Abstract: The present invention provides a method for production of stable and highly specific heterodimeric immunoglobulin constructs, e.g., bispecific antibodies, retaining desirable properties of native IgG and lacking undesirable heavy chain-light chain mispairing, that can simultaneously bind two target molecules and are more potent in the treatment of complex diseases.

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 BCMA monoclonal antibody, conferring specific immunity against BCMA positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas, multiple myeloma and leukemia.

Abstract: The present invention relates to a method for treating cancer. This method involves providing a first agent comprising a first targeting component coupled to a first cancer therapeutic component and providing a second agent comprising a second targeting component coupled to a second cancer therapeutic component. The first and second targeting components have different biodistributions and/or pharmacokinetics. The first and second agents are administered to a subject having cancer to treat the cancer. Also disclosed is a combination therapeutic comprising the first and second agents.

Abstract: The present invention relates to a polypeptide including an Fc variant produced by substituting a portion of the amino acid sequence of the Fc domain of a human antibody with a different amino acid sequence. The present invention also relates to an antibody including the polypeptide. The Fc variant can find application in a wide range of antibodies and Fc-fusion constructs. In one aspect, the antibody or Fc fusion construct of the present invention is a therapeutic, diagnostic or laboratory reagent, preferably a therapeutic reagent. The Fc variant is suitable for use in the treatment of cancer because its in vivo half-life can be maximized by optimization of the portion of the amino acid sequence. The antibody or Fc fusion construct of the present invention is used to kill target cells that bear a target antigen, for example cancer cells. Alternatively, the antibody or Fc fusion construct of the present invention is used to block, antagonize or agonize a target antigen.

Abstract: The present invention is directed to heterodimeric anti-LAG-3×anti-CTLA-4. Also provided are nucleic acid compositions that encode the antibodies, expression vector compositions that include the nucleic acids, and host cells that include the expression vector compositions.

Abstract: Angiopoietin-like protein (ANGPTL)3/8 fusion proteins are disclosed. Nucleic acid constructs encoding ANGPTL3/8 fusion proteins also are disclosed. Methods of making and using the same also are disclosed, especially for generating antibodies against ANGPTL3 and/or ANGPTL8.

Abstract: Conjugates comprising a coagulating agent conjugated to an antibody, where the antibody specifically binds an extracellular domain epitope of a mammalian PLVAP protein, and methods of using such conjugates, including methods of treating HCC by administering the conjugates or compositions thereof, such as pharmaceutical compositions.

Abstract: The present invention relates to methods and kits for treating cardiovascular disease.

Abstract: The present invention relates to methods for treating chronic inflammatory conditions using a mast cell stabilizing compound. The invention further relates to compositions and dosage forms comprising mast cell stabilizing agents.

Abstract: Peptides have immune system modulation properties. The immunologically active peptides can be derived from the heavy-chain complementarity determining region-3 of a humanized monoclonal antibody to NaPi2B transporter. Such peptides can be used to modulate the immune system of a subject under cancer treatment.

Abstract: The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, humanized antibodies, antibody fragments, etc., that specifically bind a TREM1 protein, e.g., a mammalian TREM1 or human TREM1, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

Abstract: Anti-CD33 antibodies and antigen-binding fragments thereof and anti-CD33/anti-CD3 bispecific antibodies or antigen-binding fragments thereof are described. Also described are nucleic acids encoding the antibodies, compositions comprising the antibodies, methods of producing the antibodies, and methods of using the antibodies for treating or preventing diseases, such as cancer.

Abstract: Provided herein are anti-CD27 and anti-PD-L1 antibodies, and binding domains thereof, as well as bispecific constructs and anti-CD27 binding domain linked to an anti-PD-L1 binding domain. Also provided herein are methods of stimulating T cell activity, methods of inducing or enhancing an immune response, and methods of treating a disease or condition by administering the bispecific constructs, antibodies, or antigen binding fragments thereof, or compositions described herein to a patient in need thereof.

Abstract: Provided are methods for clinical treatment of a protein-losing enteropathy, such as lymphangiectasia, using an anti-C5 antibody, or antigen binding fragment thereof, in patients (e.g., pediatric patients).

Abstract: Described herein are mutations in the CH1/CL interface and CH3 constant regions of a bispecific antibody which facilitate heterodimerization and methods for the efficient production of bispecific antibodies. Also disclosed are therapeutic and diagnostic methods for using the antibodies.

