Abstract: Provided herein are single-chain chimeric polypeptides that include: (i) a first target-binding domain; (ii) a soluble tissue factor domain; and (iii) a second target-binding domain. Also provided here are methods of using these single-chain chimeric polypeptides and nucleic acids encoding these single-chain chimeric polypeptides.

Abstract: The present disclosure provides antibodies specific for Mucin 1. Nucleic acids that encode one or both of the variable chains of an antibody of the present disclosure are also provided, as are cells that include such nucleic acids. Also provided are compositions that include the antibodies of the present disclosure, including in some instances, pharmaceutical compositions. Methods of making and using the antibodies of the present disclosure are also provided. In certain aspects, provided are methods that include administering to an individual having a cell proliferative disorder a therapeutically effective amount of an antibody of the present disclosure, where the antibody is administered to the individual to enhance an immune response, e.g., a T cell response, to abnormally proliferating cells of the cell proliferative disorder. The antibodies are also useful in various diagnostic, and monitoring applications, which are also provided.

Abstract: Provided herein is an implant for delivering a hydrophobic active agent to a target tissue. The implant may include a scaffold defining a first surface and a second surface opposite the first surface, wherein the scaffold is substantially impermeable to a hydrophobic active agent, and a silicone tubing having a wall permeable to the active agent, wherein a first length of the silicone tubing is affixed to the first surface of the scaffold, wherein the two ends of the silicone tubing extend from the first surface, and wherein a path outlined by a second length of the tubing within the first length is circuitous. Also provided is a method of using the implant to locally deliver a hydrophobic active agent to a target tissue, and kits that find use in performing the present method.

Abstract: The present invention provides engineered Natural Killer (NK) cells and methods of producing engineered NK cells. The engineered NK cells and compositions containing the engineered NK cells are useful for treating diseases such as cancer.

Abstract: The present invention relates to the diagnostic of cancerous subject. Indeed, the inventors observed by using a Q-PCR based methods and sequencing methods that quantification of specific single stranded DNA fragments obtained from cell free nucleic acids (cfDNA) may discriminate cfDNA from healthy and cancer derived subjects. Single stranded DNA fragments obtained from CfDNA or specific range of single stranded DNA fragments are rather lower or higher when derived from healthy subject than from cancer subject. More, specific ratios for different size or range of single stranded DNA fragments varies between cancer subjects and healthy individuals. These values are sufficiently and significantly different to be used as values to determine whether a human subject may have cancer or not as a screening test.

Abstract: An object of the present invention is to provide a bispecific antibody comprising an antigen-binding domain that binds to CD40 and an antigen-binding domain that binds to an epithelial cell adhesion molecule (EpCAM). The present invention relates to a bispecific antibody comprising an antigen-binding domain that binds to CD40 and an antigen-binding domain that binds to EpCAM.

Abstract: The present invention relates to pathogen-resistant plants. In one aspect, plants comprising a heterologous expression cassette are provided, wherein the expression cassette comprises a polynucleotide that inhibits expression of a fungal pathogen gene and wherein the plant has increased resistance to a fungal pathogen or multiple pathogens compared to a control plant lacking the expression cassette. In another aspect, contacting a plant or a plant part with double stranded RNAs or small RNAs that inhibit expression of a fungal target gene or genes from multiple pathogens, wherein the plant has increased resistance to a pathogen or multiple pathogens compared to control plants that has not been contacted with the RNAs. Methods of making and cultivating pathogen-resistant plants are also provided.

Abstract: A method of detecting the presence of a prostate cancer in a human subject comprising the steps of (a) obtaining a histologically normal prostate tissue sample from the patient and (b) quantifying the epithelial thickness or gland lumen roundness of the tissue, wherein an increase in epithelial thickness or a decrease in gland lumen roundness indicates the presence of prostate cancer or a prostate cancer field defect.

