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.

Antibodies that include a sulfatase motif-containing tag in a constant region of an immunoglobulin (Ig) light chain polypeptide are disclosed. The sulfatase motif can be converted by a formylglycine-generating enzyme (FGE) to produce a formylglycine (fGly)-modified Ig light chain polypeptide. An fGly-modified Ig light chain polypeptide of the antibody can be covalently and site-specifically bound to a moiety of interest to provide an antibody conjugate. The disclosure also encompasses methods of production of such tagged Ig light chain polypeptides, fGly-modified Ig light chain polypeptides, and antibody conjugates, as well as methods of use of same.

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.

A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that present a choice of two human light chain variable gene segments such that the immunoglobulin light chains expresses by the mouse comprise one of the two human light chain variable gene segments. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided.

This invention provides a bispecific antibody that (i) specifically binds to the extracellular portion of human angiotensin converting enzyme 2 (hACE2); (ii) specifically binds to the extracellular portion of human TMPRSS2 (hTMPRSS2); (iii) does not significantly inhibit the ability of hACE2 to cleave angiotensin II and/or a synthetic MCA-based peptide; and (iv) specifically inhibits the entry into hACE2.sup.+/hTMPRSS2.sup.+ human cells of a pseudovirus bearing SARS-CoV-2 S protein. This invention also provides related pharmaceutical compositions, recombinant nucleic acid molecules, vectors, AAV particles, therapeutic and prophylactic methods, and kits.

Methods for cancer treatment include administering to a cancer patient an anti-CD38 antibody-attenuated human IFN alpha-2b construct and lenalidomide or pomalidomide. Tumors that may be treated according to these methods include tumors which comprise CD-38 expressing tumor cells, including B-cell lymphoma, multiple myeloma, non-Hodgkin's lymphoma, chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphocytic leukemia.

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.

Peptides and uses thereof, such as a common light chain in an antibody, are provided.

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.