Patent application EP19178939A (EP), filed 2019-06-07
Publication number: EP3747903A1
Title: METHOD AND KIT FOR TESTING POTENCY OF IMMUNOGLOBULIN COMPOSITIONS
Abstract: The present invention relates to the field of immunotherapeutics. It provides a method for characterisation and quality control, in particular for determining the potency of an immunoglobulin composition comprising immunoglobulins derived from a plurality of human donors, the method comprising contacting the immunoglobulin composition with pneumolysin, adding erythrocytes to the immunoglobulin composition and determining lysis of the erythrocytes. The invention also provides a corresponding use of pneumolysin, as well as a kit and composition useful in said method. The method can be used for quality control of immunoglobulin concentrate, e.g., of an IgM-containing immunoglobulin composition comprising IgM, IgA and IgG antibodies, and in a method of preparing an immunoglobulin composition. The immunoglobulin compositions obtainable from said method may be used, e.g., in the treatment of pneumonia, e.g., severe community-acquired pneumonia, which may be caused, e.g., by Streptococcus pneumoniae.
IPC codes: C07K  14/   315            A I
C07K  16/    12            A I
G01N  33/   569            A I
G01N  33/   577            A I
Claims: number: 1
text: A method for characterisation and quality control of an immunoglobulin composition comprising at least 30 g/L immunoglobulins derived from a plurality of human donors, the method comprising
number: 2
text: The method of claim 1, further comprising
d) thereby determining the potency of said immunoglobulin composition.
number: 3
text: Use of pneumolysin for characterisation and quality control of an immunoglobulin composition comprising at least 30 g/L immunoglobulins derived from a plurality of human donors.
number: 4
text: The method of any of claims 1 or 2 or the use of claim 2, wherein the immunoglobulin composition comprises IgG, IgM and/or IgA, preferably, all three classes, e.g., the percentage of IgM being about 5-90 % (w/total antibody w).
number: 5
text: The method of any of claims 1-2 or -5 or the use of any of claims 3-4, wherein the immunoglobulin composition is derived from plasma or serum, optionally, plasma.
number: 6
text: The method of any of claims 1-2 or 4-5 or the use of any of claims 3-5, wherein step a) is carried out at 37°C for 15 min to 24 h, preferably, for 20-60 min.
number: 7
text: The method of any of claims 1-2 or 4-6 or the use of any of claims 3-6, wherein the erythrocytes are selected from a group comprising human erythrocytes, sheep red blood cells, and rabbit red blood cells, wherein human erythrocytes are preferred.
number: 8
text: The method of any of claims 1-2 or 4-7 or the use of any of claims 3-7, wherein the concentration is 1-4.5% (v/v) erythrocytes.
number: 9
text: The method of any of claims 1-2 or 4-8 or the use of any of claims 3-8, wherein the mixture of step b) is incubated at 37°C for 5 min to 48 h, preferably, for 40-120 min.
number: 10
text: The method of any of claims 1-2 or 4-9 or the use of any of claims 3-9, wherein the lysis of the erythrocytes is determined by detecting the concentration of haemoglobin in a centrifugation supernatant of the mixture of b at 370-590 nm, wherein the concentration is preferably detected at about 405 nm.
number: 11
text: A method for determining the potency of an immunoglobulin composition comprising at least 30 g/L immunoglobulins derived from a plurality of human donors, comprising carrying out the method of any of claims 1-2 or 4-10.
number: 12
text: The method of any of claims 1-2 or 4-11 or the use of any of claims 3-11, wherein the degree of lysis of the erythrocytes is inversely correlated to the potency of the immunoglobulin composition.
number: 13
text: The method of any of claims 1-2 or 4-12 or the use of any of claims 3-12, wherein the potency of the immunoglobulin composition is compared to the potency of a standard immunoglobulin composition, preferably, to a standard IgM-containing immunoglobulin composition, and the ratio of the potency of the immunoglobulin composition to the potency of the standard immunoglobulin composition is the relative potency.
number: 14
text: A method for preparing a standardized immunoglobulin composition comprising at least 30 g/L immunoglobulins derived from a plurality of donors, comprising
number: 15
text: A kit for carrying out the method of any of claims 1 or 3-14, comprising
number: 16
text: A composition comprising a standard human immunoglobulin composition, preferably, comprising about 23% IgM, about 56% IgG and about 21%IgA (w/total antibody w), and pneumolysin, wherein the composition optionally further comprises erythrocytes.