Abstract: The present application provides a recombinant fusion protein containing an anti-PD-L1 antibody or an antibody fragment thereof, with each paratope of the anti-PD-L1 antibody or antibody fragment thereof linked via a linker to an extracellular Ig-like domain of a signal-regulatory protein (SIRP) at N-terminus of a heavy chain variable region or a light chain variable region constituting the paratope, wherein the recombinant fusion protein can bind to CD47, PD-L1 and FcR simultaneously. The present application also provides a nucleic acid molecule encoding the recombinant fusion protein, an expression vector containing the nucleic acid molecule, a method for producing the recombinant fusion protein and a method for treating a disease associated with over-expression of CD47 and/or PD-L1 using the recombinant fusion protein.

Abstract: Fixed dose HER2 antibody formulations for subcutaneous administration are provided along with their use in the treatment of cancer. The formulations include fixed dose subcutaneous formulations of pertuzumab and subcutaneous co-formulations of pertuzumab and trastuzumab, and their use in the treatment of cancer.

Abstract: Provided herein are methods of treating cancer using agonistic antibodies that specifically bind to immunostimulatory receptors, wherein the antibodies are administered in an amount and/or frequency sufficient to achieve and/or maintain a receptor occupancy of less than about 80%, for example, a receptor occupancy of about 20% to about 80%. Also provided are methods of determining human doses for such agonistic antibodies, and methods for monitoring receptor occupancy of the agonistic antibodies in order to maintain effective antibody levels in, e.g., human patients. Also provided are methods of measuring soluble OX40 in a subject. Also provided are methods of treating cancer, comprising administering to the subject an effective amount of each of an anti-OX40 antibody and an anti-PD-1 antibody.

Abstract: The present invention relates to the field of the production, identification and selection of biological binding molecules such as antibodies or fragments thereof, as well as to their use in the therapy and prophylaxis of cancer diseases, such as, in particular, malignant B-cell neoplasia. The binding molecules are able to selectively bind to autonomously active or autonomously activated B-cell receptors, the autonomously active or autonomously activated B-cell receptors being characterized by the presence of structural domains to which the binding molecule selectively binds and which are responsible for the autonomously active or autonomously activated state of the B-cell receptors.

Abstract: Methods are provided for treating a subject having a MYC-driven neoplasia. Aspects of the methods include administering to the subject an amount of an inhibitor of a target gene effective to treat the subject for the MYC-driven neoplasia. Methods are also provided for identifying a MYC-dependent target gene in a MYC-driven neoplasia. Aspects of the method include identifying the MYC-dependent target gene based on a phenotype detected in a first tumor cell line conditionally expressing MYC that is absent or quantitatively different in a second tumor cell line conditionally repressing MYC when the two cell lines are contacted with a CRISPR-based gene silencing agent. Kits and cell lines for practicing the methods of the disclosure are also provided.

Abstract: The present invention provides for purified or highly pure recombinant monoclonal antibodies that bind to human colorectal and pancreatic carcinoma-associated antigens (CPAA), along with nucleic acid sequences encoding the antibody chains, and the amino acid sequences corresponding to said nucleic acids and uses for said sequences.

Abstract: Disclosed are surprising new methods and kits for treating patients, particularly cancer patients, using bavituximab in combination therapies with immuno-oncology (IO) agents such as checkpoint inhibitor antibodies. The methods and kits are based on the surprising finding that human patients treated with bavituximab and checkpoint inhibitor antibodies have a statistically significant prolonged survival in controlled studies.

Abstract: The disclosure provides novel antigen-binding proteins that bind STEAP1 and methods of use.

Abstract: The invention relates to monoclonal antibodies, in particular against a peptide of the BAMBI protein, as well as the uses thereof and methods comprising same. Preferably, the antibodies are used for the treatment of autoimmune diseases.

Abstract: In certain embodiments, described herein is a method of treating a subject infected with a pathogen encoding an Fc-binding protein comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an Fc region of an immunoglobulin G antibody. Also described herein is a method for treating cancer in a subject undergoing oncolytic viral therapy comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an Fc region of an immunoglobulin G antibody. Further described herein is a method of activating natural killer (NK) cells in a subject infected with a pathogen, comprising administering to the subject a pharmaceutical composition comprising an Fc region of an immunoglobulin G antibody.

