Novo Nordisk A/s

Inger Lautrup-Larsen

Per Balschmidt

Frantisek Hubalek

Svend Ludvigsen

Peter Kresten Nielsen

Svend Havelund

Thomas Børglum Kjeldsen

Asser Sloth Andersen

Ulla Ribel-Madsen

Per Noergaard

Per Nørgaard

Rita Slaaby

Per NØRGAARD

The present invention relates to novel insulin analogs comprising mutations at position A14 in the A chain and at positions B27, B28, B29 and B30 in the B chain and exhibiting resistance towards protease; a method for the preparation of such insulin analogs; insulin preparations containing the insulin analogs of the invention; and, a method of treating diabetes mellitus using these insulin analogs.

Protease-stabilized insulin analogues

Expression of FGF21 in apmt2 knock out strain reduces the O-glycosylation significantly and does not decrease the expression level. Expression in mkc7 knock out strain can decrease degradation of FGF21 and analogues thereof. Point mutations at position R17 and R36 can decrease degradation of FGF21 and analogues thereof when they are expressed in yeast.

Process for preparing FGF21 with low degree of O-glycosylation

The present invention relates to novel insulin analogues exhibiting resistance towards protease, wherein at least two amino acids are substituted and/or deleted relative to the parent insulin molecule. A method for the preparation of such insulin analogues, insulin preparations containing the insulin analogues of the invention and a method of treating diabetes mellitus using these insulin analogues is also provided.

Protease resistant insulin analogues

The invention provides an improved method for producing polypeptides with a C-terminal glycine in a yeast transformant being characterized in having a non functional KEX1 gene. The method is in particular well suited to produce polypeptides with an aromatic amino acid residue attached to the C-terminal glycine. The yeast strain may have further non-functional protease genes selected from PEP4, YPS1, MKCI, YPS3, YPS5, YPS6, YPS7, PRB1, STE13 and KEX2.

Method for making polypeptides

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Virum, Denmark

Inger Lautrup-Larsen