Office action: search_report, dated 2020-12-09
Rejection reasons: novelty_epc_54
inventive_step_epc_56
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ref_id: - LEA-ANN S. KIRKHAM ET AL, "Otitis-Prone Children Produce FunctionalAntibodies to Pneumolysin andPneumococcal Polysaccharides", AMERICAN SOCIETY FOR MICROBIOLOGY: CLINICAL AND VACCINE IMMUNOLOGY, US, (20170301), vol. 24, no. 3, doi:10.1128/CVI.00497-16, ISSN 1556-6811, pages 1 - 11, XP055641146 [X] 16 * the whole document * * abstract * * page  9; figures 1-5; table 1 * [I] 1-15
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severity: obviousness
ref_id: - DE LOS TOYOS J ET AL, "Functional analysis of pneumolysin by use of monoclonal antibodies", INFECTION AND IMMUNITY, AMERICAN SOCIETY FOR MICROBIOLOGY, US, (19960201), vol. 64, no. 2, ISSN 0019-9567, pages 480 - 484, XP002366575 [ID] 1-13 * the whole document * * abstract * * especially sub-chapter: Inhibition of hemolytic activity.; page  481, column  left * [Y] 14-16
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severity: obviousness
ref_id: - GARCIA-SUAREZ M ET AL, "Protection against pneumococcal pneumonia in mice by monoclonal antibodies to pneumolysin", INFECTION AND IMMUNITY, AMERICAN SOCIETY FOR MICROBIOLOGY, US, (20040801), vol. 72, no. 8, doi:10.1128/IAI.72.8.4534-4540.2004, ISSN 0019-9567, pages 4534 - 4540, XP002366576 [Y] 1-15 * the whole document *
ref_type: npl
severity: obviousness
ref_id: - SUAREZ-ALVAREZ BEATRIZ ET AL, "Characterisation of mouse monoclonal antibodies for pneumolysin: Fine epitope mapping and V gene usage", IMMUNOLOGY LETTERS, ELSEVIER BV, NL, (20030908), vol. 88, no. 3, doi:10.1016/S0165-2478(03)00081-6, ISSN 0165-2478, pages 227 - 239, XP002357322 [Y] 1-15 * the whole document *
ref_type: npl
severity: obviousness
ref_id: - MASAYA YAMAGUCHI ET AL, "Streptococcus pneumoniae Invades Erythrocytes and Utilizes Them to Evade Human Innate Immunity", PLOS ONE, US, (20131023), vol. 8, no. 10, doi:10.1371/journal.pone.0077282, ISSN 1932-6203, page e77282, XP055296830 [Y] 1-15 * the whole document *
ref_type: npl
severity: obviousness
ref_id: - Daniel M Musher ET AL, "534 @BULLET CID 2001:32 (15 February) @BULLET Musher et al. Nonspecificity of Assaying for IgG Antibody to Pneumolysin in Circulating Immune Complexes as a Means to Diagnose Pneumococcal Pneumonia Medical Service (Infectious Disease Section), Houston Veterans Affairs Medical Center, and Departments", MAJOR, (20010209), pages 534 - 538, URL: https://academic.oup.com/cid/article-pdf/32/4/534/1258021/32-4-534.pdf, (20191111), XP055641234 [Y] 1-15 * the whole document *
ref_type: npl
severity: obviousness
ref_id: - AURELIJA ZVIRBLIENE ET AL, "Production and characterization of monoclonal antibodies against vaginolysin: Mapping of a region critical for its cytolytic activity", TOXICON, ELMSFORD, NY, US, vol. 56, no. 1, doi:10.1016/J.TOXICON.2010.03.007, ISSN 0041-0101, (20100801), pages 19 - 28, (20100316), XP002648819 [Y] 1-15 * the whole document *
ref_type: npl
severity: obviousness
ref_id: - A. MARTNER ET AL, "Streptococcus pneumoniae Autolysis Prevents Phagocytosis and Production of Phagocyte-Activating Cytokines", INFECTION AND IMMUNITY, US, (20090901), vol. 77, no. 9, doi:10.1128/IAI.00290-09, ISSN 0019-9567, pages 3826 - 3837, XP055641113 [Y] 1-15 * the whole document *
ref_type: npl
severity: obviousness
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ref_type: npl
severity: background
Final disposition: pending (2020-12-09)