Abstract: Embodiments of the methods and compositions provided herein relate to chimeric antigen receptors (CARs) that specifically bind to B7H3. Some embodiments relate to cell-based immunotherapy targeting tumors, such as tumors comprising B7H3+ cells.

Abstract: The present invention provides high efficiency targeted and marker-less single, double, triple, quadruple, and quintuple integrations by using CRISPR in host cells, including Pichia.

Abstract: Methods for treating and for preventing filovirus infections are disclosed, as well as compositions therefor.

Abstract: This disclosure relates to the genetic modification of DNMT3A gene in immune cells. In certain embodiments, the modified immune cells may be used in adoptive T cells therapies to enhance immune responses against cancer or chronic infections. In certain embodiments, the disclosure relates to deleting, changing, or inserting nucleotides within the DNMT3A gene in immune cells, e.g., human CD8 T cells, such that the DNMT3A gene product does not function for methylation. In certain embodiments, modification of the DNMT3A gene provides an improvement in antigen-specific T cells functions and/or an enhancement of the longevity of the cells.

Abstract: The present invention relates to chimeric antigen receptors (CARs) directed to cells expressing a dysfunctional or non-functional P2X purinoceptor 7 receptor. Further provided are methods of targeting neoplastic cells and tumours expressing a dysfunctional or non-functional P2X purinoceptor 7 receptor and methods of treating and preventing cancer is a subject.

Abstract: The invention relates to the field of treatment or prevention of obesity-related disorders, atherosclerosis or a coagulation disorder. In particular, the present invention relates to the use of an activator of IFN? receptor for the treatment or prevention of such disorders or conditions, and corresponding methods of treatment.

Abstract: Antigen binding proteins that bind to human CGRP receptor (CGRP R) are provided. Nucleic acids encoding the antigen binding protein, vectors, and cells encoding the same are also provided. The antigen binding proteins can inhibit binding of CGRP R to CGRP, and are useful in a number of CGRP R related disorders, including the treatment and/or prevention of migraine headaches.

Abstract: Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody or fragment thereof that targets PCSK9. The disclosure also provides a method of preventing and/or treating disease, such as cardiovascular disease or hypercholesterolemia, in a subject using the composition of the invention.

Abstract: Single domain antibodies are provided, which are capable of specifically binding to an epitope of a human complement factor selected from the group consisting of C1q, C3, C4 and/or the proteolytic derivatives C3b and C4b. Further the use of the antibodies are provided for methods in modulating the activity of the complement system as well 5 as methods of treating disorders associated with complement activation.

Abstract: The present application relates to anti-mesothelin constructs (such as antimesothelin antibodies, cytokine fusion proteins that comprise the anti-mesothelin constructs), methods of preparing the anti-mesothelin constructs and methods of using the constructs (e.g., methods of treating a disease or condition). The present application also relates to a combination therapy for treating cancer that comprises administering anti-mesothelin agent and a cytokine (such as IL-21 or IL-15). Combination therapy may further comprises administration of an anti-Her2 agent.

Abstract: Compositions and methods of use thereof for modulating LAIR-1 are provided. For example, immunomodulatory agents are provided that reduce LAIR-1 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. Exemplary agents include (i) a soluble LAIR-2 polypeptide or fusion protein, (ii) a soluble LAIR-1 polypeptide or fusion protein, (iii) a function blocking anti-LAIR-1 antibody, (iv) an antibody that depletes LAIR-1 positive cells, and (y) combinations thereof. Immunomodulatory agents are also provided that increase LAIR-1 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. Exemplary agents include: (i) a function activating anti-LAIR-1 antibody, (ii) a function blocking anti-LAIR-2 antibody, and (iii) a combination thereof.

Abstract: The present invention relates to a ligand binding molecule whose ligand binding activity is attenuated by the cleavage of a cleavage site and a method for producing the same, a complex formed by the ligand binding molecule and a ligand, a fusion protein comprising the ligand binding molecule and a ligand, and a pharmaceutical composition comprising the ligand binding molecule or a fusion protein of the ligand binding molecule and a ligand.

Abstract: The present invention relates to a humanized anti-human CTLA4 monoclonal antibody. The present invention also relates to a preparation method and application of the humanized anti-human CTLA4 monoclonal antibody.

Abstract: There is disclosed compositions and methods relating to or derived from anti-CD38 antibodies. More specifically, there is disclosed fully human antibodies that bind CD38, CD38-antibody binding fragments and derivatives of such antibodies, and CD38-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease.

