The invention provides anti-human alpha-synuclein antibodies and methods of using the same.

The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular the TAA Serine protease inhibitor Kazal-type 2 (SPINK2). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and SPINK2 binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of SPINK2 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Provided herein are proteins, antibodies, assays and methods useful for modulating growth factor levels and/or activities. In some embodiments, such growth factors are members of the TGF- superfamily of proteins.

Presented herein are novel phosphotyrosine binding compositions, including antibodies and antibody fragments. The inventors of the present disclosure have resolved the crystal structures of two widely utilized pan-specific pY antibodies, PY20 and 4G10. These two known antibodies, although developed independently from animal immunizations, have surprisingly similar modes of recognition of the phosphate group, and revealed a generic binding structure among pan-specific pY antibodies. Based on this newly discovered convergent structure, engineered CDR-L3 loops were developed that impart greatly improved affinity to pY binding antibodies and other pY binding compositions. The inventions disclosed herein include antibodies and antibody fragments bearing these novel CDR-L3 sequences and methods of using such pY binding compositions for the detection of phosphotyrosine-bearing proteins.

The present invention provides monoclonal antibodies that bind to the natriuretic peptide receptor 1 (NPR1) protein, and methods of use thereof. In various embodiments of the invention, the antibodies are fully human antibodies that bind to NPR1. In some embodiments, the antibodies of the invention are useful for activating NPR1 activity, thus providing a means of treating or preventing a disease, disorder or condition associated with NPR1 in humans.

Methods for computational affinity maturation are described wherein a candidate antibody sequence is optimized for affinity, stability, or both, first utilizing computational saturation mutagenesis to identify and mutations at those positions that satisfy a predefined first threshold of affinity score or stability score, generating sequences comprising all combinations of the mutations at each position, computing the affinity score, stability score, or both and ranking the variant antibody sequences according to a predefined second threshold, then from the affinity score or stability score of all generated sequences identify the optimized antibody sequences. The method is ideally carried out on multiple CPUs where a server generates the sequences, the CPUs evaluate the affinity or stability score, reports the results to the server, which ranks all of the data from the CPUs to identify the optimal candidates. Optimal candidates can then be expressed and experimentally evaluated to identify future clinical or research reagent antibodies.

Described herein are antibodies, fragments thereof and multi-specific binding agents that bind an Epstein-Barr virus (EBV) latent membrane protein 2 (LMP2) peptide presented by HLA class I molecules, in particular, HLA-A02. Also provided herein are methods of using the same or compositions thereof for the detection, prevention and/or therapeutic treatment of diseases characterized by expression of an EBV-LMP2 peptide presented by HLA-A02, in particular, Burkit's lymphoma, Hodgkin's lymphoma and nasopharyngeal carcinoma.

The present disclosure provides immunotherapeutic compositions and methods for enhancing an immune response and for treating cancer or inflammatory conditions mediated by autoreactive B cells in a subject. In some aspects, multispecific antigen-binding constructs are provided that recognize at least one tumor antigen or B-lineage cell antigen and NKp30 and/or another activating NK receptor. In some aspects, multispecific antigen-binding constructs are provided that recognize at least two tumor antigens or two antigens expressed by B-lineage cells, NKp30, and another activating NK receptor. The multispecific antigen-binding constructs and methods disclosed herein can be used for the treatment of cancer, even a cancer characterized by a CD16 deficient microenvironment and/or characterized by target cells (e.g., cancer cells) having a low level of expression of the tumor antigen.

The present invention relates to antibodies and antigen binding fragments thereof, which bind to a complex of GARP and TGF-1, particularly a complex of human GARP and human TGF-1. These antibodies and antigen binding fragments exhibit a combination of advantageous properties including high affinity antigen binding and the ability to inhibit the release of active TGF- from regulatory T cells. The antibodies and antigen binding fragments of the present invention are relatively resistant to deamidation, isomerization and oxidation, such that they display improved stability.

The present invention relates, in general, to polypeptides capable of transmigrating the blood-brain barrier, and uses thereof. More specifically, the present invention relates to polypeptides derived by site-directed mutagenesis of an existing antibody fragment and uses thereof, and methods of making such molecules. The polypeptides of the present invention show enhanced blood-brain barrier crossing and brain exposure levels in vitro and in vivo.