Patent application EP16174019A (EP), filed 2016-06-10
Publication number: EP3254671A1
Title: HIGH CONCENTRATION IMMUNOGLOBULIN COMPOSITION FOR PHARMACEUTICAL APPLICATION
Abstract: [0001]    The present invention relates to a liquid composition comprising polyclonal immunoglobulins, at least one viscosity modulating amino acid, selected from arginine and histidine, and at least one stabilising amino acid, selected from glycine and proline, wherein more than 90% of the polyclonal immunoglobulins are in the form of monomers or dimers and less than 5% in the form of polymers, and wherein the immunoglobulin concentration in the composition is above 160 g/L and the pH is in the range from 5.2 to 5.9. The invention further relates to a liquid composition for use in medical treatment, to amino acids for formulating a highly concentrated polyclonal immunoglobulins as well as a method of formulating.
IPC codes: A61K  47/    18            A I
A61K   9/    00            A I
A61K   9/    08            A I
Claims: number: 1
text: A liquid composition comprising polyclonal immunoglobulins, at least one viscosity modulating amino acid, selected from arginine and histidine, and at least one stabilising amino acid, selected from glycine and proline, wherein more than 90% of the polyclonal immunoglobulins are in the form of monomers or dimers and less than 5% in the form of polymers, and wherein the immunoglobulin concentration in the composition is above 160 g/L and the pH is in the range from 5.5 to 5.9.
number: 2
text: The liquid composition according to claim 1, wherein the immunoglobulin concentration is in the range from 150 to 300 g/L, in particular in the range from 160 to 260 g/L.
number: 3
text: The liquid composition according to claim 1 or 2, wherein the pH is in the range from 5.6 to 5.8.
number: 4
text: The liquid composition according to any of claims 1 to 3, characterised by
number: 5
text: The liquid composition according to any of claims 1 to 4, wherein the total concentration of the stabilizing amino acid(s) and the viscosity reducing amino acid(s) is in the range from 100 to 400 mM, preferably in the range from 150 to 350 mM, more preferably in the range from 200-300 mM, in particular in the range from 225 to 275 g/L.
number: 6
text: The liquid composition according to any of claims 1 to 5, wherein the
number: 7
text: The liquid composition according to any of claims 1 to 6, wherein the concentration of stabilizing amino acid(s) is in the range from 130 to 220 mM, preferably in the range from 150 to 200 mM, preferably in the range from 160 to 190 mM, in particular in the range from 170 to 180 mM.
number: 8
text: The liquid composition according to any of claims 1 to 7, wherein the concentration of viscosity modulating amino acid(s) is in the range from 50 to 100 mM, preferably in the range from 60 to 90 mM, preferably in the range from 65 to 85 mM, in particular in the range from 70-80 mM.
number: 9
text: The liquid composition according to any of claims 1 to 8, wherein the concentration of proline is in the range from 140 to 160 mM and the concentration of arginine is in the range from 70 to 100 mM.
number: 10
text: The liquid composition according to any of claims 1 to 9 wherein the preparation has a storage stability of at least 40 months, preferably of at least 60 months at 2 to 8°C, more preferably of at least 69 months.
number: 11
text: The liquid composition according to any of claims 1 to 10, wherein the composition contains sodium acetate, preferably in the range from 10 to 30 mM, more preferably about 20 mM and/or sodium chloride, preferably in the range from 10 to 30 mM, more preferably about 20 mM.
number: 12
text: The liquid composition according to any of claims 1 to 11, containing one or more excipients selected from surfactant, detergent or saccharide or a combination thereof.
number: 13
text: The liquid composition according to any of claims 1 to 12, wherein the composition has haemagglutinins titers of ≤16 for anti-A and ≤8 for anti-B when being determined by the Direct Coombs Test.
number: 14
text: The liquid composition according to any of claims 1 to 13, wherein the composition is an immunoglobulin G composition with an immunoglobulin G content of 185 to 215 g/L, a pH value of 5.5 to 5.9 and a dynamic viscosity of >12 up to 30 mPa*s, when being formulated with 150 to 210 mM glycine and 50-105 mM arginine.
number: 15
text: A liquid composition for use in medical treatment, wherein the liquid composition is defined in according to any of claims 1 to 14, and wherein the treatment comprises administering the liquid composition to a patient by intramuscular injection or subcutaneous injection.
number: 16
text: A method of formulating a highly concentrated polyclonal immunoglobulin composition, comprising the steps of:
Office action: search_report, dated 2017-12-13
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Final disposition: pending (2017-12-13)