Abstract: Provided herein are humanized anti-factor Bb antibodies, methods of producing the antibodies and methods of using the antibodies.

Abstract: The present disclosure relates to compositions and methods for inhibiting bacterial aggregation, and in particular, to compositions and methods that inhibit autotransporter-mediated bacterial aggregation or attachment. Described herein are autotransporter binding molecules such as antibodies and antigen binding fragments thereof. The autotransporter binding molecules block self-association between autotransporters and autotransporter-mediated surface attachment.

Abstract: The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing Claudin-6 (CLDN6), including tumor-related diseases such as ovarian cancer, lung cancer, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, malignant melanoma, head and neck cancer, sarcoma, bile duct cancer, cancer of the urinary bladder, kidney cancer, colon cancer, placental choriocarcinoma, cervical cancer, testicular cancer, and uterine cancer.

Abstract: The present invention relates to a neutralising antibody which is capable of binding to neurotensin with high affinity. The antibody of the present invention neutralises the activity of neurotensin, in particular the oncogenic activities of neurotensin. In particular, the present invention relates to a neutralising antibody which binds to the human neurotensin long fragment, and having a heavy chain variable region which comprises a H-CDR1 region having at least 90% of identity with SEQ ID NO:2, a H-CDR2 region having at least 90% of identify with SEQ ID NO:3 and a H-CDR3 region having at least 90% of identity with SEQ ID NO:4; and a light chain variable region comprising a L-CDR1 region having at least 90% of identity with SEQ ID NO:6, a L-CDR2 having at least 90% of identity with SEQ ID NO:7 and a L-CDR3 region having at least 90% of identity with SEQ ID NO:8. The present invention also provides the use of such antibodies in the treatment of cancer.

Abstract: The invention relates to water soluble 18F-prosthetic groups and the synthesis and use of 18F-labeled biological molecules containing the 18F-prosthetic groups for imaging various processes within the body, for detecting the location of molecules associated with disease pathology, and for monitoring disease progression are disclosed.

Abstract: Provided is a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs disclosed herein. Aspects of the disclosure relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs. Provided are antibodies and antigen binding systems that comprise a binding motif that binds CD20 and optionally a binding motif that binds CD19, and methods of producing and using the same. Antibodies and antigen binding systems of the present disclosure comprise CARs that comprise an anti-CD20 binding motif and an anti-CD19 binding motif. Provided are compositions, such as antibodies and CARs that are or comprise an anti-CD20/anti-CD19 antigen binding system of the present disclosure, and cell therapies comprising the same, are useful, e.g., in the treatment of cancer.

Abstract: Provided are survivin specific antibodies, nucleic acids encoding the antibodies and methods for treating tumors comprising survivin-expressing cells by administration of the antibodies. The antibody compositions were found to be effective in inhibiting the growth of tumors.

Abstract: A stable liquid pharmaceutical formulation according to the present invention includes an antibody or antigen-binding fragment thereof, a surfactant, a sugar or a sugar derivative, a buffer, and a stabilizer. The stable liquid pharmaceutical formulation according to the present invention has low viscosity not only when antibody content is low but also when antibody content is high, and exhibits superior long-term storage stability based on superior stability observed under accelerated conditions and harsh conditions.

Abstract: There is described a chimeric antigen receptor (CAR) which comprises an antigen binding domain which selectively binds to Receptor Tyrosine Kinase Like Orphan Receptor 1 (ROR1), and its use. Also described is a T cell comprising the CAR and its use in the treatment of cancer.

Abstract: The invention relates to methods of treating a patient suffering from an IL-33-mediated disorder, such as asthma, comprising administering to the patient an IL-33 axis binding antagonist based on the genotype of the /L1RL1gene, the genotype of a polymorphism in genomic vicinity to the IL-33 gene, the expression level of periostin or the expression level of soluble ST2. The invention further relates to methods of determining whether a patient is at increased risk of an IL-33-mediated disorder, as well as methods of determining whether a patient suffering from such a disorder is likely to respond to a treatment comprising an IL-33 axis binding antagonist, based on the genotype of the /L1RL1gene the genotype of a polymorphism in genomic vicinity to the IL-33 gene, the expression level of periostin or the expression level of soluble ST2.

