Abstract: The present invention provides antigen-binding proteins that specifically bind to an HLA-displayed human papillomavirus (HPV) peptide, and therapeutic and diagnostic methods of using those binding proteins.

Abstract: The invention provides pan-influenza vaccine compositions (i.e., vaccine compositions useful against multiple influenza viruses such as H1N1, H2N2, H5N2, etc.), a vaccination regimen for immunization against such influenza diseases, and its use in medicine and in augmenting immune responses to various antigens present in such viruses and to methods of preparation of such compositions. In particular, the invention relates to polyvalent multi-targeting immunogenic compositions comprising influenza viral antigens or antigen preparations thereof from multiple strains associated with human pandemic outbreaks in combination with accessory delivery vehicle(s) and adjuvants.

Abstract: The invention relates to vaccines for the prevention or treatment of infectious diseases, and to methods of preparing or delivering such vaccines. In particular, a vaccine for use in the prevention or treatment of disease is used in a dose of, via a parenteral route without adjuvant less than 0.03 µg antigen and with adjuvant less than 0.003 µg antigen, and via a mucosal route without adjuvant less than 1 µg antigen and/or the equivalent of 1.6 × 107 PFU and with adjuvant less than 0.04 µg antigen and/or the equivalent of 1.

Abstract: Provided herein are recombinant negative-strand RNA virus genomes (e.g., recombinant rabies virus genomes) and recombinant negative-strand RNA viruses (e.g., recombinant rabies viruses) and methods for their use in delivering a guide RNA and, optionally, a transgene, into a target cell. Also provided are packaging systems and methods of using the packaging systems to produce recombinant negative-strand RNA viruses.

Abstract: The invention relates to vaccines, and in particular, to vaccines for preventing, treating or ameliorating coronavirus infections, such as severe acute respiratory syndrome coronavirus (SARS), SARS-CoV-2 and Middle East respiratory syndrome-related coronavirus (MERS). The invention is especially concerned with self-amplifying RNA replicons and genetic constructs or vectors encoding such RNA replicons, and their use in vaccine delivery for preventing infections of coronavirus. The invention extends to pharmaceutical compositions comprising such RNA constructs, and methods and uses thereof.

Abstract: Microneedle and microneedle devices including implantable tips (e.g., silk-based tips) for sustained dermal delivery of a coronavirus and/or influenza vaccine, kits, as well as methods of manufacturing and using the same are described herein. In other embodiments, compositions and methods for controlled- or sustained-administration of a coronavirus vaccine and/or an influenza vaccine to provide improved immunogenicity and/or broad-spectrum immunity to a subject are also described.

Abstract: Pharmaceutical compositions, in particular vaccine compositions, for preventing or at least reducing the severity of, respectively, viral respiratory infections through application of said composition to a human subject post-exposure or at least presumed post-exposure of said subject to a virus causing said viral respiratory infections or pre-exposure of said subject to said virus. More particularly, in specific embodiments, the invention provides pharmaceutical compositions as such comprising at least one antigenic component of the infectious virus and a TLR-3 agonist.

Abstract: A multivalent vaccine for preventing CoV infection includes more than one protein antigen derived from antigens encoded within a CoV genome. At least one of the more than one protein antigen derived from antigens encoded within a CoV genome is a protein antigen, RNA-encoded genetic information, DNA-encoded genetic information, or genetic information within a genetic vector.

Abstract: Described herein are compositions and methods for the prevention of pathogens such as conditions in an animal (e.g., a subject). In some cases, a composition or method described herein can comprise a liposome, which may be used to encapsulate one or more STING agonists. In some cases, a liposome of a composition or method described herein may comprise one or more antigens attached to, integrated into, or associated with a liposomal membrane of the liposome.

Abstract: The present disclosure relates to replication-competent controlled herpesviruses whose transient replication in a desired inoculation site region of a subject can be activated by the delivery of an appropriate heat dose to the inoculation site region. In related recombinant viruses, activation requires delivery of a heat dose in the presence in the inoculation site region of an effective concentration of a small-molecule regulator. The viruses are further engineered to be capable of replicating efficiently in the desired inoculation site region but essentially not in nerve ganglia and other nerve cells.

Abstract: A recombinant viral vector, an immunogenic composition comprising the same, and uses. The recombinant viral vector comprises a polynucleotide encoding a cytokine, the cytokine being one or more selected from IL-7, IL-15, IL-21 or GM-CSF. The recombinant viral vector is useful in preparing an antitumor vaccine.

