity partner) coupled to a solid surface, to an indicator, and/or to a second binding agent; and (b) determining said analyte based on complexes formed in step (a); wherein one of said first affinity partner and said second affinity partner is a polypeptide comprising the amino acid sequence of SEQ ID NO:1 or a sequence at least 50% identical thereto, and wherein the other of said first affinity partner and said second affinity partner is a polypeptide comprising the amino acid sequence of SEQ ID NO:2 or a sequence at least 50% identical thereto.

Abstract: A method for increase the presentation of ETEC CS6 antigen on a cell surface, comprising the step of contacting cells expressing said antigen with an aqueous solution comprising 0.6-2.2 percent phenol by weight, such that the presentation of said antigen is increased by at least 100%. A method for the manufacture of a killed whole cell vaccine for immunization against CS6-expressing ETEC. Cells and vaccines obtainable by the above methods.

Abstract: The present invention relates to compositions and fusion proteins containing at least two Mycobacterium sp. antigens, and polynucleotides encoding such compositions and fusion proteins. The invention also relates to methods for their use in the treatment, prevention and/or diagnosis of tuberculosis infections.

Abstract: Provided is a method for artificially and efficiently inducing ectopic embryogenesis without fertilization in a seed plant. The present method includes introducing and expressing, in a seed plant, nucleic acid that includes a base sequence that codes a protein having an embryogenesis induction function.

Abstract: The present application describes stapled peptide degron chimeras, which act as protein degradation inducing moieties, either by combining a stapled peptide that binds a disease-related protein with a small molecule degron, such as a cereblon- or VHL-binding small molecule as the degron, or a polypeptide sequence degron, such as a Cop1-binding Trib peptide as the degron; or by combining a stapled peptide degron with a peptide, such as a stapled peptide, or a small molecule that binds a disease-related protein. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of stapled peptide degron chimeras which can be utilized in the treatment of proliferative disorders or other conditions whereby elimination of a disease-causing or disease-related protein would have a therapeutic benefit. The present application also provides methods for making compounds of the application and intermediates thereof.

Abstract: Disclosed herein are fusion proteins comprising a truncated thrombostasin protein having at least 85% sequence homology to a thrombostasin protein, wherein the thrombostasin protein has a carboxy terminal deletion; and a fusion partner protein that is a non-thrombostasin protein. Further disclosed are vaccine compositions thrombostasin proteins having a comprising a carboxy terminal deletion, and methods for inhibiting a response to a thrombostasin protein in a host in need thereof, comprising the disclosed fusion proteins or vaccine compositions. Further disclosed are methods for the preparation of a fusion protein composition.

Abstract: The inventors generated new mutated Annexin A5 polypeptides to which the binding of heme is drastically reduced, but the binding to phosphatidylserine-bearing membranes remains at the same level in presence of heme or during intravascular hemolysis. Thus mutated polypeptides can therefore be particularly suitable for therapeutic purposes, in order to harness reactions enhanced by PS or PS-bearing membranes, most particularly in pathologies where thrombotic, vaso-occlusive and hemolytic conditions co-exist.

Abstract: Systems and method for providing chaperone activity to a protein-containing compound is disclosed. The method includes selecting a nucleic acid based on one or more of the nucleic acid's particular properties and a specific sequence of the nucleic acid and applying the nucleic acid to a compound comprising one or more proteins to provide chaperone activity to the compound.

Abstract: The present disclosure is directed to systems and methods for synthesizing a recombinant polymeric amyloid and recombinant polymeric amyloid fibers. In some embodiments, the methods comprise synthesizing tandem repeats of an amyloid peptide and a glycine-rich linker peptide in vivo in a heterologous host. In other embodiments, the recombinant polymeric amyloid fibers comprise a plurality of polymeric amyloid fibrils each comprising a plurality of ?-sheet crystals, wherein the ?-sheet crystals comprise tandem repeats of an amyloid peptide and a glycine-rich linker peptide, and wherein the plurality of ?-sheet crystals are aligned in parallel with a fiber axis.

