The screening method of the present invention is useful for screening drugs such as insulin secretagogues having an insulin secretagogue activity with minimized side effects (hypoglycemia induction, etc.). The transformant in which a polynucleotide encoding the fusion protein used for the screening method is introduced, the screening kit comprising the transformant, etc. are also useful for screening excellent drugs.

The present invention relates to a method for the non-denaturing preparation of peptide or protein nanoprecipitates, or of peptide or protein and metal ion nanocoprecipitales, in which said protein or said peptide has a molecular weight no higher than 20 kDa, preferably no higher than 15 kDa, advantageously no higher than 10 kDa, and more advantageously no higher than 8 kDa. Said method includes a step of preparing a mixture of an aqueous solution of peptides or proteins, a nonsolvent of the peptide or protein, and optionally a water-soluble metal salt. The present invention also relates to a nanoprecipitate that can be obtained by the method according to the invention, as well as to a pharmaceutical composition comprising same, for use in the treatment or prevention of diabetes.

The present invention relates to a method for the non-denaturing preparation of peptide or protein nanoprecipitates, or of peptide or protein and metal ion nanocoprecipitales, in which said protein or said peptide has a molecular weight no higher than 20 kDa, preferably no higher than 15 kDa, advantageously no higher than 10 kDa, and more advantageously no higher than 8 kDa. Said method includes a step of preparing a mixture of an aqueous solution of peptides or proteins, a nonsolvent of the peptide or protein, and optionally a water-soluble metal salt. The present invention also relates to a nanoprecipitate that can be obtained by the method according to the invention, as well as to a pharmaceutical composition comprising same, for use in the treatment or prevention of diabetes.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

Long-acting co-agonists of the glucagon and GLP-1 receptors are described.

Long-acting co-agonists of the glucagon and GLP-1 receptors are described.

The present invention relates to long-acting insulin analogues having an increased in vivo half-life in which the amino acid at position 22 of the B-chain of native insulin is substituted and one or more amino acids of the A-chain or B-chain of native insulin are additionally substituted, and to long-acting insulin analogue derivatives having a further increased in vivo half-life in which an albumin-binding domain is additionally fused to the long-acting insulin analogues. The insulin analogues or insulin analogue derivatives according to the present invention have a significantly increased in vivo half-life, and thus can provide convenience to diabetic patients who self-administer insulin by injection.

The present invention relates to long-acting insulin analogues having an increased in vivo half-life in which the amino acid at position 22 of the B-chain of native insulin is substituted and one or more amino acids of the A-chain or B-chain of native insulin are additionally substituted, and to long-acting insulin analogue derivatives having a further increased in vivo half-life in which an albumin-binding domain is additionally fused to the long-acting insulin analogues. The insulin analogues or insulin analogue derivatives according to the present invention have a significantly increased in vivo half-life, and thus can provide convenience to diabetic patients who self-administer insulin by injection.

Certain aspects of the present invention are directed to a method for making a protein blocking assembly reversibly linking a therapeutic protein to a blocking group via a linker moiety. Additional aspects of the invention are directed to the protein blocking assembly, and to methods of administering the protein blocking assembly to a subject, where the protein is cleaved from the protein blocking assembly.