Abstract: The present disclosure is directed to IgE EMPD peptide immunogen constructs and formulations thereof for the treatment of IgE-mediated allergic diseases. The IgE EMPD peptide immunogen constructs have a B cell epitope peptide of more than 20 amino acids, preferably cyclic, linked through an optional spacer to heterologous T helper cell (Th) epitopes derived from pathogen proteins. These peptide immunogen constructs and formulations thereof can stimulate the generation of highly specific antibodies in vaccinated hosts that are directed against the IgE EMPD peptide and are crossreactive with membrane-bound IgE on B lymphocytes committed to IgE secretion. The antibodies induced by the peptide immunogen constructs and formulations thereof in vaccinated hosts can induce apoptosis of IgE-expressing B cells and mediate Antibody Dependent Cellular Cytototoxity (ADCC), resulting in reduction of antigen-specific IgE and total IgE levels in vaccinated hosts to effectively treat IgE-mediated allergic pathology.

Abstract: The invention pertains to a complex of an OMV, a vertebrate antimicrobial peptide (AMP) and an antigen, wherein the AMP is non-covalently complexed with the OMV and wherein the antigen is conjugated to the AMP. Preferably, the antigen is covalently linked to the AMP. The invention further concerns the induction of an immune response using the complex of the invention as well as a method for producing the complex of the invention.

Abstract: The present disclosure provides, among other things, a pharmaceutical composition that includes a lipid nanoparticle adjuvant and an anti-human papillomavirus (HPV) comprising HPV virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82.

Abstract: Provided herein are methods of treating or reducing idiopathic orbital inflammation (IOI), also known as idiopathic orbital inflammatory syndrome, nonspecific orbital inflammation (NSOI), orbital inflammatory pseudotumor, and orbital inflammatory syndrome (OIS), or one or more symptoms thereof, in a subject with IOI, comprising administering to the subject an effective amount of an insulin-like growth factor 1 receptor (IGF-1R) inhibitor, and pharmaceutical composition comprising an amount of an insulin-like growth factor 1 receptor (IGF-1R) inhibitor effective for treating or reducing one or more effects of idiopathic orbital inflammation (IOI), or one or more symptoms thereof, in a subject with IOI.

Abstract: Methods are provided herein for determining and administering optimized dosing of therapeutic anti-CD47 agents, in a schedule that provides safe escalation of dose while achieving a therapeutic level in a clinically effective period of time. The methods can comprise the steps of clearance, escalation, and maintenance. In one embodiment the dosing regimen administers an initial (i) sub-therapeutic dose of an anti-CD47 agent or (ii) a cytoreductive therapy to achieve a safe level of circulating tumor cells for subsequent treatment (clearance); escalating the dose of an anti-CD47 agent until a therapeutic dose is reached (escalation); and maintaining the therapeutic dose for a period of time sufficient to reduce tumor cells in the bone marrow of the patient (maintenance). In an alternative dosing regimen, a patient determined to have a safe level of circulating tumor cells at presentation is treated by the steps of escalation and maintenance without initial clearance.

Abstract: Disclosed herein are compositions and methods for tumor treatment involving administering to a subject having a tumor with an amount effective to limit tumor growth or metastasis of an ephrin B1 inhibitor, or a pharmaceutically acceptable salt thereof; and/or an inhibitor of tumor exosomal release, or a pharmaceutically acceptable salt thereof

Abstract: Provided herein are modified antibodies, pharmaceutical compositions thereof, as well as nucleic acids, and methods for making and discovering the same. The modified antibodies described herein are modified with a peptide. The peptide binds at or near the antigen binding site of the antibody at physiological pH, thus reducing binding affinity of the antibody for a target antigen. At acidic pH, the binding interaction of the peptide at or near the antigen binding site is disrupted, thus enabling binding with a target antigen.

Abstract: The present invention relates to the field of cancer biology and immunology. More specifically, the present invention relates to the use of genetically modified immune cells in combination with certain chemotherapeutic agents for the treatment of cancer, wherein the genetically modified immune cells are resistant to said chemotherapeutic agents.

