Provided herein are compositions and methods for producing milk proteins, which allow for safe, sustainable and humane production of milk proteins for commercial use, such as use in food compositions. The disclosure further teaches methods of increasing the production/accumulation of casein proteins in host cells by co-expressing a kinase capable of phosphorylating the casein protein. Specifically, the disclosure provides host cells comprising a heterologous casein protein and a heterologous casein. Stable transgenic plants expressing heterologous caseins and heterologous kinase proteins are also provided. In some embodiments, the heterologous casein proteins of the disclosure are contained within fusion proteins comprising at least first protein and a second protein, wherein at least one of the first protein and the second protein is a milk protein, or fragment thereof. The disclosure also provides methods for producing the recombinant fusions proteins, and food compositions comprising the same.

The present disclosure provides methods for manufacturing a fXa derivative protein at large scale leading to high yield of highly pure protein product. The method may include adding a detergent to a sample that contains a polynucleotide construct encoding the protein and purifying the protein through a soybean trypsin inhibitor (STI)-based affinity chromatograph, an ion exchange and mixed mode chromatograph and a hydrophobic interaction.

The invention relates to a method for purifying biologically active GLA-domain coagulation proteins, comprising the following steps: a) bringing a sample that contains one or more GLA-domain coagulation proteins and may contain biologically inactive molecules of GLA-domain protein(s), into contact with an affinity support on which nucleic aptamers that bind specifically to at least one biologically active GLA-domain coagulation protein are immobilized, in order to form complexes between (i) said nucleic aptamers and (ii) said GLA-domain coagulation protein(s), b) releasing the GLA-domain coagulation protein(s) from the complexes formed in step a), and c) recovering said biologically active GLA-domain coagulation protein(s) in a purified form.

Compositions and methods are provided for the cell-mediated targeted killing of diseased cells based on the presence of an intracellular antigen, rather than a surface-bound marker. The targeting cells are modified to express a cytotoxic protein that is delivered into a targeted cell, and after delivery is selectively activated by the presence of a cytoplasmic protein of interest. In one embodiment of the invention, the cytotoxic molecule is a Granzyme B (GrB) polypeptide. In the compositions of the invention, GrB is modified to render its cytotoxic enzymatic functions inactive, until the presence of an intracellular antigen unlocks the GrB molecule to enable enzymatic activities.

Compositions and methods are provided for the cell-mediated targeted killing of diseased cells based on the presence of an intracellular antigen, rather than a surface-bound marker. The targeting cells are modified to express a cytotoxic protein that is delivered into a targeted cell, and after delivery is selectively activated by the presence of a cytoplasmic protein of interest. In one embodiment of the invention, the cytotoxic molecule is a Granzyme B (GrB) polypeptide. In the compositions of the invention, GrB is modified to render its cytotoxic enzymatic functions inactive, until the presence of an intracellular antigen unlocks the GrB molecule to enable enzymatic activities.

The modified polypeptides include at least one amino acid substitution that allows the polypeptide to bind better to the S surface glycoprotein of coronaviruses that use ACE2 as a cell entry receptor, either through direct increases in affinity or through improved folding and expression of ACE2. Use of the modified ACE2 polypeptides for inhibiting CoV entry, replication and/or spread, for pre-exposure and post-exposure CoV prophylaxis, and for treating a CoV infection (e.g. COVTD-19), is also described.

Disclosed are a modified FIX (factor IX) polypeptide comprising a leucine, cysteine, aspartic acid, glutamic acid, histidine, lysine, asparagine, glutamine or tyrosine in position 338; pharmaceutical preparations containing said modified FIX polypeptide; a nucleotide sequence coding for the modified FIX polypeptide; and a method for producing the modified FIX polypeptide.

The present invention relates to the conjugation of Factor VII polypeptides with heparosan polymers. The resultant conjugates may be used to deliver Factor VII, for example in the treatment or prevention of bleeding disorders.

The present invention provides a chimeric protein having the formula: Casp-Ht1-Ht2 wherein Casp is a caspase domain; Ht1 is a first heterodimerization domain; and Ht2 is a second heterodimerization domain and wherein, in the presence of a chemical inducer of dimerization (CID), an identical pair of the chimeric proteins interact such that Ht1 from one chimeric protein heterodimerizes with Ht2 from the other chimeric protein, causing homodimerization of the two caspase domains. The invention also provides a cell comprising such a protein and its use in adoptive cell therapy.

Antibodies and antibody fragments that specifically bind to glycoprotein IIb/IIIa (GPIIb/IIIa) are disclosed. Chimeric molecules comprising such antibodies or antigen-binding fragments are also disclosed. In addition, methods of using the disclosed antibodies, antibody fragments, and chimeric molecules, e.g., to target agents to platelets and for the treatment or prevention of diseases or disorders are provided.