Abstract: Given developing resistance of tumor cells to current chemotherapeutic and targeted therapeutic agents, novel cancer therapies with enhanced potency and specificity are substantially required. Applicant has provided herein extracellular nanoparticle vesicles that redirect immune effector cells towards cancer cells for killing. Relative to conventional immunotherapeutic antibodies with defined orientation and geometry for their distinct antigen-binding arms, antibodies displayed on spherical exosomes can promote formation of immunological synapses as well as enhanced efficacy to activate immune cells.

Abstract: Disclosed herein are composite polypeptide. According to various embodiments, the composite polypeptide includes a parent polypeptide and a metal binding motif capable of forming a complex with a metal cation. The composite polypeptide may be conjugated with a linker unit having a plurality of functional elements to form a multi-functional molecular construct. Alternatively, multiple composite polypeptides may be conjugated to a linker unit to form a molecular construct, or a polypeptide bundle. Linker units suitable for conjugating with the composite polypeptide having the metal binding motif are also disclosed.

Abstract: The present invention relates to a composition for prevention or treatment of hair loss. The composition is effectively delivered into hair papilla cells in a hair loss area, which is a target area, wherein a cytokine or enzyme highly expressed in the hair loss area causes a drug to be separated from a compound contained in the composition so that the drug effectively exhibits activity, which ultimately promotes hair growth and/or hair regrowth.

Abstract: The present invention provides a method of promoting local bone growth by administering a therapeutic amount of a Sost antagonist to a mammalian patient in need thereof. Preferably, the Sost antagonist is an antibody or FAB fragment selectively recognizing any one of SEQ ID NOS: 1-23. The Sost antagonist may be coadministered together or sequentially with a matrix conducive to anchoring new bone growth. Orthopedic and Periodontal devices comprising an implantable portion adapted to be permanently implanted within a mammalian body and bearing an external coating of a Sost antagonist are also disclosed, as it a method of increasing bone density by administering to a mammalian patient a therapeutic amount of a Sost antagonist together with an antiresorptive drug.

Abstract: This disclosure relates to methods for improving the therapeutic index of a chemotherapeutic drug in the treatment of patients afflicted with cancer, including, for example, reducing chemotherapy-related toxicity (e.g., liver toxicity).

Abstract: The present application is directed to bispecific polypeptides comprising a first domain binding an antigen on an antigen presenting cell (ARC) and a second domain binding an antigen on an immune cell expressing a chimeric antigen receptor (CAR). Nucleic acids, vectors and host cells used in producing the polypeptide of the invention are also disclosed. Compositions comprising the bispecific polypeptides and methods of treating cancer and stimulating activation and expansion of immune cells in vivo and in vitro are also disclosed.

Abstract: The present invention generally relates to methods of theranostic compounds and their use to selectively kill a class of cancer cells. Methods and means related to the treatment of cancers which overexpress the KRAS gene and/or eIF5A gene with inhibitors of eIF5A hypusination, including G7, are disclosed.

Abstract: Antibodies and antigen binding fragments thereof that bind to human protein tyrosine phosphatase beta (HPTP?), and uses thereof.

Abstract: The present invention provides a method of promoting local bone growth by administering a therapeutic amount of a Sost antagonist to a mammalian patient in need thereof. Preferably, the Sost antagonist is an antibody or FAB fragment selectively recognizing any one of SEQ ID NOS: 1-23. The Sost antagonist may be coadministered together or sequentially with a matrix conducive to anchoring new bone growth. Orthopedic and Periodontal devices comprising an implantable portion adapted to be permanently implanted within a mammalian body and bearing an external coating of a Sost antagonist are also disclosed, as it a method of increasing bone density by administering to a mammalian patient a therapeutic amount of a Sost antagonist together with an antiresorptive drug.

