Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing proteins or protein domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing proteins or domains, are provided.

Abstract: The present invention includes ENPP1 polypeptides with improved in vivo half-lives. The invention further provides an ENPP1 polypeptide fusion comprising an ENPP1 polypeptide fused to a Fc region of an immunoglobulin, wherein the polypeptide fusion comprises at least one point mutation.

Abstract: The present disclosure relates to a method for obtaining an antibody or antigen-binding fragment thereof that specifically binds to and against a tumor sample, comprising: administering autologous dendritic cells to a subject; taking immune cells and a tumor sample from the subject; constructing an antibody library of the immune cells; and screening the antibody library to obtain the antibody or a fragment thereof specifically binding to and against the tumor sample. The disclosure also relates to a method for engineering immune cells, an antibody or antigen-binding fragment thereof that specifically binds to and against a tumor sample and uses thereof.

Abstract: The present invention relates to an anti-tyrosinase antibody for inhibiting tyrosinase and use thereof, and more particularly, to an anti-tyrosinase antibody including a heavy chain CDR and a light chain CDR of specific sequences, or an antigen-binding fragment thereof. The anti-tyrosinase antibody is expected to be effectively utilized for improving skin whitening or treating skin pigmentation disorders by inhibiting tyrosinase activity.

Abstract: The present disclosure relates to cell penetrating anti-DNA binding proteins. Compositions comprising these binding proteins may be may be useful for delivering agents to cells and treating diseases such as cancer.

Abstract: The present disclosure relates to methods, cells and compositions for producing a product of interest, e.g., a recombinant protein. In particular, the present disclosure provides improved mammalian cells expressing the product of interests, where the cells (e.g., Chinese Hamster Ovary (CHO) cells) have modulated lactogenic activity. The present disclosure also relates to methods and compositions for modulating pyruvate kinase muscle (PKM) expression (e.g., PKM-1 expression) in a mammalian cell to thereby reduce or eliminate the lactogenic activity of the cell, as well compositions comprising a cell having reduced or eliminated lactogenic activity and methods of using the same.

Abstract: Compositions and methods of use thereof for modulating B7-H4 are provided. For example, immunomodulatory agents are provided that reduce B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to increase an immune response in a subject in need thereof. Immunomodulatory agents are also provided that increase B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to reduce an immune response in a subject in need thereof.

Abstract: The present invention relates to the identification of biological markers of ovarian cancer. Specifically, cancer-associated autoantibodies to ANXA1, ARP3, SAHH, SERPH, ARAP1, OTUB1, ATP1A1, UBA1, and CFAH have been identified in subjects with early stage ovarian cancer. These autoantibodies can be utilised for a range of purposes including methods for detecting ovarian cancer, methods for screening for early stage ovarian cancer, and methods for assessing treatment response as well as disease progression and recurrence. The autoantibodies also represent prognostic markers of ovarian cancer development.

Abstract: The present invention provides compositions and methods for treating cancer and inhibiting cytokine release syndrome (CRS). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of a CD40 antagonist or a CAR-T cell expressing a CD40 antagonist in combination with a therapeutically effective amount of a CD3 multispecific antigen binding molecule.

Abstract: This invention is directed to recombinant Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) arrays and recombinant nucleic acid constructs encoding Type 1-E CASCADE complexes, plasmids, retroviruses and bacteriophage comprising the same, and methods of use thereof for modifying genomes and expression. Further disclosed are methods of modifying (editing) the genome of target organisms using the constructs.

Abstract: This invention relates to recombinant Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) arrays and recombinant nucleic acid constructs encoding Type I-E CASCADE complexes, plasmids, retroviruses and bacteriophage comprising the same, and methods of use thereof for killing one or more cells in a population of bacterial and/or archaeal cells.

Abstract: The present disclosure provides humanized antibodies and antigen-binding fragments thereof that specifically bind to SFRP2 and compositions comprising such humanized antibodies or antigen-binding fragments thereof. In some aspects, the humanized antibodies or antigen-binding fragments can be used to treat diseases or conditions associated with increased SFRP2, such as cancer. In some aspects, the antibodies or antigen-binding fragments can be used to treat osteosarcoma.

Abstract: The present invention provides bispecific antibody constructs characterized by comprising a first domain binding to MUC17, a second domain binding to an extracellular epitope of the human and the Macaca CD3? chain and optionally a third domain, which is a specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

Abstract: Anti-tumour immune responses to modified self-epitopes. The present invention relates to the use of tumour-associated epitopes in medicine and in particular in the treatment of cancer. The epitopes stimulate an immune reaction against the tumour and have a modification selected from deimination of arginine to citrulline, nitration of tyrosine, oxidation of tryptophan and deamination of glutamine or asparagine. The invention also relates to nucleic acids comprising sequences that encode such epitopes for use in the treatment of cancer.

Abstract: The invention disclosed concerns a fixed dose combination (FDC) of pertuzumab, trastuzumab, and, optionally, recombinant human hyaluronidase (rHuPH20), which is administered subcutaneously to patients. The final efficacy and safety data for the FeDeriCa clinical trial, United States Prescribing Information (USPI) (including home-use) methods, and primary analysis of the PHranceSCa clinical trial are disclosed and claimed.

Abstract: The present disclosure is related to systems and methods to be used as aids in the diagnosis of risk for oral cancer, potentially malignant oral lesion (PMOL), and/or oral epithelial dysplasia (OED) by identifying cellular phenotype characteristics of cell samples, including percentage of mature squamous cells, presence or absence of nuclear actin in mature squamous cells, percentage of non-mature squamous cells, percentage of small round cells, percentage of white blood cells, and percentage of lone nuclei.

Abstract: A method and system for determining one or more sources of a cell free deoxyribonucleic acid (cfDNA) test sample from a test subject. The cfDNA test sample contains a plurality of deoxyribonucleic acid (DNA) molecules with numerous CpG sites that may be methylated or unmethylated. A trained deconvolution model comprises a plurality of methylation parameters, including a methylation level at each CpG site for each source, and a function relating a sample vector as input and a source of origin prediction as output. The method generates a test sample vector comprising a site methylation metric relating to DNA molecules from the test sample that are methylated at that CpG site. The method inputs the test sample vector into the trained deconvolution model to generate a source of origin prediction indicating a predicted DNA molecule contribution of each source.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.

Abstract: Provided are cytokine fusion proteins comprising a first cytokine fused to a second cytokine, for example, interleukin-2 (IL-2) or interferon-? (IFN-?) fused to the N-terminus of tumor necrosis factor-? (TNF-?), and related compositions and methods of use thereof for treating cancers, either as standalone agents or in combination with autologous tumor vaccines and/or immune checkpoint modulatory agents.

Abstract: The specification relates generally to the post-genomic identification of therapeutic targets and agents. In particular the specification relates to PSMD9 inhibitors and methods for preventing or treating metabolic disorders such as fatty liver disease that are associated with dysregulation of lipid homeostasis.