Abstract: Diagnosis, treatment and prophylaxis of diseases and conditions associated with smooth muscle cell (SMC) dysfunction are provided through the inhibition or IL-11-mediated signalling.

Abstract: The present disclosure provides a cytokine-based bioactivatable drug construct (“VitoKine”) platform that aims to reduce systemic mechanism-based toxicities and lead to broader therapeutic utility for proteins and cytokines such as IL-15 and IL-2 for the treatment of cancer, autoimmune diseases, inflammatory diseases, viral infection, transplantation and various other disorders. The novel VitoKine constructs of the present invention comprise: 1) a tissue or disease site targeting moiety D1 domain (“D1”), 2) a bioactivatable moiety D2 domain (“D2”), and a concealing moiety D3 domain (“D3”). Importantly, because the “active moiety” of the VitoKine construct will remain inert until activated locally by proteases that are upregulated in diseased tissues, this will limit binding of the active moiety to the receptors or to the targets in the peripheral or on the cell-surface of non-diseased cells and tissue to prevent over-activation of the pathway and reduce undesirable “on-target” “off tissue” toxicities.

Abstract: The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.

Abstract: The present disclosure relates to cleavable carriers and cleavable carrier-linked cytokine prodrugs wherein the cleavable carrier is an engineered Fc domain comprising at least one tumor-associated protease cleavage site. Upon cleavage at the cleavage site of the carrier Fc domain, the cytokine is released from a masking moiety. The platform provides enzymatically induced prodrug activation. The present disclosure further provides pharmaceutical compositions comprising said cleavable carrier-linked cytokine prodrugs, their use as a medication as well as methods of treatment of diseases and administration.

Abstract: The disclosure relates to a liquid pharmaceutical composition of aldesleukin/SDS aggregates and its use in the treatment of auto-immune disease, inflammatory disorders, gene therapies and cancer. A method for preparing said composition is also described.

Abstract: Provided is a peptide provided herein includes at least one peptide unit, and the peptide unit may include at least one B-cell epitope, at least one Th epitope, and an appropriate number of auxiliary parts. The peptide unit is a portion designed to uniformly induce only the intended antibody while exhibiting a certain level of immunogenicity in the body of a subject. In addition, the peptide unit is designed with a relatively short length, and thus has the characteristics of easy synthesis and a low production cost. The peptide has properties suitable for use as an immunotherapeutic due to the characteristics of the peptide unit described above. In the present specification, the design principles of the peptide and the peptide unit are disclosed in detail.

Abstract: The invention provides materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders. In particular, the invention provides novel acylated glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: The present invention is in the therapeutic field of drugs for medical conditions relating to diabetes. More specifically the invention relates to insulin analogues of human insulin. The invention provides pharmaceutical compositions comprising such insulin analogues and the uses if the such analogues for the treatment or prevention of medical conditions relating to diabetes.

Abstract: The invention features polypeptides that include an extracellular ActRIIB variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIB variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, bone damage, low red blood cell levels (e.g., anemia or blood loss), fibrosis, and/or pulmonary hypertension.

Abstract: The invention relates to a peptide comprising an amino acid sequence selected from the group consisting of (i) SEQ ID NO: 1 to SEQ ID NO: 113, and (ii) a variant sequence thereof which maintains capacity to bind to MHC molecule(s) and/or induce T cells cross-reacting with said variant peptide, or a pharmaceutically acceptable salt thereof.

Abstract: The current disclosure relates to, inter alia, mutant derivatives of PD-1 protein. The current disclosure also relates to compositions and methods that find use in the treatment of diseases, such as immunotherapies for cancer and autoimmunity.

Abstract: This invention relates to vectors for delivery of human leukocyte antigen G to the eye and/or to cornea explants and methods of using the same for treatment and/or prevention of corneal transplant rejection and other disorders associated with an immune response and/or vascularization.

Abstract: Immunogenic fusion proteins against infectious animal diseases. A fusion protein is disclosed, which comprises a CD40-binding domain; an antigen of a pathogen; a translocation domain located between the CD40-binding domain and the antigen, and a furin and/or cathepsin L cleavage site located between the CD40-binding domain and the translocation domain. Also disclosed are pharmaceutical compositions, expression vectors and use of the fusion proteins of the invention for eliciting an antigen-specific cell-mediated immune response, or for reducing, inhibiting, treating and/or ameliorating an infectious animal disease caused by a pathogen in an animal in need thereof.

