Abstract: The disclosure discloses a preparation of type I collagen-like fibers and a method for regulating and controlling the periodic length of fiber stripes thereof, belonging to the technical field of genetic engineering. The disclosure produces a three-segment chimeric collagen P-CL-P pattern by inserting a continuous Gly-Xaa-Yaa triplet collagen sequence in the middle based on the N- and C-terminal (GPP)n sequences. The self-assembly is driven by the interaction between the N- and C-terminal (GPP)n triple helixes to form banded fibers with periodic bright and dark stripes. According to the method of the disclosure, a fiber from a clean source, which can self-assemble to form periodic bright and dark stripes can be prepared, the structure of which is similar to type I collagen, the preparation process is simple, the collagen fiber with low cost can be produced on a large scale, and the method has broad application prospects in the field of biological materials.

Abstract: The invention herein described, provides, among other things, self-buffering protein formulations. Particularly, the invention provides self-buffering pharmaceutical protein formulations that are suitable for veterinary and human medical use. The self-buffering protein formulations are substantially free of other buffering agents, stably maintain pH for the extended time periods involved in the distribution and storage of pharmaceutical proteins for veterinary and human medical use. The invention further provides methods for designing, making, and using the formulation. In addition to other advantages, the formulations avoid the disadvantages associated with the buffering agents conventionally used in current formulations of proteins for pharmaceutical use.

Abstract: Provided by the present invention is a chimeric antigen receptor comprising a co-stimulatory receptor, the chimeric antigen receptor having a structure of scFv(X)-(Y)CD3zeta-2A-(Z); X comprises a tumortargeting antibody or a ligand or receptor capable of specifically binding to a tumor; Y is an intracellular region of the co-stimulatory receptor, and Z is a co-stimulatory receptor that is selected from among ICOS, CD28, CD27, HVEM, LIGHT, CD40L, 4-1BB, OX40, DR3, GITR, CD30, TIMI, SLAM, CD2, CD226. Further provided by the present invention are CAR-T cells that are constructed by means of a recombinant expression vector of the described chimeric antigen receptor, a preparation method therefor and an application thereof. The CAR-T cells described in the present invention significantly improve the tumor-killing abilities and amplification abilities thereof.

Abstract: The presently disclosed subject matter relates to compositions, systems and methods of screening one or more species of polypeptide in a complex mixture of polypeptides, e.g., multi-subunit proteins. For example, the subject matter relates to ligands used in connection with affinity capillary electrophoresis, as well as methods and systems for detecting polypeptides in a mixture of multimers that include multispecific antibodies, e.g., bispecific antibodies.

Abstract: Provided are compositions for increasing the half-life of a polypeptide or polypeptides in a canine and methods of their use. The compositions involve variant canine IgG Fc regions.

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: The invention provides a recombinant chimeric antigen receptor (CAR) gene, a vector containing the same, a CAR-T cell and a use thereof. The recombinant CAR gene comprises a nucleic acid sequence encoding an antigen-binding portion of a CD30 antibody, a transmembrane portion and a CD137 cytoplasmic functional region and a CD3zeta cytoplasmic functional region linked in any order; also provides a method of treating Hodgkin's lymphoma or anaplastic large cell lymphoma or other CD30-positive tumors using the CAR-T cells of the invention.

Abstract: The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, auto-immune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.

Abstract: The invention includes a bioelectronic interface comprising a self-assembling unit, wherein the self-assembling unit comprises a variant GPCR fusion protein bound to an S-layer fusion protein. The invention also encompasses a biosensor or device comprising the bioelectronic interface and methods of screening for a ligand of a GPCR.

Abstract: The present invention refers to a method for determining the ability of an immunoglobulin to bind to a post-translationally modified target in an intracellular environment, which folds and it is post-translationally modified as a native protein intracellularly. The present invention also refers to antibodies obtained by the above method and uses thereof.

Abstract: The invention provides T cells comprising nucleic acid sequence encoding a chimeric antigen receptor and a nucleic acid sequence encoding an enhancer of T cell priming, compositions including the T cells, and methods of using the T cells to treat diseases associated with the expression of disease-associated antigens.