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: The present invention provides for diagnostic kits for identifying cancer patients who are more susceptible to cancer therapies employing endostatin and other angiogenesis inhibitors, based upon the discovery that Nucleolin is a specific receptor for Endostatin. In particular, the diagnostic kits include antibody molecules against Nucleolin, DNA or RNA molecules that specifically bind to nucleic acid molecules encoding Nucleolin. The present invention also discloses methods of screening for angiogenesis inhibitors which specifically interact with Nucleolin, and act as angiogenesis inhibitors in an analogous manner as Endostatin. In addition, the present invention discloses methods of inhibiting the proliferation of endothelial cells or angiogenesis of tumor by administering an anti-nucleolin antibody linked to a cytotoxic agent such as tumor necrosis factor alpha to the endothelial cells.

Abstract: Provided herein are single-chain chimeric polypeptides that include: (i) a first target-binding domain; (ii) a soluble tissue factor domain; and (iii) a second target-binding domain. Also provided here are methods of using these single-chain chimeric polypeptides and nucleic acids encoding these single-chain chimeric polypeptides.

Abstract: The present invention relates to a heterotandem bicyclic peptide complex which comprises a first peptide ligand, which binds to EphA2, conjugated via a linker to two second peptide ligands, which bind to CD137. The invention also relates to the use of said heterotandem bicyclic peptide complex in preventing, suppressing or treating cancer.

Abstract: The present invention replaces an amino acid residue of a specific region of a parent antibody so as to improve the stability of the antibody, thereby improving druggability. A variant antibody of the present invention, compared to a parent antibody hz1E11, has significantly improved stability while having nearly the same productivity and efficacy. Therefore, the variant antibody of the present invention exhibits, in the development of HER2-specific antibodies, excellent characteristics such as reduction in production costs, inhibition of efficacy reduction and reduction of side effects.

Abstract: The present invention provides antibody polypeptides with binding specificity for human kallikrein-2 (hK2), wherein the antibody polypeptide comprises (a) a heavy chain variable region comprising the amino acid sequences of SEQ ID NO:1 and SEQ ID NO:2 and SEQ ID NO:3 and/or (b) a light chain variable region comprising the amino acid sequences of SEQ ID NO:4 and SEQ ID NO:5 and SEQ ID NO:6, and wherein the heavy chain variable region and light chain variable region comprise framework amino acid sequences from one or more human antibodies. The invention further provides use of said antibody polypeptides in the diagnosis and treatment of prostate cancer.

Abstract: The present invention relates to a modified natural killer (NK) cell and its use in personalised medicine. The modified NK cells of the present invention are non-immunogenic, meaning that they are able to be administered to any recipient subject without being rejected by the host immune system (they are “universal”). In a first embodiment the non-immunogenic NK cells are modified to express CD3 to allow a T-cell Receptor (TcR) to be expressed. In a further embodiment the non-immunogenic NK cells are further modified to express a TcR together with the CD3 co-receptor. Co-expression of CD3 with a specific TcR results in the modified NK cells showing antigen-specific cytotoxicity towards target cells. Universal NK cells can thus be targeted against specific antigens, and may thus be used in personalised medicine, particularly in the field of oncology.

Abstract: Provided are a LAG-3 antibody, an antigen-binding fragment thereof, and a pharmaceutical application thereof. Further, provided are a chimeric antibody comprising a CDR of the LAG-3 antibody, a humanized antibody, a pharmaceutical composition comprising the LAG-3 antibody and the antigen-binding fragment thereof, and an application of the pharmaceutical composition as an antineoplastic drug. Particularly, provided is an application of a humanized LAG-3 antibody in preparation of drugs for treatment of diseases involving immune cells.

Abstract: Provided herein is a conjugate comprising two residues of structurally and/or mechanistically different anticancer bioactive agents, coupled to one another by a biocleavable linking moiety, as well as methods of treating cancer using the same and pharmaceutical compositions comprising the same.

Abstract: The present invention relates to a microbubble complex comprising a microbubble having an outer shell comprising a mixture of native and denatured albumin encapsulating a perfluorocarbon gas, a therapeutic agent, a bifunctional linker having one end attached to the therapeutic agent and the other attached to a ligand and wherein the ligand is bound to the other shell of the microbubble through hydrophobic interactions. Also included are methods for delivering the aforementioned microbubble complex to a tissue target.

