Novo Nordisk A/s

Svend Havelund

Ib Jonassen

Jan Markussen

Thomas Hoeg-Jensen

Per Balschmidt

Per Hertz Hansen

Ulla Ribel-Madsen

Peter Kurtzhals

Peter Madsen

Frantisek Hubalek

Niels Christian Kaarsholm

Jakob Brandt

Helle Birk Olsen

Morten Schlein

Asser Sloth Andersen

Dorte Bjerre Steensgaard

Palle Jakobsen

Patrick William Garibay

Svend Ludvigsen

Tina Møller Tagmose

Mathias Norrman

Jeppe Sturis

Susanne Hostrup

Helle Naver

Thomas B&oslash;rglum Kjeldsen

John Halstro Slashedm

John Halstrom

Janos Tibor Kodra

Thomas Børglum Kjeldsen

Peter Kresten Nielsen

Christian Poulsen

Knud Vad

János Tibor Kodra

Holger Martin Strauss

Rosa Rebecca Erritzoee Hansen

Jesper Soendergaard Pedersen

Inger Lautrup-Larsen

Tine Glendorf

Soren Ostergaard

Simon Bjerregaard Jensen

Per Nørgaard

Lauge Schaffer

Anne Plum

Elsebeth Norup

Liselotte Langkjaer

Liselotte Langkjae Buttedr

Karen-Margrethe Pedersen

Kasper Huus

Annette Frost Petterson

Thomas H&oslash;eg-Jensen

Annette Frost Pettersson

Signe Ridderberg

John B Halstrøm

Rosa Rebecca Erritzøe Hansen

Jesper Søndergaard Pedersen

Ulla Ribel

The invention concerns a soluble insulin preparation comprising NϵB29-hexadecandioyl-γ-Glu-(desB30) human insulin in a concentration from 1800 nmol/ml to 4200 nmol/ml, Zinc ions in a concentration from 4.0 Zn/6Ins to 7.0 Zn/6Ins, Niacinamide in a concentration from 110 mM to 220 mM or treprostinil in a concentration from 0.02 μg/ml to 1 μg/ml, Citrate in a concentration from 6 mM to 40 mM, and pH in the range from 7.0 to 8.0. The invention further comprises a method for using the soluble insulin preparation for reducing the blood glucose level in a mammal and a process for preparing the soluble insulin preparations.

High concentration insulin formulation

The invention is related to insulin compositions with a high content of zinc atoms per six molecules of acylated insulin. The insulin is an acylated insulin and may be mixed with a further insulin analogue such as the rapid acting insulin Asp B28 human insulin.

Insulin compositions and method of making a composition

The present invention is in the field of pharmaceutical compositions for the treatment of medical conditions relating to diabetes. More specifically the invention provides pharmaceutical compositions comprising a long-acting acylated derivative of a human insulin analogue, and to the medical use of such compositions for basal insulin administration therapy.

Insulin containing pharmaceutical compositions

The present invention is in the field of pharmaceutical compositions for the treatment of medical conditions relating to diabetes. More specifically the invention provides pharmaceutical compositions comprising a long-acting acylated derivative of a human insulin analog, and to the medical use of such compositions for basal insulin administration therapy.

The present invention relates to a method for spray-drying of protein solutions and the spray-dried protein product. The invention also relates to pharmaceutical compositions containing such spray-dried protein, to methods of treating diabetes and hyperglycaemia using the spray-dried protein of the invention and to the use of such spray-dried protein in the treatment of diabetes and hyperglycaemia.

Method for drying a protein composition, a dried protein composition and a pharmaceutical composition comprising the dried protein

The invention concerns a soluble pharmaceutical formulation comprising an insulin derivative wherein the formulation further comprises more than 4 zinc atoms per 6 molecules of the insulin derivative, and a citric acid monohydrate and/or a histidine compound used in an amount sufficient to increase the tendency of the insulin derivative to self-associate into dodecamers. The invention further comprises a process for preparing the soluble pharmaceutical formulation.

Pharmaceutical formulations comprising an insulin derivative

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 present invention relates to novel human insulin derivatives which are soluble at physiological pH values and have a prolonged profile of action. The invention also relates to methods of providing such derivatives, to pharmaceutical compositions containing them, to methods of treating diabetes and hyperglycaemia using the insulin derivatives of the invention and to the use of such insulin derivatives in the treatment of diabetes and hyperglycaemia.

Insulin derivative

If albumin is added to a pharmaceutical formulation containing acylated insulin described in WO 2009/022005 and WO 2009/022013, the acylated insulin can be kept in solution after subcutaneous injection.

Pharmaceutical solution of non covalently bound albumin and acylated insulin

The present invention is related to insulin derivatives having a side chain attached either to the &#x3b1;-amino group of the N-terminal amino acid residue of B chain or to an &#x3b5;-amino group of a Lys residue present in the B chain of the parent insulin molecule via an amide bond which side chain comprises one or more residues of ethyleneglycol, propyleneglycol and/or butyleneglycol containing independently at each termini a group selected from &#x2014;NHand &#x2014;COOH; a fatty diacid moiety with 4 to 22 carbon atoms, at least one free carboxylic acid group or a group which is negatively charged at neutral pH; and possible linkers which link the individual components in the side chain together via amide or ether bonds, said linkers optionally comprising a free carboxylic acid group.

Insulin derivatives

The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the &#x3b1;-amino group of the N-terminal amino acid residue of the B chain or to the &#x3b5;-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula:&#x2014;W&#x2014;X&#x2014;Y&#x2014;Zwherein W, X, Y and Z are as defined in the disclosure.

The invention is related to fast acting insulin analogues which can form soluble mix-tures (pre-mixed or self-mixed) with long acting insulin analogues. The fast action is achieved through monomerizing substitutions/deletions in the C-terminus of the B-chain of human insulin and the mixability with long acting insulin analogues is achieved through a substitution of the Zn-binding His in position B10 of human insulin with a Gln amino acid residue. In one embodiment the invention is related to fast acting insulin analogues in which at least one of the natural amino acid residues in position B22-B30 in the human B-chain has been substituted with another amino acid residue having the effect of promoting formation of the monomeric form of insulin, the His amino acid residue in position 10 in the B-chain is substituted with a Gln and wherein further one or more of the amino acid residues in position B22-B30 optionally have been deleted.

Rapid acting insulin analogues

Insulin preparations comprising an insulin compound or a mixture of two or more insulin compounds, a nicotinic compound and an amino acid.

Preparation comprising insulin, nicotinamide and an amino acid

The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the &#x3b1;-amino group of the N-terminal amino acid residue of the B chain or to the &#x3b5;-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula:-W-X&#x2014;Y-Zwherein W, X, Y and Z are as defined in the disclosure.

A pharmacologically active peptide hormone derivative in which the parent peptide hormone has been modified by introducing either a lipophilic substituent, W, in the N-terminal amino acid or a lipophilic substituent, Z, in the C-terminal amino acid of the parent peptide hormone or an analogue thereof, said lipophilic substituent having from 8 to 40 carbon atoms, has a protracted profile of action.

Peptide derivatives

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Bagsvaerd, Denmark

Svend Havelund