Abstract: The present invention relates to monomeric fusion proteins comprising the extracellular part of the thymic stromal lymphopoietin receptor (TSLPR) and the extracellular part of the interleukin-7 receptor alpha (IL-7Ralpha) as inhibitors of thymic stromal lymphopoietin (TSLP) activity. The invention relates further to the use of said inhibitors as a medicament in the treatment of—but not limited to—inflammatory diseases, cancer and fibrosis.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain.

Abstract: The present invention relates to a binding molecule comprising at least three binding specificities, wherein (a) the first specificity is for a Hepatitis B virus (HBV) surface antigen selected from HBV small surface antigen, HBV medium surface antigen and HBV large surface antigen; (b) (i) the second and third specificity are for CD3 and CD28, respectively; or (ii) the second and third specificity are selected from specificities for CD16, CD56, NKp30, NKp46, 4-1BB and NKG2D; and (c) each binding specificity is provided by one or more binding sites, each binding site being independently provided by (i) a set of six complementarity determining regions (CDRs), wherein said set of six CDRs consists of a first set of three CDRs and a second set of three CDRs, wherein said first and said second set is each comprised in an immunoglobulin domain; or (ii) a set of three CDRs, wherein said set of three CDRs is comprised in an immunoglobulin domain.

Abstract: The invention provides compositions and methods useful for the depletion of cells, such as CD45+, CD135+, CD34+, CD90+, and/or CD110+ cells, and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, ligands, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD45+, CD135+, CD34+, CD90+, or CD110+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD45+, CD135+, CD34+, CD90+, or CD110+ cancer cells or autoimmune cells.

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: 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: The present invention relates, in part, to, chimeric proteins which include the extracellular domain of colony stimulating factor 1 receptor (CSF1R) and their use in the treatment of diseases, such as immunotherapies for cancer and/or an inflammatory disease.

Abstract: Chimeric antigen receptors containing tumor necrosis factor receptor superfamily member transmembrane domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD19, e.g., by administering a recombinant T cell comprising the CD19 CAR as described herein, in combination with one or more B-cell inhibitors, e.g., inhibitors of one or more of CD10, CD20, CD22, CD34, CD123, FLT-3, ROR1, CD79b, CD179b, or CD79a. The disclosure additionally features novel antigen binding domains and CAR molecules directed to CD20 and CD22, and uses, e.g., as monotherapies or in combination therapies. The invention also provides kits and compositions described herein.

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: Glycoproteins comprising a glycan of the formula (102) are disclosed; wherein b is 0 or 1; the GlcNAc residue optionally fucosylated; and Su(A)x is a sugar derivative comprising x functional groups A, wherein x is 1, 2, 3 or 4 and A is independently selected from the group consisting of an azido group, a keto group, an alkynyl group, a thiol group, a halogen, a sulfonyloxy group, a halogenated acetamido group, a mercaptoacetamido group and a sulfonylated hydroxyacetamido group. Protein-conjugates having glycoproteins according to the invention conjugated to a molecule of interest (e.g., an active substance) are also disclosed. Examples include modified antibodies, antibody-conjugates, and antibody-drug conjugates (ADCs). Processes for the preparation of the modified glycoproteins according to the invention and methods for the preparation of a protein-conjugate according to the invention are mentioned.

Abstract: Porcine circovirus (PCV2) vaccine compositions comprising a peptide antigen derived from a PCV2 capsid protein are described. In various embodiments, the peptide antigen contains amino acids of the capsid protein from about amino acid 47 to about amino acid 202. In some embodiments, the peptide antigen is optionally linked to an artificial T helper epitope and/or mixed with T helper epitopes derived from the ORF1 and ORF3 proteins of PCV2. Methods of using PCV2 vaccine compositions are also described. In various embodiments, a vaccine composition is used in animals for the prevention of PCV2 infection. In other embodiments, a PCV2 vaccine composition is used as an antigen for diagnosing PCV2 infection.

Abstract: The disclosure provides a chimeric antigen receptor (CAR) comprising a) an antigen binding domain of HA22, a transmembrane domain, and an intracellular T cell signaling domain; or b) an antigen binding domain of BL22, a transmembrane domain, and an intracellular T cell signaling domain comprising CD28 and/or CD137. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

Abstract: The invention provides methods for the rapid identification and selection of cell lines suitable for biopharmaceuticals production, which do no utilize animal derived components.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

Abstract: The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method provides a multispecific antibody having a common light chain associated with each heteromeric polypeptide having an antibody binding domain. Additionally the method further involves introducing into the multispecific antibody a specific and complementary interaction at the interface of a first polypeptide and the interface of a second polypeptide, so as to promote heteromultimer formation and hinder homomultimer formation; and/or a free thiol-containing residue at the interface of a first polypeptide and a corresponding free thiol-containing residue in the interface of a second polypeptide, such that a non-naturally occurring disulfide bond is formed between the first and second polypeptide.

