Abstract: This disclosure relates to an animal model of human disease. More specifically, this disclosure relates to a rodent model of mood disorders such as unipolar depression and an anxiety disorder. Disclosed herein are genetically modified rodent animals that carry a humanized G protein-coupled receptor 156 (GPR156) gene that encodes a mutant human GPR156 protein comprising Asp at an amino acid position corresponding to position 533 in a full length wild type human GPR156 protein.

Abstract: The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human MUC16. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing MUC16, such as ovarian tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TRKB locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TRKB locus express a human TRKB protein or a chimeric transthyretin protein, fragments of which are from human TRKB. Methods are provided for using such non-human animals comprising a humanized TRKB locus to assess in vivo efficacy of human-TRKB-targeting reagents such as nuclease agents designed to target human TRKB.

Abstract: A genetically modified rodent is provided that comprises a modified Acvr1 gene that comprises a conditional altered exon 7 encoding R258G in anti sense orientation, flanked by site-specific recombinase recognition sites, wherein the altered exon is inverted to sense orientation upon action of a recombinase, resulting in ectopic bone formation.

Abstract: The present disclosure provides aseptic vial piercing and sterilization systems, and methods of assembling, using and sterilizing same. The systems and methods utilize a pre-sterilized primary container including a first end, a first cavity, a second end with an opening in communication with the first cavity, a septum at least partially sealing the opening, and a product within the first cavity. The systems and methods include an injection assembly including a first end portion of a hollow flowpath forming member. The injection assembly and the primary container may be assembled in a non-sterile environment to form a second cavity extending about the first end portion of the flowpath forming member and to the primary container. The second cavity may then be selectively sterilized in a non-deleterious manner to the product to allow the first end portion to aseptically pierce the septum to extend into the first cavity.

Abstract: B-cell maturation antigen (BCMA) is expressed on malignant plasma cells. The present invention provides novel bispecific antibodies (bsAbs) that bind to both BCMA and CD3 and activate T cells via the CD3 complex in the presence of BCMA-expressing tumor cells. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing BCMA. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced BCMA-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including multiple myeloma.

Abstract: Methods and system for identifying and/or quantifying a protein are provided herein.

Abstract: In situ Raman spectroscopy methods and systems for characterizing or quantifying a protein purification intermediate and/or final concentrated pool during production or manufacture are provided. In one embodiment, in situ Raman spectroscopy is used to characterize or quantify protein purification intermediates critical quality attributes during downstream processing (i.e., after harvest of the protein purification intermediate). For example, the disclosed in situ Raman spectroscopy methods and systems can be used to characterize and quantify protein purification intermediates as the protein purification intermediates are purified, condensed, or otherwise formulated into the final drug product to be sold or administered.

Abstract: Methods of predicting an in vivo serum concentration of an antibody with a post-translational modification of interest after administration of the antibody are provided, as are methods for predicting a subject's exposure to post-translational variants of the antibody. The methods include predicting a percentage of the antibody with the post-translational modification of interest using an in vivo rate constant determined for the post-translational modification, and multiplying the predicted percentage of the antibody with the post-translational modification of interest by the in vivo concentration of the antibody to determine the concentration of the antibody with the post-translational modification of interest.

Abstract: Embodiments of the present disclosure are directed to methods and systems for assessing integrity of chromatography columns, systems, and processes. The methods and systems can comprise one or more of extracting a block and signal combination for analysis, performing a transition analysis, performing one or more statistical process controls, and/or implementing in-process controls based on the statistical process controls.

Abstract: Stable lyophilized therapeutic protein compositions and their methods of manufacture are provided. Specifically, the use of water as a solid cake plasticizer and protein stabilizer is described. Also, the inclusion of a multicomponent stabilizer comprising a larger molecular entity and a smaller molecular entity is described. Also, the inclusion of post-drying annealing under certain conditions improves protein stability. Proteins are predicted to remain stable over 24 months at 25° C.

Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion in an immunoglobulin constant region CH1 gene (optionally a deletion in a hinge region) of an IgG, IgA, IgD, and/or IgE, and wherein the mouse is capable of expressing a functional IgM. Genetically modified mice are described, including mice having a functional IgM gene and modified to have a deletion of a CH1 domain and a hinge region in a heavy chain constant domain that is not an IgM, e.g., in an IgG heavy chain constant domain. Genetically modified mice that make human variable/mouse constant chimeric heavy chain antibodies (antibodies that lack a light chain), fully mouse heavy chain antibodies, or fully human heavy chain antibodies are provided.

Abstract: Genetically modified non-human animals are provided that express an immunoglobulin variable domain that comprises at least one histidine, wherein the at least one histidine is encoded by a substitution of a non-histidine codon in the germline of the animal with a histidine codon, or the insertion of a histidine codon in a germline immunoglobulin nucleic acid sequence. Immunoglobulin genes comprising histidines in one or more CDRs, in an N-terminal region, and/or in a loop 4 region are also provided. Immunoglobulin variable domains comprising one or more histidines (e.g., histidine clusters) substituted for non-antigen-binding non-histidine residues. Non-human animals that are progeny of animals comprising modified heavy chain variable loci (V, D, J segments), modified light chain variable loci (V, J segments), and rearranged germline light chain genes (VJ sequences) are also provided. Non-human animals that make immunoglobulin domains that bind antigens in a pH-sensitive manner are provided.

Abstract: A method of controlling a bioreactor system includes providing a cell culture in a bioreactor, wherein conditions in the bioreactor enable the cell culture to produce a protein of interest (POI), measuring process parameters (PPs) of the culture within the bioreactor by RAMAN, wherein the process parameters are selected from the group consisting of nutrient concentration, viable cell concentration, and protein attributes, measuring a predetermined weight of the bioreactor with the cell culture, removing cell-free spent media from the cell culture using a first output conduit at a first specified rate, removing cells from the cell culture using a second output conduit at a second specified rate, and introducing one or both of fresh media or nutrients into the cell culture using an input conduit at a third specified rate.

Abstract: The present disclosure provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present disclosure can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the disclosure, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present disclosure results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone.

Abstract: A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses a single light chain variable domain derived from a single rearranged light chain variable region gene in the germline of the non-human animal, wherein the single rearranged light chain variable region gene comprises a substitution of at least one non-histidine encoding codon with a histidine encoding codon. Methods of making non-human animals that express antibodies comprising a histidine-containing universal light chain are provided.

Abstract: The present disclosure pertains to compositions comprising anti-VEGF proteins and methods for producing such compositions.

Abstract: The present disclosure pertains to compositions comprising aflibercept and methods for producing such compositions in chemically defined media and using chromatography to reduce amounts of certain aflibercept variants.

Abstract: A bispecific antibody format providing ease of isolation is provided, comprising immunoglobulin heavy chain variable domains that are differentially modified in the CH3 domain, wherein the differential modifications are non-immunogenic or substantially non-immunogenic with respect to the CH3 modifications, and at least one of the modifications results in a differential affinity for the bispecific antibody for an affinity reagent such as Protein A, and the bispecific antibody is isolable from a disrupted cell, from medium, or from a mixture of antibodies based on its affinity for Protein A.

Abstract: According to one aspect of the disclosure, packaging for a sterile syringe having a nominal size of less than 1 mL may include a flexible tray having a cavity for containing the syringe. The cavity may include an opening, one or more sidewalls, and a base. A lip may surround the opening, may extend radially outward from the cavity, and may define a periphery of the tray. A removable cover may have a periphery that is adhered to the lip, and the removable cover may be permeable to a gaseous sterilant, including one or more of vaporized hydrogen peroxide or ethylene oxide. A projection may be associated with the base of the cavity and may extend away from the base of the cavity in a direction opposite to the opening of the cavity.