Abstract: The present invention relates to a fusion protein and the use thereof. The fusion protein includes, from N to C terminals, a first moiety, an Fc segment, a linking moiety comprising a moiety selected from a linker and a protein or polypeptide selected from IL2 or scFv, and a substrate moiety of transpeptidase A; the linker includes a sequence selected from the group consisting of (1) (GGGGS)n, wherein when the linking moiety includes the protein or polypeptide and the linker, n?1; when the linking moiety only includes the linker, n?3; and (2) (EAAAK)n, n?1; the substrate moiety includes LPXTG. The fusion protein can be directly connected to cells to enable the cells to have a targeting property, is more simple than an existing method for preparing targeting cells by means of cell transfection, and can also reduce the risk possibly generated by an effector cell genome operation.

Abstract: The present disclosure provides ex vivo armed T cell (EAT) compositions that comprise multi-specific (e.g., bispecific) antibodies that bind to CDS and at least one additional target antigen (e.g., antigen that is expressed by tumor cells and/or a DOTA label). The EAT compositions of the present technology are useful for adoptive immunotherapy in a subject in need thereof.

Abstract: A chimeric antigen receptor, containing a ligand binding domain, a transmembrane domain, a co-stimulatory domain, and an intracellular signaling domain, the co-stimulatory domain containing CD94 and/or LT? intracellular regions. The present invention further relates to engineered immune cells containing such a chimeric antigen receptor, and uses thereof in the treatment of diseases, such as cancer, autoimmune diseases, and infections.

Abstract: The present invention relates to compositions and methods for the treatment of lupus, particularly systemic lupus erythematosus. The present invention involves, amongst other things, a binding protein comprising a T cell receptor (TCR) ?-chain variable (V? or Valpha) domain and a TCR ?-chain variable (V? or Vbeta) domain, wherein the binding protein is capable of binding to a complex of a fragment of a Smith protein and an HLA-DR15 or HLA-DR3 molecule.

Abstract: Synthetic bacterial messenger RNA can be used to prepare autologous, allogenic or direct nucleic acid cancer vaccines. Cancer cells are transfected either in vitro or in vivo with mRNA obtained from DNA that encodes an immunogenic bacterial protein. An immune response to the cancer is generated from direct administration of the mRNA in vivo or administration of vaccines prepared from cancer cells in vitro. Codon modification of the mRNA can optimize expression of an immunogenic polypeptide in cancer cells.

Abstract: This disclosure relates to compositions and methods for treating cancer by modulating the artemin pathway.

Abstract: Disclosed herein are liquid diluents, formulations, and kits for preparing reconstituted suspensions of a proton pump inhibitor (e.g., omeprazole). The present disclosure also provides formulations for liquid diluents that do not have a tendency for gel formation following exposure to freeze-thaw cycles.

Abstract: The disclosure provides products configured for oral use, the products including one or more agents adapted to or configured to reduce irritation that may be associated with release of a component from the products. Xylitol in particular may be useful as an irritation reducing agent. The disclosure further provides methods of reducing irritation associated with the release of one or more components from an oral composition or product.

Abstract: Disclosed herein are stability-enhanced formulations that comprise a therapeutic protein and a stability-improving amount of a stabilizing excipient, wherein the stabilized-enhanced formulation is characterized by an improved stability parameter in comparison to a control formulation otherwise identical to the stability-enhanced formulation but lacking the stabilizing excipient. Further disclosed herein are methods of improving stability of therapeutic formulations or improving parameters of protein-related processes.

Abstract: A pharmaceutical composition comprising a GHRH molecule or a pharmaceutically acceptable salt thereof is described, as well as uses thereof and a kit for preparing such a pharmaceutical composition. In an embodiment, GHRH molecule or pharmaceutically acceptable salt thereof is trans-3-hexenoyl-GHRH(1-44)-NH2 or a pharmaceutically acceptable salt thereof. In an embodiment, a pharmaceutical composition comprising about 1.23 to about 1.32 mg of a GHRH molecule such as trans-3-hexenoyl-GHRH(1-44)-NH2 at a concentration of about 7.5 mg/mL or more, as well as uses thereof and a kit for preparing such a pharmaceutical composition, are described. Uses of such a pharmaceutical composition to obtain plasmatic levels of e.g., trans-3-hexenoyl-GHRH(1-44)-NH2 that are bioequivalent to administration of 2 mg of trans-3-hexenoyl-GHRH(1-44)-NH2 at a concentration of 1 mg/mL in a subject are also described.