Abstract: The present invention relates to agents for use in treating cancer. The agent to be used is an antagonist of Dsg2, wherein the antagonist modulates the function of the amino acid sequence: TQDVFVGSVEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO:1), or a fragment or variant thereof, of the EC2 domain of Dsg2. Also included in the invention are specific polypeptides and pharmaceutical preparations. Also included in the invention is a method of screening for antagonists of Dsg2, wherein the antagonist modulates the function of the amino acid sequence: TQDVFVGSVEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO: 1), or a fragment or variant thereof, of the EC2 domain of Dsg2.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention relates to targeting the stromal cell population in a tumor microenvironment. For example, in one embodiment, the invention provides a composition that is targeted to fibroblast activation protein (FAP). The invention includes a chimeric antigen receptor (CAR) which comprises an anti-FAP domain, a transmembrane domain, and a CD3zeta signaling domain.

Abstract: Provided herein are methods for modulating one or more of a T-helper cell or monocyte lineage cell-mediated immune response in a subject, the method comprises administering to the subject an effective amount of a compound which binds to surface membrane immunoglobulin D (smIgD). Also provided are methods of diagnosis of one or more of a T-helper cell or monocyte lineage cell-mediated immune disease, and compositions and kits for use in such methods.

Abstract: The present invention relates to the field glycosylation engineering of proteins. More particular, the present invention is directed to the glycosylation engineering of proteins to provide proteins with improved therapeutic properties, e.g., antibodies, antibody fragments, or a fusion protein that includes a region equivalent to the Fc region of an immunoglobulin, with enhanced Fc-mediated cellular cytotoxicity.

Abstract: A T cell receptor molecule (TCR) containing an alpha chain portion and a beta chain portion wherein the alpha chain portion contains three complementarity determining regions (CDRs): CDR1?: SSYSPS CDR2?: YTSAATL CDR3?: VVSPF-SGGGADGLT or comprising or consisting of SPPSGGGADGLT and the beta chain portion contains three complementarity determining regions (CDRs): CDR1?: DFQATT CDR2?: SNEGSKA CDR3?: comprising SARDGGEG or comprising or consisting of RDGGEGSETQY, or wherein up to three amino acid residues in one or more CDRs are replaced by another amino acid residue. The invention also includes polynucleotides encoding the TCR molecules, and host cells containing the said polynucleotides. Patient derived T cells may have the polynucleotides encoding the TCR molecules introduced therein, and the engineered T cells may be introduced into the patient in order to combat a WT1-expressing malignancy.

Abstract: Antibodies and antigen binding fragments that specifically binds to Siglec-15 are described herein. These antibodies or antigen binding fragments may have the ability of inhibiting differentiation of osteoclasts and/or the ability of inhibiting the bone resorption activity of osteoclasts. Compositions and cells expressing anti-Siglec-15 antibodies or antigen binding fragments are also disclosed herewith. Anti-Siglec-15 antibodies may also be useful for the treatment of bone loss, or bone diseases. Methods for the detection or diagnosis of bone loss or bone-related diseases are also described.

Abstract: The present invention relates to immunoglobulins that bind IgE and Fc?RIIb with high affinity, said compositions being capable of inhibiting cells that express membrane-anchored IgE. Such compositions are useful for treating IgE-mediated disorders, including allergies and asthma.

Abstract: The present invention provide purified Flt4 receptor tyrosine kinase polypeptides and fragments thereof, polynucleotides encoding such polypeptides, antibodies that specifically bind such polypeptides, and uses therefor.

Abstract: Provided are glycoengineered populations of Fc domain-containing binding proteins with a reduced anti-drug immune response (ADA). Also provided are methods of treating disease using such compositions, and methods and host for making such compositions.

Abstract: Monoclonal antibodies that specifically bind to M.96. Also included are methods of using these antibodies to treat mammals having or at risk of having 006-mediated diseases, or to diagnose % Q mediated diseases.