Abstract: Provided herein is a platform technology for the generation of properly paired bispecific antibodies. Some of the antibodies generated have Fc region modifications, in particular in their CH3 domains by lysine repositioning to drive heterodimerization of the two heavy chains of the bispecific antibody. Some of the antibodies generated have Fab arm modifications to prevent mispairing of light chains. Specifically, the CH1 and CL domains of one of the Fab arms of the bispecific antibody are substituted with an IgE CH2 domain or an IgM CH2 domain.

Abstract: The present disclosure relates to methods of re-oxidizing an antigen-binding protein.

Abstract: The present invention relates to fully human antibodies and conjugates thereof, which specifically bind to the extracellular domain of receptor tyrosine kinase-like orphan receptor 2 (ROR2).

Abstract: Provided are compositions and methods for producing large repertoires of recombinant nanobodies with high affinities and specificities against any antigen. Included are methods for making and identifying nanobodies produced by camelids, the nanobodies themselves, modifications of the nanobodies, expression vectors encoding the nanobodies, cDNAs encoding the nanobodies, cells comprising the expression vectors and/or cDNA, and methods of making the nanobodies recombinantly. Antigen-specific nanobodies and antigen binding fragments thereof having a Kd for the antigen in a sub-micromolar range are provided.

Abstract: Disclosed is a synthetic T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of thyroglobulin (TG), TG470-478. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

Abstract: An object is to produce a new anti-B7-H4 antibody having high specificity and affinity and provide a composition for treating cancer making use thereof. A monoclonal antibody that specifically binds to an extracellular domain protein of a human B7-H4 protein is newly produced and an “anti-B7-H4 antibody-effector cell complex” in which the monoclonal antibody and an effector cell are bound in order to enhance the antibody-dependent cellular cytotoxicity of the monoclonal antibody or a bispecific antibody comprising an antigen recognition region of the monoclonal antibody and an effector cell antigen recognition region is further produced and used as a composition for treating cancer.

Abstract: The present invention discloses a novel means capable of producing a blood chimeric animal in which a state of retaining blood cells originating in a heterologous animal at a high percentage is sustained for a long period of time. The method for producing a non-human animal that retains blood cells originating in a heterologous animal, according to the present invention, comprises transplanting hematopoietic cells of a heterologous animal into a non-human animal, in which hematopoietic cells the function of a gene that acts on the hematopoietic system is modified, The gene that acts on the hematopoietic system is, for example, Lnk gene, When a medium to large mammal is used as a recipient, the survival rate of hematopoietic cells originating in a heterologous animal is dramatically increased such that blood chimerism of 10% or more can be maintained even in a 16 month old animal.

Abstract: Provided herein, in one aspect, is a method of preventing or delaying the onset of clinical type 1 diabetes (T1D), comprising: providing a non-diabetic subject who is at risk for T1D; determining that the non-diabetic subject (1) is substantially free of antibodies against zinc transporter 8 (ZnT8), (2) is HLA-DR4+, and/or (3) is not HLA-DR3+; and administering a prophylactically effective amount of an anti-CD3 antibody to the non-diabetic subject.

Abstract: The present invention relates to variant Fc-containing molecules, such as antibodies and Fc-fusion molecules, having glycosylation characteristics favorable to largescale production of therapeutic molecules containing such variant Fc. Described herein are compositions and methods to improve glycosylation maturation of and to minimize the culture process-dependent effects of Fc-containing molecules, e.g., Fc-fusion molecules and antibodies. Creating single and multiple amino acid substitutions within the Fc domain with the aim to improve high mannose processing and glycosylation maturation.

Abstract: The present invention provides novel and stable pharmaceutical compositions comprising bispecific single chain antibody constructs, cyclodextrins and a buffer.

Abstract: The present invention relates to human CD3 antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific antibody molecules capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.

Abstract: The present disclosure relates to protein arrays and methods of using the same for the detection, quantification and characterization of biomolecules that specifically bind to the array among various other biomolecules in a biological sample. Specifically, the present disclosure relates to protein arrays that include a plurality of immunoglobulin molecules derived from shark single-domain heavy chain antibody lacking light-chains but including at least one variable antigen-binding domain with a binding site for an antigen. The immunoglobulin molecules are immobilized on a substrate via a linker. Further encompassed herein are diagnostic devices and kits, comprising the protein array and methods of using same.