Abstract: An immunoconjugate includes an anti-Globo H antibody, or a binding fragment thereof, and a therapeutic agent or a label, having the formula: Ab?(L?D)m, wherein Ab is the anti-Globo H antibody or the binding fragment thereof, L is a linker or a direct bond, D is the therapeutic agent or the label, and m is an integer from 1 to 8. The antibody may be a monoclonal antibody, which may be a humanized antibody. A method for treating a cancer includes administering to a subject in need of such treatment a pharmaceutically effective amount of an immunoconjugate containing an antibody against Globo H, or a binding fragment thereof, and a therapeutic agent covalently conjugated with the antibody.

Abstract: Methods and compositions are provided for improved nucleic acid amplification assays. In some embodiments, the nucleic acid amplification assay is a tagged amplicon primer extension (TAPE) nucleic acid amplification reaction.

Abstract: A novel and thermostable lyophilized pharmaceutical composition of Romiplostim (Fcpeptide fusion protein) along with buffer, bulking agent, stabilizer, and surfactant at pH range of 4.0-6.0.

Abstract: The present disclosure relates to isolated polypeptides that inhibit Wnt signaling, pharmaceutical compositions comprising the isolated polypeptides, and methods of use thereof. Nucleic acids, cells, and methods of production related to the isolated polypeptides and compositions are also disclosed.

Abstract: The invention relates to treating individuals with cancer by using blood plasma or blood plasma fractions as treatment.

Abstract: This invention relates to binding molecules that bind specifically to TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) and cadherin-17 (CDH17) and their use in medicine, pharmaceutical compositions comprising the same, and methods of using the same as agents for treatment and/or prevention of cancer.

Abstract: The present invention relates to methods of cancer therapy using subcutaneous administration of antibody-drug conjugates (ADCs). Preferably, the ADC comprises an antibody that binds to Trop-2, CEACAM5, CEACAM6, CD20, CD22, CD30, CD46, CD74, Her-2, folate receptor, or HLA-DR. More preferably, the drug is SN-38. Subcutaneous administration is at least as effective as intravenous administration of the same ADC. Surprisingly, subcutaneous administration can be used without inducing unmanageable adverse local toxicity at the injection site. Subcutaneous administration is advantageous in requiring less frequent administration, substantially reducing the amount of time required for intravenous administration, and reducing the levels of systemic toxicities observed with intravenous administration.

Abstract: This invention relates to prostate-specific membrane antigen (PSMA) antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are ?PSMA antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the ?PSMA antibodies of the invention are conjugated to one or more toxins. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, dolastatin analogs, and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a 5T4 monoclonal antibody, conferring specific immunity against 5T4 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia, and for solid tumors such as colon, stomach, and ovarian tumors.

Abstract: The invention relates to classification, diagnosis and treatment of cancers. In one embodiment, the present invention provides methods and kits that classify cancers into various subtypes based on expression patterns of AKT pathway components. In another embodiment, the present invention provides methods and kits that diagnose cancer subtypes by evaluating expression patterns of AKT pathway components. In still another embodiment, the present invention provides methods and kits that treat a cancer subtype by administering an alkylating agent or a PI3K/AKT/mTOR inhibitor to a patient. Cancers suitable with various embodiments of the invention include but are not limited to brain tumors, gliomas and GBM.

Abstract: Described herein are Fc variants and methods for the efficient production of antibodies and other multimeric protein complexes (collectively referred to herein as heteromultimeric proteins). Heteromultimeric proteins may be capable of specifically binding to more than one target. The targets may be, for example, different epitopes on a single molecule or located on different molecules. The methods combine efficient, high gene expression level, appropriate assembly, and ease of purification for the heteromultimeric proteins. The invention also provides methods of using these heteromultimeric proteins, and compositions, kits and articles of manufacture comprising these antibodies.

Abstract: The present invention comprises compositions, methods, and devices for enhancing an endogenous immune response against a cancer. Devices and methods provide therapeutic immunity to subjects against cancer.