Abstract: The invention concerns the field of cell culture technology. It concerns RNA having a specific sequence, expression vectors encoding said RNA, production host cell lines comprising said RNA, and methods of producing recombinant biopharmaceutical products using engineered host cell with altered levels of said RNAs, such as small non-coding RNAs, preferably microRNAs (miRNAs). The invention also relates to engineered host cells with altered levels in one or more of said RNAs. Those cell lines have improved secretion and/or growth characteristics in comparison to control cell lines.

Abstract: Genetically modified mice are provided that express human ? variable (hV?) sequences, including mice that express hV? sequences from an endogenous mouse ? light chain locus, mice that express hV? sequences from an endogenous mouse ? light chain locus, and mice that express hV? sequences from a transgene or an episome wherein the hV? sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human ? variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human ? variable sequences, including human antibodies, are provided.

Abstract: The invention provides engineered heteromultimeric protein complexes constructed using one, two, or three tethers and methods for making, using, and purifying such complexes, such as antibodies with different binding properties.

Abstract: The invention relates, in one aspect, generally to novel concept of guided selection of antibody variable domains, combination and expression entirely in vivo. An application is to produce multivalent polypeptides. The present invention relates to multivalent (eg, multispecific) antibodies, antibody chains and polypeptides, as well as heavy chain-only antibodies (H2 antibodies) that are devoid of light chains. The invention further relates to the selection, maturation and production of these in vivo in non-human vertebrates and non-human vertebrate cells. To this end the invention also relates to such non-human vertebrates and cells. The invention also relates to the provision of means to produce and select heavy chain-only antibodies and heavy chains comprising variable domains that have undergone affinity maturation.

Abstract: The present invention relates to Bispecific antibodies against human TWEAK and human IL17 (bispecific TWEAK-IL17 antibodies), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof

Abstract: This invention provides fully human monoclonal antibodies that recognize IL-17F and/or the heterodimeric IL-17A/IL-17F complex, but do not recognize IL-17A. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.

Abstract: The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Abstract: Provided herein are monovalent antibody constructs. In specific embodiments is a monovalent antibody construct comprising: an antigen-binding polypeptide construct which monovalently binds an antigen; and a dimeric Fc polypeptide construct comprising a CH3 domain, said construct comprising two monomeric Fc polypeptides, wherein one said monomeric Fc polypeptide is fused to at least one polypeptide from the antigen-binding polypeptide construct. These therapeutically novel molecules encompass monovalent constructs that display an increase in binding density and Bmax (maximum binding at a target to antibody ratio of 1:1) to a target cell displaying said antigen as compared to a corresponding monospecific bivalent antibody construct with two antigen binding regions. Provided herein are methods for creation of monovalent antibody constructs that shows superior effector efficacy as compared to the corresponding bivalent antibody construct at equimolar concentrations.

Abstract: This invention provides antibodies that recognize the B Cell Maturation Antigen (BCMA) and that bind naïve B cells, plasma cells, and/or memory B cells. The invention further provides methods for depleting naïve B cells, plasma cells, and memory B cells, and for treating B cell-related disorders, including lymphomas and autoimmune diseases.

Abstract: The invention relates to variants of an antibody or antigen-binding fragment that binds specifically to an endosialin tumor endothelial marker 1 (TEM1), and prophylactic, diagnostic, and therapeutic methods using the same.

Abstract: Provided are polypeptides comprising a variant IgG Fc domain, wherein the polypeptides exhibit reduced or ablated effector functions (e.g., ADCC and/or CDC) and increased stability and plasma half-life compared to a parent polypeptide. Also provided are compositions, methods of treatment, and methods to diminish Fc-induced effector function in a parent polypeptide.

Abstract: Engineered multivalent and multispecific binding proteins that bind immune cell receptors and/or autoantigens are provided, along with methods of making and uses in the prevention, diagnosis, prognosis and/or treatment of disease.

Abstract: The present invention relates to anti-FLT3 antibodies with a modified Fc region comprising the amino acid substitutions 239D and 332E to enhance antibody-dependent cell cytotoxicity (ADCC) of these antibodies. The invention further relates to pharmaceutical compositions containing these antibodies, nucleic acids encoding these antibodies as well as methods of using such antibodies.