Abstract: The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and a selective BCL-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a CD20-expressing cancer.

Abstract: The present disclosure relates to a polypeptide containing an Fc domain in which a part of an amino acid sequence of a human antibody Fc domain is substituted with another amino acid sequence, or an aglycosylated antibody containing the same. The Fc domain of the present disclosure is optimized by substituting a part of an amino acid sequence of a wild-type Fc domain with another amino acid sequence. Therefore, it is useful in treatment of cancer due to superior selective binding ability to Fc?RIIIa among Fc receptors, and can be prepared as a homogeneous aglycosylated antibody through bacterial culture.

Abstract: The present invention relates to compositions comprising erenumab and one or more erenumab variants, including isomerization variants, deamidation variants, acidic variants, and HMW species. Pharmaceutical formulations comprising the erenumab compositions and methods of using and characterizing the compositions are also described.

Abstract: The present disclosure relates to a multi-specific antibody molecule comprising or consisting of three polypeptides: a) a polypeptide chain of formula (I):(Vxx)nVx-Cx-X-V1; and b) a polypeptide chain of formula (II): (Vyy)nVy-Cy c) a polypeptide of formula (III):V2 wherein Vx represents a variable domain, Vxx represents a variable domain, Cx represents a constant region, X represents a linker, V represents a variable domain, Vy represents a variable domain, Vyy represents a variable domain, Cy represents a constant region, V2 represents a variable domain, nindependently represents 0 or 1, wherein the polypeptide chain of formula (I) and the polypeptide chain of formula (II) is aligned such that the constant regions Cx and Cy are paired and the variable domains Vx and Vy are paired to form a binding domain and optionally a disulphide bond is present between V1 and V2, in particular where a disulphide bond is present.

Abstract: Disclosed herein are antibodies or immunogenic fragments thereof that specifically bind to Epstein-Barr virus (EBV) glycoprotein 350 (gp350) or 220 or one or more epitopes of EBV gp350 and neutralize EBV infection. Also disclosed are immunogenic peptides comprising one or more gp350 epitopes, EBV antibody-small molecule conjugates and pharmaceutical compositions comprising the antibody or an immunogenic fragment thereof, one or more epitopes of EBV gp350, one or more immunogenic peptides, or the EBV antibody-small molecule conjugate. The antibodies, epitopes, immunogenic peptides, conjugates, and pharmaceutical compositions can be used to treat or prevent EBV infections and EBV-associated conditions and diseases.

Abstract: The present invention provides, among other things, methods of formulating nucleic acid-containing nanoparticles with an enzyme to afford efficient delivery of payload to a cell or tissue of interest via subcutaneous administration. In some embodiments, the present invention provides a process in which mRNA-loaded lipid nanoparticles are co-mixed with various amounts of hyaluronidase and administered via subcutaneous administration. The resulting payload can be efficiently delivered to the liver and other organs or tissues of a treated subject.

Abstract: The present invention relates to anti-human OX40L antibodies, new medical uses and methods.

Abstract: Described herein are methods for selecting cancer patients for treatment with a combination therapy comprising entinostat and a second therapeutic agent. In particular, methods are provided for the examination of a non-cancer cell type, myeloid-derived suppressor cells, e.g., those which are CD14-positive and HLA-DR-(lo/negative), as a therapeutic indicator in the setting of entinostat combination therapies.

Abstract: A population of genetically engineered immune cells (e.g., T cells), which express a chimeric antigen receptor (CAR) specific to CD19 and contain a disrupted TRAC gene, a disrupted B2M gene, or both, for use in treating a B cell malignancy.

Abstract: The present invention provides antibodies that bind to CD47 with high affinity and specificity, and their use in treatment of a cancer.

Abstract: The disclosure provides methods of treating inflammation without inducing immune suppression. The method comprises administering a therapeutically effective amount of an IL-6 antagonist at a dose sufficient to reduce inflammation without causing immune suppression.

Abstract: Methods and pharmaceutical compositions for treatment of amyloid deposition diseases using chimeric (e.g., mouse-human) antibody are disclosed, including a method for treating amyloid deposition diseases with cardiac involvement by administering pharmaceutical compositions comprising a chimeric anti-amyloid fibril antibody. The methods herein can improve myocardial function in patients diagnosed with light chain amyloid light chain amyloidosis (ALA) having a cardiac involvement in as little as three weeks after treatment.