Abstract: The present invention relates to methods of using the expression of ILTL3 ligand or ILT3 on certain types of cancer cells as a diagnostic tool. Methods are provided for treating ILT3-ligand expressing cancers, such as T-cell acute lymphoblastic leukemia (T-cell acute lymphoblastic leukemia), for example by administering ILT3, the extracellular domain of ILT3 or ILT3Fc conjugated to a cytotoxic agent to kill the targeted cancer cell. Other methods are provided for treating cancers that express ILT3 on their surface, such as monocytic forms of AML, for example by administering anti-ILT3 antibodies conjugated to a cytotoxic agent.

Abstract: The present invention contemplates use of encapsulated aqueous and non-aqueous reagents, solutions and solvents and their use in laboratory procedures. These encapsulated aqueous or non-aqueous reagents, solutions and solvents can be completely contained or encapsulated in microcapsules or nanocapsules that can be added to an aqueous or non-aqueous carrier solution or liquid required for medical and research laboratory testing of biological or non-biological specimens.

Abstract: Disclosed is a tumor-targeting fusion protein comprising at least (i) a IL-15 peptide or a variant or functional fragment thereof, (ii) a IL-15R? polypeptide or a variant or functional fragment thereof, (iii) a Fc domain or a variant or functional fragment thereof, and (iv) a RGD polypeptide or a variant thereof. The fusion protein is preferably configured as RGD polypeptide-Fc domain-IL-15 polypeptide-IL-15R? polypeptide. The tumor-targeting fusion proteins provided herein improves the anti-tumor effects of IL-15 and prolongs the half-life of IL-15, while targeting tumor sites and acting upon tumor cells. In addition, the fusion proteins are capable of being expressed at high efficiency and purified. The high efficiency of anti-tumor activity enables the fusion proteins to be an excellent candidate for tumor immunotherapy.

Abstract: Evaluations of a document are generated that indicate likelihoods of the document achieving its objectives. The evaluations are based on predictive characteristics of one or more outcomes of the client document that are indicative of whether the document will achieve its objectives. Specifically, a server receives the document from a client device. The server extracts a set of features from the document. The evaluations of the document are generated based on the predictive characteristics for the one or more outcomes of the document. The generated evaluations are provided to the client device such that the document can be optimized to achieve its desired objectives. The optimized document may also be sent to a posting server for posting to a computer network. The known outcomes of the optimized document are collected through reader responses to the document and analyzed to improve evaluations for other documents.

Abstract: The invention provides the identification of oncogenic pathways activated in cytologically normal airway cells of individuals having or at risk of having lung disease, as well as specific gene expression patterns (biomarkers) associated with pathway activation. These biomarkers and pathways may provide prognostic and/or diagnostic indicators in lung disease, e.g., lung cancer. Additionally, these pathways and biomarkers may provide therapeutic targets for the treatment of lung disease, as well as markers for the assessment of treatment efficacy.

Abstract: Provided is a composition containing neuropeptide Y for inhibiting side effects of anticancer agents. The neuropeptide Y of the present invention exhibits an effect of mitigating side effects, especially bone marrow injury and neurological disorders, occurring due to the administration of anticancer agents, and thus may be useful as an anticancer adjuvant which may mitigate side effects of anticancer agents and enhance the effect of anticancer agents.

Abstract: Provided herein are antigen-binding proteins (ABPs) that selectively bind to TIGIT and its isoforms and homologs, and compositions comprising the ABPs. Also provided are methods of using the ABPs, such as therapeutic and diagnostic methods.

Abstract: The present invention relates to, inter alia, compositions and methods, including chimeric proteins that find use in the treatment of disease, such as immunotherapies for cancer and autoimmunity. In part, the invention provides, in various embodiments, fusions of extracellular domains of transmembrane proteins that can have stimulatory or inhibitory effects.

Abstract: A pharmaceutical composition for use in promoting wound healing and/or accelerating closure of an open wound in a subject in need thereof is disclosed. The composition comprises a therapeutically effective amount of a recombinant polypeptide comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 2; and a pharmaceutically acceptable vehicle, carrier, diluent, excipients, and/or salt.

Abstract: In some aspects, the present disclosure provides compositions comprising an N4-based MMC ligand, a cell targeting group, and a fluorophore or a therapeutic compound comprising a formula: wherein the variables are as defined herein. In some embodiments, these compositions may be used in the imaging techniques or in the treatment of a disease or disorder such as cancer.