Abstract: This disclosure provides methods and landing pad constructs for generation of parental cell lines suitable for targeted integration. A method is provided by the parental cell line development; this is, the introduction of binding sites of BPV1 E2 protein to landing pad vectors so that expressed BPV1 E2 protein could locate the vector to transcriptionally active region in the genome. Cells with high expression level of reporter genes are selected for the next stage and will be used in the development of cell lines expressing another recombinant protein by recombination mediated cassette exchange (RMCE). Landing pad constructs include recombination target sites for site-specific recombinases, and therefore, it could be replaced with gene-of-interest expression construct containing the same set of recombination target sites. This yields the generation of producer cell lines with less effort compared to traditional cell line development by random integration.

Abstract: This disclosure relates generally to methods and agents for treating an ocular disease or disorder. More particularly, the present disclosure relates to the use of CD14 antagonist antibodies for treating an ocular disease or disorder.

Abstract: This invention concerns anti-inflammatory agents, compositions, and methods for treating inflammatory disorders.

Abstract: The present invention relates to compositions and methods employing conjugates that include a self-assembly and disassembly (SADA) polypeptide and a binding domain. The present invention encompasses the recognition that conjugates with a SADA polypeptide have certain improved biological properties. SADA-conjugates are described, along with uses thereof (e.g., as therapeutic or diagnostic agents) and methods of manufacture.

Abstract: An object of the present invention is to elucidate a molecular mechanism of ligand-independent activation of EphA2 in cancer cells, make EphA2 a more useful target in the treatment of cancer, and provide a cancer testing method and the like using the mechanism. The present invention provides, for example, a cancer testing method including a step of measuring an amount of an EphA2 protein fragment having a molecular weight of from 30 kDa to 80 kDa in a sample derived from a subject.

Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.

Abstract: Combinations of anti-cancer antibodies and inhibitory antibodies to CD223 overcome immune suppression in cancer patients. The inhibitory antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.

Abstract: Provided herein are agonistic antibodies, or antigen binding portions thereof, that bind to human CD40. Such antibodies optionally comprise Fc regions with enhanced specificity for Fc?RIIb. The invention also provides methods of treatment of cancer or chronic infection by administering the antibodies of the invention to a subject in need thereof.

Abstract: The present invention is directed to methods for treating cancer, preferably a solid tumor or hematological malignancy, including for example pancreatic cancer, lung cancer (including but not limited to non-small cell lung cancer (NSCLC)), prostate cancer, colorectal cancer, breast cancer, melanoma or non-Hodgkin's lymphoma, comprising administering to a subject in need thereof a therapeutically effective amount of co-therapy comprising, consisting or consisting essentially of (a) a small molecule CSF-1R inhibitor and (b) an agonistic antibody that binds CD40.

Abstract: A first immunoglobulin ? chain variable region-binding peptide includes an amino acid sequence of SEQ ID NO: 21 with substitution of one or more amino acid residues at the 15th position, the 16th position, the 17th position or the 18th position, wherein an acid dissociation pH thereof is shifted to a neutral side. A second immunoglobulin ? chain variable region-binding peptide further includes deletion, substitution and/or addition of 1-20 amino acid residues at positions other than the 15th position, the 16th position, the 17th position and the 18th position. A third immunoglobulin ? chain variable region-binding peptide includes an amino acid sequence with a sequence identity of 80% or more to the amino acid sequence of the first immunoglobulin ? chain variable region-binding peptide.

Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.

Abstract: A kappa light chain-binding polypeptide comprising or consisting essentially of one or more binding domains of Peptostreptococcus Protein L, each of said domains being selected from the group consisting of domain 2, domain 3 and domain 4.

Abstract: The present invention provides for a method for improving properties of an antibody such as an expression level and stability. A method for obtaining an antibody with an improved expression level and/or stability by modifying a human antibody or a humanized antibody, characterized by that at least any one of the amino acid residues at position 8, 12, 15 or 18 (according to Kabat numbering) in a light chain variable region (hereinafter referred to as “VL chain”) of a human antibody or a humanized antibody is substituted with a different amino acid other than proline or cysteine, and a human antibody or a humanized antibody or a human antibody fragment or a humanized antibody fragment with an improved expression level and/or stability which are obtained by said method.

Abstract: The invention provides methods of using sequence based analysis and rational strategies to improve the solubility of immunobinders, and in particular of single chain antibodies (scFvs). The invention provides methods of engineering immunobinders, and in particular scFvs, by performing one or more substitutions with hydrophilic residues identified by analysis of a database of selected, stable scFv sequences. The invention also provides immunobinders with optimized solubility prepared according to the engineering methods of the invention.