Abstract: The present invention provides method of increasing the percentage of monomer in a composition of recombinantly expressed antibody molecules characterised in that the antibody molecule comprises at least one Fv with specificity for an antigen of interest comprising one VH and one VL wherein said VH and VL are connected directly or indirectly via one or more linkers and are stabilised by a disulfide bond therebetween, said method comprises: a) a conversion step of treating the composition with a denaturant selected from urea and/or Guanidine hydrochloride; b) wherein step a) is performed in the presence of a reducing agent or after treatment with a reducing agent.

Abstract: The present invention relates to methods for the treatment of metastatic cancer. Methods of treating metastatic cancer by administration of a set of drugs overcome multiple mechanisms of melphalan resistance and hypersensitize cancer cells to melphalan are described. The methods involve the administration of drug(s) that induce oxidative stress in cancer cells, in conjunction with melphalan on a defined schedule.

Abstract: The disclosure provides stable pharmaceutical compositions comprising an anti-CD79b immunoconjugate and a surfactant. The disclosure also provides methods for using such compositions for the treatment of cancer.

Abstract: The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an intracellular signaling molecule in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

Abstract: The present invention relates to bispecific antibodies that specifically bind a T-cell activating antigen and a Tumor Antigen (TA), comprising a first Fab fragment and a second Fab fragment, wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged; and wherein the bispecific antibody does not comprise a Fc domain; methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Abstract: This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind Calcitonin Gene Related Peptide (CGRP). These anti-CGRP antibodies, or antigen-binding fragments thereof, have a high affinity for CGRP, function to inhibit CGRP, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., a human) and can be used to treat CGRP-associated disorders, while avoiding the adverse side effects associated with the current CGRP antagonist therapies.

Abstract: The invention relates to methods for producing an antibody which is specific for a mutant p53 polypeptide over wildtype p53 polypeptide, comprising using the mutant p53 polypeptide as an immunogen wherein the polypeptide comprises: (i) an antigen sequence, comprising an amino acid sequence of the mutant p53 polypeptide including the mutation and at least one amino acid immediately adjacent to the mutation, and (ii) a scaffold sequence for providing the antigen sequence in a solvent-accessible configuration, in particular wherein the scaffold sequence is thioredoxin. In the specific embodiments, antibodies against mutant p53 comprising R175H, R248Q or R273H are generated. Also disclosed are the uses of the antibodies for diagnosis, prognosis and stratification of patient groups and further encompasses the use of antibodies for imaging and treatment of cancer.

Abstract: A peptide for regulating fat metabolism is described. The peptide is selected from the group consisting of: YLGASVPSPDPLEP (SEQ ID NO: 1); YLNNGLGAPAPYPDPLEP (SEQ ID NO: 4); PDPLEP (SEQ ID NO: 14); and PSPDPLEP (SEQ ID NO: 16).

Abstract: The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and/or survival of NK cells.

Abstract: The present invention generally relates to T-cells, such as CD8+ T-cells, CD4+ T-cells, CD3+ T-cells, ?? T-cells or natural killer (NK) T-cells, transfected/transduced with a fusion protein which is recruited by the use of trivalent, bispecific antibody molecule which specifically binds to/interacts with the extracellular domain of the fusion protein. More precisely, the present invention relates to a kit comprising the nucleic acid molecules, vectors and/or the fusion proteins of the present invention and the trivalent, bispecific antibody molecules of the present invention. Further aspects of the inventions are expression vectors comprising nucleic acid molecules encoding the fusion proteins as well as the trivalent, bispecific antibody molecules. Further, a process for the production of the trivalent, bispecific antibody molecules of the invention and a medicament/pharmaceutical composition comprising said trivalent, bispecific antibody molecules are described.

Abstract: Disclosed herein are immunoconjugates comprising a CD46 binding domain and effector agent. Further provided herein are methods of treating cancer comprising administering to a subject having cancer a pharmaceutical composition comprising immunoconjugates comprising a CD46 binding domain and effector agent.

