The present invention relates to bispecific antigen binding proteins that are capable of binding to both the human CGRP receptor and the human PAC1 receptor. Pharmaceutical compositions comprising the bispecific antigen binding proteins as well as methods for producing them are also disclosed. Methods of using the bispecific antigen binding proteins to ameliorate or treat conditions associated with the two receptors, such as chronic pain, migraine, and cluster headache, are also described.

The present invention provides antibody compositions, including, e.g., antibodies, engineered antibodies and antibody fragments that bind to a tumor necrosis factor receptor superfamily member (i.e., 18), and compositions comprising one or more additional therapeutic agents. Provided compositions are useful in enhancing CD4+ and CD8+ T cell responses, and in the treatment, amelioration and prevention of diseases that can be counteracted with an augmented immune response, e.g., cancers. Also provided are methods of use of combinations that find use in treatment or prevention of cancerous or infectious conditions and disorders.

The present invention relates to transgenic mammals that express canine-based immunoglobulins, including transgenic rodents that express canine-based immunoglobulins for the development of canine therapeutic antibodies.

A humanized antibody or antigen binding fragment that binds to the poliovirus receptor (PVR) can be utilized in the preparation of antibody drug conjugates (ADCs) to target nucleic acids, peptides and proteins, drugs and radiopharmaceuticals to cancer cells. These antibodies or antigen binding fragments can also be used for checkpoint blockade where binding to PVR (CD 155) blocks the PVR from binding TIGIT. The humanized antibodies can be used either alone or in combination with other checkpoint inhibitors known in the art. The humanized antibody or antigen binding fragment of this invention can also modulate the PVR-DNAM-1 axis in order to upregulate DNAM 1 (CD 226) expression on T cells or NK cells, thereby helping to restore immunosurveillance mechanisms. The antibody or antigen binding fragment that bind to PVR can also be incorporated in CAR-T cells or CAR NK cells. Bispecific antibodies can also be produced by incorporating the anti-CD 155 antibodies or antigen binding fragments to engage T cells or NK cells to fight cancers that express CD155. The anti-CD 155 antibodies disclosed here also bind to Nectin 4 thus expanding the potential clinical use to targeting cancers that express CD 155 or Nectin 4.

The invention provides a method for alleviating discogenic pain by administering a therapeutic agent that disrupts neuronal and/or vascular elements in the disc, which is typically a degenerated disc. Disruption of neuronal elements in the disk includes destroying nerve endings without substantially affecting the central body of the nerve, suppressing activation of the nerve endings, and inhibiting the growth of nerve endings into the disk. Disruption of vascular elements includes causing the vascular extensions to retract from the disk, or suppressing the formation of such extensions. The therapeutic agent may be administered locally via an interbody pump, a bolus or a depot, or may be administered systemically.

The present application is directed to heterodimeric antibodies and methods of use.

Disclosed herein are isolated humanized monoclonal antibodies that specifically bind Japanese encephalitis virus (JEV) with a binding affinity of about 1.0 nM or less. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. Methods of treating, preventing, and/or ameliorating JEV infection in a subject with JEV also are disclosed. Additionally, the antibodies can be used to detect JEV in a sample, and methods of diagnosing JEV infection, or confirming a diagnosis of JEV infection in a subject, are disclosed herein that utilize these antibodies.

Antibodies are provided that specifically bind seven human ELR.sup.+ CXC chemokines. The antibodies of the invention are useful for treating various inflammatory/autoimmune diseases, such as inflammatory bowel disease (IBD), plaque psoriasis, and palmoplantar pustulosis; and cancer, such as renal cancer or ovarian cancer.

The present invention is directed to antibodies and fragments thereof (especially chimeric and humanized) having binding specificity for HGF and their use in therapy and diagnosis. These antibodies inhibit or block HGF-associated activities including HGF's effects on cell proliferation, invasion, angiogenesis, metastasis and fibrosis. Particularly the antibodies may be used as a monotherapy or in combination therapies in treating cancer, other proliferative disorders and other conditions wherein inhibition of HGF and/or the HGF/HGF-R (c-met) interaction is desired.

The invention provides improved non-human vertebrates and non-vertebrate cells capable of expressing antibodies comprising human variable region sequences. The present invention is directed to the provision of long HCDR3s from non-human vertebrates and cells. The present invention is also directed to the provision of novel V, D and J pairings in immunoglobulin heavy and light chain loci. Novel, biased antibody diversities and potentially expanded diversities are provided. The invention also provides for novel and potentially expanded diversity or diversity that is biased towards variable gene usage common to antibodies useful for treating and/or preventing certain diseases or conditions, such as infectious diseases. The invention also provides methods of generating antibodies using such vertebrates, as well as the antibodies per se, therapeutic compositions thereof and uses.