A method of preparing a conditionally active polypeptide from a parent polypeptide, comprising steps of evolving a DNA encoding the parent polypeptide by increasing a net charge of the parent polypeptide using one or more techniques selected from increasing a total number of codons of charged amino acid residues in the DNA and decreasing a total number of codons of uncharged amino acid residues in the DNA to create mutant DNAs; expressing the mutant DNAs to obtain mutant polypeptides; and selecting the conditionally active polypeptide from the mutant polypeptides which exhibits a decrease in activity in a first assay at a first value of a condition compared to the same activity in a second assay at a second value of the same condition. The conditionally active polypeptide, pharmaceutical compositions containing same, nanoparticle and drug conjugates thereof and uses thereof are also provided.

The present invention relates to a method for producing an active form of a long-acting insulin analogue derivative, in which the amino acid at position 22 of the insulin B-chain is substituted from arginine (Arg) to lysine (Lys), so that the insulin analogue can be converted to an active form without cleavage of the B-chain even when it is reacted with clostripain. In a conventional method of converting pro-insulin to an active form by use of trypsin, an albumin binding domain is cleaved, making it difficult to convert the long-acting insulin analogue derivative to an active form. The production method according to the present invention overcomes this difficulty, and thus it can be effectively used for the production of a long-acting therapeutic agent for treatment of diabetes.

The present invention relates to a method for producing an active form of a long-acting insulin analogue derivative, in which the amino acid at position 22 of the insulin B-chain is substituted from arginine (Arg) to lysine (Lys), so that the insulin analogue can be converted to an active form without cleavage of the B-chain even when it is reacted with clostripain. In a conventional method of converting pro-insulin to an active form by use of trypsin, an albumin binding domain is cleaved, making it difficult to convert the long-acting insulin analogue derivative to an active form. The production method according to the present invention overcomes this difficulty, and thus it can be effectively used for the production of a long-acting therapeutic agent for treatment of diabetes.

Provided herein are compositions and methods to make and use engineered cells, for the purpose of increasing the cell density of a culture comprising metazoan cells and for the production of a cultured edible product.

Provided herein are compositions and methods to make and use engineered cells, for the purpose of increasing the cell density of a culture comprising metazoan cells and for the production of a cultured edible product.

A compound for the sequestration of undesirable antibodies associated with hemophilia A, in particular when treated by factor VIII replacement therapy. The compound includes a biopolymer scaffold and at least two peptides derived from factor VIII with a sequence length of 6-13 amino acid, wherein each of the peptides independently includes a 6-amino-acid fragment of the amino-acid sequence of factor VIII, optionally wherein at most three, preferably at most two, more preferably at most one amino acid is independently substituted by any other amino acid. Also provided are pharmaceutical compositions including the compound, as well as methods for treating hemophilia A.

The present invention inter alia relates to the use of phosphotidylserine or pathogenic sugar targeted therapeutics for the management and treatment of microbial infections, including Zika, Dengue, West Nile, Ebola, H1N1, enteroviruses, Leishmaniasis, Malaria and Coronaviruses SARS-COV. In an aspect, the invention concerns a fusion construct comprising an Ig-Fc domain or other protein scaffold, such as albumin, and a peptide, protein, or antibody fragment binding to phosphatidylserine and/or a peptide or protein binding to and/or recognizing a PAMP expressed by a microbe. Other aspects are described.

The present invention inter alia relates to the use of phosphotidylserine or pathogenic sugar targeted therapeutics for the management and treatment of microbial infections, including Zika, Dengue, West Nile, Ebola, H1N1, enteroviruses, Leishmaniasis, Malaria and Coronaviruses SARS-COV. In an aspect, the invention concerns a fusion construct comprising an Ig-Fc domain or other protein scaffold, such as albumin, and a peptide, protein, or antibody fragment binding to phosphatidylserine and/or a peptide or protein binding to and/or recognizing a PAMP expressed by a microbe. Other aspects are described.

A method of preparing a conditionally active polypeptide from a parent polypeptide, comprising steps of evolving a DNA encoding the parent polypeptide by increasing a net charge of the parent polypeptide using one or more techniques selected from increasing a total number of codons of charged amino acid residues in the DNA and decreasing a total number of codons of uncharged amino acid residues in the DNA to create mutant DNAs; expressing the mutant DNAs to obtain mutant polypeptides; and selecting the conditionally active polypeptide from the mutant polypeptides which exhibits a decrease in activity in a first assay at a first value of a condition compared to the same activity in a second assay at a second value of the same condition. The conditionally active polypeptide, pharmaceutical compositions containing same, nanoparticle and drug conjugates thereof and uses thereof are also provided.

A method of preparing a conditionally active polypeptide from a parent polypeptide, comprising steps of evolving a DNA encoding the parent polypeptide by increasing a net charge of the parent polypeptide using one or more techniques selected from increasing a total number of codons of charged amino acid residues in the DNA and decreasing a total number of codons of uncharged amino acid residues in the DNA to create mutant DNAs; expressing the mutant DNAs to obtain mutant polypeptides; and selecting the conditionally active polypeptide from the mutant polypeptides which exhibits a decrease in activity in a first assay at a first value of a condition compared to the same activity in a second assay at a second value of the same condition. The conditionally active polypeptide, pharmaceutical compositions containing same, nanoparticle and drug conjugates thereof and uses thereof are also provided.