Abstract: The present disclosure relates to fluorescent biosensors and methods of use thereof. In particular, provided herein is a genetically encoded fluorescent indicator (GEFI) comprising a circular-permuted fluorescent protein (cpFP) and an inhibitory molecule bound to the cpFP. In the basal state, the inhibitory molecule prevents fluorescence from the circular-permuted fluorescent protein. Upon conformational change and/or cleavage of the bond between the inhibitory molecule and the cpFP, the cpFP is disinhibited, thereby permitting fluorescence from the cpFP. The biosensors described herein may be used in methods for detecting a variety of cell-signaling events.

Abstract: The present invention provides codon optimized Factor VIII sequences, vectors and host cells comprising codon optimized Factor VIII sequences, polypeptides encoded by codon optimized Factor VIII sequences, and methods of producing such polypeptides. The present invention also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject a codon optimized Factor VIII nucleic acid sequence or the polypeptide encoded thereby.

Abstract: The present application is directed to methods for modulating afucosylation of an antibody product that is produced in a bioreactor. The methods include the addition of mannose to the bioreactor to control the afucosylation of the antibody product, including increasing by afucosylation by 1% or more, relative to untreated bioreactor products.

Abstract: The present disclosure relates, in part, to anti-influenza antibodies (and antigen binding fragments thereof) and combinations thereof for preventing and treating influenza infection. Presently disclosed combinations provide surprising synergistic effects and can potently prevent, inhibit, or neutralize an influenza infection, such as an influenza A virus (IAV) infection an influenza B virus (IBV) infection, or both.

Abstract: The present disclosure provides for IL2 engrafted into the CDR sequences of an antibody having preferred therapeutic profiles over molecules known and used in the clinic. In particular, the provided antibody cytokine engrafted protein compositions increase or maintain CD8+ T effector cells while reducing the activity of Treg cells. Additionally, provided compositions convey improved half-life, stability and produceability over recombinant human IL2 formulations such as Proleukin®.

Abstract: A method of treating a subject suffering from a cancer, comprising the steps of obtaining a sample of a cancer cell from the subject; determining a sequence of a phosphatidylinositol 3-kinase catalytic subunit (PIK3CA) protein in the sample; and administering a first amount of a DKK1 inhibitor to the subject determined to have the sequence of PIK3CA protein that includes an activating mutation. The cancer is an epithelial endometrial cancer or an epithelial ovarian cancer.

Abstract: The disclosure provides antibodies that are useful for, among other things, inhibiting terminal complement (e.g., the assembly and/or activity of the C5b-9 TCC) and C5a anaphylatoxin-mediated inflammation and, thus, treating complement-associated disorders. The antibodies have a number of improved properties relative to eculizumab, including, e.g., increased serum half-life in a human.

Abstract: The invention provides antibodies that specifically bind transthyretin (TTR). The antibodies can be used for treating or effecting prophylaxis of diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis). The antibodies can also be used for diagnosing TTR amyloidosis and inhibiting or reducing aggregation of TTR, among other applications.

Abstract: The present invention is based on the surprising finding that the MPC5B4 anti-periostin monoclonal antibody can effectively prevent and treat inflammation, fibrosis and worsening of pulmonary inflammation and respiratory diseases in various animal models. The MPC5B4 anti-periostin monoclonal antibody recognizes specifically the peptide sequence of SEQ ID NO:1, corresponding to the amino acid sequence 136-151 located within the fasciclin (FAS)1-1 domain of the periostin protein (POSTN), inhibiting its binding to the ?v?3 integrin.

Abstract: A bispecific binding molecule is provided, which comprises two identical antibody heavy chains and a single chain component which is a polypeptide chain comprising two identical antibody light chains linked to a single chain binding module with affinity for a target which mediates transport of the bispecific binding molecule across the blood-brain barrier (BBB). Also provided are therapeutic, prophylactic, prognostic and diagnostic uses of the bispecific binding molecule.

