The present invention relates, in part, to cell-based gene therapies, including those targeting, by way of non-limiting example, TDP43 and A? aggregates, for the use in neurodegenerative disorders, including without limitation Amyotrophic Lateral Sclerosis (ALS) and Alzheimer's Disease, respectively.

Human IgG1, IgG2, and IgG4 mutants having mutations in the hinge domain and exhibiting altered binding activity to Fc? receptors such as Fc?RIIB (CD32B). Also provided herein are methods for selectively activating immune responses in a subject using a therapeutic agent capable of targeting both an immune cell surface receptor and Fc?RIIB.

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.

A method of producing an antibody fragment for a target antigen includes administering an immunizing mixture containing the target antigen to a cartilaginous fish for at least two times; collecting a blood sample from the cartilaginous fish; extracting RNAs from the blood sample; subjecting said RNAs to reverse transcription to obtain a complementary DNA, and optionally amplifying the cDNA to obtain a mixture of amplified cDNAs followed by purification. Also covered are methods of producing an antibody fragment from a shark; antibody fragments obtained from the method; a kit comprising antibody fragments; and methods of determining the presence and/or amount of a target antigen in a sample.

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.

The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAG3 as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.

The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAG3 as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.

The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAG3 as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.

Provided herein are methods of producing a recombinant polypeptide containing two chains, such as an immune mobilizing monoclonal T-cell receptor against cancer (ImmTAC) protein including an alpha chain and a beta chain. In particular, methods are provided for producing heterologous secretory proteins in bacteria through utilization of optimized expression vectors and culture processes.

Provided is an isolated TrkB agonist antibody that binds to an epitope contained in one of the extracellular domains of TrkB and is capable of activating TrkB, wherein the extracellular domains comprises extracellular D1, D2, D3, D4, D5 domains and juxtamembrane domain of TrkB. Methods of using the TrkB agonist antibody in treating or reducing the risk of a TrkB associated conditions in a subject, wherein said condition is selected from cell differentiation, synaptic development, neural injury repairing and/or neurite branching.