The present disclosure relates to compounds (e.g., antibodies, antigen-binding fragments thereof, bispecific molecules, or chimeric antigen receptor polypeptides) that bind to a neoepitope of mutant nucleophosmin (NPM1c) in complex with, or presented by, a class I major histocompatibility complex (MHC class I) protein, or cells expressing such compounds, and their use in methods for treating, or ameliorating one or more symptoms of, cancer.

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.

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

The invention is in the field of TNF signalling. Compounds have been identified which are capable of modulating signalling of TNF trimers through receptors. Methods of identifying such compounds are therefore provided. The compounds themselves have utility in therapy.

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

Provided is a long-acting PCSK9-specific binding protein and application thereof. Provided is an MV072 protein with unique complementarity-determining regions, i.e., a binding protein specifically binding to proprotein convertase subtilisin kexin type 9 (PCSK9). The protein can specifically bind to PCSK9, effectively inhibit the function of PCSK9 and reduce plasma LDL cholesterol level. Further provided is an application of the binding protein in treating diseases related to or influenced by the function of PCSK9.

Provided herein are HLA-PEPTIDE targets and antigen binding proteins that bind HLA-PEPTIDE targets. Also disclosed are methods for identifying the HLA-PEPTIDE targets as well as identifying one or more antigen binding proteins that bind a given HLA-PEPTIDE target.

Disclosed herein are methods and compositions for targeting a complex comprising a neoantigen presenting protein and a neoantigen in cancer. Further disclosed herein are antibodies that selectively bind to a complex comprising a neoantigen presenting protein and a neoantigen, as well as methods of use thereof.

The present invention relates to an antigen-binding molecule comprising a heavy chain variable region comprising a heavy-chain complementarity-determining region 1 (HCDR1) comprising an amino acid sequence represented by Sequence No. 1, an HCDR2 comprising an amino acid sequence represented by Sequence No. 2, and an HCDR3 comprising an amino acid sequence represented by Sequence No. 3; a light-chain variable region comprising a light-chain complementarity-determining region 1 (LCDR1) comprising an amino acid sequence represented by Sequence No. 4, an LCDR2 comprising an amino acid sequence represented by Sequence No. 5, and an LCDR3 comprising an amino acid sequence represented by Sequence No. 6; wherein the antigen-binding molecule is a T cell receptor (TCR); and to a cell line expressing the same.

The present invention relates generally to the field of antigen binding proteins such as antibodies, in particular those which bind to HLA-DQ2.5:DQ2.5-glia-α1a, or which bind to HLA-DQ2.5:DQ2.5-glia-α2. The invention further relates to compositions and immunoconjugates comprising such antibodies and to methods of producing such antibodies. The invention also relates to methods and uses which employ such antibodies, for example in the treatment of celiac disease.