Abstract: Provided herein are methods, compositions and kits for preventing and treating malaria. Also included herein are kits for preventing and treating malaria.

Abstract: Provided herein are methods and compositions related to the treatment of sepsis using anti-ANGPTL3 antibodies.

Abstract: VEGF-binding molecules, preferably VEGF-binding immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with VEGF-mediated effects on angiogenesis. Nucleic acids encoding VEGF-binding molecules, host cells and methods for preparing same.

Abstract: A method of treating Crohn's disease in a patient administers an IL-23 specific antibody, e.g., guselkumab, at an initial subcutaneous dose and subsequent subcutaneous doses in order for the patient to respond to the antibody and meet one or more of the clinical endpoints.

Abstract: The present invention relates to IL-34 antibodies, compositions comprising the same, and methods of using the antibodies and or compositions thereof for treating immune-mediated diseases such as neurodegenerative diseases, for example Alzheimer's Disease or a tauopathy disease.

Abstract: An anti-IL-22 antibody or antibody fragment that binds to both human IL-22 and a mammalian IL-22 as well as modified anti-IL-22 antibodies and antibody fragments. Pharmaceutical compositions and kits comprising the antibody or antibody fragment are also provided. Also provided are methods for treatment of various IL-22 mediated conditions and diseases.

Abstract: The present invention relates to an epitope of Lrig1 (leucine-rich and immunoglobulin-like domains protein 1) protein, which is an antigen present on the surface of regulatory T cells, and to an antibody or an antigen-binding fragment that specifically binds thereto.

Abstract: The invention provides agonistic anti-human VISTA antibodies and antibody fragments. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.

Abstract: An anti-NKp46 antibody or antigen-binding fragment thereof, a derivative comprising said antibody or antigen-binding fragment thereof, a pharmaceutical composition, and related application in treating cancers are provided. The anti-NKp46 antibody or antigen-binding fragment thereof is capable of specifically binding to NKp46 including 3 CDRs selected from sequences shown in SEQ ID NOS: 44-133.

Abstract: The instant disclosure provides multispecific molecules that specifically bind to CD96 (e.g., human CD96) and/or TIGIT (e.g., human TIGIT) and isolated antibodies that specifically bind to TIGIT (e.g., human TIGIT). Also provided are pharmaceutical compositions comprising these multispecific molecules and antibodies, nucleic acids encoding these multispecific molecules and antibodies, expression vectors and host cells for making these multispecific molecules and antibodies, and methods of treating a subject using these multispecific molecules and antibodies.

Abstract: The present disclosure provides chimeric antigen receptors, compostions, and methods thereof. In one embodiment the present disclosure provides a method of treating autoimmune diseases, asthma, and preventing or mediating organ rejection in a subject.

Abstract: Multispecific proteins that bind and specifically redirect NK cells to lyse a target cell of interest are provided without non-specific activation of NK cells in absence of target cells. The proteins have utility in the treatment of disease, notably cancer or infections disease.

Abstract: The present invention relates to a bispecific antibody comprising at least a first binding domain and a second binding domain, wherein said first binding domain binds to an organic fluorophore and wherein said second binding domain binds to CD3, and to a combination thereof with a labelled binding agent that binds specifically to a target antigen, wherein the labelled binding agent is labelled with an organic fluorophore.

Abstract: The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease.

Abstract: Provided herein is a composition comprising a fusion protein or a fragment or a variant thereof comprising an anti-PD1 antibody or a fragment/variant thereof and a TGF-? trap. Provided herein is a composition comprising a fusion protein or a fragment thereof or a variant thereof comprising an anti-PD1 antibody or a fragment/variant thereof and a ADA2 polypeptide. Also provided herein are methods of using the composition in treating cancer.

Abstract: Provided herein are cross-reactive antibodies (or antigen binding fragments thereof) that bind to human CTLA4, activatable antibodies that bind to human CTLA4, nucleic acid molecules encoding the same, pharmaceutical compositions thereof, and methods of their therapeutic use (e.g., for treatment of cancer).