Abstract: The response of subjects suffering from cancer to MAPK inhibitors is dramatically impaired by secondary resistances and rapid relapse. So far, the molecular mechanisms driving these resistances are not completely understood. The inventors show that expression of 10 SLITRK6 (SLIT and NTRK-like family, member 6) is induced by a MAPK inhibitor (e.g. Vemurafenib) and the inhibition of its induction in presence of the MAPK inhibitor induces synthetic lethality. Thus, the only inhibition of SLITRK6 by an inhibitor of activity or expression should potentiate the antitumor effect of the MAPK inhibitors and avoid the emergence of a resistance to those compounds. Furthermore the specific expression of 15 SLITRK6 also paves the way of strategies based on depletion of the residual cancer cells by targeting them with anti-SLITRK6 antibodies capable of mediating ADCC or antibody-drug conjugates binding to SLITRK6.

Abstract: The invention provides a process for preparing a cell-binding agent chemically coupled to a drug. The process comprises covalently attaching a linker to a cell-binding agent, a purification step, conjugating a drug to the cell-binding agent and a subsequent purification step.

Abstract: The present invention relates to a gene delivery complex comprising: a biocompatible polymer backbone; and pegylated lactoferrin connected to the biocompatible polymer backbone by means of a covalent bond. The gene delivery complex is orally administered into an individual, can be absorbed in vivo by means of a lactoferrin receptor, and enables the in vivo delivery of a target gene and the expression thereof.

Abstract: Combination therapies comprising administering radioimmunoconjugates and one or more checkpoint inhibitors.

Abstract: Disclosed herein are oligonucleotides, such as nucleic acid inhibitor molecules, having a 4?-phosphate analog and methods of using the same, for example, to modulate the expression of a target gene in a cell. The oligonucleotide of the disclosure comprises a 5?-terminal nucleotide represented by Formula III: wherein Ra, Rb, B, X2 and Y are as defined in the specification. The phosphate analogs are bound to the 4?-carbon of the sugar moiety (e.g., a ribose or deoxyribose or analog thereof) of the 5?-terminal nucleotide of an oligonucleotide. Typically, the phosphate analog is an oxymethylphosphonate, where the oxygen atom of the oxymethyl group is bound to the 4?-carbon of the sugar moiety or analog thereof.

Abstract: Herein is reported a method for producing a bispecific antibody comprising the step of incubating (i) an antibody Fab fragment or a scFv antibody comprising within the 20 C-terminal amino acid residues the amino acid sequence LPX1TG (SEQ ID NO: 01), (ii) a one-armed antibody comprising a full length antibody heavy chain, a full length antibody light chain, and an Fc-heavy chain, whereby the full length antibody heavy chain and the full length antibody light chain are cognate antibody chains that thereof forms an antigen binding site, whereby the full length antibody heavy chain and the Fc-heavy chain are covalently linked to each other via one or more disulfide bonds forming an antibody hinge region, and whereby the Fc-heavy chain has an oligoglycine amino acid sequence at its N-terminus, and (iii) a Sortase A enzyme.

Abstract: The invention provides improved methods of conjugating an agent to a thiol moiety in a protein that contains at least one disulfide bond and at least one trisulfide bond. Exemplary embodiments include the production of antibody drug conjugates substantially free of impurities created in the presence of reactive sulfide moieties in the production processes.

Abstract: Methods for the treatment of CD30-expressing cancers are provided. The methods comprise administering to a subject in need thereof a weekly dose of from about 0.8 mg/kg to about 1.8 mg/kg of an antibody-drug conjugate compound having formula (I); or a pharmaceutically acceptable salt thereof; wherein: mAb is an anti-CD30 antibody unit, S is a sulfur atom of the antibody, A- is a Stretcher unit, and p is from about 3 to about 5.

Abstract: The present disclosure relates to compositions and methods of killing cells in vitro or in vivo. In particular examples, the method includes contacting a cell having a cell surface protein with a therapeutically effective amount of an antibody-IR700 molecule, wherein the antibody specifically binds to the cell surface protein. In particular examples the antibody recognizes a tumor-specific antigen on the surface of a tumor cell. The cell is subsequently irradiated, such as at a wavelength of 660 to 740 nm at a dose of at least 1 J cm?2, thereby killing the cell. Also provided are wearable devices that include an article of clothing, jewelry, or covering; and an NIR LED incorporated into the article, which can be used with the disclosed methods.

