Novo Nordisk Healthcare Ag

Michael Bech Jensen

Birthe Lykkegaard Hansen

Troels Kornfelt

Anders Klarskov Petersen

Andrew Neil Bowler

Christian Rischel

Anders Dybdal Nielsen

Kirsten Kramer Jakobsen

Karen Pilgaard

The present invention relates to pharmaceutical compositions comprising: (i) at least 10 mg/mL of a Factor VII polypeptide; (ii) a buffering agent suitable for keeping pH in the range of from about 5.0 to about 9.0; (iii) at least one aromatic preservative in a concentration of at least 0.1 mg/mL; and (iv) at least one antioxidant in a concentration of at least 0.1 mg/mL; the composition optionally comprising further components, with the proviso that such further components are not Factor VII polypeptide stabilizing agents selected from (a) metal-containing agents, wherein said metal is selected from the group consisting of first transition series metals of oxidation state +II, except zinc; and (b) stabilizing agents comprising a &#x2014;C(&#x2550;N&#x2014;Z1-R1)-NH&#x2014;Z2-R2 motif.

High concentration factor VII polypeptide formulations comprising an aromatic preservative and an antioxidant

The invention relates to chemically as well as physically stable compositions comprising Factor VII or a Factor VII-related polypeptide such that these compositions can be stored, handled and used at room temperature.

Stabilised solid compositions of factor VII polypeptides

The invention relates to chemically as well as physically stable kits and compositions comprising polypeptides, in particular Factor VII or Factor VII-related polypeptides, such that these compositions can be stored, handled and used at room temperature.

Stabilised compositions of factor VII polypeptides

Provided are storage containers for proteinaceous pharmaceutical compositions which are characterized in, among other things, comprising (i) a wall portion, wherein an inner wall material thereof is selected from silica-coated glass, silicone-coated glass, polymers of non-cyclic olefins, cycloolefin polymers and cycloolefin/linear olefin copolymers and (ii) one or more closure portions not constituting part of the wall portion, and which contains a formulation of a protein. Also provided are new methods of storing proteinaceous compositions. In one aspect, the stored protein is characterized as having an amino-terminal &#x3b3;-carboxyglutamic acid (Gla) domain with 9-12 Gla residues.

Protein stabilization in solution

A liquid aqueous composition comprising (i) a factor VII polypeptide; (ii) an agent suitable for keeping pH in the range of from about 4.0 to about 8.0; (iii) an agent selected from the list of: a calcium salt, a magnesium salt, or a mixture thereof; wherein the concentration of (iii) is at least 15 mM is described.

Liquid composition of factor VII polypeptides

The present invention is directed to liquid, aqueous pharmaceutical compositions stabilized against chemical and/or physical degradation containing Factor VII polypeptides, and methods for preparing and using such compositions, as well as vials containing such compositions, and the use of such compositions in the treatment of a Factor VII-responsive syndrome. The main embodiment is represented by a liquid, aqueous pharmaceutical composition comprising at least 0.01 mg/mL of a Factor VII polypeptide (i); a buffering agent (ii) suitable for keeping pH in the range of from about 4.0 to about 9.0; and at least one stabilizing agent (iii) comprising a &#x2014;C(&#x2550;N&#x2014;Z&#x2014;R)&#x2014;NH&#x2014;Z&#x2014;Rmotif, e.g. benzamidine compounds and guanidine compounds such as arginine.

Liquid, aqueous pharmaceutical compositions of factor VII polypeptides

The present invention is directed to liquid, aqueous pharmaceutical compositions stabilised against chemical and/or physical degradation containing Factor VII polypeptides, and methods for preparing and using such compositions, as well as vials containing such compositions, and the use of such compositions in the treatment of a Factor VII-responsive syndrome. The main embodiment is represented by a liquid, aqueous pharmaceutical composition comprising at least 0.01 mg/mL of a Factor VII polypeptide (i); a buffering agent (ii) suitable for keeping pH in the range of from about 4.0 to about 9.0; and at least one stabilising agent (iii) comprising a &#x2014;C(&#x2550;N&#x2014;Z&#x2014;R)&#x2014;NH&#x2014;Z&#x2014;Rmotif, e.g. benzamidine compounds and guanidine compounds such as arginine.

A liquid aqueous composition comprising (i) a factor VII polypeptide, (ii) an agent suitable for keeping pH in the range of from about 4.0 to about 8.0; (iii) an agent selected from the list of: a calcium salt, a magnesium salt, or a mixture thereof; wherein the concentration of (iii) is at least 15 mM.

The invention concerns a liquid aqueous composition comprising (i) a factor VII polypeptide, (ii) an agent suitable for keeping pH in the range of from about 4.0 to about 9.0; (iii) an agent selected from the group consisting of: a calcium salt, a magnesium salt, or a mixture thereof; wherein the concentration of (iii) is less than 15 mM; and (iv) An ionic strength modifying agent; wherein the ionic strength of the composition is at least 200 mM.

The present invention is directed to liquid, aqueous pharmaceutical compositions stabilized against chemical and/or physical degradation containing Factor VII polypeptides, and methods for preparing and using such compositions, as well as vials containing such compositions, and the use of such compositions in the treatment of a Factor VII-responsive syndrome. The main embodiment is represented by a liquid, aqueous pharmaceutical composition comprising at least 0.01 mg/mL of a Factor VII polypeptide (i); a buffering agent (ii) suitable for keeping pH in the range of from about 4.0 to about 9.0; and at least one stabilizing agent (iii) comprising a &#x2014;C(&#x2550;N-Z-R)&#x2014;NH-Z-Rmotif, e.g. benzamidine compounds and guanidine compounds such as arginine.

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Allerød, Denmark

Michael Bech Jensen