The present invention is in the therapeutic field of drugs for medical conditions relating to diabetes. More specifically the invention relates to insulin analogues of human insulin. The invention provides pharmaceutical compositions comprising such insulin analogues and the uses if the such analogues for the treatment or prevention of medical conditions relating to diabetes.

The present invention is in the therapeutic field of drugs for medical conditions relating to diabetes. More specifically the invention relates to insulin analogues of human insulin. The invention provides pharmaceutical compositions comprising such insulin analogues and the uses if the such analogues for the treatment or prevention of medical conditions relating to diabetes.

A conjugate of a physiologically active polypeptide and immunoglobulin Fc with attenuated immune response is disclosed. Also disclosed are a method for preparing the conjugate, a composition for reducing an immune response including the conjugate, and a method for reducing the immune response of the physiologically active polypeptide. A method for maintaining the reduction in the intrinsic binding affinity of the conjugate for an Fc gamma receptor and/or a complement, and a composition including the conjugate are also disclosed.

A conjugate of a physiologically active polypeptide and immunoglobulin Fc with attenuated immune response is disclosed. Also disclosed are a method for preparing the conjugate, a composition for reducing an immune response including the conjugate, and a method for reducing the immune response of the physiologically active polypeptide. A method for maintaining the reduction in the intrinsic binding affinity of the conjugate for an Fc gamma receptor and/or a complement, and a composition including the conjugate are also disclosed.

Polypeptides that fold into biologies are stabilized by diselenide bonds between selenocysteine amino acids. Methods to produce such polypeptides in genomically recoded organisms (GRO) can be scaled up for industrial production. Since diselenides have the same geometric bond angles and torsions as disulfides, as well as very similar bond lengths, they can be substituted into polypeptides without disrupting the three dimensional structure of the polypeptides. Diselenides render the polypeptides resistant to reduction when they are exposed to blood serum or to reducing components of blood serum or to reducing components components within cells.

Polypeptides that fold into biologies are stabilized by diselenide bonds between selenocysteine amino acids. Methods to produce such polypeptides in genomically recoded organisms (GRO) can be scaled up for industrial production. Since diselenides have the same geometric bond angles and torsions as disulfides, as well as very similar bond lengths, they can be substituted into polypeptides without disrupting the three dimensional structure of the polypeptides. Diselenides render the polypeptides resistant to reduction when they are exposed to blood serum or to reducing components of blood serum or to reducing components components within cells.

A pharmaceutical composition comprises an effective amount of an insulin analogue comprising modified A-chain and B-chain polypeptides. The modified A chain comprises one or more substitutions relative to wild-type human insulin A-chain selected from a Gln, His or Glu substitution at position A8, a Glu or Ala substitution at position A14, and an Ala, Gln, Gly, or Thr substitution at position A21. The modified B-chain polypeptide comprises one or more modifications relative to wild-type human insulin B-chain selected from a deletion of the amino acid or amino acids at position B1, B1 and B2, or B1-B3, an Ala or Glu substitution at position B2, a Glu or Ala substitution at position B3, an Ala substitution at position B4; and a Glu or Lys substitution at position B29. The composition comprises one or more of iloprost, citrate, EDTA and a polyphosphate compound. The composition may be used to treat diabetes.

Methods for inhibiting an autoimmune disease by administering to a subject a therapeutically effective amount of a composition that induces conversion of naive T cells into Foxp3+ regulatory T cells to induce immunosuppression in the subject. Methods for detecting in a subject an autoimmune disease or a predisposition to a autoimmune disease, and methods for assessing the efficacy of a therapy for an autoimmune disease, particularly type 1 diabetes.

Methods for inhibiting an autoimmune disease by administering to a subject a therapeutically effective amount of a composition that induces conversion of naive T cells into Foxp3+ regulatory T cells to induce immunosuppression in the subject. Methods for detecting in a subject an autoimmune disease or a predisposition to a autoimmune disease, and methods for assessing the efficacy of a therapy for an autoimmune disease, particularly type 1 diabetes.

There is provided a method to synthesise peptides, a peptide being synthesised based on the amino acid sequence of a template peptide, peptides provided by the method and use of the peptides.