Abstract: The present disclosure relates to compositions and methods of killing cells. In particular examples, the method includes contacting a cell having a cell surface protein with a therapeutically effective amount of an antibody-IR700 molecule, wherein the antibody specifically binds to the cell surface protein, such as a tumor-specific antigen on the surface of a tumor cell. The cell is subsequently irradiated, such as at a wavelength of 660 to 740 nm at a dose of at least 1 J cm?2. The cell is also contacted with one or more therapeutic agents (such as an anti-cancer agent), for example about 0 to 8 hours after irradiating the cell, thereby killing the cell. Also provided are methods of imaging cell killing in real time, using fluorescence lifetime imaging. Also provided are wearable devices that include an article of clothing, jewelry, or covering; and an NIR LED incorporated into the article, which can be used with the disclosed methods.

Abstract: The present invention relates to novel antibodies that are specific for human serum albumin (HSA).

Abstract: Fusion molecules of a cytokine or portion thereof and a polypeptide which targets the fusion protein to phosphatidylserine, pharmaceutical compositions thereof, and methods for their use in targeting a cytokine or portion thereof to a pathological site and treating a disease or condition responsive to cytokine treatment are provided.

Abstract: This invention relates to stable formulations that can be prepared to high concentration of active agent using low amounts of detergents and to methods for producing such formulations. In particular, this invention relates to formulations containing the L19-TNF? immunocytokine.

Abstract: A modified EGF protein, a production method therefor, and a use thereof are disclosed. The modified EGF protein allows an effective delivery of EGF into the cell and exhibits an enhanced half-life span. A method for producing the modified EGF protein includes culturing conditions where host cell growth phase and protein expression phase employ different temperature conditions. A use of the modified EGF protein is also disclosed.

Abstract: The present disclosure provides methods for prophylactically treating a subject for viral infections comprising topically administering a ranpirnase composition. The disclosure also provides compositions that could be used for prophylactic treatment.

Abstract: The present invention relates to non-membrane disruptive and p53 activating stapled peptides, as well as methods of treatment of cancer involving the use of these peptides. In one embodiment, the peptide comprises or consist of the amino acid sequence of TSFXaa1EY-WXaa3LLXaa2, where Xaa1 is (R)-2-(7?-octenyl)alanine or derivative thereof, or is (R)-2-(4?-pentenyl)alanine or derivative thereof; and Xaa2 and Xaa3 are independently any type of amino acid or modified amino acid. In another embodiment, the peptide comprising or consisting of the amino acid sequence of TSFXaa1EYW Xaa3LLXaa2ENXaa5, wherein Xaa1 and Xaa3 are any type of amino acid or modified amino acid; Xaa2 is S, or P, or (S)-2-(4?-pentenyl)alanine or a derivative of (S)-2-(4?-pentenyl)alanine; and wherein Xaa5 is F or Y.

Abstract: Methods for inhibiting tissue ossification or calcification in a subject, comprising administering a therapeutically effective amount of BMP I inhibitor-loaded microparticles to a subject in need thereof, wherein the administration provides local and sustained release of the BMP I inhibitor thereby inhibiting tissue ossification or calcification.

Abstract: The invention relates to protein conjugates and in particular conjugates of more than two protein or polypeptides. The compounds include a trivalent linker moiety that enables efficient production of desired products.

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: A method of purifying a plurality of metal oxide particles produced from a synthesis process comprising the step of washing a plurality of metal oxide particles in a first solvent composition comprising of at least one aliphatic ether, and at least one flocculant. In one embodiment, the plurality of metal oxide particles are iron oxide particles produced from a thermal decomposition synthesis process between an iron-oleate complex and oleic acid in 1-octadecene, wherein the first solvent composition comprises a 1:1 (vol/vol) ratio of an aliphatic ether in the form of diethyl ether and a flocculant in the form of methanol. The washed iron oxide particles are further washed in a second solvent composition comprising a 1:1 (vol/vol) ratio of hexane and ethanol, and then finally dispersed in hexane. The resulting iron oxide particles find use as a contrast agent for magnetic resonance imaging (MRI) or as magnetic particles in magnetic separation, magnetism-directed targeting or magnetism-induced heating.