Abstract: The present invention provides compositions or formulations comprising the combination of a compound of 5-[3-(4-benzyloxyphenylthio)-fur-2-yl]-imidazolidin-2,4-dione or a salt thereof or hydrate of the foregoing, and a cyclodextrin; or in further combination with an excipient comprising L-Arginine or other additives, wherein the compositions or formulations increases water solubility and oral bioavailability of 5-[3-(4-benzyloxyphenylthio)-fur-2-yl]-imidazolidin-2,4-dione and its related compounds. The method of making or using the compositions or formulations is also disclosed. Such compositions or formulations may be used in treatment of certain diseases including asthma through inhibition of matrix metalloproteinase-12.

Abstract: The present invention relates to a conjugate in which FL118 is linked to an acid-sensitive linker, and an immunoconjugate using the same. The present invention is characterized in that at least one FL118 drug of Formula 1 is linked to an antibody or antigen-binding site-containing fragment thereof through an acid-sensitive linker; wherein after being targeted to cancer cells by an antigen-binding site that targets an antigen of cancer cells, the acid-sensitive linker is degraded in acidic atmosphere around cancer (pH?7) to free at least a part of the FL118 drug of Formula 1 and the free FL118 drug of Formula 1 penetrates a cell membrane and moves into the cells; and wherein FL118 drug of Formula 1 inhibits the action an efflux pump to enrich the intracellular free FL118 drug of Formula 1.

Abstract: The present invention relates to a pyrrolobenzodiazepine dimer prodrug and a ligand-linker conjugate compound thereof, a composition containing these, and therapeutic use thereof particularly as an anticancer drug. The stability of the compounds themselves and the stability thereof in plasma are excellent and the compounds are advantageous in terms of manifestation of toxicity, and thus the compounds are industrially useful in that it is possible to target proliferative diseases such as cancer, to perform a specific treatment, to maximize the drug efficacy, and to minimize the occurrence of side effects.

Abstract: Presented herein, in certain aspects, are conjugates capable of binding phosphatidylserine (PS) and toll-like receptors (TLRs), and their uses for the treatment of selected diseases and disorders, such as cancer.

Abstract: The present disclosure relates to the field of pharmaceutical preparations, dosage regimens, and administration of an antibody-drug conjugate (ADC). More specifically, the ADC is composed of an anti-trophoblast cell surface antigen 2 (TROP2) antibody connected via a linker to an anticancer agent, such as topoisomerase I inhibitor.

Abstract: Provided herein are methods for the treatment of cancers with antibody drug conjugates (ADC) using provided markers.

Abstract: The invention relates to a conjugate for transferring a saponin of the monodesmosidic triterpene glycoside type or of the bidesmosidic triterpene glycoside type from outside a cell into said cell, the conjugate comprising a single-domain antibody, capable of binding to said cell, covalently bound to a saponin. The invention also relates to a pharmaceutical combination comprising a first pharmaceutical composition comprising the conjugate of the invention and a second pharmaceutical composition comprising an active pharmaceutical ingredient, or to a pharmaceutical composition comprising the conjugate of the invention and an active pharmaceutical ingredient. In addition, the invention relates to the pharmaceutical combination of the invention or the pharmaceutical composition of the invention, for use as a medicament, or for use in the treatment or the prophylaxis of a cancer, an auto-immune disease, an infection, an enzyme deficiency, a gene defect.

Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Abstract: The present disclosure provides an antibody-drug conjugate loaded with binary toxins. By connecting MMAF with another drug unit in series at the cysteine binding site on the antibody, the two can exert a significant synergistic effect, thereby effectively improving the effect of killing tumor cells. This provides a new solution for the development of high-efficiency and low-toxic ADCs.

Abstract: Provided herein are methods of treating B-cell proliferative disorders (such as Follicular Lymphoma and diffuse large B cell lymphoma) using immunoconjugates comprising anti-CD79b antibodies in combination with a Bcl-2 inhibitor (such as venetoclax) and an anti-CD20 antibody (such as obinutuzumab or rituximab).

Abstract: The present invention provides specific sites for modifying antibodies or antibody fragments by replacing at least one native amino acid in the constant region of a parental antibody or antibody fragment with cysteine, which can be used as a site of attachment for a payload or linker-payload combination.

Abstract: Provided herein are methods of treating cancer with an antibody that binds an immune cell engager in combination with an antibody-drug conjugate.

Abstract: The present invention provides anti-CLDN18.2 antibody-drug conjugates which are effective for treating and/or preventing cancer diseases associated with cells expressing CLDN18.2, including gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, and cancer of the gallbladder and metastases thereof.

