The present patent consists of an engineered multimeric protein complex as antibody substitute composed of human proteins, with an m-fold symmetry, with each m-fold element containing a modified monomeric protein derived from a symmetric human multimeric protein complex fused to a module containing n fused, modified human beta solenoid proteins (mBSP), and that fused to a human derived pathogen binding domain (PBD), as well as a separate antibody substitute composed of P human PBD complexes. The invention may find application in prophylactic and therapeutic treatments for viral infections, especially for COVID19 by neutralizing the SARS-CoV-2 virus.

A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. Engineering T cells with this novel receptor engenders anti-gen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.

The present invention relates to recombinant binding proteins comprising one or more designed ankyrin repeat domains with binding specificity for coronavirus spike proteins, nucleic acids encoding such proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such proteins, nucleic acids or pharmaceutical compositions in the treatment of coronavirus diseases, particularly diseases caused by SARS-CoV-2.

The present invention pertains to the field of protein engineering, and provides means for obtaining stable molecules that specifically bind to a target selected amongst a large variety of ligands families. In particular, the present invention provides methods for obtaining a molecule specifically binding to a target of interest, through a combinatorial mutation/selection approach with an OB-fold protein as a starting molecule. In particular, the target of interest can be of a different chemical nature form that of the native target of the OB-fold protein used as the starting molecule.

Fibronectin type III (.sup.10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative .sup.10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes .sup.10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are .sup.10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.

The present invention generally relates to bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease.

Lipocalin muteins specific to a predetermined antigen can be transduced into a T cell to bring therapeutic benefits to patients in need. In one example, a lipocalin mutein specific to a predetermined antigen (e.g., a target differentially expressed on the surface of a tumor cell) can be transduced into a T cell membrane to serve as an antigen receptor, offering benefits over conventionally deployed antibody-derived protein moieties such as a single chain variable fragment (scFv). Benefits include a more stable structure, leading to superior target engagement, for example. Further, lipocalin muteins specific to a predetermined antigen (e.g. an immunomodulatory target such as an immune checkpoint or costimulatory molecule) can be transduced into a T cell for secretion thereby, bringing an added therapeutic benefit. Specific examples of such modified T cells and methods of making and using the same are provided herein.

The present invention relates to the field of biomedicine and antibody engineering. Specifically, it relates to mono and multispecific multivalent single chain polypeptide molecules and derivatives thereof, preferably to multispecific single chain (tandem) trimerbodies with defined stoichiometry, to nucleic acid sequences and vectors encoding thereof, and host cells expressing the same. It further relates to methods of producing thereof, pharmaceutical compositions, kits, methods of treatment, use as diagnostics or imaging reagents and combination therapies using thereof.

Fibronectin type III (.sup.10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative .sup.10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes .sup.10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are .sup.10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.

Disclosed is a synthetic T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of thyroglobulin (TG), TG.sub.470-478. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.