Abstract: This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind Programmed Death 1 (PD-1). These PD-1 antibodies, or antigen-binding fragments thereof, have a high affinity for PD-1, function to inhibit PD-1, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., a human), are capable of increasing T-cell proliferation and IL-2 secretion in a mixed lymphocyte reaction, and can be used to treat human diseases (e.g., cancer, infectious diseases, autoimmune diseases, asthma, transplant rejection, and inflammatory disorders).

Abstract: Presented herein, in certain embodiments, are compositions comprising binding agents that specifically bind to syndecan-1 and uses thereof.

Abstract: Novel fusion molecules and uses are disclosed.

Abstract: Drug conjugates of formula [D-(X)b-(AA)w-(L)-]n-Ab wherein: D is a drug moiety having the following formula (I) or a pharmaceutically acceptable salt, ester, solvate, tautomer or stereoisomer thereof, wherein: A is selected from (II) and (III) R1, R2 and R3 is H, ORa, OCORa, OCO—ORa, alkyl, alkenyl, alkynyl, etc.; R3? is, CORa, COORa, CONRaRb, etc; each of R4 to R10 and R12 is alkyl, alkenyl or alkynyl; R11 is H, CORa, COORa, alkyl, alkenyl or alkynyl, or R11 and R12+N+C atoms to which they are attached may form a heterocyclic group; each of R13 and R14 is H, CORa, COORa, alkyl, alkenyl or alkynyl; each Ra and Rb is H, alkyl, alkenyl, alkynyl, etc.

Abstract: The present invention generally relates to compounds comprising antibodies, antigen-binding fragments thereof, polypeptides, and immunoconjugates that bind to TROP2 (TACSTD2). The present invention also relates to methods of using such TROP2-binding molecules for diagnosing and treating diseases, such as malignancies.

Abstract: A closed-loop insulin delivery system is described. More particularly, the presently disclosed insulin delivery system can comprise glucose-responsive vesicles that release insulin in response to hypoxia triggered by enzymatic reduction of glucose. In addition or as an alternative to insulin, the delivery system can release other diabetes treatment agents, such as non-insulin-based diabetes treatment agents. The vesicles can be prepared from a hypoxia sensitive polymer, such as a hypoxia-sensitive hyaluronic acid (HS-HA). The HS-HA can comprise hydrophobic groups that can be reduced in hypoxic environments to form hydrophilic groups. The vesicles can be loaded into microneedles and microneedle array patches for use in the treatment of diabetes or to otherwise regulate blood glucose levels in subjects in need of such treatment.

Abstract: The present invention relates to antibody-drug conjugates (ADCs) wherein a plurality of active agents are conjugated to an antibody through at least one branched linker. The branched linker may comprise a branching unit, and two active agents are coupled to the branching unit through a secondary linker and the branching unit is coupled to the antibody by a primary linker. The active agents may be the same or different. In certain such embodiments, two or more such branched linkers are conjugated to the antibody, e.g., 2-4 branched linkers, which may each be coupled to a different C-terminal cysteine of a heavy or light chain of the antibody. The branched linker may comprise one active agent coupled to the branching unit by a first branch and a second branch that comprises a polyethylene glycol moiety coupled to the branching unit. In certain such embodiments, two or more such branched linkers are conjugated to the antibody, e.g.

Abstract: Novel antibodies, such as single domain antibodies (sdAbs), or fragments thereof that specifically bind a transferrin are described. Compositions, methods and systems for increasing the half-life of a target protein in a serum using an antibody or fragment thereof against a transferrin are described.

Abstract: Disclosed herein, inter alia, are compositions and methods useful for improving detection of analytes. The compositions and methods provided include polymer-wrapped viral particles useful, inter alia, for the detection of PSMA.

Abstract: In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.