Abstract: Compositions, methods, and uses of recombinant B7-H4 protein or binding motifs to B7-H4 protein that can reduce the immune suppression effect of B7-H4 in relation to T cell activation, proliferation, and conversion. Preferably, the recombinant B7-H4 protein has a plurality of mutations in N-glycosylation residue to reduce its inhibitory effect to T cell activation and proliferation. The recombinant protein having binding motifs to B7-H4 protein preferably includes a binding motif to IgC domain and another binding motif to IgV domain such that the immune-suppressive effects by two Ig-like domains are concurrently reduced.

Abstract: The present disclosure provides a superparamagnetism-modified and neutrophil exosome biomimetic vesicle-based biological preparation for drug delivery, and a preparation method thereof, belonging to the technical field of engineered nanovesicle drug loading systems. The superparamagnetism-modified and neutrophil exosome biomimetic vesicle-based biological preparation for drug delivery prepared by the preparation method acts on tumor cell lines. It is found that the superparamagnetism-modified and neutrophil exosome biomimetic vesicle-based biological preparation for drug delivery can specifically target tumor cells, induce tumor cell apoptosis, and inhibit tumor growth. The biological preparation significantly extends a survival time of mice and improves an efficacy of drugs against cancers.

Abstract: Methods for sensitizing tumors and/or cancers in subjects to therapeutic agents are provided. In some embodiments, the methods include administering to the subject one or more compositions that include an effective amount of an inhibitor of TRIM37 activity. Also provided are methods for sensitizing tumors and/or cancers in subjects to therapeutic agents by administering to the subjects one or more compositions that include an effective amount of an inhibitor of TRIM37 activity and purified and isolated antibodies and fragments thereof that have at least one paratope and further have a linker sequence through which the antibody can be conjugated to a carrier in which the linker sequence includes the amino acid sequence ((X)3Cys(X)3, wherein each X is independently any amino acid.

Abstract: Described herein is a nanoparticle system including a multivalent nanoparticle core having a plurality of ?-hairpin peptides conjugated thereto. Also included are pharmaceutical compositions and methods of making the nanoparticle system. Further included are immunotherapy methods including administering the nanoparticle system to a subject in need thereof, such as a human cancer patient.

Abstract: The present invention concerns a complex comprising an active agent, a polymer and an iron oxide nanoparticle. The complex may also comprise an active agent. Also described are methods of releasing an active agent from the complex, for instance by irradiating the complex with radio waves. Also described are compositions and articles comprising the complex. Also described are methods of therapy and particularly methods of treatment of cancer involving the complex described herein. In addition, the invention concerns a polymer which is particularly useful in preparing the complex described herein. The polymer is capable of undergoing a phase change at a predetermined temperature, such as 39-42° C. In one embodiment, the polymer is a copolymer of N-isopropylacrylamide, acrylic acid and acrolein. In another embodiment, the polymer is a copolymer of N-isopropylacrylamide acrylamide and allyl mercaptan.

Abstract: Provided herein are rAAV and other vectors and compositions useful for treating a patient having CMT2 comprising: (a) a recombinant nucleic acid sequence encoding an engineered human mitofusin 2 coding sequence operably linked to regulatory sequences which direct expression thereof in a human target cell. Also provided are rAAV and other vectors and compositions useful for treating a patient having CMT2 comprising: (b) a nucleic acid sequence encoding at least one miRNA specific for an endogenous human mitofusin 2 sequence in a human CMT2A subject, wherein the miRNA coding sequence is operably linked to regulatory sequences which direct expression thereof in the subject. Further provided are compositions containing both the engineered hMfn2 coding sequence and the at least one miRNA coding sequence, wherein the engineered human mitofusin 2 coding sequence has a sequence which differs from endogenous human mitofusin 2 in the CMT2A patient in the target site of the encoded miRNA.

Abstract: The present invention concerns an expression system for systemic administration comprising a sequence encoding a FKRP protein, and: a promoter sequence allowing the expression at a therapeutically acceptable level of FKRP in the skeletal muscles and a target sequence of an miRNA expressed in the heart; or a promoter sequence allowing the expression at a therapeutically acceptable level of FKRP in the skeletal muscles and presenting a promoter activity at a toxically acceptable level in the heart; and its use for the treatment of various diseases linked to FKRP deficiencies.

Abstract: Provided is an invention based, in part, on novel gene constructs that encode a microdystrophin protein for use in gene therapy. The microdystrophin gene constructs and expression cassettes were engineered for improved therapy with respect to efficacy, potency and safety to the subject when expressed by a viral vector in muscle cells and/or CNS cells.