Abstract: Structural isomers in sc(Fv)2 compositions of anti-human Mpl antibody and humanized anti-human Mpl antibody were separated, and the obtained structural isomers were cleaved at their linkers to confirm that the structural isomers are of single chain diabody type and bivalent scFv type. In addition, the agonistic activities of these structural isomers were revealed to be significantly different. Furthermore, the present inventors discovered that the content ratio of the structural isomers in sc(Fv)2 compositions could be regulated by altering temperature, modifying lengths of the linkers of sc(Fv)2, or amino acids in their variable regions.

Abstract: The present invention pertains to a method for controlling the circulation half-life of antibodies by adjusting the amount of sialic acid in the carbohydrates attached to the Fab part of the antibodies. Furthermore, the present invention provides antibodies having an increased circulation half-life.

Abstract: This invention provides antibodies that interact with or bind to human B7 related protein-1 (B7RP1) and antibodies that bind to and neutralize the function of B7RP1 thereby. The invention also provides pharmaceutical compositions of said antibodies and methods for neutralizing B7RP1 function, and particularly for treating immune disorders (e.g., inappropriate immune response) by administering a pharmaceutically effective amount of anti-B7RP1 antibodies. Methods of detecting the amount of B7RP1 in a sample using anti-B7RP1 antibodies are also provided.

Abstract: The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab.

Abstract: The present invention relates to novel humanized, chimeric and murine antibodies that have binding specificity for the human CC chemokine ligand 20 (CCL20). The present invention further relates to heavy chains and light chains of said antibodies. The invention also relates to isolated nucleic acids, recombinant vectors and host cells that comprise a sequence which encodes a heavy chain and/or a light chain of said antibodies, and to a method of preparing said antibodies. The anti-CCL20 antibodies of the invention can be used in therapeutic applications to treat, for example, inflammatory and autoimmune disorders and cancer.

Abstract: A method for engineering an immunoglobulin having a variable domain and at least one modification in at least two structural loops of the immunoglobulin and determining the binding of the immunoglobulin to an epitope of an antigen, where the unmodified immunoglobulin does not significantly bind to said epitope, comprising the steps of providing a nucleic acid encoding an immunoglobulin having at least two structural loops, modifying at least one nucleotide residue of each of the structural loops, transferring the modified nucleic acid in an expression system, expressing the modified immunoglobulin, contacting the expressed modified immunoglobulin with an epitope, and determining whether the modified immunoglobulin binds to the epitope.

Abstract: Methods are described for modifying the isoelectric point of an antibody while retaining its antigen-binding activity, comprising modifying the charge of at least one exposable amino acid residue on the surface of the complementarity determining region (CDR). The disclosure also provides methods for purifying multispecific antibodies, comprising modifying isoelectric point, and methods for improving the plasma pharmacokinetics of antibodies with a modified isoelectric point. The disclosure further provides antibodies with a modified isoelectric point, pharmaceutical compositions comprising the antibodies as an active ingredient, and methods for producing the antibodies and compositions.

Abstract: The present invention relates to Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and to methods of using such polypeptides for treating or preventing cancer and other diseases. The Fc region-containing polypeptides of the present invention are preferably immunoglobulins (e.g., antibodies), in which the Fc region comprises at least one amino acid substitution relative to the corresponding amino acid sequence of a wild type Fc region, and which is sufficient to attenuate post-translational fucosylation and mediate improved binding to an activating Fc receptor and reduced binding to an inhibitory Fc receptor. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by Fc?R is desired (e.g.

Abstract: A method of engineering immunoglobulins which each have one or more amino acid modifications in at least one structural loop region of such immunoglobulins, where the modified loop region specifically binds to an epitope of an antigen to which an unmodified immunoglobulin does not significantly bind.

Abstract: The present invention relates to the use of at least one anti-CD 160 antibody, preferably a compound selected from CL1-R2 monoclonal antibody (which may be obtained by the hybridoma CNCM 1-3204), its conservative fragments and its conservative derivatives, for preparing a drug designed to treat neovascular eye diseases.

Abstract: The invention provides novel caninized anti-NGF antibodies (such as caninized anti-NGF antagonist antibodies and antigen binding proteins), and polynucleotides encoding the same. The invention further provides use of said antibodies or antigen binding proteins and/or nucleotides in the treatment and/or prevention of NGF related disorders, particularly pain.

Abstract: The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to MAdCAM, preferably human MAdCAM and that function to inhibit MAdCAM. The invention also relates to human anti-MAdCAM antibodies and antigen-binding portions thereof. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins derived from human anti-MAdCAM antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-MAdCAM antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-MAdCAM antibodies.