Abstract: Methods for making modified Fc regions of antibodies and antibody fragments, both human and humanized, and having enhanced stability and efficacy, are provided. Antibodies comprising Fc regions with core fucose residues removed, and attached to oligosaccharides comprising terminal sialyl residues, are provided. Antibodies comprising homogeneous glycosylation of Fc regions with specific oligosaccharides are provided. Fc regions conjugated with homogeneous glycoforms of monosaccharides and trisaccharides, are provided. Methods of preparing human antibodies with modified Fc using glycan engineering, are provided.

Abstract: Markers of acute myeloid leukemia stem cells (AMLSC) are identified. The markers are differentially expressed in comparison with normal counterpart cells, and are useful as diagnostic and therapeutic targets.

Abstract: The present disclosure relates to, inter alia, a method of quantitating an amount of an antibody molecule from a mixture comprising two or more antibody molecules, comprising separating each of the two or more antibody molecules from the mixture by hydrophobic interaction chromatography high performance liquid chromatography (HIC-HPLC) and quantitating an amount of each antibody molecule, wherein the molecular weight of each antibody molecule is within 15 kDa of any other antibody molecule in the mixture and either each antibody molecule is different from another antibody molecule in the mixture by more than about 0.25 unit on the Kyte & Doolittle hydropathy scale or each of the antibody molecules when run alone on HIC-HPLC elutes at distinct run time with little overlap from the other antibody molecules in the mixture, or both.

Abstract: The application provides methods of diagnosis, prognosis, prophylaxis and treatment of CD30+ cancers.

Abstract: Methods for diagnosing or treating immune disorders in a subject are provided. The methods are based on the detection or modulation of Refractory state Inducing Factor (RIF).

Abstract: Substituted cyclohexyl chemical entities of Formula (I): wherein Ra, G, and Rb have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive therapies; modulating and treating disorders mediated by nociceptin activity or dopamine signaling; treating neurological disorders, neurodegenerative diseases, depression, and schizophrenia; enhancing the efficiency of cognitive and motor training; and treating peripheral disorders, including renal, respiratory, gastrointestinal, liver, genitourinary, metabolic, and inflammatory disorders.

Abstract: The present invention relates to novel compositions and methods for regulating an immune response in a subject. More particularly, the invention relates to specific antibodies that regulate the activity of NK cells and allow a potentiation of NK call cytotoxicity in mammalian subjects. The invention also relates to fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly in therapy, to increase NK cell activity or cytotoxicity in subjects.

Abstract: Provided herein are modified anti-SARS-COV-2 antibodies or antigen binding fragments thereof having extended half life and optimized immune activities. Disclosed herein is also directed to pharmaceutical compositions comprising the same and a method for treating or preventing a disease in human patients that is caused by or related to the infection of SARS-COV-2.

Abstract: The present disclosure relates generally to the fields of immunology and molecular biology. More specifically, provided herein are pharmaceutical combinations comprising (A) antibodies, or antigen-binding portions thereof, directed against LY75, and (B) a second anti-cancer entity; nucleic acids encoding antibody combinations; methods for preparing antibody combinations; and methods for the treatment of diseases, such as cancers mediated by LY75 expression or activity.

Abstract: Neutralizing antibodies through recombinant protein expression were identified by mining antibody repertoires by high-throughput second generation sequencing. Sequencing across the majority of light and heavy chain variable regions of chicken immunoglobulins was performed at two immunological time points: a non-immune (naive) state and a post-hyperimmunization state. The mRNA was extracted from unsorted and unselected PBMC populations and identification of antigen-specific antibody sequences leveraged the significant disparity of abundance of an individual B cell clone in non-immune and immunized states. Through bioinformatic analysis, candidate amino acid sequences for variable heavy chain and light chains were identified. Recombinant polypeptides with the binding domains having the identified amino acid sequences for variable heavy chain and light chains were expressed and screened using immunoassays to confirm antigen-specificity.

Abstract: Disclosed are chimeric antigen receptor (CAR) polypeptides comprising a CD229 antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Disclosed are nucleic acid sequences capable of encoding a CAR polypeptide comprising a CD229 antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Also disclosed are vectors and cells comprising one or both of the CAR polypeptides and nucleic acid sequences capable of encoding CAR polypeptides. Also disclosed are methods of treating.